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Prevalence and risk factors of incidental prostate cancer in certain surgeries for benign prostatic hyperplasia: A systematic review and meta-analysis

Int Braz J Urol. 2022 Feb 2;47. doi: 10.1590/S1677-5538.IBJU.2021.0653. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to explore the prevalence and clinical risk factors in patients diagnosed with incidental prostate cancer (IPC) during certain surgeries (transurethral resection of the prostate [TURP], open prostatectomy [OP], and holmium laser enucleation of the prostate [HoLEP]) after clinically suspected benign prostatic hyperplasia (BPH).

MATERIALS AND METHODS: Literature search of the MEDILINE, Web of Science, Embase, and Cochrane Library databases was performed to identify eligible studies published before June 2021. Multivariate adjusted odds ratios (ORs) and associated 95% confidence intervals (CIs) of the prevalence and clinical risk factors of IPC were calculated using random or fixed-effect models.

RESULTS: Twenty-three studies were included in the meta-analysis. Amongst the 94.783 patients, IPC was detected in 24.715 (26.1%). Results showed that the chance of IPC detection (10%, 95% CI: 0.07-4.00; P<0.001; I2=97%) in patients treated with TURP is similar to that of patients treated with HoLEP (9%, 95% CI: 0.07-0.11; P<0.001; I2=81.4%). However, the pooled prevalence estimate of patients treated with OP was 11% (95% CI: -0.03-0.25; P=0.113; I2=99.1%) with no statistical significance. We observed increased incidence of IPC diagnosis after BPH surgery amongst patients with higher prostate-specific antigen (PSA) level (OR: 1.13, 95% CI: 1.04-1.23; P=0.004; I2=89%), whereas no effect of age (OR: 1.02, 95% CI: 0.97-1.06; P=0.48; I2=78.8%) and prostate volume (OR: 0.99, 95% CI: 0.96-1.03; P=0.686; I2=80.5%) were observed.

CONCLUSIONS: The prevalence of IPC was similar amongst patients undergoing TURP, HoLEP, and OP for presumed BPH. Interestingly, increased PSA level was the only independent predictor of increasing risk of IPC after BPH surgery rather than age and prostate volume. Hence, future research should focus on predictors which accurately foretell the progression of prostate cancer to determine the optimal treatment for managing patients with IPC after BPH surgery.

PMID:35195386 | DOI:10.1590/S1677-5538.IBJU.2021.0653

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Retrospective bullying trajectories in adults with self-reported oral language difficulties

Int J Lang Commun Disord. 2022 Feb 23. doi: 10.1111/1460-6984.12708. Online ahead of print.

ABSTRACT

BACKGROUND: Previous research has consistently evidenced that children with speech and language difficulties suffer more bullying victimisation during middle school years, whereas other educative stages remain less explored. Moreover, there are divergent results in previous evidence about the types of victimisation (physical, verbal, relational) youths may experience.

AIMS: To examine the retrospective developmental trajectories of bullying victimisation in adults with and without self-reported oral language difficulties across seven educational stages (preschool to university). Special attention was given to the prevalence and types of victimisation.

METHODS & PROCEDURES: A total of 336 participants (ages between 18 and 65, M = 30.3) from a sample of 2259 participants that fully answered an online survey were classified as having experienced oral language difficulties (LD) not associated with a biomedical condition. A comparable control group (n = 336; ages between 18 and 72, M = 30.0) was randomly selected for statistical between-groups contrasts. Responses to the California Bullying Victimization Scale-Retrospective (CBVS-R) were analysed by generalised estimating equations (GEE) including language groups, types of bullying, and educational stages as explanatory variables. Specific language group comparisons in terms of percentages were conducted using chi-square tests.

OUTCOMES & RESULTS: GEE results suggested that experiencing LD was associated with an overall increase in the likelihood of bullying victimisation, Wald’s χ2 (1) = 8.41, p < 0.005 for the main effect of the LD group, along almost all educational stages, Wald’s χ2 (6) = 3.13, p = 0.69 for the LD group × educational stage interaction. Finally, a higher proportion of participants in the LD group reported having suffered teasing behaviours at the second cycle of elementary, the first cycle of secondary, and baccalaureate. They also reported with a higher proportion being physically hurt at preschool and having received sexual comments at the second cycle of elementary, Wald’s χ2 (93) = 259.87, p < 0.001 for the LD group × educational stage × type of bullying interaction.

CONCLUSIONS & IMPLICATIONS: People with oral language difficulties experience more bullying victimisation behaviours than their typically developing peers. Heightened bullying prevalence in children with language difficulties seems to emerge as early as 6-9 years old and persists along the rest of schooling. Not all victimisation forms seem to show differential increased rates in people with speech/language difficulties, evidencing important implications for bullying assessment. Results highlight the need to provide particular support to individuals with language difficulties against bullying during the entire schooling.

PMID:35195330 | DOI:10.1111/1460-6984.12708

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Quantitative MRI Differentiates Electromyography Severity Grades of Denervated Muscle in Neuropathy of the Brachial Plexus

J Magn Reson Imaging. 2022 Feb 23. doi: 10.1002/jmri.28125. Online ahead of print.

ABSTRACT

BACKGROUND: Quantitative MRI (qMRI) metrics reflect microstructural skeletal muscle changes secondary to denervation and may correspond to conventional electromyography (EMG) assessments of motor unit recruitment (MUR) and denervation.

HYPOTHESIS: Differences in quantitative T2 , diffusion-based apparent fiber diameter (AFD), and fat fraction (FF) exist between EMG grades, in patients with clinically suspected neuropathy of the brachial plexus.

STUDY TYPE: Prospective.

POPULATION: A total of 30 subjects (age = 37.5 ± 17.5, 21M/9F) with suspected brachial plexopathy.

FIELD STRENGTH/SEQUENCE: 3-Tesla; qMRI using fast spin echo (T2 -mapping), multi-b-valued diffusion-weighted echo planar imaging (for AFD), and dual-echo Dixon gradient echo (FF-mapping) sequences.

ASSESSMENT: qMRI values were compared against EMG grades (MUR and denervation). qMRI values (T2 , AFD, and FF) were obtained for five regional shoulder muscles. A 4-point scale was used for MUR/denervation severity.

STATISTICAL TESTS: Linear mixed models and least-squares pairwise comparisons were used to evaluate qMRI differences between EMG grades. Predictive accuracy of EMG grades from qMRI was quantified by 10-fold cross-validated logistic models. A P value < 0.05 was considered statistically significant.

RESULTS: Mean (95% confidence interval) qMRI for “full” MUR were T2 = 39.40 msec (35.72-43.08 msec), AFD = 78.35 μm (72.52-84.19 μm), and FF = 4.54% (2.11-6.97%). Significant T2 increases (+8.36 to +14.67 msec) and significant AFD decreases (-11.04 to -21.58 μm) were observed with all abnormal MUR grades as compared to “full” MUR. Significant changes in both T2 and AFD were observed with increased denervation (+9.59 to +15.04 msec, -16.25 to -18.66 μm). There were significant differences in FF between some MUR grades (-1.45 to +2.96%), but no significant changes were observed with denervation (P = 0.089-0.662). qMRI prediction of abnormal MUR or denervation was strong (mean accuracy = 0.841 and 0.810, respectively) but moderate at predicting individual grades (accuracy = 0.492 and 0.508, respectively).

DATA CONCLUSION: Quantitative T2 and AFD differences were observed between EMG grades in assessing muscle denervation.

LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

PMID:35195321 | DOI:10.1002/jmri.28125

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White-matter microstructural alterations in patients with functional constipation: A tract-based spatial statistics study

Neurogastroenterol Motil. 2022 Feb 23:e14338. doi: 10.1111/nmo.14338. Online ahead of print.

ABSTRACT

BACKGROUND: Highly prevalent functional constipation (FC) belongs to the category of functional gastrointestinal disorders. Neuroimaging studies have demonstrated brain functional and morphometric changes in patients with FC. However, whether FC is associated with white-matter (WM) microstructural alterations remains unclear.

METHODS: Diffusion tensor imaging (DTI) and tract-based spatial statistics (TBSS) were introduced to investigate WM microstructural changes as calculated by fractional anisotropy (FA), mean (MD), axial (AD), and radial diffusivity (RD) in 26 FC patients and 31 healthy controls.

KEY RESULTS: Patients with FC relative to healthy controls had significantly decreased FA with increased MD/RD in the genu (GCC) and body (BCC) of the corpus callosum, right cingulum (Cing), bilateral anterior corona radiata (ACR), bilateral superior corona radiata (SCR), and left posterior corona radiata (PCR) (pFWE < 0.05). Between-group difference was only in the left SCR and PCR when regressing out anxiety and depression as covariates.

CONCLUSIONS AND INFERENCES: These WM tracts are mainly responsible for sensory and emotional information communication and corresponding functional integration; thus, our findings indicate an association between FC and WM microstructural abnormalities in regions involved with visceral afferent and emotional-arousal processing. Alterations in WM microstructures including the CC, cingulum, and ACR are more related to psychological symptoms than constipation, which might have greater impact on brain structures.

PMID:35195324 | DOI:10.1111/nmo.14338

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Universal gestational diabetes screening and antepartum stillbirth rates in Austria-A population-based study

Acta Obstet Gynecol Scand. 2022 Feb 23. doi: 10.1111/aogs.14334. Online ahead of print.

ABSTRACT

INTRODUCTION: Occult or untreated gestational diabetes (GDM) is a well-known risk factor for adverse perinatal outcomes and may contribute to antepartum stillbirth. We assessed the impact of screening for GDM on the rate of antepartum stillbirths in non-anomalous pregnancies by conducting a population-based study in 974 889 women in Austria.

MATERIAL AND METHODS: Our database was derived from the Austrian Birth Registry. Inclusion criteria were singleton live births and antepartum stillbirths ≥24+0 gestational weeks, excluding fetal congenital malformations, terminations of pregnancy and women with pre-existing type 1 or 2 diabetes. Main outcome measures were (a) overall stillbirth rates and (b) stillbirth rates in women at high risk of GDM (i.e., women with a body mass index ≥30 kg/m2 , history of previous intrauterine fetal death, GDM, previous macrosomic offspring) before (2008-2010, “phase I”) and after (2011-2019, “phase II”) the national implementation of universal GDM screening with a 75 g oral glucose tolerance test in Austrian pregnant women by 2011.

RESULTS: In total, 940 373 pregnancies were included between 2008 and 2019, of which 2579 resulted in intrauterine fetal deaths at 33.51 ± 5.10 gestational weeks. After implementation of the GDM screening, a statistically significant reduction in antepartum stillbirth rates among non-anomalous singletons was observed only in women at high risk for GDM (4.10‰ [95% confidence interval (CI) 3.09-5.43] in phase I vs. 2.96‰ [95% CI 2.57-3.41] in phase II; p = 0.043) but not in the general population (2.76‰ [95% CI 2.55-2.99] in phase I vs. 2.74‰ [95% CI 2.62-2.86] in phase II; p = 0.845). The number needed to screen with the oral glucose tolerance test to subsequently prevent one case of (non-anomalous) intrauterine fetal death was 880 in the high-risk and 40 000 in the general population.

CONCLUSIONS: The implementation of a universal GDM screening programme in Austria in 2011 has not led to any significant reduction in antenatal stillbirths among non-anomalous singletons in the general population. More international data are needed to strengthen our findings.

PMID:35195277 | DOI:10.1111/aogs.14334

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A multicenter, open-label, single-arm study of anamorelin (ONO-7643) in patients with cancer cachexia and low body mass index

Cancer. 2022 Feb 23. doi: 10.1002/cncr.34154. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer cachexia is a syndrome characterized by anorexia and decreased body weight. This study evaluated the efficacy and safety of anamorelin, an orally active, selective ghrelin receptor agonist, in patients with cancer cachexia and a low body mass index (BMI).

METHODS: This multicenter, open-label, single-arm study enrolled Japanese patients with non-small cell lung cancer or gastrointestinal cancer with cancer cachexia (BMI < 20 kg/m2 , involuntary weight loss > 2% in the last 6 months, and anorexia). Patients were administered 100 mg of anamorelin once daily for up to 24 weeks. The primary end point was a composite clinical response (CCR) at 9 weeks, which was defined as an increase in body weight of ≥5% from the baseline, an increase of ≥2 points in the score of the 5-item Anorexia Symptom Scale of the Functional Assessment of Anorexia/Cachexia Therapy, and being alive.

RESULTS: One hundred two patients were eligible and enrolled. The means and standard deviations for age and BMI were 71.0 ± 8.2 years and 17.47 ± 1.48 kg/m2 , respectively. The CCR rate at 9 weeks was 25.9% (95% confidence interval [CI], 18.3%-35.3%), which met the primary end point with a lower 95% CI exceeding the prespecified minimum of 8%. Improvements in body weight and anorexia were durable and were accompanied by improvements in patients’ global impression of change for appetite/eating-related symptoms and overall condition. Adverse drug reactions occurred in 37 of 101 treated patients (36.6%), with the most common being glycosylated hemoglobin increases, constipation, and peripheral edema.

CONCLUSIONS: Anamorelin improved body weight and anorexia-related symptoms in patients with cancer cachexia and a low BMI with durable efficacy and favorable safety and tolerability.

LAY SUMMARY: Anamorelin is a drug that stimulates appetite and promotes weight gain. This clinical trial was aimed at determining its efficacy and safety in Japanese cancer patients with a low body mass index and cachexia, a syndrome associated with anorexia and weight loss. Anamorelin was found to improve body weight and anorexia-related symptoms in these patients, and these effects were durable for up to 24 weeks. Moreover, anamorelin was generally well tolerated. These findings suggest that anamorelin is a valuable treatment option for patients with cancer cachexia and a low body mass index.

PMID:35195274 | DOI:10.1002/cncr.34154

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Effect of perioperative FLOT versus ECF/ECX on short-term outcomes after surgery for resectable oesophagogastric adenocarcinoma: propensity score-matched study

BJS Open. 2022 Jan 6;6(1):zrac003. doi: 10.1093/bjsopen/zrac003.

ABSTRACT

BACKGROUND: Perioperative FLOT (fluorouracil plus leucovorin, oxaliplatin, and docetaxel) chemotherapy is a recent regimen used to treat resectable oesophagogastric (OG) adenocarcinoma, associated with improved overall survival versus earlier chemotherapy strategies. This study compared short-term perioperative morbidity in a large tertiary centre series of FLOT to a matched cohort receiving ECX/ECF (epirubicin, cisplatin, capecitabine (X) or 5-fluorouracil (F)).

METHODS: Consecutive patients completing four perioperative cycles of FLOT and proceeding to surgery with resectable OG adenocarcinoma were included. This was matched to patients from a historic ECX/ECF cohort from the same institution. A propensity score was calculated, and a secondary analysis using a propensity-matched group performed.

RESULTS: Cohorts were matched by tumour location and operations performed. In total there were 129 (64.5 per cent) oesophageal and 71 (35.5 per cent) gastric resections (FLOT 57 oesophageal, 43 gastric; ECF/ECX 64 oesophageal, 36 gastric). The median length of stay after surgery was 12 days in the FLOT group versus 15 in ECF/ECX (P = 0.035). There were no significant differences in overall perioperative complications and, specifically, no difference in OG anastomotic leaks, analysed by site (gastric (FLOT 0/79 (0 per cent) versus ECX 2/79 (2.5 per cent); P = 0.123), oesophageal (FLOT 4/121 (3.3 per cent) versus ECX 5/121 (4.1 per cent); P = 0.868) or type of surgery (open FLOT 1/121 (0.8 per cent) versus ECX 3/121 (2.5 per cent); P = 0.368; minimally invasive (FLOT 3/121 (2.5 per cent) versus ECX 2/121 (1.7 per cent); P = 0.555)). There was no statistical difference in leak-related return to theatre, 30-day (FLOT 0 (0 per cent) versus ECX 3/100 (3.0 per cent); P = 0.081), or 90-day (FLOT 0 (0 per cent) versus ECX 2/100 (2.0 per cent); P = 0.155) mortality.

CONCLUSION: In terms of surgical complications, FLOT and ECX/ECF were equally safe in patients undergoing resection for OG adenocarcinoma.

PMID:35195263 | DOI:10.1093/bjsopen/zrac003

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A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study

Eur Heart J. 2022 Feb 23:ehac093. doi: 10.1093/eurheartj/ehac093. Online ahead of print.

ABSTRACT

AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations.

METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS.

CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.

TAKE-HOME MESSAGE: The incorporation of polygenic risk into clinical care setting may provide a valuable risk stratification guidance to identify high-risk individuals for targeted intervention in primary prevention of CAD.

PMID:35195259 | DOI:10.1093/eurheartj/ehac093

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Survival of patients who opt for dialysis versus conservative care: a systematic review and meta-analysis

Nephrol Dial Transplant. 2022 Feb 23:gfac010. doi: 10.1093/ndt/gfac010. Online ahead of print.

ABSTRACT

BACKGROUND: Non-dialytic conservative care (CC) has been proposed as a treatment option for patients with kidney failure. This systematic review and meta-analysis aims to compare survival outcomes between dialysis and CC in studies where patients made an explicit treatment choice.

METHODS: Five databases were systematically searched from origin up to February 25th, 2021 for studies comparing survival outcomes among patients choosing dialysis versus CC. Adjusted and unadjusted survival rates were extracted and meta-analysis performed where applicable. Risk of bias analysis was performed according to the Cochrane Risk Of Bias In Non-randomised Studies – of Interventions (ROBINS-I).

RESULTS: Twenty-two cohort studies were included covering 21,344 patients. Most studies were prone to selection bias and confounding. Patients opting for dialysis were generally younger, had less comorbid conditions, functional impairments and frailty than patients who chose CC. Unadjusted median survival from treatment decision or eGFR <15mL/min/1.73m2 ranged between 20-67 months for dialysis and 6-31 months for CC. Meta-analysis of twelve studies that provided adjusted hazard ratios (HRs) for mortality showed a pooled adjusted HR of 0.47 (95% CI 0.39-0.57) for patients choosing dialysis compared to CC. In subgroups of patients with higher age or severe comorbidities, the reduction of mortality risk remained statistically significant, although analyses were unadjusted.

CONCLUSIONS: Patients opting for dialysis have an overall lower mortality risk compared to patients opting for CC. However, high risk of bias and heterogeneous reporting preclude definitive conclusions and results cannot be translated to an individual level.

PMID:35195249 | DOI:10.1093/ndt/gfac010

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Morpho-functional comparison of differentiation protocols to create iPSC-derived cardiomyocytes

Biol Open. 2022 Feb 15;11(2):bio059016. doi: 10.1242/bio.059016. Epub 2022 Feb 23.

ABSTRACT

Cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) offer an attractive platform for cardiovascular research. Patient-specific iPSC-CMs are very useful for studying disease development, and bear potential for disease diagnostics, prognosis evaluation and development of personalized treatment. Several monolayer-based serum-free protocols have been described for the differentiation of iPSCs into cardiomyocytes, but data on their performance are scarce. In this study, we evaluated two protocols that are based on temporal modulation of the Wnt/β-catenin pathway for iPSC-CM differentiation from four iPSC lines, including two control individuals and two patients carrying an SCN5A mutation. The SCN5A gene encodes the cardiac voltage-gated sodium channel (Nav1.5) and loss-of-function mutations can cause the cardiac arrhythmia Brugada syndrome. We performed molecular characterization of the obtained iPSC-CMs by immunostaining for cardiac specific markers and by expression analysis of selected cardiac structural and ionic channel protein-encoding genes with qPCR. We also investigated cell growth morphology, contractility and survival of the iPSC-CMs after dissociation. Finally, we performed electrophysiological characterization of the cells, focusing on the action potential (AP) and calcium transient (CT) characteristics using patch-clamping and optical imaging, respectively. Based on our comprehensive morpho-functional analysis, we concluded that both tested protocols result in a high percentage of contracting CMs. Moreover, they showed acceptable survival and cell quality after dissociation (>50% of cells with a smooth cell membrane, possible to seal during patch-clamping). Both protocols generated cells presenting with typical iPSC-CM AP and CT characteristics, although one protocol (that involves sequential addition of CHIR99021 and Wnt-C59) rendered iPSC-CMs, which were more accessible for patch-clamp and calcium transient experiments and showed an expression pattern of cardiac-specific markers more similar to this observed in human heart left ventricle samples.

PMID:35195246 | DOI:10.1242/bio.059016