Feasibility of a bone and soft tissue chimeric anterolateral thigh free flap? anatomic study and report of two cases for oral cavity reconstruction

Publication date: Available online 20 December 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): J.A. LoGiudice, J.G. Yan, B.L. Massey, J. Neilson, N. Flugstad, J. Mann
The anterolateral thigh flap (ALT) is a workhorse for a spectrum of reconstructive problems including head and neck defects. Its versatility as a chimeric flap employing a variety of soft tissues with a robust pedicle is useful for three-dimensional defects. The authors investigated the anatomical relationship between the vascular supply to the ALT and anterior femur. We studied 16 fresh cadaver limbs to identify the typical branching patterns to the femur off the descending branch of the lateral circumflex femoral artery. These patterns can facilitate dissection of this type of chimeric ALT. The authors have integrated a bone component of vascularised femur in this flap off the lateral circumflex femoral artery system to address oral cancer defects in two patients. A retrospective review of these cases correlating with the anatomic study was undertaken. Both patients had recurrent disease with limited donor site options. Both had extensive floor of mouth and tongue defects as well as small mandible defects of 2 cm. Both went on to heal at the donor and recipient sites at 32 months' follow-up.



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Issue Information - Cover and Editorial Board

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Issue Information - TOC

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The function of BTG3 in colorectal cancer cells and its possible signaling pathway

Abstract

Purpose

B-cell translocation gene 3 (BTG3) has been identified as a candidate driver gene for various cancers, but its specific role in colorectal cancer (CRC) is poorly understood. We aimed to investigate the relationship between expression of BTG3 and clinicopathological features and prognosis, as well as to explore the effects and the role of a possible BTG3 molecular mechanism on aggressive colorectal cancer behavior.

Methods

BTG3 expression was assessed by immunohistochemistry (IHC) on specimens from 140 patients with CRC. The association of BTG3 expression with clinicopathological features was examined. To confirm the biological role of BTG3 in CRC, two CRC cell lines expressing BTG3 were used and BTG3 expression was knocked down by shRNA. CCK-8, cell cycle, apoptosis, migration, and invasion assays were performed. The influence of BTG3 knockdown was further investigated by genomic microarray to uncover the potential molecular mechanisms underlying BTG3-mediated CRC development and progression.

Results

BTG3 was downregulated in colorectal cancer tissues and positively correlated with pathological classification (p = 0.037), depth of invasion (p = 0.016), distant metastasis (p = 0.024), TNM stage (p = 0.007), and overall survival (OS) and disease-free survival (DFS). BTG3 knockdown promoted cell proliferation, migration, invasion, relieved G2 arrest, and inhibited apoptosis in HCT116 and LoVo cells. A genomic microarray analysis showed that numerous tumor-associated signaling pathways and oncogenes were altered by BTG3 knockdown. At the mRNA level, nine genes referred to the extracellular-regulated kinase/mitogen-activated protein kinase pathway were differentially expressed. Western blotting revealed that BTG3 knockdown upregulated PAK2, RPS6KA5, YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data.

Conclusions

BTG3 expression might contribute to CRC carcinogenesis. BTG3 knockdown might strengthen the aggressive colorectal cancer behavior.

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Mammography screening: A major issue in medicine

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): Philippe Autier, Mathieu Boniol
Breast cancer mortality is declining in most high-income countries. The role of mammography screening in these declines is much debated.Screening impacts cancer mortality through decreasing the incidence of number of advanced cancers with poor prognosis, while therapies and patient management impact cancer mortality through decreasing the fatality of cancers. The effectiveness of cancer screening is the ability of a screening method to curb the incidence of advanced cancers in populations. Methods for evaluating cancer screening effectiveness are based on the monitoring of age-adjusted incidence rates of advanced cancers that should decrease after the introduction of screening. Likewise, cancer-specific mortality rates should decline more rapidly in areas with screening than in areas without or with lower levels of screening but where patient management is similar. These two criteria have provided evidence that screening for colorectal and cervical cancer contributes to decreasing the mortality associated with these two cancers. In contrast, screening for neuroblastoma in children was discontinued in the early 2000s because these two criteria were not met. In addition, overdiagnosis – i.e. the detection of non-progressing occult neuroblastoma that would not have been life-threatening during the subject's lifetime – is a major undesirable consequence of screening.Accumulating epidemiological data show that in populations where mammography screening has been widespread for a long time, there has been no or only a modest decline in the incidence of advanced cancers, including that of de novo metastatic (stage IV) cancers at diagnosis. Moreover, breast cancer mortality reductions are similar in areas with early introduction and high penetration of screening and in areas with late introduction and low penetration of screening. Overdiagnosis is commonplace, representing 20% or more of all breast cancers among women invited to screening and 30–50% of screen-detected cancers. Overdiagnosis leads to overtreatment and inflicts considerable physical, psychological and economic harm on many women. Overdiagnosis has also exerted considerable disruptive effects on the interpretation of clinical outcomes expressed in percentages (instead of rates) or as overall survival (instead of mortality rates or stage-specific survival). Rates of radical mastectomies have not decreased following the introduction of screening and keep rising in some countries (e.g. the United States of America (USA)). Hence, the epidemiological picture of mammography screening closely resembles that of screening for neuroblastoma.Reappraisals of Swedish mammography trials demonstrate that the design and statistical analysis of these trials were different from those of all trials on screening for cancers other than breast cancer. We found compelling indications that these trials overestimated reductions in breast cancer mortality associated with screening, in part because of the statistical analyses themselves, in part because of improved therapies and underreporting of breast cancer as the underlying cause of death in screening groups. In this regard, Swedish trials should publish the stage-specific breast cancer mortality rates for the screening and control groups separately. Results of the Greater New York Health Insurance Plan trial are biased because of the underreporting of breast cancer cases and deaths that occurred in women who did not participate in screening. After 17 years of follow-up, the United Kingdom (UK) Age Trial showed no benefit from mammography screening starting at age 39–41.Until around 2005, most proponents of breast screening backed the monitoring of changes in advanced cancer incidence and comparative studies on breast cancer mortality for the evaluation of breast screening effectiveness. However, in an attempt to mitigate the contradictions between results of mammography trials and population data, breast-screening proponents have elected to change the criteria for the evaluation of cancer screening effectiveness, giving precedence to incidence-based mortality (IBM) and case—control studies. But practically all IBM studies on mammography screening have a strong ecological component in their design. The two IBM studies done in Norway that meet all methodological requirements do not document significant reductions in breast cancer mortality associated with mammography screening. Because of their propensity to exaggerate the health benefits of screening, case–control studies may demonstrate that mammography screening could reduce the risk of death from diseases other than breast cancer.Numerous statistical model approaches have been conducted for estimating the contributions of screening and of patient management to reductions in breast cancer mortality. Unverified assumptions are needed for running these models. For instance, many models assume that if screening had not occurred, the majority of screen-detected asymptomatic cancers would have progressed to symptomatic advanced cancers. This assumption is not grounded in evidence because a large proportion of screen-detected breast cancers represent overdiagnosis and hence non-progressing tumours. The accumulation of population data in well-screened populations diminishes the relevance of model approaches.The comparison of the performance of different screening modalities – e.g. mammography, digital mammography, ultrasonography, magnetic resonance imaging (MRI), three-dimensional tomosynthesis (TDT) – concentrates on detection rates, which is the ability of a technique to detect more cancers than other techniques. However, a greater detection rate tells little about the capacity to prevent interval and advanced cancers and could just reflect additional overdiagnosis. Studies based on the incidence of advanced cancers and on the evaluation of overdiagnosis should be conducted before marketing new breast-imaging technologies.Women at high risk of breast cancer (i.e. 30% lifetime risk and more), such as women with BRCA1/2 mutations, require a close breast surveillance. MRI is the preferred imaging method until more radical risk-reduction options are eventually adopted. For women with an intermediate risk of breast cancer (i.e. 10–29% lifetime risk), including women with extremely dense breast at mammography, there is no evidence that more frequent mammography screening or screening with other modalities actually reduces the risk of breast cancer death.A plethora of epidemiological data shows that, since 1985, progress in the management of breast cancer patients has led to marked reductions in stage-specific breast cancer mortality, even for patients with disseminated disease (i.e. stage IV cancer) at diagnosis. In contrast, the epidemiological data point to a marginal contribution of mammography screening in the decline in breast cancer mortality. Moreover, the more effective the treatments, the less favourable are the harm–benefit balance of screening mammography.New, effective methods for breast screening are needed, as well as research on risk-based screening strategies.



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Outcomes in women with invasive ductal or invasive lobular early stage breast cancer treated with anastrozole or exemestane in CCTG (NCIC CTG) MA.27

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): K. Strasser-Weippl, G. Sudan, R. Ramjeesingh, L.E. Shepherd, J. O'Shaughnessy, W.R. Parulekar, P.E.R. Liedke, B.E. Chen, P.E. Goss
BackgroundHistological subtype, (invasive ductal breast cancer (IDBC)/invasive lobular breast cancer (ILBC)), might be a marker for differential response to endocrine therapy in breast cancer.MethodsClinical trial MA.27 compared 5 years of adjuvant anastrozole or exemestane in postmenopausal patients with hormone receptor positive early breast cancer. We evaluated IDBC versus ILBC (based on original pathology reports) as predictor for event-free survival (EFS) and overall survival (OS).ResultsA total of 5709 patients (5021 with IDBC and 688 with ILBC) were included (1876 were excluded because of missing or other histological subtype). Median follow-up was 4.1 years. Overall, histological subtype did not influence OS or EFS (HR (hazard ratio) 1.14, 95% confidence interval (CI) [0.79–1.63], P = 0.49 and HR 1.04, 95% CI [0.77–1.41], P = 0.81, respectively). There was no significant difference in OS between treatment with exemestane versus treatment with anastrozole in the IDBC group (HR = 0.92, 95% CI [0.73–1.16], P = 0.46). In the ILBC group, a marginally significant difference in favour of treatment with anastrozole was seen (HR = 1.79, 95% CI [0.98–3.27], P = 0.055). In multivariable analysis a prognostic effect of the interaction between treatment and histological subtype on OS (but not on EFS) was noted, suggesting a better outcome for patients with ILBC on anastrozole (HR 2.1, 95% CI [0.99–4.29], P = 0.05). After stepwise selection in the multivariable model, a marginally significant prognostic effect for the interaction variable (treatment with histological subtype) on OS (but not on EFS) was noted (Ratio of HR 2.1, 95% CI [1.00–4.31], P = 0.05).ConclusionOur data suggest an interaction effect between treatment and histology (P = 0.05) on OS. Here, patients with ILBC cancers had a better OS when treated with anastrozole versus exemestane, whereas no difference was noted for patients with IDBC.Clinical Trial informationNCT00066573.



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The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer

Publication date: February 2018
Source:European Journal of Cancer, Volume 90
Author(s): Eric Van Cutsem, Robert J. Mayer, Stéphanie Laurent, Robert Winkler, Cristina Grávalos, Manuel Benavides, Federico Longo-Munoz, Fabienne Portales, Fortunato Ciardiello, Salvatore Siena, Kensei Yamaguchi, Kei Muro, Tadamichi Denda, Yasushi Tsuji, Lukas Makris, Patrick Loehrer, Heinz-Josef Lenz, Atsushi Ohtsu
BackgroundIn the phase III RECOURSE trial, trifluridine/tipiracil (TAS-102) extended overall survival (OS) and progression-free survival (PFS) with an acceptable toxicity profile in patients with metastatic colorectal cancer refractory or intolerant to standard therapies. The present analysis investigated the efficacy and safety of trifluridine/tipiracil in RECOURSE subgroups.MethodsPrimary and key secondary end-points were evaluated using a Cox proportional hazards model in prespecified subgroups, including geographical subregion (United States of America [USA], European Union [EU], Japan), age (<65 years, ≥65 years) and v-Ki-ras2 Kirsten rat sarcoma 2 viral oncogene homologue (KRAS) status (wild type, mutant). Safety and tolerability were reported with descriptive statistics.ResultsEight-hundred patients were enrolled: USA, n = 99; EU, n = 403; Japan, n = 266. Patients aged ≥65 years and those with mutant KRAS tumours comprised 44% and 51% of all patients in the subregions, respectively. Final OS analysis (including 89% of events, compared with 72% in the initial analysis) confirmed the survival benefit associated with trifluridine/tipiracil, with a hazard ratio (HR) of 0.69 (95% confidence interval [CI] 0.59–0.81; P = 0.0001). Median OS in the three regions was 6.5–7.8 months in the trifluridine/tipiracil arm and 4.3–6.7 months in the placebo arm (USA: HR 0.56; 95% CI 0.34–0.94; P = 0.0277; EU: HR 0.62; 95% CI 0.48–0.80; P = 0.0002; Japan: HR 0.75; 95% CI 0.57–1.00; P = 0.0470). Median PFS was 2.0–2.8 months for trifluridine/tipiracil and 1.7–1.8 months for placebo; HRs favoured trifluridine/tipiracil in all regions. Similar clinical benefits of trifluridine/tipiracil were observed in elderly patients and in those with mutant KRAS tumours. There were no marked differences among subregions in terms of safety and tolerability.ConclusionsTrifluridine/tipiracil was effective in all subgroups, regardless of age, geographical origin or KRAS status.This trial is registered with ClinicalTrials.gov: NCT01607957.



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High circulating miR-18a, miR-20a, and miR-92a expression correlates with poor prognosis in patients with non-small cell lung cancer

Abstract

The purpose of this study was to assess the predictive value of angiogenic miRNAs for disease-free survival (DFS) and overall survival (OS) of patients with non-small cell lung cancer (NSCLC). In total, 196 patients with NSCLC (tumor lymph nodes metastasis (TNM) stage I–III) were enrolled and peripheral blood samples were collected. Total RNA was extracted from blood samples, and the relative expression levels of candidate miRNAs were evaluated by real time-polymerase chain reaction (RT-PCR). The median follow-up period was 56.7 months, and the final follow-up date was in August 2016. The median DFS of all patients was 30.0 (14.0–49.0) months, whereas the median OS was 41.5 (23.0–58.0) months. Furthermore, the 5-year DFS and OS rates were 11.3% and 32.3%, respectively. Kaplan–Meier (K–M) curves showed that high plasma miR-18a (P < 0.001), miR-20a (P < 0.001), miR-92a (P < 0.001), miR-126 (P < 0.001), miR-210 (P = 0.003), and miR-19a (P = 0.027) expressions levels correlated with a worse DFS. Moreover, patients with high plasma miR-18a, miR-20a, miR-92a, miR-210, and miR-126 expression levels had a shorter OS than patients with low expression levels of these miRNAs (all P <= 0.001). Furthermore, multivariate Cox regression analyses revealed that high plasma expression levels of miR-18a, miR-20a, and miR-92a as well as lymphatic node metastasis (all P < 0.001) were independent risk factors for both DFS and OS in patients with NSCLC. Thus, the circulating miR-18a, miR-20a, and miR-92a levels may serve as novel and promising prognostic biomarkers in patients with NSCLC.

Circulating miR-18a, miR-20a, and miR-92a levels may serve as novel and promising prognostic biomarkers in patients with non-small cell lung cancer.

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In reference to should infants who fail their newborn hearing screen undergo cytomegalovirus testing?

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Childbirth and Trauma, 1940s–1980s

Abstract

This article analyzes trauma in mid-twentieth century hospital births, focusing on the United States, but with additional evidence drawn from Great Britain and France. As many as half of women today experience childbirth as traumatic and no evidence suggests that the figure was lower a half-century ago. Drawing on women's birth narratives and psychiatric literature, this article highlights the striking consistency over time in how women describe their experiences of traumatic birth. By the 1970s, however, women proved less ready to accept their trauma as the product of their own psychological shortcomings. Under the sway of second-wave feminism, they pushed back against care they defined as inhumane in both conventional maternity care and in natural childbirth. Psychiatry too demonstrates change over time. Hegemonic at midcentury, Freudian thinking began to yield to critiques that questioned gender norms and the preeminence of the subconscious. Based on private letters to maternity caregivers and between physicians, as well as a wide array of medical journal articles, popular magazines, and newsletters from childbirth education and birth advocacy organizations, this article argues that, despite different approaches to trauma in birth and clarity about how best to minimize it, contemporary maternity care has to date proven unable to heed the lessons of history.

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The Island of Alternatives: Power, Medical Science, and “Gentle Birthing” in Socialist Czechoslovakia

Abstract

Beginning in the early 1980s, medical experts and birthing women increasingly voiced criticism of what had long been the technocratic, depersonalized nature of obstetric treatment in Czechoslovakia, despite the limited opportunities for them to do so publicly. A few maternity hospitals responded to the complaints by introducing radically different regimens of care. This article examines the history of one reformist project that took place in the small town of Ostrov nad Ohří. Ostrov means "island" in Czech and, during the last decade of Communist rule in Czechoslovakia, the Ostrov hospital became an island of alternative obstetric care, embracing Leboyer's method of "gentle birthing," acupuncture, fathers in delivery rooms, and assorted technological innovations that aimed to spark fundamental change in familial and social relationships, and humanize childbirth. While many medical professionals decried these reforms as nonsensical and dangerous, a number of parents-to-be flocked to Ostrov to give birth, circumventing the official rules mandating that they receive healthcare in their area of residence. This proactive consumerist behavior among expectant parents, in tandem with the call of some physicians for more attention to individual and family needs, despite the opposing official political discourse, is evidence of a grassroots movement for market-oriented principles in healthcare that reflected broader societal change during the last decade of the Communist regime.

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Risk and Reputation: Obstetricians, Cesareans, and Consent

Abstract

When physicians performed cesarean sections in the nineteenth century, they customarily sought agreement from all present before proceeding. In contrast, after the introduction of electronic fetal monitoring in the late 1960s, obstetricians obtained permission for a cesarean by offering a choice that ensured consent—give birth by cesarean or give birth vaginally to a damaged or dead baby. This article argues that the manner in which physicians obtained consent for cesareans in the nineteenth century was one factor that kept the cesarean rate low, while the manner in which physicians obtained consent in the late twentieth and early twenty-first centuries was one factor driving up the cesarean rate. The dissimilar approaches to consent did serve a common purpose, however. Each preserved physicians' reputations. With the surgery likely to end in a woman's death in the nineteenth century, consensus ensured that a bad outcome would be a shared burden. And because the fetal monitor, in exaggerating the risks of vaginal birth, changed the nature of the malpractice climate for obstetricians, the late-twentieth-century approach to consent similarly protected physicians. As one early twenty-first-century obstetrician quipped, "You don't get sued for doing a C-section. You get sued for not doing a C-section."

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Back to Bed: From Hospital to Home Obstetrics in the City of Chicago

Abstract

This article analyzes the role of doctors and activists in Chicago who successfully redefined the practice and politics of childbirth both locally and ultimately nationwide. It begins with the story of Joseph DeLee's Chicago Maternity Center, responsible for supervising over 100,000 home births between 1932 and 1972. Most of the mothers cared for by the Center were nonwhite, poor, and had little or no access to prenatal care, yet their babies had a far higher survival rate than the nationwide average. Thousands of medical students from all over the Midwest experienced their first deliveries not in hospitals, but in these homes. The article then addresses a very different demographic: a rising number of middle-class white families in the suburbs of Chicago who, beginning in the 1950s, opted for out-of-hospital births. Many of them learned about home birth through their involvement in La Leche League, the breastfeeding organization formed in a Chicago suburb in 1956. Seemingly separated by class, race, and locale, the link between these two groups of home birthers was the philosophy and training in place at the Chicago Maternity Center.

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Introduction to a Special Issue: Childbirth History is Everyone's History

More than any other endeavor, save death, the history of childbirth is quite literally everyone's history. The stories recounted in this volume remind us of the broad themes that have dominated the history of childbirth in the United States for the last century and continue to resonate today. These include debates over the place of birth, the benefits and limitations of medical intervention and technology in birth, the status of women as providers of care and decision makers concerning their own maternity care.

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Susan C. Lawrence. Privacy and the Past: Research, Law, Archives, Ethics

LawrenceSusan C.. Privacy and the Past: Research, Law, Archives, Ethics. New Brunswick, Rutgers University Press, 2016. x, 169 pp., 2 tables, $49.95.

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Dennis A. Doyle. Psychiatry and Racial Liberalism in Harlem: 1936-1968

DoyleDennis A.. Psychiatry and Racial Liberalism in Harlem: 1936–1968. Rochester, New York, University of Rochester Press, 2016. vii, 260 pp., $99.00.

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Amos Morris-Reich. Race and Photography. Racial Evidence as Scientific Evidence, 1876–1980

Morris-ReichAmos. Race and Photography. Racial Evidence as Scientific Evidence, 1876–1980. Chicago, University of Chicago Press, 2016. 320 pp., illus. $32.50

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Jennifer S. Singh. Multiple Autisms: Spectrums of Advocacy and Genomic Science

SinghJennifer S.. Multiple Autisms: Spectrums of Advocacy and Genomic Science. Minneapolis, University of Minnesota Press, 2016. xv, 284 pp., $27.00.

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Jonathan Lamb. Scurvy: The Disease of Discovery

LambJonathan. Scurvy: The Disease of Discovery. Princeton, Princeton University Press, 2017. xiii, 305 pp., illus. $35.00.

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Jeremy A. Greene, Flurin Condrau, and Elizabeth Siegel Watkins, eds. Therapeutic Revolutions: Pharmaceuticals and Social Change in the Twentieth Century

GreeneJeremy A., CondrauFlurin, and WatkinsElizabeth Siegel, eds. Therapeutic Revolutions: Pharmaceuticals and Social Change in the Twentieth Century. Chicago, University of Chicago Press, 2016. 321 pp., $40.00.

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Nora E. Jaffary. Reproduction and Its Discontents in Mexico: Childbirth and Contraception from 1750 to 1905

JaffaryNora E.. Reproduction and Its Discontents in Mexico: Childbirth and Contraception from 1750 to 1905. Chapel Hill, The University of North Carolina Press, 2016.

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David Wright. SickKids: The History of the Hospital for Sick Children

WrightDavid. SickKids: The History of the Hospital for Sick Children. Toronto, University of Toronto Press, 2016. 480 pp., illus. $39.95.

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Nancy Tomes. Remaking the American Patient: How Madison Avenue and Modern Medicine Turned Patients into Consumers

TomesNancy. Remaking the American Patient: How Madison Avenue and Modern Medicine Turned Patients into Consumers. Chapel Hill, University of North Carolina Press, 2016. xviii, 538 pp., illus.

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Lisa Diedrich. Indirect Action: Schizophrenia, Epilepsy, AIDS, and the Course of Health Activism

DiedrichLisa. Indirect Action: Schizophrenia, Epilepsy, AIDS, and the Course of Health Activism. Minneapolis, University of Minnesota Press, 2016. 290 pp.

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Ian Burney and Neil Pemberton. Murder and the Making of English CSI

BurneyIan and PembertonNeil. Murder and the Making of English CSI. Baltimore, Johns Hopkins University Press, 2016. 248 pp., illus. $24.95.

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Steve Silberman. Neurotribes: The Legacy of Autism and the Future of Neurodiversity

SilbermanSteve. Neurotribes: The Legacy of Autism and the Future of Neurodiversity. New York, Avery, 2015. ix, 534 pp., $29.95.

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Susan E. Cayleff. Nature’s Path: A History of Naturopathic Healing in America

CayleffSusan E.. Nature's Path: A History of Naturopathic Healing in America. Baltimore, Johns Hopkins University Press, 2016. 397 pp., $39.95.

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Randall M. Packard. A History of Global Health: Interventions into the Lives of Other Peoples

PackardRandall M.. A History of Global Health: Interventions into the Lives of Other Peoples. Baltimore, Johns Hopkins University Press, 2016. 432 pp., illus. $65.00 (cloth).

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ADGRV1 is implicated in myoclonic epilepsy

Summary

Objective

To investigate the significance of variation in ADGRV1 (also known as GPR98, MASS1, and VLGR1), MEF2C, and other genes at the 5q14.3 chromosomal locus in myoclonic epilepsy.

Methods

We studied the epilepsy phenotypes of 4 individuals with 5q14.3 deletion and found that all had myoclonic seizures. We then screened 6 contiguous genes at 5q14.3, MEF2C, CETN3, MBLAC2, POLR3G, LYSMD3, and ADGRV1, in a 95-patient cohort with epilepsy and myoclonic seizures. Of these genes, point mutations in MEF2C cause a phenotype involving seizures and intellectual disability. A role for ADGRV1 in epilepsy has been proposed previously, based on a recessive mutation in the Frings mouse model of audiogenic seizures, as well as a shared homologous region with another epilepsy gene, LGI1.

Results

Six patients from the myoclonic epilepsy cohort had likely pathogenic ultra-rare ADGRV1 variants, and statistical analysis showed that ultra-rare variants were significantly overrepresented when compared to healthy population data from the Genome Aggregation Database. Of the remaining genes, no definite pathogenic variants were identified.

Significance

Our data suggest that the ADGRV1 variation contributes to epilepsy with myoclonic seizures, although the inheritance pattern may be complex in many cases. In patients with 5q14.3 deletion and epilepsy, ADGRV1 haploinsufficiency likely contributes to seizure development. The latter is a shift from current thinking, as MEF2C haploinsufficiency has been considered the main cause of epilepsy in 5q14.3 deletion syndrome. In cases of 5q14.3 deletion and epilepsy, seizures likely occur due to haploinsufficiency of one or both of ADGRV1 and MEF2C.

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Morphological, biochemical and mechanical properties of articular cartilage and subchondral bone in rat tibial plateau are age related

Abstract

The purpose of this study was to investigate age-related changes in the morphological, biochemical and mechanical properties of articular cartilage (AC) and subchondral bone in the rat tibial plateau. Female Wistar rats were grouped according to age (1, 3, 5, 7, 9, 11, 13, 15, 16 and 17 months, with 10 rats in each group). The ultrastructures, surface topographies, and biochemical and mechanical properties of the AC and subchondral bone in the knee joints of the rats were determined through X-ray micro-tomography, histology, immunohistochemistry, scanning electron microscopy (SEM), atomic force microscopy and nanoindentation. We found that cartilage thickness decreased with age. This decrease was accompanied by functional condensation of the underlying subchondral bone. Increased thickness and bone mineral density and decreased porosity were observed in the subchondral plate (SP). Growth decreased collagen II expression in the tibial cartilage. The arrangement of trabeculae in the subchondral trabecular bone became disordered. The thickness and strength of the fibers decreased with age, as detected by SEM. The SP and trabeculae in the tibial plateau increased in roughness in the first phase (1–9 months of age), and then were constant in the second phase (11–17 months of age). Meanwhile, the roughness of the AC changed significantly in the first phase (1–9 months of age), but the changes were independent of age thereafter. This study gives a comprehensive insight into the growth-related structural, biochemical and mechanical changes in the AC and subchondral bone. The results presented herein may contribute to a new understanding of the pathogenesis of age-related bone diseases.

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MUC1-C Induces PD-L1 and Immune Evasion in Triple-Negative Breast Cancer

The immune checkpoint ligand PD-L1 and the transmembrane mucin MUC1 are upregulated in triple-negative breast cancer (TNBC), where they contribute to its aggressive pathogenesis. Here, we report that genetic or pharmacological targeting of the oncogenic MUC1 subunit MUC1-C is sufficient to suppress PD-L1 expression in TNBC cells. Mechanistic investigations showed that MUC1-C acted to elevate PD-L1 transcription by recruitment of MYC and NF-κB p65 to the PD-L1 promoter. In an immunocompetent model of TNBC in which Eo771/MUC1-C cells were engrafted into MUC1 transgenic mice, we showed that targeting MUC1-C associated with PD-L1 suppression, increases in tumor-infiltrating CD8+ T cells and tumor cell killing. MUC1 expression in TNBCs also correlated inversely with CD8, CD69, and GZMB, and downregulation of these markers associated with decreased survival. Taken together, our findings show how MUC1 contributes to immune escape in TNBC, and they offer a rationale to target MUC1-C as a novel immunotherapeutic approach for TNBC treatment.Significance: These findings show how upregulation of the transmembrane mucin MUC1 contributes to immune escape in an aggressive form of breast cancer, with potential implications for a novel immunotherapeutic approach. Cancer Res; 78(1); 1–11. ©2017 AACR.

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KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment

KRAS is one of the most frequently mutated oncogenes in cancer, being a potent initiator of tumorigenesis, a strong inductor of malignancy, and a predictive biomarker of response to therapy. Despite the large investment to understand the effects of KRAS activation in cancer cells, pharmacologic targeting of KRAS or its downstream effectors has not yet been successful at the clinical level. Recent studies are now describing new mechanisms of KRAS-induced tumorigenesis by analyzing its effects on the components of the tumor microenvironment. These studies revealed that the activation of KRAS on cancer cells extends to the surrounding microenvironment, affecting the properties and functions of its constituents. Herein, we discuss the most emergent perspectives on the relationship between KRAS-mutant cancer cells and their microenvironment components. Cancer Res; 78(1); 1–8. ©2017 AACR.

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Epigenetic Reprogramming Strategies to Reverse Global Loss of 5-Hydroxymethylcytosine, a Prognostic Factor for Poor Survival in High-grade Serous Ovarian Cancer

PURPOSE: A major challenge in platinum-based cancer therapy is the clinical management of chemoresistant tumors, which have a largely unknown pathogenesis at the level of epigenetic regulation. EXPERIMENTAL DESIGN: We evaluated the potential of using global loss of 5-hydroxymethylcytosine (5-hmC) levels as a novel diagnostic and prognostic epigenetic marker to better assess platinum-based chemotherapy response and clinical outcome in high-grade serous tumors (HGSOC), the most common and deadliest subtype of ovarian cancer. Furthermore, we identified a targetable pathway to reverse these epigenetic changes, both genetically and pharmacologically. RESULTS: This study shows that decreased 5-hmC levels are an epigenetic hallmark for malignancy and tumor progression in HGSOC. In addition, global 5-hmC loss is associated with a decreased response to platinum-based chemotherapy, shorter time to relapse, and poor overall survival in newly diagnosed HGSOC patients. Interestingly, the rescue of 5-hmC loss restores sensitivity to platinum chemotherapy in vitro and in vivo, decreases the percentage of tumor cells with cancer stem cell markers, and increases overall survival in an aggressive animal model of platinum resistant disease. CONCLUSIONS: Consequently, a global analysis of patient 5-hmC levels should be included in future clinical trials, which use pretreatment with epigenetic adjuvants to elevate 5-hmC levels and improve the efficacy of current chemotherapies. Identifying prognostic epigenetic markers and altering chemotherapeutic regimens to incorporate DNMTi pretreatment in tumors with low 5-hmC levels could have important clinical implications for newly diagnosed HGSOC disease.

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Loss-of-function mutations in Calcitonin receptor (CALCR) identify highly aggressive glioblastoma with poor outcome

Purpose Despite significant advances in the understanding of the biology, the prognosis of glioblastoma (GBM) remains dismal. The objective was to carry out whole exome sequencing (WES) of Indian glioma and integrate with that of TCGA to find clinically relevant mutated pathways. Experimental Design WES of different astrocytoma samples (n=42; Indian cohort) was carried out and compared to that of TCGA cohort. An integrated analysis of mutated genes from Indian and TCGA cohorts was carried out to identify survival association of pathways with genetic alterations. Patient-derived glioma stem-like cells, glioma cell lines and mouse xenograft models were used for functional characterization of Calcitonin Receptor (CALCR) and establish it as a therapeutic target. Results A similar mutation spectrum between Indian cohort and TCGA cohort was demonstrated. An integrated analysis identified GBMs with defective "Neuroactive ligand-receptor interaction" pathway (n=23; 9.54%) have significantly poor prognosis (p0.0001). Further, GBMs with mutated Calcitonin receptor (CALCR) or reduced transcripts levels predicted poor prognosis. Exogenously added Calcitonin (CT) inhibited various properties of glioma cells and pro-oncogenic signaling pathways in a CALCR-dependent manner. Patient-derived mutations in CALCR abolished these functions with the degree of loss-of-function negatively correlating with patient survival. WT CALCR, but not the mutant versions, inhibited Ras-mediated transformation of immortalized astrocytes in vitro. Further, CT inhibited patient derived neurospheres growth and in vivo glioma tumor growth in a mouse model. Conclusions We demonstrate CT-CALCR signaling axis is an important tumor suppressor pathway in glioma and establish CALCR as a novel therapeutic target for GBM.

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Motor learning and metaplasticity in striatal neurons: relevance for Parkinson’s disease

Abstract

Nigro-striatal dopamine transmission is central to a wide range of neuronal functions, including skill learning, which is disrupted in several pathologies such as Parkinson's disease. The synaptic plasticity mechanisms, by which initial motor learning is stored for long time periods in striatal neurons, to then be gradually optimized upon subsequent training, remain unexplored. Addressing this issue is crucial to identify the synaptic and molecular mechanisms involved in striatal-dependent learning impairment in Parkinson's disease. In this study, we took advantage of interindividual differences between outbred rodents in reaching plateau performance in the rotarod incremental motor learning protocol, to study striatal synaptic plasticity ex vivo. We then assessed how this process is modulated by dopamine receptors and the dopamine active transporter, and whether it is impaired by overexpression of human α-synuclein in the mesencephalon; the latter is a progressive animal model of Parkinson's disease. We found that the initial acquisition of motor learning induced a dopamine active transporter and D1 receptors mediated long-term potentiation, under a protocol of long-term depression in striatal medium spiny neurons. This effect disappeared in animals reaching performance plateau. Overexpression of human α-synuclein reduced striatal dopamine active transporter levels, impaired motor learning, and prevented the learning-induced long-term potentiation, before the appearance of dopamine neuronal loss. Our findings provide evidence of a reorganization of cellular plasticity within the dorsolateral striatum that is mediated by dopamine receptors and dopamine active transporter during the acquisition of a skill. This newly identified mechanism of cellular memory is a form of metaplasticity that is disrupted in the early stage of synucleinopathies, such as Parkinson's disease, and that might be relevant for other striatal pathologies, such as drug abuse.

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Early use of 80 Hz subthalamic stimulation in Parkinson's disease as an alternative for High-frequency stimulation induced gait changes and postural instability

Publication date: Available online 20 December 2017
Source:Brain Stimulation
Author(s): Marcelo D. Mendonça, Raquel Barbosa, Alexandra Seromenho-Santos, Carla Reizinho, Paulo Bugalho




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Vestibulo-cochlear function in inflammatory neuropathies

Publication date: Available online 20 December 2017
Source:Clinical Neurophysiology
Author(s): Marisa Blanquet, Jens A. Petersen, Antonella Palla, Dorothe Veraguth, Konrad P. Weber, Dominik Straumann, Alexander A. Tarnutzer, Hans H. Jung
ObjectiveWe aimed to quantify peripheral-vestibular deficits that may contribute to imbalanced stance/gait in patients with inflammatory neuropathies.MethodsTwenty-one patients (58±15y [mean age±1SD]; chronic-inflammatory-demyelinating-polyneuropathy=10, Guillain-Barré Syndrome=5, Anti-MAG peripheral neuropathy=2, multifocal-motor-neuropathy=4) were compared with 26 healthy controls. All subjects received video-head-impulse testing (vHIT), caloric irrigation and cervical/ocular vestibular-evoked myogenic-potentials (VEMPs). The Yardley vertigo-symptom-scale (VSS) was used to assess vertigo/dizziness. Postural stability was assessed using the functional gait-assessment (FGA). Pure-tone audiograms (n=18), otoacoustic emissions (n=12) and auditory brainstem responses were obtained (n=12).ResultsSemicircular-canal hypofunction was noted in 9/21 (43%) patients (vHIT=6; caloric irrigation=5), whereas otolith function was impaired in 12/21 (57%) (oVEMPs=8; cVEMPs=5), resulting in vestibular impairment of at least one sensor in 13/21 (62%). On average, 2.4±1.1 vestibular end organs (each side: anterior/posterior/horizontal canal, utriculus, sacculus; total=10) were affected. The VSS-scores were higher in patients (16.8±8.6 vs. 9.5±6.2, p=0.002) but did not correlate with the number of affected organs. Auditory neuropathy was found in 1/12 (8%) patients.ConclusionImpairment of one or more vestibular end organs was frequent, but usually mild, possibly contributing to imbalance of stance/gait in inflammatory neuropathies.SignificanceWhile our data does not support routine vestibular testing in inflammatory neuropathies, this may be considered in selected cases.



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Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition, consolidation, and interlimb transfer of motor skills in healthy young adults

Publication date: Available online 20 December 2017
Source:Clinical Neurophysiology
Author(s): M.P. Veldman, N.M. Maurits, M.A.M. Nijland, N.E. Wolters, J.C. Mizelle, T. Hortobágyi
ObjectivePlasticity of the central nervous system likely underlies motor learning. It is however unclear, whether plasticity in cortical motor networks is motor learning stage-, activity-, or connectivity-dependent.MethodsFrom electroencephalography (EEG) data, we quantified effective connectivity by the phase slope index (PSI), neuronal activity by event-related desynchronization, and sensorimotor integration by N30 during the stages of visuomotor skill acquisition, consolidation, and interlimb transfer.ResultsAlthough N30 amplitudes and event-related desynchronization in parietal electrodes increased with skill acquisition, changes in PSI correlated most with motor performance in all stages of motor learning. Specifically, changes in PSI between the premotor, supplementary motor, and primary motor cortex (M1) electrodes correlated with skill acquisition, whereas changes in PSI between electrodes representing M1 and the parietal and primary sensory cortex (S1) correlated with skill consolidation. The magnitude of consolidated interlimb transfer correlated with PSI between bilateral M1s and between S1 and M1 in the non-practiced hemisphere.ConclusionsSpectral and temporal EEG measures but especially PSI correlated with improvements in complex motor behavior and revealed distinct neural networks in the acquisition, consolidation, and interlimb transfer of motor skills.SignificanceA complete understanding of the neuronal mechanisms underlying motor learning can contribute to optimizing rehabilitation protocols



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Cortical sources of resting state electroencephalographic rhythms probe brain function in naïve HIV individuals

Publication date: Available online 20 December 2017
Source:Clinical Neurophysiology
Author(s): Claudio Babiloni, Giuseppe Noce, Alfredo Pennica, Paolo Onorati, Paolo Capotosto, Claudio Del Percio, Paolo Roma, Valentina Correr, Elisa Piccinni, Ginevra Toma, Andrea Soricelli, Francesco Di Campli, Laura Gianserra, Lorenzo Ciullini, Antonio Aceti, Elisabetta Teti, Loredana Sarmati, Gloria Crocetti, Raffaele Ferri, Valentina Catania, Maria Teresa Pascarelli, Massimo Andreoni, Stefano Ferracuti
ObjectiveHere we evaluated the hypothesis that resting state electroencephalographic (EEG) cortical sources correlated with cognitive functions and discriminated asymptomatic treatment-naïve HIV subjects (no AIDS).MethodsEEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cognitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest.ResultsWidespread sources of delta (< 4 Hz) and alpha (8-12 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p < 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70-75%).ConclusionsRegional EEG abnormalities in quiet wakefulness characterized treatment-naïve HIV subjects at the individual level.SignificanceThis EEG approach may contribute to the management of treatment-naïve HIV subjects at risk of cognitive deficits.



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Book Review: Flaps Practical Reconstructive Surgery

No abstract available

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Nerve Repair Manual: A Practical Approach to Injuries and Repair in the Brachial Plexus and Upper Extremity

No abstract available

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Noordhoff Craniofacial Foundation—Online Operative Syllabus and Video Review

No abstract available

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Defining the Anatomy of the Tendinous Intersections of the Rectus Abdominis Muscle and Their Clinical Implications in Functional Muscle Neurotization

Purpose Little is known about the definitive course of the tendinous intersections from anterior to posterior through the rectus abdominis (RA) muscle. The implications of a full thickness intersection may have effects on the ability to neurotize the RA. We hypothesized that these tendinous inscriptions would be fully adherent to the anterior rectus sheath, but there would be an incomplete penetrance into the posterior surface, thereby allowing for muscle fibers and neurovascular structures to run the entire course of the RA muscle. Methods Fifty-five cadaveric, hemiabdominal walls were evaluated. Measurements were taken of RA muscle thickness, depth of penetrance of the tendinous intersections, and intersection thickness. Results Of the 32 cadavers, 2 had 4 paired tendinous intersections and the remaining 30 cadavers had 3 paired tendinous intersections. Rectus abdominis muscle belly tended to be thicker at midbelly, between intersections than at the level of the corresponding intersection. A total of 168 tendinous intersections were assessed. Thirty (18%) of these inscriptions proved to be full thickness extending from anterior rectus sheath to posterior rectus sheath without any intervening muscle or neurovascular structures. Twenty-three (42%) of the 55 hemiabdomens assessed had at least one full-thickness tendinous intersection. Conclusions The majority of RA muscles have 3 paired tendinous intersections. Most intersections are incomplete and only encompass the anterior rectus sheath. However, there may be a higher percentage of full-thickness intersections than previously appreciated and the clinical relevance behind these remains unclear.

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Poly Implants Prosthèse Breast Implants: A Case Series and Review of the Literature

Background Silicone breast implants from the French manufacturer Poly Implants Prosthèse (PIP) were recalled from the European market after the French regulator has revealed the implants contain non–medical-grade silicone filler. In December 2011, following a large increase in reported rupture rate and a possible cancer risk, the French Ministry of Health recommended consideration of the PIP explantation, regardless of their condition. In 2012, the Israel Ministry of Health recommended to replace the implants only upon suspected implant rupture. Objectives The aims of this study were to characterize breast-augmented Israeli patients with PIP implants, compare their outcomes with those of breast-augmented patients with different implant types, and review the current PIP literature. Methods Breast-augmented patients who underwent an elective breast implant exchange in Israel between January 2011 and January 2017 were included in the study. Data were collected from electronic and physical medical files. Results There were 73 breast-augmented female patients with 146 PIP breast implants included in this study. Average implant age was 6.7 ± 2.79 years. Mean implant size was 342.8 ± 52.9 mL. Fourteen women (19 implants [16%]) had a high-grade capsular contracture (Baker grade 3–4). During exchange, 28 implants were found to be ruptured (19.2%). Conclusions Less than 10 years following breast augmentation, PIP implants demonstrated higher rupture rate compared with other implants. Our data are comparable to overall available rupture rate. Among patients with definitive rupture diagnosis, an elective implant removal should be recommended. In cases of undamaged implants, plastic surgeons should also seriously consider PIP implant explantation. When the patient does not desire to remove the implant, an annual physical examination and breast ultrasound are recommended, beginning a year after augmentation.

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Effects of the Metallic Port in Tissue Expanders on Dose Distribution in Postmastectomy Radiotherapy: A Tridimensional Experimental Model of Dosimetry in Breast Reconstruction

Abstract The purpose of this research was to develop an experimental model of dosimetry using a breast phantom and evaluate the effects of the metallic port in tissue expanders on dose distribution in postmastectomy radiotherapy. Dose distribution was assessed using an experimental acrylic dosimetry simulator in the absence and presence of a metallic disc (MD), which is similar to that used in tissue expanders containing a magnetic port, by collecting coronal and sagittal radiochromic films. Dosimetry film analysis did not show any changes in dose distribution, except for a MD shadow in the sagittal film where the dose distribution rate was on average 14% lower than in other areas. This model very closely resembled actual breast reconstruction with a tissue expander containing a magnetic port. Scattering or attenuation of the irradiation dose due to interference of the MD was not evident in areas that could jeopardize the effectiveness of radiation therapy. Therefore, the presence of the MD inside the tissue expander does not likely have an impact on radiotherapy effectiveness during immediate breast reconstruction.

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Complications After Total Skin-Sparing Mastectomy and Expander-Implant Reconstruction: Effects of Radiation Therapy on the Stages of Reconstruction

Background Many patients undergoing total-skin sparing mastectomy (TSSM) and 2-staged expander-implant (TE-I) reconstruction require postmastectomy radiation therapy (PMRT). Additionally, many patients undergoing TSSM for recurrent cancer have a history of lumpectomy and radiation therapy (XRT). Few studies have looked at the impact of XRT on the stages of TE-I reconstruction. Methods Patients undergoing TSSM and immediate TE-I reconstruction between 2006 and 2013 were identified from a prospectively maintained database. Rates of TE-I loss and severe infection requiring intravenous antibiotics were compared in patients with prior XRT (85 cases) and PMRT (133 cases). Complications were divided by stage of reconstruction: first stage (TSSM and TE placement) and second stage (TE-I exchange). Results Mean follow-up time was 2.5 years. Patients with prior XRT had more complications after the first stage of reconstruction than the second (TE-I loss: 15% vs 5%, P = 0.03; infection: 20% vs 8%, P = 0.04). Patients receiving PMRT had low complication rates after the first stage, when they had not yet received radiation (TE-I loss: 2%; infection: 5%). However, complication rates after TE-I exchange (TE-I loss, 18%; infection, 31%) were significantly higher, and nearly 4-fold higher than patients with prior XRT. Conclusions Patients with prior XRT are at high risk for complications after the first stage of TE-I reconstruction after TSSM; however, the risk of complications at the second stage is comparable to patients without radiation exposure and significantly lower than patients receiving PMRT. Patients receiving radiation therapy should be given appropriate preoperative counseling regarding their risks.

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Minimal Invasive Rhinoplasty: Fat Injection for Nasal Dorsum Contouring

No abstract available

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Objective Effects of Breast Reduction Surgery on Physical Fitness

Background Reduction mammaplasty is known for excellent outcomes and patient satisfaction. Although patients report improvements in pain, weight loss, and exercise levels, objective data on physical fitness benefits are limited. Methods Using the Stanford Military Data Repository, we identified 89 US Army active duty women with at least 1 pre- and postoperative Army Physical Fitness Test (APFT) who underwent reduction mammaplasty during 2011 to 2014. We used paired t tests to compare pre- and postoperative APFT score means and raw values for push-ups, sit-ups, and the 2-mile run. Results There were 56 subjects (62.9%) who improved in total APFT scores. Total score means increased from 235.9 preoperatively to 243.4 postoperatively (P = 0.0065). Of 28 subjects with at least 2 APFT scores before and after surgery, 20 (71.4%) improved in total scores. The subgroup's mean total score increased from 237.8 to 251.3 (P = 0.0009). Comparing individual pre- and postprocedure APFTs, all subjects demonstrated a mean 3.9% (SD, 0.1) improvement in total scores, and the subpopulation of 28 improved by 6.3% (SD, 0.1). In all events, mean performance values trended toward better postoperative scores. Differences were statistically significant for the total population for the number of sit-ups (P = 0.035), and, for the subgroup of 28, differences were statistically significant for the total score (P = 0.0009), sit-ups (P = 0.0002), and push-ups (P = 0.0134). Conclusions Reduction mammaplasty was associated with postoperative physical fitness improvements among US Army active duty women. Soldier data are useful for objectively assessing physical fitness effects of breast reduction surgery.

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An Outcomes Study on the Effects of the Singapore General Hospital Burns Protocol

Introduction The Singapore General Hospital Burns Protocol was implemented in May 2014 to standardize treatment for all burns patients, incorporate new techniques and materials, and streamline the processes and workflow of burns management. This study aims to analyze the effects of the Burns Protocol 2 years after its implementation. Methods Using a REDCap electronic database, all burns patients admitted from May 2013 to April 2016 were included in the study. The historical preimplementation control group composed of patients admitted from May 2013 to April 2014 (n = 96). The postimplementation prospective study cohort consisted of patients admitted from May 2014 to April 2016 (n = 243). Details of the patients collected included age, sex, comorbidities, total body surface area (TBSA) burns, time until surgery, number of surgeries, number of positive tissue and blood cultures, and length of hospital stay. Results There was no statistically significant difference in the demographics of both groups. The study group had a statistically significant shorter time to surgery compared with the control group (20.8 vs 38.1, P

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Determining the False-Negative Rate Using Fluorescence Image–Assisted Sentinel Lymph Node Biopsy in Cutaneous Melanoma

Introduction Despite the advances in cutaneous melanoma management, the false-negative rates (FNRs) of sentinel lymph node biopsy (SLNB) are still high. These rates are dependent not only on the technique but also on definitional terms and percentage of head/neck melanoma (highest false-negative SLNB). Fluorescence imaging technology is well acquainted in plastic surgery and other specialties. Having demonstrated that fluorescence-assisted SLNB is effective in melanoma, we are interested in determining its FNR. Methods We obtained institutional review board approval to follow up prospectively all patients with cutaneous melanoma who underwent radioisotope/fluorescence-assisted SLNB with the intent to capture 100 negative SLNB patients. Inclusion criteria were as follows: (1) National Comprehensive Cancer Network criteria; (2) an SLNB report; (3) at least 24 months of follow-up in the negative SLNB group. The outcome variables were FNR and adjusted FNR of SLNB, considering the criterion standard of assessing the accuracy of SNLB. The FNR was defined as the proportion of patients with false-negative SLNB to patients with true-positive and false-negative SLNB [false negative/(false negative + true positive)]. Adjusted FNR refers to the previously described false-negative SLNB, but in the absence of local/in-transit recurrence or distant metastases. Furthermore, false-negative incidence (false-negative/negative SLNB patients) was also calculated. Length of follow-up was date of surgery to the date of last follow-up/death. Results A total of 125 participants, with 52.0% being male and 48.0% being female, were included. One hundred patients had an SLNB negative for metastases, whereas the rest had positive SLNB results. Median follow-up time of the cohort and that of the negative SLNB group were 36.7 (2.6–58.5) and 37.9 (24.0–58.5) months, respectively. A relatively high number (24.8%) of head/neck melanoma were included. We identified 2 cases of false-negative SLNB, with one having in-transit metastases. Thus, the FNR and adjusted FNR were 7.4% and 3.7%, respectively. The false-negative incidence and adjusted false-negative incidence were 2.0% and 1.0%, respectively. Conclusions This is the first prospective study examining the FNR of fluorescence-assisted SLNB for patients with cutaneous melanoma. Our study reveals that this technique has one of the lowest FNRs published, especially considering the large percentage of participants with head/neck melanoma involved.

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Upper Extremity Patterns of Injury and Management at a Plastic and Reconstructive Surgery Referral Center in Mexico City

Background Acute upper extremity injuries remain one of the most common consultations in the emergency departments for plastic surgery services. These injuries can affect a person's quality of life and negatively affect work-related or social interactions if not properly managed. We aim to evaluate our experience and management in a specialized referral center in Mexico City. Methods A retrospective review was performed. All patients with hand trauma managed by our service from July 2010 to June 2015 were included; their demographic characteristics were described as well as the most common patterns of injury, management, and outcome. Results A total of 4751 patients with injuries in the upper extremities were included, 77% were males with a mean age of presentation of 26.9 ± 17.9 years; the age group most commonly affected was between 16 to 30 years (39%); 54% of the cases affected the right hand. Lacerative wounds were the most common mechanism of injury (60.7%), followed by blunt trauma (28.7%). Management was surgical in 87% of the cases. Conclusions Upper extremity trauma encompasses a wide range of clinical presentations, from simple lacerations to catastrophic injuries that require extensive or multiple reconstructive procedures. The clear understanding of the trauma mechanisms and how they are related with certain patterns of injury might maximize awareness and guide a surgeon's management effectively.

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Localized Leg Volume Index: A New Method for Body Type–Corrected Evaluation of Localized Leg Lymphedematous Volume Change

Background Volume measurement is one of the most common evaluations for lower-extremity lymphedema. However, volume comparison between different patients with different physique may be inappropriate, and it is difficult to evaluate localized limb volume change using leg volume evaluation. Methods Localized leg volumes (Vk, k = 1–5) and localized leg volume indices (LEVIk) at 5 points (1, thigh; 2, knee; 3, lower leg; 4, ankle; 5, foot) of 106 legs of 53 examinees with no leg edema were calculated based on physical measurements, leg circumferences and lengths, and body mass index (BMI). Interrater and intrarater reliabilities of LEVIk were assessed, and Vk and LEVIk were compared between lower BMI (BMI 0.98). Between lower and higher BMI groups, significant differences were observed in all Vk: V1 (P = 3.7 × 10−7), V2 (P = 4.7 × 10−8), V3 (P = 4.5 × 10−5), V4 (P = 1.6 × 10−3), and V5 (P = 2.4 × 10−4). Regarding LEVI between groups, significant differences were seen in LEVI3 (P = 0.009), LEVI4 (P = 0.004), and LEVI5 (P = 1.3 × 10−7); no significant difference was seen in LEVI1 (P = 0.23) or LEVI2 (P = 0.51). Conclusions Localized leg volume index is a highly reproducible and convenient method for evaluation of localized volume change of the lower extremity, which is less affected by body type compared with leg volumetry.

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Joint Denervation in the Digits: Technique and Patient Satisfaction

Background Traditional approaches to treating painful osteoarthritis of the fingers include arthrodesis and arthroplasty. Although highly effective for pain control, arthrodesis sacrifices joint motion and can be complicated by nonunion, malunion, and infection. Implant arthroplasty preserves motion but is likewise subject to complications—particularly at the level of the proximal interphalangeal joint. In contrast, finger joint denervation is a simple outpatient procedure that maintains joint motion. In this study, we describe our surgical techniques for joint denervation and review our survey of patient satisfaction. Methods A retrospective review was performed of all patients undergoing finger joint denervation for osteoarthritis at our institution from 2012 to 2014. Each patient was contacted by phone and asked to rate their pre- and postoperative pain and function. Patients were also asked about any complications experienced and if they would choose to undergo the operation again. Results Over the 2-year period, 12 patients underwent denervation of 23 joints. Of the 12 patients in the study, 11 undergoing 22 joint denervations were available for our survey. Patient-reported pain scores fell from a median of 5/5 preoperatively to 0/5 after recovery (P

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Evidence-Based Medicine in Plastic Surgery: Are We There Yet?

Background The practice of evidence-based medicine in plastic surgery is no longer a trend but a reality, with a growing number of studies published in recent years using evidence-based medicine as an assessment tool. Objective The aim of this study was to verify whether the number of citations to articles with a high level of evidence is greater than articles with low level of evidence. Methods A search was conducted in the 4 main international journals of plastic surgery. All original articles published in 2011 were analyzed, selected, and classified based on the study design. The articles were then divided into 2 groups: group 1, high level of evidence; and group 2, low level of evidence. Next, Scopus was searched for the number of citations of each article in the 2 subsequent years. The proportion of the number of citations received by articles in groups 1 and 2 was statistically compared. Results The articles with the highest level of evidence were the most cited among original articles, with 48.6% of them being cited more than 10 times over 2 years, whereas only 18.4% of articles in group 2 were cited with the same frequency. The mean number of citations was 12.6 citations per article in group 1 and 6.56 citations in group 2, with a significant difference between groups (P

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Osseointegrated Prosthetic Ear Reconstruction in Cases of Skin Malignancy: Technique, Outcomes, and Patient Satisfaction

Background Ear reconstruction with osseointegrated prosthetic implants is a well-established method of reconstruction after resection of skin malignancies on the external ear. There is limited literature reporting technique, outcomes, and patient satisfaction. Methods We evaluated our outcomes over a 5-year period looking at osseointegrated prosthetic reconstruction after auriculectomy for external ear skin malignancies. We report demographics, disease characteristics, technique, and complications. The patients were surveyed looking at 6 domains: satisfaction, stability, comfort, ease of use, level of self-consciousness, and preoperative education. Results Of the 21 patients included in the study, 14 (67%) were treated for invasive melanoma (Breslow depth, >0.8mm), 4 (19%) for squamous cell carcinoma, 2 (10%) for basal cell carcinoma, and 1 (5%) for an atypical fibroxanthoma. Complications rates were low. There were no cases of infection, hematoma, or bleeding. In 2 patients (9.5%), 1 of the 3 implants failed to osseointegrate and was removed, but the prosthesis was able to be secured with the remaining 2 posts. There were 3 cases (14%) of delayed healing and 1 with excessive granulation tissue growth. Survey results showed high satisfaction in all measured domains. Conclusions In cases of skin malignancy requiring total or subtotal auriculectomy, prosthetic ear reconstruction with osseointegrated implants is a good alternative to reconstruction with autologous tissue. Our experience demonstrates good outcomes and with low complication rates and high patient satisfaction.

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Immune cells and non-immune cells with immune function in mammalian cochleae

Publication date: Available online 20 December 2017
Source:Hearing Research
Author(s): Bo Hua Hu, Celia Zhang, Mitchell D. Frye
The cochlea has an immune environment dominated by macrophages under resting conditions. When stressed, circulating monocytes enter the cochlea. These immune mediators, along with cochlear resident cells, organize a complex defense response against pathological challenges. Since the cochlea has minimal exposure to pathogens, most inflammatory conditions in the cochlea are sterile. Although the immune response is initiated for the protection of the cochlea, off-target effects can cause collateral damage to cochlear cells. A better understanding of cochlear immune capacity and regulation would therefore lead to development of new therapeutic treatments. Over the past decade, there have been many advances in our understanding of cochlear immune capacity. In this review, we provide an update and overview of the cellular components of cochlear immune capacity with a focus on macrophages in mammalian cochleae. We describe the composition and distribution of immune cells in the cochlea and suggest that phenotypic and functional characteristics of macrophages have site-specific diversity. We also highlight the response of immune cells to acute and chronic stresses and comment on the potential function of immune cells in cochlear homeostasis and disease development. Finally, we briefly review potential roles for cochlear resident cells in the immune activities of the cochlea.



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Three-Dimensional Analysis of the Ear Morphology

Abstract

Background

For surgical treatment of the face, detailed surgical planning is necessary to avoid later unaesthetic results. Most of the studies in the literature concentrate on the ears' anatomy during childhood and adolescence. Nearly no study evaluates the anatomy of ears of people aged 50 or older. It was our aim to measure and evaluate the ear's anatomy in Caucasians between the ages of 21 and 65.

Methods

Three-dimensional scans of 240 volunteers were taken. The subjects were divided into groups of males and females and each of them into three groups by age (21–35, 36–50, 51–65). Landmarks were placed in these scans. Distances, relations and angles between them were recorded.

Results

The distance between the subaurale and superaurale significantly increases (p < 0.001) during the aging process in males and females. Also, the width of the ear, measured between the preaurale and postaurale, significantly increased (p = 0.007) with advancing age. When the length of the ear is divided into four parts by anatomical landmarks, it extended the most in the lower quadrant with increasing subject age.

Conclusion

The ear of Caucasians does not stop changing its shape during adulthood. Even after the body has stopped growing, the ear still does. With the measured values in this study, it should be possible for the surgeon to plan the operation in advance and achieve satisfactory aesthetic outcomes.

Level of Evidence V

This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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Assessing Normal Smiling Function Through 3D–3D Surfaces Registration: An Innovative Method for the Assessment of Facial Mimicry

Abstract

Smiling has a great importance, both from a functional and an aesthetic point of view. The introduction of modern 3D acquisition and elaboration methods may provide additional help in the evaluation of facial mimicry. This study aims at proposing an innovative method to assess facial and labial movements in different types of smiles. Twenty healthy subjects (10 males, 10 females, mean age 27.5 years, SD 4.5 years), were recorded through a stereophotogrammetric system in neutral position and in three types of smiles: Mona-Lisa smile, canine smile, full-denture smile. All the 3D smiling models were superimposed on the corresponding neutral one and point-to-point root mean square (RMS) differences were computed. Labial surface areas in rest position and during each smile were calculated as well, together with the percentage modification in different types of smile. RMS values (facial and labial models), labial surface areas and percentage modifications were compared through ANCOVA tests to verify possible statistically significant differences according to sex and type of smile (p < 0.05). Intercanthal labial width was considered a covariate. RMS values progressively increased from Mona-Lisa to full-denture smile; statistically significant differences were found among all types of smiles, both for facial and labial models (p < 0.05), while no statistically significant sex and sex × smile interactions were found (p > 0.05). Labial surface and percentage of modification showed statistically significant differences according to both sex and type of smile (p < 0.05). The study provides a novel contribution to the field of sexual dimorphism in smiling.

Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://ift.tt/18t7xNj.

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Feasibility of a bone and soft tissue chimeric anterolateral thigh free flap? anatomic study and report of two cases for oral cavity reconstruction

The anterolateral thigh flap (ALT) is a workhorse for a spectrum of reconstructive problems including head and neck defects. Its versatility as a chimeric flap employing a variety of soft tissues with a robust pedicle is useful for three-dimensional defects. The authors investigated the anatomical relationship between the vascular supply to the ALT and anterior femur. We studied 16 fresh cadaver limbs to identify the typical branching patterns to the femur off the descending branch of the lateral circumflex femoral artery.

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Vestibulo-cochlear function in inflammatory neuropathies

Inflammatory neuropathies are a heterogeneous group of peripheral nerve disorders linked by their immune-related pathogenesis. They are caused by auto-immune inflammation within the peripheral nerves associated with destruction of myelin and/or axons (Lunn et al., 2009). Inflammatory neuropathies may be acute (e.g., Guillain-Barré Syndrome, GBS) or chronic (e.g., Chronic Inflammatory Demyelinating Neuropathy, CIDP; Multifocal Motor Neuropathy, MMN) and are closely related to neuropathies associated with paraproteinemia (Lunn et al., 2009).

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Spectral and temporal electroencephalography measures reveal distinct neural networks for the acquisition, consolidation, and interlimb transfer of motor skills in healthy young adults

Motor practice results in skill acquisition, an asymptotic process leading to quicker and more accurate movements (Willingham, 1998). Synapses that form de novo and strengthen in the offline period after motor practice make the newly acquired motor skill stable and less susceptible to interference because the skill becomes consolidated into motor memory (Brashers-Krug et al., 1996; Shadmehr and Holcomb, 1997; Dayan and Cohen, 2011). Curiously, unilateral motor practice also improves skill performance in the contralateral non-practiced limb, most likely through synaptic adaptations in the hemisphere ipsilateral to the practiced limb (Hortobagyi et al., 2011; Veldman et al., 2015; Nojima et al., 2012; Lee and Carroll, 2007).

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Cortical sources of resting state electroencephalographic rhythms probe brain function in naïve HIV individuals

Human immunodeficiency virus (HIV) causes neurological, cognitive, and behavioral symptoms during the progression of the infection (Reger et al., 2002; Anthony and Bell 2008; Antinori et al., 2007). From an epidemiological point of view, subclinical neuropathy was reported in 10-40% of asymptomatic subjects with HIV and 53-100% in those with the AIDS (Chavanet et al., 1988; Gastaut et al., 1989). Also, 50-70% of subjects with HIV suffer from neurologic and the so-called HIV-associated neurocognitive disorders (HANDs) including deficits of episodic memory, attention, cognitive-motor, and executive functions such as planning and problem solving (Selnes, 2005).

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Is tracheotomy on the decline in otolaryngology? A single institutional analysis

A recent study reported decreasing trends in tracheotomy procedures by its otolaryngology service. We set out to determine whether the previously reported decrease in otolaryngology performed tracheotomies by one institution is a local or generalizable phenomenon.

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Safety and efficacy of intratympanic ciprofloxacin otic suspension post-tubes in a real-world pediatric population

Otorrhea frequently follows tympanostomy tube (TT) placement. We evaluated otorrhea following single 6mg OTO-201 (OTIPRIO®, ciprofloxacin otic suspension 6%) intraoperative injection into each middle ear in a variety of effusion types and concurrent procedures in children undergoing TT placement. Secondary objective: Efficacy based on Medicaid status and safety.

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Locator Spoon

Customised plates derived from 3-dimensional images are popular in reconstruction of the mandible with a fibular free flap. We have found that customised plates reduce the operating time and produce a predictable aesthetic outcome.

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Children’s Sleep Problems are Associated with Poorer Student-Teacher Relationship Quality

Children's sleep problems are associated with poorer student functioning in the school environment, including impairment in peer relationships, yet no studies have examined sleep functioning in relation to the student-teacher relationship. The objective of this study was to examine whether child-rated total sleep problems or specific sleep problem domains (bedtime problems, nighttime problems, or daytime sleepiness) were associated with teacher-rated student-teacher closeness and conflict after controlling for student mental health symptoms known to be associated with both greater sleep problems and poorer student-teacher relationship quality.

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Restless Legs Syndrome “Patient Odyssey” Survey of Disease Burden on Patient and Spouses/Partners

Restless Legs Syndrome has been shown to impact quality of life using standardized scales, typically from tertiary referral centers. Little data exists that has evaluated specific life adaptation required by RLS patients, and no survey has ever looked at the impact of RLS on family members.

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Mortality and use of psychotropic medication in sleep apnoea patients: a population-wide register-based study

This study aimed to evaluate all-cause mortality in relation to the use of benzodiazepines, antidepressants and antipsychotics in obstructive sleep apnoea (OSA) patients and matched controls.

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Cognitive Mechanisms of Sleep Outcomes in a Randomized Clinical Trial of Internet-Based Cognitive Behavioral Therapy for Insomnia

In a randomized clinical trial, to investigate the role of sleep-related cognitive variables in the long-term efficacy of an online, fully automated cognitive behavioral therapy intervention for insomnia (Sleep Healthy Using the Internet [SHUTi]).

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A comparative study of methods for automatic detection of rapid eye movement abnormal muscular activity in narcolepsy

To evaluate rapid eye movement (REM) muscular activity in narcolepsy by applying five algorithms to electromyogram (EMG) recordings, and to investigate its value for narcolepsy diagnosis.

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Can working memory training improve children’s sleep?

Improving children's sleep could lead to significant benefits in several functional domains. Recent research in adults suggests intensive, adaptive cognitive training may be beneficial in improving sleep, although there is limited understanding whether this approach yields similar results in children.

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In Memoriam Michel Jouvet 1925-2017

Michel Jouvet 1925-2017.

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The Antagonistic Effect of Selenium on Lead-Induced Immune Dysfunction via Recovery of Cytokine and Heat Shock Protein Expression in Chicken Neutrophils

Abstract

Lead (Pb) is a ubiquitous and toxic heavy metal and it can damage the immune system in humans and animals. Many researchers have reported that Selenium (Se) could possess various pharmacological effects in mammals. However, few studies have been carried out to investigate the protective role of Se in birds, especially in chickens. In this study, we investigated the protective effects of Se against Pb-induced inflammatory responses and the expression of heat shock proteins (HSPs) in peripheral blood neutrophils. One hundred eighty Hy-Line brown chickens were randomly divided into the control group (Con group), Se supplementation group (+Se group), Pb supplementation group (+Pb group), and the Se and Pb compound group (Se+Pb group). On the 90th day of the experiment, the peripheral blood was collected to extract neutrophils, and then, the levels of HSPs and cytokines were examined. The results showed that, after Pb treatment, the levels of IL-(1β, 1R, 4, 8, 10, and 12β), TGF-β4, and HSP (27, 40, 60, 70, and 90) mRNA were significantly increased and levels of IL-2 and IFN-γ mRNA were decreased compared with those in the control group. Compared with the control group, the protein levels of HSP60 and HSP70 were also increased in the Pb treatment group. Co-administration of Se (1 mg/kg/day) and Pb resulted in a reversal of the Pb-induced cytokine changes in neutrophils accompanied by a significant decrease in HSPs. Our study demonstrated that Pb could decrease the immune function via changing the expression of cytokines and HSPs in chicken neutrophils, but Se could relieve the toxic effect induced by Pb.

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Clinical Presentation and Outcomes of Diagnostic Endoscopy in Newly Presenting Children with Gastrointestinal Symptoms.

Objectives: Paediatric endoscopy is an important diagnostic tool however there is little published data to guide clinicians in selecting patients for endoscopy. This study aimed to evaluate a single centre's experience of newly presenting children focusing on presenting symptoms, investigations and diagnostic yield. Methods: Clinical factors and endoscopic plus histological findings over a six-month period were assessed. Only first diagnostic endoscopies were included. All biopsies were reviewed in a weekly histopathology multidisciplinary team meeting with a final agreed outcome. Abnormal histology was used as the gold standard for reporting abnormality. Results: 218 endoscopies were reviewed in 164 children. 65% were histologically normal (49% of children had macroscopically and histologically normal findings). Macroscopic and histological abnormalities (respectively) were 44% and 28% of oesophagogastroduodenoscopy (OGD) patients, 25% and 25% of colonoscopy alone, and 53% and 53% of those undergoing both OGD and colonoscopy (OGD&Col). For OGD-only patients, excluding those with raised anti-tissue transglutaminase antibodies (anti-tTG), vomiting led to the highest rate of abnormal histology (22%). For colonoscopy-only and OGD&Col patients, per rectum bleeding led to the highest rates of abnormal histology (14% and 29% respectively), after excluding those with laboratory abnormalities (anaemia and raised erythrocyte sedimentation rate) suggestive of inflammatory bowel disease (IBD). Conclusions: This study showed that half of all first diagnostic endoscopies in our unit had neither macroscopic nor histological abnormalities. There was discrepancy between macroscopic abnormalities and histological findings in OGD. Prospective studies are needed to develop guidelines in appropriately predicting abnormality and selecting patients for endoscopy. (C) 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Non-cirrhotic Portal Fibrosis in a Young Girl.

No abstract available

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CFTR protein function modulation therapy is finally targeting CF-related gastrointestinal disease.

No abstract available

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The PRKD1 E710D hotspot mutation is highly specific in separating polymorphous adenocarcinoma of the palate from adenoid cystic carcinoma and pleomorphic adenoma on FNA

BACKGROUND

Polymorphous adenocarcinoma (PAC) of the palatal minor salivary glands, previously known as polymorphous low-grade adenocarcinoma, is the second most common intraoral malignant salivary gland carcinoma after adenoid cystic carcinoma (ACC) and carries an excellent prognosis. Unfortunately, PAC demonstrates cytological overlap with 2 other salivary gland tumors frequently encountered in the same location, namely ACC and pleomorphic adenoma (PA). Recently, the protein kinase D1 (PRKD1) hotspot mutation E710D was demonstrated to be specific for PAC and to be present in the majority of cases. The objective of the current study was to investigate the value of PRKD1 hotspot sequencing in identifying PAC in paired fine-needle aspiration (FNA) and surgical specimens from cases of PAC, ACC, and PA.

METHODS

Paired May-Grunwald-Giemsa-stained FNA and corresponding surgical specimens were collected from 18 PAC cases, 25 ACC cases, and 21 PA cases. Both sets of specimens were subjected to dideoxynucleotide sequencing of PRKD1 exon 15, including the PRKD1 E710D hotspot.

RESULTS

Of the PAC cases, approximately 50% demonstrated identical PRKD1 E710D hotspot mutations on the FNA specimen and corresponding surgical specimen. Two ACC specimens had point mutations within the sequenced region in the FNA specimen as well as the surgical specimen, but none were located in the hotspot region. None of the PA cases demonstrated PRKD1 mutations. The specificity of the PRKD1 hotspot mutation for identifying PAC among ACC and PA cases was 100% whereas the sensitivity was 50%.

CONCLUSIONS

The PRKD1 E710D hotspot mutation is highly specific for identifying PAC on FNA among cases of ACC and PA, whereas the sensitivity is only modest. Alternative PRKD1 mutations exclude PAC, and are more suggestive of ACC. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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Age-related changes of CD4+ T cell migration and cytokine expression in germ-free and SPF mice periodontium

Publication date: March 2018
Source:Archives of Oral Biology, Volume 87
Author(s): Koichiro Irie, Takaaki Tomofuji, Daisuke Ekuni, Daiki Fukuhara, Yoko Uchida, Kota Kataoka, Shuichiro Kobayashi, Takeshi Kikuchi, Akio Mitani, Yoshihiro Shimazaki, Manabu Morita
ObjectiveIncreasing age is a potential risk factor for periodontal tissue breakdown, which may be affected by commensal flora. The aim of this study evaluated age-related changes in CD4⁺ T cells, C-C chemokine ligand 5 (CCL5), interleukin (IL)-17A, and receptor activator of nuclear factor-kappa B ligand (RANKL) expression using germ-free (GF) and conventionally reared (SPF) mice.DesignGF and SPF mice at 8 (n = 6/group) and 22 weeks old (n = 6/group) were used. Immunohistochemical analyses were performed to determine the effects of aging on protein expression in periodontal tissues. Age-related changes in alveolar bone were quantified using micro-CT analysis.ResultsSPF mice, but not GF mice, showed an age-related increase in alveolar bone loss (P < 0.01). SPF mice at 22 weeks of age increased expression of CD4⁺ T cells, CCL5, IL-17A, and RANKL compared to those at 8 weeks of age in connective tissue and alveolar bone surface (P < 0.01). Furthermore, there was increased CD4⁺ T cells, which were co-expressed with IL-17A and RANKL in SPF mice at 22 weeks of age. On the other hand, the GF mice did not show any significant differences in CD4⁺ T cells, CCL5, IL-17A and RANKL expression between the two age groups.ConclusionsSPF mice induced an age-related increase in CD4⁺ T cells co- expressed with IL-17A and RANKL, with occurring alveolar bone loss. In contrast, GF mice did not show age-related changes in CD4⁺ T cell migration and cytokine expression.



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Cardiovascular Monitoring During Video Urodynamic Studies in Persons With Spinal Cord Injury

Objective The aims of the study were to observe cardiovascular responses during video urodynamic studies and to identify correlations between autonomic dysreflexia events and video urodynamic study findings in spinal cord injuries. Design Thirty-four persons with spinal cord injury were enrolled and investigated using continuous cardiovascular monitoring during video urodynamic studies. Associations between cardiovascular responses and video study variables were analyzed. Results Bladder type–specific cardiovascular responses occurred during the study. The incidence of overactive detrusor during urodynamic study and bladder trabeculation on voiding cystourethrogram was significantly higher in autonomic dysreflexia persons with spinal cord injury (P

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Effects of Transcranial Direct Current Stimulation Plus Physical Therapy on Gait in Patients With Parkinson Disease: A Randomized Controlled Trial

Objective The aim of the study was to study the combined effects of transcranial direct current stimulation (tDCS) and physical therapy on the walking ability of patients with Parkinson disease (PD). Study Design The study used an experimental, double-blinded, randomized controlled trial. Results After intervention, group 1 (only tDCS) demonstrated a significant increase in gait speed by 0.13 to 0.14 m/sec (17.8%–19.2%) and an increase in step length by 5.9 to 6.1 cm (14.0%–14.5%), whereas group 2 (tDCS and physical therapy) revealed a significant increase in gait speed by 0.10 to 0.13 m/sec (14.9%–19.4%) and step length by 4.5 to 5.4 cm (10.6%–12.8%) and group 3 (sham tDCS and physical therapy) showed a significant increase in gait speed by 0.09 to 0.14 m/sec (13.0%–20.3%) and step length by 3.0 to 5.4 cm (6.8%–12.3%). All these results lasted for at least 8 wks after intervention. Upon comparing the parameters of gait among the three groups at every follow-up visit, no significant difference was observed. Conclusions Anodal tDCS or physical therapy could be used alone or together as a combination treatment to improve the walking speed of patients with Parkinson disease. The effects lasted for approximately 8 wks. The combination treatment was not superior to the use of tDCS or physical therapy alone.

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Effects of Light-Emitting Diode Therapy on Muscle Hypertrophy, Gene Expression, Performance, Damage, and Delayed-Onset Muscle Soreness: A Case–Control Study With a Pair of Identical Twins

No abstract available

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Effects of Myofascial Release on Pressure Pain Thresholds in Patients With Neck Pain: A Single-Blind Randomized Controlled Trial

Objective This study aimed to investigate the efficacy of myofascial release therapy (MRT) for improving pressure pain thresholds (PPTs) and pain in patients with mechanical neck pain. Design Forty-one participants with neck pain were randomly allocated to either a MRT group (five sessions) or a physical therapy (PT) group (ten sessions) for 2 wks. The multimodal PT program included ultrasound therapy (US), transcutaneous electric nerve stimulation, and massage. Visual analog scale (VAS) and PPTs in suboccipital and upper trapezius muscles were measured at baseline, at the end of treatment, and at 1 month follow-up. Results At the end of treatment, significant mean differences in VAS (−0.99, 95% confidence interval [CI] = −1.82 to −0.16), in both left (0.28, 95% CI = 0.06 to 0.50) and right (0.40, 95% CI = 0.16 to 0.63) suboccipital PPTs and in the right trapezius PPT (0.38, 95% CI = 0.07 to 0.69) were observed. At 1-month follow-up, significant mean differences were found for VAS (−1.85, 95% CI = −2.76 to −0.94) and both left (0.46, 95% CI = 0.12 to 0.80) and right (0.38, 95% CI = 0.06 to 0.69) suboccipital PPTs. Conclusions This study provides evidence that MRT could be better than a multimodal PT program for short-term improvement of pain and PPTs in patients with neck pain.

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Cochrane Rehabilitation: Organization and Functioning

No abstract available

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Pre-therapy Neural State of Bilateral Motor and Premotor Cortices Predicts Therapy Gain After Subcortical Stroke: A Pilot Study

Objective The aim of the study was to examine whether neural state of spared motor and premotor cortices captured before a therapy predicts therapy-related motor gains in chronic subcortical stroke. Design Ten survivors, presenting chronic moderate upper limb impairment, underwent proton magnetic resonance spectroscopy, magnetic resonance imaging, clinical, and kinematics assessments before a 4-wk impairment-oriented training. Clinical/kinematics assessments were repeated after therapy, and motor gain was defined as positive values of clinical upper limb/elbow motion changes and negative values of trunk motion changes. Candidate predictors were N-acetylaspartate-neuronal marker, glutamate-glutamine-indicator of glutamatergic neurotransmission, and myo-inositol-glial marker, measured bilaterally within the upper limb territory in motor and premotor (premotor cortex, supplementary motor area) cortices. Traditional predictors (age, stroke length, pre-therapy upper limb clinical impairment, infarct volume) were also investigated. Results Poor motor gain was associated with lower glutamate-glutamine levels in ipsilesional primary motor cortex and premotor cortex (r = 0.77, P = 0.01 and r = 0.78, P = 0.008, respectively), lower N-acetylaspartate in ipsilesional premotor cortex (r = 0.69, P = 0.02), higher glutamate-glutamine in contralesional primary motor cortex (r = −0.68, P = 0.03), and lower glutamate-glutamine in contralesional supplementary motor area (r = 0.64, P = 0.04). These predictors outperformed myo-inositol metrics and traditional predictors (P ≈ 0.05–1.0). Conclusions Glutamatergic state of bilateral motor and premotor cortices and neuronal state of ipsilesional premotor cortex may be important for predicting motor outcome in the context of a restorative therapy.

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Interventional Spine Considerations for Dural Ectasia in a Patient With Marfan Syndrome

For patients with Marfan syndrome who present with radicular low back pain, interventional spine providers should be familiar with dural ectasia with variable diffuse thinning of the posterior wall of the lumbar spine and sacrum. Providers should carefully weigh the risks and benefits of offering elective procedures because altered anatomy may put these patients at higher risk of dural puncture. Patient selection is essential because hydrostatic pressures and/or neural tension should also be considered as potential pain generators that may not be relieved by steroid injections. Careful evaluation of recent magnetic resonance images and vigilant procedural technique is highly recommended.

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Women Physicians Are Underrepresented in Recognition Awards From the Association of Academic Physiatrists

Objective Determine representation by gender for individual recognition awards presented to physicians by the Association of Academic Physiatrists (AAP). Design Cross-sectional survey was used. Lists of individual recognition award recipients for the 27-yr history of the AAP awards (1990–2016) were analyzed. The primary outcome measures were the total numbers of men versus women physician award recipients overall and for the past decade (2007–2016). Results No awards were given to women physicians for the past 4 yrs (2013–2016) or in half of the award categories for the past decade (2007–2016). No woman received the outstanding resident/fellow award since its inception (2010–2016). There was a decrease in the proportion of awards given to women in the past decade (2007–2016, 7 of 39 awards, 17.9%) as compared with the first 17 yrs (1990–2006, 10 of 46 awards, 21.7%). Furthermore, compared with their proportional membership within the specialty, women physicians were underrepresented for the entire 27-yr history of the AAP awards (1990–2016, 17 of 85 awards, 20%). According to the Association of American Medical Colleges, the proportion of full-time female physical medicine and rehabilitation faculty members was 38% in 1992 and 41% in 2013. Conclusions Women physicians have been underrepresented by the AAP in recognition awards. Although the reasons are not clear, these findings should be further investigated.

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Increased Reliability of Quantitative Ultrasound Measures of the Supraspinatus Tendon Using Multiple Image Analysts and Analysis Runs

Quantitative ultrasound (QUS) is an inexpensive and promising tool for sensitive measurement of tendon pathology. However, few studies have reported the psychometric properties of measurements obtained using this technique for assessments of the supraspinatus tendon. The present study was undertaken to determine the variance contributed by several sources of error (participant, ultrasound operator, image analyst, analysis session) to QUS measures of the supraspinatus tendon. Transverse images of the supraspinatus tendon were captured from eleven subjects (22 shoulders) by two ultrasonographers, and each image was analyzed by two image analysts who each completed two analysis runs. Generalizability theory and intraclass correlations were used to assess the reliability of seven QUS metrics. Measures of tendon/cartilage thickness demonstrated the greatest degree of overall dependability (ϕ = 0.84), followed by echogenicity (ϕ = 0.56), variance (ϕ = 0.55), and entropy (ϕ = 0.47), suggesting that these measures of the supraspinatus tendon may be promising metrics for assessing differences in tendon health. Interrater reliability between ultrasound operators ranged from low to moderate for different QUS metrics, but using more than one image analyst and performing repeated measurement analysis runs on each image help increase reliability of QUS measures for the supraspinatus tendon.

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