Seizures and memory impairment induced by patient-derived anti-N-methyl-D-aspartate receptor antibodies in mice are attenuated by anakinra, an interleukin-1 receptor antagonist.

OBJECTIVE: Neuroinflammation associated with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis may facilitate seizures. We previously showed that intraventricular administration of cerebrospinal fluid from patients with anti-NMDAR encephalitis to mice precipitates seizures, thereby confirming that antibodies are directly pathogenic. To determine whether interleukin (IL)-1-mediated inflammation exacerbates autoimmune seizures, we asked whether blocking the effects of IL-1 by anakinra, a selective IL-1 receptor antagonist, blunts antibody-induced seizures. METHODS: We infused C57BL/6 mice intraventricularly with purified serum IgG from patients with anti-NMDAR encephalitis or monoclonal anti-NMDAR IgG; subdural electroencephalogram was continuously recorded. After a 6-day interval, mice received anakinra (25 mg/kg sc, twice daily) or vehicle for 5 days. Following a 4-day washout period, we performed behavioral tests to assess motor function, anxiety, and memory, followed by hippocampus tissue analysis to assess astrocytic (glial fibrillary acidic protein [GFAP]) and microglial (ionized calcium-binding adapter molecule [Iba]-1) activation. RESULTS: Of 31 mice infused with purified patient NMDAR-IgG (n = 17) or monoclonal NMDAR-IgG (n = 14), 81% developed seizures. Median baseline daily seizure count during exposure to antibodies was 3.9; most seizures were electrographic. Median duration of seizures during the baseline was 82.5 s. Anakinra administration attenuated daily seizure frequency by 60% (p = .02). Anakinra reduced seizure duration; however, the effect was delayed and became apparent only after the cessation of treatment (p = .04). Anakinra improved novel object recognition in mice with antibody-induced seizures (p = .03) but did not alter other behaviors. Anakinra reduced the expression of GFAP and Iba-1 in the hippocampus of mice with seizures, indicating decreased astrocytic and microglial activation. SIGNIFICANCE: Our evidence supports a role for IL-1 in the pathogenesis of seizures in anti-NMDAR encephalitis. These data are consistent with therapeutic effects of anakinra in other severe autoimmune and inflammatory seizure syndromes. Targeting inflammation via blocking IL-1 receptor-mediated signaling may be promising for developing novel treatments for refractory autoimmune seizures.

Effect of Hospital Teaching Status on Mortality and Procedural Complications of Percutaneous Paracentesis in the United States: A Four-Year Analysis of the National Inpatient Sample.

Objectives Numerous previous studies investigated the impact of medical training settings on outcomes of hospitalized patients. However, the impact of teaching hospital status on outcomes of percutaneous paracentesis, to the best of our knowledge, has never been studied before. Methods Hospitalized patients who underwent percutaneous paracentesis were identified from the National Inpatient Sample database from 2016 to 2019 across the United States (US) teaching and non-teaching hospitals. Outcomes studied were differences in risk of mortality, postprocedural outcomes, and healthcare resource utilization. Multivariate logistic analysis was performed using STATA software (StataCorp LLC, College Station, Texas, US) and results were adjusted for patient and hospital characteristics and comorbidities. Results Inpatient mortality rates were significantly higher in patients undergoing paracentesis at US teaching hospitals (adjusted odds ratio (aOR) 1.29, 95%CI 1.23-1.35, p<0.001) compared to non-teaching hospitals. Similarly, higher risk of procedural complications including hemoperitoneum (aOR 1.90, 95%CI 1.65-2.20, p<0.001), hollow viscus perforation (aOR 1.97, 95%CI 1.54-2.51, p<0.001), and vessel injury/laceration (aOR 15.3, 95%CI 2.12-110.2, p=0.007) were noticed in the study group when compared to controls. Furthermore, hospital teaching status was associated with prolonged mean length of stay (9.33 days vs 7.42 days, adjusted mean difference (aMD) 1.81, 95%CI 1.68-1.94, p<0.001) and increased charge of care ($106,014 vs $80,493, aMD $24,926, 95%CI $21,617-$28,235, p <0.001) Conclusion Hospitalized patients undergoing paracentesis in US teaching hospitals have an increased risk of mortality, postprocedural complications, prolonged length of stay, and increased charge of care when compared to non-teaching hospitals.

The Pattern of Dyslipidemia in Chronic Liver Disease Patients.

Introduction Patients with chronic liver disease are expected to report derangements in serum lipid profiles. Lipid profile monitoring is not a part of the routine management of these patients in our hospital. Few recent studies show how lipid profile varies with the severity of disease and should be considered in the management planning of such patients. The objective of this study was to determine the pattern of dyslipidemia in chronic liver disease patients. Materials and methods A cross-sectional study was conducted involving 171 patients of all genders aged between 18 years and 60 years presenting with chronic liver disease with disease severity graded on Child-Pugh class as A, B, and C. Lipid profile was acquired in all these patients and was compared across various subgroups. Individual serum lipid parameters were graded as normal, high, or very high. Each patient was required to provide written informed consent. Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp. Armonk, NY) was used to analyze data statistically, taking a p-value of ≤0.05 as significant. Results The mean age of patients was 51.2±7.3 years. The male to female ratio came out to be 1.5:1, with 103 (60.2%) male and 68 (39.8%) female patients included in the study. The disease was classified as Child-Pugh A in 20 (11.7%) patients, Child-Pugh B in 67 (39.2%) patients, and Child-Pugh C in 84 (49.1%) patients. Forty-four (25.7%) patients were hypertensive while 62 (36.3%) were diabetic. The mean body mass index (BMI) of these patients was 25.9±2.4 kg/m2. Mean serum values among Child-Pugh A, Child-Pugh B, and Child-Pugh C of low-density lipoproteins (LDL) (113.15±14.08 vs. 95.58±14.25 vs. 53.46±5.90 mg/dl; p-value 0.001), high-density lipoproteins (HDL) (50.60±3.19 vs. 40.70±2.95 vs. 35.40±3.88 mg/dl; p-value 0.001), total cholesterol (174.20±17.33 vs. 164.00±17.82 vs. 128.64±24.73 mg/dl; p-value 0.001), and triglycerides (127.15±8.98 vs. 100.84±27.12 vs. 93.36±25.56 mg/dl; p-value 0.001) decreased significantly with increasing severity of disease. Nineteen (11.1%) patients had hyperlipidemia (serum values of two or more parameters above normal) while 152 (88.9%) patients had normal lipid profile. When stratified, no statistically significant difference was found in the frequency of hyperlipidemia across various subgroups based on the patient's gender, age, duration, and severity of the disease, BMI, or diabetic and hypertensive status. Conclusions A substantial proportion of patients with chronic liver disease had hyperlipidemia which varied with the severity of disease on Child-Pugh classification. Routine monitoring of the lipid profile of such patients is necessary for timely identification and management of dyslipidemia to improve the outcome of such patients. It also suggests an important role of lipid profile in the risk stratification and treatment of chronic liver disease patients and warrants further studies in this regard.

The Outcomes of Extracorporeal Shock Wave Lithotripsy for High-Density Renal Stone on Non-Contrast Computed Tomography.

Introduction Urinary lithiasis is usually managed by extracorporeal shock wave lithotripsy (ESWL). Patients are examined using non-contrast computed tomography (NCCT) in order to evaluate the feasibility of ESWL, according to where the stone is located and how big is its size. The objective of this study is to determine the outcomes of ESWL in patients having high-density renal stone, evaluated using NCCT. Materials and methods A descriptive case series study was conducted in the Department of Urology, Sindh Institute of Urology & Transplantation, Karachi for six months. Patients of either gender aged between 25-50 years, who presented with solitary renal and ureteric calculi of 0.5-2 cm in diameter and high-density renal stones [>750 hounsfield units (HU)] were enrolled. ESWL was performed and a satisfactory outcome was defined as complete stone clearance in less than or equal to three ESWL sessions. Statistical Package for Social Sciences (SPSS) (IBM Corp., Armonk, NY) was used to analyze frequencies and percentages of the number of ESWL sessions, complete renal stone clearances, and satisfactory outcomes at the end of 12 weeks. A p-value of <0.05 was considered significant. Results The mean age of the patient was reported to be 34.08 ± 9.53 years. 51.6% male preponderance was noticed. Renal and ureteric stones were found in 69.7% and 30.3% of patients, respectively. 21.3% of patients showed stone clearance after two ESWL sessions, 27% of patients after three ESWL sessions, and 51.6% of patients after four ESWL sessions. Stone clearance was found in 58.2% of patients and a satisfactory outcome was found in 42.6% of patients. Conclusions Our results signify a satisfactory outcome of extracorporeal shock wave lithotripsy for high-density renal stone on non-contrast computed tomography. Further studies on a larger scale are needed to validate these results.

Mean Changes in Estimated Glomerular Filtration Rate in Patients Undergoing Percutaneous Nephrolithotomy Having Renal Stone Disease.

Background Urinary stone disease is associated with renal impairment because of obstruction and infection. Comorbidities include hypertension, dyslipidemia, diabetes, and impaired renal function. Furthermore, as recurrences are common in urolithiasis, such patients undergo many treatments throughout their life. Percutaneous nephrolithotomy (PCNL) is an effective treatment for renal stones with a diameter greater than 2 cm. The primary objective of this study was to observe the mean changes in estimated glomerular filtration rate (GFR) in patients undergoing PCNL having renal stone disease. Methodology This cross-sectional study was conducted for six months between June and November 2020 at a tertiary care hospital in Karachi, Pakistan. All male and female patients aged between 15 and 70 years who were diagnosed with renal stones using X-ray of the kidney, ureter, and bladder or using ultrasound of the abdomen and planned for PCNL were selected. Patients with any duration of kidney stone disease were included. Statistical Package for Social Sciences version 20.0 (IBM Corp., Armonk, NY, USA) was used to statistically analyze the data. Results The mean age of the patients was 41.11 ± 14.30 (17-70) years. A total of 61 (38.1%) patients were female and 99 (61.9%) were male. Mean preoperative GFR was 91.22 ± 5.88 mL/min which decreased to 83.64 ± 5.70 mL/min at 48 hours post-PCNL. GFR significantly decreased after surgery (p = 0.0001). Conclusions During early postoperative days, GFR was decreased in patients undergoing PCNL. Factors that may impair renal function should be avoided during the first few days after undergoing PCNL. Further large-scale studies are needed to investigate these changes in GFR in post-PCNL patients.

Frequency of Human Immunodeficiency Virus in Patients Admitted with Acute Stroke.

Introduction Stroke is a leading cause of chronic disability and death in both developing and developed countries. A significant proportion of stroke patients are human immunodeficiency virus (HIV) positive. About half of the HIV patients experience some sort of neurological deficit in their lifetimes. The exact reason for the occurrence of stroke in HIV infected patients is poorly understood. The purpose of our study is to determine the frequency of HIV among patients admitted with acute stroke. Materials and methods This cross-sectional study is conducted at a major metropolitan hospital in Karachi for six months. A total of 130 patients of stroke between the ages of 30 and 70 years of either gender were included in this study. A complete history was taken and a physical examination was performed. Each patient underwent a battery of tests that included HIV serology, lipid profile, electrocardiography (ECG), chest X-ray (posteroanterior (PA) view), and computed tomography (CT) scan of the brain. Carotid Doppler ultrasonography to assess carotid artery stenosis was also ordered. The means and standard deviations of age and cluster of differentiation 4 (CD4) cell count were calculated. The frequencies and proportions of gender, diabetes mellitus (DM), hypertension (HTN), smoking, obesity, dyslipidemia, carotid artery stenosis, and HIV status were calculated. Stratification was done by applying the chi-square test and assuming p-value ≤0.05 as significant. This helped analyze the association of age, gender, DM, HTN, smoking, obesity, dyslipidemia, and carotid artery stenosis to the frequency of HIV. Results The mean age of the study population was 55.54 ± 11.166 years. There were 39 (30%) patients <50 years of age while 91 (70%) patients were ≥50 years of age. Gender distribution showed that 86 (66.15%) patients were male, and 44 (33.85%) patients were female. Furthermore, 71 (54.62%) patients were hypertensive, 53 (40.77%) were diabetic, 62 (47.69%) were smokers, 49 (37.69%) were obese, 52 (40%) had dyslipidemia, and 77 (59.23%) had carotid artery stenosis. The frequency of HIV was noted at 24 (18.46%). The mean CD4 count was estimated at 241 ± 103.295 cells/mm3. Stratification showed a significant relationship between the frequency of HIV with only gender (p=0.01) and dyslipidemia (p=0.037). Conclusion HIV infection in patients with stroke is not uncommon. Patients who are male, younger in age, have dyslipidemia, belong to a low socioeconomic class, or have a bad sexual history are more likely to have HIV as an underlying cause of stroke. The exact pathogenesis of such a stroke and the role of antiretroviral therapy in the prevention and treatment of this group of stroke are not completely understood and need further analysis.

When the Heart Cries Wolf: Myocardial Bridging Presenting as Angina-like Chest Pain.

Myocardial bridging (MB) is the most common congenital coronary anomaly and refers to an intramural course of an epicardial coronary artery. The proximal segment of the left anterior descending artery (LAD) is the most commonly involved vessel and is often seen in patients with hypertrophic cardiomyopathy (HCM). We present a case of a 64-year-old female with left-sided non-exertional chest pain. Electrocardiography (EKG) and echocardiography were negative, however, stress EKG was positive with deep ST-segment depressions. Coronary angiography revealed mid-segment compression of LAD during systole, returning to its normal caliber during diastole. The patient remained asymptomatic during the hospital course and was later discharged on beta-blocker therapy. This case is different from others in a sense that it presented with severe pain like angina and mid-segment of LAD is involved rather than the proximal segment where it commonly occurs. This case report will help clinicians overcome the diagnostic challenge in patients presenting with atypical chest pain.

Slurring of Speech and Lip Paresthesia: Symptoms of Levodopa End of Dose Wearing Off in Parkinson's Disease.

The prolonged use of levodopa for treating Parkinson's disease is associated with motor and nonmotor complications. These include wearing-off, delayed-on, partial-on, no-on, and on-off phenomena. In the wearing-off effect, symptoms return before a patient's next scheduled dose of levodopa. Patients may present with motor, sensory, or autonomic fluctuations. In this report, we present a female patient experiencing numbness of lips and slurred speech as a symptom of wearing-off effect. The major differential for sudden numbness of lips and slurred speech includes transient ischemic attacks. Therefore, it is imperative to identify the cause of these episodes so that appropriate treatment can be initiated. Our patient underwent extensive cardiac and neurological investigations, the findings of which were unremarkable. Her symptoms were likely due to levodopa wearing-off. Her condition improved on changing her levodopa to a sustained release form with more frequent dosing along with the addition of ropinirole to her treatment regimen.