Combination therapy for management of pemphigus patients with unexpected therapeutic response to rituximab: A report of five cases.

Key Clinical Message: The immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment, especially in male patients and those with high BMI. Abstract: Rituximab (RTX) has recently been proposed as an alternative first-line therapy for pemphigus patients. However, there are some rare reports of worsening of pemphigus following RTX therapy in the literature. This study aimed to evaluate the efficacy and safety of using a combination treatment of mycophenolate mofetil or dapsone and methotrexate in case of nonresponse, exacerbation or development of allergic reactions following rituximab therapy in pemphigus patients. In this case series, archive files of pemphigus patient in a tertiary care hospital from 2016 to 2021 who were treated with rituximab were reviewed and those with failure in treatment process including nonresponsiveness, exacerbation or development of allergic reactions to rituximab were identified and assessed. The study includes five patients out of 1245 RTX-treated patients, who did not respond to RTX (one patient) or experienced an exacerbation of disease (two patients) or development of allergic reactions (two patients). Male patients with high BMI (BMI > 25) whose response to rituximab was not good at first cycle and happened to receive rituximab later in the course of disease, had highest number of relapses and benefited the most from this combination immunosuppressive treatment as an alternative for repeating rituximab cycles. The lower risk of relapse and a better chance of remission might indicate the efficacy of adjuvant immunosuppressant therapy in patients with no-response, exacerbation, or allergic reaction to rituximab. These therapeutic effects were better observed in patients who received lower doses of rituximab which could suggest that the immunosuppressant agents should be considered earlier in the course of the disease, possibly after the first failed trial of rituximab therapy.

Machine learning for classification of cutaneous sebaceous neoplasms: implementing decision tree model using cytological and architectural features.

BACKGROUND: This observational study aims to describe and compare histopathological, architectural, and nuclear characteristics of sebaceous lesions and utilized these characteristics to develop a predictive classification approach using machine learning algorithms. METHODS: This cross-sectional study was conducted on Iranian patients with sebaceous tumors from two hospitals between March 2015 and March 2019. Pathology slides were reviewed by two pathologists and the architectural and cytological attributes were recorded. Multiple decision tree models were trained using 5-fold cross validation to determine the most important predictor variables and to develop a simple prediction model. RESULTS: This study assessed the characteristics of 123 sebaceous tumors. Histopathological findings, including pagetoid appearance, neurovascular invasion, atypical mitosis, extensive necrotic area, poor cell differentiation, and non-lobular tumor growth pattern, as well as nuclear features, including highly irregular nuclear contour, and large nuclear size were exclusively observed in carcinomatous tumors. Among non-carcinomatous lesions, some sebaceoma and sebaceous adenoma cases had features like high mitotic activity, which can be misleading and complicate diagnosis. Based on multiple decision tree models, the five most critical variables for lesion categorization were identified as: basaloid cell count, peripheral basaloid cell layers, tumor margin, nuclear size, and chromatin. CONCLUSIONS: This study implemented a machine learning modeling approach to help optimally categorize sebaceous lesions based on architectural and nuclear features. However, studies of larger sample sizes are needed to ensure the accuracy of our suggested predictive model.

Suicidality risk after using cannabis and cannabinoids: An umbrella review.

The increasing prevalence and burden of suicide have led to numerous studies to identify its risk factors. Cannabis is the most common illicit substance detected in suicide victims' toxicology tests. This study aims to identify and appraise systematic reviews investigating suicidality after using cannabis and cannabinoids. Seven databases and two registries were searched without restrictions for systematic reviews investigating cannabis effects on suicidality. AMSTAR-2 was used for quality assessment and corrected covered area and citation matrix were used to determine overlap. Twenty-five studies were included, of which 24 were on recreational use and one was on therapeutic use. Only three of the studies on recreational use reported no effect or inconsistent results. Evidence generally showed a positive association between cannabis use and suicidal ideation and attempt among the general population, military veterans, and bipolar or major depression patients. A bidirectional causal association between cannabis and suicidal ideation was also mentioned. Moreover, a younger age of initiation, long-term use, and heavy consumption were reported to be associated with even worse suicidal outcomes. On the contrary, current evidence indicates that the therapeutic cannabis is safe. In conclusion, the literature supports the cannabis-suicidality association in recreational use but considers cannabidiol safe for treatment. Further studies with quantitative and interventional approaches are recommended.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

Background: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. Methods: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. Results: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). Conclusion: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Antecedentes: La esclerosis múltiple (EM) es una enfermedad inmunomediada que se ha relacionado con varios factores de riesgo, como diversas infecciones virales. Realizamos este estudio para establecer una relación entre la infección por COVID-19 y la gravedad de la EM. Métodos: En un estudio de casos y controles, reclutamos pacientes con esclerosis múltiple remitente-recurrente (EMRR). Los pacientes se dividieron en dos grupos según la PCR positiva para COVID-19 al final de la fase de inscripción. Cada paciente fue seguido prospectivamente durante 12 meses. Los antecedentes demográficos, clínicos y médicos anteriores se recogieron durante la práctica clínica habitual. Las evaluaciones se realizaron cada 6 meses. La resonancia magnética se realizó en el momento de la inscripción y 12 meses después. Resultados: Trescientos sesenta y dos pacientes participaron en este estudio. Los pacientes con EM con infección por COVID-19 tuvieron aumentos significativamente más altos en el número de lesiones de resonancia magnética (p = 0,019; OR = 6,37 [IC 95%: 1,54-26,34]) y puntajes EDSS (p = 0,017), pero no se encontraron diferencias en el total de recaídas anuales o en las tasas de recaída. Las infecciones por COVID-19 se correlacionaron positivamente con la progresión de EDSS (p = 0,02) y la cantidad de nuevas lesiones en la resonancia magnética (p = 0,004) y predijeron la probabilidad de la cantidad de nuevas lesiones en la resonancia magnética con una probabilidad de 5,92 (p = 0,018). Conclusión: COVID-19 puede conducir a puntajes de discapacidad más altos en la población de EMRR y está asociado con el desarrollo de nuevas lesiones realzadas con Gd en imágenes de resonancia magnética. Sin embargo, no se observó diferencia entre los grupos en cuanto al número de recaídas durante el seguimiento.

COVID-19 and its implications on the clinico-radiological course of multiple sclerosis: A case-control study.

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease that has been related to several risk factors such as various viral infections. We carried out this study in order to establish a relationship between COVID-19 infection and MS severity. METHODS: In a case-control study, we recruited patients with relapsing-remitting multiple sclerosis (RRMS). Patients were divided into two groups based on positive COVID-19 PCR at the end of the enrollment phase. Each patient was prospectively followed for 12 months. Demographical, clinical, and past medical history were collected during routine clinical practice. Assessments were performed every six months; MRI was performed at enrollment and 12 months later. RESULTS: Three hundred and sixty-two patients participated in this study. MS patients with COVID-19 infection had significantly higher increases in the number of MRI lesions (p: 0.019, OR(CI): 6.37(1.54-26.34)) and EDSS scores (p: 0.017), but no difference was found in total annual relapses or relapse rates. COVID-19 infections were positively correlated with EDSS progression (p: 0.02) and the number of new MRI lesions (p: 0.004) and predicted the likelihood of the number of new MRI lesions by an odds of 5.92 (p: 0.018). CONCLUSION: COVID-19 may lead to higher disability scores in the RRMS population and is associated with developing new Gd-enhancing lesions in MRI imaging. However, no difference was observed between the groups regarding the number of relapses during follow-up.

Ketamine and Other Glutamate Receptor Modulating Agents for Treatment-Resistant Depression: A Systematic Review of Randomized Controlled Trials.

Objective: Available treatments of depression have limited efficacy and unsatisfactory remission rates. This study aims to review randomized controlled trials (RCTs) investigating effects of glutamate receptor modulators in treating patients with resistant depression. Method : The study protocol was registered in PROSPERO (CRD42021225516). Scopus, ISI Web of Science, Embase, Cochrane Library, Google Scholar, and three trial registries were searched up to September 2020 to find RCTs evaluating glutamate receptor modulators for resistant depression. The difference between intervention and control groups in changing depression scores from baseline to endpoint was considered the primary outcome. Version 2 of the Cochrane risk-of-bias tool for randomized trials was used to assess the quality of the RCTs. No funding was received. Results: Thirty-eight RCTs were included. Based on the included studies, compelling evidence was found for ketamine (with or without electroconvulsive therapy, intravenous or other forms), nitrous oxide, amantadine, and rislenemdaz (MK-0657); the results for MK-0657, amantadine, and nitrous oxide were only based on one study for each. Lithium, lanicemine, D-cycloserine, and decoglurant showed mixed results for efficacy, and, riluzole, and 7-chlorokynurenic acid were mostly comparable to placebo. A limited number of studies were available that addressed drugs other than ketamine. Conclusion: The study cannot determine the difference between statistical and clinical significance between the agents and placebo due to high heterogeneity among the RCTs. Nevertheless, ketamine could be used as an efficacious drug in TRD; still, additional studies are needed to delineate the optimum dosage, duration of efficacy, and intervals. Further studies are also recommended on the effectiveness of glutamatergic system modulators other than ketamine on treatment-resistant depression.

Carpal Tunnel Syndrome: Open or Endoscopic Release Surgery Method?

Background: Carpal tunnel syndrome (CTS) or median nerve neuropathy is among the causes of numbness, paresthesia, and sensory and motor dysfunction in the affected hand. The objective of this study was to compare open and endoscopic carpal tunnel release (ECTR) methods. Methods: A multicenter, historical cohort study was performed on 47 hands in 46 patients with a clinical diagnosis of CTS and a failed trial of conservative treatment. Samples were divided into two groups consisting of 23 patients receiving open carpal tunnel release (OCTR) and ECTR. Outcome measurements had been carried out six weeks after the operation and included handgrip strength, post-op pain, and missing job days. Results: Patients in both groups were comparable regarding baseline characteristics such as age, gender, and handgrip strength. Both methods significantly improved handgrip strength. No significant difference was detected between the two groups concerning handgrip strength improvement (P=0.700) and sick leave days (P=0.564). Open carpal tunnel release resulted in more significant post-op pain (mean 5.91±1.24 compared to 2.43±0.73 after endoscopic release), which was significant (P=0.000). No complications were reported with any technique. Conclusion: This study revealed that apart from post-op pain, other investigated endpoints were similar in both groups. Although the small sample size has limited our ability to draw a conclusive statement, these data suggest that there is no need to utilize the endoscopic technique for the optimum result, especially when this method requires more advanced equipment and could increase surgery costs. Therefore, both approaches can result in good clinical outcomes.

Ketamine for suicidality: An umbrella review.

The urgent need for appropriate treatment for suicide, the tenth leading cause of death, has led to numerous studies. This study aims to systematically identify and appraise systematic reviews with or without meta-analyses investigating ketamine in suicidal ideation and behaviours. Scopus, ISI, Embase, PubMed, CINAHL, PsycINFO, Cochrane Library, Google Scholar and two registries were searched without any restrictions for systematic reviews investigating the efficacy of ketamine on suicidal ideation and behaviours. The primary outcome was the final inference of ketamine effectiveness. A formal narrative synthesis was conducted, and the AMSTAR-2 tool was used to evaluate the quality of the studies. Of 27 studies that addressed ketamine for suicidal ideation, only four reported mixed or negative results, and out of nine reviews, esketamine was significantly beneficial only in five. A transient rise in pulse rate and blood pressure, dissociation, confusion, blurred vision, nausea and vertigo were the most common adverse effects; however, most were mild. More than two-thirds of the included studies qualified as of low or critically low quality. Preliminary evidence for the short-term efficacy of ketamine in suicidality was noted by the majority of reviews; however, long-term effects remained unknown. Due to the low quality of many studies and the limitations of core studies, further research is required.

Changes in COVID-19 IgM and IgG antibodies in emergency medical technicians (EMTs).

INTRODUCTION: Serologic testing can provide a safe and fast approach for assessing SARS-CoV-2 antibodies. These tests can be utilized as a complementary method in diagnosis and patients' follow-up, and can also be helpful in epidemiological studies. This study aimed to describe temporal changes in the incidence of COVID-19 IgM and IgG antibodies in emergency medical technicians (EMTs) within a specified time period. METHODS: All EMTs working for Tehran Emergency Medical Service (EMS) center during May to September 2020 were eligible for this study. Those EMTs who were suspected/probable/confirmed cases of COVID-19, based on WHO defined criteria and were willing to participate, entered the study. The EMTs underwent serology testing four weeks after the occurrence of exposure (in suspected cases) or onset of their symptoms (in probable/confirmed cases). Cases were further confirmed by RT-PCR and/or lung CT, and antibody testing was performed for the second and third time with 12-week intervals. Finger-stick blood sampling was utilized for the specimen collection in three different phases. Samples were then analyzed by a commercial immunochromatography-based kit for qualitative measurement of serum IgM and IgG antibodies against the COVID-19 S-protein antigen. RESULTS: Two hundred eighty-four participants met the inclusion criteria; their mean age was 35.9 (SD = 7.6) years and consisted of 244 (85.9%) males. COVID-19 was confirmed in 169 out of 284 participants. Subsequently, 142 and 122 participants were included in phases 2 and 3 of the study, respectively. The number of seronegative patients exceeded seropositive ones in all three phases. At baseline, 162 (57%) patients were seronegative, 27 (9.5%) were only positive for IgG, 3 (1.1%) were only positive for IgM, and 92 (32.4%) were positive for both antibodies; Seventy-eight (54.9%) were seronegative, and 31 (21.8%) were positive for both antibodies in the second phase; These values were 85 (69.6%) and 8 (6.6%) for the third phase, respectively. Among the people who were positive IgG in the first phase (80 people), 56.3% were still positive in the second phase and 27.5% in both subsequent phases. CONCLUSION: The results of our study show that there is a significant reduction in COVID-19 antibody seropositivity over time.