Αρχειοθήκη ιστολογίου

Δευτέρα 31 Οκτωβρίου 2022

Higher levels of cerebrospinal fluid and plasma neurofilament light in human immunodeficiency virus-associated distal sensory polyneuropathy

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Abstract
Background
Neurofilament light chain (NFL) concentrations, reflecting axonal damage, are seen in several polyneuropathies, but have not been studied in HIV distal sensory polyneuropathy (DSP). We evaluated NFL in CSF and plasma in relation to DSP in people with HIV (PWH) from two independent cohorts, and in people without HIV (PWoH).
Methods
Cohort 1 consisted of PWH from the CHARTER Study. Cohort 2 consisted of PWH and PWoH from the HIV Neurobehavioral Research Center (HNRC). We evaluated DSP signs and symptoms in both cohorts. Immunoassays measured NFL in CSF for all and for plasma as well in Cohort 2.
Results
Cohort 1 consisted of 111 PWH, mean ± SD age 56.8 ± 8.32 years, 15.3% female, 38.7% black, 49.6% white, current CD4+ T-cells (median, IQR) 532/µL (295, 785), 83.5% with plasma HIV RNA ≤ 50 copies/mL. Cohort 2 consisted of 233 PWH of similar demographics to PWH in Cohort 1, but also 51 PWoH, t ogether age 58.4 ± 6.68 years, 41.2% female, 18.0% black, Hispanic, non-Hispanic white 52.0%, 6.00% white. In both cohorts of PWH, CSF and plasma NFL were significantly higher in both PWH with DSP signs. Findings were similar, albeit not significant, for PWoH. The observed relationships were not explained by confounds.
Conclusions
Both plasma and CSF NFL were elevated in PWH and PWoH with DSP. The convergence of our findings with others demonstrates that NFL is a reliable biomarker reflecting peripheral nerve injury. Biomarkers such as NFL might provide, validate, and optimize clinical trials of neuroregenerative strategies in HIV DSP.
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Outcome and associated predictors for non‐surgical management of large cyst‐like periapical lesions: A CBCT‐based prospective cohort study.

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Abstract

Aim

The aim of this cone-beam computed tomography (CBCT) based study was to evaluate the outcome of non-surgical root canal treatment (RCT) performed for the management of large cyst like periapical lesions (LCPL) and to identify the predictive factors affecting healing.

Methodology

54 subjects (77 permanent maxillary anterior teeth) with LCPL (>10mm) of endodontic origin were included. A single operator performed standardised multi-visit RCT. Patients were clinically and radiographically examined at 6,12 months and a CBCT scan was taken at 24 months. Two independent blinded evaluators measured the pre and postoperative volume of periapical lesions on CBCT scans using ITK snap software (version 3.8.0-beta-20181028-win64). The outcome was assessed as a percentage change in lesion volume and dichotomized as success (resolved/reduced) or failure (unchanged/enlarged). Ten pre-operative (gender; age; intraoral draining sinus, soft tissue swelling, tooth discoloration, pulp canal obliteration, open apex, root resorption, cortical bone defect and lesion volume) and four intraoperative (apical extent and density of root filling; number of treatment visits and type of root filling) predictive factors were observed. Bivariate and stepwise multivariable linear regres sion analysis was performed to identify independent predictors affecting treatment outcomes. The significance level was set at 5%.

Results

A recall rate of 88% was achieved. The success rate of RCT was 82.2% (8.9% resolved, 73.3% reduced). Median lesion volume reduction was 75% (IQR 61%-93%). No pre or intra-operative factors were related to treatment failure. However, presence of preoperative cortical bone defect (palatal versus no cortical defect, β= -51.5; 95% CI: -86.9 to -16, p = 0.006) and apical extent of obturation (long versus flush, β= -27.2; 95% CI: -53.8 to -0.6, p = 0.04) were negatively associated with reduction in lesion volume (%).

Conclusion

LCPL may be successfully managed with RCT. Preoperative cortical bone defect and apical extent of obturation may negatively influence osseous healing.

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Total calcium, dairy foods and risk of colorectal cancer: a prospective cohort study of younger US women

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Abstract
Background
Although colorectal cancer (CRC) incidence is declining among adults aged ≥65 years, CRC incidence in younger adults has been rising. The protective role of calcium in colorectal carcinogenesis has been well established, but evidence is lacking on whether the association varies by age at diagnosis. We investigated the association between total calcium intake and risk of overall CRC and CRC before age 55 years.
Methods
In the Nurses' Health Study II (1991–2015), 94 205 women aged 25–42 years at baseline were included in the analysis. Diet was assessed every 4 years through validated food frequency questionnaires. Multivariable-adjusted hazard ratios (HRs) and 95% CIs for CRC were estimated using the Cox proportional hazards model.
Results
We documented 349 incident CRC cases during 2 202 604 person-years of follow-up. Higher total calcium intake was associated with a reduced risk of CRC. Compared with those with <750 mg/day of total calcium intake, the HR of CRC was 0.61 (95% CI, 0.38–0.97) for those who consumed ≥1500 mg/day (P for trend = 0.01). The HR per 300 mg/day increase was 0.85 (95% CI, 0.76–0.95). There was a suggestive inverse association between total calcium intake and CRC before age 55 years (HR per 300 mg/day increase, 0.87; 95% CI, 0.75–1.00), suggesting the importance of calcium intake in the younger population.
Conclusions
In a cohort of younger women, which reflects the birth cohorts, time periods and age ranges paralleling the recent rise in CRC, higher calcium intake was associated with a decreased risk of CRC.
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Κυριακή 30 Οκτωβρίου 2022

Postoperative analysis of osseous midface reconstructions: The value of imaging and a novel scoring system for complexity and operative success

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Abstract

Background

Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction.

Methods

One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score.

Results

Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04).

Conclusions

We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.

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Diagnostic efficacy of positron emission computerized tomography scans in suspicious laryngeal findings postorgan preservation treatment

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Abstract

Background

Larynx preservation protocols (LPP) for glottic primary squamous cell carcinoma has gained popularity worldwide. Direct laryngoscopy (DL) with biopsy is mandated when recurrence is suspected. The efficacy of 18Fluoro-deoxy-glucose positron emission computerized tomography (PET-CT) as alternative first-line diagnostic investigation in suspected recurrence was evaluated.

Methods

A retrospective study of patients with suspicious fiber-optic findings at more than 12 weeks after LPP. Sensitivity, specificity, and the negative predictive value (NPV) of DL and PET-CT were compared.

Results

Seventy-two patients presenting 105 cases of suspicious events were included in this study. Fifty-two events were initially investigated by DL and 53 events by PET-CT. The sensitivity of DL and PET-CT was 56.25% and 100%, respectively. The NPV was 84% for DL and 100% for PET-CT (p = 0.015).

Conclusion

Negative PET scans after LPP are highly accurate in ruling out recurrent/persistent disease and may spare the patient from negative biopsies.

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Effect of a high‐fat meal on the relative bioavailability of HMPL‐689

alexandrossfakianakis shared this article with you from Inoreader

Abstract

Purpose

The aim of this study was to investigate the effect of a high-fat meal on the single-dose pharmacokinetics (PK) and tolerability of HMPL-689 in Chinese healthy volunteers.

Methods

In this study, 34 eligible male volunteers received a single 30 mg dose of HMPL-689 capsules following an overnight fast or a high-fat breakfast prior to dosing. Blood samples were collected at the designated time points for pharmacokinetic analysis. Safety and tolerability were assessed throughout the study.

Results

Total 32 healthy male volunteers were completed in the study. The GMRs of AUC0-t, AUC0-∞, Cmax and their 90% CIs were 1.12 (1.09, 1.15), 1.12 (1.09, 1.15), and 0.64 (0.58, 0.70), respectively, in healthy male subjects after oral administration of HMPL-689 following intake of a high-fat diet versus under fasting state. The 90% CI of Cmax GMR fell outside the acceptable equivalent range (0.8-1.25). In addition, the median Tmax of HMPL-689 was 1.0 hours and 4.0 hours under the fasting and the fed conditions.

Conclusions

The study indicated that intake of a high-fat diet had an impact on the in vivo PK profile of HMPL-689 in healthy Chinese male subjects, which could obviously reduce the oral absorption rate of HMPL-689 and had little effect on the extent of oral absorption (AUC).

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Comparative analysis and trends in liver transplant hospitalizations with clostridium difficile infections: A 10‐year national cross‐sectional study

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ABSTRACT

Goals and Background

Clostridium difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in the United States. We aimed to determine comparative trends in inpatient outcomes of liver transplant (LT) patients based on CDI during hospitalizations.

Methods

The national inpatient sample (NIS) database was used to conduct the present retrospective study regarding CDI among the LT hospitalizations from 2009, to 2019. Primary outcomes included ten-year comparative trends of the length of stay (LOS) and mean inpatient charges (MIC). Secondary outcomes included comparative mortality and LT rejection trends.

Results

There was a 14.05% decrease in CDI in LT hospitalizations over the study period (P = 0.05). The trend in LOS did not significantly vary (P = 0.9). MIC increased significantly over last decade in LT hospitalizations with CDI (P < 0.001). LT hospitalizations of autoimmune etiology compared against non-autoimmune did not increase association with CDI, adjusted odds ratio (aOR) 0.97 [95% confidence interval (CI) 0.75-1.26, P = 0.87]. CDI was associated with increased mortality in LT hospitalizations, aOR 1.84 [95% confidence interval (CI) 1.52-2.24, P < 0.001].  In-hospital mortality for LT hospitalizations with CDI decreased by 7.75% over the study period (P = 0.3). CDI increased transplant rejections, aOR 1.3 [95% CI 1.08-1.65, P < 0.001]. There was a declining trend in transplant rejection for LT hospitalization with CDI from 5% to 3% over the study period (P = 0.0048).

Conclusion

CDI prevalence doesnot increase based on autoimmune LT etiology. It increases mortality in LT hospitalizations; however, trend for mortality and transplant rejections has been declining over the last decade.

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The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

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The Use of Dissemination and Implementation to Improve Multimodal Analgesia in Head and Neck Surgery

The use of a multimodal analgesia approach in a Randomized Clinical Trial including acetaminophen, ketorolac, gabapentin, and a neurogenic extremity block in patients undergoing major head and neck ablative and reconstructive surgery significantly reduced the need for opioids in the immediate postoperative period of a seven-day hospital stay. Coordination of care and reducing variability in pain medication administration were highly dependent on dissemination and implementation processes put in place for perioperative phases of care.


Objectives

To optimize the delivery of multimodal analgesia to patients undergoing major head and neck oncologic surgeries.

Methods

Pilot study included patients enrolled to receive either scheduled acetaminophen and as-needed opioids (control group) or scheduled acetaminophen, gabapentin, ketorolac, and as-needed opioids (experimental group). RCT, a hybrid type 1 effectiveness-implementation pragmatic trial, was designed to test the effectiveness of the intervention. Arm A received scheduled acetaminophen and as-needed opioids. Arm B received scheduled gabapentin, ketorolac, a regional nerve block at the free tissue donor site, scheduled acetaminophen and as-needed opioids.

Results

Pilot: Thirty-one patients undergoing major head and neck surgery were enrolled. Mean MMEs administered in control group (n = 15) was 251.60 mg (SD = 224.57 mg); mean MMEs in Experimental group (n = 16) was 195.78 mg (SD = 131.08 mg), p = 0.401. LOS was 8.0 days in control versus 7.0 days in experimental group (p = 0.054).

RCT: Interim analysis for safety and futility was planned during trial's design after 30 patients (n = 14 Arm A, and n = 16 Arm B). Mean MMEs administered were 135.1 mg in Arm A, (SD = 86.0 mg) versus mean MME of 51.3 mg in Arm B (SD = 43.3 mg, (p < 0.05)). Given clear superiority results, the trial was prematurely terminated. Functional pain scores, LOS, and complications were similar between the arms (p > 0.05). Variability of mean MME was compared before and after implementation of the management protocols: SD in RCT#1 was 181.46 mg versus 124.6 mg in RCT#2.

Conclusion

Multimodal analgesia significantly reduced the need for opioids in patients undergoing major head and neck surgery.

Level of Evidence

1, Randomized Clinical Trial Laryngoscope, 2022

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The Influence of Age on the Frequency of Rhythmic Masticatory Muscle Activity During Sleep in General Population differs from that in Clinical Research Samples

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Abstract

Introduction

During sleep, limb and jaw muscle motor activity can be quantified by electromyography (EMG). The frequency of periodic limb activity during sleep increases with age in both the general and clinical research populations. The literature is controversial regarding stability, over age, of the frequency of rhythmic masticatory muscle activity (RMMA), which is one biomarker of sleep bruxism (SB). The purpose of this retrospective sleep laboratory study was to assess if any change in RMMA frequency occurs over age in the general population (GP) and two clinical research (CR) samples.

Method

RMMA signals from polysomnography (PSG) recordings of 465 individuals, irrespective of SB awareness, were analysed. The sample comprised 164 individuals from the GP of Sao Paulo, and 301 individuals from Montreal and Osaka CR samples.

Data were divided into two subgroups, younger (15–39) and older (40–80) participants. RMMA was classified as low frequency (<2 events/hr) or high (>2 events/hr). Pearson correlation (R) and B (slope) analyses were performed with power estimations.

Results

In the GP sample, no significant change over age was noted in the RMMA index/year. In the CR samples, a significant reduction was observed in the RMMA index/year (-0.05) with age (R2=0.042; p<0.001; 3.5 to 1.5 RMMA/hr from 20 to 60 years old).

Conclusions

In the GP, the RMMA index remained stable over age. In the CR samples, a significant, reduction was observed. Prospective studies with multiple home sleep recordings, in both general and clinical research populations, are needed before extrapolating from the present findings.

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The evolution of fertility preservation care models in a large pediatric cancer and blood disorders center

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Abstract

Background

Children and adolescents who receive gonadotoxic treatments are at risk for future infertility. While there is a growing focus on integrating fertility preservation (FP) within pediatric cancer and blood disorder centers, wide variations in care models and methods exist across institutions. The purpose of this work is to describe the evolution of FP care models within a large pediatric hematology/oncology center.

Methods

Models of care and associated timeframes are described, including a pre-FP program model, establishment of a formal FP program, integration of nurse navigators, and the addition of FP consult stratification based on urgency (urgent/nonurgent). The number of patient consults within each model, patient sex, diagnosis (oncologic/hematologic), and consult timing (pre-gonadotoxic treatment/posttreatment completion) were abstracted from the clinical database.

Results

The number of annual consults increased from 24 during the pre-FP program model (2015) to 181 during the current care model (2020). Over time, the proportion of consults for females and patients with nonmalignant hematologic disorders increased. Patient stratification reduced the proportion of consults needing to be completed urgently from 75% at the advent of the FP program to 49% in the current model.

Conclusions

The evolution of care models within our FP program allowed for growth in the number of consults completed, expansion of services to more patients with nonmalignant hematologic disorders, and more consults for female patients. Nurse navigators play a critical role in care facilitating referrals, coordination, and patient education. Urgency stratification has allowed FP team members to manage increasing FP-related encounters.

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