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Background/Objectives: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and hemophagocytic lymphohistiocytosis (HLH) are life-threatening conditions characterized by immune dysregulation. Several reports have identified an overlap between these entities; however, clinical characteristics, triggers, and outcomes remain poorly defined. The objective of this study was to characterize the clinical features and outcomes of DRESS/HLH overlap syndrome. Methods: We conducted a PRISMA-guided systematic review of PubMed, Embase, and MEDLINE. Studies were included if they reported cases meeting criteria for DRESS syndrome and HLH. Results: Thirty-six patients were included, 75% female and 27.8% pediatric. Initial misdiagnosis occurred in 30.6% and was associated with higher mortality (45.5% vs. 20.0%). Antibiotics were the most frequent triggers (36.1%) and 11.1% of patients had no trigger identified. Mean latency was 27.9 days for DRESS syndrome and 35 days for HLH, with shorter latency in antibiotic-associated cases. DRESS syndrome and HLH most commonly occurred sequentially (n = 22, 61.1%) and in 52.8% of cases DRESS preceded HLH. Fever and rash were present in 88.9%. Laboratory abnormalities included hyperferritinemia (91.7%), eosinophilia (77.8%), anemia (75.0%), and thrombocytopenia (75.0%). Hepatic involvement was nearly universal (94.4%), followed by renal involvement (36.1%). Viral reactivation was observed in 38.9%, multiorgan failure in 36.1%, and ICU admission in 19.4% of cases. Mortality was 27.8% and higher in steroid-refractory cases and those with multiorgan failure. Treatment included corticosteroids (97.2%), with IVIG (33.3%), etoposide (13.9%), and cyclosporine (5.6%) used in severe cases. Conclusions: DRESS-HLH overlap represents a severe hyperinflammatory syndrome with high mortality. Early recognition and escalation of therapy are essential to improve outcomes. This is the largest and most uniformly characterized cohort of DRESS/HLH overlap reported to date, and the first to stratify mortality by diagnostic accuracy, temporal pattern, corticosteroid responsiveness, and multiorgan failure. Because the syndrome is rare and the evidence base consists almost entirely of single-case reports, multicenter collaboration and a prospective registry are needed to define incidence and optimal therapy.

Abstract Background: Clostridium ramosum ( C. ramosum ) is an anaerobic gram-positive bacillus of the human intestine and a rare cause of bacteremia. This retrospective cohort study evaluated clinical characteristics and outcomes of a multicenter cohort of adults with C. ramosum bacteremia. Methods: This multicenter retrospective cohort included adults (≥ 18 years) with true C. ramosum bacteremia at Mayo Clinic hospitals in Arizona, Florida, Minnesota, and Wisconsin from September 1, 2012, through December 31, 2025. Data were collected through search for C. ramosum in microbiological culture records. Clinical characteristics assessed included immune status, source of bacteremia, presence of sepsis, neutropenic fever, monomicrobial vs. polymicrobial bacteremia, antimicrobial resistance patterns, antimicrobial therapy, length of stay and 30-day all cause mortality. Exploratory odds ratios (ORs) with 95% confidence intervals (CIs) were reported. Results: Among 90 patients with a positive C. ramosum blood culture, 17 were classified as contaminants and 73 comprised the study cohort. Median age was 66.0 years (IQR, 56.0–75.0); 44 (60.3%) were male and 33 (45.2%) were immunocompromised (including 26 with active malignancy, while the remaining 7 were received biologic immunosuppression). The most common infection sources were gastrointestinal (32/73, 43.8%) and central line-related (8/73, 11%). At presentation, 50.7% of patients met criteria for sepsis and 15/73 (20.5%), were in septic shock. Of 73 isolates tested, 31/73 (44.3%) were clindamycin resistant and 9/73 (12.9%) tested intermediate. Anaerobic-active antimicrobial therapy was received by 53/73 (72.6%). Thirty-day mortality was 11/73 (15.1%). Mortality was 30.0% (6/20) with therapy without reliable anaerobic activity and 9.4% (5/53) with anaerobic-active antimicrobial therapy (OR, 4.02; 95% CI, 0.88–19.46; P = 0.060). The median hospital LOS was 8.0 days. Among 30-day survivors, anaerobic active antimicrobial therapy was associated with a shorter median LOS compared to therapy without reliable anaerobic activity (8.5 vs. 12.0 days). Immunocompromised patients had higher odds of monomicrobial C. ramosum bacteremia than immunocompetent patients (OR 3.16, 95% CI 1.19–8.39; p = 0.03). Patients with polymicrobial bacteremia had higher odds of sepsis (OR, 3.89; 95% CI, 1.43–10.55; P = 0.008) and septic shock (OR, 5.66; 95% CI, 1.17–27.36; P = 0.020). Patients with malignancy or neutropenia demonstrated significantly lower odds of presenting in septic shock (p = 0.018; p = 0.029 retrospectively). Microbiological clearance was achieved in 91.3% (42/46) of evaluable cases. Conclusions: This largest reported cohort defines the clinical and microbiological profile of C. ramosum bacteremia. Frequent clindamycin nonsusceptibility is clinically actionable. Several clinical associations found on univariable analysis should be further investigated in larger studies.

Background/Objectives: Hospital-at-home (HaH) programs have emerged as an alternative model to brick-and-mortar (BaM) hospital management of acute conditions such as heart failure, pneumonia, pyelonephritis, and chronic obstructive pulmonary disease exacerbation among the others. However, the clinical management of acute pancreatitis in the HaH setting has never been described in the literature. The primary objective of this study was to describe the demographic and clinical characteristics of patients with acute pancreatitis managed in a Mayo Clinic Advanced Care at home (ACH) program. The secondary objective was to describe feasibility and short-term clinical outcomes. Methods: This multistate, multicenter, retrospective descriptive study included 40 unique patients with acute pancreatitis managed at ACH between 13 October 2020 and 1 June 2024. Repeat admissions were excluded from the primary analysis. Results: The most common etiologies were idiopathic (42.5%), gallstone-related (22.5%), and alcohol-related (12.5%). Peripancreatic fluid collections occurred in 17.5%, necrotizing pancreatitis in 10.0%, pleural effusion in 12.5%, and infected pancreatitis in 7.5%. Intravenous antiemetics were administered to 22.5%, intravenous fluids to 62.5%, and intravenous opioids to 7.5%. Median total hospital length of stay was 5.0 days (IQR, 3.0–8.25), including a median of 3.0 days (IQR, 2.0–4.0) in ACH. Four patients (10.0%; exact 95% CI, 2.8–23.7%) were transferred from ACH to BaM care. Seven-day and 30-day readmission rates were 10% (95% CI: 2.8%, 23.7%) and 5% (95%CI: 0.6%, 16.9%), respectively. The 30-day emergency department visit was 0%. Although 30-day mortality was 2.5% (95% CI: 0.0%, 13.2%), in-program mortality was 0%. Conclusions: Among a highly selected group of clinically stable patients meeting the program’s eligibility criteria, management of acute pancreatitis in ACH was feasible and was associated with low observed rates of unplanned escalations and short-term adverse outcomes.

Background: Influenza-associated encephalopathy, encephalitis, and acute necrotizing encephalopathy (ANE) are rare but potentially life-threatening neurological complications of influenza. Adult cases remain poorly characterized because the available literature is largely limited to isolated case reports and small case series. Methods: A PRISMA-guided scoping review of the MEDLINE database was conducted through 31 May 2026. Published adult cases of influenza-associated encephalopathy, encephalitis, and ANE were identified and analyzed for demographic characteristics, clinical presentation, neuroimaging findings, treatment, and outcomes. Results: Eighty-three adult cases reported between 1958 and 2026 were included. The mean age was 45.6 ± 17.8 years, and 57.8% were male. Two-thirds did not have any underlying comorbidities. Neurological symptoms developed a mean of 4.6 days after influenza onset, with influenza A accounting for 80.7% of infections. Fever (91.6%), altered mental status (86.7%), and seizures (36.1%) were the most common manifestations. Encephalitis was the predominant presentation (44.5%), followed by encephalopathy (31.3%) and ANE (24.1%). MRI most frequently demonstrated cerebral hemispheric lesions (53.0%) and bilateral thalamic involvement (36.4%), while EEG abnormalities were reported in 69.6% of patients. Overall mortality was 22.9%, highest among patients with ANE (45.0%). Among survivors, 28.9% experienced persistent neurological sequelae. Conclusions: Influenza-associated encephalopathy, encephalitis, and ANE are rare in adults but are associated with substantial morbidity and mortality. This review represents the largest adult cohort reported to date and provides important insights into the clinical spectrum, neurodiagnostic findings, and outcomes of these uncommon complications. This review highlights significant gaps in knowledge and the need for collaborative multicenter studies to improve the diagnosis, treatment, and outcome of these severe complications of influenza infection.

Background: Anaplasmosis is an emerging tick-borne infection that typically presents as a non-specific febrile illness, with variable degrees of cytopenias and liver tests abnormalities. Severe complications remain atypical and uncommon. Case Report: We report a case of acute pulmonary embolism (PE) occurring during confirmed anaplasmosis in a 73-year-old male with no traditional thromboembolic risk factors. The patient presented with fever, constitutional symptoms, thrombocytopenia, leukopenia, and abnormal liver tests, raising suspicion for a tick-borne illness. Despite early clinical improvement on doxycycline, persistent tachycardia triggered further evaluation and uncovered an acute PE. Comprehensive workup at admission and repeated 14 months later excluded inherited and acquired thrombophilias, malignancies, autoimmune diseases, and alternative infectious etiologies. The patient was treated with doxycycline 100 mg orally twice daily for 10 days and anticoagulation with unfractionated heparin followed by 6 months of apixaban for a first episode of provoked PE. He attained complete clinical recovery without recurrence of thrombosis at the two-year follow-up. Discussion: Infectious diseases are increasingly recognized as contributors to thrombosis through inflammation-mediated hypercoagulability and endothelial dysfunction. Pulmonary involvement in anaplasmosis typically manifests as pneumonitis, pneumonia or acute respiratory distress syndrome, but thrombotic complications such as PE are exceedingly rare. This case highlights a rare but clinically significant vascular complication of anaplasmosis and underscores the importance of considering thromboembolic events in patients with persistent or unexplained tachycardia. Conclusions: As the incidence of anaplasmosis continues to rise, greater awareness of its potential cardiovascular manifestations is essential. Early recognition and prompt treatment with doxycycline remain critical, while further studies are needed to better define the thrombotic risk associated with this infection.

Abstract Background Human granulocytic anaplasmosis (HGA) can cause severe illness requiring intensive care, but factors associated with critical illness among hospitalized patients are incompletely described. Method We performed a retrospective multicenter cohort study of adults hospitalized with PCR-confirmed HGA at Mayo Clinic Rochester and affiliated Mayo Clinic Health System sites in Minnesota and Wisconsin from 2014 through 2024. Patients who required ICU-level care were compared with those managed on general medical wards using exploratory univariate analyses (Fisher exact and Kruskal–Wallis tests). Results Among 101 hospitalized patients, 12 (12%) required ICU-level care. Symptoms documented at hospital presentation/admission were more frequent in ICU patients, including vomiting (64% vs 30%) and abdominal pain (55% vs 26%). On admission, ICU patients had lower sodium (mean 128.8 vs 132.3 mmol/L) and higher total bilirubin (mean 1.3 vs 0.8 mg/dL). Platelet nadir during hospitalization was lower in ICU patients (mean 54.8 × 109/L vs 84.1 × 109/L). Peak ferritin, measured in a subset, was markedly higher in ICU patients (median 21 666 vs 961 µg/L). The composite endpoint of HGA-related complications or serious treatment-related adverse events occurred more often in ICU patients (75% vs 17%); one death occurred in the ICU group. Conclusions In hospitalized adults with HGA, ICU-level care was associated with gastrointestinal symptoms at presentation/admission, admission hyponatremia and hyperbilirubinemia, lower platelet nadir, and marked hyperferritinemia when measured. Because these findings were derived from univariate group-level comparisons with substantial overlap between groups, they should be viewed as hypothesis-generating rather than individually predictive or sufficient as stand-alone triage criteria.

Background: Acute transverse myelitis (ATM) is an inflammatory disorder of the spinal cord with heterogeneous etiologies, including autoimmune, infectious, paraneoplastic, and drug-induced causes. Tumor necrosis factor-alpha (TNF-α) inhibitors have been infrequently associated with inflammatory central nervous system events, including transverse myelitis. TNF-inhibitor-associated myelitis typically presents with short-segment lesions, a normal brain MRI, and partial responsiveness to corticosteroids. Longitudinally extensive transverse myelitis (LETM) and steroid-refractory cases are uncommon. Case Presentation: A 39-year-old woman with psoriatic arthritis treated with etanercept for two years presented with subacute progressive bilateral lower-extremity sensory loss and weakness. MRI revealed a T2 hyperintense spinal cord lesion extending from T11 to L1 with gadolinium enhancement, consistent with transverse myelitis, while brain MRI was normal. Cerebrospinal fluid analysis showed lymphocytic pleocytosis, elevated protein, oligoclonal bands, and increased kappa free light chains. Extensive infectious, metabolic, paraneoplastic, and autoimmune testing, including aquaporin-4 and MOG antibodies, was negative. Despite high-dose intravenous corticosteroids and the discontinuation of etanercept, the patient experienced clinical worsening with lesion expansion, meeting criteria for LETM, and developed urinary retention. She subsequently underwent plasma exchange, resulting in radiologic improvement and moderate clinical recovery. Conclusions: This case highlights an atypical presentation of TNF-inhibitor-associated myelitis characterized by a biphasic course, longitudinally extensive spinal cord involvement, steroid refractoriness, and responsiveness to plasma exchange. These features suggest either an unusually severe TNF-inhibitor-related inflammatory phenotype or a TNF-inhibitor-triggered antibody-mediated demyelinating process. Reports of TNF-inhibitor-associated myelitis evolving into longitudinally extensive, steroid-refractory disease remain limited, and this presentation may broaden the recognized clinical spectrum of TNF-α-related CNS inflammatory events. Close neurologic follow-up and heightened awareness of severe CNS complications associated with TNF-α inhibitors are warranted.

Babesiosis and Lyme disease are tick-borne infections endemic to the northeastern and upper Midwestern United States. Although both diseases can involve multiple organ systems, acute liver failure (ALF) is exceedingly uncommon. Co-infection with Babesia microti and Borrelia burgdorferi may exacerbate disease severity, create diagnostic uncertainty, and delay appropriate therapy. We describe a 77-year-old man with type II diabetes mellitus, stage IV chronic kidney disease, and heart failure with preserved ejection fraction who presented with dyspnea, cough, and peripheral edema. Initial evaluation suggested decompensated heart failure and acute kidney injury consistent with cardiorenal syndrome. Within 24 h, however, he developed ALF (total bilirubin 6.8 mg/dL; aspartate aminotransferase 2656 U/L; alanine aminotransferase 1421 U/L; INR 3.5), thrombocytopenia (95 × 10 9 /L), acute anemia (hemoglobin 7.7 g/dL), and encephalopathy. Initial infectious, autoimmune, and ischemic evaluations were unrevealing. Despite empiric antimicrobial therapy with intravenous ceftriaxone, vancomycin, and doxycycline, his condition rapidly deteriorated, and he died. Postmortem testing identified B. microti parasitemia of 2.4% and B. burgdorferi co-infection. This case highlights the importance of considering tick-borne coinfections in patients presenting with ALF and shock, even in the absence of classic features such as fever, rash, or overt hemolysis. Increased clinician awareness of atypical presentations of endemic tick-borne diseases may help reduce diagnostic delays and improve outcomes in severe or unusual clinical scenarios.

Abstract Background Outcomes of patients with acute pyelonephritis (AP) treated in a hospital-at-home setting have not been comprehensively evaluated in the United States. Methods We performed a multicenter, retrospective cohort study of adults diagnosed with and managed for AP in Mayo Clinic's Advanced Care at Home (ACH) program between July 2020 and January 2025. Collected data included demographics, Charlson Comorbidity Index (CCI), genitourinary comorbidities, severity of illness (SOI), and risk of mortality (ROM) scores, as well as pyelonephritis-related complications. Outcomes included length of stay (LOS), escalation of care, and 30-day postdischarge emergency department (ED) visits, readmissions, and mortality. Results A total of 165 patients met inclusion criteria. Median age was 67 years; SOI scores were moderate in 33.3%, major in 52.1%, and extreme in 8.5%. ROM scores were moderate in 30.3%, major in 38.2%, and extreme in 6.7%. Median CCI score was 5, and all patients had preexisting genitourinary conditions. On admission, 30.9% met sepsis criteria, acute kidney injury was present in 47.3%, and bacteremia developed in 33.3%. Median LOS in the ACH program was 3.1 days. Only 4.8% required escalation to a brick-and-mortar hospital. Readmission occurred in 17.0%, and 4.8% had ED visits. No in-program deaths occurred. Conclusions This multicenter retrospective study shows that AP, including cases with high illness severity and complex comorbidities, can be managed safely and effectively in a hospital-at-home setting with careful patient selection and robust infrastructure to support timely escalation when needed.

Visceral disseminated varicella-zoster virus infection (VD-VZV) involves the hematogenous spread of VZV from the skin to the internal organs. Though rare, it is potentially life-threatening, predominantly affecting immunocompromised individuals. Diagnosis is often delayed due to nonspecific symptoms mimicking other viral illnesses. While the vesicular rash is a hallmark sign, it is absent in approximately 5% of cases. Visceral involvement may precede cutaneous lesions, complicate early recognition, and increase the risk of severe complications. This scoping review screened 594 articles of which 153 met the inclusion criteria, yielding 156 individual cases. Patients were predominantly male (53.8%), with a mean age of 42.3 years. The overall mortality rate was 25.0%. Multiple organs were involved in 46.1% of cases. The most frequently affected were the lungs (56%), liver (44%), heart (16%), kidneys (11%), pancreas (11%), stomach (10%), and esophagus (6%). Antivirals were administered in 89.1% of cases, while corticosteroids were used in 22.4%, with no significant impact on outcomes. Early diagnosis, achieved in 65.4% of patients, was significantly associated with survival (p = 0.043). Mortality was significantly associated with underlying comorbidities (p = 0.004), especially autoimmune diseases requiring immunosuppression (p = 0.048). Septic shock or multi-organ dysfunction (MODS), hepatitis, acute kidney injury, and acute liver failure were linked to higher mortality in univariate analysis. Multivariate analysis identified comorbidities (p < 0.001), septic shock/MODS (p = 0.008), and acute liver failure (p = 0.039) as independent predictors of mortality. Patients with septic shock/MODS had over twice the risk of death (OR = 2.24; p = 0.008). This review underscores the diagnostic challenges and high mortality of VD-VZV. Early recognition and timely administration of antiviral treatment appear critical for survival. Greater clinical awareness and further research are needed to guide management.