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Objectives: This study aims to characterize the risks and benefits of in-OR extubation after cardiac surgery., Design: This is a retrospective chart review., Setting: Single tertiary care hospital., Participants: Cardiac surgical patients >18 years. Exclusion criteria included patients extubated after 6 h in the ICU, those with a history of congenital heart disease (CHD), those intubated prior to arrival to the OR, procedures including circulatory arrest and/or selective cerebral perfusion, cardiothoracic transplantation, and intraoperative death. De-identified data was collected via the hospital's electronic medical record., Interventions: None., Measurements and Main Results: Perioperative data was collected for 726 patients, of which 303 (42 %) were extubated in the OR. Multivariable regression models were derived with covariates based on expert clinical reasoning. When compared to fast track extubation, in-OR extubation was independently associated with decreased index hospitalization length of stay (-1.74, 95 % CI [-2.22, -1.08], p < 0.001) and decreased incidence of in-hospital new post-operative atrial fibrillation (OR 0.56 95 % CI [0.37, 0.86], p < 0.01). There were no differences in persistent vasoactive therapy requirement, postoperative mechanical circulatory support or extubation failure., Conclusions: In-OR extubation is associated with decreased index hospitalization length of stay and decreased new onset in-hospital atrial fibrillation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Sporadic cases of atypical hemolytic uremic syndrome (aHUS) have been described in the literature in association with COVID-19 infection and vaccination in adults and pediatric patients. The exact mechanisms underlying COVID-19-associated thrombotic microangiopathies (TMAs) remain incompletely understood. Herein, we present a detailed meta-analysis of the clinical characteristics, outcomes, and management strategies of COVID-19-associated aHUS and thrombotic thrombocytopenic purpura (TTP)., Methods: This study was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses updated guidelines. PubMed was utilized for searching for case reports and series. Adverse outcome at last follow-up was defined as estimated glomerular filtration rate < 30 ml/min per 1.73 m 2 (patients with aHUS), no remission with therapy, or patient death. Data were analyzed using Wilcoxon rank and Chi-square tests., Results: Our analysis cohort included 118 studies reporting on 170 patients. These included 84 cases of aHUS and 86 cases of TTP resulting from COVID-19 infection ( n  = 92) or vaccination ( n  = 78). Significantly more cases of aHUS were reported after infection ( n  = 65) than immunization ( n  = 19), compared to TTP, where the reverse was true ( n  = 27 and n  = 59, respectively; P  < 0.001). In patients with aHUS with stage 3 acute kidney injury (AKI), requirement of kidney replacement therapy (KRT) was seen in three-fourths of the cohort for a median of 15. In patients with TTP, severe COVID-19 infection ( P  = 0.04) predicted nonremission or death at last follow-up. Administration of i.v., rituximab and caplacizumab were protective ( P  = 0.03 and P  = 0.06, respectively). Immune TTP (iTTP) was reported more often than HUS following mRNA vaccines (81% vs. 58%; P  = 0.06)., Conclusion: COVID-19 infection and vaccination are a potential trigger for onset or relapse of aHUS and TTP, especially in patients who are not on maintenance complement inhibitors or immunosuppression., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Introduction: In CheckMate 227 Part 1, nivolumab plus ipilimumab prolonged overall survival (OS) versus chemotherapy in patients with metastatic NSCLC, regardless of tumor programmed death-ligand 1 (PD-L1) expression. Here, we report post hoc exploratory systemic and intracranial efficacy outcomes and safety by baseline brain metastasis status at 5 years' minimum follow-up., Methods: Treatment-naive adults with stage IV or recurrent NSCLC without EGFR or ALK alterations, including asymptomatic patients with treated brain metastases, were enrolled. Patients with tumor PD-L1 greater than or equal to 1% were randomized to nivolumab plus ipilimumab, nivolumab, or chemotherapy; patients with tumor PD-L1 less than 1% were randomized to nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy groups. Assessments included OS, systemic and intracranial progression-free survival per blinded independent central review, new brain lesion development, and safety. Brain imaging was performed at baseline (all randomized patients) and approximately every 12 weeks thereafter (patients with baseline brain metastases only)., Results: Overall, 202 of 1739 randomized patients had baseline brain metastases (nivolumab plus ipilimumab: 68; chemotherapy: 66). At 61.3 months' minimum follow-up, nivolumab plus ipilimumab prolonged OS versus chemotherapy in patients with baseline brain metastases (hazard ratio = 0.63; 95% confidence interval: 0.43-0.92) and in those without (hazard ratio = 0.76; 95% confidence interval: 0.66-0.87). In patients with baseline brain metastases, 5-year systemic and intracranial progression-free survival rates were higher with nivolumab plus ipilimumab (12% and 16%, respectively) than chemotherapy (0% and 6%). Fewer patients with baseline brain metastases developed new brain lesions with nivolumab plus ipilimumab (4%) versus chemotherapy (20%). No new safety signals were observed., Conclusions: With all patients off immunotherapy for more than or equal to 3 years, nivolumab plus ipilimumab continued to provide a long-term, durable survival benefit in patients with or without brain metastases. Intracranial efficacy outcomes favored nivolumab plus ipilimumab versus chemotherapy. These results further support nivolumab plus ipilimumab as an efficacious first-line treatment for patients with metastatic NSCLC, regardless of baseline brain metastasis status., (Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.)

Tuberculosis is emerging worldwide across diverse populations and geographies; unrestricted by the social divide and the geographical barriers in today's interconnected world. This rise in its prevalence can be linked to multiple factors including urbanisation, spurt in global travel, population explosion, migration and HIV infection. The varied and complex clinical presentation of intracranial tuberculosis tricks even the best of the clinicians. This along with the other facets associated with its management including drug resistance, paradoxical reaction, underlying HIV infection can make it particularly challenging. Imaging has a definitive role in the evaluation and follow-up of intracranial tuberculosis and MRI is the cornerstone in this regard. Typical features of intracranial tuberculosis are well-described. However, it is not infrequent to encounter atypical and bizarre presentations, both clinically and on imaging. A holistic clinical and imaging review of difficult cases, including newer MRI techniques, is necessary for the neuroradiologist, neurologist and the neurosurgeon to arrive at the right diagnosis in a timely fashion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Urinothorax is an uncommon thoracic complication of genitourinary (GU) tract disease, which is most frequently caused by obstructive uropathy, but may also occur as a result of iatrogenic or traumatic GU injury. It is underrecognized because of a perceived notion as to the rarity of the diagnosis and the absence of established diagnostic criteria. Urinothorax is typically described as a paucicellular, transudative pleural effusion with a pleural fluid/serum creatinine ratio >1.0. It is the only transudate associated with pleural fluid acidosis (pH < 7.40). When the pleural fluid analysis demonstrates features of a transudate, pH <7.40 and a pleural fluid/serum creatinine ratio >1.0, a confident clinical diagnosis of urinothorax can be established. A technetium 99m renal scan can be considered a confirmatory test in patients who lack the typical pleural fluid analysis features or fail to demonstrate evidence of obstructive uropathy that can be identified via conventional radiographic modalities. Management of a urinothorax requires a multidisciplinary approach with an emphasis on the correction of the underlying GU tract pathology, and once corrected, this often leads to a rapid resolution of the pleural effusion., (Copyright © 2017 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

The incidence of postoperative nausea and vomiting (PONV) can be as high as 80% in patients with risk factors (e.g., females, history of motion sickness). PONV delays postoperative recovery and costs several hundred million dollars annually. Cell-based assays show that halogenated ethers (e.g., isoflurane) activate 5-HT 3 receptors, which are found on gastrointestinal vagal afferents and in the hindbrain - key pathways for producing nausea and vomiting. This project evaluated the role of the vagus and activation of the hindbrain in isoflurane-induced emesis in musk shrews, a small animal model with a vomiting reflex, which is lacking in rats and mice. Sham-operated and abdominal vagotomized shrews were exposed to 1 to 3% isoflurane to determine effects on emesis; vagotomy was confirmed by lack of vagal transport of the neuronal tracer Fluoro-Gold. In an additional study, shrews were exposed to isoflurane and hindbrain c-Fos was measured at 90min after exposure using immunohistochemistry. There were no statistically significant effects of vagotomy on isoflurane-induced emesis compared to sham-operated controls. Isoflurane exposure produced a significant increase in c-Fos-positive cells in the nucleus of the solitary tract and vestibular nuclei but not in the area postrema or dorsal motor nucleus. These results indicate that the abdominal vagus plays no role in isoflurane-induced emesis and suggest that isoflurane activates emesis by action on the hindbrain, as shown by c-Fos labeling. Ultimately, knowledge of the mechanisms of inhalational anesthesia-induced PONV could lead to more targeted therapies to control PONV., Competing Interests: Conflict of interests The authors declare no conflicts of interest., (Copyright © 2016 Elsevier B.V. All rights reserved.)

The molecular mechanisms underlying learning and memory impairment in patients with HIV-associated neurological disease have remained unclear. Calcium/calmodulin-dependent kinase II (CaMKII) has key roles in synaptic potentiation and memory storage in neurons and also may have immunomodulatory functions. To determine whether HIV and simian immunodeficiency virus (SIV) induce alterations in CaMKII expression and/or activation (autophosphorylation) in the brain, we measured CaMKII alterations by quantitative immunoblotting in both an in vitro HIV/neuronal culture model and in vivo in an SIV-infected macaque model of HIV-associated neurological damage. Using primary rat hippocampal neuronal cultures treated with culture supernatants harvested from HIV-1-infected human monocyte-derived macrophages (HIV/MDM), we found that CaMKII activation declined after exposure of neurons to HIV/MDM. Consistent with our in vitro measurements, a significant decrease in CaMKII activation was present in both the hippocampus and frontal cortex of SIV-infected macaques compared with uninfected animals. In SIV-infected animals, total CaMKII expression in the hippocampus correlated well with levels of synaptophysin. Furthermore, CaMKII expression in both the hippocampus and frontal cortex was inversely correlated with viral load in the brain. These findings suggest that alterations in CaMKII may compromise synaptic function in the early phases of chronic neurodegenerative processes induced by HIV.

Determinations of SACE activity were performed in 80 patients with sarcoidosis, 55 normal controls, and 29 patients with asthma, by the spectrophotometric method of Cushman and Cheung. SACE levels were significantly higher in both untreated and steroid-treated patients with sarcoidosis than in normal controls: 46.2 +/- 20.6 (S.D.), nm/min/ml, 38.1 +/- 23.1, and 26.8 +/- 1.8, respectively. There were no significant differences between steroid-treated and untreated patient groups. However, an inverse correlation was observed between SACE levels and steroid dose, suggesting the possibility of a dose dependency for steroid-induced depression of SACE. Elevated SACE levels (2 S.D. above mean controls) were present in 67% of untreated sarcoidosis patients. The prevalence of elevated SACE levels was not significantly higher when the patient population was examined with respect to duration of disease, radiological stage, and the presence of abnormality in pulmonary function tests. When patients were divided according to the frequency of clinical criteria of disease activity, the presence of two or more criteria was associated with elevated SACE levels in 88% of patients. But SACE levels were elevated in 32% of patients judged to have dormant disease by clinical criteria. SACE levels had an 81% accuracy in prediction of disease activity and a 79% accruacy for prediction of inactivity. It was concluded that SACE elevations have definite diagnostic value in sarcoidosis and are helpful in establishing the presence of disease activity but are not sufficient to fully separate active from inactive disease groups.