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Purpose To retrospectively investigate the clinical and functional outcomes of patients who underwent knotted medial-row rotator cuff repair (KT-RCR) compared with patients who underwent knotless medial-row rotator cuff repair (KL-RCR). Methods A retrospective chart review of patients who underwent double-row transosseous-equivalent rotator cuff repair in 2016 was performed at a single institution with 2-year follow-up. Information regarding demographic characteristics, preoperative tear size (magnetic resonance imaging), surgical variables (including method of suture stabilization), preoperative and postoperative American Shoulder and Elbow Surgeons (ASES) scores, and all complications (e.g., cuff failure, adhesive capsulitis, and persistent pain) was compiled. Results A total of 189 patients met the inclusion criteria: 72 in the KL-RCR group and 117 in the KT-RCR group. No significant difference in preoperative ASES scores was found between the KL-RCR and KT-RCR groups (48.3 vs 45.4, P = .327). Postoperative ASES scores did not differ between the groups (82.4 for KL-RCR vs 78.8 for KT-RCR, P = .579). We found no significant difference in cuff failure rates after 2 years, determined by magnetic resonance imaging (5.6% for KL-RCR vs 6.1% for KT-RCR, P > .999), or complication rates (11.1% for KL-RCR vs 8.6% for KT-RCR, P = .743). Conclusions The knotted approach and knotless approach to double-row rotator cuff repair showed similar outcome scores, cuff failure rates, and complication rates at minimum 2-year follow-up. Level of Evidence Level III, retrospective therapeutic comparative trial.

Inferior vena cava (IVC) thrombosis is an uncommon complication associated with IVC filters (IVCFs), with studies reporting rates ranging from 1% to 31%. Few observational studies have described the risk factors associated with IVCF thrombosis, despite the significant clinical sequelae such as post-thrombotic syndrome, venous claudication, and venous ulceration. To better describe IVCF thrombosis and the risk factors, data were queried from Vascular Quality Initiative (VQI) participating centers.IVCF data were obtained from the international VQI database from 2013 to 2019. The patients included in the present analysis had 2 years of follow-up data available. The baseline demographics, medical comorbidities, medication, and procedural, anatomic, and postoperative variables were assessed using Kaplan-Meier survival curves with log-rank tests, Student's t tests, or Mann-Whitney U tests for IVCF thrombosis at 2 years. Cox regression analyses were used to identify independent predictors of IVCF thrombosis. A subgroup analysis of those who had presented with venous thromboembolism (VTE) was also performed.A total of 62 U.S. and Canadian VQI-participating centers included 12,874 cases of IVCF placement. Of the 5780 cases with 2 years of follow-up available, 78 (1.3%) had developed IVCF thrombosis. Those who had experienced IVCF thrombosis had had significantly lower rates of diabetes, coronary artery disease, preoperative antiplatelet medications, preoperative statin use, and lower rates of discharge and follow-up antiplatelet medications. On univariable analysis, the cases of IVCF thrombosis also had higher rates of pulmonary embolism and VTE on admission, internal jugular venous access (vs femoral vein access), temporary IVCF use, follow-up anticoagulation, follow-up IVCF complication, follow-up access site thrombosis, and rates of new or propagated deep vein thrombosis at follow-up, and longer postoperative hospital stays. Multivariable analysis demonstrated that the independent predictors of IVCF thrombosis included new or propagated deep vein thrombosis at follow-up (hazard ratio [HR], 16.3; 95% confident interval [CI], 9.8-27.3; P .001), no antiplatelet therapy at follow-up (HR, 4.8; 95% CI, 1.9-12.5; P = .001), internal jugular venous access (HR, 2.2; 95% CI, 1.4-3.5; P = .001), the presence of VTE on admission (HR, 2.7; 95% CI, 1.4-5.1; P = .002), and temporary IVCF placement (HR, 2.5; 95% CI, 1.1-5.6; P = .031). In an analysis of the subgroup of patients with VTE on admission, similar predictive factors were identified in a multivariable model. Massive pulmonary embolism was also predictive of IVCF thrombosis in this subgroup.The rate of IVCF thrombosis remained low in a contemporary international database. The results from the present study of5000 patients with IVCFs suggest that antiplatelet therapy should be administered after IVCF placement to decreased the risk of IVCF thrombosis.

Background Although multiple risk factors for development of pneumonia in patients with trauma sustained in a motor vehicle accident have been studied, the effect of prehospital time on pneumonia incidence post-trauma is unknown. Research Question Is prolonged prehospital time an independent risk factor for pneumonia? Study Design and Methods We retrospectively analyzed prospectively collected clinical data from 806,012 motor vehicle accident trauma incidents from the roughly 750 trauma hospitals contributing data to the National Trauma Data Bank between 2010 and 2016. Results Prehospital time was independently associated with development of pneumonia post-motor vehicle trauma (P Interpretation Increased prehospital time is an independent risk factor for development of pneumonia and increased mortality in patients with trauma caused by a motor vehicle accident. Although prehospital time is often not modifiable, its recognition as a pneumonia risk factor is important, because prolonged prehospital time may need to be considered in subsequent decision-making.

Hemodialysis (HD) dependence and autogenous fistula use for HD span the spectrum of age. This study examines age-related outcomes of autogenous fistulas for HD access in a large population-based cohort of patients.A retrospective cohort study of all patients who initiated HD in the United States Renal Database System (2007-2014). χOf the 303,281 patients studied, 48,892 (16.1%) were younger than 50 years, 55,817 (18.4%) were 50 to 59 years, 79,138 (26.1%) were 60 to 69 years, 75,200 (24.8%) were 70 to 79 years, and 44,234 (14.6%) were 80 years or older. There was a decrease in autogenous fistula maturation with increasing age. Primary patency at 5 years comparing patients 50 vs 50 to 59 vs 60 to 69 vs 70 to 79 vs 80+ years was 24% vs 23% vs 21% vs 20% vs 18% (P .001). Primary assisted patency at 5 years was 38% vs 40% vs 37% vs 35% vs 33% (P .001). Secondary patency at 5 years was 48% vs 50% vs 47% vs 45% vs 42% (P .001). The risk-adjusted analyses revealed a progressive decrease in primary, primary assisted, and secondary patency with increasing age. As expected, patient survival decreased with increasing age.In this population-based cohort of HD patients, there was a decrease in autogenous fistula maturation, primary patency, primary assisted patency, secondary patency, and patient survival with increasing age. Despite the relative decline in outcomes associated with older age, decisions about arteriovenous access creation in older patients should be individualized, taking overall clinical status and outcomes of alternatives modes of access into consideration.

Objective To compare the mean glandular dose (MGD), cancer detection rate (CDR), and recall rate (RR) among screening examinations of patients with breast implants utilizing various digital breast tomosynthesis (DBT)-based imaging protocols. Methods This IRB-approved retrospective study included 1998 women with breast implants who presented for screening mammography between December 10, 2013, and May 29, 2020. Images were obtained using various protocol combinations of DBT and 2D digital mammography. Data collected included MGD, implant type and position, breast density, BI-RADS final assessment category, CDR, and RR. Statistical analysis utilized type II analysis of variance and the chi-square test. Results The highest MGD was observed in the DBT only protocol, while the 2D only protocol had the lowest (10.29 mGy vs 5.88 mGy, respectively). Statistically significant difference in MGD was observed across protocols (P < 0.0001). The highest per-view MGD was among DBT full-field (FF) views in both craniocaudal and mediolateral oblique projections (P < 0.0001). No significant difference was observed in RR among protocols (P = 0.17). The combined 2D (FF only) + DBT implant-displaced (ID) views protocol detected the highest number of cancers (CDR, 7.2 per 1000), but this was not significantly different across protocols (P = 0.48). Conclusion The combination of 2D FF views and DBT ID views should be considered for women with breast implants in a DBT-based screening practice when aiming to minimize radiation exposure without compromising the sensitivity of cancer detection. Avoidance of DBT FF in this patient population is recommended to minimize radiation dose.

Background Adults and children with sensorineural hearing loss (SNHL) have trouble understanding speech in rooms with reverberation when using hearing aid amplification. While the use of amplitude compression signal processing in hearing aids may contribute to this difficulty, there is conflicting evidence on the effects of amplitude compression settings on speech recognition. Less clear is the effect of a fast release time for adults and children with SNHL when using compression ratios derived from a prescriptive procedure. Purpose The aim of the study is to determine whether release time impacts speech recognition in reverberation for children and adults with SNHL and to determine if these effects of release time and reverberation can be predicted using indices of audibility or temporal and spectral distortion. Research Design This is a quasi-experimental cohort study. Participants used a hearing aid simulator set to the Desired Sensation Level algorithm m[i/o] for three different amplitude compression release times. Reverberation was simulated using three different reverberation times. Participants Participants were 20 children and 16 adults with SNHL. Data Collection and Analyses Participants were seated in a sound-attenuating booth and then nonsense syllable recognition was measured. Predictions of speech recognition were made using indices of audibility, temporal distortion, and spectral distortion and the effects of release time and reverberation were analyzed using linear mixed models. Results While nonsense syllable recognition decreased in reverberation release time did not significantly affect nonsense syllable recognition. Participants with lower audibility were more susceptible to the negative effect of reverberation on nonsense syllable recognition. Conclusion We have extended previous work on the effects of reverberation on aided speech recognition to children with SNHL. Variations in release time did not impact the understanding of speech. An index of audibility best predicted nonsense syllable recognition in reverberation and, clinically, these results suggest that patients with less audibility are more susceptible to nonsense syllable recognition in reverberation.

Background Myoglobin and creatine kinase (CK) are both established markers of muscle injury but their hospital admission values have never been compared to predict post-traumatic acute kidney injury (AKI). Methods An observational registry study of consecutive trauma patients admitted to a major regional trauma centre. The primary outcome was stage 1 or more AKI in the first 7 days after trauma. We assessed the association of hospital admission myoglobin or CK with development of AKI both alone and when added to two existing risk prediction models for post traumatic AKI. Results Of the 857 trauma patients (median age 36 [25–52], 96% blunt trauma, median ISS of 20 [12–47]) included, 102 (12%) developed AKI. Admission myoglobin performed better than CK to predict AKI any stage with an AUC–ROC of 0.74 (95% CI 0.68–0.79) and 0.63 (95% CI 0.57–0.69), respectively (p p Conclusions Admission myoglobin better predicts the development of AKI and severe rhabdomyolysis after major trauma. Admission myoglobin should be added in established predictive models of post-traumatic AKI to early identify high-risk patients.

BACKGROUND: High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. METHODS: NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO(2)) concentration. RESULTS: Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO(2) concentrations remained between 0.70 ppm (0.63–0.79) and 0.75 ppm (0.67–0.83) in the INO group and between 0.74 ppm (0.68–0.78) and 0.88 ppm (0.70–0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. CONCLUSIONS: This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.

Objective The objective of this study was to determine baseline health-related quality of life (QoL) in patients with pancreatic adenocarcinoma (PA), peri-ampullary cancers, and benign pancreaticobiliary (PB) conditions at the time of the first visit to a PB surgery clinic, and to explore the relationship between QoL, demographics, clinical parameters, complications and survival. Summary background data Few studies have examined baseline QoL measures, the impact of co-morbidities, age, gender and smoking on subsequent post-operative complications and survival in patients with PA, related PB cancers, and with benign PB conditions. Methods Data were collected from scheduled patients at a PB surgery clinic between 2013 and 2018. The Brief Pain Inventory, Fact-Hepatobiliary Scale, and Facit-Fatigue questionnaires were administered. QoL parameters were compared between PB cancer patients and those with benign disease. Results 462 individuals with PB cancers and benign diseases exhibited baseline physical well-being, functional well-being, fatigue, and overall QoL at or below the 75th percentile of wellness at the time of the first office visit. Younger age, smoking, and mental health comorbidities contributed significantly to decreased QoL. PA patients were seven times more likely to die in the follow-up period than the benign disease group. Black patients had higher pain scores and were three times more likely to have a post-surgery complication. Gender differences were identified regarding fatigue, pain and overall QoL. Conclusions This large cohort of PB cancer and benign disease patients exhibited significantly impaired baseline QoL. GI problems, weight loss, smoking, cardiovascular, pulmonary disease and history of anxiety and depression contributed significantly to reduced QoL. The study sheds a cautionary light on the burden of PB disease at the time of surgical evaluation and its relationship to diminished QoL.

Objective Heart Failure (HF) is one of the leading causes of hospitalization in the United States accounting for ≈800,000 hospital discharges and $11 billion in annual costs. Delirium occurs in approximately 30% of elderly hospitalized patients and its incidence is significantly higher among those admitted to the critical care units. Despite this, there has been limited exploration of the clinical and economic impact of delirium in patients hospitalized with acute HF. We hypothesized that delirium in HF is associated with excess mortality and hospital costs. Methods We queried the 2001-2014 Nationwide Inpatient Sample to identify hospitalizations that included a primary discharge diagnosis of HF (ICD-9-CM: 428.xx) and stratified them by presence or absence of delirium (ICD-9-CM: 239.0, 290.41, 293.0, 293.1, 348.31). Differences in in-hospital mortality, length of stay (LOS), and hospital costs were assessed using propensity-score matched cohorts. Results Major predictors of delirium included advanced age, Caucasian race, underlying dementia or psychiatric diagnoses, higher Elixhauser Comorbidity Index, renal failure, cardiogenic shock, and coronary artery bypass surgery. In the propensity-score matched analysis of 76,411 hospitalization with delirium compared to 76,612 without delirium, in-hospital mortality (odds ratio: 1.67, 95% CI: 1.51–1.77), LOS (rate ratio [RR]: 1.47, 95% CI: 1.45–1.51), and hospital costs (RR: 1.44, 95% CI: 1.41–1.48) were all statistically higher in the presence of delirium (all p Conclusion In patients hospitalized with HF, delirium is an independent predictor of increased in-hospital mortality, longer LOS, and excess hospital costs despite adjustment for baseline characteristics.

Introduction The first COVID-19 cases occurred in the US in January of 2020, leading to the implementation of shelter in place. This study seeks to define the impact of shelter in place on the epidemiology of pediatric trauma. Methods We examined pediatric trauma admissions at 5 Level 1 and 1 Level 2 US pediatric trauma centers between January 1 and June 30, 2017–2020. Demographic and injury data were compared between pre– and post–shelter in place patient cohorts. Results A total of 8772 pediatric trauma activations were reviewed. There was a 13% decrease in trauma volume in 2020, with a nadir at 16 days following implementation of shelter in place. Injury severity scores were higher in the post–shelter in place cohort. The incidence of nonmotorized vehicle accidents and gunshot wounds increased in the post–shelter in place cohort. Conclusion We found an overall decrease in pediatric trauma volume following shelter in place. However, injuries tended to be more severe. Our findings help inform targeted injury prevention campaigns during future pandemics., Highlights • Shelter-in-place policies led to a 13% decrease in overall pediatric trauma volume. • Biggest decrease occurred in the 30 days surrounding the start of shelter in place. • Nonmotorized vehicle accidents and gunshot wounds increased with shelter in place. • Injury severity was higher among the shelter-in-place cohort compared to controls. • The incidence of nonaccidental trauma did not change with shelter in place.

Objective To characterize the health-related quality of life reported by patients who received an ileal conduit (IC), Indiana pouch, or neobladder urinary diversion after radical cystectomy. Materials and Methods The Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index survey was administered to patients with bladder cancer undergoing radical cystectomy and urinary diversion from 2015-2018. Surveys were completed prior to radical cystectomy and then longitudinally throughout the postoperative course. Results A total of 146 patients completed questionnaires over a median of 12.3 months, 83 (56.8%) received an IC, 31 (21.2%) an Indiana pouch, and 32 (21.9%) an orthotopic neobladder. There were no significant differences in health related quality of life among urinary diversion groups considering the Trial Outcome Index scores, general overall FACT-G assessment, or total Functional Assessment of Cancer Therapy-Vanderbilt Cystectomy Index instruments. Patients who received IC were older and had higher Charlson Comorbidity Index scores (p Conclusions To our knowledge this is the first and largest quality of life analysis comparing all three methods of urinary diversion in a longitudinal fashion utilizing a standardized, validated, treatment-specific health survey. Proper preoperative counseling is critical to ensure understanding of the benefits of available urinary diversion.

Objectives Joblessness is common in survivors from critical care. Our aim was to describe rates of return to work versus unemployment following coronavirus disease 2019 acute respiratory distress syndrome requiring intensive care admission. Design Single-center, prospective case series. Setting Critical Care Follow-Up Clinic, Humanitas Clinical and Research Center-IRCCS, Rozzano, Italy. Patients One-hundred one consecutive laboratory-confirmed coronavirus disease 2019 patients were discharged from our hospital following an ICU stay between March 1, 2020, and June 30, 2020. Twenty-five died in the ICU. Seventy-six were discharged alive from hospital. Two patients refused participation, while three were unreachable. The remaining 71 were alive at 6 months and interviewed. Interventions Baseline and outcome healthcare data were extracted from the electronic patient records. Employment data were collected using a previously published structured interview instrument that included current and previous employment status, hours worked per week, and timing of return to work. Health-related quality of life status was assessed using the Italian EQ-5D-5L questionnaire. Measurements and main results Of the 71 interviewed patients, 45 (63%) were employed prior to coronavirus disease 2019, of which 40 (89%) of them worked full-time. Thirty-three (73%) of the previously employed survivors had returned to work by 6 months, 10 (22%) were unemployed, and 2 (5%) were newly retired. Among those who returned to work, 20 (85%) of them reported reduced effectiveness at work. Those who did not return to work were either still on sick leave or lost their job as a consequence of coronavirus disease 2019. Reported quality of life of survivors not returning to work was worse than of those returning to work. Conclusions The majority of coronavirus disease 2019 survivors following ICU in our cohort had returned to work by 6 months of follow-up. However, most of them reported reduced work effectiveness. Prolonged sick leave and unemployment were common findings in those not returning.

Prostate cancer (PC) etiology is up to 57% heritable, with the remainder attributed to environmental exposures. There are limited studies regarding national level environmental exposures and PC aggressiveness, which was the focus of this study METHODS: SEER was queried to identify PC cases between 2010 and 2014. The environmental quality index (EQI) is a county-level metric for 2000-2005 combining data from 18 sources and reports an overall ambient environmental quality index, as well as 5 environmental quality sub-domains (air, water, land, built, and sociodemographic) with higher values representing lower environmental quality. PC stage at diagnosis was determined and, multivariable logistic regression models which adjusted for age at diagnosis (years) and self-reported race (White, Black, Other, Unknown) were used to test associations between quintiles of EQI scores and advanced PC stage at diagnosis.The study cohort included 252,164 PC cases, of which 92% were localized and 8% metastatic at diagnosis. In the adjusted regression models, overall environmental quality EQI (OR 1.20, CI 1.15-1.26), water EQI (OR: 1.34, CI: 1.27-1.40), land EQI (OR: 1.35, CI: 1.29-1.42) and sociodemographic EQI (OR: 1.29, CI: 1.23-1.35) were associated with metastatic PC at diagnosis. For these domains there was a dose response increase in the OR from the lowest to the highest quintiles of EQI. Black race was found to be an independent predictor of metastatic PC at diagnosis (OR: 1.36, CI: 1.30-1.42) and in stratified analysis by race; overall EQI was more strongly associated with metastatic PC in Black men (OR: 1.53, CI: 1.35-1.72) compared to White men (OR: 1.18, CI: 1.12-1.24).Lower environmental quality was associated with advanced stage PC at diagnosis. The water, land and sociodemographic domains showed the strongest associations. More work should be done to elucidate specific modifiable environmental factors associated with aggressive PC.

Aim Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. Methods After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. Results During CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

The long-term trajectory of kidney function recovery or decline for survivors of critical illness is incompletely understood. Characterising changes in kidney function after critical illness and associated episodes of acute kidney injury (AKI), could inform strategies to monitor and treat new or progressive chronic kidney disease. We assessed changes in estimated glomerular filtration rate (eGFR) and impact of AKI for 1301 critical care survivors with 5291 eGFR measurements (median 3 [IQR 2, 5] per patient) between hospital discharge (2004–2008) and end of 7 years of follow-up. Linear mixed effects models showed initial decline in eGFR over the first 6 months was greatest in patients without AKI (− 9.5%, 95% CI − 11.5% to − 7.4%) and with mild AKI (− 12.3%, CI − 15.1% to − 9.4%) and least in patients with moderate-severe AKI (− 4.3%, CI − 7.0% to − 1.4%). However, compared to patients without AKI, hospital discharge eGFR was lowest for the moderate-severe AKI group (median 61 [37, 96] vs 101 [78, 120] ml/min/1.73m2) and two thirds (66.5%, CI 59.8–72.6% vs 9.2%, CI 6.8–12.4%) had an eGFR of 2 through to 7 years after discharge. Kidney function trajectory after critical care discharge follows a distinctive pattern of initial drop then sustained decline. Regardless of AKI severity, this evidence suggests follow-up should incorporate monitoring of eGFR in the early months after hospital discharge.

Parkinson’s disease (PD) is characterized by progressive dopamine (DA) neuron loss in the substantia nigra pars compacta (SNc). In contrast, DA neurons in the ventral tegmental area (VTA) are relatively protected from neurodegeneration, but the underlying mechanisms for this resilience remain poorly understood. Recent work suggests that expression of the vesicular glutamate transporter 2 (VGLUT2) selectively impacts midbrain DA neuron vulnerability. We investigated whether altered DA neuron VGLUT2 expression determines neuronal resilience in rats exposed to rotenone, a mitochondrial complex I inhibitor and toxicant model of PD. We discovered that VTA/SNc DA neurons that expressed VGLUT2 are more resilient to rotenone-induced DA neurodegeneration. Surprisingly, the density of neurons with detectable VGLUT2 expression in the VTA and SNc increases in response to rotenone. Furthermore, dopaminergic terminals within the nucleus accumbens, where the majority of VGLUT2-expressing DA neurons project, exhibit greater resilience compared to DA terminals in the caudate/putamen. More broadly, VGLUT2-expressing terminals are protected throughout the striatum from rotenone-induced degeneration. Together, our data demonstrate that a distinct subpopulation of VGLUT2-expressing DA neurons are relatively protected from rotenone neurotoxicity. Rotenone-induced upregulation of the glutamatergic machinery in VTA and SNc neurons and their projections may be part of a broader neuroprotective mechanism. These findings offer a putative new target for neuronal resilience that can be manipulated to prevent toxicant-induced DA neurodegeneration in PD. SIGNIFICANCE STATEMENT: Environmental exposures to pesticides contribute significantly to pathological processes that culminate in Parkinson’s disease (PD). The pesticide rotenone has been used to generate a PD model that replicates key features of the illness including dopamine neurodegeneration. To date, longstanding questions remain: are there dopamine neuron subpopulations resilient to rotenone, and if so, what are the molecular determinants of this resilience? Here we show that the subpopulation of midbrain dopaminergic neurons that express the vesicular glutamate transporter 2 (VGLUT2) are more resilient to rotenone-induced neurodegeneration. Rotenone also upregulates VGLUT2 more broadly in the midbrain, suggesting VGLUT2 expression generally confers increased resilience to rotenone. VGLUT2 may therefore be a new target for boosting neuronal resilience to prevent toxicant-induced DA neurodegeneration in PD.

The recovery of gastrointestinal functions is an important determinant of course of acute pancreatitis and the timing of hospital discharge. Here, we evaluated association between fluid resuscitation volume and opioid use with clinically significant ileus development in patients with acute pancreatitis. Consecutive adults admitted with acute pancreatitis between January 2014 and December 2019 to our academic and two community hospital were included. The Bedside Index for Severe Acute Pancreatitis (BISAP) and systemic inflammatory response syndrome (SIRS) were used to predict severity of pancreatitis based on their readily availability. Severity of pancreatitis was determined based on the Revised Atlanta classification. Fluid resuscitation volume and opioid use were collected as administered on day 1 and day 2.Clinically significant ileus was determined based on treating physician’s assessment. Forty-nine (11%) of 441 unique patients included in the study developed clinically significant ileus. Demographics of patients with or without ileus were similar between the two groups. On univariate analysis, the presence of SIRS syndrome ( 3 BISAP score (p

Background Women of childbearing age (WCBA) and women of menopausal age (WMENO) have distinct nutritional needs. Understanding nutrient intake and status in these life stages is critical for tailoring dietary recommendations. Objectives The objectives of this study were to evaluate total estimated usual nutrient intakes from food and food plus supplements and to compare these to established recommendations for WCBA and WMENO life stages and examine associations between self-reported estimated usual intakes and nutrient status biomarkers. Methods Twenty-four-hour dietary recall data from 2011–2016 NHANES were used to estimate usual intake of nutrients from food and food plus supplements for WCBA (aged 15–44 y, n = 4,134) and WMENO (aged 40–65 y, n = 3,438). Estimates of mean usual intake were derived and compared across clinically defined nutrient biomarker categories. Results Both young (aged 15–30 y) and older (aged 31–44 y) WCBA had intakes from food below the Estimated Average Requirement (EAR) for calcium (49% and 44%, respectively), magnesium (62%, 44%), and vitamins A (50%, 44%), C (47%, 46%), D (>97%, >97%), and E (92%, 88%). Similarly, perimenopausal (aged 40–50 y) and menopausal (aged 51–65 y) women had intakes from food below the EAR for calcium (48% and 74%, respectively), magnesium (50%, 49%), and vitamins A (44%, 37%), C (44%, 41%), D (>97%, >97%), and E (88%, 86%). Nutrient gaps decreased with supplement usage. For folate, vitamins D and B-12, and DHA, women in the lowest biomarker category (indicating increased risk of deficiency) had significantly lower intake from food (315.2 ± 25.9 compared with 463.8 ± 5.2 µg dietary folate equivalents, 3.5 ± 0.1 compared with 4.2 ± 0.1 µg, 3.6 ± 0.2 compared with 4.3 ± 0.1 µg, and 0.037 ± 0.005 compared with 0.070 ± 0.006 g, respectively; P

Background Although resuscitation with IV fluids is the cornerstone of sepsis management, consensus regarding their association with improvement in clinical outcomes is lacking. Research Question Is there a difference in the incidence of respiratory failure in patients with sepsis who received guideline-recommended initial IV fluid bolus of 30 mL/kg or more conservative resuscitation of less than 30 mL/kg? Study Design and Methods This was a retrospective analysis of prospectively collected clinical data conducted at an academic medical center in Omaha, Nebraska. We abstracted data from 214 patients with sepsis admitted to a single academic medical center between June 2017 and June 2018. Patients were stratified by receipt of guideline-recommended fluid bolus. The primary outcome was respiratory failure defined as an increase in oxygen flow rate or more intense oxygenation and ventilation support; oxygen requirement and volume were measured at admission, 6 h, 12 h, 24 h, and at discharge. Subgroup analyses were conducted in high-risk patients with congestive heart failure (CHF) as well as those with chronic kidney disease (CKD). Results A total of 62 patients (29.0%) received appropriate bolus treatment. The overall rate of respiratory failure was not statistically different between patients who received appropriate bolus or did not (40.3% vs 36.8%; P = .634). Likewise, no differences were observed in time to respiratory failure (P = .645) or risk of respiratory failure (adjusted hazard ratio, 1.1 [95% CI, 0.7-1.7]; P = .774). Results were similar within the high-risk CHF and CKD subgroups. Interpretation In this single-center retrospective study, we found that by broadly defining respiratory failure as an increase in oxygen requirements, a conservative initial IV fluid resuscitation strategy did not correlate with decreased rates of hypoxemic respiratory failure.

Highlights • PDSA methodology was used to implement a pancreas SBRT in an academic satellite network. • Oncologic outcomes were favorable with no serious adverse events. • This technical note provides groundwork for safe establishment of SBRT pancreas programs., Background With increasing interest in stereotactic body radiotherapy (SBRT) for unresectable pancreatic cancer, quality improvement (QI) initiatives to develop integrated clinical workflows are crucial to ensure quality assurance (QA) when introducing this challenging technique into radiation practices. Materials/Methods: In 2017, we used the Plan, Do, Study, Act (PDSA) QI methodology to implement a new pancreas SBRT program in an integrated community radiation oncology satellite. A unified integrated information technology infrastructure was used to virtually integrate the planned workflow into the community radiation oncology satellite network (P – Plan/D – Do). This workflow included multiple prospective quality assurance (QA) measures including multidisciplinary evaluation, prospective scrutiny of radiation target delineation, prospective radiation plan evaluation, and monitoring of patient outcomes. Institutional review board approval was obtained to retrospectively study and report outcomes of patients treated in this program (S – Study). Results: There were 12 consecutive patients identified who were treated in this program from 2017 to 2020 with a median follow-up of 27 months. The median survival was 13 months, median local failure free survival was 12 months and median progression free survival was 6 months from SBRT. There were no acute or late Common Terminology Criteria for Adverse Effects (CTCAE) version 5 toxicities ≥ Grade 3. Conclusion: We report the successful implementation of a community pancreas SBRT program involving multiple prospective QA measures, providing the groundwork to safely expand access to pancreas SBRT in our community satellite network (A – Act).

Background Although imaging, endoscopy, and inflammatory biomarkers are associated with future Crohn disease (CD) outcomes, common laboratory studies may also provide prognostic opportunities. We evaluated machine learning models incorporating routinely collected laboratory studies to predict surgical outcomes in U.S. Veterans with CD. Methods Adults with CD from a Veterans Health Administration, Veterans Integrated Service Networks (VISN) 10 cohort examined between 2001 and 2015 were used for analysis. Patient demographics, medication use, and longitudinal laboratory values were used to model future surgical outcomes within 1 year. Specifically, data at the time of prediction combined with historical laboratory data characteristics, described as slope, distribution statistics, fluctuation, and linear trend of laboratory values, were considered and principal component analysis transformations were performed to reduce the dimensionality. Lasso regularized logistic regression was used to select features and construct prediction models, with performance assessed by area under the receiver operating characteristic using 10-fold cross-validation. Results We included 4950 observations from 2809 unique patients, among whom 256 had surgery, for modeling. Our optimized model achieved a mean area under the receiver operating characteristic of 0.78 (SD, 0.002). Anti-tumor necrosis factor use was associated with a lower probability of surgery within 1 year and was the most influential predictor in the model, and corticosteroid use was associated with a higher probability of surgery. Among the laboratory variables, high platelet counts, high mean cell hemoglobin concentrations, low albumin levels, and low blood urea nitrogen values were identified as having an elevated influence and association with future surgery. Conclusions Using machine learning methods that incorporate current and historical data can predict the future risk of CD surgery.

Cardiac troponin (cTn) is mainly used to diagnose acute coronary syndrome (ACS). However, cTn can also be elevated in critically ill patients secondary to demand ischemia or myocardial injury. The impact of cardiology consultation on the clinical outcomes of patients admitted to medical intensive care unit (ICU) with elevated cTn is unclear.A retrospective analysis of medical ICU patients with elevated cTn without evidence of ACS between January 2013 through December 2018. Patients were stratified based on documentation of cardiology consultation. The primary outcome was 1-year mortality. Secondary outcomes were in-hospital and 30-day mortality, the length of stay (LOS), further cardiac testing, 30-day readmission rate, new prescription of cardiac medications, and the predictors of a cardiology consultation.Of 846 patients screened, 766 patients were included, of whom 63.2% had cardiology consultation. Cardiology consultation group had longer median LOS (7 vs. 5 days, P = 0.007), additional cardiac testing (90.3% vs. 67.7%, P 0.001), and more new cardiac medications (52.1% vs. 16.3%, P 0.001). No difference was noted in-hospital mortality (adjusted odds ratio [aOR], 0.6, 95% CI, 0.4-1.1, P = .117), 30-day mortality (aOR = 0.8, 95% CI, 0.5-1.4, P = .425), 1- year mortality (aOR, 1.4, 95% CI, 0.9-2.2, P = .193), or cardiac-specific 30-day readmission rate (aOR, 7.0, 95% CI, 0.7-14.9, P = .137). History of coronary artery disease (CAD) was the most independent predictor for a cardiology consult (aOR, 2.2, 95% CI, 1.3-3.8, P .001).Cardiology consultation for elevated cTn in medical ICU patients was associated with increased cardiac testing and LOS, without significant impact on mortality.

Background Fluoroquinolones (FQs) are known to be accompanied by significant risks. However, the incidence of adverse events (ADEs) resulting in unplanned drug discontinuation when used for periprosthetic joint infections (PJIs) is currently unknown. Methods This study included 156 patients over the age of 18 treated for staphylococcal PJI with debridement, antibiotics, and implant retention between 1 January 2007 and 21 November 2019. Of the 156 patients, 64 had total hip arthroplasty (THA) and 92 had total knee arthroplasty (TKA) infections. The primary outcome was rate of unplanned drug discontinuation. Secondary outcomes included incidence of severe ADEs, unplanned rifamycin discontinuation, mean time to unplanned regimen discontinuation, and all-cause mortality. Results Overall, unplanned drug discontinuation occurred in 35.6% of patients in the FQ group and 3% of patients in the non-FQ group. The rate of unplanned discontinuation of FQ regimens as compared with non-FQ regimens was 27.5% vs 4.2% (P = .021) in THA infections and 42% vs 2.4% (P Conclusions A significantly higher rate of unplanned drug discontinuation was associated with FQ as compared with non-FQ regimens. This provides a real-world view of the implications of FQ-related ADEs on unplanned discontinuation when used in prolonged durations for the management of staphylococcal PJIs.

Background Cancer of unknown primary (CUP) presenting as bone‐predominant (BCUP) or lymph node‐only disease (LNCUP) represents two clinically distinct subsets of nonvisceral CUP. These present a diagnostic challenge with a large differential of putative primary cancers and defy the “one‐treatment‐fits‐all” approach. Materials and Methods We identified patients with BCUP (n = 29) and LNCUP (n = 63) using a prospectively collected CUP database and tumor registry of patients seen at MD Anderson Cancer Center between 2001 to 2017. Clinicopathological characteristics, treatments, and outcomes were abstracted. A control group of non‐BCUP/LNCUP cases (n = 443) from the database was used for comparison. Kaplan‐Meier method was used to estimate overall survival and compared using log‐rank test. Results In this cohort, 64% and 60% patients had disseminated disease at diagnosis and 39% and 23% had Culine poor‐risk disease in BCUP and LNCUP, respectively. Median overall survival (OS) for BCUP was 14.5 months and for LNCUP was 32.6 months. For BCUP, gemcitabine plus platinum was the most common initial chemotherapy (54%). For LNCUP, carboplatin plus paclitaxel was the most common initial chemotherapy (38%). Radiation was given to 74% of patients with BCUP and 37% of those with LNCUP. On multivariate analysis, poor‐risk Culine group (hazard ratio [HR], 1.76; p < .001) and high neutrophil‐to‐lymphocyte ratio (HR, 2.38, p < .001) were associated with worse OS. Conclusion BCUP and LNCUP are rare subsets within CUP with varying prognosis. Poor‐risk Culine group and high neutrophil‐to‐lymphocyte ratio are associated with poor survival. Select patients with limited metastases can have long‐term survival with aggressive multimodality treatment. Careful clinicopathological review can facilitate chances of site‐directed therapy. Implications for Practice Cancer of unknown primary (CUP) rarely presents as bone‐predominant (BCUP) or lymph node‐only (LNCUP) disease. This article describes a cohort of each and compares with a larger CUP cohort. Patients with BCUP have unique issues with fractures and pain, often receiving radiation. Overall survival of 14.5 months was similar to a larger CUP comparison cohort. Patients with LNCUP had improved overall survival at 32.6 months, with longer survival in patients without disseminated disease. Culine poor‐risk group and neutrophil‐to‐lymphocyte ratio were associated with worse overall survival. Tips regarding diagnosis and management of these rare malignant subsets are provided., Considering the limited understanding of bone‐predominant or lymph‐node‐only cancers of unknown primary, this article describes the clinical features and outcome data of these two unique conditions.

Our objective was to review and exemplify how selected applications of artificial intelligence (AI) might facilitate and improve inflammatory bowel disease (IBD) care and to identify gaps for future work in this field. IBD is highly complex and associated with significant variation in care and outcomes. The application of AI to IBD has the potential to reduce variation in healthcare delivery and improve quality of care. AI refers to the ability of machines to mimic human intelligence. The range of AI’s ability to perform tasks that would normally require human intelligence varies from prediction to complex decision-making that more closely resembles human thought. Clinical applications of AI have been applied to study pathogenesis, diagnosis, and patient prognosis in IBD. Despite these advancements, AI in IBD is in its early development and has tremendous potential to transform future care.

Background: Real-world data on patients newly initiating ixekizumab is limited. Our study describes the characteristics of patients who initiated ixekizumab and other biologics for psoriasis treatment in North American dermatological practices. Materials & methods: Characteristics of patients ascertained at registry enrollment are described via means and frequencies. Results: Compared with other biologic initiators, ixekizumab initiators had: longer disease duration (17.1 vs 15.1 years); more were considered least severe by body surface area (33 vs 26%); moderate-to-severe by IGA (56 vs 48%); were biologic-experienced (80 vs 52%); obese (54 vs 47%); and experienced greater impact in work productivity (5.3 vs 2.9%) versus other biologic initiators. Conclusion: Psoriasis patients initiating ixekizumab had more severe disease, biologic experience, and worse patient-reported outcomes than those initiating other biologics.

Background Diametrically opposed positions exist regarding the deleterious effects of elevated lactate. There are data suggesting that it is a detrimental proxy for tissue hypoperfusion and anaerobic metabolism in sepsis and an alternative viewpoint is that some of the hyperlactatemia produced maybe adaptive. This study was conducted to explore the relationship between serum lactate levels, mean arterial blood pressure (MAP), and sympathetic stimulation in patients with sepsis. Methods Retrospective analysis of prospectively collected clinical data from four community-based hospitals and one academic medical center. 8173 adults were included. Heart rate (HR) was used as a surrogate marker of sympathetic stimulation. HR, MAP, and lactate levels were measured upon presentation. Results MAP and HR interacted to affect lactate levels with the highest levels observed in patients with low MAP and high HR (3.6 mmol/L) and the lowest in patients with high MAP and low HR (2.2 mmol/L). The overall mortality rate was 12.4%. Each 10 beats/min increase in HR increased the odds of death 6.0% (95% CI 2.6% to 9.4%), each 1 mmol/L increase in lactate increased the odds of death 20.8% (95% CI 17.4% to 24.2%), whereas each 10 mmHg increase in MAP reduced the odds of death 12.3% (95% CI 9.2% to 15.4%). However, HR did not moderate or mediate the association between lactate and death. Conclusions In septic patients, lactate production was associated with increased sympathetic activity (HR ≥ 90) and hypotension (MAP

We sought to review the appropriate patient selection criteria, available clinical literature, technical modifications, and future directions associated with the use of robotic technology to perform salvage robotic-assisted radical prostatectomy (SRARP). Recent studies have investigated the emerging role of SRARP following primary focal therapies, imaging technologies for preoperative staging and risk assessment, and novel bioengineering and technical modifications to improve postoperative functional outcomes. SRARP represents a potentially curative but underutilized treatment for men who develop localized recurrence of prostate cancer (PCa) following primary radiotherapy treatment or primary focal therapy. While SRARP may be associated with potentially significant complications including rectal injury, erectile dysfunction, and stress urinary incontinence, several centers have published their experience with the procedure and several technical modifications to the standard RALP have been utilized to reduce the risk of these potential treatment side effects. Further standardization of pathology reporting, novel technological and imaging advances, and multi-institutional collaboration will be necessary to improve future SRARP outcomes.

Urges for nonsuicidal self-injury (NSSI) are important precursors to NSSI acts and may serve as a point of intervention. A close understanding of the phenomenology of NSSI urges and the contexts in which they occur is therefore warranted. We used ambulatory assessment to examine the environmental, interpersonal, and affective contexts of NSSI urges. We recruited 56 participants with borderline personality disorder who reported on urges and contexts for 21 days with six random daily prompts, resulting in 5,750 completed assessments. Twenty-two participants reported 160 NSSI urges. We provide extensive descriptive results characterizing the interaction partners, activities, and events participants reported in association with NSSI urges. Results from a logistic multilevel model using the full sample (testing associations between all contexts and urges simultaneously) revealed that urges were more likely to occur at higher levels of negative affect, when rejection was experienced, and later in the day. Urges were not associated with disagreements or feeling let down, being at home versus away, being alone versus in company, socializing versus doing another activity, and it being a weekday versus weekend. Additional growth curve analysis for negative affect using the subsample of 22 participants who reported urges showed that, over the course of urge days compared with nonurge days, negative affect increased before urges, peaked during the urge, and then decreased, approximating a quadratic curve. We conclude that urges occurred primarily in the context of negative affect and rejection, which is consistent with theories on intra- and interpersonal functions of NSSI. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

OBJECTIVES Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P CONCLUSIONS Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.

There is limited real-world evidence on using ixekizumab in psoriasis patients. Therefore, we characterized patients with psoriasis initiating ixekizumab and report 6-month changes in disease and patient-reported outcomes.Adult patients with psoriasis who initiated ixekizumab and completed a 6-month follow-up visit were enrolled from the Corrona Psoriasis Registry. Disease characteristics and outcomes were assessed at ixekizumab initiation. Outcomes included the mean 6-month change in Psoriasis Area and Severity Index (PASI), body surface area (BSA), Investigator Global Assessment (IGA), and IGA*BSA.From baseline to follow-up in all patients (We provide real-world evidence on the benefits of ixekizumab for treating psoriasis, regardless of baseline disease severity, weight, or concomitant PsA.

Background There is limited data on the efficacy of direct oral anticoagulants (DOACs) for the treatment of left ventricular thrombus. Currently, vitamin K antagonists (VKAs) remain the preferred oral anticoagulant for left ventricular thrombus. In this retrospective study, we assessed the safety and efficacy of DOACs in comparison to VKAs in patients with a new diagnosis of left ventricular thrombus. Methods We retrospectively identified all patients admitted to the 5 Catholic Health Initiative Omaha hospitals with a diagnosis of left ventricular thrombus between January 2012 and March 2019 and were discharged on oral anticoagulants. Patients were stratified into 2 groups: VKAs or DOACs and followed for up to 1 year. We compared the outcomes of ischemic stroke, bleeding, and echocardiographic resolution of left ventricular thrombus between the 2 groups. Results A total of 99 patients were included in this study (mean age: 61 years, 29% females). Of these, 80 (81%) were discharged on VKAs and 19 (19%) on DOACs. Stroke within 1 year of diagnosis occurred in 2 patients in the VKA group and none in the DOAC group (P = 0.49). Bleeding events were observed in 5 patients (4 in the VKA group and 1 in the DOAC group; P = 0.96). Ninety patients had follow-up echocardiogram; resolution of left ventricular thrombus was similar between the 2 groups (VKAs vs DOACs: 81% vs 80%; P = 0.9). Conclusion In patients with left ventricular thrombus, DOACs and VKAs had similar rates of stroke and bleeding. These findings need confirmation in randomized clinical trials.

Introduction: Patients (pts) with CLL may be at particular risk of severe COVID-19 given advanced age and immune dysregulation. Two large series with limited follow-up have reported outcomes for pts with CLL and COVID-19 (Scarfò, et al. Leukemia 2020; Mato, et al. Blood 2020). To provide maximal clarity on outcomes for pts with CLL and COVID-19, we partnered in a worldwide effort to describe the clinical experience and validate predictors of survival, including potential treatment effects. Methods: This international collaboration represents a partnership between investigators at 141 centers. Data are presented in two cohorts. Cohort 1 (Co1) includes pts captured through efforts by European Research Initiative on CLL (ERIC), Italian CAMPUS CLL Program, and Grupo Español de Leucemia Linfática Crónica. The validation cohort, Cohort 2 (Co2), includes pts from US (66%), UK (23%), EU (7%), and other countries (4%). There is no overlap in cases between cohorts. CLL pts were included if COVID-19 was diagnosed by PCR detection of SARS-CoV-2 and they required inpatient hospitalization. Data were collected retrospectively 2/2020 - 5/2020 using standardized case report forms. Baseline characteristics, preexisting comorbidities (including cumulative illness rating scale (CIRS) score ≥6 vs. The primary endpoint of this study was to estimate the case fatality rate (CFR), defined as the proportion of pts who died among all pts hospitalized with COVID-19. Chi-squared test was used to compare frequencies; univariable and multivariable analyses utilized Cox regression. Predictors of inferior OS in both Co1 and Co2 were included in multivariable analyses. Kaplan-Meier method was used to estimate overall survival (OS) from time of COVID-19 diagnosis (dx). Results: 411 hospitalized, COVID-19 positive CLL pts were analyzed (Co1 n=281, Co2 n=130). Table 1 describes baseline characteristics. At COVID-19 dx, median age was 72 in Co1 (range 37-94) and 68 in Co2 (range 41-98); 31% (Co1) and 45% (Co2) had CIRS ≥6. In Co1, 48% were treatment-naïve and 26% were receiving CLL-directed therapy at COVID-19 dx (66% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.6% chemo/chemoimmunotherapy (CIT), 1.4% PI3Ki, 4% other). In Co2, 36% were never treated and 49% were receiving CLL-directed therapy (65% BTKi ± anti-CD20, 19% Venetoclax ± anti-CD20, 9.4% multi-novel agent combinations, 1.6% CIT, 1.6% PI3Ki, 1.6% anti-CD20 monotherapy, 1.6% other). Most pts receiving CLL-directed therapy had it held at COVID-19 diagnosis (93% in Co1 and 81% in Co2). Frequency of most COVID-19 symptoms/laboratory abnormalities were similar in the two cohorts including fever (88% in both), lymphocytosis (ALC ≥30 x 109/L; 27% vs. 21%), and lymphocytopenia (ALC < 1.0 x 109/L; 18% vs. 28%), while others varied between Co1 and Co2 (p Median follow-up was 24 days (range 2-86) in Co1 and 17 days (1-43) in Co2. CFRs were similar in Co1 and Co2, 30% and 34% (p=0.45). 54% and 43% were discharged while 16% and 23% remained admitted at last follow-up in Co1 and Co2, respectively. The proportion of pts requiring supplemental oxygen was similar (89% vs. 92%) while rate of ICU admission was higher in Co2 (20% vs. 48%, p Conclusions : In the largest cancer dx-specific cohort reported, pts with CLL hospitalized for COVID-19 had a CFR of 30-34%. Advanced patient age at COVID-19 diagnosis was an independent predictor of OS in two large cohorts. This CFR will serve as a benchmark for mortality for future outcomes studies, including therapeutic interventions for COVID-19 in this population. The effect of CLL treatment on OS was inconsistent across cohorts; COVID-19 may be severe regardless of treatment status. While there were no significant differences in distribution of current lines of therapy between cohorts, prior chemo exposure was more common in Co1 vs. Co2, which may account for difference in OS. Extended follow-up will be presented. Disclosures Roeker: American Society of Hematology: Research Funding; Abbott Laboratories: Other: spouse with minority ownership interest ; AbbVie: Other: spouse with minority ownership interest . Scarfo:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees. Abrisqueta:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau. Eyre:AbbVie: Consultancy, Honoraria, Other: travel support; Gilead: Consultancy, Honoraria, Other: travel support; Janssen: Consultancy, Honoraria, Other: travel support; KITE, AZ, Loxo Oncology at Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Muntañola Prat:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel grants; participated in advisory boards. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Leslie:AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Epizyme: Speakers Bureau; Karyopharm: Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees. Allan:Acerta, Genentech, Abbvie, Sunesis, Ascentage, Pharmacyclics, Janssen, AstraZeneca, BeiGene: Consultancy; Celgene, Genentech, Janssen, TG Therapeutics: Research Funding; Abbvie, Janssen, AstraZeneca, Pharmacyclics: Honoraria. Furman:Incyte: Consultancy; Genentech: Consultancy; Sunesis: Consultancy; Pharmacyclics: Consultancy; Loxo Oncology: Consultancy; Oncotarget: Consultancy; Janssen: Consultancy, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Abbvie: Consultancy; Beigene: Consultancy; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy; Verastem: Consultancy. Pagel:BeiGene, Astrazeneca, Loxo Oncology, Gilead: Consultancy. Hernandez-Rivas:Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Rovi: Membership on an entity's Board of Directors or advisory committees. Patel:Genentech: Consultancy, Speakers Bureau; Adaptive Biotechnologies: Consultancy; Janssen: Consultancy, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy; Kite: Consultancy; Pharmacyclics: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau. Motta:Roche: Honoraria; Janssen: Honoraria. Lamanna:AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Verastem: Research Funding; Bei-Gene: Research Funding; TG Therapeutics: Research Funding; Acerta: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche-Genentech: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Vitale:Janssen: Honoraria. Kamdar:Roche: Research Funding. Österborg:BeiGene: Research Funding; Kancera: Current equity holder in publicly-traded company, Research Funding; Sanofi: Consultancy; Karolinska Univeristy Hospital, Stockholm, Sweden: Current Employment. Hanson:Janssen-Cilag: Research Funding; Gilead: Research Funding; AbbVie: Honoraria. Eichhorst:ArQule: Consultancy, Honoraria, Other: travel support, Research Funding; BeiGene: Consultancy, Honoraria, Other: travel support, Research Funding; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding; AstraZeneca: Consultancy, Honoraria, Other: travel support, Research Funding; Oxford Biomedica: Consultancy, Honoraria, Other: travel support, Research Funding; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding; F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: travel support, Research Funding. Reda:Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees. Varettoni:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel/accommodations/expenses; AbbVie: Other: Travel/accommodations/expenses; Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees. Marchetti:Gilead: Consultancy; Novartis: Speakers Bureau; Amgen: Speakers Bureau; AbbVie: Other: Sponsored meetings; Takeda: Other: Sponsored meetings; Pfeizer: Other: Sponsored meetings. Munir:F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland; Alexion: Honoraria. Zabalza:Janssen: Honoraria, Other: travel grants; Roche: Other: travel grants; Novartis: Other: travel grants. Janssens:Amgen: Consultancy, Other: travel grants; speaker fees; Abbvie: Consultancy, Other: travel grants; speaker fees; Celgene: Consultancy, Other: travel grants; speaker fees; Janssen: Consultancy, Other: travel grants; speaker fees; Gilead: Consultancy, Other: travel grants; speaker fees; Novartis: Consultancy, Other: travel grants; speaker fees; Sanofi-Genzyme: Consultancy, Other: travel grants; speaker fees; Roche: Consultancy, Other: travel grants; speaker fees. Niemann:AstraZeneca: Honoraria, Research Funding; CSL Behring: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Sunesis: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Danish Cancer Society: Honoraria, Research Funding; Novo Nordisk Foundation: Honoraria, Research Funding. Perini:Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau; Abbvie: Speakers Bureau. Patten:AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Honoraria. Marasca:Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Honoraria. Iyengar:Janssen: Honoraria; Gilead: Honoraria. Ferrari:Abbvie: Honoraria. El-Sharkawi:Roche: Other: Conference fees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Itchaki:Abbvie Inc: Consultancy, Research Funding. Ma:Novartis: Research Funding; Juno: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Bioverativ: Consultancy, Honoraria; BeiGene: Honoraria, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; TG Therapeutics: Research Funding. Van Der Spek:AMGEN: Other: Teaching activities. Seymour:Seattle Genetics: Research Funding; Merck: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; Genentech: Research Funding; Bristol-Myers Squibb: Research Funding. Rigolin:Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Mauro:Roche: Other; Octopharma: Other; Takeda-Shire: Other; Gilead: Other; Janssen: Other; Abbvie: Other. Laurenti:Janssen: Honoraria; Gilead: Honoraria; AbbVie: Honoraria; Roche: Honoraria. Levin:Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation; Roche: Membership on an entity's Board of Directors or advisory committees, Other: travel compensation. Špaček:Gilead: Honoraria; Abbvie: Honoraria; Janssen: Honoraria. Walewska:AbbVie: Other: sponsored for educational meetings, Speakers Bureau; Janssen: Other: sponsored for educational meetings, Speakers Bureau; Gilead: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees. Wiestner:Pharmacyclics LLC, an AbbVie Company; Acerta, Merck, Nurix, Verastem, and Genmab: Research Funding; National Institutes of Health: Patents & Royalties: and other intellectual property. Broom:Gilead: Other: Travel support, Speakers Bureau. Kater:Abbvie: Research Funding; Roche: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Genentech: Research Funding. Ujjani:AstraZeneca: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Verastem Oncology: Consultancy, Honoraria; Gilead/Kite: Consultancy, Research Funding; Atara: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; MorphoSys: Consultancy. Vandenberghe:Celgene: Other: sponsorship to attend Lugano lymphoma meeting in 2019; Gilead: Other: travel grants, Research Funding; Abbvie: Other: travel grants, Research Funding; Janssen: Other: travel grants; Roche: Other: travel grants, Research Funding. Chong:Novartis: Membership on an entity's Board of Directors or advisory committees; Tessa: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; KITE Pharma: Membership on an entity's Board of Directors or advisory committees. Pu:Takeda Pharmaceuticals: Consultancy. Brown:Janssen, Teva: Speakers Bureau; Gilead, Loxo, Sun, Verastem: Research Funding; Abbvie, Acerta, AstraZeneca, Beigene, Invectys, Juno/Celgene, Kite, Morphosys, Novartis, Octapharma, Pharmacyclics, Sunesis, TG Therapeutics, Verastem: Consultancy. Trentin:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Octapharma: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria. Farina:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Sanchez:Abbvie: Other: travel grants; Amgem: Other: travel grants; Janssen: Other: travel grants; Celgene: Other: travel grants; Roche: Other: travel grants. Shadman:Abbvie, Genentech, Astra Zeneca, Sound Biologics , Pharmacyclics, Verastem, ADC therapeutics, Beigene, Cellectar, BMS, Morphosys and Atara Biotherapeutics: Consultancy; Mustang Bio, Celgene, Pharmacyclics, Gilead, Genentech, Abbvie, TG therapeutics, Beigene, Astra Zeneca, Sunesis, Beigene: Research Funding. Foglietta:Janssen: Honoraria; Gilead: Honoraria. Jaksic:Roche: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Sportoletti:AbbVie: Honoraria; Janssen: Honoraria. Barr:Morphosys: Consultancy; Gilead: Consultancy; AstraZeneca: Consultancy, Research Funding; Verastem: Consultancy; Seattle Genetics: Consultancy; TG therapeutics: Consultancy, Research Funding; Abbvie/Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy; Merck: Consultancy; Genentech: Consultancy; Janssen: Consultancy. Ruchlemer:Abbvie Inc: Consultancy, Research Funding. Kersting:Celgene: Other: travel grant; Janssen: Research Funding; Abbvie: Research Funding. Huntington:Pharmacyclics: Honoraria; AbbVie: Consultancy; Novartis: Consultancy; Genentech: Consultancy; DTRM: Research Funding; Celgene: Consultancy, Research Funding; Bayer: Consultancy, Honoraria; Astrazeneca: Honoraria; TG Therapeutics: Research Funding. Herishanu:Roche: Honoraria; Sanofi: Honoraria; Medison: Honoraria; Janssen: Honoraria; Abbvie: Honoraria; AstraZeneca: Honoraria. Jacobs:TG Therapeutics, Inc.: Research Funding; Astra Zeneca: Consultancy, Speakers Bureau; AbbVie: Consultancy, Speakers Bureau; Pharmacyclics: Research Funding, Speakers Bureau; Seattle Genetics: Consultancy; Verastem: Consultancy; Janssen: Consultancy, Speakers Bureau; Genentech: Speakers Bureau; Sanofi Genzyme: Speakers Bureau. Portell:BeiGene: Consultancy, Research Funding; Pharmacyclics: Consultancy; TG Therapeutics: Research Funding; Infinity: Research Funding; Roche/Genentech: Consultancy, Research Funding; Xencor: Research Funding; Bayer: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; AbbVie: Research Funding. Rambaldi:Sanofi: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Astellas: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); BMS/Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); University of Milan: Current Employment; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support. Received travel support., Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support from Gilead.; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Research grant from Amgen Inc.; Omeros: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Advisory board and speaker fees from Pfizer.. Brander:Verastem: Consultancy, Honoraria, Other, Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; NCCN: Other; Novartis: Consultancy, Other; Teva: Consultancy, Honoraria; Tolero: Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding; ArQule: Consultancy, Other, Research Funding; Ascentage: Other, Research Funding; AstraZeneca: Consultancy, Honoraria, Other, Research Funding; BeiGene: Other, Research Funding; DTRM: Other, Research Funding; Genentech: Consultancy, Honoraria, Other, Research Funding; Juno/Celgene/BMS: Other, Research Funding; MEI Pharma: Other, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Honoraria, Other, Research Funding; Pfizer: Consultancy, Other; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other, Research Funding. Rossi:Abbvie: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Consultancy, Honoraria; Celgene: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Novartis: Other: Advisory board; Astellas: Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Alexion: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Coscia:Karyopharm Therapeutics: Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Coombs:Abbvie: Consultancy, Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; MEI Pharma: Honoraria; LOXO Oncology: Honoraria; Octapharma: Honoraria; Novartis: Honoraria. Schuster:Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Foà:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees; Incyte: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cuneo:Astra Zeneca: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Bosch:Jansen: Honoraria; Abbvie: Honoraria; Novartis: Honoraria; Astra Zeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Roche: Honoraria. Stamatopoulos:AstraZeneca: Honoraria; Janssen, Gilead, Abbvie: Honoraria, Research Funding. Ghia:Adaptive, Dynamo: Consultancy, Honoraria; Novartis: Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria. Mato:Adaptive: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; BeiGene: Consultancy; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding.

During the surge of Coronavirus Disease 2019 (COVID-19) infections in March and April 2020, many skilled-nursing facilities in the Boston area closed to COVID-19 post-acute admissions because of infection control concerns and staffing shortages. Local government and health care leaders collaborated to establish a 1000-bed field hospital for patients with COVID-19, with 500 respite beds for the undomiciled and 500 post-acute care (PAC) beds within 9 days. The PAC hospital provided care for 394 patients over 7 weeks, from April 10 to June 2, 2020. In this report, we describe our implementation strategy, including organization structure, admissions criteria, and clinical services. Partnership with government, military, and local health care organizations was essential for logistical and medical support. In addition, dynamic workflows necessitated clear communication pathways, clinical operations expertise, and highly adaptable staff.

Hereditary hemorrhagic telangiectasia (HHT; also known as Osler-Weber-Rendu syndrome) is an inherited vascular disorder with a spectrum of clinical manifestations depending on lesion distribution. Epistaxis, mucocutaneous telangiectasia, and gastrointestinal bleeding are most common. Patients with pulmonary arteriovenous malformations are at serious risk of cerebral embolic stroke and abscess due to paradoxical embolism, indicating the need for early diagnosis and intervention. Herein, we report a 14-year-old boy who presented to his pediatrician's office with hypoxemia and personal history of epistaxis, family history of HHT, and radiologic workup demonstrating pulmonary and cerebral arteriovenous malformations. He was diagnosed with HHT and treated by endovascular embolization.

Cardiac contractile function is largely mediated by the regulation of Ca2+ cycling throughout the lifespan. The sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump is paramount to cardiac Ca2+ regulation, and it is well established that SERCA dysfunction pathologically contributes to cardiomyopathy and heart failure. Phospholamban (PLN) is a well-known inhibitor of the SERCA pump and its regulation of SERCA2a—the predominant cardiac SERCA isoform—contributes significantly to proper cardiac function. Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase involved in several metabolic pathways, and we and others have shown that it regulates SERCA function. In this mini-review, we highlight the underlying mechanisms behind GSK3’s regulation of SERCA function specifically discussing changes in SERCA2a and PLN expression and its potential protection against oxidative stress. Ultimately, these recent findings that we discuss could have clinical implications in the treatment and prevention of cardiomyopathies and heart failure.

Automated image analysis methods have shown potential for replicating expert interpretation of histology and endoscopy images, which traditionally require highly specialized and experienced reviewers. Inflammatory bowel disease (IBD) diagnosis, severity assessment, and treatment decision-making require multimodal expert data interpretation and integration, which could be significantly aided by applications of machine learning analyses. This review introduces fundamental concepts of machine learning for imaging analysis and highlights research and development of automated histology and endoscopy interpretation in IBD. Proof-of-concept studies strongly suggest that histologic and endoscopic images can be interpreted with similar accuracy as knowledge experts. Encouraging results support the potential of automating existing disease activity scoring instruments with high reproducibility, speed, and accessibility, therefore improving the standardization of IBD assessment. Though challenges surrounding ground truth definitions, technical barriers, and the need for extensive multicenter evaluation must be resolved before clinical implementation, automated image analysis is likely to both improve access to standardized IBD assessment and advance the fundamental concepts of how disease is measured.

A 66-year-old male patient presented with fever, headache, mental status changes, and nuchal rigidity with a lumbar puncture revealing neutropenic pleocytosis, and a presumptive diagnosis of bacterial meningitis was made. A careful history revealed that symptoms started within hours of starting oral trimethoprim-sulfamethoxazole. Additional history uncovered a nearly identical episode 1 year earlier after 1 dose of trimethoprim-sulfamethoxazole. All microbiologic diagnostic testing for meningitis was negative and all antimicrobials were discontinued. The patient had resolution of symptoms by 96 hours after last dose of trimethoprim-sulfamethoxazole and went on to full recovery. Based on history, clinical course, and a score of 7 on the Naranjo scale, he was diagnosed with recurrent trimethoprim-sulfamethoxazole-induced aseptic meningitis (TSIAM). This case illustrates the profound importance of thorough medication history and medication reconciliation.

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Background Preclinical studies have identified both NAD+ and sirtuin augmentation as potential strategies for the prevention and treatment of AKI. Nicotinamide riboside (NR) is a NAD+ precursor vitamin and pterostilbene (PT) is potent sirtuin activator found in blueberries. Here, we tested the effect of combined NR and PT (NRPT) on whole blood NAD+ levels and safety parameters in patients with AKI. Methods We conducted a randomized, double-blind, placebo-controlled study of escalating doses of NRPT in 24 hospitalized patients with AKI. The study was comprised of four Steps during which NRPT (5 subjects) or placebo (1 subject) was given twice a day for 2 days. NRPT dosing was increased in each Step: Step 1250/50 mg, Step 2500/100 mg, Step 3750/150 mg and Step 41,000/200 mg. Blood NAD+ levels were measured by liquid chromatography-mass spectrometry and safety was assessed by history, physical exam, and clinical laboratory testing. Results AKI resulted in a 50% reduction in whole blood NAD+ levels at 48 h compared to 0 h in patients receiving placebo (p = 0.05). There was a trend for increase in NAD+ levels in all NRPT Steps individually at 48 h compared to 0 h, but only the change in Step 2 reached statistical significance (47%, p = 0.04), and there was considerable interindividual variability in the NAD+ response to treatment. Considering all Steps together, NRPT treatment increased NAD+ levels by 37% at 48 h compared to 0 h (p = 0.002). All safety laboratory tests were unchanged by NRPT treatment, including creatinine, estimated glomerular filtration rate (eGFR), electrolytes, liver function tests, and blood counts. Three of 20 patients receiving NRPT reported minor gastrointestinal side effects. Conclusion NRPT increases whole blood NAD+ levels in hospitalized patients with AKI. In addition, NRPT up to a dose of 1000 mg/200 mg twice a day for 2 days is safe and well tolerated in these patients. Further studies to assess the potential therapeutic benefit of NRPT in AKI are warranted. Trial registration NCT03176628, date of registration June 5th, 2017.

OBJECTIVES Multiple studies have demonstrated an obesity paradox such that obese ICU patients have lower mortality and better outcomes. We conducted this study to determine if the mortality benefit conferred by obesity is affected by baseline serum lactate and mean arterial pressure. DESIGN Retrospective analysis of prospectively collected clinical data. SETTING Five community-based and one academic medical center in the Omaha, NE. PATIENTS 7,967 adults hospitalized with sepsis. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Patients were categorized by body mass index as underweight, normal weight, overweight, or obese. Multivariable logistic regression models were used to estimate the odds of in-hospital death by body mass index category; two-way interactions between body mass index and each covariate were also evaluated. Subgroup and sensitivity analyses were conducted using an ICU cohort and Acute Physiology and Chronic Health Evaluation III scores, respectively. The overall unadjusted mortality rate was 12.1% and was consistently lower in higher body mass index categories (all comparisons, p < 0.007). The adjusted mortality benefit observed in patients with higher body mass index was smaller in patients with higher lactate levels with no mortality benefit in higher body mass index categories observed at lactate greater than 5 mmol/L. By contrast, the association between lower MAP and higher mortality was constant across body mass index categories. Similar results were observed in the ICU cohort. Finally, the obesity paradox was not observed after including Acute Physiology and Chronic Health Evaluation III scores as a covariate. CONCLUSIONS Our retrospective analysis suggests that although patient size (i.e., body mass index) is a predictor of in-hospital death among all-comers with sepsis-providing further evidence to the obesity paradox-it adds that illness severity is critically important whether quantified as higher lactate or by Acute Physiology and Chronic Health Evaluation III score. Our results highlight that the obesity paradox is more than a simple association between body mass index and mortality and reinforces the importance of illness severity.

Background. Individuals with cystic fibrosis (CF) have persistent lung infections, necessitating the frequent use of antibiotics for pulmonary exacerbations. Some respiratory pathogens have intrinsic resistance to the currently available antibiotics, and any pathogen may acquire resistance over time, posing a challenge to CF care. Gaseous nitric oxide has been shown to have antimicrobial activity against a wide variety of microorganisms, including common CF pathogens, and offers a potential inhaled antimicrobial therapy. Case Presentation. Here, we present the case of a 16-year-old female with CF who experienced a precipitous decline in lung function over the prior year in conjunction with worsening antibiotic resistance of her primary pathogen, Burkholderia multivorans. She received 46 intermittent inhalations of 160 parts-per-million nitric oxide over a 28-day period. The gas was administered via a mechanical ventilator fitted with nitrogen dioxide scavenging chambers. Conclusions. High-dose inhaled nitric oxide was safe, well tolerated, and showed clinical benefit in an adolescent with cystic fibrosis and pulmonary colonization with Burkholderia multivorans.

This study examined the specificity of both individual PVTs and three different PVT batteries in individuals undergoing neuropsychological evaluation for dementia in order to establish both appropriate individual test cutoffs and multiple-PVT failure criterion.Participants were 311 validly performing patients with no cognitive impairment (n = 24), mild cognitive impairment (MCI; n = 115), mild dementia (n = 122), or moderate dementia (n = 50). Cutoffs associated with ≥90% specificity were established for 11 individual PVTs across impairment severity groups. Aggregate false positive rates according to number of PVTs failed were examined for two 4-PVT batteries and one 7-PVT battery. One-way ANOVAs with post-hoc comparisons were conducted for each PVT.Performance on 9 of 11 PVTs significantly differed according to impairment severity. PVT cutoffs achieving ≥90% specificity also generally varied by group. For PVTs previously validated in non-dementia samples, slight adjustments from established cutoffs were generally required to maintain adequate specificity in MCI and mild dementia groups, with greater modifications required in the moderate dementia group. A criterion of ≥2 PVT failures resulted in ≥90% specificity in both 4-PVT batteries across groups. In the 7-PVT battery, adequate specificity was achieved with ≥2 failures in MCI and ≥3 failures in the mild dementia group.The incorporation and interpretation of several easily assimilated multiple-PVT batteries in dementia evaluations are explored. Additionally, data regarding individual PVT performance according to cognitive impairment severity are provided to aide validity assessment of both patients undergoing dementia evaluation and examinees who are less impaired.

Background 5-aminosalicylate (5-ASA) medications have a long history of use for the treatment of inflammatory bowel disease and continue to be widely prescribed today. The effectiveness of 5-ASAs in ulcerative colitis is clear; however, studies have shown little benefit for induction or maintenance treatment of Crohn disease (CD). We aimed to quantify usage and examine trends in 5-ASA prescription rates in patients with CD. Methods Using a retrospective design, we queried a national database of commercially insured patients (Truven-Health databases) between 2009 and 2014 to identify patients with CD aged 18 to 65 years. Prescription rates for 5-ASA medications including sulfasalazine, mesalamine, olsalazine, and balsalazide were calculated for each calendar year. Regression models were used to examine year-to-year trends in prescription rates and identify patient factors associated with 5-ASA use. Results We identified 132,804 patients with CD, of whom 37.3% (n = 49,529) received a 5-ASA prescription during the study period. From 2009 to 2014, the overall prescription rates of 5-ASAs declined from 42.9% to 30.0% (P < 0.001). Patient factors independently associated with 5-ASA use included younger age, male sex, multimorbidity, and a health maintenance organization insurance plan, while controlling for the region of residence. Conclusions About 1 in 3 privately insured patients with CD received 5-ASA prescriptions despite their questionable effectiveness; however, in an encouraging trend, prescription rates significantly decreased from 2009 to 2014. This high prescription rate may reflect a gap in providers’ knowledge regarding the available evidence—an opportunity for cost savings with improved health care delivery.

Cancer patients and their families experience a range of physical, psychological and financial adverse effects. Community-based cancer centres offer a range of services and interventions, free of charge, to support those affected by cancer. While shown to be effective, there is a lack of information on the costs of these services. Our aim was to estimate the resource impact of a community-based cancer support centre. Over a 7-month period, there were 2032 contacts with 238 clients whose average age was 60 years. The most frequently used services were transport to treatment (20%), complementary therapies (48%), exercise classes (10%) and counselling (9%). This cost analysis estimated total annual cost to provide all services was €313,744. Average annual cost per person was €1138. Current uptake at the centre represents 8% of all cancer incidences in seven counties surrounding the centre. If uptake increases by 10%, scenario analyses predict an increase in total costs increase to €429,043 and a decrease in costs per patient to €915. As cancer incidences increase, the need for supportive care is growing. Community-based services have been established to meet these needs and fill this gap in national health services. Long-term sustainability of these centres is uncertain as they are entirely reliant on donations and volunteers. This analysis estimates the costs of one such community-based cancer support centre, for the first time in Ireland. Findings can be used to inform future planning of cancer supportive care services, including establishing links between tertiary and community-based centres, and cost effectiveness analyses, nationally and internationally.

Encapsulation of median nerves is a hallmark of overuse‐induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG‐3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develops. Young adult female rats performed a high repetition high force (HRHF) lever‐pulling task for 18 weeks. Rats were then euthanised at 18 weeks (HRHF untreated), or rested and systemically treated for 6 weeks with either an anti‐CCN2 monoclonal antibody (HRHF‐Rest/FG‐3019) or IgG (HRHF‐Rest/IgG), with results compared with nontask control rats. Neuropathology was evident in HRHF‐untreated and HRHF‐Rest/IgG rats as increased perineural collagen deposition and degraded myelin basic protein (dMBP) in median nerves, and increased substance P in lower cervical dorsal root ganglia (DRG), compared with controls. Both groups showed functional declines, specifically, decreased sensory conduction velocity in median nerves, noxious cold temperature hypersensitivity, and grip strength declines, compared with controls. There were also increases of ATF3‐immunopositive nuclei in ventral horn neurons in HRHF‐untreated rats, compared with controls (which showed none). FG‐3019‐treated rats showed no increase above control levels of perineural collagen or dMBP in median nerves, Substance P in lower cervical DRGs, or ATF3‐immunopositive nuclei in ventral horns, and similar median nerve conduction velocities and thermal sensitivity, compared with controls. We hypothesize that neural fibrotic processes underpin the sensorimotor declines by compressing or impeding median nerves during movement, and that inhibiting fibrosis using an anti‐CCN2 treatment reverses these effects.

OBJECTIVEDeep vein thrombosis (DVT) is a major focus of patient safety indicators and a common cause of morbidity and mortality. Many practices have employed lower-extremity screening ultrasonography in addition to chemoprophylaxis and the use of sequential compression devices in an effort to reduce poor outcomes. However, the role of screening in directly decreasing pulmonary emboli (PEs) and mortality is unclear. At the University of Mississippi Medical Center, a policy change provided the opportunity to compare independent groups: patients treated under a prior paradigm of weekly screening ultrasonography versus a post–policy change group in which weekly surveillance was no longer performed.METHODSA total of 2532 consecutive cases were reviewed, with a 4-month washout period around the time of the policy change. Criteria for inclusion were admission to the neurosurgical service or consultation for ≥ 72 hours and hospitalization for ≥ 72 hours. Patients with a known diagnosis of DVT on admission or previous inferior vena cava (IVC) filter placement were excluded. The primary outcome examined was the rate of PE diagnosis, with secondary outcomes of all-cause mortality at discharge, DVT diagnosis rate, and IVC filter placement rate. A p value < 0.05 was considered significant.RESULTSA total of 485 patients met the criteria for the pre–policy change group and 504 for the post–policy change group. Data are presented as screening (pre–policy change) versus no screening (post–policy change). There was no difference in the PE rate (2% in both groups, p = 0.72) or all-cause mortality at discharge (7% vs 6%, p = 0.49). There were significant differences in the lower-extremity DVT rate (10% vs 3%, p < 0.01) or IVC filter rate (6% vs 2%, p < 0.01).CONCLUSIONSBased on these data, screening Doppler ultrasound examinations, in conjunction with standard-of-practice techniques to prevent thromboembolism, do not appear to confer a benefit to patients. While the screening group had significantly higher rates of DVT diagnosis and IVC filter placement, the screening, additional diagnoses, and subsequent interventions did not appear to improve patient outcomes. Ultimately, this makes DVT screening difficult to justify.

NEW FINDINGS What is the central question of this study? Inhibition of glycogen synthase kinase-3 (GSK3) has been shown to improve cardiac SERCA2a function. Lithium can inhibit GSK3, but therapeutic doses used in treating bipolar disorder can have toxic effects. It has not been determined whether subtherapeutic doses of lithium can improve cardiac SERCA function. What is the main finding and its importance? Using left ventricles from wild-type mice, we found that subtherapeutic lithium feeding for 6 weeks decreased GSK3 activity and increased cardiac SERCA function compared with control-fed mice. These findings warrant the investigation of low-dose lithium feeding in preclinical models of cardiomyopathy and heart failure to determine the therapeutic benefit of GSK3 inhibition. ABSTRACT The sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA) pump is responsible for regulating calcium (Ca2+ ) within myocytes, with SERCA2a being the dominant isoform in cardiomyocytes. Its inhibitor, phospholamban (PLN), acts by decreasing the affinity of SERCA for Ca2+ . Changes in the SERCA2a:PLN ratio can cause Ca2+ dysregulation often seen in patients with dilated cardiomyopathy and heart failure. The enzyme glycogen synthase kinase-3 (GSK3) is known to downregulate SERCA function by decreasing the SERCA2a:PLN ratio. In this study, we sought to determine whether feeding mice low-dose lithium, a natural GSK3 inhibitor, would improve left ventricular SERCA function by altering the SERCA2a:PLN ratio. To this end, male wild-type C57BL/6J mice were fed low-dose lithium via drinking water (10 mg kg-1 day-1 LiCl for 6 weeks) and left ventricles were harvested. GSK3 activity was significantly reduced in LiCl-fed versus control-fed mice. The apparent affinity of SERCA for Ca2+ was also increased (pCa50 ; control, 6.09 ± 0.03 versus LiCl, 6.26 ± 0.04, P

Objectives To demonstrate the feasibility, surgical technique and initial outcomes of robotic vaginoplasty with peritoneal flap (Davydov) technique for vaginal reconstruction. Methods Following appropriate preoperative patient counseling, 11 consecutive patients underwent robotic vaginoplasty with the da Vinci (Intuitive Surgical, Sunnyvale CA) multi-port Xi and single port (SP) robotic platforms. Perioperative and postoperative outcomes of interest were retrospectively collected. Results Between March 2019 and October 2019, a total of 11 patients have undergone robotic vaginoplasty with peritoneal flap technique at our institution – 9 using the da Vinci SP platform and 2 using the da Vinci Xi platform. Reasons for vaginoplasty included primary gender-affirming genital reconstruction, vaginal stenosis after gender confirmation surgery, and vaginal hypoplasia secondary to disorders of sexual development. Mean operative time was 267.2 +/- 85.9 minutes. Initial post-operative mean vaginal depth was 13.9 +/- 0.5 cm. Mean estimated blood loss was 131.8 +/- 92.9 ml. Mean length of stay was 5.2 +/- 0.6 days and time to return of bowel function was 1.7 +/- 0.9 days. Thirty-day readmission rate was 18% (N = 2/11) with 1 patient (9%) requiring surgical revision of the neovagina. Conclusions Robotic-assisted Davydov technique is a potentially applicable, efficacious and safe method of vaginal reconstruction in cis-gender and transgender individuals.