Hepatitis and Vasodilatory Shock due to an Unsuspected Culprit: A Rare Presentation of Multisystem Langerhans Cell Histiocytosis.

Introduction: Langerhans cell histiocytosis (LCH) is a rare hematologic condition which can affect multiple organ systems and has variable presentation. LCH is more commonly seen as a malignancy of childhood. LCH in adulthood can have poor outcomes depending on the involvement of critical organs. Case Presentation: We report a case of a 71-year-old female who presented with progressive weakness, weight loss, diarrhea, and jaundice, and had been undergoing outpatient workup for elevated liver enzymes for the last 2 years. She required admission to the intensive care unit for vasodilatory shock, requiring vasopressor and chronotropic support. Imaging showed an underlying multiorgan process involving the gastrointestinal tract, liver, spleen, and central nervous system. A repeat liver biopsy after a prior inconclusive one revealed the diagnosis of multisystem LCH presenting as secondary sclerosing cholangitis. Conclusion: The uniqueness of this multisystem LCH case lies not only in its rarity but also in the diagnostic journey that necessitated a repeat biopsy for a conclusive diagnosis. Early identification and targeted intervention can help in ensuring better patient outcomes, especially when the presentation can overlap with various other possible conditions.

Are sodium-glucose co-transporter-2 inhibitors associated with improved outcomes in diabetic patients admitted to intensive care units with septic shock?

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been shown to reduce organ dysfunction in renal and cardiovascular disease. There are limited data on the role of SGLT2i in acute organ dysfunction. We conducted a study to assess the effect of SGLT2i taken prior to intensive care unit (ICU) admission in diabetic patients admitted with septic shock. METHODS: This retrospective cohort study used electronic medical records and included diabetic patients admitted to the ICU with septic shock. We compared diabetic patients on SGLT2i to those who were not on SGLT2i prior to admission. The primary outcome was in-hospital mortality, and secondary outcomes included hospital and ICU length of stay, use of renal replacement therapy, and 28- and 90-day mortality. RESULTS: A total of 98 diabetic patients was included in the study, 36 in the SGLT2i group and 62 in the non-SGLT2i group. The Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation III scores were similar in the groups. Inpatient mortality was significantly lower in the SGLT2i group (5.6% vs. 27.4%, P=0.008). There was no significant difference in secondary outcomes. CONCLUSIONS: Our study found that diabetic patients on SGLT2i prior to hospitalization who were admitted to the ICU with septic shock had lower inpatient mortality compared to patients not on SGLT2i.

Peripheral artery disease and the risk of venous thromboembolism.

Background: Peripheral artery disease (PAD) impacts 3-12% of patients worldwide and is characterized by endothelial dysfunction and inflammatory pathways which are also common to venous thromboembolism (VTE), but there is a paucity of evidence regarding VTE risk in PAD patients. We investigated whether PAD is an independent risk factor for VTE. Patients and methods: We reviewed medical records of patients undergoing ABI studies at Mayo Clinic from 01/1996-02/2020. We classified patients by ABI (low [<1.0], normal [1.0-1.4], or elevated [>1.4]), as well as by specific low ABI subgroup: severely reduced (ABI: 0.00-0.39), moderately reduced (0.40-0.69), mildly reduced (0.70-0.90), and borderline reduced (0.91-0.99). The primary outcome was incident VTE event (acute lower extremity deep vein thrombosis or pulmonary embolism) after ABI measurement. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, active smoking, cancer, previous VTE, thrombophilia, anticoagulation, and revascularization. Results: 39,834 unique patients (mean age 66.3±14.3 years, median follow-up 34 months) were identified. 2,305 VTE events occurred in patients without PAD (13.0%), 2,218 in low ABI patients (13.0%), and 751 in elevated ABI patients (14.8%). After risk factor adjustment, VTE risk was modestly increased for PAD overall (HR: 1.12, 95% CI [1.06, 1.18]), including low ABI (HR: 1.11, 95% CI [1.04, 1.18]) and elevated ABI groups (HR: 1.15, 95% CI [1.04, 1.26]), compared to patients without PAD. The greatest VTE risk was in severely low ABI patients (HR: 1.46, 95% CI [1.31, 1.64]). Conclusions: In a large longitudinal cohort, we present strong clinical evidence of PAD, with low and elevated ABI, as an independent VTE risk factor, with the highest risk seen in patients with severely low ABI. Continued research is required to further investigate this relationship and its intersection with functional performance status to optimize VTE risk reduction or anticoagulation strategies in the PAD population.

Patient Age at Diagnosis of Peripheral Artery Disease and Its Impact on Cardiovascular and Limb Outcomes.

Peripheral artery disease (PAD) prevalence increases with age, but the relation between age at PAD diagnosis and outcomes is unclear. We investigated the cardiovascular and limb outcomes of patients diagnosed with PAD at different ages. We studied patients with PAD aged ≥18 years who were diagnosed between 1996 and 2020 at Mayo Clinic. Patients were grouped by diagnosis age (<50, 50 to 59, 60 to 69, ≥70 years) and ankle brachial index (ABI): low ABI (<1.0) or elevated ABI (>1.4). Primary outcomes were cardiovascular events (CVEs; myocardial infarction or ischemic stroke) and limb events (LEs; critical limb ischemia or amputation). Competing risk analysis was performed to calculate adjusted hazard ratios. The cohort included 22,073 patients with PAD (low ABI: 77.1%; elevated ABI: 22.9%). CVEs were observed in 8.2% of patients and LEs in 15.6%. The highest CVE risk was observed in patients diagnosed with PAD before age 50 (compared with patients diagnosed after age 70; hazard ratio 2.33 [95% confidence interval 1.95 to 2.78]). CVE risk decreased with older age at diagnosis. Although younger groups demonstrated higher LE risk, there was no clear association with diagnosis age. These patterns of risk were seen both in low and elevated ABI subgroups but in greater magnitude with elevated ABI. Younger patients diagnosed with PAD face increased risk of myocardial infarction and ischemic stroke compared with patients diagnosed at an older age. CVE risk notably exceeds LE risk. In conclusion, younger age at PAD diagnosis may be an important risk factor, which warrants more aggressive interventions focused on CVE prevention.

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events.

OBJECTIVE: To evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality. PATIENTS AND METHODS: We identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality. RESULTS: A total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities. CONCLUSION: In this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.

Refractory Left Focal Motor Status Epilepticus as Initial Clinical Presentation of Acute Basilar Artery Thrombosis.

Seizures are uncommon with posterior circulation strokes. They are more often associated with anterior circulation strokes, with only a limited number of cases of status epilepticus reported to be related to brain stem ischemia. The literature includes case reports of generalized tonic-clonic seizures and associated status epilepticus as an initial presentation of acute basilar artery thrombosis. However, there are only rare cases reporting focal motor seizure as status epilepticus in the setting of acute basilar artery thrombosis, an important clinical presentation that should prompt evaluation for acute brain stem ischemia.

Abnormal vascular physiology in the lower extremities as a risk factor for ischemic stroke and mortality.

CONTEXT: Peripheral artery disease (PAD) is highly prevalent in the general population, affecting up to 25% of patients 55 years of age or older. There is a known association with acute ischemic stroke, but limited large cohort studies exist pertaining to the relationship between PAD severity and incident ischemic stroke. OBJECTIVES: To evaluate the risk of incident ischemic stroke and mortality along the spectrum of low and elevated ankle brachial index (ABI) measurement. METHODS: We performed a retrospective extraction of ABI data of all adult patients who underwent lower extremity physiology study for any indication from January 1, 1996 to June 30, 2018 in the Mayo Clinic health system. PAD was categorized into severe, moderate, mild, and borderline based on ABI measurements and poorly compressible arteries (PCA). These were compared with normal ABI measurements. Associations of PAD/PCA with new ischemic stroke events and all cause mortality were analyzed. Hazard ratios (HR) were calculated using multivariable Cox proportional regression with 95% confidence intervals. RESULTS: A total of 39,834 unique patients were included with a median follow up duration of 4.59 years. All abnormal ABI groups, except borderline PAD, were associated with increased risk of incident ischemic stroke after multivariate regression compared to normal ABI. A severity-dependent association was observed between PAD and ischemic stroke with moderate (HR, 1.22 [95% CI, 1.10-1.35]) and severe (HR, 1.19 [95% CI, 1.02-1.40]) categories conferring similar risk in comparison to normal ABI. Patients with PCA carried the greatest ischemic stroke risk (HR, 1.30 [95% CI, 1.15-1.46]). Similarly, abnormal ABI groups were associated with a significant risk for all cause mortality in a severity-dependent manner, with severe PAD conferring the greatest risk (HR, 3.07 [95% CI, 2.88-3.27]). CONCLUSIONS: This study adds to the growing body of evidence that both PAD and PCA are independent risk factors for incident ischemic stroke and all cause mortality. The association of PAD severity and PCA with risk of ischemic stroke may help clinicians with risk stratification and determining treatment intensity.

Identifying and Addressing Barriers to Systemic Thrombolysis for Acute Ischemic Stroke in the Inpatient Setting: A Quality Improvement Initiative.

OBJECTIVES: To identify barriers to inpatient alteplase administration and implement an interdisciplinary program to reduce time to systemic thrombolysis. PATIENTS AND METHODS: Compared with patients presenting to the emergency department with an acute ischemic stroke (AIS), inpatients are delayed in receiving alteplase for systemic thrombolysis. Institutional AIS metrics were extracted from the electronic medical records of patients presenting as an inpatient stroke alert. All patients who received alteplase for AIS were included in the analysis. A gap analysis was used to assess institutional deficiencies. An interdisciplinary intervention was initiated to address these deficiencies. Efficacy was measured with pre- and postintervention surveys and institutional AIS metric analysis. Statistical significance was determined using the Student t test. We identified 5 patients (mean age, 73 years; 100% (5/5) male; 80% (4/5) white) who met inclusion criteria for the preintervention period (January 1, 2017, to December 31, 2017) and 10 patients (mean age, 71 years; 50% male; 80% white) for the postintervention period (October 31, 2018, to July 1, 2020). RESULTS: We found barriers to rapid delivery of thrombolytic treatment to include alteplase availability and comfort with bedside reconstitution. Interdisciplinary intervention strategies consisted of stocking alteplase on additional floors as well as structured education and hands-on alteplase reconstitution simulations for resident physicians. The mean time from stroke alert to thrombolysis was shorter postintervention than preintervention (57.4 minutes vs 77.8 minutes; P=.03). CONCLUSION: A coordinated interdisciplinary approach is effective in reducing time to systemic thrombolysis in patients experiencing AIS in the inpatient setting. A similar program could be implemented at other institutions to improve AIS treatment.

Low-Cost Virtual Reality Headsets Reduce Perceived Pain in Healthy Adults: A Multicenter Randomized Crossover Trial.

Objectives: Recent studies have established the usage of virtual reality (VR) to help alleviate acute and chronic pain. VR technology can be cost prohibitive and cheaper alternatives are desired. In this study, a Google Cardboard headset ($15) combined with a smartphone was used as a low-cost VR device to assess efficacy in altering the perception of pain. Materials and Methods: The cold pressor test, a minimal-risk method, was used to simulate pain. Participants immersed their hands into ice water, with and without VR, in a crossover manner, and their pain perception data were recorded. Results: Forty-eight healthy volunteer participants completed the study between 2017 and 2018. Participants were randomized to right hand control, left control, right experimental, and left experimental groups, respectively, before the crossover. Data collected included pain threshold (time at which participants first reported pain), pain tolerance (time at which participants removed their hand), and pain intensity (highest reported pain level on a [1-10] scale). Approximately two-thirds of participants had improvements in pain threshold and pain tolerance with a mean improvement of +13.0 seconds (P = 0.0045) for pain threshold and +29.8 seconds (P = 0.0003) for pain tolerance. Pain intensity had a reduction of 0.43 points (P = 0.0371). Conclusion: Our results demonstrate that inexpensive VR devices, such as the Google Cardboard headset used in this study, may be a safe, portable, and cost-effective way to alter the perception and improve tolerance of pain.

Nonconvulsive status epilepticus secondary to acute porphyria crisis.

Both variegate and acute intermittent porphyria can manifest with various neurological symptoms. Although acute symptomatic seizures have been previously described, they are typically tonic-clonic and focal impaired awareness seizures. Convulsive status epilepticus and epilepsia partialis continua are rare and have been described on a case report basis. To our knowledge, there are no previously reported cases describing non-convulsive status epilepticus (NCSE) with electroencephalogram (EEG) documentation in the setting of acute porphyria crisis. We report a unique presentation of NCSE, which resolved after administering levetiracetam in a patient with variegate porphyria, without a known seizure disorder.

A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination.

Meiosis produces haploid gametes through a succession of chromosomal events, including pairing, synapsis, and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO (small ubiquitin-like modifier)-modification and ubiquitin-proteasome systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin, and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpointlike process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.