Category: Nevin Manimala

Neuroimage Clin. 2021 Feb 10;30:102582. doi: 10.1016/j.nicl.2021.102582. Online ahead of print.

ABSTRACT

Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.

PMID:33636541 | DOI:10.1016/j.nicl.2021.102582

Vet Immunol Immunopathol. 2021 Feb 19;234:110216. doi: 10.1016/j.vetimm.2021.110216. Online ahead of print.

ABSTRACT

The pathogenesis of chronic inflammatory enteropathies (CIE) in dogs involves dysregulated innate immune responses. The receptor for advanced glycation end products (RAGE), a pattern recognition receptor, plays a role in chronic inflammation. Abrogation of proinflammatory RAGE signaling by ligand binding (e.g., S100/calgranulins) to soluble RAGE (sRAGE) might also be a novel therapeutic avenue. Serum sRAGE levels are decreased in canine CIE, but gastrointestinal tissue RAGE expression has not been investigated in dogs. Thus, the study aimed to evaluate the gastrointestinal mucosal RAGE expression in dogs with CIE. Further, the potential binding of RAGE to canine S100/calgranulin ligands was investigated. Epithelial RAGE expression was quantified in gastrointestinal (gastric, duodenal, ileal, and colonic) biopsies from 12 dogs with CIE and 9 healthy control dogs using confocal laser scanning microscopy. RAGE expression was compared between both groups of dogs and was tested for an association with patient characteristics, clinical variables, histologic lesion severity, and biomarkers of extra-gastrointestinal disease, systemic or gastrointestinal inflammation, function, or protein loss. Statistical significance was set at p < 0.05. RAGE:S100/calgranulin binding was assessed by immunoassay and electrophoretic techniques. RAGE expression was detected in all 59 biopsies from diseased and healthy control dogs evaluated. Epithelial RAGE expression in the duodenum and colon was significantly higher in dogs with CIE than in healthy controls (p < 0.04). Compared to healthy controls, RAGE expression in dogs with CIE also tended to be higher in the ileum but lower in the stomach. A slight (statistically not significant) shift towards more basal intestinal epithelial RAGE expression was detected in CIE dogs. Serum sRAGE was proportional to epithelial RAGE expression in the duodenum (p < 0.04), and RAGE expression in the colon inversely correlated with biomarkers of protein loss in serum (both p < 0.04). Several histologic morphologic and inflammatory lesion criteria and markers of inflammation (serum C-reactive protein and fecal calprotectin concentration) were related to epithelial RAGE expression in the duodenum, ileum, and/or colon. in vitro canine RAGE:S100A12 binding appeared more pronounced than RAGE:S100A8/A9 binding. This study showed a dysregulation of epithelial RAGE expression along the gastrointestinal tract in dogs with CIE. Compensatory regulations in the sRAGE/RAGE axis are an alternative explanation for these findings. The results suggest that RAGE signaling plays a role in dogs with CIE, but higher anti-inflammatory decoy receptor sRAGE levels paralleled RAGE overexpression. Canine S100/calgranulins were demonstrated to be ligands for RAGE.

PMID:33636544 | DOI:10.1016/j.vetimm.2021.110216

Epilepsy Behav. 2021 Feb 23;117:107711. doi: 10.1016/j.yebeh.2020.107711. Online ahead of print.

ABSTRACT

OBJECTIVE: It remains unclear whether transcranial magnetic stimulation (TMS) can replace the Wada test to determine language hemisphere dominance (HD). Using the Wada test as the gold standard, this study aimed to investigate the accuracy of navigated TMS (nTMS) in determining language HD.

METHODS: This study enrolled nine right-handed patients with drug-resistant epilepsy. We hypothesized that application of nTMS to language-related areas of the language-dominant hemisphere would induce positive manifestation of language dysfunction (LD). To test our hypothesis, the patients were instructed to perform a visual object-naming task while nTMS was applied to the anterior (e.g., Broca’s area) and posterior (e.g., Wernicke’s area) regions, which are closely related to language processing. The Wada test result was used as the gold standard, and the diagnostic value of nTMS was assessed using the Kappa consistency test.

RESULTS: The nTMS-induced LD positive rate for the bilateral anterior language areas (85.7%) was higher than that for the posterior language areas (57.1%). There was high consistency between nTMS stimulation of the left anterior and posterior language areas and the Wada test results for determining language HD. In contrast, the consistency of stimulation of the right anterior and posterior transfer sites was moderate (Kappa value = 0.545, P = 0.171) and low, respectively. For the latter, no statistical calculation was performed because stimulation of the right posterior speech area was negative in all patients compared with the Wada test results.

CONCLUSIONS: Our findings revealed that using nTMS to stimulate language-related left anterior and posterior areas could predict language HD with high accuracy. When the stimulation performance of these areas is positive, nTMS and the Wada test are equally accurate. Observing only negative performance may indicate that language HD has been transferred to the right side.

PMID:33636527 | DOI:10.1016/j.yebeh.2020.107711

Epilepsy Behav. 2021 Feb 12;117:107855. doi: 10.1016/j.yebeh.2021.107855. Online ahead of print.

ABSTRACT

OBJECTIVES: We assessed the impact of COVID-19 on children with epilepsy and their families, focusing on epilepsy management, family routines, learning, and adherence to Centers for Disease Control and Prevention (CDC) pandemic guidelines (e.g., social distancing, mask wearing) within the first six months of the pandemic. Group differences in COVID-19 impact on families were also examined based on race and ethnicity, being medically and/or geographically underserved, and insurance status.

METHODS: Participants (n = 131) included children with epilepsy and their families from two clinical trials. The Impact of COVID-19 on Pediatric Epilepsy Management (ICPEM) measure was developed and administered to caregivers online from April 2020 to September 2020 across four large pediatric hospitals. Administration of the ICPEM occurred both during routine study assessments and an additional acute time point to obtain information early in the pandemic (e.g., April and May 2020). Descriptive statistics and t-tests were used for analyses.

RESULTS: Data indicate minor to moderate impact of COVID-19 on pediatric epilepsy management. Caregivers of children with epilepsy reported the most impact on education and social functioning. Adherence to CDC guidelines was reported to be high. Those having public insurance reported greater difficulties obtaining daily anti-seizure medications compared to those with private insurance.

CONCLUSIONS: This study presents important initial data regarding the impact of COVID-19 epilepsy management and daily functioning in children with epilepsy and their families. While the acute impact of COVID-19 restrictions appear to be mild to moderate, it is unclear what the long-term impact of the pandemic will be on families of children with epilepsy.

PMID:33636530 | DOI:10.1016/j.yebeh.2021.107855

Health Expect. 2021 Feb 26. doi: 10.1111/hex.13214. Online ahead of print.

ABSTRACT

BACKGROUND: Less than 20% of youth who experience mental health difficulties access and receive appropriate treatment. This is exacerbated by barriers such as stigma, confidentiality concerns and lack of mental health literacy. A youth team developed the Wellness Quest: a health literacy tool to enable help-seeking youth to advocate for themselves.

OBJECTIVE: To evaluate the content, presentation and utility of the Wellness Quest tool among youth.

PARTICIPANTS: Participants aged 14 to 26.

METHODS: A youth research team conducted five focus groups and one online survey to evaluate the Wellness Quest tool. Thematic analysis was used to analyse the qualitative data, and descriptive statistics were used to explore the survey results.

MAIN RESULTS: Overall evaluations of the Wellness Quest were positive: participants felt it would be useful during their mental health help-seeking journey. Participants expressed the need for information about services for specific populations, such as Indigenous, immigrants, refugees and 2SLGBTQ + youth. They expressed that the tool should be available in complementary online and print versions.

DISCUSSION: Improving mental health literacy may improve mental health by enabling youth and those who support them to recognize and respond to signs of distress and understanding where and how to get help. The Wellness Quest tool may equip youth with the knowledge to make informed decisions and advocate for their own mental health, thereby facilitating help-seeking among youth.

PATIENT OR PUBLIC CONTRIBUTION: Youth as service users led all stages of the project, from designing and conducting the study and analysing the data to writing the manuscript.

PMID:33636052 | DOI:10.1111/hex.13214

Int J Clin Pract. 2021 Feb 26:e14118. doi: 10.1111/ijcp.14118. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the prediction values of the preoperative NLR, LMR, PLR, MPV, RDW for recurrence and progression of patients with non-muscle invasive bladder cancer (NMIBC).

METHODS: In this prospective study, 94 consecutive patients, newly diagnosed with NMIBC between July 2017 – August 2018 were included. The blood samples were collected from patients before transurethral resection of bladder tumor (TURB) and NLR, LMR, PLR, RDW, MPV values were calculated. The effect of these preoperative inflammatory parameters and other clinicopathological parameters on recurrence and progression rates were evaluated. Kaplan-Meier and multivariate Cox regression analyses were performed to identify significant prognostic variables.

RESULTS: The mean follow-up was 11 ± 6.4 months. Recurrence was observed in 35.1% and progression was detected in 7.4% of the patients. Neutrophil-lymphocyte ratio was statistically significantly associated with both recurrence (p = 0.01) and progression (p = 0.035) whereas lymphocyte-monocyte ratio was only associated with recurrence (p = 0.038). In the survival analyses, the relationship between recurrence and LMR was confirmed in both univariate (p = 0.021) and multivariate (p = 0.022) analyses. The relationship between NLR and recurrence was confirmed in univariate analysis (p = 0.019), however in multivariate analysis was found to be statistically insignificant (p = 0.051).

CONCLUSIONS: Lymphocyte-monocyte ratio might be an easy obtainable, non-invasive and cost-effective method for predicting recurrence of disease in patients with non-muscle invasive bladder cancer.

PMID:33636055 | DOI:10.1111/ijcp.14118

Adv Clin Exp Med. 2021 Feb 26. doi: 10.17219/acem/130357. Online ahead of print.

ABSTRACT

BACKGROUND: The laparoscopic totally extraperitoneal inguinal hernia repair (TEP), unlike the Lichtenstein tension-free mesh repair, allows for inspecting the femoral canal area for the presence of an occult femoral hernia.

OBJECTIVES: To determine the incidence of an unsuspected femoral hernia in patients undergoing TEP repair.

MATERIAL AND METHODS: Data was collected prospectively from 180 patients (23 women) who underwent hernia repair, including examination of the femoral canal, between November 2017 and March 2019, and the incidence of a femoral hernia was determined. Correlations between the incidence of a femoral hernia and sex, age and the type of inguinal hernia diagnosed in the patients (indirect, direct, both indirect and direct) were assessed.

RESULTS: Femoral hernias were found in 14 patients (7.77%). None of the hernias had previously been detected clinically. The incidence of a femoral hernia was higher in women (6/23, 26.07%) than in men (8/157, 5.09%). The incidence of a femoral hernia was higher in older patients: the average age of patients with a femoral hernia was 57.86 years (median: 60 years), whereas the average age of patients without a femoral hernia was 49.92 years (median: 49 years). However, the correlation was not statistically significant. No correlation was found between the incidence of a femoral hernia and the type of inguinal hernia diagnosed in the patients (direct, indirect, both indirect and direct).

CONCLUSIONS: The TEP repair allows for detecting and repairing an occult femoral hernia.

PMID:33636062 | DOI:10.17219/acem/130357

Int J Clin Pract. 2021 Feb 26:e14115. doi: 10.1111/ijcp.14115. Online ahead of print.

ABSTRACT

AIMS: To evaluate the effect of pre-RIRS ESWL on the efficiency and safety of RIRS in the treatment of proximal ureter stones.

METHODS: The patients in the study population were divided into 2 groups. Group-1 was composed of patients who had undergone ESWL for proximal ureter stones before RIRS, and Group-2 was composed of patients who directly underwent RIRS without any prior ESWL. The clinical and demographic properties of the patients were analysed in the RIRSearch database. The operative outcomes, peroperative complications, postoperative complications, hospitalization time and the stone-free rates were compared between the groups.

RESULTS: There were 56 patients in Group-1 and 95 patients in Group-2. The demographic and clinical properties were similar between the groups. The stone-free rates, peroperative complications and postoperative complications were also similar between the groups; however, the fluoroscopy time was significantly higher in Group-1 (p=.043). The cut-off duration of 10 weeks between ESWL and RIRS had reasonable/favourable discriminating ability, with a 51% sensitivity and 88% specificity rate for stone-free status.

CONCLUSION: Performing ESWL on the proximal ureter stones before RIRS did not change the efficacy and safety of RIRS. The time between the patient’s last ESWL session and RIRS had a predictive value for stone-free status, but did not have any effect on complications.

PMID:33636023 | DOI:10.1111/ijcp.14115

Prostate. 2021 Feb 26. doi: 10.1002/pros.24110. Online ahead of print.

ABSTRACT

BACKGROUND: AR-V7-positive metastatic prostate cancer is a lethal phenotype with few treatment options and poor survival.

METHODS: The two-cohort nonrandomized Phase 2 study of combined immune checkpoint blockade for AR-V7-expressing metastatic castration-resistant prostate cancer (STARVE-PC) evaluated nivolumab (3 mg/kg) plus ipilimumab (1 mg/kg), without (Cohort 1) or with (Cohort 2) the anti-androgen enzalutamide. Co-primary endpoints were safety and prostate-specific antigen (PSA) response rate. Secondary endpoints included time-to-PSA-progression-free survival (PSA-PFS), time-to-clinical/radiographic-PFS, objective response rate (ORR), PFS lasting greater than 24 weeks, and overall survival (OS).

RESULTS: Thirty patients were treated with ipilimumab plus nivolumab (N = 15, Cohort 1, previously reported), or ipilimumab plus nivolumab and enzalutamide (N = 15, Cohort 2) in patients previously progressing on enzalutamide monotherapy. PSA response rate was 2/15 (13%) in cohort 1 and 0/15 in cohort 2, ORR was 2/8 (25%) in Cohort 1 and 0/9 in Cohort 2 in those with measureable disease, median PSA-PFS was 3.0 (95% confidence interval [CI]: 2.1-NR) in cohort 1 and 2.7 (95% CI: 2.1-5.9) months in cohort 2, and median PFS was 3.7 (95% CI: 2.8-7.5) in cohort 1 and 2.9 (95% CI: 1.3-5.8) months in cohort 2. Three of 15 patients in cohort 1 (20%, 95% CI: 7.1%-45.2%) and 4/15 patients (26.7%, 95% CI: 10.5%-52.4%) in cohort 2 achieved a durable PFS lasting greater than 24 weeks. Median OS was 8.2 (95% CI: 5.5-10.4) in cohort 1 and 14.2 (95% CI: 8.5-NA) months in cohort 2. Efficacy results were not statistically different between cohorts. Grade-3/4 adverse events occurred in 7/15 cohort 1 patients (46%) and 8/15 cohort 2 patients (53%). Combined cohort (N = 30) baseline alkaline phosphatase and cytokine analysis suggested improved OS for patients with lower alkaline phosphatase (hazards ratio [HR], 0.30; 95% CI: 0.11-0.82), lower circulating interleukin-7 (IL-7) (HR, 0.24; 95% Cl: 0.06-0.93) and IL-6 (HR, 0.13; 95% Cl: 0.03-0.52) levels, and higher circulating IL-17 (HR, 4.53; 95% CI: 1.47-13.93) levels. There was a trend towards improved outcomes in men with low sPD-L1 serum levels.

CONCLUSION: Nivolumab plus ipilimumab demonstrated only modest activity in patients with AR-V7-expressing prostate cancer, and was not sufficient to justify further exploration in unselected patients. Stratification by baseline alkaline phosphatase and cytokines (IL-6, -7, and -17) may be prognostic for outcomes to immunotherapy.

PMID:33636027 | DOI:10.1002/pros.24110

J Thromb Haemost. 2021 Feb 26. doi: 10.1111/jth.15277. Online ahead of print.

ABSTRACT

BACKGROUND: Dabigatran etexilate (DE), a direct oral thrombin inhibitor, has been evaluated in children with venous thromboembolism (VTE) using oral solution, pellets, or capsules.

OBJECTIVES: This study evaluated DE pharmacokinetics (PK) in children with VTE and the appropriateness of a DE pediatric age- and weight-based dosing algorithm. Patients/Methods A population PK model was fitted to data from four single-arm and one randomized, comparative pediatric VTE studies (358 children aged birth to <18 years; 2748 PK observations) and one healthy-adult study (32 males aged <40 years; 1523 PK observations) using nonlinear mixed-effects modeling. A stepwise, covariate, model-building procedure evaluated the influence of covariates (e.g., age, body weight, body surface area [BSA]-normalized renal function, and sex). The final model was used to evaluate the pediatric dosing algorithm, with simulations comparing pediatric trough exposure with reference exposure defined for the pediatric studies.

RESULTS: The population PK of dabigatran was adequately described by a two-compartment model with first-order elimination and absorption. Age, weight, BSA-normalized renal function, and sex were statistically significant covariates (all P<0.05). Apparent clearance increased with age (independently of body weight), diminished with decreasing BSA-normalized renal function, and was lower in females than males. All disposition parameters increased with body weight escalation (allometric scaling). Simulations confirmed that for all DE formulations, the final pediatric dosing algorithms achieved reference exposure without dose adjustment.

CONCLUSIONS: Using a population PK model of DE for children with VTE, simulations showed that the final dosing algorithms were appropriate for all DE formulations; no dose titration was needed.

PMID:33636042 | DOI:10.1111/jth.15277