Hackensack Meridian Health

Tuberculous meningitis (TBM), a severe form of extrapulmonary tuberculosis, requires sustained therapeutic drug concentrations in the central nervous system (CNS). Linezolid is a promising treatment for TBM due to excellent CNS penetration and bactericidal activity against Mycobacterium tuberculosis. However, co-administration with rifampicin may alter linezolid pharmacokinetics (PK), potentially reducing efficacy due to drug-drug interactions. We utilized data from the Adjunctive Linezolid for the Treatment of TubERculous Meningitis trial, a phase II study evaluating high-dose (35 mg/kg) versus standard-dose (10 mg/kg) rifampicin, with or without linezolid, in adults with TBM. Plasma sampling occurred on days 1 (dense) and 14 (sparse) with cerebrospinal fluid (CSF) sampling. Population PK modeling and simulation were employed to characterize linezolid disposition in plasma and CSF. Eighteen participants contributed 73 plasma and 30 CSF samples to the analysis. Plasma concentrations were best described by a 1-compartment model with linear absorption and clearance, linked to a CSF compartment. High-dose rifampicin increased linezolid clearance by 34.2%, reducing systemic and CNS exposure. Simulations demonstrated that 1200 mg once-daily dosing failed to maintain therapeutic plasma and CSF linezolid concentrations when co-administered with high-dose rifampicin. In contrast, 600 mg twice-daily achieved adequate linezolid exposures even with higher rifampicin doses. High-dose rifampicin significantly increases linezolid clearance, reducing plasma and CSF drug levels. However, twice-daily linezolid may mitigate this effect and maintain therapeutic concentrations. These findings underscore the importance of optimizing linezolid dosing when used with rifampicin in TBM and support evaluation in larger studies to guide treatment strategies.

BackgroundPatients with metastatic breast cancer (MBC) experience significant quality-of-life decrements, but there are few supportive care interventions specifically designed for this group that significantly improve quality of life. Ecological momentary assessment (EMA) and related ecological momentary interventions (EMIs) may be particularly beneficial for patients with MBC. However, no studies have previously examined the use of EMIs in the context of metastatic cancer.ObjectiveThe purpose of this study was to qualitatively assess experiences with EMA and preferences for intervention content and mode among patients living with MBC, with an emphasis on EMIs.MethodsWomen with MBC (n=29) were recruited from a longitudinal, observational study of quality of life using an EMA design. In-depth qualitative interviews assessed participants’ perspectives on the EMA design, including its feasibility, acceptability, and relevance to participants’ MBC experiences. Guided by participants’ EMA data, the interviews also examined the impact of self-monitoring and possible interventions when patients reported high symptom burden and/or low quality of life. Interviews were audio-recorded, transcribed verbatim, and analyzed using open coding, axial coding, and selective coding. The codebook was developed by reviewing a randomly selected subset of transcripts (n=5) and creating inductive, data-driven codes using the raw data, which were deductively organized into overarching themes.ResultsParticipants were mainly White (17/29, 59%), heterosexual (23/29, 79%), currently working (17/29, 59%), and held at least a bachelor’s degree (17/29, 59%). Participants had been living with MBC for a median of 2.5 years (range 0.2‐16.6 years). Most were diagnosed with hormone receptor-positive (23/29, 79%) and HER2-negative (21/29, 72%) breast cancer. Qualitative analysis identified 5 major themes. The participants reflected on their reasons for enrolling in the study, including interest in study activities and giving back to the MBC community (theme 1: participant engagement). Most participants found the EMA format easy to complete, and they provided recommendations for improving the design of future studies, including altering the timing and frequency of questionnaires (theme 2: feedback on study design). While less common, some participants discussed how engaging with the EMA protocol altered their experiences or behaviors (theme 3: impact of self-monitoring). Participants also discussed their reactions to seeing their EMA data, including their mixed thoughts on real-time data sharing (theme 4: responses to data). Finally, participants suggested programs and resources to improve their overall quality of life, reflecting on their interest in real-time interventions and peer-to-peer support (theme 5: recommendations for future interventions).ConclusionsPatients with MBC are willing to use EMA methodologies for data collection on quality of life and are open to EMIs with varying content and formats. Given variations in daily functioning between and within patients, a just-in-time adaptive intervention framework may be well suited for this population.

BACKGROUND Central nervous system (CNS) manifestations of tuberculosis (TB) account for approximately 1-2% of all TB cases worldwide. Tuberculomas, which are granulomatous lesions of the CNS diagnostically confirmed through biopsy, can mimic more common intracranial pathologies, including abscesses and neoplasms. This report describes a patient with pulmonary TB who presented with seizure and was ultimately diagnosed with a right temporal lobe TB mimicking a brain abscess. CASE REPORT A 30-year-old woman with alcohol use disorder, polysubstance use, and pulmonary TB previously treated with rifampin, isoniazid, pyrazinamide, and ethambutol (RIPE) presented to the emergency department (ED) following a generalized seizure. Anti-tuberculous therapy had been interrupted for several months due to alcohol-related hepatotoxicity. Prior imaging demonstrated a small right temporal lobe lesion, which subsequently enlarged and developed rim-enhancing features after RIPE therapy was interrupted. Given the diagnostic uncertainty and her clinical course, neurosurgical intervention was pursued. Craniotomy with surgical exploration and biopsy revealed necrotizing granulomas and a Ziehl-Neelsen stain confirmed acid-fast bacilli (AFB), confirming intracranial tuberculoma. Postoperatively, she was restarted on a modified anti-tuberculous regimen. CONCLUSIONS Intracranial tuberculoma should remain a key differential diagnosis for ring-enhancing lesions, even in immunocompetent patients and in low-incidence regions. Further, it underscores the importance of maintaining therapy continuity to prevent disease progression. Importantly, when response to therapy is uncertain or adherence is questionable, clinicians should maintain a low threshold for deciding to perform early biopsy to confirm the etiology.

BackgroundJewish shechita and Islamic halal are distinct yet similar forms of slaughter by exsanguination via ventral neck incision (SEVNI); neither permits preslaughter stunning. SEVNI has been criticized on the grounds that the vertebral arteries in cattle, which remain intact after SEVNI, may continue to supply blood to the brain, potentially delaying loss of consciousness (LOC) and causing unnecessary pain and distress to the animal. In this context, LOC is the loss of cortical awareness, which by definition abolishes sensibility and pain perception. The objective of this review is to evaluate the literature that specifically addresses the role of the vertebral artery in brain perfusion following SEVNI.MethodsThis study was not funded. A non-registered systematic search of PubMed, Google Scholar, the Cochrane Library, Medline, and Web of Science (last searched 02/10/2026) identified experimental, observational and physiological studies that assessed vertebral artery hemodynamics and/or evaluated the functional significance of the vertebral artery in cattle. Non-cattle studies, studies lacking relevant measures, reviews, commentaries, and abstracts without full text were excluded. Quantitative pooling (meta-analysis) was not performed due to methodological and outcome variability therefore results were synthesized narratively.ResultsThirteen studies were included, with all articles independently reviewed by co-authors to minimize risk of bias. Using the ROBINS-I framework, the overall risk of bias across included studies was assessed as moderate. Across the reviewed studies, evidence consistently demonstrated that immediately following SEVNI, vertebral blood flow and pressure decrease to negligible levels, with most residual flow diverted away from the cerebral cortex.LimitationsStudy limitations include heterogeneous study designs, variable outcomes and methods.ConclusionThe available evidence indicates that vertebral artery flow following SEVNI is unlikely to be sufficient to sustain cortical perfusion, support integrated cortical function or delay LOC.

Capivasertib is capable of precipitating lethal diabetic ketoacidosis in patients with or without a history of diabetes.Early hyperglycemia after drug initiation should be considered a medical emergency and treated

Introduction: Migraine has been reported to be associated with an increased risk of spontaneous cervical artery dissection (sCeAD), a leading cause of ischemic stroke, particularly in young adults. Migraine may increase vulnerability to ischemia, making brain tissue more susceptible to ischemic injury. Nevertheless, migraine patients have been reported to have higher Calcitonin Gene-Related Peptide (CGRP) levels which has a vasodilatory effect that may protect against ischemia. We aim to determine if a history of migraine influences clinical presentation and outcome of sCeAD. Methods: We performed a post-hoc analysis of the STOP-CAD registry, a large international multicenter study of patients with sCeAD. Clinical, demographic, and imaging data were compared between patients with and without history of migraine applying statistical tests as appropriate for continuous variables (t-tests) and for categorical variables (Chi-square/Fisher’s exact test). Logistic regression, Kaplan-Meier survival analysis, and Cox regression with clustered standard errors were used to assess associations between migraine, sCeAD features and outcome adjusting for potential confounders. Results: STOP-CAD included 668 participants (16.6%) with a history of migraine and 3,355 (83.4%) without migraine. Patients with migraine were younger and more frequently female. In a univariate analysis, patients with migraine compared to patients without migraine had significantly fewer presentations with ischemic stroke, a higher rate of transient ischemic attacks, lower NIHSS scores at admission and better functional outcomes at discharge (mRankin<2). These results remained significant after adjusting for potential confounders: ischemic stroke (OR 0.53, 95% CI 0.42–0.67, p<0.001); NIHSS admission (OR 0.60, 95% CI 0.47–0.76, p<0.001) and mRankin<2 at discharge (OR 1.65, 95%CI 1.34-0.23, p=0.001). Conclusion: In this cohort study, migraine patients with sCeAD were significantly less likely to have an ischemic stroke at admission and had better functional outcome at discharge. Migraine might influence the clinical presentation of sCeAD and modulate the severity of cerebral ischemia. Future research should evaluate the role of potential pathophysiological mechanisms, particularly of CGRP.

Introduction: Intracranial stenting during endovascular thrombectomy (EVT) is a common practice in the setting of failed reperfusion or severe stenosis. Immediate stent patency requires periprocedural antiplatelet therapy (APT). How APT intensity interacts with prior intravenous thrombolysis (IVT) to influence hemorrhagic risk remains uncertain. We aimed to assess whether the APT regimen modifies the association of IVT with early intracranial hemorrhage after intracranial stenting during EVT. Methods: This was a subanalysis of the RESISTANT registry, a multicenter, international, retrospective cohort (2016 to 2023) of adults with acute ischemic stroke who underwent intracranial stenting during EVT. APT regimens were categorized as conservative (intravenous or oral aspirin alone, or aspirin plus an oral P2Y12 inhibitor) and aggressive (any regimen including intravenous GPIIb/IIIa inhibitor or intravenous cangrelor). Four main groups were compared according to the APT regimen (conservative/aggressive) and the use of IVT (+/-). The primary outcome was a composite of sICH and parenchymal hematoma types 1 and 2 (sICH-PH2-PH1). Multivariable logistic regression models were used to evaluate the interaction between IVT and APT, adjusting for clinically relevant covariates. Results: Among the 823 included patients, 44 (5.3%) received conservative APT with IVT, 130 (15.8%) received conservative APT without IVT, 145 (17.6%) received aggressive APT with IVT, and 504 (61.2%) received aggressive APT without IVT. Among patients who received IVT, sICH-PH2-PH1 rates were 9.3% with conservative APT and 10.7% with aggressive APT; among those without IVT, rates were 3.2% and 9.9%, respectively. Administration of IVT (adjusted odds ratio [aOR] 5.84, 95%CI 1.07 to 43.92; p=0.05) and aggressive APT (aOR 4.81, 95% CI 1.41 to 30.22; p=0.03) were each associated with higher odds of hemorrhagic complications, with a significant IVT by APT interaction (P interaction =0.05; Figures 1 and 2 ). Within the aggressive APT plus IVT subgroup, sICH-PH2-PH1 occurred in 20% of patients treated with cangrelor and 6.1% treated with a glycoprotein IIb/IIIa inhibitor ( Figure 3 ). Conclusion: Among patients requiring intracranial stenting, aggressive periprocedural APT and prior IVT are each associated with higher hemorrhagic risk, with the combination showing the worst observed crude outcome. Prospective evaluation of protocolized APT pathways in the IVT setting is warranted.