Cancer Trends in Inborn Errors of Immunity: A Systematic Review and Meta-Analysis.

BACKGROUND: Patients with inborn errors of immunity (IEI) are susceptible to developing cancer due to defects in the immune system. The prevalence of cancer is higher in IEI patients compared to the immunocompetent population and cancers are considered as an important and common cause of death in IEI patients. OBJECTIVES: To systematically review demographic, genetic and cancer-related data of IEI patients with a history of malignancy. Moreover, we performed a meta-analysis aiming to determine the frequency of cancer in patients with different types of IEI. METHODS: We conducted electronic searches on Embase, Web of Science, PubMed, and Scopus (until September 2023) introducing terms related to IEI and cancer. Studies with human subjects with confirmed IEI who had developed at least one malignancy during their lifetime were included. RESULTS: A total number of 4607 IEI patients with a cancer history were included in the present study. Common variable immunodeficiency (CVID) had the highest number of reported cases (1284 cases), mainly due to a higher relative proportion of patients with predominantly antibody deficiencies (PAD) and their increased life expectancy contributing to the higher detection and reporting of cancers among these patients. The most common malignancy was hematologic/blood cancers (3026 cases, mainly diffuse large B cell lymphoma). A total number of 1173 cases (55.6%) succumbed to cancer, with the highest rate of bone marrow failure (64.9%). Among the patients with monogenic defects in IEI-associated genes, the majority of cases had ATM deficiency (926 cases), but the highest cancer frequency rate belonged to NBS1 deficiency (50.5%). 1928 cases out of total 4607 eligible cases had detailed data to allow further statistical analysis that revealed BRCA2 deficiency had the earliest cancer development (~ 38 months), lowest cure frequency, and highest fatality rate (85%), while ATM deficiency had the lowest cure frequency and highest fatality rate (72%) among total cases reviewed with exclusion of Fanconi anemia. CONCLUSION: The overall reported cancer frequency in the cases reviewed with and without exclusion of Fanconi anemia was 11.1% (95% confidence interval: 9.8-12.5%) and 12.0% (95% confidence interval: 10.6-13.5%), respectively. Our study revealed that the incidence of cancer is significantly dependent on the molecular and pathway defects in IEI patients, and individualized early screening and appropriate treatment, might improve the prognosis of these patients.

CSF and blood levels of Neurofilaments, T-Tau, P-Tau, and Abeta-42 in amyotrophic lateral sclerosis: a systematic review and meta-analysis.

Recent literature suggests that markers of neuroaxonal damage, such as neurofilaments and tau protein, might serve as potential biomarkers for ALS. We conducted this systematic review and meta-analysis study to compare cerebrospinal fluid (CSF) and blood levels of total tau (t-tau), phosphorylated tau (p-tau), amyloid beta peptide 42 (Abeta-42), and neurofilaments in ALS patients and controls. A systematic search of Cochrane Library, PubMed, Embase, and ISI Web of Science was conducted on March 18, 2022, and updated on January 26, 2023. Observational studies that compared the concentrations of neurofilament light chain (NfL), neurofilament heavy chain (NFH), t-tau, p-tau, or Abeta-42 in CSF or peripheral blood of ALS patients and controls were included. Data from relevant studies were independently extracted and screened for quality using a standard tool, by at least two authors. Meta-analysis was conducted when a minimum of 3 studies reported the same biomarker within the same biofluid. A total of 100 studies were eligible for at least one meta-analysis. CSF and blood levels of NfL (standardized mean difference (SMD) [95% CI]; CSF: 1.46 [1.25-1.68]; blood: 1.35 [1.09-1.60]) and NFH (CSF: 1.32 [1.13-1.50], blood: 0.90 [0.58-1.22]) were significantly higher in ALS patients compared with controls. The pooled differences between ALS patients and controls were not significant for CSF t-tau, blood t-tau, and CSF Abeta-42, but CSF p-tau was lower in ALS patients (-0.27 [-0.47- -0.07]). Significantly decreased p-tau/t-tau ratios were found in ALS patients compared with controls (-0.84 [-1.16- -0.53]). Heterogeneity was considerable in most of our meta-analyses. CSF and blood neurofilament levels, as well as the CSF p-tau/t-tau ratio, might be potential candidates for improving ALS diagnosis. Further research is warranted to better understand the underlying mechanisms and the clinical implications of these biomarker alterations.

Isavuconazole in the Treatment of Chronic Forms of Coccidioidomycosis.

Coccidioidomycosis is a fungal infection with a range of clinical manifestations. Currently used antifungal agents exhibit variable efficacy and toxicity profiles that necessitate evaluation of additional therapeutic options. Improvement was observed in the majority of patients treated with isavuconazole, with clinical failures observed only in those with coccidioidal meningitis.

Multicentric Case Series and Literature Review of Coccidioidal Otomastoiditis.

Coccidioidomycosis involving the ear, mastoid bone, or both is uncommon. We describe 5 new cases from the United States and review 4 cases reported in the literature of otomycosis and mastoiditis caused by Coccidioides. Of the 9 cases, 8 were linked to residence in or travel to California. Two patients had poorly controlled diabetes mellitus, 7 had otomastoiditis, 1 had otitis externa without mastoid involvement, and 1 had mastoiditis without otic involvement. Four patients had concurrent or prior pulmonary coccidioidomycosis. Ipsilateral facial nerve palsies developed in 2 patients. All patients received antifungal treatment for varying durations, and 8 of the 9 patients underwent surgical debridement. Clinicians should consider coccidioidomycosis as a differential diagnosis for otomastoiditis in patients with geographic risks.

The Association Between Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder Symptoms in Medical Students.

ABSTRACT: Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are the two most prevalent neurodevelopmental disorders affecting communication and behavior. The co-occurrence of these conditions is probable and can contribute to several challenges in adaptive functioning and academic achievement.In this cross-sectional study, 168 Iranian medical students (107 female, 61 male) studying at Tehran University of Medical Sciences in 2021 were enrolled. We administered the Ritvo Autism Asperger Diagnostic Scale-Revised (RAADS-R) and Adult ADHD Self-Report Scale (ASRS) questionnaires online to assess different symptoms of ASD and ADHD in our sample. In this study, the RAADS-R was translated into Persian and validated for the first time in Iran.The correlation tests demonstrated a significant association between the total score and different subscales' scores of the RAADS-R and the total score and the two subscales' scores of the ASRS questionnaire ( p < 0.001, 0.27 < Spearman correlation coefficient < 0.51). This study also illustrated a high prevalence of ASD and ADHD symptoms among the participants. Moreover, male respondents had a significantly higher prevalence of ASD symptoms (57.3% in males vs . 28.03% in females, p < 0.001).This study indicated that the distinct impairments in behavior and cognition attributed to ASD and ADHD could be common manifestations in medical students. Given that the co-occurrence of these disorders may lead to significant challenges in their professional life, the early diagnosis and subsequent support for medical students with co-occurring expressions of ASD and ADHD could be extremely helpful, as it could indirectly improve the medical services provided to patients by future physicians, leading to an improvement in public health.

Controversies in the Management of Central Nervous System Coccidioidomycosis.

Central nervous system infection with Coccidioides spp. is fatal if untreated and complications occur even when therapy is directed by experienced clinicians. We convened a panel of clinicians experienced in the management of coccidioidal meningitis to summarize current controversies and provide consensus for the management of this difficult infection.

The role of Toll-like receptors and neuroinflammation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder, characterized by motor and non-motor symptoms, significantly affecting patients' life. Pathologically, PD is associated with the extensive degeneration of dopaminergic neurons in various regions of the central nervous system (CNS), specifically the substantia nigra. This neuronal loss is accompanied by the aggregation of misfolded protein, named α-synuclein. MAIN TEXT: Recent studies detected several clues of neuroinflammation in PD samples using postmortem human PD brains and various PD animal models. Some evidence of neuroinflammation in PD patients included higher levels of proinflammatory cytokines in serum and cerebrospinal fluid (CSF), presence of activated microglia in various brain regions such as substantia nigra, infiltration of peripheral inflammatory cells in affected brain regions, and altered function of cellular immunity like monocytes phagocytosis defects. On the other side, Toll-like receptors (TLRs) are innate immune receptors primarily located on microglia, as well as other immune and non-immune cells, expressing pivotal roles in recognizing exogenous and endogenous stimuli and triggering inflammatory responses. Most studies indicated an increased expression of TLRs in the brain and peripheral blood cells of PD samples. Besides, this upregulation was associated with excessive neuroinflammation followed by neurodegeneration in affected regions. Therefore, evidence proposed that TLR-mediated neuroinflammation might lead to a dopaminergic neural loss in PD patients. In this regard, TLR2, TLR4, and TLR9 have the most prominent roles. CONCLUSION: Although the presence of inflammation in acute phases of PD might have protective effects concerning the clearance of α-synuclein and delaying the disease advancement, the chronic activation of TLRs and neuroinflammation might lead to neurodegeneration, resulting in the disease progression. Therefore, this study aimed to review additional evidence of the contribution of TLRs and neuroinflammation to PD pathogenesis, with the hope that TLRs could serve as novel disease-modifying therapeutic targets in PD patients in the future.

Microfluidic devices for detection of RNA viruses.

There is a long way to go before the coronavirus disease 2019 (Covid-19) outbreak comes under control. qRT-PCR is currently used for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Covid-19, but it is expensive, time-consuming, and not as sensitive as it should be. Finding a rapid, easy-to-use, and cheap diagnostic method is necessary to help control the current outbreak. Microfluidic systems provide a platform for many diagnostic tests, including RT-PCR, RT-LAMP, nested-PCR, nucleic acid hybridization, ELISA, fluorescence-Based Assays, rolling circle amplification, aptamers, sample preparation multiplexer (SPM), Porous Silicon Nanowire Forest, silica sol-gel coating/bonding, and CRISPR. They promise faster, cheaper, and easy-to-use methods with higher sensitivity, so microfluidic devices have a high potential to be an alternative method for the detection of viral RNA. These devices have previously been used to detect RNA viruses such as H1N1, Zika, HAV, HIV, and norovirus, with acceptable results. This paper provides an overview of microfluidic systems as diagnostic methods for RNA viruses with a focus on SARS-CoV-2.

Rhenium-188 radiosynovectomy for chronic haemophilic synovitis: Evaluation of its safety and efficacy in haemophilic patients.

INTRODUCTION: Radiocolloids labelled with less costly and more accessible radionuclides such as rhenium-188 are of interest to developing countries compared with those labelled with rhenium-186 and yttrium-90. AIM: This study was aimed to evaluate the efficacy and safety of radiosynovectomy using rhenium-188 in patients with chronic haemophilic synovitis and recurrent hemarthrosis. METHODS: In this quasi-experimental prospective study, 20 haemophilic patients were evaluated at preinjection, and at 1, 3, 6 and 12 months after injection. Magnetic resonance imaging (MRI) was done to measure synovial thickness and to calculate Denver score. Joint radiographs were taken to measure the Pettersson score. The Gilbert questionnaire, Functional Independence Score in Hemophilia (FISH) and visual analogue scale (VAS) for pain were completed, and the number of bleeding episodes and factor consumption were recorded at each follow-up visit. RESULTS: The number of bleeding episodes, the amount of factor consumption per month, VAS pain scores and synovial thickness decreased significantly over time (P < .05). Gilbert and FISH scores showed significant improvement (P < .001). However, Pettersson score and Denver score showed no significant changes after injection. Minor complications including temporary pain and swelling occurred in 20% of patients, and no major complication was observed after rhenium-188 injection. CONCLUSION: Our results indicated high clinical impact, efficacy, safety and low invasion of rhenium-188 in radiosynovectomy of haemophilic patients. Considering the availability and relatively low cost of rhenium-188 in developing countries, this can be a good treatment option for haemophilic patients with recurrent hemarthrosis, particularly when the synovial hypertrophy is not massive yet.

Isavuconazole in the Treatment of Coccidioidal Meningitis.

Patients with coccidioidal meningitis require lifelong antifungal therapy. Cumulative toxicity and lack of antifungal efficacy require salvage therapy in the treatment of some patients. In a retrospective review of nine patients with coccidioidal meningitis treated with isavuconazole, successful therapy was seen in three patients and stable disease was confirmed in six patients. Isavuconazole may be a useful addition to the therapeutic choices currently available for coccidioidal meningitis.

Interlaboratory agreement of coccidioidomycosis enzyme immunoassay from two different manufacturers.

Coccidioidomycosis, a fungal infection endemic to the Southwestern United States, is challenging to diagnose. The coccidioidomycosis enzyme immunoassay (EIA) test is the least expensive and simplest to perform to detect coccidioidomycosis antibodies in the serum. Concerns regarding falsely positive immunoglobulin (Ig) M EIA test results have led to questions about the agreement of commercially available EIA test kits among laboratories. We sought to evaluate the laboratory agreement of the EIA test at three laboratories using both IMMY and Meridian EIA test kits. Sensitivity and specificity of EIA IgM and IgG were calculated as secondary outcomes. The percent agreement of the EIA IgM and IgG test results among all three laboratories was 90% and 89% for IMMY test kits, respectively, and 67% and 80.5% for Meridian test kits, respectively. Agreement between IgM and IgG combined test results was 85.5% and 70.5%, for IMMY and Meridian, respectively. Combined IgM and IgG assays demonstrated a sensitivity of 68% (62.7%-76%) and a specificity of 99.3% (98%-100%) [IMMY] and a sensitivity of 72.4% (57.3%-87.3%) and a specificity of 91.3% (74%-100%) [Meridian]. In summary, results from the IMMY EIA test kit agreed more often across laboratories than Meridian EIA results, especially for the IgM assay. Isolated positive IgM EIA results using the Meridian test kit should be interpreted with caution and consideration of clinical information and test methodology. Further study of the sensitivity and specificity of coccidioidomycosis EIA test kits is warranted.

Evaluation of Amphotericin B Lipid Formulations for Treatment of Severe Coccidioidomycosis.

Patients with severe coccidioidomycosis infections are often treated with either amphotericin B lipid complex (ABLC) or liposomal amphotericin B (L-AmB). Outcome data with these agents in severe coccidioidomycosis cases are currently lacking. The purpose of this study is to evaluate the efficacy and toxicity of ABLC and L-AmB in treating severe coccidioidomycosis. A retrospective pre-post study design was employed. Chart reviews were completed from 1 January 2005 to 31 December 2014 for all patients who received lipid-based amphotericin B. Inclusion criteria included having a follow-up complement fixation (CF) titer or a treatment emergent adverse event (TEAE) prior to follow-up. Patients with meningeal involvement and pregnant patients were excluded. Treatment outcomes were assessed based on documented completion of therapy as well on symptoms, complement fixation titer, and changes to laboratory monitoring parameters. A total of 108 patients were identified, 69 of whom met the inclusion criteria. There were no statistical differences in demographics or disease burden in those that received ABLC and those that received L-AmB, except that those who received L-AmB were more likely to have previously diagnosed chronic kidney disease (nL-AmB = 4, 12.5% vs nABLC = 0, 0.0%; P = 0.042) and to have a lower creatinine clearance at the start of therapy (L-AmB = 79.6 mg/dl versus ABLC = 100.4 mg/dl; P = 0.008). Successful treatment was achieved in 27 (73.0%) of ABLC patients and 22 (68.8%) of L-AmB patients (P = 0.700). Amphotericin B was discontinued due to documented completion of therapy for 17 (45.9%) ABLC patients and 18 (56.3%) L-AmB patients (P = 0.553). Acute kidney injury (AKI) was the documented reason of treatment cessation for 10 (27.0%) ABLC and 1 (3.1%) L-AmB patient (P = 0.007). ABLC and L-AmB both appear to be equally efficacious in the treatment of severe coccidioidomycosis. L-AmB may have less renal toxicity than ABLC and may be the preferred agent in baseline renal impairment.

Coccidioidal Meningitis: A Review on Diagnosis, Treatment, and Management of Complications.

PURPOSE OF REVIEW: This article summarizes the diagnosis and treatment of coccidioidal meningitis (CM) and its complications. An overview of current and prospective pharmacologic treatment options and monitoring parameters is provided. A consensus has not been reached regarding universally accepted therapeutic serum levels for azoles because of insufficient evidence. We describe the preferred therapeutic drug level ranges that our institution uses to monitor azole therapy. RECENT FINDINGS: Ho et al. described the preparation and administration of intrathecally delivered amphotericin B deoxycholate. Thompson et al. described possible benefits of controversial adjuvant corticosteroid therapy for secondary prevention of vasculitic infarction secondary to CM. CM was universally fatal until the advent of intrathecal amphotericin B deoxycholate therapy, the introduction of which changed the natural history of the disease in much the same way as penicillin changed the natural history of bacterial meningitis. Although there was still significant morbidity, survival rates drastically increased to approximately 70%. The introduction of azole therapy has decreased the side effects and burden of treatment but without a significant change in CM-related mortality and morbidity compared with the use of intrathecal amphotericin B deoxycholate therapy.

Intrathecal Amphotericin B: A 60-Year Experience in Treating Coccidioidal Meningitis.

Coccidioidal meningitis (CM) is a devastating complication of coccidioidomycosis. Since the late 1950s, intrathecal (IT) amphotericin B deoxycholate (AmBd) has been successfully used to treat and often cure this disease, reducing mortality rates from 100% to approximately 30%. The introduction of azoles further revolutionized the treatment of coccidioidal infections. However, IT AmBd remains the only known curative option in the management of CM. While the use of IT AmBd is well described in many articles, few discuss the actual methods behind preparation, titration, and dosing strategies utilized. The practitioners at Kern Medical (Bakersfield, California) have >60 years of experience in the utilization of IT AmBd and the treatment of CM. This article describes the practice experience in the treatment of CM, preparation of IT AmBd, and the different dosing strategies used in regard to route of administration (ie, cisternal, lumbar, ventricular).

Adjunctive Corticosteroid Therapy in the Treatment of Coccidioidal Meningitis.

Coccidioidal meningitis (CM) has high morbidity, and adjunctive measures to improve outcomes are needed. Using an established multicenter retrospective cohort study of CM (N = 221), we found that patients receiving adjunctive corticosteroids had a significant reduction in secondary cerebrovascular events (P = .0049). Those with CM-associated cerebrovascular events (8%) may benefit from short-term corticosteroids.

Clostridium paraputrificum in a Middle-Aged Male With Liver Disease.

Clostridium paraputrificum is a gram-positive anaerobic spore-forming bacillus with a pathological prevalence of <1% among all Clostridium species. However, despite being a rare bacterium, there have been reported cases of C paraputrificum causing a wide range of varying pathologies. Herein presented is a case of cirrhosis secondary to alcoholism complicated by developing C paraputrificum bacteremia suspected due to gastrointestinal mucosal damage. There is literature demonstrating certain comorbid conditions having an impact on the overall prognosis of patients with C paraputrificum bacteremia.

Dietary inflammatory index and neuropsychiatric disorders.

Neuropsychiatric disorders (NPDs) are considered a potential threat to mental health. Inflammation predominantly plays a role in the pathophysiology of NPDs. Dietary patterns are widely postulated to be involved in the physiological response to inflammation. This review aims to discuss the literature on how dietary inflammatory index (DII) is related to inflammation and, consequently, NPDs. After comprehensive scrutiny in different databases, the articles that investigated the relation of DII score and various NPDs and psychological circumstances were included. The association between dietary patterns and mental disorders comprising depression, anxiety, and stress proved the role of a proinflammatory diet in these conditions' exacerbation. Aging is another condition closely associated with DII. The impact of proinflammatory and anti-inflammatory diet on sleep quality indicated related disorders like sleep latency and day dysfunctions among the different populations are in relation with the high DII score. The potential effects of genetic backgrounds, dietary patterns, and the gut microbiome on DII are discussed as well. To plan preventive or therapeutic interventions considering the DII, these factors, especially genetic variations, should be considered as there is a growing body of literature indicating the role of personalized medicine in different NPDs. To the best of our knowledge, there is a limited number of RCTs on this subject, so future research should evaluate the causality via RCTs and look for therapeutic interventions with an eye on personalized medicine using information about DII in NPDs.

Catastrophic Case of West Nile Virus Rhombencephalitis in AIDS.

West Nile Virus (WNV) belongs to the Flaviviridae family of viruses. It was first isolated and identified in 1937. Patients typically present with flu-like symptoms or are asymptomatic; however, neuroinvasive West Nile can lead to significant neurological impairment. Herein presented is a catastrophic case of WNV rhombencephalitis in a male patient newly diagnosed with AIDS. This report sheds light on the potential for severe neurological complications in co-infected patients and emphasizes the importance of early recognition.

Opportunities and challenges of artificial intelligence and distributed systems to improve the quality of healthcare service.

The healthcare sector, characterized by vast datasets and many diseases, is pivotal in shaping community health and overall quality of life. Traditional healthcare methods, often characterized by limitations in disease prevention, predominantly react to illnesses after their onset rather than proactively averting them. The advent of Artificial Intelligence (AI) has ushered in a wave of transformative applications designed to enhance healthcare services, with Machine Learning (ML) as a noteworthy subset of AI. ML empowers computers to analyze extensive datasets, while Deep Learning (DL), a specific ML methodology, excels at extracting meaningful patterns from these data troves. Despite notable technological advancements in recent years, the full potential of these applications within medical contexts remains largely untapped, primarily due to the medical community's cautious stance toward novel technologies. The motivation of this paper lies in recognizing the pivotal role of the healthcare sector in community well-being and the necessity for a shift toward proactive healthcare approaches. To our knowledge, there is a notable absence of a comprehensive published review that delves into ML, DL and distributed systems, all aimed at elevating the Quality of Service (QoS) in healthcare. This study seeks to bridge this gap by presenting a systematic and organized review of prevailing ML, DL, and distributed system algorithms as applied in healthcare settings. Within our work, we outline key challenges that both current and future developers may encounter, with a particular focus on aspects such as approach, data utilization, strategy, and development processes. Our study findings reveal that the Internet of Things (IoT) stands out as the most frequently utilized platform (44.3 %), with disease diagnosis emerging as the predominant healthcare application (47.8 %). Notably, discussions center significantly on the prevention and identification of cardiovascular diseases (29.2 %). The studies under examination employ a diverse range of ML and DL methods, along with distributed systems, with Convolutional Neural Networks (CNNs) being the most commonly used (16.7 %), followed by Long Short-Term Memory (LSTM) networks (14.6 %) and shallow learning networks (12.5 %). In evaluating QoS, the predominant emphasis revolves around the accuracy parameter (80 %). This study highlights how ML, DL, and distributed systems reshape healthcare. It contributes to advancing healthcare quality, bridging the gap between technology and medical adoption, and benefiting practitioners and patients.