Citations

This Inside Story describes the experiences of the authors, who both received cancer diagnoses during their fellowships.

SLE is a chronic multisystem autoimmune disease that affects the kidneys in approximately 50% of patients, with the prevalence rising to as high as 70% in certain populations, such as African American and Asian people. Antimalarials—and particularly hydroxychloroquine (HCQ)—are currently considered a mainstay of therapy, together with immunosuppressants. Over the past decades, several studies have extensively investigated the mechanisms of action of antimalarial agents and their potential beneficial properties in patients with SLE in general. However, the evidence for the therapeutic benefit of HCQ in patients with lupus nephritis (LN) derives mainly from observational studies, conducted in an era before the refinement of induction and maintenance protocols for immunosuppressive therapy. Despite the paucity of high-quality evidence on its efficacy in LN, the nephrology community widely supports the universal use of HCQ in patients with LN, and recommendations for its use are firmly entrenched in various clinical practice guidelines. Nonetheless, the use of antimalarials may also carry inherent risks, underscoring the importance of personalized approaches in these patients. Herein, we comprehensively review the available literature on antimalarials in LN, aiming to update the current evidence, limitations, and future perspectives for the use of antimalarials in adults.

Abstract Purpose: Cardiovascular health disparities are present in African Americans, but it remains unknown whether this phenomenon affect Somali Americans. Study of Somali Americans is warranted due to distinct genetic and cultural differences from African Americans of western African ancestry. Orthostatic hemodynamic responses have implications for cardiovascular risk, especially among African American females. We sought to examine race and sex differences in systolic (SAP) and diastolic (DAP) arterial pressure and heart rate (HR) responsiveness to standing. We hypothesized that SAP, DAP, and HR change from supine to standing position would be higher in Somali Americans. Methods: We studied blood pressure and HR responsiveness in 139 (70 Somali; age: 29±10 years, 69 White; age: 31±9 years) participants. Supine SAP, DAP, and HR were measured after at least five minutes of supine rest, and again after one minute of standing. SAP, DAP, and HR change was compared between groups. Results: ΔSAP and ΔDAP were similar between groups (race × sex: p>0.05). However, HR responsiveness to orthostasis varied between race and sex comparisons (race×sex: p=0.011). Somali females exhibited an augmented HR response to orthostasis compared to White females (Δ19±13 vs. 11±9 beats/min, p=0.005) and Somali males (Δ19±13 vs. 12±9 beats/min, p=0.020). Conclusion: ΔHR to standing is augmented in young female Somali Americans. These findings highlight an early potential impairment in hemodynamic regulation that may heighten future cardiovascular risk. Further work is warranted to identify the potential autonomic nervous system underpinnings that may contribute to potentiated orthostatic responses and cardiovascular risk in Somali American females. Clinical Trial Registration: www.clinicaltrials.gov; unique identifier, NCT04124848; NCT05411029; NCT03308578.

Multimodal technology is poised to revolutionize clinical practice by integrating artificial intelligence with traditional diagnostic modalities. This evolution traces its roots from Hippocrates’ humoral theory to the use of sophisticated AI-driven platforms that synthesize data across multiple sensory channels. The interplay between historical medical practices and modern technology challenges conventional patient–clinician interactions and redefines diagnostic accuracy. Highlighting applications from neurology to radiology, the potential of multimodal technology emerges, suggesting a future where AI not only supports but enhances human sensory inputs in medical diagnostics. This shift invites the medical community to navigate the ethical, practical, and technological changes reshaping the landscape of clinical medicine.

Despite evidence that specialized care for seriously ill nursing home (NH) residents is needed, barriers to accessing palliative care (PC) remain. A significant issue is the complexity of the referral process that inhibits timely and equitable access to care. This qualitative descriptive study explored the PC referral process in NHs. Using rapid qualitative analysis with semi-structured interview data from NH staff, primary care, and specialty PC providers ( N = 17) in six states, this study outlines a multistep referral process along with barriers and proposed solutions. Key recommendations include comprehensive PC education program development, implementation of an evidence-based PC screening tool, and the holistic integration of PC services in NHs.

ABSTRACT During virus replication in cultured cells, copy-back defective viral genomes (cbDVGs) can arise. CbDVGs are powerful inducers of innate immune responses in vitro , but their occurrence and impact on natural infections of human hosts remain poorly defined. We asked whether cbDVGs were generated in the brain of a patient who succumbed to subacute sclerosing panencephalitis (SSPE) about 20 years after acute measles virus (MeV) infection. Previous analyses of 13 brain specimens of this patient indicated that a collective infectious unit (CIU) drove lethal MeV spread. In this study, we identified 276 replication-competent cbDVG species, each present in over 100 copies in the brain. Six species were detected in multiple forebrain locations, implying that they travelled long-distance with the CIU. The cbDVG to full-length genomes ratio was often close to 1 (0.6–1.74). Most cbDVGs were 324–2,000 bases in length, corresponding to 2%–12% of the full-length genome; all are predicted to have complementary terminal sequences. If improperly encapsidated, these sequences have the potential to form double-stranded structures that can induce innate immune responses. To assess this, we examined the transcriptome of all brain specimens. Several interferon and inflammatory response genes were upregulated, but upregulation levels did not correlate with cbDVG levels in the specimens. Thus, the CIU that drove MeV pathogenesis in this brain includes, in addition to two complementary full-length genome populations, many locally restricted and few widespread cbDVG species. The widespread cbDVG species may have been positively selected but how they impacted pathogenesis remains to be determined. IMPORTANCE Copy-back defective viral genomes (cbDVGs) can drive virus–host interactions. They can suppress virus replication directly, by competing with full-length genomes, or indirectly by stimulating antiviral immunity. In vitro , cbDVG can slow down infections and promote persistence, but there is limited documentation of their presence in human hosts or of their impact on disease. We had the unique opportunity to analyze the brain of a patient who succumbed to subacute sclerosing panencephalitis, a rare but lethal consequence of measles. We detected more than 270 distinct cbDVG species; most were restricted to one specimen, but several reached all lobes of the forebrain, suggesting positive selection. Our analyses provide the missing knowledge of the diversity of cbDVG in a natural infection of a human host. They also reveal that a collective infectious unit that caused lethal human brain disease includes few widespread cbDVG, in addition to two ubiquitous complementary full-length genome populations.

Introduction/Objectives: We aimed to investigate the effect of family structure on depression program outcomes for adolescents enrolled in a depression-focused, primary care-based collaborative care program. Methods: This was a retrospective study of primary care patients ages 12 to 18 years seen at a Midwestern academic center with data obtained by medical record review. We used logistic regression models to assess the effect of family structure on program graduation and achievement of a single Patient Health Questionnaire 9–Modified for Adolescents (PHQ-9M) score <5 at any time while enrolled. Results: Adolescents were divided into 2 groups, Both Parents in Household (n = 179) and Parents Not Together (n = 161). The Both Parents in Household group had higher rates of graduation (38.0% vs 23.6%, P = .005) and achieving single PHQ-9M scores <5 (64.1% vs 46.2%, P = .002) than the Parents Not Together group. Discussion: Youth residing with both parents had higher rates of successful outcomes in a depression-focused collaborative care program.

Background: Angiosarcomas are rare tumors that can be difficult to diagnose due to subtle changes in the vascular endothelium. When there is evidence to suggest malignancy, such as a pathologic fracture, further investigation is needed, and a high suspicion for angiosarcoma needs to be present so that appropriate immunohistochemical stains are utilized on biopsied tissue. In situations where such suspicion is high and prior biopsies have been negative, performance of splenectomy, can be both diagnostic and therapeutic when splenomegaly is present. Case Report: This is a case of a 52-year-old woman with splenomegaly, initially attributed to infection, in the setting of upper respiratory symptoms and thrombocytopenia. Three months later, however, she presented with back pain. Imaging showed lytic bone lesions with pathologic vertebral fracture and numerous liver lesions that were too small to characterize further. Initial biopsies of the liver and bone did not reveal a pathologic process. Several months later, still without a unifying diagnosis, she presented to our institution. MRI of the brain was done for neurologic concerns and showed pathologic enhancement in the calvarium. A PET scan showed diffuse avidity of the skeleton and spleen. After discussing the case with a hematologist, splenectomy was performed for both diagnostic and therapeutic purposes. Angiosarcoma was identified in the spleen and in a PET-directed bone biopsy. With a definitive diagnosis, she returned home and subsequently elected to pursue hospice care. Conclusion: When there is a high clinical suspicion for malignant angiosarcoma, a multidisciplinary approach is necessary to direct both tissue acquisition and necessary histochemical staining.