Lung recruitment prevents collapse during laparoscopy in children: A randomised controlled trial

BACKGROUND Capnoperitoneum and anaesthesia impair lung aeration during laparoscopy in children. These changes can be detected and monitored at the bedside by lung ultrasound (LUS). OBJECTIVE The aim of our study was to assess the impact of general anaesthesia and capnoperitoneum on lung collapse and the potential preventive effect of lung recruitment manoeuvres, using LUS in children undergoing laparoscopy. DESIGN Randomised controlled study. SETTING Single-institution study, community hospital, Mar del Plata, Argentina. PATIENTS Forty-two children American Society of Anesthesiologists I–II aged 6 months to 7 years undergoing laparoscopy. INTERVENTIONS All patients were studied using LUS before, during and after capnoperitoneum. Children were allocated to a control group (C-group, n=21) receiving standard protective ventilation, or to a lung recruitment manoeuvre group (RM-group) (n=21), in which lung recruitment manoeuvres were performed after recording baseline LUS images before capnoperitoneum. Loss of aeration was scored by summing a progressive grading from 0 to 3 assigned to each of 12 lung areas, based on the detection of four main ultrasound patterns: normal aeration = 0, partial loss-mild = 1, partial loss-severe = 2, total loss-consolidation = 3. MAIN OUTCOME MEASURES Lung aeration score and atelectasis assessed by ultrasound. RESULTS Before capnoperitoneum and recruitment manoeuvres in the treated group the two groups presented similar ultrasound scores (5.95 ± 4.13 vs. 5.19 ± 3.33, P = 0.5). In the RM-group, lung aeration significantly improved both during (2.71 ± 2.47) and after capnoperitoneum (2.52 ± 2.86), compared with the C-group (6.71 ± 3.54, P 

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Ultrasound in Anesthesia, Critical Care, and Pain Management

No abstract available

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Interventional Spine and Pain Procedures in Patients on Antiplatelet and Anticoagulant Medications (Second Edition): Guidelines From the American Society of Regional Anesthesia and Pain Medicine, the European Society of Regional Anaesthesia and Pain Therapy, the American Academy of Pain Medicine, the International Neuromodulation Society, the North American Neuromodulation Society, and the World Institute of Pain

The American Society of Regional Anesthesia and Pain Medicine (ASRA) 2012 survey of meeting attendees showed that existing ASRA anticoagulation guidelines for regional anesthesia were insufficient for their needs. Those surveyed agreed that procedure-specific and patient-specific factors required separate guidelines for pain and spine procedures. In response, a guidelines committee was formed. After preliminary review of published complications reports and studies, the committee stratified interventional spine and pain procedures according to potential bleeding risk: low-, intermediate-, and high-risk procedures. The ASRA regional anesthesia anticoagulation guidelines were largely deemed appropriate for the low- and intermediate-risk categories, but the high-risk category required further investigation. The first guidelines specific to interventional spine and pain procedures were published in 2015. Recent reviews evaluating bleeding complications in patients undergoing specific interventional pain procedures, the development of new regional anesthesia and acute pain guidelines, and the development of new anticoagulants and antiplatelet medications necessitate complementary updated guidelines. The authors desired coordination with the authors of the recently updated regional and acute pain anticoagulation guidelines. The latest evidence was sought through extensive database search strategies and the recommendations were evidence based when available and pharmacology driven otherwise. We could not provide strength and grading of these recommendations because there are not enough well-designed large studies concerning interventional pain procedures to support such grading. Although the guidelines could not always be based on randomized studies or on large numbers of patients from pooled databases, it is hoped that they will provide sound recommendations and the evidentiary basis for such recommendations. This publication is intended as a living document to be updated periodically with consideration of new evidence. Accepted for publication September 1, 2017. Address correspondence to: Samer Narouze, MD, PhD, Center for Pain Medicine, Western Reserve Hospital, 1900 23rd St, Cuyahoga Falls, OH 44223 (e-mail: narouzs@hotmail.com). Brian D. Sites, MD, was acting Editor-in-Chief for this submission. S.N. is a paid member of an advisory board for Abbott Laboratories. D.P. receives research funding from Abbott Laboratories and Medtronic. He serves as a consultant to Abbott, Boston Scientific, Medtronic, Nevro, and Halyard. T.D. is a paid consultant for Axonics, Abbott, Bioness, Flowonix Medical, Jazz Pharmaceuticals, Nalu, SpineThera, Saluda Medical, Mainstay Medical, Vertos, Vertiflex. R.R. receives funding from Boston Scientific, Biodelivery Science Inc, and Jazz Pharma. In addition, R.R. receives ongoing research grants from Nektar, Biogen, Pfizer, SPR Therapeutics, Neuros, Mainstay, Saluda, Nevro, and Stimwave and also serves as chair of Data Safety Monitoring Boards and Clinical Events Committee of Mainstay and Saluda trials. He also serves as a speaker for AstraZeneca. M.A.H. serves on the Clinical Events Committee for a study funded by Saluda Medical Americas, Inc. and the Data Safety Monitoring Committee for a study funded by Mainstay Medical International PLC. He otherwise declares no potential conflicts of interest. The other authors declare no conflict of interest. S.N. and H.T.B. equally contributed to the manuscript. Copyright © 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Sensory Assessment and Regression Rate of Bilateral Oblique Subcostal Transversus Abdominis Plane Block in Volunteers

Background and Objectives The analgesic effect and duration of a transversus abdominis plane (TAP) block remain controversial. Transversus abdominis plane blocks are effective for somatic/incisional pain but do not provide analgesia for visceral pain from intra-abdominal procedures. The purpose of this study was to assess the area and extent of cutaneous sensory blockade and the regression of dermatomal anesthesia after bilateral oblique subcostal TAP block. Methods This observational, prospective clinical study consisted of 12 healthy volunteers. All volunteers received a bilateral oblique subcostal TAP block under real-time ultrasound guidance with 20 mL of 0.375% ropivacaine. The anterior abdominal cutaneous area was divided into 3 parts (midabdomen, left-lateral abdomen, right-lateral abdomen) using 2 lines drawn in a parasagittal fashion 5 cm lateral to the midline. The area of cutaneous sensory blockade involving the anterior abdomen was assessed 30 minutes after institution of the block using a cold stimulus. This was followed by repeated measurements using a cold stimulus applied along parasagittal lines drawn 3 cm lateral to the midline at 0.5, 6, 10, 14, 18, 22, and 26 hours after blockade. Results The area of cutaneous sensory blockade of the abdomen was 332 (SD, 73) cm2; that of the midabdomen was 253 (SD, 29) cm2, which represented an average of 90% of the area of the midabdomen; and that of the lateral abdominal wall (combination of left-lateral abdomen and right-lateral abdomen) was 79 (SD, 62) cm2, which represented an average of 26% of total lateral abdominal area. Dermatomes T7–T12 of the midabdomen were successfully blocked in all volunteers after using the bilateral oblique subcostal technique. However, T6 and L1 were only variably blocked. The area of cutaneous sensory block of the anterior abdomen regressed over the ensuing 22 hours in the following manner: 90%, 87%, 73%, 50%, 22%, 3%, and 0% at 0.5, 6, 10, 14, 18, 22, and 26 hours, respectively. Conclusions Bilateral oblique subcostal TAP block produces a widespread cutaneous sensory blockade with a consistent dermatomal distribution in the midabdomen for a considerable effective duration. Accepted for publication July 17, 2017. Address correspondence to: Quanguang Wang, MD, Department of Anesthesiology, the First Affiliated Hospital of Wenzhou Medical University, Shangcai Village, South White Elephant Town, Wenzhou City, Zhejiang Province, China 325000 (e-mail: quanguangwang@sina.com). Y.C. and K.S. contributed equally to this work and should be considered co–first authors. The authors declare no conflict of interest. Y.C. helped design the study, prepare the manuscript, and collect and analyze data. K.S. helped design the study, prepare the manuscript, and analyze data. Y.X. helped analyze data and prepare the manuscript. X.Z. helped conduct the study. T.J.P. participated in manuscript preparation and critical manuscript review and approved the final manuscript. X.X. helped design the study, prepare the manuscript, and analyze data. Q.W. helped design the study, prepare the manuscript, and analyze data. Copyright © 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Ethnic Differences Identified by Pain Sensitivity Questionnaire Correlate With Clinical Pain Responses

Background and Objectives The Pain Sensitivity Questionnaire, English version (PSQ-E), is predictive of pain-related responses to experimental stimuli. Ethnic differences have been noted in experimental measures of pain sensation using quantitative sensory testing. The present study sought to determine if the PSQ-E also identified similar ethnic differences. Methods Fifty-seven subjects who self-identified as African Americans (AAs) and who were scheduled to undergo a low-back interventional procedure completed the PSQ-E and other questionnaires. Their data were compared with an age-, sex-, and opioid usage–matched sample of 57 self-identified non-Hispanic white (NHW) subjects. Pain ratings on a visual analog scale (VAS) were obtained following 2 standardized injections of subcutaneous lidocaine (VAS1—infiltration in hand, VAS2—infiltration of procedural site). Correlations between PSQ-E scores, VAS measures, and other inventories were tested. Results The PSQ-E scores and clinical and experimental pain scores were all significantly elevated in AA compared with NHW patients (P

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Erector Spinae Plane Block for Surgery of the Posterior Thoracic Wall in a Pediatric Patient

Objective Historically, regional anesthesia for surgery on the posterior thoracic wall has been limited to neuraxial and paravertebral nerve blocks. The erector spinae plane (ESP) block is a novel technique that anesthetizes the dorsal rami of the spinal nerves innervating the posterior thoracic wall. We report the use of the ESP block for this clinical application in a pediatric patient. Case Report A healthy 3-year-old girl was scheduled for resection of a giant paraspinal lipoma extending over the T4–T7 dermatomes. She received a preoperative single-shot ESP block at the level of the T1 transverse process; this level was chosen to avoid the lipoma and cover the planned surgical incision over the T2–T8 dermatomes. Hemodynamic stability and excellent pain control perioperatively were obtained with minimal anesthetic requirements and no systemic analgesics apart from fentanyl administered for induction of anesthesia. Return to normal function (ambulation, feeding, and communication) was achieved within 2 hours after surgery. A pain score of 0 on the FLACC (Face, Legs, Activity, Cry, Consolability) scale was maintained until discharge from the hospital 4 hours after the surgery. First analgesic use was 18 hours after hospital discharge. No complications were reported. Conclusions The ESP block is an effective option for surgery on the posterior thoracic wall. The opioid- and anesthetic-sparing effects exhibited in this case facilitated rapid postoperative recovery and early discharge. Accepted for publication July 30, 2017. Address correspondence to: Maria Alejandra Hernandez, MD, Department of Anesthesia, Pereira Rossell Pediatric Hospital, Bulevar Gral, Artigas 1550, 11600 Montevideo, Uruguay (e-mail: Hernandez.malaquina.alejandra@gmail.com). This work should be attributed to the Department of Anesthesia. Dr Orlando Alassia Children's Hospital, Santa Fe, Argentina. The authors declare no conflict of interest. Copyright © 2017 by American Society of Regional Anesthesia and Pain Medicine.

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Local Application of Ultrasound Attenuates Neuropathic Allodynia and Proinflammatory Cytokines in Rats After Thoracotomy

Background and Objectives We aimed to investigate the effect of therapeutic ultrasound (TU) on pain sensitivity and the concentration inflammatory cytokines in a thoracotomy rat model. Methods Rats were distributed randomly into 4 groups: (1) sham operated, (2) thoracotomy and rib retraction (TRR), (3) TRR rats that received TU (TRR + TU-1), and (4) TRR rats that received TU with the ultrasound turned off (TRR + TU-0). Ultrasound was set at 1-MHz frequency (1.0-W/cm2 intensity and 100% duty cycle for 5 minutes), began on postoperative day (POD) 10, and then continued once per day, 5 days a week for 3 weeks. Results The TRR and TRR + TU-0 rats encountered tactile hypersensitivity from PODs 10 to 28. Mechanical withdrawal thresholds were increased (all P

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A morphological comparison of the extraforaminal ligament between the cervical and thoracic regions

Abstract

Purpose

The current study was conducted to clarify the morphology of the extraforaminal ligament (EFL) at the cervicothoracic junction and to compare the attachment of the EFL and the positional relation between the EFL and the spinal nerves, additionally to clarify the details within the connecting bundles at the cervicothoracic junction.

Materials and methods

The EFLs from the 4th cervical to the 4th thoracic vertebrae were dissected in 56 sides of 28 Japanese cadavers (11 males, 17 females). The range of age was 62.0–99.0 years. In addition, connecting bundles were analyzed by histological examination.

Results

Ventral to the spinal nerve, the capsulotransverse ligament (CTL), transforaminal ligament (TFL) and the ligament between the 7th cervical vertebra and the 1st rib were attached to the transverse process and rib. The EFL ventral to the 1st thoracic nerve was not observed in all sides. Dorsal to the spinal nerve, the anterior part of the superior costotransverse ligament (ASCL) and the ligament homologous to the ASCL were attached to the transverse process and rib. The superior radiating ligament (SRL) and the ligament homologous to the SRL were identified. The connecting bundles identified between the 7th cervical and the 1st thoracic nerve were histologically confirmed to consist of nerves and vessels.

Conclusions

The EFLs at the cervicothoracic junction were found to be homologous. The connecting bundles were observed between the 7th cervical and the 1st thoracic nerve. Interestingly, the 1st thoracic level alone might be a unique level at the cervicothoracic junction.

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A morphological comparison of the extraforaminal ligament between the cervical and thoracic regions

Abstract

Purpose

The current study was conducted to clarify the morphology of the extraforaminal ligament (EFL) at the cervicothoracic junction and to compare the attachment of the EFL and the positional relation between the EFL and the spinal nerves, additionally to clarify the details within the connecting bundles at the cervicothoracic junction.

Materials and methods

The EFLs from the 4th cervical to the 4th thoracic vertebrae were dissected in 56 sides of 28 Japanese cadavers (11 males, 17 females). The range of age was 62.0–99.0 years. In addition, connecting bundles were analyzed by histological examination.

Results

Ventral to the spinal nerve, the capsulotransverse ligament (CTL), transforaminal ligament (TFL) and the ligament between the 7th cervical vertebra and the 1st rib were attached to the transverse process and rib. The EFL ventral to the 1st thoracic nerve was not observed in all sides. Dorsal to the spinal nerve, the anterior part of the superior costotransverse ligament (ASCL) and the ligament homologous to the ASCL were attached to the transverse process and rib. The superior radiating ligament (SRL) and the ligament homologous to the SRL were identified. The connecting bundles identified between the 7th cervical and the 1st thoracic nerve were histologically confirmed to consist of nerves and vessels.

Conclusions

The EFLs at the cervicothoracic junction were found to be homologous. The connecting bundles were observed between the 7th cervical and the 1st thoracic nerve. Interestingly, the 1st thoracic level alone might be a unique level at the cervicothoracic junction.

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Retroperitoneal ectopic brain: Case report and literature review

Heterotopic neural tissue (HNT) has been identified in many sites. In our literature review, we have found only two cases of HNT located in the retroperitoneum. As far as we know, cytological features of HNT have not been described. We here report a case of retroperitoneal HNT diagnosed by fine-needle aspiration (FNA) cytology and subsequent resection. Our patient was a male infant born at 26 weeks' gestation. A retroperitoneal solid-cystic lesion measuring 3.8 cm was identified by abdominal ultrasound. FNA was performed and cytology showed highly cellular smears with single cells and masses of fibrillary material. Cells were small with rounded irregular nuclei and variable cytoplasm. Multinucleated cells, cells with neuronal morphology, calcifications, and hemosiderophages could also be seen. The lesion was excised and histology showed fibrillary areas, glial cells, neurons, and ependymal cells. Synaptophysin, GFAP, and EMA were expressed in distinct areas and cell types. No recurrences were observed.

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Letter to the editor: Uncommon cells in cerebrospinal fluid cytology

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Cytological features in eight patients with ALK-rearranged lung cancer

Background

ALK-rearranged lung cancer has been recently identified. Although signet-ring cell morphology and mucinous cribriform pattern are considered to be characteristic of ALK-rearranged lung cancer. Some studies have also suggested cytological features.

Methods

This study investigated cytological features of ALK-rearranged lung cancer in eight patients.

Results

Cytologically, the tumor cell group varied from isolated to large clusters. Small nucleoli, fine granular to vesicular chromatin, and nuclear groove were observed in all patients. Furthermore, extracellular and intracellular mucin and signet-ring cells were identified in five patients.

Conclusion

This study demonstrated that the presence of extracellular and intracellular mucin, signet-ring cells, small nucleoli, fine granular to vesicular chromatin, and nuclear groove in cytological samples may be a diagnostic clue for ALK-rearranged lung cancer.

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Endoscopic ultrasound guided fine-needle aspiration: What variables influence diagnostic yield?

Background

Endoscopic ultrasound (EUS) guided fine-needle aspiration (FNA) plays an important role in the diagnosis of various lesions. We sought to determine factors that influence the diagnostic yield of EUS–FNA, specifically, the presence of a cytopathologist, FNA site, and the endoscopist's skill.

Methods

The data on cytopathologist's availability, duration of procedure, number of passes made, and diagnostic material for cell block (CB) preparation was collected over an 18 months period.

Results

230 specimens (218 patients) were obtained from pancreas (114), lymph node (64), submucosal lesions of the gastrointestinal tract (27), liver (8), and miscellaneous (17) sites. The results were classified as informative (77.8%) and non-informative (NI) (22.2%). The NI rate was significantly high, when a cytopathologist was absent (P = .0008). As the likelihood of cytopathologist's presence increased from 35.8% to 82.9%, the CB quality increased (P < .0001). In the absence of a cytopathologist, the likelihood of NI result increased more than 2-fold (P = .03) and of an inadequate CB increased 3-fold (P < .0001). The more experienced endoscopist "C" (compared to the less experienced "A + B") was less likely to get inadequate material (40.5% vs. 66.3%) (P = .0001).

Conclusion

The diagnostic yield of EUS–FNA is significantly related to the presence of an on-site cytopathologist and endoscopist's skill in procuring diagnostic material.

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Amyloidosis diagnosed in cytology specimen of pleural effusion: A case report

Amyloidosis is a rare condition resulting from extracellular deposition of amyloid, a fibrillary material derived from various precursor proteins. Involvement of the pleura by amyloidosis is a rare but serious complication. Pleural amyloidosis is primarily diagnosed by identifying amyloid deposition by histology on pleural biopsy specimens. Hereby, we report a case of systemic amyloidosis where we were able to identify amyloid in a pleural effusion specimen sent for cytopathology evaluation. A 59-year-old male with newly diagnosed multiple myeloma and systemic amyloidosis underwent therapeutic thoracentesis. The H&E stained cell block sections revealed a single, less than one millimeter focus of waxy material surrounded by a rim of reactive mesothelial cells suspicious for amyloid deposit in a background of fibrin, lymphocytes, and reactive mesothelial cells. The focus stained salmon pink with Congo-red special stain and showed apple-green birefringence under polarized light. Our finding suggests that pleural involvement in patients with systemic amyloidosis can be identified on effusion specimens and avert the need for more invasive procedures like pleural or pulmonary parenchymal biopsies.

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Hypopharyngeal Evaluation in Obstructive Sleep Apnea with Awake Flexible Laryngoscopy: Validation and Updates to Cormack-Lehane and Modified Cormack-Lehane Scoring Systems

Abstract

Objective

To validate the use of Cormack-Lehane and Modified Cormack-Lehane scoring systems to classify patterns of hypopharyngeal airway visualization seen during awake flexible laryngoscopy among patients with obstructive sleep apnea.

Study Design

Validation study using samples collected from a prospective database.

Setting

University Medical Center.

Participants

Data was obtained from a retrospective review of a prospective database of flexible fiberoptic examination recordings in 274 consecutive OSA subjects (Stanford Sleep Medicine/Surgery Clinic).

Main Outcome Measures

Single still images from awake fiberoptic laryngoscopy examinations of the vocal cords from 90 different patients were presented to 2 experts and 4 novice raters. Raters used two grading systems (Cormack-Lehane scale and Modified Cormack-Lehane) to rate vocal cord visualization. Percent agreement and Cohen's kappa statistical analysis were used to evaluate inter-rater reliability and intra-rater reliability for each grading system. Feedback from the participants was then used to propose updates to further improve upon the existing grading scales for their applicability to awake flexible endoscopy.

Results

The Cormack-Lehane and Modified Cormack-Lehane scale both communicate un-obstructed and restricted views of the vocal cords reliably. Compared to the 4-grade scale, however, a modified 5-grade Vocal Cord Grading System allows for better objective communication of common variations in hypopharyngeal airway visualization.

Conclusion

We propose a 5-Grade Vocal Cord Grading System that builds upon existing grading systems to allow for efficient and reliable communication of hypopharyngeal airway examination during awake fiberoptic laryngoscopy.

This article is protected by copyright. All rights reserved.

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Severe ophthalmoplegia and myocarditis following the administration of pembrolizumab

Publication date: Available online 26 December 2017
Source:European Journal of Cancer
Author(s): Fadi Nasr, Elie El Rassy, Georgina Maalouf, Carine Azar, Fadi Haddad, Jeanine Helou, Caroline Robert




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When politicians really decide that nation health is a top priority: the Danish model

Publication date: Available online 26 December 2017
Source:European Journal of Cancer
Author(s): Marc Hamoir




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Neural stem cells in neuropsychiatric disorders

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Roberto Sacco, Emanuele Cacci, Gaia Novarino
The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies.



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Adaptive and reversible resistance to Kras inhibition in pancreatic cancer cells

Activating mutations in KRAS are the hallmark genetic alterations in pancreatic ductal adenocarcinoma (PDAC) and the key drivers of its initiation and progression. Longstanding efforts to develop novel KRAS inhibitors have been based on the assumption that PDAC cells are addicted to activated KRAS, but this assumption remains controversial. In this study, we analyzed the requirement of endogenous Kras to maintain survival of murine PDAC cells, using an inducible shRNA-based system that enables temporal control of Kras expression. We found that the majority of murine PDAC cells analyzed tolerated acute and sustained Kras silencing by adapting to a reversible cell state characterized by differences in cell morphology, proliferative kinetics, and tumor-initiating capacity. While we observed no significant mutational or transcriptional changes in the Kras-inhibited state, global phosphoproteomic profiling revealed significant alterations in cell signaling, including increased phosphorylation of focal adhesion pathway components. Accordingly, Kras-inhibited cells displayed prominent focal adhesion plaque structures, enhanced adherence properties, and increased dependency on adhesion for viability in vitro. Overall, our results call into question the degree to which PDAC cells are addicted to activated KRAS, by illustrating adaptive non-genetic and non-transcriptional mechanisms of resistance to Kras blockade. However, by identifying these mechanisms, our work also provides mechanistic directions to develop combination strategies that can help enforce the efficacy of KRAS inhibitors.

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GADD45{beta} loss ablates innate immunosuppression in cancer

T cell exclusion from the tumour microenvironment (TME) is a major barrier to overcoming immune escape. Here we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumour-associated inflammation and T cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma (HCC) and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of pro-inflammatory tumour-associated macrophages (TAM) and intratumoural immune infiltration, thereby diminishing oncogenesis. Our results provide a basis to interpret clinical evidence that elevated expression of GADD45B confers poor clinical outcomes in most human cancers. Further, they suggest a therapeutic target in GADD45β for re-programming TAM to overcome immunosuppression and T cell exclusion from the TME.

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Germinal centers determine the prognostic relevance of tertiary lymphoid structures and are impaired by corticosteroids in lung squamous cell carcinoma

In solid tumors, the presence of lymph node-like structures called tertiary lymphoid structures (TLS) is associated with improved patient survival. However, little is known about how TLS form in cancer, how their function affects survival, and whether they are affected by cancer therapy. In this study, we used multi-spectral microscopy, quantitative pathology and gene expression profiling to analyze TLS formation in human lung squamous cell carcinoma (LSCC) and in an experimental model of lung TLS induction. We identified a niche of CXCL13+ perivascular and CXCL12+LTB+ and PD-L1+ epithelial cells supporting TLS formation. We also characterized sequential stages of TLS maturation in LSCC culminating in the formation of germinal centers (GC). In untreated patients, TLS density was the strongest independent prognostic marker. Further, TLS density correlated with GC formation and expression of adaptive immune response-related genes. In patients treated with neoadjuvant chemotherapy, TLS density was similar but GC formation was impaired and the prognostic value of TLS density was lost. Corticosteroids are co-administered with chemotherapy to manage side effects in LSCC patients, so we evaluated whether they impaired TLS development independently of chemotherapy. TLS density and GC formation were each reduced in chemotherapy-naive LSCC patients treated with corticosteroids before surgery, compared to untreated patients, a finding that we confirmed in the experimental model of lung TLS induction. Overall, our results highlight the importance of GC formation in TLS during tumor development and treatment.

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Survival of cancer stem-like cells under metabolic stress via CaMK2{alpha}-mediated upregulation of sarco/endoplasmic reticulum calcium ATPase expression

Purpose: Cancer cells grow in an unfavorable metabolic milieu in the tumor microenvironment and are constantly exposed to metabolic stress such as chronic nutrient depletion. Cancer stem-like cells (CSCs) are intrinsically resistant to metabolic stress, thereby surviving nutrient insufficiency and driving more malignant tumor progression. In this study, we aimed to demonstrate the potential mechanisms by which CSCs avoid Ca2+-dependent apoptosis during glucose deprivation. Experimental design: We investigated cell viability and apoptosis under glucose deprivation, performed genome-wide transcriptional profiling of paired CSCs and parental cells, studied the effect of calcium/calmodulin-dependent protein kinase 2 alpha (CaMK2α) gene knockdown, and investigated the role of nuclear factor kappa B (NFB) in CSCs during time-dependent Ca2+-mediated and glucose deprivation-induced apoptosis. We also observed the effect of combined treatment with 2-deoxy-d-glucose, a metabolic inhibitor that mimics glucose deprivation conditions in mouse xenograft models, and thapsigargin, a specific inhibitor of SERCA. Results: We demonstrated the coordinated up-regulation of sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) in CSCs. SERCA, in turn, is transcriptionally regulated by CaMK2α via NFB activation. Combined treatment with 2-deoxy-d-glucose and thapsigargin, a specific inhibitor of SERCA, significantly reduced tumor growth compared to that in untreated control animals or those treated with the metabolic inhibitor alone. Conclusions: The current study provides compelling evidence that CaMK2α acts as a key anti-apoptosis regulator in metabolic stress-resistant CSCs by activating NFB. The latter induces expression of SERCA, allowing survival in glucose-deprived conditions. Importantly, our combination therapeutic strategy provides a novel approach for the clinical application of CSC treatment.

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Exploration of a Novel Intermediate Response Endpoint in Immunotherapy Clinical Studies

Purpose: Both objective response rate (ORR) and progression-free survival as defined by RECIST are weakly associated with overall survival (OS) in trials evaluating immunotherapy drug products.  We proposed a novel intermediate response endpoint (IME) for evaluating immunotherapies.  Experimental Design: We defined IME response as having no non-target lesion progression, no new lesion appearance, and reaching a target lesion response determined by baseline tumor burden, tumor reduction depth, and tumor change dynamic within one year after randomization. Database used consisted of data from randomized active-controlled immunotherapy trials. Criterion for IME was developed based on patient level data from a training dataset, and further evaluated using independent testing dataset. A patient level responder analysis comparing OS between patients with and without an IME response was conducted using combined data.  Association between trial level OS hazard ratio (HR) and IME odds ratio was analyzed using a weighted linear regression model. Results: A total of 5806 patients from 9 randomized studies were included in the database. At patient level, patients with IME response had improved OS compared to non-responders (HR 0.09). At trial level, association between OS and IME was moderate (R2 = 0.68). Conclusion: The IME was moderately associated with OS, and the association appeared to be stronger than the association observed between RECIST-defined ORR and OS.  However, the analyses conducted in this research are exploratory and further evaluation is needed before using this endpoint in future studies.

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Vaccination protects against invasive HPV-associated cancers

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Neurophysiological correlates of word processing deficits in isolated reading and isolated spelling disorders

Publication date: Available online 24 December 2017
Source:Clinical Neurophysiology
Author(s): Sarolta Bakos, Karin Landerl, Jürgen Bartling, Gerd Schulte-Körne, Kristina Moll
ObjectiveIn consistent orthographies, isolated reading disorders (iRD) and isolated spelling disorders (iSD) are nearly as common as combined reading-spelling disorders (cRSD). However, the exact nature of the underlying word processing deficits in isolated versus combined literacy deficits are not well understood yet.MethodsWe applied a phonological lexical decision task (including words, pseudohomophones, legal and illegal pseudowords) during ERP recording to investigate the neurophysiological correlates of lexical and sublexical word-processing in children with iRD, iSD and cRSD compared to typically developing (TD) 9-year-olds.ResultsTD children showed enhanced early sensitivity (N170) for word material and for the violation of orthographic rules compared to the other groups. Lexical orthographic effects (higher LPC amplitude for words than for pseudohomophones) were the same in the TD and iRD groups, although processing took longer in children with iRD. In the iSD and cRSD groups, lexical orthographic effects were evident and stable over time only for correctly spelled words.ConclusionsOrthographic representations were intact in iRD children, but word processing took longer compared to TD. Children with spelling disorders had partly missing orthographic representations.SignificanceOur study is the first to specify the underlying neurophysiology of word processing deficits associated with isolated literacy deficits.



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Hemitransdomal versus Dome-Binding Suture

Facial plast Surg
DOI: 10.1055/s-0036-1598014

The dome-binding suture (DBS) and hemitransdomal suture (HTS) are suture techniques used to narrow and define the nasal tip. The DBS can create a pinched, unnatural appearance, while the HTS puts the lateral crus in a more favorable orientation. This allows a natural contour between the nasal tip and alar lobule while maintaining alar margin support. Objective measurement of the rotational axis of the lateral crus between the DBS and the HTS has not been reported in the literature. To determine whether the DBS or HTS technique results in a more favorable rotational axis of the lateral crus as measured by the alar surface septal angle (ASSA). Open rhinoplasty with cephalic trim and placement of a DBS or HTS was performed in 6 cadaveric heads, for a total of 12 lower lateral cartilages at the VirtuOHSU Simulation and Surgical Training Center at Oregon Health and Science University (OHSU). ASSA measurements were taken at baseline and after placement of either a DBS or HTS. A total of 36 ASSA measurements were obtained. The median baseline ASSA prior to suture placement was 142 degrees (interquartile range [IQR]: 131.5–145 degrees), following DBS placement was 141 degrees (IQR: 33–150.5 degrees), and following HTS placement was 112 degrees (IQR: 108–117 degrees). There was no statistically significant difference of ASSA measurements between baseline and DBS placement (p = 0.24), but there was a statistically significant difference between baseline and HTS (p < 0.0001) and between DBS and HTS (p < 0.0001). The HTS technique creates a more favorable rotational axis of the lateral crus as compared with the DBS, as measured by the ASSA. This study provides objective data to support the use of the HTS for nasal tip contouring.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Frontal Fibrosing Alopecia: A Retrospective Analysis of 72 Patients from a German Academic Center

Facial plast Surg
DOI: 10.1055/s-0037-1615281

Frontal fibrosing alopecia (FFA) describes the scarring, band-like recession of the frontotemporal hairline. Treatment is difficult, and currently, no evidence-based therapy exists. The purpose of this study is to report clinical features and treatment responses in a large cohort of patients with FFA. The authors analyzed a series of 72 patients with a clinical or histologic diagnosis of FFA. A total of 70 patients were female (97.2%), and 2 were male (2.8%). In females, the first onset of FFA was postmenopausal in 81.4% (n = 57). Documented eyebrow loss was present in 61.1% (n = 44), whereas involvement of eyelashes and body hair was reported in only 4.2% (n = 3) and 5.6% (n = 4), respectively. Clinical symptoms were itching (40.3%, n = 29) and trichodynia (4.2%, n = 3) in the alopecic area. Virtually all patients were treated with topical high-potency steroids. Additional treatments were topical tacrolimus, systemic retinoids, and hydroxychloroquine. A total of 48 patients (66.7%) received a combination of high-potency steroids with topical pimecrolimus. In this subgroup, subjective improvement or disease stabilization was reported by 64.6% (n = 31), and the hairline was stabilized on average after 9 to 12 months of therapy. The combination therapy of topical high-potency steroids with pimecrolimus may be an effective and steroid-saving treatment for FFA.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Otoplasty Online Information: A Comprehensive Analysis of the Websites and Videos that Patients View Regarding Cosmetic Ear Surgery

Facial plast Surg
DOI: 10.1055/s-0037-1615280

Physicians should be aware of both websites and videos available online regarding the otoplasty procedure to provide quality care. This study systematically analyzes the authorships, reliability, quality, and readability of the websites, as well as the authorships and primary objectives of the videos regarding otoplasty. Validated instruments were used to analyze the reliability, quality, and readability of websites, and videos were systematically categorized and analyzed. A Google search was conducted, and the first five pages of results were included in this study. After excluding unrelated websites, the remaining 44 websites were categorized by authorship (physician, patient, academic, or unaffiliated) and were analyzed using the validated DISCERN instrument for reliability and quality, as well as various other validated instruments to measure readability. A YouTube search was also conducted, and the first 50 relevant videos were included in the study. These videos were categorized by authorship and their primary objective. Website authorships were physician-dominated. Reliability, quality, and overall DISCERN score differ between the four authorship groups by a statistically significant margin (Kruskall–Wallis test, p < 0.05). Unaffiliated websites were the most reliable, and physician websites were the least reliable. Academic websites were of the highest quality, and patient websites were of the lowest quality. Readability did not differ significantly between the groups, though the readability measurements made showed a general lack of material easily readable by the general public. YouTube was likewise dominated by physician-authored videos. While the physician-authored videos sought mainly to inform and to advertise, patient-authored videos sought mainly to provide the patient's perspective. Academic organizations showed very little representation on YouTube, and the YouTube views on otoplasty videos were dominated by the top 20 videos, which represented over 93% of the total views of videos included in this study.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Is thoracic outlet syndrome common after nuss procedure?

We try to discuss the results of Nagasao and Colleagues, claiming thoracic outlet syndrome is not a rare complication after Nuss procedure. According to our experience, this syndrome is not common.

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Re: antibiotic prophylaxis in breast reduction surgery: a systematic review and meta-analysis.

We read with interest the article by Drs. Zapata-Copete, Aguilera-Mosquera and Garcia-Perdomo recommending the use of antibiotic prophylaxis in lowering surgical site infection in breast reduction surgery1. The study, however, is open to criticism in its design and originality of outcomes.

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The Roles of Vowel Fronting, Lengthening, and Listener Variables in the Perception of Vocal Femininity

Purpose

The goal of this study was to test whether fronting and lengthening of lax vowels influence the perception of femininity in listeners whose dialect is characterized as already having relatively fronted and long lax vowels in male and female speech.

Method

Sixteen English words containing the /ɪ ɛ ʊ ɑ/ vowels were produced by a male speaker with 2 degrees of vowel fronting. Then, the vowel duration was manipulated in 3 steps. Thirty-nine listeners from the Southern United States judged how feminine each word sounded to them on an interval scale.

Results

The results of mixed-effects modeling showed that the words with more fronted and longer variants of the vowels were perceived as more feminine than the same words with less fronted and shorter variants of the vowels. These effects, however, were modulated by the vowel type, listener's area of upbringing, and gender.

Conclusions

Fronting (except for /ʊ/) and lengthening of lax vowels make words sound more feminine for Southern listeners, which has implications for clients who wish to modify the perception of femininity invoked by their speech. The relative strength of the gender and regional associations of these vowel characteristics should be further examined across dialects.

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F0 Characteristics of Newsreaders on Varied Emotional Texts in Tamil Language

The objective of this study was to profile speaking F0 and its variations in newsreaders on varied emotional texts.

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Immune Mechanisms of Oral Immunotherapy

Publication date: Available online 26 December 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Michael D. Kulis, Sarita U. Patil, Erik Wambre, Brian P. Vickery
Oral immunotherapy (OIT) has reproducibly demonstrated successful desensitization in food-allergic subjects completing clinical trials and, in some studies, sustained unresponsiveness. These clinical outcomes have been associated with characteristic modifications in the allergen-specific immune response, but a detailed synthesis of OIT's mechanisms of action is lacking. In this Rostrum, we review the current evidence regarding the human immune response to OIT, explore possible mechanisms, and identify knowledge gaps for future research.



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A Propensity Matched Comparison for Open and Endovascular Treatment of Post-carotid Endarterectomy Restenosis

Publication date: Available online 26 December 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Walter Dorigo, Aaron Fargion, Elena Giacomelli, Raffaele Pulli, Fabrizio Masciello, Sara Speziali, Giovanni Pratesi, Carlo Pratesi
ObjectivesTo compare results of open and endovascular management of post-carotid endarterectomy (CEA) restenosis.MethodsThis was a retrospective single centre matched case control study. From 2005 to 2015, 148 consecutive interventions for post-CEA restenosis were performed: 80 cases received carotid artery stenting (CAS) and 68 cases received redo CEA. Propensity score based matching was performed in a 1:1 ratio to compare outcomes. Coronary artery disease, degree of the carotid restenosis, timing of the re-intervention with respect to the primary intervention (greater or less than 24 months) and the presence of ipsilateral brain lesions were the covariates included in the matching. Peri-operative outcomes were analysed with χ² tests, while late results were estimated by Kaplan–Meier methods.ResultsAfter propensity matching, 32 CAS interventions were matched with 32 redo CEAs. There were no peri-operative deaths or strokes. Cranial nerve palsy occurred in seven patients in the redo CEA group. Median duration of follow-up was 36 months (interquartile range 24–60; range 6–120). The estimated 5 year survival rate was 94% in the CAS group and 72% in the redo CEA group (p=.1, log rank 2.4). There were no significant differences between the groups in terms of stroke free survival. In the CAS group, no severe restenosis were found, while in the redo CEA group eight patients had severe restenosis or occlusion of the operated carotid artery. Freedom from secondary restenosis at 4 years was 100% in the CAS group and 72.5% in the redo CEA group (p=.005, log rank 7.9). The corresponding figures in terms of freedom from secondary re-intervention were 100% and 83%, respectively (p=.02, log rank 4.8).ConclusionsCAS and redo CEA in patients with post-CEA restenosis provided similar peri-operative results in a sample of equivalent patients. CAS patients had better follow-up results in terms of secondary restenosis and re-interventions. Further analysis is required with a larger number of patients and a longer follow-up time.



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Inhibition of autophagy potentiates the anti-metastasis effect of phenethyl isothiocyanate through JAK2/STAT3 pathway in lung cancer cells

Abstract

Phenethyl isothiocyanate (PEITC) is a natural compound abundant in cruciferous vegetables. PEITC possesses anti-tumor effect in various human malignances. Our previous study has shown that benzyl isothiocyanates (BITC) induce autophagy in lung cancer cells. However, whether autophagy play a role in the inhibitory effect of PEITC on lung cancer metastasis is unclear. In this study, we found that PEITC suppressed migration and invasion of lung cancer cells by regulating MMP2. It also induced autophagy, evidenced by the formation of acidic vesicular organelles (AVOs), the punctate pattern of LC3, the accumulation of LC3-II, and the expression of Beclin-1. Inhibition of autophagy by 3-MA and chloroquine (CQ) or knock down of Beclin-1 enhanced PEITC-caused metastasis inhibition. JAK2/STAT3 pathway was suppressed by PEITC, and further inhibited by 3-MA and CQ or Beclin-1 knock down, as a result of decreased expression of p-JAK2 and p-STAT3. Blocking JAK2/STAT3 pathway by inhibitor AG490 and Stattic suppressed cell migration and decreased the expression of MMP2, MMP9, Twist and c-Myc. Further in vivo study showed that PEITC inhibited tumor growth, induced autophagy and suppressed JAK2/STAT3 pathway, and inhibitor CQ enhanced this effect. Taken together, our results demonstrate that PEITC inhibits metastasis potential of lung cancer cells, and induces autophagy. The autophagy induced by PEITC preserves metastasis potential of lung cancer cells, via activation of JAK2/STAT3 pathway. Inhibition of autophagy enhanced the inhibitory effect of PEITC on metastasis potential of lung cancer cells. Our finding suggests that targeting autophagy could be a promising strategy for anti-metastasis therapies. This article is protected by copyright. All rights reserved

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Binaural Speech Understanding With Bilateral Cochlear Implants in Reverberation

Purpose

The purpose of this study was to investigate whether bilateral cochlear implant (CI) listeners who are fitted with clinical processors are able to benefit from binaural advantages under reverberant conditions. Another aim of this contribution was to determine whether the magnitude of each binaural advantage observed inside a highly reverberant environment differs significantly from the magnitude measured in a near-anechoic environment.

Method

Ten adults with postlingual deafness who are bilateral CI users fitted with either Nucleus 5 or Nucleus 6 clinical sound processors (Cochlear Corporation) participated in this study. Speech reception thresholds were measured in sound field and 2 different reverberation conditions (0.06 and 0.6 s) as a function of the listening condition (left, right, both) and the noise spatial location (left, front, right).

Results

The presence of the binaural effects of head-shadow, squelch, summation, and spatial release from masking in the 2 different reverberation conditions tested was determined using nonparametric statistical analysis. In the bilateral population tested, when the ambient reverberation time was equal to 0.6 s, results indicated strong positive effects of head-shadow and a weaker spatial release from masking advantage, whereas binaural squelch and summation contributed no statistically significant benefit to bilateral performance under this acoustic condition. These findings are consistent with those of previous studies, which have demonstrated that head-shadow yields the most pronounced advantage in noise. The finding that spatial release from masking produced little to almost no benefit in bilateral listeners is consistent with the hypothesis that additive reverberation degrades spatial cues and negatively affects binaural performance.

Conclusions

The magnitude of 4 different binaural advantages was measured on the same group of bilateral CI subjects fitted with clinical processors in 2 different reverberation conditions. The results of this work demonstrate the impeding properties of reverberation on binaural speech understanding. In addition, results indicate that CI recipients who struggle in everyday listening environments are also more likely to benefit less in highly reverberant environments from their bilateral processors.

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Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements

Background

Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction.

Methods

We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively.

Results

There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores.

Conclusions

Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated.

Trial registration number

ClinicalTrials.gov: NCT02069509.

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The sinonasal microbiota, neural signaling, and depression in chronic rhinosinusitis

Background

The complex relationships between the human microbiota, the immune system, and the brain play important roles in both health and disease, and have been of increasing interest in the study of chronic inflammatory mucosal conditions. We hypothesized that the sinonasal microbiota may act as a modifier of interkingdom neural signaling and, subsequently, mental health, in the upper respiratory inflammatory condition chronic rhinosinusitis (CRS). In this study we investigated associations between the sinonasal microbiota; local concentrations of the neurotransmitters serotonin, dopamine, and γ-aminobutyric acid (GABA); and depression severity in a cohort of 14 CRS patients and 12 healthy controls.

Methods

Subject demographics, clinical severity scores, depression index scores, and sinonasal swab and mucus samples were collected at the time of surgery. Bacterial communities were characterized from swabs by 16S rRNA gene-targeted sequencing and quantified by quantitative polymerase chain reaction. Mucus concentrations of the neurotransmitters serotonin, dopamine, and GABA were quantified by enzyme-linked immunosorbent assay.

Results

Several commonly "health-associated" sinonasal bacterial taxa were positively associated with higher neurotransmitter concentrations and negatively associated with depression severity. In contrast, several taxa commonly associated with an imbalanced sinonasal microbiota negatively associated with neurotransmitters and positively with depression severity. Few significant differences were identified when comparing between control and CRS subject groups, including neurotransmitter concentrations, depression scores, or sinonasal microbiota composition or abundance.

Conclusion

The findings obtained lend support to the potential for downstream effects of the sinonasal microbiota on neural signaling and, subsequently, brain function and behavior.

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Osteologic analysis of ethnic differences in supernumerary ethmoidal foramina: implications for endoscopic sinus and orbit surgery

Background

Knowledge of the position of the ethmoidal arteries is critical to enable safe endoscopic sinus and orbital surgery. The presence of a third or "middle" ethmoid variant has recently become more relevant as endoscopic intraconal surgery continues to advance. The purpose of this study was to quantify the presence of supernumerary (ie, over 2) ethmoid foramina in different ethnicities and genders.

Methods

Morphometric osteologic measurements were performed in 273 orbits. Prevalence of supernumerary ethmoid foramina and orbital length data were obtained from human skulls of Asian (n = 54), Caucasian (n = 70), African (n = 39), Hispanic (n = 49), and Middle Eastern (n = 61) derivation. Correlations between gender, ethnicity, symmetry, orbital floor, and lamina papyracea length were assessed by analysis of variance, paired t test, and χ² test.

Results

Supernumerary foramina were identified in 95 of 273 orbits (34.79%). A significantly higher prevalence was seen in Asian (42.59%), African (41.02%), and Hispanic (41.00%) skulls as compared with Caucasian (25.71%) and Middle Eastern (22.95%) skulls (p < 0.05 for all). The length of the orbital floor was significantly shorter in the Asian (3.35 ± 1.52 cm) specimens (p < 0.01). Asians were found to have the highest risk of ethmoid artery injury compared with the other ethnic groups (ratio of number of supernumerary foramina to orbital floor length = 0.72).

Conclusion

Supernumerary ethmoidal foramina were common among all orbits studied. Orbits of Asian and African derivation had significantly greater numbers of ethmoidal foramina, both unilaterally and symmetrically and within a shorter orbital length, suggesting a greater proximity between the ethmoidal vessels. Surgeons should be alert to the possible presence of middle ethmoidal vessels during endoscopic sinus and orbital approaches.

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Implementing The Paris System for Reporting Urinary Cytology results in a decrease in the rate of the “atypical” category and an increase in its prediction of subsequent high-grade urothelial carcinoma

BACKGROUND

In the current study, the authors evaluated the impact of implementing The Paris System for Reporting Urinary Cytology (PSRUC) on the prevalence of various cytological categories and their association with a subsequent diagnosis of high-grade urothelial carcinoma (HGUC).

METHODS

A comparative study was conducted over the 6-month period before PSRUC implementation (2013), including 1653 patients and 2371 specimens versus a 6-month period after implementation of the PSRUC (2016), including 1478 patients and 2392 specimens. The following cytological categories were correlated with the subsequent biopsy result when available (355 cases): negative for HGUC (NHGUC), atypical urothelial cells (AUC), suspicious for HGUC, and HGUC.

RESULTS

Although 18.6% of specimens were diagnosed as AUC in 2013, the percentage was 14.4% in 2016 (P < .0001). Concurrently, the prevalence of the "benign" category increased from 2013 to 2016 (75.4% vs 80%; P < .0001). After implementation of the PSRUC, there was no significant change noted with regard to the association between the categories of NHGUC, suspicious for HGUC, and HGUC and a subsequent HGUC biopsy diagnosis. However, the predictive value of an AUC diagnosis increased from 28.3% to 46.1% (P = .077). Most important, after the implementation of the PSRUC, there was a significant difference noted with regard to the predictive association for HGUC between the NHGUC and AUC groups (13.6% vs 46.1%; P = .003), a difference that was not found to be statistically significant before implementation of the PSRUC (18% vs 28.3%; P = .175).

CONCLUSIONS

There was a much higher risk of HGUC conveyed by AUC cytology after implementation of the PSRUC, justifying more aggressive investigations of patients who receive an AUC diagnosis. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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The Mendelsohn Maneuver and its Effects on Swallowing: Kinematic Analysis in Three Dimensions Using Dynamic Area Detector CT

Abstract

This study investigated the effects of Mendelsohn maneuver with three-dimensional kinematic analysis. Nine female speech-language pathologists (nine females, mean ± SD 27.1 ± 3.5 years old) underwent 320-row area detector scan during swallows of 4-ml nectar-thick liquid using with no maneuvers (control) and with Mendelsohn maneuver (MM). Critical event timing (hyoid, soft palate, epiglottis, laryngeal vestibule, true vocal cords (TVC), UES), hyoid and laryngeal excursion, cross-sectional area of UES, and volume of pharyngeal cavity and bolus were measured and compared between two swallows. In MM, all the events were significantly prolonged with delayed termination time (p < 0.05) except UES opening. The onset, termination, and duration of UES opening were not significantly affected by MM nor was timing of bolus transport. The hyoid bone was positioned significantly higher at maximum displacement (p = 0.011). Pharyngeal constriction ratio was 95.1% in control and 100% of all subjects in MM. Duration of minimum pharyngeal volume was significantly longer in MM than in control (p = 0.007). The MM produces several distinct changes in the kinematics of swallowing in healthy subjects with no dysphagia. The changes in the timing and magnitude of hyoid displacements and prolonged closure of the pharynx during swallowing suggest the utility of MM for improving the safety and efficiency of swallowing in selected cases.

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Effect of lumbar spinal fusion surgery on the association of self-report measures with objective measures of physical function

Publication date: March 2018
Source:Gait & Posture, Volume 61
Author(s): Felix Stief, Andrea Meurer, Johanna Wienand, Michael Rauschmann, Marcus Rickert
BackgroundSelf-report measures are used to evaluate surgery outcome but are not necessarily indicative of actual disabilities.Research questionThe aim of the present study was to determine the association between self-report assessments of quality of life and objective measures of function in patients with symptomatic lumbar degenerative disease. Additionally, we evaluated the effect of lumbar spinal fusion surgery on this relationship.MethodsBefore and 6 month after surgery 26 patients completed self-report questionnaires and assessments of 3D gait analysis and trunk range of motion (ROM) during standing.ResultsBefore surgery, questionnaires were not correlated with any of the gait parameters and with only 2 trunk ROM parameters. Six month after surgery, the questionnaires showed 12 significant correlations with gait parameters and 19 with trunk ROM parameters. A better Oswestry Disability Index (ODI) (r = 0.464, p = .026), EQ-5D (r = −0.440, p = .036), and EQ VAS (r = −0.472, p = .023) score were correlated with a reduced anterior thorax tilt during walking. Maximum forward flexion of the trunk during standing was correlated with a better EQ-5D (r = 0.684, p = .001) and ODI (r = −0.560, p = .008) score as well as with reduced pain scores.SignificanceThe lack of association between self-reported questionnaires and objective measures of function before surgery was likely due to psychological distress, correlating with emotional and cognitive function rather than true functional capacities. The influence of these psychological factors might be reduced after surgery due to a reduction of low back pain. To obtain an accurate assessment of impairment, there is a need to evaluate function by measuring objective physiologic parameters that are unsusceptible to voluntary or affective influences.



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Reply to Distinguishing between CISNET model results versus CISNET models

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Distinguishing between CISNET model results versus CISNET models

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Molecular testing for thyroid nodules: Review and current state

Thyroid nodules affect nearly two-thirds of the world population. Fine-needle biopsy with cytologic evaluation remains the diagnostic test of choice to distinguish benign from malignant thyroid nodules yet fails to discriminate as benign or malignant in up to one-third of cases. This review discusses the limitation of current cytopathologic evaluation, the development of thyroid molecular testing, and the strengths and limitations of commercially available tests. Initial cytomolecular testing sought to identify specific gene mutations associated with thyroid cancer. Although the presence of a mutation was strongly associated with cancer, the likelihood of identifying a mutation was low; therefore, the test had low sensitivity. Subsequent tests developed have sought to improve the accuracy of cytomolecular testing for thyroid fine-needle aspirations, both to reassure patients and providers when malignancy may be absent and to confirm the malignancy when present. The development of cytomolecular testing for thyroid nodules has informed and improved current understanding of thyroid nodule formation and progression. When used appropriately and with clear understanding of the advantages and disadvantages, cytomolecular testing has the potential to improve patient care in the setting of indeterminate thyroid nodules by helping to guide both the need for and the extent of thyroid surgery. Cancer 2017. © 2017 American Cancer Society.

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Feasibility of systematic handgrip strength testing in digestive cancer patients treated with chemotherapy: The FIGHTDIGO study

BACKGROUND

Handgrip strength (HGS) is a widely studied noninvasive test. Weak strength (dynapenia) seems to be associated with high morbidity and mortality in different populations, notably oncology populations. Despite this, HGS testing is not used in daily practice in oncology. The study was aimed at evaluating the feasibility and acceptability of HGS testing in patients with digestive cancer treated with ambulatory chemotherapy.

METHODS

In this prospective, single-center study, enrolled patients were followed for 6 months. Two consecutive bilateral measures were performed with a Jamar dynamometer during each patient's appointments in the unit for intravenous treatment. A questionnaire was completed by patients and medical team members.

RESULTS

There were 203 consecutive patients, and 201 were recruited. In all, 1704 of 1716 measurements (99.3%) were performed, and 201 patients (99.0%) performed at least 1 measure; 190 (94.5%) performed all expected measures. One hundred sixty-four of 171 participating patients (95.9%) found the test easy to perform, and 167 (97.7%) did not find the test restrictive. All of the 14 medical team members found the test easy to perform, unrestrictive, and undisruptive in their daily practice.

CONCLUSIONS

HGS testing is routinely feasible, inexpensive, and well accepted by patients and medical teams in an ambulatory digestive cancer unit. Cancer 2017. © 2017 American Cancer Society.

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Intended and unintended consequences: Ethics, communication, and prognostic disclosure in pediatric oncology

BACKGROUND

The majority of patients desire all available prognostic information, but some physicians hesitate to discuss prognosis. The objective of the current study was to examine outcomes of prognostic disclosure among the parents of children with cancer.

METHODS

The authors surveyed 353 parents of children with newly diagnosed cancer at 2 tertiary cancer centers, and each child's oncologist. Using multivariable logistic regression, the authors assessed associations between parental report of elements of prognosis discussions with the oncologist (quality of information/communication and prognostic disclosure) and potential consequences of these discussions (trust, hope, peace of mind, prognostic understanding, depression, and anxiety). Analyses were stratified by oncologist-reported prognosis.

RESULTS

Prognostic disclosure was not found to be associated with increased parental anxiety, depression, or decreased hope. Among the parents of children with less favorable prognoses (<75% chance of cure), the receipt of high-quality information from the oncologist was associated with greater peace of mind (odds ratio [OR], 5.23; 95% confidence interval [95% CI], 1.81-15.16) and communication-related hope (OR, 2.54; 95% CI, 1.00-6.40). High-quality oncologist communication style was associated with greater trust in the physician (OR, 2.45; 95% CI, 1.09-5.48) and hope (OR, 3.01; 95% CI, 1.26-7.19). Accurate prognostic understanding was less common among the parents of children with less favorable prognoses (OR, 0.39; 95% CI, 0.17-0.88). Receipt of high-quality information, high-quality communication, and prognostic disclosure were not found to be significantly associated with more accurate prognostic understanding.

CONCLUSIONS

The results of the current study demonstrate no evidence that disclosure is associated with anxiety, depression, or decreased hope. Communication processes may increase peace of mind, trust, and hope. It remains unclear how best to enhance prognostic understanding. Cancer 2017. © 2017 American Cancer Society.

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The Mendelsohn Maneuver and its Effects on Swallowing: Kinematic Analysis in Three Dimensions Using Dynamic Area Detector CT

Abstract

This study investigated the effects of Mendelsohn maneuver with three-dimensional kinematic analysis. Nine female speech-language pathologists (nine females, mean ± SD 27.1 ± 3.5 years old) underwent 320-row area detector scan during swallows of 4-ml nectar-thick liquid using with no maneuvers (control) and with Mendelsohn maneuver (MM). Critical event timing (hyoid, soft palate, epiglottis, laryngeal vestibule, true vocal cords (TVC), UES), hyoid and laryngeal excursion, cross-sectional area of UES, and volume of pharyngeal cavity and bolus were measured and compared between two swallows. In MM, all the events were significantly prolonged with delayed termination time (p < 0.05) except UES opening. The onset, termination, and duration of UES opening were not significantly affected by MM nor was timing of bolus transport. The hyoid bone was positioned significantly higher at maximum displacement (p = 0.011). Pharyngeal constriction ratio was 95.1% in control and 100% of all subjects in MM. Duration of minimum pharyngeal volume was significantly longer in MM than in control (p = 0.007). The MM produces several distinct changes in the kinematics of swallowing in healthy subjects with no dysphagia. The changes in the timing and magnitude of hyoid displacements and prolonged closure of the pharynx during swallowing suggest the utility of MM for improving the safety and efficiency of swallowing in selected cases.

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The Gut Microbiome in Neuromyelitis Optica

Abstract

Neuromyelitis optica (NMO) is a rare, disabling, sometimes fatal central nervous system inflammatory demyelinating disease that is associated with antibodies ("NMO IgG") that target the water channel protein aquaporin-4 (AQP4) expressed on astrocytes. There is considerable interest in identifying environmental triggers that may elicit production of NMO IgG by AQP4-reactive B cells. Although NMO is considered principally a humoral autoimmune disease, antibodies of NMO IgG are IgG1, a T-cell-dependent immunoglobulin subclass, indicating that AQP4-reactive T cells have a pivotal role in NMO pathogenesis. When AQP4-specific proliferative T cells were first identified in patients with NMO it was discovered that T cells recognizing the dominant AQP4 T-cell epitope exhibited a T helper 17 (Th17) phenotype and displayed cross-reactivity to a homologous peptide sequence within a protein of Clostridium perfringens, a commensal bacterium found in human gut flora. The initial analysis of gut microbiota in NMO demonstrated that, in comparison to healthy controls (HC) and patients with multiple sclerosis, the microbiome of NMO is distinct. Remarkably, C. perfringens was the second most significantly enriched taxon in NMO, and among bacteria identified at the species level, C. perfringens was the one most highly associated with NMO. Those discoveries, along with evidence that certain Clostridia in the gut can regulate the balance between regulatory T cells and Th17 cells, indicate that gut microbiota, and possibly C. perfringens itself, could participate in NMO pathogenesis. Collectively, the evidence linking microbiota to humoral and cellular immunity in NMO underscores the importance for further investigating this relationship.

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Gastric Pyloric Gland Adenoma: A Multicenter Clinicopathologic Study of 67 Cases

Abstract

Aims

There is limited information regarding the clinicopathologic and immunohistochemical characteristics of gastric pyloric gland adenomas (PGAs).

Methods and Results

Sixty seven cases of gastric PGA from 57 patients were analyzed. PGAs occurred with similar frequency in men and women (47.4% and 52.6%, respectively) with a mean age of 66 years. Most presented in the gastric body/fundus (67.2%). Fifteen cases (22.4%) developed in a background of autoimmune gastritis (AIG), whereas normal mucosa was seen in 35.8%. Only 16.4% (11 cases) developed in patients with a genetic predisposition, most commonly familial adenomatous polyposis. Low-grade lesions had a mean size of 1.5 cm, while PGAs with high-grade dysplasia (HGD) or adenocarcinoma had a mean size of 3.5 cm (p < 0.001) and more commonly showed tubulovillous architecture (50.0% versus 25.6% in low-grade dysplasia; p = 0.040). Most PGAs (61.2%) co-expressed MUC5AC and MUC6 (mixed type), which was significantly associated with HGD or adenocarcinoma (p = 0.013). AIG was also associated with HGD (p = 0.027), but genetic predisposition did not correlate with the grade of dysplasia (p = 0.793). The recurrence rate of PGA was similar for high- (11.8%) and low-grade lesions (7.4%) (p = 0.624).

Conclusions

The risk of HGD increases with the size of PGA, tubulovillous architecture, and the presence of AIG as well as mixed immunophenotype. Since the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be completely excised if possible, particularly if they are large or show high-grade features.

This article is protected by copyright. All rights reserved.

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Corrigendum to “Projections from the lowest lumbar and sacral-caudal segments to the cerebellar cortex in the rat: An anterograde tracing study” [Neurosci. Res. 114 (January) (2017) 43–54]

Publication date: Available online 26 December 2017
Source:Neuroscience Research
Author(s): Matsuo Matsushita




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An insertion mutation in HOXC13 underlies pure hair and nail ectodermal dysplasia with lacrimal duct obstruction

Abstract

Pure hair and nail ectodermal dysplasia (PHNED; MIM 602032, 614929, and 614931) is an autosomal recessive ED that is characterized by hypotrichosis and nail dystrophy only, without further ectodermal or non-ectodermal alterations. To date, homozygous mutations in three genes have been reported to cause PHNED: KRT85 (MIM 602767), encoding keratin, type II cuticular Hb5 like; KRT74 (MIM 608248), encoding keratin, type II cytoskeletal 74; and HOXC13 (MIM 142976), encoding Homeobox C13. Here, we studied the genetic basis of PHNED in an Iranian kindred, displaying double consanguinity (Fig. 1a-g).

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Response to: ‘Human orf complicated by epidermolysis acquisita’

Abstract

Dear editor, we read with great interest the article 'Human orf complicated by epidermolysis bullosa acquisita' by Zeulgaray and colleagues.¹ Recently, a Moroccan patient who contracted orf (fig. 1a) after slaughtering a sheep during Eid Al-Adha was admitted to our hospital and developed a similar pruritic vesiculobullous eruption predominantly on the hands and forearms (fig. 1b). Hematoxylin and eosin staining of punch biopsies from areas of the vesicullobullous eruption showed spongiotic dermatitis with eosinophilia, most consistent with an id reaction.

This article is protected by copyright. All rights reserved.

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Aberrant DNA methylation is associated with aggressive clinicopathological features and poor survival in cutaneous melanoma

Abstract

Background

Promoter methylation of tumor suppressor genes (TSGs) has recently been implicated in the pathogenesis of several types of cancer. Regarding melanoma, over a hundred genes that contribute to its pathogenesis have been identified to be aberrantly hypermethylated. This is a retrospective observational study that aims to analyze the prevalence of CpG island methylation in a series of primary melanoma, to identify the associations with the main clinicopathological features, and to explore the prognostic significance of methylation in melanoma survival.

Materials and Methods

DNA methylation was analyzed using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in a series of 170 melanoma formalin-fixed paraffin embedded (FFPE) tumor samples. The relationship between the methylation status, known somatic mutations and clinicopathological features was evaluated. Disease-free survival (DFS) and overall survival (OS) were displayed by the Kaplan-Meier method.

Results

In the entire cohort, one or more genes were detected to be methylated in 55% of the patients. The most prevalent methylated genes were RARB 31%, PTEN 24%, APC 16%, CDH13 16%, ESR1 14%, CDKN2A 6%, and RASSF1 5%. An association between aberrant methylation and aggressive clinicopathological features was observed (older age, increased Breslow, presence of mitosis and ulceration, fast-growing melanomas, advancing stage, and TERT mutations). Furthermore, Kaplan-Meier survival analysis showed a correlation of methylation and poorer DFS and overall survival OS.

Conclusions

Aberrant methylation of TSGs is a frequent event in melanoma. It is associated to aggressive clinicopathological features and poorer survival. Epigenetic alterations may represent a significant prognostic marker with utility in routine practice.

This article is protected by copyright. All rights reserved.

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A possible association between BP230-type bullous pemphigoid and dementia: report of two elderly cases

Bullous pemphigoid (BP) is the most common autoimmune blistering disease, and it features itchy oedematous erythemas and tense bullae on the whole body most commonly in the elderly. BP180 is the most common autoantigens of BP, and BP230 is the only target of autoantibodies in approximately 8% of patients with BP¹. It has been reported that elderly patients with BP sometimes have comorbidities associated with neurological disease (ND) including dementia². BP antigens and their isoforms can be identified in skin as well as in neuronal tissues, suggesting that exposure of the neuronal antigen may lead to an immune reaction against the epithelial isoform³. Here, we describe two elderly cases of BP with dementia in which the autoantibodies reacted to BP230 but not to BP180 (BP230-BP).

This article is protected by copyright. All rights reserved.

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Point mutation in p14ARF-specific exon 1β of CDKN2A causing familial melanoma and astrocytoma

Abstract

Rarely, melanoma is dominantly inherited, with CDKN2A mutations accounting for >85% of mutation-positive families (1). CDKN2A encodes two, non-homologous proteins, p16 and p14^ARF, with individually unique first exons (1α and 1β, respectively) and alternative reading frames. Over 95% of the CDKN2A mutations in familial melanoma occur in the p16 transcript (1).

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Outcomes of surgery for hepatocellular carcinoma with tumor thrombus in the inferior vena cava or right atrium

Abstract

The prognosis of hepatocellular carcinoma (HCC) patients with tumor thrombus (TT) in the inferior vena cava (IVC) or right atrium (RA) is extremely poor. We reviewed the recent surgical treatments and outcomes of this form of advanced HCC. TT is classified into three types according to its anatomic location relative to the heart: the inferior hepatic type (type I), where the TT is in the IVC below the diaphragm; the superior hepatic type (type II), where the TT is in the IVC above the diaphragm, but still outside the RA; and the intracardiac type (type III), where the TT is above the diaphragm and has entered the RA. Type I can be treated relatively easily by standard radical hepatectomy. For type II, the intrathoracic IVC is approached via the abdominal cavity and an incision in the diaphragm with total hepatic vascular exclusion (THVE). For type III, hepatectomy plus thrombectomy is generally performed under cardiopulmonary bypass. If the TT is only just inside the RA, THVE can be performed by mobilizing the liver caudally. The median overall survival of HCC patients with TT in the IVC or RA, who undergo curative resection, is 19.0–30.8 months. As postoperative recurrence is likely to develop, even after curative surgery, effective postoperative adjuvant chemotherapy is required.

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Recent advances in the study of hepatitis B virus covalently closed circular DNA

Abstract

Chronic hepatitis B infection is caused by hepatitis B virus (HBV) and a total cure is yet to be achieved. The viral covalently closed circular DNA (cccDNA) is the key to establish a persistent infection within hepatocytes. Current antiviral strategies have no effect on the pre-existing cccDNA reservoir. Therefore, the study of the molecular mechanism of cccDNA formation is becoming a major focus of HBV research. This review summarizes the current advances in cccDNA molecular biology and the latest studies on the elimination or inactivation of cccDNA, including three major areas: (1) epigenetic regulation of cccDNA by HBV X protein, (2) immune-mediated degradation, and (3) genome-editing nucleases. All these aspects provide clues on how to finally attain a cure for chronic hepatitis B infection.

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Tau burden and the functional connectome in Alzheimer’s disease and progressive supranuclear palsy

Abstract

Alzheimer's disease and progressive supranuclear palsy (PSP) represent neurodegenerative tauopathies with predominantly cortical versus subcortical disease burden. In Alzheimer's disease, neuropathology and atrophy preferentially affect 'hub' brain regions that are densely connected. It was unclear whether hubs are differentially affected by neurodegeneration because they are more likely to receive pathological proteins that propagate trans-neuronally, in a prion-like manner, or whether they are selectively vulnerable due to a lack of local trophic factors, higher metabolic demands, or differential gene expression. We assessed the relationship between tau burden and brain functional connectivity, by combining in vivo PET imaging using the ligand AV-1451, and graph theoretic measures of resting state functional MRI in 17 patients with Alzheimer's disease, 17 patients with PSP, and 12 controls. Strongly connected nodes displayed more tau pathology in Alzheimer's disease, independently of intrinsic connectivity network, validating the predictions of theories of trans-neuronal spread but not supporting a role for metabolic demands or deficient trophic support in tau accumulation. This was not a compensatory phenomenon, as the functional consequence of increasing tau burden in Alzheimer's disease was a progressive weakening of the connectivity of these same nodes, reducing weighted degree and local efficiency and resulting in weaker 'small-world' properties. Conversely, in PSP, unlike in Alzheimer's disease, those nodes that accrued pathological tau were those that displayed graph metric properties associated with increased metabolic demand and a lack of trophic support rather than strong functional connectivity. Together, these findings go some way towards explaining why Alzheimer's disease affects large scale connectivity networks throughout cortex while neuropathology in PSP is concentrated in a small number of subcortical structures. Further, we demonstrate that in PSP increasing tau burden in midbrain and deep nuclei was associated with strengthened cortico-cortical functional connectivity. Disrupted cortico-subcortical and cortico-brainstem interactions meant that information transfer took less direct paths, passing through a larger number of cortical nodes, reducing closeness centrality and eigenvector centrality in PSP, while increasing weighted degree, clustering, betweenness centrality and local efficiency. Our results have wide-ranging implications, from the validation of models of tau trafficking in humans to understanding the relationship between regional tau burden and brain functional reorganization.

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iSepsis- “Less is More”: The New paradigm in Critical Care

"Less is More": The New paradigm in Critical Care

EMCrit Project by Paul Marik.

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Surgical anatomy of neurovascular structures related to ventral C1–2 complex: an anatomical study

Abstract

Objective

Transoral odontoidectomy and ventral C1–2 stabilization are important surgical procedures, performed to decompress ventral spinal cord, and to stabilize craniovertebral junction. These procedures require knowledge regarding surgical anatomy of neurovascular structures ventral to the C1–2 complex. The aim of this study is to evaluate the relationships between neurovascular structures and bony landmarks in ventral atlantoaxial complex.

Materials and methods

This study was performed on six formaldehyde fixed cadaveric head and neck specimens. Relevant anatomical parameters, including distances from the midsagittal line to internal carotid arteries (ICA), vertebral arteries (VA), and hypoglossal nerves (HN), were measured using electronic calipers.

Results

The mean distance between ICA and midsagittal line was observed as 26.13 mm at the level of axis and 24.67 mm at the level of the atlas. The mean distance between VA and midsagittal line was observed as 15.38 mm at the level of axis and 26.54 mm at the level of the atlas. The mean distance between HN and midsagittal line was observed as 33.27 and 33.58 mm at the level of the atlas and axis, respectively.

Conclusion

This study confirmed that ICA and HN proceeded ventrally or laterally along the lateral aspect of the C1 lateral mass; therefore, the area located ventrally along the medial components of the C1 lateral mass was the safe zone for anterior surgical approach.

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Surgical anatomy of neurovascular structures related to ventral C1–2 complex: an anatomical study

Abstract

Objective

Transoral odontoidectomy and ventral C1–2 stabilization are important surgical procedures, performed to decompress ventral spinal cord, and to stabilize craniovertebral junction. These procedures require knowledge regarding surgical anatomy of neurovascular structures ventral to the C1–2 complex. The aim of this study is to evaluate the relationships between neurovascular structures and bony landmarks in ventral atlantoaxial complex.

Materials and methods

This study was performed on six formaldehyde fixed cadaveric head and neck specimens. Relevant anatomical parameters, including distances from the midsagittal line to internal carotid arteries (ICA), vertebral arteries (VA), and hypoglossal nerves (HN), were measured using electronic calipers.

Results

The mean distance between ICA and midsagittal line was observed as 26.13 mm at the level of axis and 24.67 mm at the level of the atlas. The mean distance between VA and midsagittal line was observed as 15.38 mm at the level of axis and 26.54 mm at the level of the atlas. The mean distance between HN and midsagittal line was observed as 33.27 and 33.58 mm at the level of the atlas and axis, respectively.

Conclusion

This study confirmed that ICA and HN proceeded ventrally or laterally along the lateral aspect of the C1 lateral mass; therefore, the area located ventrally along the medial components of the C1 lateral mass was the safe zone for anterior surgical approach.

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Postoperative mortality and morbidity following non-cardiac surgery in a healthy patient population

Abstract

Purpose

Perioperative mortality ranges from 0.4% to as high as nearly 12%. Currently, there are no large-scale studies looking specifically at the healthy surgical population alone. The primary objective of this study was to report 30-day mortality and morbidity in healthy patients and define any risk factors.

Methods

Using the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) dataset, all patients assigned an American Society of Anesthesiologists physical status (ASA PS) classification score of 1 or 2 were included. Further patients were excluded if they had a comorbidity or underwent a procedure not likely to classify them as ASA PS 1 or 2. Multivariable logistic regression was performed to identify predictors of the outcomes, in which odds ratios (OR) and 95% confidence intervals (95% CI) were reported.

Results

There were 687,552 healthy patients included in the final analysis. Following surgery, 0.7, 7.0, and 0.7 per 1000 persons experienced 30-day mortality, sepsis, and stroke or myocardial infarction, respectively. Healthy patients greater than 80 years of age had the highest odds for mortality (OR 17.7, 95% CI 12.4–25.1, p < 0.001). Case duration was associated with increased mortality, especially in cases greater than or equal to 6 h (OR 3.0, 95% CI 2.0–4.5, p < 0.001).

Conclusions

Thirty-day mortality and morbidity is, as expected, lower in the healthy surgical population. Age may be an indication to further risk stratify patients that are ASA PS 1 or 2 to better reflect perioperative risk.

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Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO)

Abstract

Objective

To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck.

Methods

In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings.

Results

Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease.

Conclusion

Despite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

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Re-irradiation with curative intent in patients with squamous cell carcinoma of the head and neck: a national survey of usual practice on behalf of the Italian Association of Radiation Oncology (AIRO)

Abstract

Objective

To report the results of a national survey investigating the pattern of practice of curative re-irradiation (ReRT) for recurrent squamous cell carcinoma of the head and neck.

Methods

In March 2016, a 22-item, 4-section questionnaire was sent to all Italian Radiation Oncology centers. Sections were focused on assessing the expertise level of each center and collecting specific information on reRT prescription modalities in the adjuvant and definitive settings.

Results

Overall, 77 centers completed the survey. The majority (50/77, 64.9%) of participating radiation oncologists were senior consultants (> 10 years of experience). Of the responding centers, 63 (81.8%) performed curative ReRT, while 14 (18.1%) did not, mainly (5/14, 35.7%) due to the avoidance of severe toxicity. The use of adjuvant ReRT was reported by less than half of the interviewed radiation oncologists (36/77, 46.7%). In case of unresectable local recurrence, definitive ReRT was claimed to be adopted in 55/77 (71.4%) for non-nasopharyngeal and 47/77 (61%) for nasopharyngeal cancer. The preferred treatment technique was Intensity Modulated Radiation Therapy (IMRT) followed by Stereotactic Body Radiation Therapy (SBRT). When IMRT was applied, the most common (19/55 responders, 34.5%) selection of treatment volume consisted of the Gross Tumor Volume (GTV) + 0.5 cm margin to account for microscopic disease.

Conclusion

Despite the absence of definitive evidence-based recommendations, a possible consideration for ReRT in case of unresectable recurrent head and neck cancer was reported by over 80% of radiation oncologists taking part in the national survey.

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Enzalutamide and CXCR7 inhibitor Combination Treatment Suppresses Cell Growth and Angiogenic Signaling in Castration-Resistant Prostate Cancer Models

Abstract

Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4-2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub-G1) in VCaP and C4-2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p-EGFR (Y1068), p-AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133-4 patient-derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 μm²) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control-treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors. This article is protected by copyright. All rights reserved.

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The sphingosine kinase 2 inhibitor ABC294640 displays anti-non-small cell lung cancer activities in vitro and in vivo

Abstract

Non-small cell lung cancer (NSCLC) accounts for about 85-90% of lung cancer cases, and is the number one killer among cancers in the U.S. The majority of lung cancer patients do not respond well to conventional chemo- and/or radio-therapeutic regimens, and have a dismal 5-year survival rate of ∼15%. The recent introduction of targeted therapy and immunotherapy gives new hopes to NSCLC patients, but even with these agents, not all patients respond, and responses are rarely complete. Thus, there is still an urgent need to identify new therapeutic targets in NSCLC and develop novel anti-cancer agents. Sphingosine kinase 2 (SphK2) is one of the key enzymes in sphingolipid metabolism. SphK2 expression predicts poor survival in NSCLC patients, and is associated with Gefitinib-resistance. In this study, the anti-NSCLC activities of ABC294640, the only first-in-class orally available inhibitor of SphK2, were explored. The results obtained indicate that ABC294640 treatment causes significant NSCLC cell apoptosis, cell cycle arrest, and suppression of tumor growth in vitro and in vivo. Moreover, lipidomics analyses revealed the complete signature of ceramide and dihydro(dh)-ceramide species in the NSCLC cell-lines with or without ABC294640 treatment. These findings indicate that sphingolipid metabolism targeted therapy may be developed as a promising strategy against NSCLC. This article is protected by copyright. All rights reserved.

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