North Shore Medical Center

Abstract Tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is an exaggerated inflammatory response to Mycobacterium tuberculosis typically described in HIV-infected patients after initiation of anti-retroviral therapy (ART), as immune function is restored. It is rarely reported in HIV-negative patients, with presentation as paradoxical worsening of tuberculosis following initiation of antimycobacterial treatment. TB-IRIS is often misdiagnosed as treatment failure, drug resistance, superimposed bacterial infection, or malignancies. The case describes IRIS in an immunocompetent patient with drug-sensitive tuberculosis that was managed successfully. Case Presentation A 72-year-old Nigerian female with a recent diagnosis of pulmonary tuberculosis (PTB), on six weeks with Rifampin, Isoniazid, Pyrazinamide, and Ethambutol (RIPE) therapy, presented with dyspnea, fatigue, and edema with prior unintentional 30 pounds weight loss. She was hypoxemic, requiring intubation, and maintained on air-borne isolation. Laboratory work-up revealed a normal WBC and an unremarkable viral panel and HIV Testing. Chest X-ray showed increased confluence of biapical opacities. Chest CT Scan revealed worsening tree-in-bud opacities and consolidation encasing right upper lobe cavitary lesion. Bronchoscopy with right upper lobe bronchoalveolar lavage (BAL) was performed, revealing sparse acid-fast bacilli (AFB) with no other bacterial growth. The patient continued to have recurrent fevers and hypoxemia despite antibiotic coverage, raising concern for tuberculosis-associated immune reconstitution syndrome (TB-IRIS). Due to elevated liver function tests (LFTs), anti-tuberculosis medications were temporarily withheld. She was initiated on oral steroids with prednisone for presumed TB-IRIS. Anti-tuberculosis medications were gradually reintroduced as LFTs improved. The patient's condition improved, and she was extubated on day 7, remained afebrile, and was discharged from the ICU on day 11. Discussion The patient's clinical course, with initial improvement with confirmed adherence to the RIPE therapy regimen but subsequently worsening dyspnea, recurrent fevers, and pulmonary infiltrates with negative infectious work-up suggest a diagnosis of TB-IRIS. Though she was initiated on empirical antibiotics, subsequent bronchoscopy culture data was negative, and she did respond to steroids with resolution of her clinical symptoms and hypoxemia. Currently, there is no test to confirm or rule out the diagnosis of TB-IRIS, nor is there consensus on standard treatment. However, a four-week course of prednisone has been shown to reduce morbidity in patients with TB-IRIS. Conclusion Tuberculosis-immune reconstitution inflammatory syndrome characterized as paradoxical worsening of a Mycobacterium tuberculosis infection following initiation of anti-tuberculosis treatment can occur in both HIV-infected and uninfected patients. Further studies are needed to develop precise diagnostic criteria and optimal treatment modalities.

Abstract Introduction: A pulmonary embolism (PE) with hemodynamic compromise carries significant mortality. With concurrent patent foramen ovale (PFO), increase in right side pressures may lead to right ventricular failure and paradoxical embolization. We describe a rare case of extensive bilateral pulmonary emboli with an additional thrombus extending from the right atrium into the left atrium through a PFO requiring urgent surgical thrombectomy. Description: A 62-year-old female with a history of hypothyroidism, obstructive sleep apnea, a prior deep venous thrombosis following shoulder surgery (completed 3-months of eliquis therapy) and a left knee replacement 13 days prior to presentation (on daily 81mg aspirin), presented to the hospital after a sudden loss of consciousness during an outpatient physical therapy session. On arrival to the emergency department, her vitals were significant for blood pressure of 88/56 mmHg and hypoxia to 89% on room air, both improving after 1 liter of crystalloid fluid and supplementation with 2 liters of oxygen. Her labs at admission were significant for a D-Dimer of 1975 ng/mL (normal 0 – 230 ng/mL), and a high-sensitivity troponin of 11 ng/L (normal: 3 – 37 ng/L). A chest x-ray showed no acute cardiopulmonary abnormalities. Her subsequent computed tomography angiography (CTA) study showed bilateral PE with evidence of right heart strain with an extension of embolism through the interatrial septum into the left atrium (see figure 1). An emergent thrombectomy was performed via median sternotomy. A thromboembolism was extracted with a noted indentation where it straddled the PFO. A transesophageal echo confirmed the absence of the specimen and bidirectional flow across the PFO, which was closed during the operation. Her postoperative course was significant for the brief use of norepinephrine and dobutamine therapy, and initiation of amiodarone for ectopic beat suppression. After surgical intervention, follow up echocardiogram revealed improved right ventricular function with intact interatrial septum without evidence of flow. She was transitioned to oral anticoagulation and was discharged on postoperative day 6 in stable condition. Discussion: PE with a thrombus extending through a PFO into the left atrium on CTA is quite a rare presentation and it requires immediate interventions because of hemodynamic compromise, and also due to the risk of systemic embolization which may lead to critical consequences. Furthermore, given such a rare presentation, radiologists and treating physicians need to be aware of the possibility of clot migration through a PFO.

Hepatitis B virus (HBV) remains a global public health problem despite the availability of effective vaccine and antiviral therapy. Cytomegalovirus (CMV), another hepatotropic virus, is also very prevalent in the general population worldwide. Both HBV and CMV can persist in the host and have potential to reactivate especially with weakened host cellular immunity. Superimposed CMV infection can lead to severe HBV reactivation. The pathogenesis of the co-infection of HBV and CMV remains poorly understood. Studies reported conflicting results regarding the inhibitory effect of CMV on HBV replication. There is an unmet need on the management of co-infection of HBV and CMV; research initiatives dedicated to understanding their interactions are urgently needed.

Abstract BackgroundAlthough agitation in Alzheimer’s Disease (Agit‐AD) is a common and troubling neuropsychiatric syndrome, behavioral interventions lack consistent efficacy and there are no FDA‐approved medications. Neurobiological mechanisms that contribute to Agit‐AD include brain atrophy, degradation of neurotransmission, neuroinflammation, disrupted circadian rhythms, comorbidities and frailty. Agit‐AD is a major source of disease progression, patient disability, financial burden, and caregiver stress. Dronabinol is synthetic tetrahydrocannabinol (THC, one of the predominant biochemical constituents of cannabis). Cannabinoids may improve Agit‐AD by providing protection against neuroinflammation and excitotoxicity, regulating neurotransmitters, improving comorbidities, stabilizing circadian rhythms, and increasing cerebral blood flow.MethodTHC‐AD is a three‐week placebo‐controlled, double‐blind, RCT of dronabinol (10 mg QD) in 80 patients with severe Agit‐AD. Twice daily administration maximizes daytime coverage for agitation and minimizes sundowning. Inclusionary criteria include a diagnosis of AD, severe agitation, and being 60‐95 years old, while exclusionary criteria include serious or unstable medical illness, seizure disorder, delirium, current use of lithium, and inability to swallow a pill. Primary outcomes include a change in the Pittsburgh Agitation Scale and NPI‐C Agitation/Aggression subscales.ResultWe have enrolled 37 out of 80 participants (Table 1: mean age 78.2 years, 78.4% female, 83.8% Caucasian, mean education 13.2 years, 48.6% family history). Study participants are significantly cognitively impaired (Table 2: mean baseline MMSE of 7.1), agitated (mean NPI‐C Agitation 14.8, mean NPI‐C Aggression 6.4) and in reasonable overall health (Figure 1: General Medical Health Rating, 10.8% “excellent,” 48.6% "good" and 40.5% "fair”). Recorded AEs have been tolerable (Figure 2). Due to the COVID‐19 pandemic, we expanded our inpatient trial to include outpatient enrollments and implemented hybrid visits with telemedicine to limit in‐person interactions. To bolster our recruitment, we are collaborating with additional clinical sites, increasing dementia bed capacity, and deploying recruitment strategies for outpatients, including referrals from providers and other research trials, social media ads, and virtual community outreach. Updated results will be presented at AAIC (estimated 6‐10 additional participants).ConclusionSafe and effective interventions for severe agitation are greatly needed. This pilot trial will help to examine the safety and efficacy of dronabinol for Agit‐AD.

Nurses are confronting a number of negative mental health consequences owing to high burdens of grief during COVID-19. Despite increased vaccination efforts and lower hospitalization and mortality rates, the long-term effects of mass bereavement are certain to impact nurses for years to come. The nurse coaching process is an evidence-based strategy that nurse leaders can use to assist staff in mitigating negative mental health outcomes associated with bereavement. The End-of-Life Nursing Education Consortium brought together a team of palliative nursing experts early in the pandemic to create resources to support nurses across settings and promote nurse well-being. This article shares a timely resource for health systems and nursing administration that leverages the nurse coaching process to support bereaved staff in a safe and therapeutic environment.

Non-small cell lung cancer (NSCLC) is a heterogeneous disease, commonly defined by genetic alterations in oncogenic drivers. Targeted therapies have transformed the management of oncogene-driven lung cancers, with targeted agents now approved in the United States for 7 distinct molecular alterations. Nonetheless, acquired resistance remains an ongoing challenge, underscoring the need for alternative therapeutic approaches. Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1) axis have emerged as important therapies in the management of advanced NSCLC, but the role of these agents in patients with oncogenic driver mutations remains unclear. Here, we focus on epidermal growth factor receptor-mutant and anaplastic lymphoma kinase-rearranged NSCLC as paradigms to explore the role of immune checkpoint inhibitors in oncogene-driven NSCLC. We provide an overview of the clinical data examining programmed death ligand 1 (PD-L1) inhibitor monotherapy, PD-(L)1 inhibitors, and tyrosine kinase inhibitor combinations, as well as combinations of PD-(L)1 inhibitors and chemotherapy.

Although acute pancreatitis (AP) is associated with recurrent hospitalizations, the impact of different hospital readmissions (DHR) versus same hospital readmissions (SHR) on outcomes is unknown. We study the burden of DHR among readmissions after survival from AP hospitalizations. Among adult AP patients (Nationwide Readmissions Database), we calculated the prevalence, trends, and predictors of DHR, and its impact on mortality, hospital stay, and charges during 30- and 90-day readmissions. From 2010 to 2014, 15% and 26% of AP hospitalizations (422,950) were readmitted in 30 and 90 days, respectively. The DHR rates were similar (26.3%, 30 days; 26.4%, 90 days) and unchanged from 2010 to 2014 (Ptrends > 0.10). The predictors of DHR were similar during both readmissions and included younger age category (18-45 years), hospital characteristics (nonteaching, small bed size, nonmicropolitan/metropolitan areas), substance abuse, comorbidities, and nonreception of cholecystectomy and pancreatectomy during index hospitalizations.During readmissions (30 and 90 days), DHR was associated with adjusted odds ratio (95% confidence interval), higher mortality (1.40 [1.19-1.64] and 1.50 [1.32-1.71]), longer hospital stay (1.3 days [1.1-1.7 days] and 1.1 days [0.9-1.3 days]), and higher charges (US $16,779 [US $13,898-US $20,254] and US $14,299 [US $12,299-US $16,623]). Targeted measures are needed toward patients at risk for DHR to curb the poor outcomes.