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Morphometric Evaluation of the Recurrent Laryngeal Nerve of Wistar Rats Exposed to Pesticides

J Voice. 2021 Nov 12:S0892-1997(21)00328-3. doi: 10.1016/j.jvoice.2021.09.028. Online ahead of print.

ABSTRACT

The literature has been shown that exposition by inhalation to chemical compounds can cause vocal disorders and dysphagia in humans, in addition to other symptoms that are manifested according to the type, concentration and duration of exposure to the substance. Cypermethrin and dichlorvos are pesticides widely used in agriculture, public health, veterinary, and home environments. Despite the scientific evidence that cypermethrin and dichlorvos can cause neurodegenerative damage and motor alterations, there are no studies evaluating the toxic effects of these pesticides on the morphology of structures responsible for vocal mobility, especially to the Recurrent Laryngeal Nerve (RLN). Considering the association between vocal disorders in humans and variations in RLN and morphometry, the aim of this study was to evaluate the possible alterations in the microstructure of RLN secondary to subchronic exposure to cypermethrin (pyrethroid) and dichlorvos (organophosphate) in Wistar rats. The experimental protocol (approved by CEUA-UFCSPA: 321/15 and 323/15) consisted of 15 male Wistar rats, allocated in 3 groups: Control (n = 5, exposed to water), Cypermethrin (n = 5, exposed to cypermethrin – 1/10 of the inhalation median lethal concentration [LC50] – 0.25 mg/L) and dichlorvos (n = 5, exposed to dichlorvos – 1/10 of the LC50 – 1.5 mg/L). Inhalation exposure was performed for 4 hours, 5 times per week, for 6 weeks. The nerves were collected, histologically processed and analyzed using morphometric parameters measured using ZEN 2.6 (Zeiss – Germany). The cypermethrin and dichlorvos groups showed significant changes (P < 0.001, ANOVA) in the g-ratio and in the thickness of the myelin sheath of the RLN when compared to the control animals, however, none of the other parameters evaluated showed statistically significant differences. These findings indicate that repeated inhalation exposure to commercial products of cypermethrin and dichlorvos is able to modify the structure of the RLN and possibly generating vocal changes and / or dysphagia.

PMID:34782225 | DOI:10.1016/j.jvoice.2021.09.028

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Different Responses to Neoadjuvant Chemotherapy in Urothelial Carcinoma Molecular Subtypes

Eur Urol. 2021 Nov 12:S0302-2838(21)02138-2. doi: 10.1016/j.eururo.2021.10.035. Online ahead of print.

ABSTRACT

BACKGROUND: For muscle-invasive bladder cancer (MIBC), no tissue biomarkers are available for clinical use to predict response to neoadjuvant chemotherapy.

OBJECTIVE: To investigate how molecular subtypes impact pathological response and survival in patients receiving preoperative cisplatin-based chemotherapy.

DESIGN, SETTING, AND PARTICIPANTS: Classification of a retrospective cohort of 149 patients was performed by tumor transcriptomic profiling and immunostaining. A cohort treated with radical cystectomy alone and public data sets were used for comparison and external validation.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Complete pathological response in the cystectomy specimen (ypT0N0) and survival were compared in predefined molecular subtypes. Differential gene expression and chemotherapy response were explored beyond molecular subtypes.

RESULTS AND LIMITATIONS: Patients with genomically unstable (GU) and urothelial-like (Uro) tumors had higher proportions of complete pathological response (16/31 [52%] and 17/54 [31%]), versus five out of 24 (21%) with the basal/squamous (Ba/Sq) subtype following neoadjuvant chemotherapy and radical cystectomy. Molecular subtype was independently associated with improved survival for patients with GU tumors (hazard ratio [HR] 0.29, 95% confidence interval [CI]: 0.11-0.79) and UroC tumors (HR 0.37, 95% CI: 0.14-0.94) compared with Ba/Sq tumors, adjusting for clinical stage. In addition, expression of the gene coding for osteopontin (SPP1) showed a subtype-dependent effect on chemotherapy response.

CONCLUSIONS: Urothelial cancer of the luminal-like (GU and Uro) subtypes is more responsive to cisplatin-based neoadjuvant chemotherapy. A second-generation of subtype-specific biomarkers, for example, SPP1, may be a way forward to develop a more precision-based treatment approach for neoadjuvant chemotherapy in MIBC.

PATIENT SUMMARY: This study shows that tumor classification by gene expression profiling and molecular subtyping can identify patients who are more likely to benefit from chemotherapy before radical cystectomy for muscle-invasive bladder cancer. Together with other markers for response, molecular subtypes could have a role in selective administration of such chemotherapy.

PMID:34782206 | DOI:10.1016/j.eururo.2021.10.035

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Use of Terminology and the Effect of Training on Auditory-Perceptual Ratings of Speaking Voice by Singing Teachers

J Voice. 2021 Nov 12:S0892-1997(21)00337-4. doi: 10.1016/j.jvoice.2021.09.036. Online ahead of print.

ABSTRACT

OBJECTIVES: The purpose of this study was to investigate group differences between singing teachers and speech-language pathologists when rating dysphonic speaking voices and whether training using reference samples and the Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) improves inter-rater reliability between and among the two groups. Differences in use of terminology and ratings could reveal potential for miscommunication in the team treatment of singers with voice disorders.

STUDY DESIGN: This is a prospective pre test post test cohort study with between and within group comparisons.

METHODS: Recorded samples of dysphonic speaking voices were rated by 18 experienced singing teachers with free written descriptions and an Overall Severity (OS) rating of 0-100. Participants were then trained in application of the CAPE-V with verbal definitions and reference samples exemplifying characteristics of disordered voice. Participants rated the samples a second time using the CAPE-V. The pre and post training ratings of participants were compared to composite ratings of six speech-language pathologists.

RESULTS: Descriptive statistics indicated the mean aggregate Overall Severity rating of speech-language pathologist (SLP) raters as 25.79 (SD = 6.10, SE = 2.49), as compared to 35.05 (SD = 12.72, SE = 3.00) for singing teachers. Differences in ratings were more pronounced in samples rated by SLPs as “mild” (OS 6-20) or “mild-moderate” (OS 21-35). ANOVA revealed statistically significant group differences between SLPs and singing teachers for the parameters Overall Severity (P = 0.0109, F = 7.8) and Strain (P = 0.0085, F = 8.35). While CAPE-V training did not significantly change the OS ratings of singing teachers, it did improve their inter-rater reliability from 0.67 pre training to 0.83 post training, with agreement similar to that of SLP raters (0.86). After training, participants responded “yes” to the presence of dysphonia in disordered samples more frequently.

CONCLUSIONS: The results support the recommendation of training singing teachers in perceptual evaluation of speaking voice to increase sensitivity to the presence of organic voice disorders and to encourage compatibility in terminology used among SLPs and singing teachers.

PMID:34782224 | DOI:10.1016/j.jvoice.2021.09.036

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Lymphadenectomy for high-grade endometrial cancer: Does it impact lymph node recurrence?

Eur J Surg Oncol. 2021 Nov 9:S0748-7983(21)00813-1. doi: 10.1016/j.ejso.2021.11.009. Online ahead of print.

ABSTRACT

INTRODUCTION: The diagnostic role of lymph node (LN) assessment is established in endometrial cancer. Our study assesses whether surgical removal of metastatic LNs has oncologic benefit in high-grade endometrial cancer.

MATERIALS AND METHODS: High-grade endometrial cancer cases (2000-2010) were collected from two tertiary cancer centres. In patients with at least one positive LN, recurrence free survival (RFS) was compared by the number of LNs removed. Factors predicting nodal recurrence (NR) were explored. Univariate statistical analyses by log rank test and multivariable cox proportional hazards model were performed using SAS version 9.4.

RESULTS: Of 570 patients identified, 334 patients underwent staging lymphadenectomy, 74 (22.2%) patients had at least one positive LN. The median RFS with at least one positive lymph node was 87.1 months (95% CI ≥ 14.3) when greater than 15 LNs were removed, compared to 16.9 months (95% CI, 13.6-35.6) and 17.3 months (95% CI, 8.5-39.8) when 5-15 and less than 5 LNs were removed, respectively (p = 0.02). In the cohort of 570 patients, there were 167 disease recurrences with location described on imaging, 98 (58.7%) had a NR and 69 (41.3%) recurred at other sites. Multivariable modeling identified that only positive LNs at surgical staging predicted NR (HR 3.8, 95% CI 1.4-10.2).

CONCLUSION: In high-grade endometrial cancer, positive LNs predict NR, and RFS is longer with a more extensive LN dissection in women with positive LNs. Future prospective studies should evaluate the oncologic benefit of surgical removal of metastatic LNs in high-grade endometrial cancer.

PMID:34782183 | DOI:10.1016/j.ejso.2021.11.009

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Nutritional management and clinical outcome of critically ill patients with COVID-19: A retrospective study in a tertiary hospital

Clin Nutr. 2021 Nov 1:S0261-5614(21)00499-4. doi: 10.1016/j.clnu.2021.10.020. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Severe COVID-19 infection is characterized by an inflammatory response and lung injury that can evolve into an acute respiratory distress syndrome that needs support treatment in intensive care unit. Nutritional treatment is an important component of the management of critically ill patients and should be started in the first 48 h of ICU admission to avoid malnutrition. This study describes the characteristics of the patients treated in a tertiary hospital in Madrid during the months of March-May 2020 (first wave), the medical nutrition treatment employed and its influence in the clinical outcome of these patients.

METHODS: This is a retrospective study including COVID-19 patients admitted in ICU that needed medical nutrition treatment (MNT). Collected variables included sex, age, BMI, underlying diseases, time from hospitalisation to ICU admission, type of respiratory support (invasive mechanical ventilation (IMV) or high flow nasal cannula (HFNC) or non-invasive ventilation (non-IMV)), caloric and protein requirements (25 kcal/kg adjusted body weight (ABW), 1.3 g/kg ABW/day), MNT type (enteral nutrition (EN), parenteral nutrition (PN), mixed EN + PN), total calories (including propofol) and proteins administered, percentage of caloric and protein goal in ICU day 4th and 7th, metabolic complications, acute kidney failure (AKF), length of stay (LOS) and mortality. Data are expressed as mean ± SD, median (IQR) or frequencies. Statistical analysis was performed with the IBM SPSS Statistics for Windows, Version 25.0. p < 0.05 were considered statistically significant.

RESULTS: A total of 176 patients were included (72.7% male), 60.1 ± 13.5 years, BMI 29.9 ± 5.4 kg/m2. Underlying diseases included 47.4% overweight, 39.8% obesity, 49.1% hypertension, 41.4% dyslipidaemia. 88.6% of patients needed IMV, 89.1% prone position, 2.9% ECMO. Time to ICU admission: 2 (4.75) days. Estimated caloric and protein requirements were 1775 ± 202 kcal and 92.4 ± 10.3 g. Calories and proteins administered at days 4th and 7th were 1425 ± 577 kcal and 66 ± 26 g and 1574 ± 555 and 74 ± 37, respectively. Most of the patients received PN (alone or complementary to EN) to cover nutritional requirements (82.4% at day 4th and 77.9% at day 7th). IVM patients received more calories and proteins during the first week of ICU admission. Complications included 77.8% hyperglycaemia, 13.2% hypoglycaemia, 83.8% hypertriglyceridemia, and 35.1% AKF. ICU LOS was 20.5 (26) days. The mortality rate was 36.4%.

CONCLUSIONS: In our series, the majority of patients reached energy and protein requirements in the first week of ICU admission due to the use of PN (total or complementary to EN). Patients with HFNC or non-IMV may be at risk of malnutrition if total or complementary PN to oral diet/ONS/tube feeding is not used to cover nutritional requirements. Therefore, if EN is not possible or insufficient, PN can be safely used in critically ill patients with COVID-19 with a close monitoring of metabolic complications.

PMID:34782169 | DOI:10.1016/j.clnu.2021.10.020

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A Risk Assessment Model for Stroke in the Early Post-Transplant Period in Adult Cardiac Allograft Recipients: A UNOS Database Analysis

Transplant Proc. 2021 Nov 13:S0041-1345(21)00715-6. doi: 10.1016/j.transproceed.2021.09.025. Online ahead of print.

ABSTRACT

BACKGROUND: Stroke risk in adult cardiac allograft recipients in the early postoperative period remains less defined. This study attempts to develop a risk assessment model in this population.

METHODS: Patients (≥18 years of age) between 2005 and 2015 who underwent cardiac transplantation were selected from the United Network for Organ Sharing database. The final study cohort had 20,915 patients. Risk factors were identified and multivariate logistic regression was used to test associations. SAS software was used for analyses.

RESULTS: Male recipients had a lower risk (odds ratio [OR] 0.7 [0.6-0.92]; P < .05) for stroke. Prolonged ischemic time (OR 1.2 [1.1-1.3), mechanical ventilation (OR 1.6 [1.2-1.9]), left ventricular assist device support (OR 1.8 [1.4-2.3]), black or Hispanic ethnicity (OR 1.33 [1.04-1.7]), days in status 1A (OR 1.05 [1.01-1.1]), recipient creatinine (OR 1.2 [1.02-1.4]), and type 2 diabetes (OR 1.4 [1.1-1.7]) were significant risk factors. A risk score was generated. Patients with a score of 8 had a 5-fold increase in event rate as compared with those with a score of 0. The c-statistic for this model was 0.65.

CONCLUSIONS: For the first time, a weighted risk score GIMVECH (female gender, ischemic time, mechanical ventilation, left ventricular assist device support, ethnicity, clinical history) was generated to assess stroke in the early post-transplant period.

PMID:34782170 | DOI:10.1016/j.transproceed.2021.09.025

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Ion release and biocompatibility of Co-Cr alloy fabricated by selective laser melting from recycled Co-Cr powder: An in vitro study

J Prosthet Dent. 2021 Nov 12:S0022-3913(21)00491-1. doi: 10.1016/j.prosdent.2021.09.003. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: As the cobalt-chromium (Co-Cr) powder used in selective laser melting (SLM) is costly, reusing the remaining powder after multiple cycles provides an economic and environmental benefit. However, knowledge of the cytotoxic effect of the alloy fabricated from recycled powder is lacking.

PURPOSE: The purpose of this in vitro study was to evaluate the biological effects of the Co-Cr ions released from the alloy fabricated from the recycled powder on the human gingival fibroblasts (HGFs) and normal oral keratinocytes (NOKs).

MATERIAL AND METHODS: Disk-shaped Co-Cr specimens were fabricated by using the SLM technique from powders with different proportions of recycled to unused and from different recycling times. Co and Cr ions released from the disks immersed in the Dulbecco Modified Eagle Medium (DMEM) for 24 hours or 7 days were measured by inductively coupled plasma mass spectrometry (ICP-MS). Biocompatibility of Co-Cr alloy was detected by incubation of HGFs and NOKs in DMEM containing Co and Cr ions for 24 hours. The ANOVA test was used to evaluate statistically significant differences among different groups (α=.05).

RESULTS: Compared with the alloy fabricated from 100% unused powder, the concentrations of Co and Cr ions increased with the increase of recycled to unused powder ratio or with the increase in the recycling times. HGFs and NOKs showed an increase in apoptosis, intracellular oxidative stress (ROS), hypoxia-inducing factor1α (HIF-1α), and proinflammatory cytokines (tumor necrosis factor alpha [TNF- α], interleukin 6 [IL-6], interleukin 8 [IL-8], and vascular endothelial growth factor [VEGF]) with the increase of Co-Cr ions in a concentration-dependent manner. A significant reduction in cell proliferation was found with the increase in the concentrations of Co and Cr ions (P<.05).

CONCLUSIONS: The results of this study indicated that Co-Cr alloy fabricated from partially recycled powder or powder with different recycling times released significantly more Co and Cr ions and showed higher cytotoxicity to HGFs and NOKs than the alloy fabricated from unused powder.

PMID:34782150 | DOI:10.1016/j.prosdent.2021.09.003

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A nationwide analysis of gallbladder surgery in England between 2000 and 2019

Surgery. 2021 Nov 12:S0039-6060(21)00985-5. doi: 10.1016/j.surg.2021.10.025. Online ahead of print.

ABSTRACT

BACKGROUND: There are no reports on nationwide trends in subtotal cholecystectomy (STC) and cholecystostomy in England. We hypothesized that, as in the United States, a substantial increase in the utilization of these surgical procedures, over time, may be observed. We aimed to generate a reliable report on 4 of the most common gallbladder surgical procedures in England to allow cross-procedure comparisons and highlight significant changes in the management of benign gallbladder disease over time.

METHODS: We obtained data from NHS Digital and extracted population estimates from the Office of National Statistics. We examined the trends in the use of STC, cholecystostomy, cholecystolithotomy and total cholecystectomy (TC) between 2000 and 2019.

RESULTS: Of the 1,234,319 gallbladder surgeries performed, TC accounted for 96.8% (n = 1,194,786) and the other 3 surgeries for 3.2% (n = 39,533). The total number of gallbladder surgeries performed annually increased by 80.4% from 2000 to 2019. We detected increases in the counts of cholecystostomies by 723.1% (n = 290 in 2000 vs n = 2,387 in 2019) and STCs by 716.6% (n = 217 in 2000 vs n = 1,772 in 2019). Consequently, there was a decrease in the ratio of TC to STC (180:1 in 2000 vs 38:1 in 2019). A similar decrease was observed in the ratio of cholecystectomy to cholecystostomy (135:1 in 2000 vs 29:1 in 2019).

CONCLUSION: Increased utilization of STC and cholecystostomy was detected in England. These findings highlight the importance of regular monitoring of nationwide trends in gallbladder surgery and the associated clinical outcomes.

PMID:34782153 | DOI:10.1016/j.surg.2021.10.025

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An Electronic Health Record-Compatible Model to Predict Personalized Treatment Effects From the Diabetes Prevention Program: A Cross-Evidence Synthesis Approach Using Clinical Trial and Real-World Data

Mayo Clin Proc. 2021 Nov 12:S0025-6196(21)00708-4. doi: 10.1016/j.mayocp.2021.09.012. Online ahead of print.

ABSTRACT

OBJECTIVE: To develop an electronic health record (EHR)-based risk tool that provides point-of-care estimates of diabetes risk to support targeting interventions to patients most likely to benefit.

PATIENTS AND METHODS: A risk prediction model was developed and validated in a large observational database of patients with an index visit date between January 1, 2012, and December 31, 2016, with treatment effect estimates from risk-based reanalysis of clinical trial data. The risk model development cohort included 1.1 million patients with prediabetes from the OptumLabs Data Warehouse (OLDW); the validation cohort included a distinct sample of 1.1 million patients in OLDW. The randomly assigned clinical trial cohort included 3081 people from the Diabetes Prevention Program (DPP) study.

RESULTS: Eleven variables reliably obtainable from the EHR were used to predict diabetes risk. This model validated well in the OLDW (C statistic = 0.76; observed 3-year diabetes rate was 1.8% (95% confidence interval [CI], 1.7 to 1.9) in the lowest-risk quarter and 19.6% (19.4 to 19.8) in the highest-risk quarter). In the DPP, the hazard ratio (HR) for lifestyle modification was constant across all levels of risk (HR, 0.43; 95% CI, 0.35 to 0.53), whereas the HR for metformin was highly risk dependent (HR, 1.1; 95% CI, 0.61 to 2.0 in the lowest-risk quarter vs HR, 0.45; 95% CI, 0.35 to 0.59 in the highest-risk quarter). Fifty-three percent of the benefits of population-wide dissemination of the DPP lifestyle modification and 73% of the benefits of population-wide metformin therapy can be obtained by targeting the highest-risk quarter of patients.

CONCLUSION: The Tufts-Predictive Analytics and Comparative Effectiveness DPP Risk model is an EHR-compatible tool that might support targeted diabetes prevention to more efficiently realize the benefits of the DPP interventions.

PMID:34782125 | DOI:10.1016/j.mayocp.2021.09.012

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Variation in treatment of hip fractures and guideline adherence amongst surgeons with different training backgrounds in the Netherlands

Injury. 2021 Nov 8:S0020-1383(21)00914-1. doi: 10.1016/j.injury.2021.11.006. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: Two medical specialties, general surgery and orthopaedic surgery, with different training programs but matching trauma certification requirements, provide hip fracture surgery in the Netherlands. This study analyses treatment preferences and guideline adherence of Dutch surgeons with different surgical backgrounds.

PATIENTS AND METHODS: All hip fracture patients registered in the Dutch Hip Fracture Audit in 2018 and 2019 were included in this retrospective study. Four types of surgeons were distinguished: trauma-certified general surgeons (ST+), non-trauma certified general surgeons (ST-), trauma-certified orthopaedic surgeons (OT+) and non-trauma certified orthopaedic surgeons (OT-). Differences in patient characteristics, and practice variation in treatment choices and guideline adherence per fracture type were analysed using descriptive statistics.

RESULTS: 28,656 patients were included; 16,367 (57.1%) treated by ST+, 1,371 (4.8%) by ST-, 4,692 (16.4%) by OT+ and 6,226 (21.7%) by OT-. Few clinically relevant differences in patient characteristics and hospital processes were found between all surgeon groups. Displaced FNF were the most commonly treated fracture type for all types of surgeons. Both OT+ and OT- operated mostly (displaced) FNFs, while the fracture types treated by ST+ and ST- were more heterogeneous. For all fracture types, the orthopaedic surgeons performed THA and HA more often than general surgeons, while general surgeons more often placed SHS and IMN for specific fracture types. Guideline adherence was on average 68.4% and differed significantly per surgeon type (68.7% by ST+, 65.2% by ST-, 74.4% by OT+ and 63.6% by OT- (p<0.01)), as well as per fracture type: >90% treatment according to the guideline for trochanteric AO-31A2 and A3 fractures, 18.8% for AO-31A1 fractures and 51.7% guideline adherence for undisplaced FNF. Guideline adherence for displaced FNF varied depending on patient characteristics.

DISCUSSION: In the Netherlands, different surgical specialists treat different types of hip fractures and have different preferences concerning implants for hip fracture surgery in comparable patients. Guideline adherence of trauma- and non-trauma certified orthopaedics and general surgeons differs significantly. Reduction of practice variation should be strived for in order to improve hip fracture care.

PMID:34782116 | DOI:10.1016/j.injury.2021.11.006