Precision in Prevention: Tailoring Single-Use Negative Pressure Wound Therapy Utilization Through Artificial Intelligence-Based Surgical Site Complications Risk and Cost Modeling.

Background: Surgical site complications (SSCs) are common, yet preventable hospital-acquired conditions. Single-use negative pressure wound therapy (sNPWT) has been shown to be effective in reducing rates of these complications. In the era of value-based care, strategic allocation of sNPWT is needed to optimize both clinical and financial outcomes. Materials and Methods: We conducted a retrospective analysis using data from the Premier Healthcare Database (2017-2021) for 10 representative open procedures in orthopedic, abdominal, cardiovascular, cesarean delivery, and breast surgery. After separating data into training and validation sets, various machine learning algorithms were used to develop pre-operative SSC risk prediction models. Model performance was assessed using standard metrics and predictors of SSCs were identified through feature importance evaluation. Highest-performing models were used to simulate the cost-effectiveness of sNPWT at both the patient and population level. Results: The prediction models demonstrated good performance, with an average area under the curve of 76%. Prominent predictors across subspecialities included age, obesity, and the level of procedure urgency. Prediction models enabled a simulation analysis to assess the population-level cost-effectiveness of sNPWT, incorporating patient and surgery-specific factors, along with the established efficacy of sNPWT for each surgical procedure. The simulation models uncovered significant variability in sNPWT's cost-effectiveness across different procedural categories. Conclusions: This study demonstrates that machine learning models can effectively predict a patient's risk of SSC and guide strategic utilization of sNPWT. This data-driven approach allows for optimization of clinical and financial outcomes by strategically allocating sNPWT based on personalized risk assessments.

Cutaneous Manifestations of Cystic Fibrosis.

Cystic fibrosis (CF) is caused by a mutation in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, and features recurrent sinus and pulmonary infections, steatorrhea, and malnutrition. CF is associated with diverse cutaneous manifestations, including aquagenic wrinkling of the palms, nutrient deficiency dermatoses, and vasculitis. Rarely these are presenting symptoms of CF, prior to pulmonary or gastrointestinal sequelae. Cutaneous drug eruptions are also highly common in patients with CF (PwCF) given frequent antibiotic exposure. Finally, CFTR modulating therapy, which has revolutionized CF management, is associated with cutaneous side effects ranging from acute urticaria to toxic epidermal necrolysis. Recognition of dermatologic clinical manifestations of CF is important to appropriately care for PwCF. Dermatologists may play a significant role in the diagnosis and management of CF and associated skin complications.

GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability.

BACKGROUND: Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. METHODS: Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. RESULTS: At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. CONCLUSION: GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.

Langerhans cell histiocytosis: NACHO update on progress, chaos, and opportunity on the path to rational cures.

Langerhans cell histiocytosis (LCH) is a myeloid neoplastic disorder characterized by lesions with CD1a-positive/Langerin (CD207)-positive histiocytes and inflammatory infiltrate that can cause local tissue damage and systemic inflammation. Clinical presentations range from single lesions with minimal impact to life-threatening disseminated disease. Therapy for systemic LCH has been established through serial trials empirically testing different chemotherapy agents and durations of therapy. However, fewer than 50% of patients who have disseminated disease are cured with the current standard-of-care vinblastine/prednisone/(mercaptopurine), and treatment failure is associated with long-term morbidity, including the risk of LCH-associated neurodegeneration. Historically, the nature of LCH-whether a reactive condition versus a neoplastic/malignant condition-was uncertain. Over the past 15 years, seminal discoveries have broadly defined LCH pathogenesis; specifically, activating mitogen-activated protein kinase pathway mutations (most frequently, BRAFV600E) in myeloid precursors drive lesion formation. LCH therefore is a clonal neoplastic disorder, although secondary inflammatory features contribute to the disease. These paradigm-changing insights offer a promise of rational cures for patients based on individual mutations, clonal reservoirs, and extent of disease. However, the pace of clinical trial development behind lags the kinetics of translational discovery. In this review, the authors discuss the current understanding of LCH biology, clinical characteristics, therapeutic strategies, and opportunities to improve outcomes for every patient through coordinated agent prioritization and clinical trial efforts.

Advancing outbreak simulation training: a collaborative pilot study for dual-specialty medical trainees and infection prevention and control professionals.

BACKGROUND: In response to identified gaps in infection prevention and control (IPC) training within Scotland, a Short Life Working Group initiated an innovative outbreak simulation training programme. AIM: To enhance the knowledge and confidence of medical microbiology and infectious diseases trainees and IPC professionals in managing healthcare-associated infection (HAI) outbreaks, employing the National Infection Prevention and Control Manual guidelines. METHODS: Participants completed prerequisite online training in epidemiology and surveillance before engaging in a meticulously crafted vancomycin-resistant enterococci outbreak simulation, which mirrored a real-life incident and adhered to the standards set by the Association for Simulated Practice in Healthcare. The programme incorporated Kolb's experiential learning cycle, fostering an authentic and engaging learning environment. A total of 41 individuals participated in the synchronous online training phase, with eight individuals involved in the pilot outbreak simulation. Evaluation of the training's efficacy followed Kirkpatrick's model, combining quantitative (five-point Likert scales) and qualitative (open-ended questions and participant reflections) data collection methods. FINDINGS: Results demonstrated significant improvements in participants' knowledge, skills, and confidence in outbreak management. Feedback highlighted the realism and educational value of the simulation, with 100% agreement on its efficacy in enhancing outbreak management capabilities. CONCLUSION: The success of this pilot study underscores the potential of simulation training in IPC and paves the way for broader implementation. It emphasizes the effectiveness of structured, experiential learning in equipping healthcare professionals with practical skills and confidence for managing complex HAI outbreaks, contributing to a more competent and prepared workforce.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.

The ATR inhibitor ceralasertib potentiates cancer checkpoint immunotherapy by regulating the tumor microenvironment.

The Ataxia telangiectasia and Rad3-related (ATR) inhibitor ceralasertib in combination with the PD-L1 antibody durvalumab demonstrated encouraging clinical benefit in melanoma and lung cancer patients who progressed on immunotherapy. Here we show that modelling of intermittent ceralasertib treatment in mouse tumor models reveals CD8+ T-cell dependent antitumor activity, which is separate from the effects on tumor cells. Ceralasertib suppresses proliferating CD8+ T-cells on treatment which is rapidly reversed off-treatment. Ceralasertib causes up-regulation of type I interferon (IFNI) pathway in cancer patients and in tumor-bearing mice. IFNI is experimentally found to be a major mediator of antitumor activity of ceralasertib in combination with PD-L1 antibody. Improvement of T-cell function after ceralasertib treatment is linked to changes in myeloid cells in the tumor microenvironment. IFNI also promotes anti-proliferative effects of ceralasertib on tumor cells. Here, we report that broad immunomodulatory changes following intermittent ATR inhibition underpins the clinical therapeutic benefit and indicates its wider impact on antitumor immunity.

An economic evaluation of strategies to ensure safer drinking water in the homes of families with young children in select United States locations.

Introduction: In the United States, safe, accessible drinking water is not equitable due to source water contamination, unreliable water treatment, or hazardous plumbing infrastructure. Drinking water free of lead, nitrates, and arsenic is vital for infant and young children's health. Methods: Researchers conducted a study combining single-case study review methods and economic evaluation for 6 US policies or programs. Researchers used case-study findings, activity-based costing, publicly available US population data, and existing literature to create 5-year cost projections (2020-2024) for strategies to address lead, nitrates, or arsenic in drinking water from private wells or community water systems for families with low incomes and young children aged 0-5y. Researchers estimated the number of households reached and the costs by activity and payer of implementing each policy or program using case-specific geographic location and eligibility criteria. Results: The total number of households reached varied from 295 to 135,000 depending on water source, population of focus, and geographic location. Focused strategies reached higher proportions of families with low incomes and young children. Community water system and state-wide strategies had the broadest reach. The total annual program cost per household that received information about their water quality ranged from $75 to $2,780. Of this cost, the portion paid by the household varied from $0.12 to $1,590, not including mitigation. Conclusions: These findings can inform local decisions about policies and programs in communities seeking to increase awareness and access to safer drinking water, particularly in homes of families with low incomes and young children.

Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer.

Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.

Longitudinal Circulating Tumor DNA Modeling to Predict Disease Progression in First-Line Mutant Epidermal Growth Factor Receptor Non-Small Cell Lung Cancer.

This exploratory, post hoc analysis aimed to model circulating tumor DNA (ctDNA) dynamics and predict disease progression in patients with treatment-naïve locally advanced/metastatic epidermal growth factor receptor mutation (EGFRm)-positive non-small cell lung cancer, from the FLAURA trial (NCT02296125). Patients were randomized 1:1 and received osimertinib 80 mg once daily (q.d.) or comparator EGFR-TKIs (gefitinib 250 mg q.d. or erlotinib 150 mg q.d.). Plasma was collected at baseline and multiple timepoints until treatment discontinuation. Patients with Response Evaluation Criteria in Solid Tumors (RECIST) imaging data and detectable EGFR mutations (Ex19del/L858R) at baseline and ≥ 3 additional timepoints were evaluable. Joint modeling was conducted to characterize the relationship between longitudinal changes in ctDNA and probability of progression-free survival (PFS). A Bayesian joint model of ctDNA and PFS was developed solving differential equations with the ctDNA dynamics and the PFS time-to-event probability. Of 556 patients, 353 had detectable ctDNA at baseline. Evaluable patients (with available imaging and ≥ 3 additional timepoints, n = 320; ctDNA set) were divided into training (n = 259) and validation (n = 61) sets. In the validation set, the model predicted a median PFS of 17.7 months (95% confidence interval (CI): 11.9-28.3) for osimertinib (n = 23) and 9.1 months (95% CI: 6.3-14.8) for comparator (n = 38), consistent with observed RECIST PFS (16.4 months and 9.7, respectively). The model demonstrates that EGFRm ctDNA dynamics can predict the risk of disease progression in this patient population and could be used to predict RECIST-defined disease progression.

Pan-Tumor Analytical Validation and Osimertinib Clinical Validation in EGFR Mutant Non-Small-Cell Lung Cancer, Supporting the First Next-Generation Sequencing Liquid Biopsy in Vitro Diagnostic.

Comprehensive genotyping is necessary to identify therapy options for patients with advanced cancer; however, many cancers are not tested, partly because of tissue limitations. Next-generation sequencing (NGS) liquid biopsies overcome some limitations, but clinical validity is not established and adoption is limited. Herein, clinical bridging studies used pretreatment plasma samples and data from FLAURA (NCT02296125; n = 441) and AURA3 (NCT02151981; n = 450) pivotal studies to demonstrate clinical validity of Guardant360 CDx (NGS LBx) to identify patients with advanced EGFR mutant non-small-cell lung cancer who may benefit from osimertinib. The primary end point was progression-free survival (PFS). Patients with EGFR mutation as identified by NGS LBx had significant PFS benefit with first-line osimertinib over standard of care (15.2 versus 9.6 months; hazard ratio, 0.41; P < 0.0001) and with later-line osimertinib over chemotherapy (8.3 versus 4.2 months; hazard ratio, 0.34; P < 0.0001). PFS benefits were similar to the original trial cohorts selected by tissue-based EGFR testing. Analytical validation included accuracy, precision, limit of detection, and specificity. Analytical validity was established for EGFR mutation detection and pan-tumor profiling. Panel-wide limit of detection was 0.1% to 0.5%, with 98% to 100% per-sample specificity. Patients with EGFR mutant non-small-cell lung cancer by NGS LBx had improved PFS with osimertinib, confirming clinical validity. Analytical validity was established for guideline-recommended therapeutic targets across solid tumors. The resulting US Food and Drug Administration approval of NGS LBx demonstrated safety and effectiveness for its intended use and is expected to improve adherence to guideline-recommended targeted therapy use.

Head injury in older adults presenting to the ambulance service: who do we convey to the emergency department, and what clinical variables are associated with an intracranial bleed? A retrospective case-control study.

OBJECTIVE: Most older adults with traumatic brain injuries (TBI) reach the emergency department via the ambulance service. Older adults, often with mild TBI symptoms, risk being under-triaged and facing poor outcomes. This study aimed to identify whether sufficient information is available on the scene to an ambulance clinician to identify an older adult at risk of an intracranial haemorrhage following a head injury. METHODS: This was a retrospective case-control observational study involving one regional ambulance service in the UK and eight emergency departments. 3545 patients aged 60 years and over presented to one regional ambulance service with a head injury between the 1st of January 2020 and the 31st of December 2020. The primary outcome was an acute intracranial haemorrhage on head computed tomography (CT) scan in patients conveyed to the emergency department (ED). A secondary outcome was factors associated with conveyance to the ED by the ambulance clinician. RESULTS: In 2020, 2111 patients were conveyed to the ED and 162 patients were found to have an intracranial haemorrhage on their head CT scan. Falls from more than 2 m (adjusted odds ratio (aOR) 3.45, 95% CI 1.78-6.40), chronic kidney disease (CKD) (aOR 2.80, 95% CI 1.25-5.75) and Clopidogrel (aOR 1.98, 95% CI 1.04-3.59) were associated with an intracranial haemorrhage. Conveyance to the ED was associated with patients taking anticoagulant and antiplatelet medication or a visible head injury or head injury symptoms. CONCLUSION: This study highlights that while most older adults with a head injury are conveyed to the ED, only a minority will have an intracranial haemorrhage following their head injury. While mechanisms of injury such as falls from more than 2 m remain a predictor, this work highlights that Clopidogrel and CKD are also associated with an increased odds of tICH in older adults following a head injury. These findings may warrant a review of current ambulance head injury guidelines.

Reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy in Canada: A national prospective cohort study.

OBJECTIVE: To describe self-reported reactogenicity, pregnancy outcomes, and SARS-CoV-2 infection following COVID-19 vaccination during pregnancy. DESIGN: National, prospective cohort study. SETTING: Participants across Canada were enrolled from July 2021 until June 2022. POPULATION: Individuals pregnant during the COVID-19 pandemic, regardless of vaccination status, were included. METHODS: The Canadian COVID-19 Vaccine Registry for Pregnant and Lactating Individuals (COVERED) was advertised through traditional and social media. Surveys were administered at baseline, following each vaccine dose if vaccinated, pregnancy conclusion, and every two months for 14 months. Changes to pregnancy or vaccination status, SARS-CoV-2 infections, or significant health events were recorded. MAIN OUTCOME MEASURES: Reactogenicity (local and systemic adverse events, and serious adverse events) within 1 week post-vaccination, pregnancy and neonatal outcomes, and subsequent SARS-CoV-2 infection. RESULTS: Among 2868 participants who received 1-2 doses of a COVID-19 vaccine during pregnancy, adverse events described included: headache (19.5-33.9%), nausea (4.8-13.8%), fever (2.7-10.2%), and myalgia (33.4-42.2%). Reactogenicity was highest after the 2nd dose of vaccine in pregnancy. Compared to 1660 unvaccinated participants, there were no statistically significant differences in adverse pregnancy or infant outcomes, aside from an increased risk of NICU admission ≥ 24 h among the unvaccinated group. During follow-up, there was a higher rate of participant-reported SARS-CoV-2 infection in the unvaccinated compared to the vaccinated group (18[47.4%] vs. 786[27.3%]). CONCLUSIONS: Participant-reported reactogenicity was similar to reports from non-pregnant adults. There was no increase in adverse pregnancy and birth outcomes among vaccinated vs. unvaccinated participants and lower rates of SARS-CoV-2 infection were reported in vaccinated participants. TWEETABLE ABSTRACT: No significant increase in adverse pregnancy or infant outcomes among vaccinated versus unvaccinated pregnant women in Canada.

Immune Cell Abundance and T-cell Receptor Landscapes Suggest New Patient Stratification Strategies in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a molecularly and spatially heterogeneous disease frequently characterized by impairment of immunosurveillance mechanisms. Despite recent success with immunotherapy treatment, disease progression still occurs quickly after treatment in the majority of cases, suggesting the need to improve patient selection strategies. In the quest for biomarkers that may help inform response to checkpoint blockade, we characterized the tumor microenvironment (TME) of 162 HNSCC primary tumors of diverse etiologic and spatial origin, through gene expression and IHC profiling of relevant immune proteins, T-cell receptor (TCR) repertoire analysis, and whole-exome sequencing. We identified five HNSCC TME categories based on immune/stromal composition: (i) cytotoxic, (ii) plasma cell rich, (iii) dendritic cell rich, (iv) macrophage rich, and (v) immune-excluded. Remarkably, the cytotoxic and plasma cell rich subgroups exhibited a phenotype similar to tertiary lymphoid structures (TLS), which have been previously linked to immunotherapy response. We also found an increased richness of the TCR repertoire in these two subgroups and in never smokers. Mutational patterns evidencing APOBEC activity were enriched in the plasma cell high subgroup. Furthermore, specific signal propagation patterns within the Ras/ERK and PI3K/AKT pathways associated with distinct immune phenotypes. While traditionally CD8/CD3 T-cell infiltration and immune checkpoint expression (e.g., PD-L1) have been used in the patient selection process for checkpoint blockade treatment, we suggest that additional biomarkers, such as TCR productive clonality, smoking history, and TLS index, may have the ability to pull out potential responders to benefit from immunotherapeutic agents. SIGNIFICANCE: Here we present our findings on the genomic and immune landscape of primary disease in a cohort of 162 patients with HNSCC, benefitting from detailed molecular and clinical characterization. By employing whole-exome sequencing and gene expression analysis of relevant immune markers, TCR profiling, and staining of relevant proteins involved in immune response, we highlight how distinct etiologies, cell intrinsic, and environmental factors combine to shape the landscape of HNSCC primary disease.

Spontaneous pneumothorax or no pneumothorax at all?

Care of a simple pneumothorax in a paediatric patient is often anything but simple, and a refractory and complex pneumothorax requires thoughtful and deliberate care https://bit.ly/3NFAk9S.

Tocilizumab Is Associated with Increased Risk of Fungal Infections among Critically Ill Patients with COVID-19 and Acute Renal Failure: An Observational Cohort Study.

RESEARCH QUESTION: Does treatment with tocilizumab increase the risk of a fungal infection in critically ill patients with coronavirus-19? BACKGROUND: Numerous therapies have been evaluated as possible treatments for coronavirus-2019 caused by severe acute respiratory syndrome coronavirus-2. Tocilizumab is a humanized monoclonal antibody directed against the interleukin-6 receptor that has found a role as a therapy for patients with severe coronavirus-19 pneumonia. The immunomodulatory effects of tocilizumab may have the unintended consequence of predisposing recipients to secondary infections. We sought to assess the risk of invasive fungal disease and the therapeutic impact of tocilizumab on the hospital length of stay, duration of mechanical ventilation, and intensive-care-unit length of stay in critically ill patients with severe coronavirus-19 pneumonia. METHODS: Records of critically ill patients with coronavirus-2019 admitted from March to September 2020 at our institution were reviewed. The risk for fungal infections, intensive-care-unit length of stay, hospital length of stay, and duration of mechanical ventilation in those that received tocilizumab in addition to standard coronavirus-2019 treatments was assessed. RESULTS: Fifty-six critically ill patients treated with dexamethasone and remdesivir for coronavirus-2019 were included, of which 16 patients also received tocilizumab. The majority of the cohort was African American, Asian, or of other ethnic minorities (53.6%). Invasive fungal infections occurred in 10.7% of all patients, and infection rates were significantly higher in the tocilizumab group than in the control group (31.2% vs. 2.5%, risk difference [RD] = 28.8%, p < 0.01). The increased risk in the tocilizumab group was strongly associated with renal replacement therapy. There was a dose-response relationship between the risk of fungal infection and number of tocilizumab doses received, with 2.5% of infections occurring with zero doses, 20% with a single dose (RD = 17.5%), and 50% with two doses (RD = 47.5%) (trend test p < 0.001). In addition, ICU LOS (23.4 days vs. 9.0 days, p < 0.01), the duration of mechanical ventilation (18.9 vs. 3.5 days, p = 0.01), and hospital length of stay (LOS) (29.1 vs. 15.5, p < 0.01) were increased in patients that received tocilizumab. CONCLUSIONS: Repurposed immunomodulator therapies, such as tocilizumab, are now recommended treatments for severe coronavirus-2019 pneumonia, but safety concerns remain. In this early pandemic cohort, the addition of tocilizumab to dexamethasone was associated with an increased risk of fungal infection in those that were critically ill and received renal replacement therapy. Tocilizumab use was also associated with increased ICU and hospital LOSs and duration of mechanical ventilation.