Effectiveness of Repetitive Transcranial Magnetic Stimulation in Depression, Schizophrenia, and Obsessive-Compulsive Disorder: An Umbrella Meta-Analysis.

Objective: To analyze the safety and efficacy of repetitive transcranial magnetic stimulation (rTMS) for major depressive disorder, schizophrenia, and obsessive-compulsive disorder (OCD) via umbrella meta-analysis.Data Sources: Meta-analysis studies were searched in PubMed from inception to May 2021 using the keywords anxiety, depression, ADHD, schizophrenia, mood disorder, OCD, psychiatric disorders, GAD, bipolar disorders, ASD, PTSD, transcranial magnetic stimulation, transcranial, magnetic, stimulation. PRISMA guidelines were followed.Study Selection: Abstracts and full-length articles were reviewed for meta-analysis studies with data on the safety and efficacy of rTMS and sham and were collected for quantitative analysis. The full texts of all identified studies were independently screened and assessed to determine eligibility. Any disagreement was resolved through consensus.Data Extraction: The descriptive variables extracted included the author names, study year, sample size, studies included in the meta-analysis, study period, and type of intervention.Results: 28 meta-analyses were included; 13 were on treatment-resistant depression, 9 on schizophrenia, and 6 on OCD. In treatment-resistant depression, the rTMS group had higher odds of response compared to sham (odds ratio [OR] = 3.27; 95% CI, 2.76-3.87; P < .00001) and higher odds of remission (secondary outcome) (OR = 2.83; 95% CI, 2.33-3.45; P < .00001). rTMS was superior to sham in the reduction of negative symptoms of schizophrenia (mean difference [MD]: 0.47; 95% CI, 0.23-0.7; P < .0001). However, no significant difference was found between the effects of rTMS and sham on auditory hallucinations (MD: 0.24; 95% CI, 0.26-0.74; P = .35), which resulted in 94% heterogeneity. TMS was better than sham in reducing the severity of OCD symptoms (MD: 0.81; 95% CI, 0.53-1.10; P < .00001).Conclusions: The effectiveness of rTMS for symptom reduction in various psychiatric disorders is associated with differences in neuropathology, disease-specific target site, and frequency of rTMS.Prim Care Companion CNS Disord 2023;25(5):22r03423. Author affiliations are listed at the end of this article.

Automated detection of immune effector cell-associated neurotoxicity syndrome via quantitative EEG.

OBJECTIVE: To develop an automated, physiologic metric of immune effector cell-associated neurotoxicity syndrome among patients undergoing chimeric antigen receptor-T cell therapy. METHODS: We conducted a retrospective observational cohort study from 2016 to 2020 at two tertiary care centers among patients receiving chimeric antigen receptor-T cell therapy with a CD19 or B-cell maturation antigen ligand. We determined the daily neurotoxicity grade for each patient during EEG monitoring via chart review and extracted clinical variables and outcomes from the electronic health records. Using quantitative EEG features, we developed a machine learning model to detect the presence and severity of neurotoxicity, known as the EEG immune effector cell-associated neurotoxicity syndrome score. RESULTS: The EEG immune effector cell-associated neurotoxicity syndrome score significantly correlated with the grade of neurotoxicity with a median Spearman's R2 of 0.69 (95% CI of 0.59-0.77). The mean area under receiving operator curve was greater than 0.85 for each binary discrimination level. The score also showed significant correlations with maximum ferritin (R2 0.24, p = 0.008), minimum platelets (R2 -0.29, p = 0.001), and dexamethasone usage (R2 0.42, p < 0.0001). The score significantly correlated with duration of neurotoxicity (R2 0.31, p < 0.0001). INTERPRETATION: The EEG immune effector cell-associated neurotoxicity syndrome score possesses high criterion, construct, and predictive validity, which substantiates its use as a physiologic method to detect the presence and severity of neurotoxicity among patients undergoing chimeric antigen receptor T-cell therapy.

Diagnostic value of intraoperative fine-needle aspiration cytologic diagnosis versus frozen section-based histopathologic diagnosis in thoracic malignancies: A single institution's experience.

BACKGROUND: Primary lung cancer is the leading cause of cancer death in the United States. Most lung cancers are diagnosed in an outpatient setting, but a subset requires intraoperative diagnosis. Two intraoperative diagnostic methods are available, frozen section (FS) and fine needle aspiration (FNA) cytology. This study compares intraoperative FNA cytology and FS based diagnosis in thoracic malignancies within the same clinical practice. METHODS: Pathology reports from thoracic intraoperative FNA cytology or FS (January 2017-December 2019) were reviewed. Resection diagnosis was the gold standard. If unavailable, concurrent biopsy and final FNA cytology diagnosis were the gold standard. RESULTS: Of 300 FNA specimens (155 patients), 142 (47%) cases were benign, and 158 (53%) were malignant. Adenocarcinoma was the most common malignant diagnosis (40%), followed by squamous cell carcinoma (26%), neuroendocrine tumors (18%), and other (16%). Intraoperative FNA yielded 88% sensitivity, 99% specificity, and 92% accuracy (p < .001). Of 298 FS specimens (252 patients), 215 (72%) cases were malignant and 83 (28%) were benign. Adenocarcinomas was the most common malignant diagnosis (48%), followed by squamous cell carcinoma (25%), metastatic carcinomas (13%), and other (14%). FS yielded 97% sensitivity, 99% specificity, and 97% accuracy (p < .001). CONCLUSION: Our findings confirm FS is the gold standard for intraoperative diagnosis. FNA cytology may be useful as a non-invasive, inexpensive initial diagnostic tool intraoperatively, given the similar specificity (99% FNA, 99% FS) and accuracy (92% FNA, 97% FS). Negative FNA could be followed by the costlier and invasive FS. We encourage surgeons to utilize intraoperative FNA first.

EEG-based grading of immune effector cell-associated neurotoxicity syndrome.

CAR-T cell therapy is an effective cancer therapy for multiple refractory/relapsed hematologic malignancies but is associated with substantial toxicity, including Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS). Improved detection and assessment of ICANS could improve management and allow greater utilization of CAR-T cell therapy, however, an objective, specific biomarker has not been identified. We hypothesized that the severity of ICANS can be quantified based on patterns of abnormal brain activity seen in electroencephalography (EEG) signals. We conducted a retrospective observational study of 120 CAR-T cell therapy patients who had received EEG monitoring. We determined a daily ICANS grade for each patient through chart review. We used visually assessed EEG features and machine learning techniques to develop the Visual EEG-Immune Effector Cell Associated Neurotoxicity Syndrome (VE-ICANS) score and assessed the association between VE-ICANS and ICANS. We also used it to determine the significance and relative importance of the EEG features. We developed the Visual EEG-ICANS (VE-ICANS) grading scale, a grading scale with a physiological basis that has a strong correlation to ICANS severity (R = 0.58 [0.47-0.66]) and excellent discrimination measured via area under the receiver operator curve (AUC = 0.91 for ICANS ≥ 2). This scale shows promise as a biomarker for ICANS which could help to improve clinical care through greater accuracy in assessing ICANS severity.

Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis.

Background: Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. Methods: A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. Results: We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Conclusions: Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.

Forecasting immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor t-cell therapy.

BACKGROUND: Immune effector cell-associated neurotoxicity syndrome (ICANS) is a clinical and neuropsychiatric syndrome that can occur days to weeks following administration chimeric antigen receptor (CAR) T-cell therapy. Manifestations of ICANS range from encephalopathy and aphasia to cerebral edema and death. Because the onset and time course of ICANS is currently unpredictable, prolonged hospitalization for close monitoring following CAR T-cell infusion is a frequent standard of care. METHODS: This study was conducted at Brigham and Women's Hospital from April 2015 to February 2020. A cohort of 199 hospitalized patients treated with CAR T-cell therapy was used to develop a combined hidden Markov model and lasso-penalized logistic regression model to forecast the course of ICANS. Model development was done using leave-one-patient-out cross validation. RESULTS: Among the 199 patients included in the analysis 133 were male (66.8%), and the mean (SD) age was 59.5 (11.8) years. 97 patients (48.7%) developed ICANS, of which 59 (29.6%) experienced severe grades 3-4 ICANS. Median time of ICANS onset was day 9. Selected clinical predictors included maximum daily temperature, C reactive protein, IL-6, and procalcitonin. The model correctly predicted which patients developed ICANS and severe ICANS, respectively, with area under the curve of 96.7% and 93.2% when predicting 5 days ahead, and area under the curve of 93.2% and 80.6% when predicting the entire future risk trajectory looking forward from day 5. Forecasting performance was also evaluated over time horizons ranging from 1 to 7 days, using metrics of forecast bias, mean absolute deviation, and weighted average percentage error. CONCLUSION: The forecasting model accurately predicts risk of ICANS following CAR T-cell infusion and the time course ICANS follows once it has begun.Cite Now.

Association of Smoking and E-Cigarette in Chronic Liver Disease: An NHANES Study.

Background: There is an increased trend of e-cigarette but the toxic effects of e-cigarette metabolites are not widely studied especially in liver disease. Hence, we aimed to evaluate the prevalence and patterns of recent e-cigarette use in a nationally representative sample of US adults and adolescents and its association amongst respondents with liver disease. Methods: We conducted a retrospective cross-sectional study using National Health and Nutrition Examination Survey (NHANES) database from 2015 to 2018. The self-reported NHANES questionnaire was used to assess liver disease (MCQ160L, MCQ170L and MCQ 510 (a-e)), e-cigarette use (SMQ900) and traditional smoking status (SMQ020 or SMQ040). We conducted univariate analysis and multivariable logistic regression models to predict the association of e-cigarette use, traditional smoking and dual smoking amongst the population with liver disease. Results: Out of total 178,300 respondents, 7,756 (4.35%) were e-cigarette users, 48,625 (27.27%) traditional smoking, 23,444 (13.15%) dual smoking and 98,475 (55.23%) non-smokers. Females had a higher frequency of e-cigarette use (49.3%) compared to dual (43%) and traditional smoking (40.8%) (P < 0.0001). Respondents with a past history of any liver disease have lower frequency of e-cigarette use compared to dual and traditional smoking, respectively (2.4% vs. 6.4% vs. 7.2%; P < 0.0001). In multivariate logistic regression models, we found that e-cigarette users (odds ratio (OR): 1.06; 95% confidence interval (CI): 1.05 - 1.06; P < 0.0001) and dual smoking (OR: 1.50; 95% CI: 1.50 - 1.51; P < 0.0001) were associated with higher odds of having history of liver disease compared to non-smokers. Conclusion: Our study found that despite the low frequency of e-cigarette use in respondents with liver disease, there was higher odds of e-cigarette use amongst patients with liver disease. This warrants the need for more future prospective studies to evaluate the long-term effects and precise mechanisms of e-cigarette toxicants on the liver.

Mental health disparities amongst sexual-minority adolescents of the US - A national survey study of YRBSS-CDC.

OBJECTIVE: We aimed to evaluate the prevalence and trend of identifying as a sexual minority among the American adolescent population. Additionally, we aimed to evaluate the prevalence and odds of substance abuse, hopelessness, and suicidality among the sexual minority adolescents compared to their heterosexual peers. METHODS: We performed a retrospective cross-sectional study using Youth Risk Behavior Surveillance System (YRBSS) data from 2015 to 2019. YRBSS divides "Sexual identity" into three groups: heterosexuals, sexual minorities (gay or lesbian or bisexual), and unsure. We identified "hopelessness and suicidality" using the survey questions exploring if participants felt sad or hopeless for >2 weeks, considered suicide, made a suicide plan, and attempted suicide requiring medical care. Univariate and multivariable survey logistic regression analyses were performed to establish an association between hopelessness, suicidality, substance abuse, and identifying as a sexual minority. RESULTS: Out of 41,377 adolescents, 4055 (9.8%) identified as a sexual minority. An increasing percentage of adolescents identified themselves as a sexual minority between 2015 to 2019 (8% to 11.2%) (pTrend<0.0001). The sexual minority had a higher prevalence of feeling sad and hopeless (63.4 vs. 28.6%), considering suicide (46 vs. 14.2%), planning suicide (38.9 vs. 11.5%), attempting suicide, and having injurious suicide attempts compared to heterosexuals. (p<0.0001) Amongst sexual minorities, the prevalence of substance abuse was higher compared to their heterosexual peers, which includes cigarettes (15 vs 7.8%), e-cigarette (27.2 vs 23.2%), inhalants (14.1 vs 5.3%), cocaine (8.4 vs 3.9%), marijuana (31.2 vs 20.2%), alcohol (36.9 vs 30.3%), steroids (6.4 vs 2.2%), heroin (4.4 vs 1.2%), and injectable drugs (4.0 vs 1.1%) (p<0.0001). In regression analysis, the sexual minority had higher odds of substance abuse, feeling sad and hopeless (aOR:4.6; 95%CI:4.0-5.2; p<0.0001), considering suicide (3.2; 2.8-3.7; p<0.0001), planning suicide (2.0; 1.7-2.3; p<0.0001) compared to heterosexual. CONCLUSION: Sexual minorities not only have higher prevalence and odds of hopelessness and suicidality but also have higher prevalence and odds of substance abuse like cigarettes, marijuana, cocaine, heroin, inhalants, and steroids. Hence, early identification, risk stratification, and interventions to reduce mental health disparities are needed.

Kidney disease and COVID-19 disease severity-systematic review and meta-analysis.

We aimed to identify prevalence and association of comorbid chronic kidney disease (CKD), acute kidney injury (AKI) and utilization prevalence of continuous renal replacement therapy (CRRT) in COVID-19-hospitalized patients as a function of severity status. With the ongoing struggle across the globe to combat COVID-19 disease, published literature has described the role of kidney disease in COVID-19 patients based on single/multicenter experiences across the globe. We extracted data from observational studies describing comorbid CKD, AKI and CRRT and outcomes and severity of COVID-19-hospitalized patients from December 1, 2019-August 20, 2020 following PRISMA guidelines. Severity of COVID-19 includes intensive care unit admission, oxygen saturation < 90%, invasive mechanical ventilation utilization, in-hospital admission and mortality. Meta-analysis was performed using a random-effects model to calculate pooled estimates, and forest plots were created. In total, 29 studies with 15,017 confirmed COVID-19 patients were included. The overall prevalence of AKI was 11.6% [(430/3693)], comorbid CKD 9.7% [(1342/13,728)] and CRRT 2.58% [(102/3946)] in our meta-analysis. We also found higher odds of comorbid CKD (pooled OR: 1.70; 95%CI: 1.21-2.40; p = 0.002), AKI (8.28; 4.42-15.52; p < 0.00001) and utilization of CRRT (16.90; 9.00-31.74; p < 0.00001) in patients with severe COVID-19 disease. Conclusion Our meta-analysis suggests that comorbid CKD, AKI and utilization of CRRT were significantly associated with COVID-19 disease severity. Clinicians should focus on early triaging of COVID-19 patients with comorbid CKD and at risk for AKI to prevent complication and mortality.

Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.

There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

Diagnostic Yield of TEE in Patients with Cryptogenic Stroke and TIA with Normal TTE: A Systematic Review and Meta-Analysis.

INTRODUCTION: The role of transesophageal echocardiography (TEE) in cryptogenic stroke and transient ischemic attack (TIA) with normal transthoracic echocardiography (TTE) remains controversial in the absence of definite guidelines. We aimed to perform a systematic review and meta-analysis to estimate an additional diagnostic yield and clinical impact of TEE in patients with cryptogenic stroke and TIA with normal TTE. METHODS: We performed a systematic review of cohort studies on PubMed using the keywords 'cryptogenic stroke', cryptogenic TIA', 'TEE', and 'TTE' with matching MeSH terms. We included studies with patients who had cryptogenic stroke or TIA and had normal TTE findings, where the study intended to obtain TEE on all patients and reported all TEE abnormalities. The studies containing patients with atrial fibrillation were excluded. All studies were evaluated for internal and external validity. Inverse variance random effects models were used to calculate the effect size, the number needed to diagnose, and the 95% confidence interval. RESULTS: We included 15 studies with 2054 patients and found LA/LAA/aortic thrombus, valvular vegetation, PFO-ASA, valvular abnormalities, and complex aortic plaques on TEE. Of these, 37.5% (29.7%-45.1%) of patients had additional cardiac findings on TEE. Management of 13.6% (8.1%-19.1%) of patients had changed after TEE evaluation. Based on current guidelines, it should change management in 4.1% (2.1%-6.2%) of patients and could potentially change management in 30.4% (21.9%-38.9%) of patients. Sensitivity analysis was also performed with only class II studies to increase internal validity, which showed additional cardiac findings in 38.4% (28.5%-48.3%), changed management in 20.2% (8.7%-31.8%), should change management in 4.7% (1.5%-7.9%), and could potentially change management in 30.4% (17.8%-43.0%) of patients. CONCLUSIONS: The diagnostic yield of TEE to find any additional cardiac findings in patients with cryptogenic stroke or TIA is not only high, but it can also change management for certain cardiac abnormalities. TTE in cryptogenic stroke or TIA may mitigate future risks by tailoring the management of these patients.

Post-Hemorrhagic Hydrocephalus and Outcomes Amongst Neonates With Intraventricular Hemorrhage: A Systematic Review and Pooled Analysis.

Introduction Intraventricular hemorrhage (IVH) is a common cause of morbidity and mortality in preterm neonates. IVH leads to complications such as posthemorrhagic hydrocephalus (PHH), which commonly occurs in neonates with a more severe degree of IVH. Hence, we aimed to evaluate the characteristics and outcomes of PHH in neonates with IVH. Methods We performed a systematic review of cases reported from January 1978 to December 2020 through the PubMed database, using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and the keywords 'intraventricular hemorrhage,' 'cerebral intraventricular hemorrhage,' and 'newborn.' A total of 79 articles were considered for analysis, and data on neonatal and maternal characteristics and outcomes were collected. The analysis was performed by using the χ2 test, Wilcoxon rank-sum test, and multivariate logistic regression model. Results We analyzed a total of 101 IVH cases, 54.5% were male and 62.4% preterm. Thirteen point nine percent (13.9%) presented with grade I, 35.6% grade II, and grade III respectively, and 8% grade IV IVH. Among the 59 (58.4%) neonates with PHH, 33.6% had resolved PHH and 24.8% had unresolved. In adjusted regression analysis, we found that neonates with resolved PHH have lower odds of having neurodevelopmental delay (OR:0.15, 95%CI:0.03-0.74; p=0.02) and death (OR:0.9;95%CI:0.01-0.99; p=0.049) as compared to unresolved PHH. Conclusion Our study showed that neonates with resolved PHH have a statistically significant lower risk of neurodevelopmental delay (NDD) and mortality. Future studies should be planned to evaluate the role of treatment and its effect on outcomes in IVH neonates with PHH as a complication.

COVID-19: a Disease with a Potpourri of Histopathologic Findings-a Literature Review and Comparison to the Closely Related SARS and MERS.

Since the coronavirus disease 2019 (COVID-19) pandemic has hit the entire world, there is ample knowledge regarding its clinical course and prognostic biomarkers. Still, the pathophysiology of COVID-19 is poorly understood. Since the first guidelines published in February 2020 for autopsy of both confirmed and suspected COVID-19 cases, there has been an increasing number of autopsies and literature reporting histopathological findings. However, our knowledge about the immunological response of various organ systems to the virus, as well as response patterns, is inadequate but is essential to understand and initiate timely and targeted antiviral, anti-inflammatory, or anticoagulative therapy. Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily considered a respiratory virus, current evidence shows that it causes life-threatening complications in almost all organ systems including the heart, brain, kidney, spleen, liver, and eyes. Hence, in this article, we reviewed the published case reports and case series in order to increase our understanding of COVID-19 pathophysiology. The main histopathological findings of the lungs include diffuse alveolar damage with activated type II pneumocytes, fibroblasts, protein-rich exudate, and hyaline membranes. Other significant histopathological findings include cardiomegaly, right ventricular dilation, splenic pulp atrophy, kidneys with severe podocytopathy, and collapsing glomerulopathy, and the brain showed hypoxic changes in the cerebellum and cerebrum. Furthermore, in this review, we also explained different pathological findings of SARS-CoV and MERS and compared them to SARS-CoV-2. This comprehensive review will improve our understanding of COVID-19 pathophysiology and various disease stages, hence promoting the application of targeted therapy.

Forty Years Since the Epidemic: Modern Paradigms in HIV Diagnosis and Treatment.

Human immunodeficiency virus (HIV) is a viral infection that, when transmitted through the exchange of certain bodily fluids, destroys various immune cells and contributes to an overall weakened immune system. If left untreated, HIV progresses to acquired immunodeficiency syndrome (AIDS) - a chronic, life-threatening condition that puts patients at risk for opportunistic infections. Since the emergence of HIV nearly a century ago, the world has seen tremendous advances in elucidating its pathology and progression. These advances have been accompanied by an increased understanding of how subsequent effects and symptoms manifest in afflicted individuals. These discoveries, coupled with the ever-improving technologies and methodologies used for detection and treatment, provide the scientific and medical community with a solid grasp of HIV. Despite this significant headway, there is still much progress to be made; medical advances have allowed people with HIV to manage their disease and live a longer, healthier life, but a definite cure is yet to be found. Thus, the following literature review serves as both an extensive compendium of our current understanding of HIV - its pathology, testing/detection, repercussions, and treatment - and an acknowledgement of the areas that still require further research.

Educational Case: Diagnostic Approach to Salivary Gland Neoplasms.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040. 1.

Risk Factors and Incidence of Acute Ischemic Stroke: A Comparative Study Between Young Adults and Older Adults.

Introduction Approximately 5-10% of strokes occur in adults of less than 45 years of age. The rising prevalence of stroke risk factors may increase stroke rates in young adults (YA). We aimed to compare risk factors and outcomes of acute ischemic stroke (AIS) among YA. Methods Adult hospitalizations for AIS and concurrent risk factors were found in the Nationwide Inpatient Sample database. Weighted analysis using chi-square and multivariable survey logistic regression was performed to evaluate AIS-related outcomes and risk factors among YA (18-45 years) and older patients. Results A total of 4,224,924 AIS hospitalizations were identified from 2003 to 2014, out of which 198,378 (4.7%) were YA. Prevalence trend of YA with AIS showed incremental pattern over time (2003: 4.36% to 2014: 4.7%; pTrend<0.0001). In regression analysis, the risk factors associated with AIS in YA were obesity (adjusted odds ratio {aOR}: 2.26; p<0.0001), drug abuse (aOR: 2.56; p<0.0001), history of smoking (aOR: 1.20; p<0.0001), infective endocarditis (aOR: 2.08; p<0.0001), cardiomyopathy (aOR: 2.11; p<0.0001), rheumatic fever (aOR: 4.27; p=0.0014), atrial septal disease (aOR: 2.46; p<0.0001), ventricular septal disease (aOR: 4.99; p<0.0001), HIV infection (aOR: 4.36; p<0.0001), brain tumors (aOR: 7.89; p<0.0001), epilepsy (aOR: 1.43; p<0.0001), end stage renal disease (aOR: 2.19; p<0.0001), systemic lupus erythematous (aOR: 3.76; p<0.0001), polymyositis (aOR: 2.72; p=0.0105), ankylosis spondylosis (aOR: 2.42; p=0.0082), hypercoagulable state (aOR: 4.03; p<0.0001), polyarteritis nodosa (aOR: 5.65; p=0.0004), and fibromuscular dysplasia (aOR: 2.83; p<0.0001). Conclusion There is an increasing trend in AIS prevalence over time among YA. Both traditional and non-traditional risk factors suggest that greater awareness is needed, with prevention strategies for AIS among young adults.

A Case Study and Review of Literature of Eruptive Syringoma in a Six-Year-Old.

Syringomas are benign tumors originating from the intraepidermal portion of eccrine sweat ducts. A six-year-old African American female presented with multiple 2-3 mm hyperpigmented papules over the neck, upper chest, and axillae bilaterally. The lesions were non-tender, non-pruritic, and did not bleed when lightly scraped. A café-au-lait macule was incidentally found in the mid-back of the patient. Histopathologically, multiple small ducts displaying a tadpole-shaped/paisley-tie pattern with fibrotic stroma were identified on hematoxylin and eosin staining. Epithelium showing nests of cells with basaloid appearance and dilated glands filled with eosinophilic material were also identified. These histopathologic findings were consistent with a diagnosis of eruptive syringoma. The patient was treated conservatively, and the lesions subsided without intervention. In most patients requesting treatment, isotretinoin is used; however, this may be an unnecessary measure in many patients. Overall, this case was significant due to the patient's young age, ethnicity, and clinical improvement in the absence of treatment.

A rare case of primary effusion lymphoma in HIV negative patient: Diagnostic challenges and literature review.

We present a rare case of primary effusion lymphoma (PEL) in a 75 year old, HIV-negative male patient with multiple comorbidities. Imaging studies revealed a massive right pleural effusion and a significant lung collapse with multiple plural soft tissue nodules. Immediate thoracentesis was performed. Cytologic evaluation of the pleural fluid showed abnormally large cell with increased nuclear to cytoplasmic ratio, irregular nuclear contours and prominent nucleoli, with phenotypic expression of HHV-8, CD138, CD30, and MUM1 markers and negative staining for epithelial and mesothelial markers. PEL is a rare and aggressive large B-cell lymphoma often affecting immunocompromised adults and is mostly associated with human herpes virus 8/Kaposi sarcoma-associated herpes virus (HHV-8/KSHV). However, cases in immunocompetent elderly patients have been reported. The cytomorphologic features of PEL overlaps with those of aggressive lymphomas such as diffuse large B-cell lymphoma, plasmablastic lymphoma, and anaplastic large-cell lymphoma. Also, mesothelioma, metastatic carcinoma or melanoma should be considered in the differential diagnosis. Hence, PEL should be kept in mind in the diagnostic algorithm of cytological evaluation of serosal fluid not only in HIV positive patients but also HIV-negative elderly patients. In this report, we aim to highlight the cytologic and immunohistochemical staining pattern of this rare entity to increase awareness of this entity among cytopathologists.

Stroke and HIV-associated neurological complications: A retrospective nationwide study.

There is an increased risk of stroke and other neurological complications in human immunodeficiency virus (HIV) infected patients with no large population-based studies in the literature. We aim to evaluate the prevalence of stroke, HIV-associated neurological complications, and identify risk factors associated with poor outcomes of stroke among HIV admissions in the United States. In the nationwide inpatient sample with adult HIV hospitalizations, patients with primary cerebrovascular disease (CeVDs) and HIV-associated neurological complications were identified by ICD-9-CM codes. We performed a retrospective study with weighted analysis to evaluate the prevalence of stroke and neurological complications and outcomes of stroke among HIV patients. We included 1,559,351 HIV admissions from 2003 to 2014, of which 22470 (1.4%) patients had CeVDs (transient ischemic attack [TIA]: 3240 [0.2%], acute ischemic stroke [AIS]: 14895 [0.93%], and hemorrhagic stroke [HS]: 4334 [0.27%]), 7781 (0.49%) had neurosyphilis, 29,925 (1.87%) meningitis, 39,190 (2.45%) cytomegalovirus encephalitis, 4699 (0.29%) toxoplasmosis, 9964 (0.62%) progressive multifocal leukoencephalopathy, and 142,910 (8.94%) epilepsy. There is increased overall prevalence trend for CeVDs (TIA: 0.17%-0.24%; AIS: 0.62%-1.29%; HS: 0.26%-0.31%; pTrend < .0001) from 2003 to 2014. Among HIV admissions, variables associated with AIS were neurosyphilis (odds ratio: 4.38; 95% confidence interval: 3.21-5.97), meningitis (4.87 [4.10-5.79]), and central nervous system tuberculosis (6.72 [3.85-11.71]). Toxoplasmosis [4.27 [2.34-7.76]), meningitis (2.91 [2.09-4.06)], and cytomegalovirus encephalitis (1.62 [1.11-2.37]) were associated with higher odds of HS compared to patients without HS. There was an increasing trend of CeVDs over time among HIV hospitalizations. HIV-associated neurological complications were associated with the risk of stroke, together with increased mortality, morbidity, disability, and discharge to long-term care facilities. Further research would clarify stroke risk factors in HIV patients to mitigate adverse outcomes.

Outcomes of COVID-19 Complications and their Possibilities as Potential Triggers of Stroke.

INTRODUCTION: There is limited literature on coronavirus disease 2019 (COVID -19) complications such as thromboembolism, cardiac complications etc. as possible trigger for stroke. Hence, we aim to evaluate the prevalence and outcomes of COVID-19 related cardiovascular complications and secondary infection and their possibility as potential triggers for the stroke. METHODS: Data from observational studies describing the complications [acute cardiac injury (ACI), cardiac arrhythmias (CA), disseminated intravascular coagulation (DIC), septic shock, secondary infection] and outcomes of COVID-19 hospitalized patients from December 1, 2019 to June 30, 2020, were extracted following PRISMA guidelines. Adverse outcomes defined as intensive care units, oxygen saturation less than 90%, invasive mechanical ventilation, severe disease, and in-hospital mortality. The odds ratio and 95% confidence interval were obtained, and forest plots were created using random-effects models. A short review of these complications as triggers of stroke was conducted. RESULTS: 16 studies with 3480 confirmed COVID-19 patients, prevalence of ACI [38%vs5.9%], CA [26%vs5.3%], DIC [4%vs0.74%], septic shock [18%vs0.36%], and infection [30%vs12.5%] was higher among patients with poor outcomes. In meta-analysis, ACI [aOR:9.93(95%CI:3.95-25.00], CA [7.52(3.29-17.18)], DIC [7.36(1.24-43.73)], septic shock [30.12(7.56-120.10)], and infection [10.41(4.47-24.27)] had higher odds of adverse outcomes. Patients hospitalized with acute ischemic stroke and intracerebral hemorrhage, had complications like pulmonary embolism, venous thromboembolism, DIC, etc. and had poor outcomes CONCLUSION: The complications like acute cardiac injury, cardiac arrhythmias, DIC, septic shock, and secondary infection had poor outcomes. Patients with stroke were having history of these complications. Long term monitoring is required in such patients to prevent stroke and mitigate adverse outcomes.