Shiari, Aryan

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.

Abstract Introduction We report a case of an 87-year-old male presenting with debilitating fatigue and multifocal airspace opacities that improved with corticosteroid therapy, later diagnosed as VEXAS syndrome. Case Presentation An 87-year-old man with a history of atrial fibrillation (on Xarelto), diastolic heart failure, coronary artery disease, sick sinus syndrome status post pacemaker placement, hypertension, and chronic kidney disease presented with profound fatigue and failure to thrive over the last few months. A CT chest showed multifocal consolidative airspace opacities (Figure 1a) interpreted as “non-resolving pneumonia.” Despite multiple antibiotic courses, symptoms persisted. Notably, the patient had no respiratory complaints and maintained oxygen saturation of 98-99% on room air. Bronchoscopy revealed bronchoalveolar lavage (BAL) fluid with lymphocytic predominance, but cultures were negative and transbronchial biopsy was non-diagnostic and lymph node biopsies revealed normal lymphocytic tissue. Hematologic evaluation for plasma cell dyscrasia and amyloidosis was negative, though he was noted to have monoclonal gammopathy of undetermined significance. Additional workup revealed EBV positivity in BAL and serum (IgG+, IgM-), and weakly positive ANA and p-ANCA levels. Rheumatology consultation concluded that clinical features were not consistent with ANCA-associated vasculitis, additionally there was no evidence of diffuse alveolar hemorrhage on bronchoscopy. Empirical prednisone therapy led to a marked improvement in fatigue and interval resolution of the pulmonary opacities (Figure 1b). However, repeated steroid tapering attempts resulted in recurrent weakness, failure to thrive, and anemia, which normalized only during corticosteroid use. Given the relapsing course, bone marrow next-generation sequencing was pursued, identifying a pathogenic UBA1 mutation, confirming VEXAS syndrome. The patient has since been initiated on a JAK2 inhibitor and is tapering off steroids. Conclusion VEXAS syndrome is a late-onset, X-linked autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It typically manifests with systemic inflammation, cytopenias, and multi-organ involvement, including pulmonary infiltrates, fevers, vasculitis, neutrophilic dermatoses, and bone marrow vacuolization of myeloid and erythroid precursors. The disease is often refractory to standard immunosuppressive therapy, with management focusing on corticosteroids and JAK inhibitors. This case underscores the importance of considering VEXAS syndrome in elderly men with unexplained systemic inflammation, autoimmune-like features and hematological abnormalities. This abstract is funded by: None

Abstract Introduction Central sleep apnea (CSA) may occur as an adverse effect of sodium oxybates, a medication commonly used to treat narcolepsy with cataplexy. Management is challenging, as sodium oxybates remain essential for symptom control in many patients, yet untreated CSA poses substantial respiratory risk. We present a rare case of sodium-oxybate–associated CSA successfully treated with adaptive servo ventilation (ASV), representing, to our knowledge, the first documented use of ASV for this indication. Methods A 49-year-old woman with longstanding narcolepsy with cataplexy presented with worsening daytime sleepiness despite stable use of sodium oxybate. She had been receiving a very high dose prescribed by an outside provider (6.75 g twice nightly), exceeding the recommended maximum of 4.5 g twice nightly, and her dose was subsequently adjusted to 4.5 g twice nightly. An in-lab polysomnogram revealed moderate central sleep apnea (AHI 21; RDI 23) with predominantly central events. Because the patient did not wish to wean or discontinue sodium oxybate—reporting that it remained the only therapy that consistently improved her sleep and cataplexy—adaptive servo ventilation (ASV) titration was pursued as the next step in management. She had previously failed multiple stimulants, wake-promoting agents, and SSRIs due to either limited efficacy or intolerable side effects. Her BMI was 18 kg/m2, she was not taking any CNS depressant medications, and her echocardiogram demonstrated a normal ejection fraction. Results The patient tolerated ASV well. Final settings included an EPAP of 5 cm H₂O with a pressure support range of 3–15 cm H₂O and minimal leak. Her adherence was excellent, with more than 93% of nights exceeding four hours of use. Residual AHI improved to 4.6 events per hour, accompanied by noticeable improvement in daytime alertness. She continued sodium oxybate without any respiratory complications. Conclusion ASV may be an effective and well-tolerated therapy for sodium-oxybate–induced CSA in patients who must continue the medication. Sodium oxybate can induce CSA by acting on GABA-B receptors in the Kölliker–Fuse and pre-Bötzinger complex, suppressing respiratory drive and depressing hypoglossal motor output. This case highlights the successful use of ASV in treating CSA secondary to oxybates when the medication cannot be weaned or discontinued. Support (if any)

Abstract Introduction Positive airway pressure (PAP) therapy is the standard treatment for obstructive sleep apnea (OSA); however, its use may be contraindicated in patients with recurrent pneumothorax, particularly in the presence of emphysematous lung disease and bleb formation. Hypoglossal nerve stimulation (HGNS) offers a non–positive-pressure alternative for appropriately selected patients. We describe what is, to our knowledge, the first reported case of successful HGNS therapy in an older adult with severe OSA and multiple recurrent pneumothoraces. Methods An 87-year-old man with severe OSA (baseline AHI 38, predominantly obstructive events) experienced multiple right-sided pneumothoraces beginning in December 2022, several of which were temporally associated with BiPAP use at 17/9 cm H₂O. His episodes required repeated interventions, including chest tubes, thoracoscopy with apical bleb resection and pleurodesis, and several pigtail catheter placements. Chest CT imaging demonstrated emphysema with multiple blebs, raising concern for the safety of continued PAP therapy. A mandibular advancement device was deemed inappropriate due to disease severity. The patient’s BMI was 27 kg/m2. HGNS was considered a suitable alternative. Results HGNS implantation was completed without complications. At activation, both the sensation and functional thresholds measured 0.8 V, with excellent tongue protrusion and waveform quality. The device was programmed to 0.8–1.8 V with a 30-minute start delay, 12-hour nightly duration, and 15-minute pause. On follow-up, the patient demonstrated excellent adherence (average 70 hours/week), progressed to level 8 (1.6 V), and reported significant clinical improvement with resolution of snoring and apneas. Functional threshold and waveform analysis at 1.6 V remained optimal. Importantly, the patient tolerated HGNS well without any further episodes of pneumothorax following implantation. Conclusion HGNS may represent a safe and effective alternative to PAP therapy in patients at risk for pneumothorax. While positive pressure ventilation can theoretically worsen pneumothorax by increasing pleural pressure, HGNS operates through an entirely different mechanism: it maintains upper airway patency without altering intrathoracic pressure dynamics, making it a potentially safer option for select high-risk OSA patients. Support (if any)

Introduction Sepsis is a global health priority with nearly 50 million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use. Methods and analysis A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10 mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7 days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing. Ethics and dissemination The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24–0 00 121). Findings will be disseminated through peer-reviewed publications and international conference presentations. Trial registration number NCT06319248 .

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.

Background: Anaplasma phagocytophilum is an emerging tick-borne zoonotic pathogen that typically causes mild infections, which are often successfully managed in outpatient settings. Immunosuppression associated with splenectomy is a well-documented risk factor for severe infections from pathogens such as Babesia microti and encapsulated bacteria. However, splenectomy has not previously been identified as a risk factor for severe anaplasmosis. Case Presentation: This report describes a rare case of severe anaplasmosis complicated by multiorgan failure in a patient who had undergone splenectomy several decades earlier. The clinical course was notable for pneumonia, acute respiratory distress syndrome, acute kidney injury, rhabdomyolysis, atrial fibrillation, and possible myocarditis. Despite the severity of the presentation, prompt initiation of doxycycline led to recovery, albeit with a significantly prolonged hospital stay. Conclusions: Patients with splenectomy might be more likely to develop a serious form of Anaplasmosis infection such as multiorgan failure. Clinicians in tick-borne endemic areas should be aware that non-specific symptoms can indicate anaplasmosis.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted, comprising an initial 10-min OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 h after extubation. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. The primary outcome measure was the occurrence of severe postoperative respiratory complications, including the need for antibiotics, increased use of supplemental oxygen, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcome data were compared between patients receiving usual care (involving post-extubation hyperinflation) and those treated under the new OPE protocol. Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs. 62%; p = 0.19) and were older (median, 70 vs. 67 years; p = 0.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs. 7.4 days; p = 0.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs. 1.1 days with usual care; p = 0.06) and shorter LOS in the intensive care unit (mean, 2.7 vs. 3.4 days; p = 0.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, −0.85 days; 95% CI, −1.65 to −0.06; p = 0.04). The OPE group had a lower percentage of postoperative complications (10% vs. 20%). Conclusions: OPE therapy after cardiac surgery is associated with decreased intensive care unit (ICU) and hospital LOS.

Abstract Background Mechanical ventilation (MV) management is an essential skill for pulmonary and critical care medicine (PCCM) fellows to master during training. The unprecedented emergence of the coronavirus disease (COVID-19) pandemic highlighted the need for advanced operator competency in MV to improve patients’ outcomes. Objective We aimed to create a standardized case-based curriculum using a blended approach of high-fidelity simulation, rapid-cycle deliberate practice, video didactics, and hands-on small group sessions for rapid accumulation of knowledge and hands-on skills for PCCM fellows before caring for critically ill patients during the COVID-19 pandemic. Methods The MV curriculum consisted of the following steps: 1) baseline written knowledge test with 15 multiple-choice questions covering MV, the latest evidence-based practices, and pathophysiology of COVID-19; 2) baseline confidence survey using a 5-point Likert scale; 3) a one-on-one session using a high-fidelity simulation manikin, a lung simulator, and a mechanical ventilator to test baseline competencies; 4) a structured debriefing tailored per fellow’s 50-point competency assessment checklist from the simulation using rapid-cycle deliberate practice; 5) video didactics; 6) a hands-on session in small groups for basic knobology, waveforms, and modes of MV; 7) a one-on-one simulation reassessment session; 8) a written knowledge posttest; and 9) a post-training confidence survey using a 5-point Likert scale. Results Eight PCCM fellows completed the training. The mean multiple-choice question score increased from 7.4 ± 2.9 to 10.4 ± 2.4 (P < 0.05), and the simulation scores increased from 17.1 ± 4.4 to 30.8 ± 3.7 (P < 0.05). Comparing the simulation reassessment to the baseline, fellows showed significant improvement (P < 0.05) in assessing indications for MV; implementing rapid sequence intubation for patients with COVID-19; initiating MV and ventilator bundle per best practices; recognizing and managing mucous plugging, ventilator dyssynchrony, and evidence-based treatments for acute respiratory distress syndrome; and developing a care plan for proning. The post-training survey revealed improved learner confidence in all competencies. Conclusion This pilot MV curriculum using a blended approach was feasible and allowed PCCM fellows to significantly improve their knowledge and hands-on skills, allowing for the appropriate use of MV during the pandemic. Self-reported improvement scores further reinforced this. The emergent need for novice learners may again be necessary for future pandemic settings where standard training models requiring extensive training time are limited.