Bone-marrow mononuclear cells and acellular human amniotic membrane improve global cardiac function without inhibition of the NLRP3 Inflammasome in a rat model of heart failure.

Recent studies have suggested that therapies with stem cells and amniotic membrane can modulate the inflammation following an ischemic injury in the heart. This study evaluated the effects of bone-marrow mononuclear cells (BMMC) and acellular human amniotic membrane (AHAM) on cardiac function and NLRP3 complex in a rat model of heart failure.On the 30th day,the echocardiographic showed improvements on ejection fraction and decreased pathological ventricular remodeling on BMMC and AHAM groups.Oxidative stress analysis was similar between the three groups,and the NLRP3 inflammasome activity were not decreased with the therapeutic use of both BMMC and AHAM,in comparison to the control group.

Dysglycemias in patients admitted to ICUs with severe acute respiratory syndrome due to COVID-19 versus other causes - a cohort study.

BACKGROUND: Dysglycemias have been associated with worse prognosis in critically ill patients with COVID-19, but data on the association of dysglycemia with COVID-19 in comparison with other forms of severe acute respiratory syndrome are lacking. This study aimed to compare the occurrence of different glycemic abnormalities in patients with severe acute respiratory syndrome and COVID-19 admitted to intensive care units versus glycemic abnormalities in patients with severe acute respiratory syndrome from other causes, to evaluate the adjusted attributable risk associated with COVID-19 and dysglycemia and to assess the influence of these dysglycemias on mortality. METHODS: We conducted a retrospective cohort of consecutive patients with severe acute respiratory syndrome and suspected COVID-19 hospitalized in intensive care units between March 11 and September 13, 2020, across eight hospitals in Curitiba-Brazil. The primary outcome was the influence of COVID-19 on the variation of the following parameters of dysglycemia: highest glucose level at admission, mean and highest glucose levels during ICU stay, mean glucose variability, percentage of days with hyperglycemia, and hypoglycemia during ICU stay. The secondary outcome was the influence of COVID-19 and each of the six parameters of dysglycemia on hospital mortality within 30 days from ICU admission. RESULTS: The sample consisted of 841 patients, of whom 703 with and 138 without COVID-19. Comparing patients with and without COVID-19, those with COVID-19 had significantly higher glucose peaks at admission (165 mg/dL vs. 146 mg/dL; p = 0.002) and during ICU stay (242 mg/dL vs. 187md/dL; p < 0.001); higher mean daily glucose (149.7 mg/dL vs. 132.6 mg/dL; p < 0.001); higher percentage of days with hyperglycemia during ICU stay (42.9% vs. 11.1%; p < 0.001); and greater mean glucose variability (28.1 mg/dL vs. 25.0 mg/dL; p = 0.013). However, these associations were no longer statistically significant after adjustment for Acute Physiology and Chronic Health Evaluation II scores, Sequential Organ Failure Assessment scores, and C-reactive protein level, corticosteroid use and nosocomial infection. Dysglycemia and COVID-19 were each independent risk factors for mortality. The occurrence of hypoglycemia (< 70 mg/dL) during ICU stay was not associated with COVID-19. CONCLUSION: Patients with severe acute respiratory syndrome due to COVID-19 had higher mortality and more frequent dysglycemia than patients with severe acute respiratory syndrome due to other causes. However, this association did not seem to be directly related to the SARS-CoV-2 infection.

Biological therapy, surgery, and hospitalization rates for inflammatory bowel disease: An observational Latin American comparative study between adults and pediatric patients.

OBJECTIVE: Compare the proportions of use of biological therapy, surgeries, and hospitalizations between adults and pediatric inflammatory bowel disease (IBD)-Crohn's disease (CD) and ulcerative colitis (UC)-patients. PATIENTS AND METHODS: Observational, retrospective, and multicenter study. Data were collected from all consecutive IBD patients seen as outpatients or admitted to hospital, during 2015-2021, in two IBD tertiary centers in a South Brazilian capital. Patients with unclassified colitis diagnosis were excluded from this study. Patients were classified as having CD or UC and sub-categorized as adult or pediatric according to age. Data were analyzed using frequency, proportion, Fisher's exact test, and Chi-square test. RESULTS: A total of 829 patients were included: 509 with CD (378 adults/131 pediatric) and 320 with UC (225/95). Among patients with CD, no differences were observed for proportions of use of biological therapy (80.2% in pediatric vs. 73.3% in adults; P=0.129), surgery (46.6% vs. 50.8%; P=0.419), or hospitalization (64.9% vs. 56.9%; P=0.122). In UC, significant differences were observed for biological therapy (40.0% vs. 28.0%; P=0.048) and hospitalization (47.4% vs. 24.0%; P<0.001). No significant difference was observed in surgery rates (17.9% vs. 12.4%; P=0.219). CONCLUSIONS: Biological therapy and incidence of hospitalization were greater among pediatric patients with UC, compared with adults; no difference was observed in the need for abdominal surgery. In CD, no significant difference was observed in the three main outcomes between the age groups.

Nonalcoholic Fatty Liver Disease and Coronary Artery Disease: Big Brothers in Patients with Acute Coronary Syndrome.

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing. This study aimed to evaluate the prevalence of NAFLD, as diagnosed by ultrasound, in patients with acute coronary syndrome (ACS) and to assess whether NAFLD is associated with the severity of coronary obstruction as diagnosed by coronary angiography. METHODS: We performed a prospective single-center study in patients hospitalized due to acute coronary syndrome who underwent diagnostic coronary angiography. Consecutive patients who presented to the emergency room were diagnosed with acute coronary syndrome and were included. All patients underwent ultrasonography of the upper abdomen to determine the presence or absence of NAFLD; NAFLD severity was graded from 0 to 3 based on a previously validated scale. All patients underwent diagnostic coronary angiography in the same hospital, with the same team of interventional cardiologists, who were blinded to the patients' clinical and ultrasonographic data. CAD was then angiographically graded from none to severe based on well-established angiographic criteria. RESULTS: This study included 139 patients, of whom 83 (59.7%) were male, with a mean age of 59.7 years. Of the included patients, 107 (77%) patients had CAD, 63 (45%) with serious injury. Regarding the presence of NAFLD, 76 (55.2%) had NAFLD including 18 (23.6%) with grade III disease. In severe CAD, 47 (60.5%) are associated with NAFLD, and 15 (83.3%) of the patients had severe CAD and NAFLD grade III. CONCLUSIONS: NAFLD is common in patients with ACS. The intensity of NAFLD detected by ultrasonography is strongly associated with the severity of coronary artery obstruction on angiography.

Investigation of the Relationship Between Electrical Stimulation Frequency and Muscle Frequency Response Under Submaximal Contractions.

Neuromuscular electrical stimulation (NMES) is a common tool that is used in clinical and laboratory experiments and can be combined with mechanomyography (MMG) for biofeedback in neuroprostheses. However, it is not clear if the electrical current applied to neuromuscular tissues influences the MMG signal in submaximal contractions. The objective of this study is to investigate whether the electrical stimulation frequency influences the mechanomyographic frequency response of the rectus femoris muscle during submaximal contractions. Thirteen male participants performed three maximal voluntary isometric contractions (MVIC) recorded in isometric conditions to determine the maximal force of knee extensors. This was followed by the application of nine modulated NMES frequencies (20, 25, 30, 35, 40, 45, 50, 75, and 100 Hz) to evoke 5% MVIC. Muscle behavior was monitored by the analysis of MMG signals, which were decomposed into frequency bands by using a Cauchy wavelet transform. For each applied electrical stimulus frequency, the mean MMG spectral/frequency response was estimated for each axis (X, Y, and Z axes) of the MMG sensor with the values of the frequency bands used as weights (weighted mean). Only with respect to the Z (perpendicular) axis of the MMG signal, the stimulus frequency of 20 Hz did not exhibit any difference with the weighted mean (P = 0.666). For the frequencies of 20 and 25 Hz, the MMG signal displayed the bands between 12 and 16 Hz in the three axes (P < 0.050). In the frequencies from 30 to 100 Hz, the muscle presented a higher concentration of the MMG signal between the 22 and 29 Hz bands for the X and Z axes, and between 16 and 34 Hz bands for the Y axis (P < 0.050 for all cases). We observed that MMG signals are not dependent on the applied NMES frequency, because their frequency contents tend to mainly remain between the 20- and 25-Hz bands. Hence, NMES does not interfere with the use of MMG in neuroprosthesis.

Peritonitis as a risk factor for long-term cardiovascular mortality in peritoneal dialysis patients: The case of a friendly fire?

AIM: Since the impact of peritonitis on long-term non-infectious mortality has not been investigated until the present, the aim of this study was to analyze the impact of peritonitis on long-term cardiovascular (CV) mortality in a large peritoneal dialysis (PD) cohort. METHODS: The analysis was based on BRAZPD II, a national prospective cohort study that recruited patients in Brazilian centres from December 2004 to January 2011. Incident adult PD patients with at least 90 days on treatment were included in the analysis. Cardiovascular death occurring after a minimum of 30 days after a peritonitis episode was considered the primary endpoint. Cox regression analysis for time-dependent variables was used for the adjustments. RESULTS: There were 2405 episodes of peritonitis in 5707 patients (48% males, 44% diabetes, 73% hypertensive). Patients with one episode of peritonitis presented a 22% increase in the hazard ratio of late CV mortality compared to those who never experienced peritonitis (HR1.22; CI95%1.01-1.47). Adjusted hazard for CV mortality showed a stepwise negative effect on survival for each additional peritonitis episode of infection: two episodes (HR1.78; CI95%1.31-2.42), three episodes (HR2.81; CI95%1.83-4.32) and four episodes (HR3.84; CI95%2.01-7.32). CONCLUSION: Peritonitis was an independent predictor of CV mortality and the frequency of peritonitis was strongly associated with an increase in this risk. This is the first study to demonstrate the impact of peritonitis on late cardiovascular mortality of PD patients, suggesting a link between acute inflammation and cardiovascular outcomes.

Adalimumab and postoperative complications of elective intestinal resections in Crohn's disease: a propensity score case-matched study.

BACKGROUND: data are scarce regarding the effect of preoperative Adalimumab (ADA) in postoperative complications in Crohn's disease (CD) patients. AIM: to compare the rates of postoperative complications after intestinal resections in CD, with and without previous exposure to ADA. METHOD: case-matched retrospective observational study of patients submitted to intestinal resections for CD. The patients were allocated to 2 groups, according to their previous exposure to ADA before surgery. The patients under ADA therapy were matched with controls (patients without previous biologics) with the propensity score method (PSM), according to age at surgery, CD location (Montreal L) and phenotype (Montreal B). Medical and surgical complications were compared. RESULTS: 123 patients were initially considered, 71 with previous biologics (32 under ADA therapy) and 52 without. The PSM selected 25 ADA patients to be matched with 25 controls from the non-biologics group. There was no difference regarding overall surgical complications (40% in the control vs 36% in the ADA group; p = 1.0000) or medical complications (36% vs 12% in the control and ADA groups, respectively; p = 0.095). In univariate analysis, previous ADA was not considered a risk factor for higher postoperative complication rates. Stomas were considered a risk factor for surgical complications, and previous steroids were associated to higher medical complication rates. CONCLUSIONS: preoperative ADA did not influence the rates of medical and surgical complications after elective intestinal resections for CD. This was the first study to include exclusively patients under ADA therapy. This article is protected by copyright. All rights reserved.

Tumor Necrosis Factor Alpha Inhibitors Did Not Influence Postoperative Morbidity After Elective Surgical Resections in Crohn's Disease.

BACKGROUND: The real impact of anti-tumor necrosis alpha (TNF) therapy in postoperative complications after intestinal resections in Crohn's disease (CD) still needs to be determined. AIMS: To compare the postoperative complication rates after elective intestinal resections in CD patients, with or without previous exposure to anti-TNF therapy. METHODS: This was a retrospective and observational study, with elective intestinal resections for CD (emergency procedures were excluded). Patients were allocated in two groups according to preoperative anti-TNF status. Surgical and medical complications were analyzed and subsequently compared between the groups. RESULTS: A total of 123 patients were included (71 with and 52 without preoperative anti-TNF). The groups were considered homogeneous, except for perianal CD, previous azathioprine, and stomas. There was no significant difference between the groups regarding overall surgical complications (32.69% in anti-TNF- vs. 39.44% in anti-TNF+ patients, p = 0.457) or overall medical complications (21.15 vs. 21.13%, respectively, p = 1.000). In univariate analysis, previous steroids, perianal CD, and stomas were considered risk factors for surgical complications, and previous steroids and hypoalbuminemia for medical complications. In multivariate analysis, previous steroids were associated with higher rates of surgical and medical complications, while hypoalbuminemia was associated with higher medical complication rates. CONCLUSIONS: There was no influence of the previous use of anti-TNF agents in postoperative surgical and medical complication rates in elective intestinal resections for CD. Previous steroids and hypoalbuminemia were associated with higher complication rates. This was the first case series of the literature describing outcomes in exclusively elective operations.

Comparison between types of dressing following catheter insertion and early exit-site infection in peritoneal dialysis.

AIMS AND OBJECTIVES: To investigate whether the type of dressing used (occlusive vs. semi-occlusive) impacts on exit-site infection. BACKGROUND: The exit-site infections are a major predisposing factor for peritoneal dialysis-related peritonitis, the main cause of technique failure and an important cause of mortality. The care taken in exit-site dressing is considered an important procedure for the prevention of trauma and contamination of this area. Nevertheless, to our knowledge, no study has yet analysed the impact of different dressing types on early exit-site infection (up to two months after catheter insertion). DESIGN: A prospective observational study involving the BRAZPD II (Brazilian Peritoneal Dialysis Multicenter Study) cohort. METHODS: All incident patients with data available for dressing type applied following peritoneal dialysis catheter insertion were included in the study. A multilevel logistic regression model was used to compare the log-odds of exit-site infections between groups. RESULTS: A total of 2460 incident patients were included. Occlusive and semi-occlusive dressings were applied in 82·6% (n = 2031) and 17·4% (n = 427) of patients, respectively. Exit-site infection incidence was not affected by the type of dressing used, with a logit for occlusive dressing of 2·15 (95% CI 0·81-5·70). The combined outcome of exit-site infection and tunnel infection also showed no significance between the groups (logit 1·46, 95% CI 0·72-2·97). CONCLUSION: Our results indicate that the type of exit-site dressing used during the healing phase following peritoneal dialysis catheter insertion has no impact on early exit-site infection rates. RELEVANCE TO CLINICAL PRACTICE: Provides evidence to support the similarity between occlusive and semi-occlusive dressing regarding infection rates in exit site of peritoneal dialysis catheter, therefore allowing the choice to be made accordingly to routine or availability.

Improving first responders' psychogenic nonepileptic seizures diagnosis accuracy: Development and validation of a 6-item bedside diagnostic tool.

OBJECTIVE: Epileptic seizures (ES) are often seen as a medical emergency, and their immediate and accurate recognition are pivotal in providing acute care. However, a number of clinical situations may mimic ES, potentially leading to misdiagnosis at the emergency room and to inappropriate prescription of antiepileptic drugs (AED) in the acute and chronic settings. Psychogenic nonepileptic seizures (PNES) play a major role in this scenario and often delay the correct diagnosis and increase treatment morbidity and cost. First responders often conduct the initial assessment of these patients, and their impression may be decisive in the prehospital approach to seizures. We sought to investigate and improve the accuracy of PNES diagnosis among professionals involved in the initial assistance to patients with seizures. METHODS: Fifty-three registered nurses, 34 emergency physicians, 33 senior year medical students, and 12 neurology residents took a short training program consisting of an initial video-based seizure assessment test (pretest), immediately followed by a 30-minute presentation of a 6-item bedside diagnostic tool and then a video-based reassessment (posttest). Baseline status and learning curves were determined. RESULTS: The distinct professional categories showed no significant differences in their ability to diagnose PNES on both pretests and posttests. All groups improved diagnostic skills after the instructional program. SIGNIFICANCE: The findings helped determine the best identifiable PNES clinical signs and to provide initial validation to a novel diagnostic instrument. In addition, our results showed that educational measures might help in the identification of PNES by first responders, which may decrease the treatment gap.

Impact of patient training patterns on peritonitis rates in a large national cohort study.

BACKGROUND: Ideal training methods that could ensure best peritoneal dialysis (PD) outcome have not been defined in previous reports. The aim of the present study was to evaluate the impact of training characteristics on peritonitis rates in a large Brazilian cohort. METHODS: Incident patients with valid data on training recruited in the Brazilian Peritoneal Dialysis Multicenter Study (BRAZPD II) from January 2008 to January 2011 were included. Peritonitis was diagnosed according to International Society for Peritoneal Dialysis guidelines; incidence rate of peritonitis (episodes/patient-months) and time to the first peritonitis were used as end points. RESULTS: Two thousand two hundred and forty-three adult patients were included in the analysis: 59 ± 16 years old, 51.8% female, 64.7% with ≤4 years of education. The median training time was 15 h (IQI 10-20 h). Patients were followed for a median of 11.2 months (range 3-36.5). The overall peritonitis rate was 0.29 per year at risk (1 episode/41 patient-months). The mean number of hours of training per day was 1.8 ± 2.4. Less than 1 h of training/day was associated with higher incidence rate when compared with the intervals of 1-2 h/day (P = 0.03) and >2 h/day (P = 0.02). Patients who received a cumulative training of >15 h had significantly lower incidence of peritonitis compared with <15 h (0.26 per year at risk versus 0.32 per year at risk, P = 0.01). The presence of a caregiver and the number of people trained were not significantly associated with peritonitis incidence rate. Training in the immediate 10 days after implantation of the catheter was associated with the highest peritonitis rate (0.32 per year), compared with training prior to catheter implantation (0.28 per year) or >10 days after implantation (0.23 per year). More experienced centers had a lower risk for the first peritonitis (P = 0.003). CONCLUSIONS: This is the first study to analyze the association between training characteristics and outcomes in a large cohort of PD patients. Low training time (particularly <15 h), smaller center size and the timing of training in relation to catheter implantation were associated with a higher incidence of peritonitis. These results support the recommendation of a minimum amount of training hours to reduce peritonitis incidence regardless of the number of hours trained per day.

Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH).

BACKGROUND: Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. METHODS: This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. RESULTS: Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). CONCLUSIONS: The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Disease duration did not influence the rates of loss of efficacy of the anti-TNF therapy in Latin American Crohn's disease patients.

BACKGROUND/AIMS: The efficacy of both Infliximab (IFX) and Adalimumab (ADA) can be reduced over time. The aim of this study was to analyze the incidence of loss of efficacy (LOE) of both IFX and ADA, and outline the influence of disease duration on its occurrence. METHODS: Retrospective, multicenter, observational cohort study, with CD patients treated with anti-TNF therapy. LOE was defined as the need for steroids, occurrence of major abdominal surgery during treatment, dose increase, interval shortening or switching of the anti- TNF agent. Patients were allocated in three subgroups based on disease duration (DD): <24 months, between 24 and 60 months and >60 months. RESULTS: 175 patients were included in the study (117 under IFX and 58 under ADA therapy). LOE occurred in 32% of patients with DD <24 months, in 33.3% with DD between 24 and 60 months and in 31.3% of subjects with DD over 60 months (p = 0.975). CONCLUSIONS: Disease duration (DD) did not influence LOE rates. These results suggest that in real-world observational practice, patients with early CD might have the same rates of LOE than patients with a disease prolonging for a longer duration.

Evaluation of Salt Intake, Urinary Sodium Excretion and Their Relationship to Overhydration in Chronic Kidney Disease Patients.

The purpose of this study was to estimate sodium intake in a group of patients with chronic kidney disease (CKD) and to correlate the results with the urinary excretion values of sodium and signs of fluid overload. We included patients with CKD in different stages. Urinary sodium was measured in 24 h urine samples. Body composition monitor (BCM) was used to estimate the hydration status. Sixty patients (38 ± 15 ml/min of GFR) presented 4.14 ± 1.71 g/24 h of urinary sodium excretion. Overhydration was detected in 50% of the patients by the BCM. There was a positive correlation between the measured sodium excretion values and BCM, ICW, ECW and TBW. In conclusion, markers of overhydration evaluated by BCM were positively correlated with urinary sodium excretion.

FasL expression in articular discs of human temporomandibular joint and association with osteoarthrosis.

BACKGROUND: Apoptosis is a programme of cell death which does not induce an inflammatory response. Recent previous research has suggested a correlation between temporomandibular internal derangement and apoptosis. Fas ligand (FasL) is an apoptosis-inducing factor, known to trigger apoptosis through distinct signal pathways. This study aims to examine, by immunohistochemistry, the expression of FasL in temporomandibular joint (TMJ) articular discs of patients with anterior disc displacement with reduction (ADDwR) and without reduction (ADDwoR) in patients with and without osteoarthrosis (OA). METHODS: Forty-two (n = 42) TMJ articular discs were divided into two cut-offs: (i) 8 control, 17 ADDwR, 17 ADDwoR, and (ii) without OA (n = 25) and with OA (n = 17). The area of immunostaining was compared statistically between groups (P < 0.05). RESULTS: Statistically significant differences were found in the expression of FasL in TMJ discs between the three groups (P = 0.001). ADDwR presented significant higher FasL expression when compared with ADDwoR (P < 0.001). Significant higher FasL expression was observed in the group without OA (P = 0.001). All patients without OA presented ADDwR, while all the patients with OA presented ADDwoR. CONCLUSION: A higher area of in situ immunostaining of FasL was found in temporomandibular discs with reduction, which is the less severe condition. Moreover, a reduced expression of FasL in the discs of patients with osteoarthrosis was found, suggesting that some aspects of apoptosis might underlie the progression of TMJ disorders.

The online educational tool "Roadmap to EEGs" significantly improved trainee performance in recognizing EEG patterns.

OBJECTIVE: We created a framework to assess the competency-based EEG curriculum, outlined by the International League Against Epilepsy (ILAE) through a video-based online educational resource ("Roadmap to EEGs") and assessed its effectiveness and feasibility in improving trainees' knowledge. METHODS: Ten video-based e-learning modules addressed seven key topics in EEG and epileptology (normal EEG, normal variants, EEG artifacts, interictal epileptiform discharges (IED), focal seizures, idiopathic generalized epilepsy (IGE), and developmental and epileptic encephalopathies (DEE)). We posted the educational videos on YouTube for free access. Pre- and post-tests, each comprising 20 multiple-choice questions, were distributed to institution leadership and advertised on social media platforms to reach a global audience. The tests were administered online to assess the participants' knowledge. Pre- and post-test questions showed different EEG samples to avoid memorization and immediate recall. After completing the post-test, participants were asked to respond to 7 additional questions assessing their confidence levels and recommendations for improvement. RESULTS: A total of 52 complete and matched pre- and post-test responses were collected. The probability of a correct response was 73% before teaching (95% CI: 70%-77%) and 81% after teaching (95% CI: 78%-84%). The odds of a correct response increased significantly by 59% (95% CI: 28%-98%, p < .001). For participants having >4 weeks of EEG training, the probability of a correct response was 76% (95% CI: .72-.79) and 81% after teaching (95% CI: .78-.84). The odds of answering correctly increased by 44% (95% CI: 15%-80%, p = .001). Participants felt completely confident in independently interpreting and identifying EEG findings after completing the teaching modules (17.1% before vs. 37.8% after, p-value < .0001). 86.5% of participants expressed a high likelihood of recommending the module to other trainees. SIGNIFICANCE: The video-based online educational resource allows participants to acquire foundational knowledge in EEG/epilepsy, and participants to review previously learned EEG/epilepsy information.

Expert accuracy and inter-rater agreement of "must-know" EEG findings for adult and child neurology residents.

OBJECTIVE: We published a list of "must-know" routine EEG (rEEG) findings for trainees based on expert opinion. Here, we studied the accuracy and inter-rater agreement (IRA) of these "must-know" rEEG findings among international experts. METHODS: A previously validated online rEEG examination was disseminated to EEG experts. It consisted of a survey and 30 multiple-choice questions predicated on the previously published "must-know" rEEG findings divided into four domains: normal, abnormal, normal variants, and artifacts. Questions contained de-identified 10-20-s epochs of EEG that were considered unequivocal examples by five EEG experts. RESULTS: The examination was completed by 258 international EEG experts. Overall mean accuracy and IRA (AC1) were 81% and substantial (0.632), respectively. The domain-specific mean accuracies and IRA were: 76%, moderate (0.558) (normal); 78%, moderate (0.575) (abnormal); 85%, substantial (0.678) (normal variants); 85%, substantial (0.740) (artifacts). Academic experts had a higher accuracy than private practice experts (82% vs. 77%; p = .035). Country-specific overall mean accuracies and IRA were: 92%, almost perfect (0.836) (U.S.); 86%, substantial (0.762) (Brazil); 79%, substantial (0.646) (Italy); and 72%, moderate (0.496) (India). In conclusion, collective expert accuracy and IRA of "must-know" rEEG findings are suboptimal and heterogeneous. SIGNIFICANCE: We recommend the development and implementation of pragmatic, accessible, country-specific ways to measure and improve the expert accuracy and IRA.

A randomized controlled educational pilot trial of interictal epileptiform discharge identification for neurology residents.

OBJECTIVE: To assess the effectiveness of an educational program leveraging technology-enhanced learning and retrieval practice to teach trainees how to correctly identify interictal epileptiform discharges (IEDs). METHODS: This was a bi-institutional prospective randomized controlled educational trial involving junior neurology residents. The intervention consisted of three video tutorials focused on the six IFCN criteria for IED identification and rating 500 candidate IEDs with instant feedback either on a web browser (intervention 1) or an iOS app (intervention 2). The control group underwent no educational intervention ("inactive control"). All residents completed a survey and a test at the onset and offset of the study. Performance metrics were calculated for each participant. RESULTS: Twenty-one residents completed the study: control (n = 8); intervention 1 (n = 6); intervention 2 (n = 7). All but two had no prior EEG experience. Intervention 1 residents improved from baseline (mean) in multiple metrics including AUC (.74; .85; p < .05), sensitivity (.53; .75; p < .05), and level of confidence (LOC) in identifying IEDs/committing patients to therapy (1.33; 2.33; p < .05). Intervention 2 residents improved in multiple metrics including AUC (.81; .86; p < .05) and LOC in identifying IEDs (2.00; 3.14; p < .05) and spike-wave discharges (2.00; 3.14; p < .05). Controls had no significant improvements in any measure. SIGNIFICANCE: This program led to significant subjective and objective improvements in IED identification. Rating candidate IEDs with instant feedback on a web browser (intervention 1) generated greater objective improvement in comparison to rating candidate IEDs on an iOS app (intervention 2). This program can complement trainee education concerning IED identification.

Immunohistochemical Profiling of PD-1, PD-L1, CD8, MSI, and p53 and Prognostic Implications in Advanced Serous Ovarian Carcinoma: A Retrospective Study.

Advanced high-grade serous ovarian carcinoma is a serious malignant neoplasm with a late diagnosis and high mortality rate. Even when treated with standard therapy, such as surgery followed by carboplatin and paclitaxel chemotherapy, the prognosis remains unfavorable. Immunotherapy is a treatment alternative that requires further study. Therefore, we aimed to evaluate the expression of PD-1, PD-L1, CD8, MSI (MLH1, MSH2, MSH6, and PMS2), and p53 in the paraffin samples of high-grade serous ovarian carcinoma. A retrospective study of 28 southern Brazilian patients with advanced serous ovarian carcinoma (EC III or IV) was conducted between 2009 and 2020. The expression of these proteins was evaluated using immunohistochemistry, and the results were correlated with the patients' clinicopathological data. At diagnosis, the mean age was 61 years, and the most common clinical stage (60%) was EC III. Among the cases, 84.6% exhibited p53 overexpression, 14.8% had MSI, 92.0% were sensitive to platinum, and more than 50.0% relapsed after treatment. Patients with MSI had a lower CD8/PD-1 ratio and more relapses (p = 0.03). In conclusion, analysis of immunotherapeutic markers in paraffin-embedded advanced serous ovarian carcinoma samples is feasible and may assist in prognosis.

Human Adipose-Derived Stem Cells Reduce Cellular Damage after Experimental Spinal Cord Injury in Rats.

Traumatic spinal cord injury (SCI) is a devastating condition without an effective therapy. Cellular therapies are among the promising treatment strategies. Adult stem cells, such as mesenchymal stem cells, are often used clinical research for their immunomodulatory and regenerative potential. This study aimed to evaluate the effect of human adipose tissue-derived stem cells (ADSC) infusion through the cauda equina in rats with SCI. The human ADSC from bariatric surgery was isolated, expanded, and characterized. Wistar rats were subjected to blunt SCI and were divided into four groups. Two experimental groups (EG): EG1 received one ADSC infusion after SCI, and EG2 received two infusions, the first one after SCI and the second infusion seven days after the injury. Control groups (CG1 and CG2) received infusion with a culture medium. In vivo, cell tracking was performed 48 h and seven days after ADSC infusion. The animals were followed up for 40 days after SCI, and immunohistochemical quantification of myelin, neurons, and astrocytes was performed. Cellular tracking showed cell migration towards the injury site. ADSC infusion significantly reduced neuronal loss, although it did not prevent the myelin loss or enhance the area occupied by astrocytes compared to the control group. The results were similar when comparing one or two cell infusions. The injection of ADSC distal to the injured area was shown to be a safe and effective method for cellular administration in spinal cord injury.