Attributable mortality of candidemia - Results from the ECMM Candida III multinational European Observational Cohort Study.

INTRODUCTION: Despite antifungal advancements, candidaemia still has a high mortality rate of up to 40%. The ECMM Candida III study in Europe investigated the changing epidemiology and outcomes of candidaemia for better understanding and management of these infections. METHODS: In this observational cohort study, participating hospitals enrolled the first ten consecutive adults with blood culture-proven candidemia. Collected data included patient demographics, risk factors, hospital stay duration (follow-up of 90 days), diagnostic procedures, causative Candida spp., management details, and outcome. Controls were included in a 1:1 fashion from the same hospitals. The matching process ensured similarity in age (10-year range), primary underlying disease, hospitalization in intensive care versus non-ICU ward, and major surgery within 2 weeks before candidemia between cases and controls. Overall and attributable mortality were described, and a survival probability for cases and controls was performed. RESULTS: One hundred seventy-one pairs consisting of patients with candidemia and matched controls from 28 institutions were included. In those with candidemia, overall mortality was 40.4%. Attributable mortality was 18.1% overall but differed between causative Candida species (7.7% for Candida albicans, 23.7% for Candida glabrata/Nakaseomyces glabratus, 7.7% for Candida parapsilosis and 63.6% for Candida tropicalis). Regarding risk factors, the presence of a central venous catheter, total parenteral nutrition and acute or chronic renal disease were significantly more common in cases versus controls. Duration of hospitalization, and especially that of ICU stay, was significantly longer in candidemia cases (20 (IQR 10-33) vs 15 days (IQR 7-28); p = 0.004). CONCLUSIONS: Although overall and attributable mortality in this subgroup analysis of matched case/control pairs remains high, the attributable mortality appears to have decreased in comparison to historical cohorts. This decrease may be driven by improved prognosis of Candida albicans and Candida parapsilosis candidemia; whereas candidemia due to other Candida spp. exhibits a much higher attributable mortality.

Biomechanical analysis of stabilization for thoracolumbar anterior spinal failure caused by osteolytic lesions, a finite element comparison of direct lateral corpectomy and posterior long segment instrumentation.

BACKGROUND CONTEXT: Osteolytic lesions caused by infection or metastatic disease of the spine can induce instability. Different surgical strategies are available to restore stability in this scenario, however little is known how various reconstruction techniques affect spinal biomechanics. PURPOSE: To analyze and quantify the biomechanical effects of three different surgical reconstruction techniques in the treatment of a T12 osteolytic model. STUDY DESIGN/SETTING: Finite element analysis of the thoracic spine with a T12 osteolytic lesion. METHODS: Using CT scans from a 20-year-old man without structural deformity, simulation of an osteolytic lesion with a 50% defect at the posterior aspect of T12 vertebral body (anterior? Posterior? Be specific) was created. (was the defect created by the force? Or was the force then delivered after the defect was created?) by a 490 N vertical force to T9. Next, three common instrumentation techniques treating the osteolytic lesion were modeled and biomechanically tested. These included: Model A, corpectomy with short segment fixation (T11-L1) and two long-segment instrumentations; Model B long segment fixation with triple rod construct; Model C long segment fixation with dual rod construct. A load of 480N was then applied on the spine models in vertically downward direction on T9. Von Mises stresses were measured (MPa) in the discs, vertebrae, and implants. RESULTS: Model A demonstrated the lowest stress on construct material, adjacent vertebral bodies, and discs but increased stress on the instrumented vertebrae. Model B was more rigid and demonstrated lower construct stress compared to Model C. However, Model C had the lowest vertebral body stress in flexion, extension, and lateral bending in the most upper instrumented vertebral body, but the highest screw pull-out stress when compared to Model A and Model B. CONCLUSIONS: This osteolytic T12 model provides unique biomechanical data that can help to tailor surgical strategies in select scenarios. While optimal outcomes are best achieved with a construct tailored to a specific patient's need for stabilization, our findings can be generalized for instances of cancerous lesions, low bone density, and infectious causes. CLINICAL RELEVANCE: The results of this study can help with the choice of appropriate surgical reconstruction technique based on patient-specific characteristics.

Analysis of aborted bariatric surgeries and potential opportunities.

BACKGROUND: Aborted bariatric surgeries are an undesirable experience for patients as they are subjected to potential physical harm and emotional distress. A thorough investigation of aborted bariatric surgeries has not been previously reported. This information may allow the discovery of opportunities to mitigate the risk of aborting some bariatric operations. METHODS: Data from the Michigan Bariatric Surgery Collaborative, a statewide bariatric surgery registry, were used to identify all aborted primary bariatric operations from June 2006 through January 2023. The reasons for aborting surgery were divided into seven categories. Stepwise logistic regression was performed to identify independent predictors of aborted procedures for potentially modifiable factors. RESULTS: A total of 115,004 patients underwent bariatric surgery with 555 (0.48%) procedures aborted. Of those having an aborted operation the mean age was 52 years and mean BMI was 49.8 with females accounting for 72%. Sleeve gastrectomy had the lowest aborted rate (0.38%) as compared to gastric bypass, adjustable gastric banding, and biliopancreatic diversion (p < 0.0001). The most common aborted surgery reason categories included adhesions and hernias, tumors and anatomic anomalies, and inadequate visualization due to either hepatomegaly or abdominal wall thickness. The most significant (p < 0.0001) independent predictors of aborted surgeries due to hepatomegaly or abdominal wall thickness were BMI ≥ 60 (OR 10.7), BMI 50 to 59 (OR 3.1) and diabetes mellitus (OR 2.7). Preoperative weight loss was a protective factor for aborting surgery due to hepatomegaly or abdominal wall thickness (OR 0.9; p < 0.0001). CONCLUSIONS: Aborted surgeries are uncommon and occur in approximately 1 in 200 primary bariatric operations with the lowest rate identified in sleeve gastrectomy. Nearly 20% of operations are aborted due to hepatomegaly or abdominal wall thickness and targeting patients with elevated BMIs and diabetes mellitus for preoperative weight loss might reduce the risk of these types of aborted procedures.

Insights into invasive fungal infection diagnostic and treatment capacities in tertiary care centres of Germany.

Introduction: In Germany, the growing incidence of invasive fungal infections (IFIs) is a significant health concern, particularly impacting individuals with compromised immune systems due to factors like increasing transplant recipients, an ageing population, and heightened use of immunosuppressive medications. Diagnosing IFI remains challenging, and the integration of biomarker assays into clinical practice is difficult. Antifungal resistance, exemplified by pan-antifungal-resistant Candida auris cases, adds complexity to treatment. This study aims to provide a concise overview of the diagnostic and treatment landscape for IFI in Germany, identifying areas for improvement and paving the way for targeted interventions. Methods: Data were collected using an online electronic case report form from October 2021 to February 2023. The survey included questions about institutional practices related to fungal infection diagnosis and treatment, with invitations extended to researchers nationwide. Results: The study surveyed 58 hospitals across Germany. Notably, 77.6% managed high-risk patients for IFI. While 86% had onsite microbiology labs, a significant difference was noted for high-risk patients (93% in specialized hospitals versus 62% in others). Microscopy services had 96% coverage, while overall access to culture was 96%. Antigen tests had 96% coverage, and antibody access was reported at 98%. PCR testing was available at 98%. Imaging access showed no significant access differences. Variability existed in amphotericin B formulations based on patient profiles. Therapeutic drug monitoring was more common in high-risk patient institutions (89.5% versus 50.0%). All analysed institutions reported access to surgery (100%). Conclusions: Addressing identified disparities in diagnostic and therapeutic resources for IFI is crucial to improving patient outcomes. The study calls for ongoing research and collaboration to optimize strategies for the prevention and treatment of IFI, emphasizing the importance of equitable access to resources, especially in high-risk patient populations.

Conversion of sleeve gastrectomy to Roux-en-Y gastric bypass: impact on reflux and weight loss.

BACKGROUND: Sleeve gastrectomy (SG) is the most commonly performed weight loss operation, and its 2 most common complications are postoperative reflux and weight recurrence. There is limited evidence to guide decision-making in treating these conditions. OBJECTIVES: To determine the efficacy of conversion of SG to Roux-en-Y gastric bypass (RYGB) for GERD management and weight loss. SETTING: Forty-one hospitals in Michigan. METHODS: We conducted a retrospective cohort study examining patients who underwent conversion of SG to RYGB from 2014 to 2022. The primary outcomes were changes in GERD-HRQL scores, anti-reflux medication use, and weight from baseline to 1 year after conversion. Secondary outcomes included 30-day postoperative complications and resource utilization. RESULTS: Among 2133 patients undergoing conversion, 279 (13%) patients had baseline and 1-year GERD-HRQL survey data and anti-reflux medication data. GERD-HRQL scores decreased significantly from 24.6 to 6.6 (P < .01). Among these, 207 patients (74%) required anti-reflux medication at baseline, with only 76 patients (27%) requiring anti-reflux medication at 1 year postoperatively (P < .01). Of the 380 patients (18%) with weight loss data, mean weight decreased by 68.4lbs, with a 24.3% decline in total body weight and 51.5% decline in excess body weight. In terms of 30-day complications, 308 (14%) patients experienced any complication and 89 (4%) experienced a serious complication, but there were no leaks, perforations, or deaths. Three-hundred and fifty-five (17%) patients presented to the emergency department and 64 (3%) patients underwent reoperation. CONCLUSIONS: This study represents the largest reported experience with conversion from SG to RYGB. We found that conversion to RYGB is associated with significant improvement in GERD symptoms, reduction in anti-reflux medication use, and significant weight loss and is therefore an effective treatment for GERD and weight regain after SG. However, the risks and benefits of conversion surgery should be carefully considered, especially in patients with significant comorbidity burden.

Individual and institutional predisposing factors of MRSA surgical site infection and outcomes-a retrospective case-control-study in 14 European high-volume surgical centres.

Objectives: To assess incidence rates of surgical site infections (SSI) by MRSA and to determine related factors and clinical outcome compared to MSSA, including country-specific, institutional and patient determinants. Patients and methods: We performed a subgroup analysis of the Europe-wide SALT (NCT03353532) study population with MRSA SSI from 14 centres in France, Germany, Italy, Spain and the UK. Results: An overall MRSA SSI incidence of 0.06% (n = 104) was found in 178 903 patients undergoing invasive surgery in 2016. Frequently observed comorbidities were chronic cardiovascular disease, diabetes and solid tumours. Compared to the overall MRSA SSI incidence, incidence rates were significantly higher in Spain (58 of 67 934 cases) and lower in Germany (16 of 46 443 cases; both P < 0.05). Centres with antibiotic stewardship (ABS) and infectious disease (ID) consultation programmes (n = 3/14) had lower MRSA rates (17 of 43 556 cases versus 61 of 83 048 cases, P < 0.05). In bivariate analyses, MRSA SSI patients were significantly older, had higher BMI and more comorbidities compared to MSSA (P < 0.05 each). Surgery performed between 6:00 and 12:00 pm led to higher MRSA proportions among S. aureus SSI (17 of 104 cases versus 62 of 640 cases, P < 0.05). Conclusions: This study shows low overall and country-specific incidence rates of MRSA SSI in Europe. We could show significant differences between countries as well as between centres with established ABS and ID consultation programmes were observed. The number of those programmes seems too small against this background.

Intramolecular Energy Transfer Competing with Light-Driven Intermolecular Proton Transfer in an Iron(II)-NHC Complex? A Query into the Role of Photobasic Ligands and MLCT States.

Inorganic photoacids and photobases comprising of photoactive transition metal complexes (TMCs) offer the ability to modulate proton transfer reactions through light irradiation, while utilizing the excellent optical properties of the latter. This provides a powerful tool for precise control over chemical reactions and processes, with implications for both fundamental science and practical applications. In this contribution, we present a novel molecular architecture amending an Fe-NHC complex with a pendant quinoline, as a prototypical photobase, as a representative earth-abundant TMC based inorganic photobase. We characterize the excited-state properties and proton-transfer dynamics using steady-state absorption and emission spectroscopy as well as pump wavelength dependent transient absorption spectroscopy in various protic solvents. The kinetics and thermodynamics of proton transfer in the quinoline moiety are influenced by both the presence of the metal center and the choice of the solvent. Furthermore, we see indications of intramolecular energy transfer from the quinoline to the MLCT state as a limiting factor for panchromatic photobasicity of the complex.

Necrotizing pancreatitis with invasive candidiasis and candidemia due to Candida albicans and pan-echinocandin-resistant Candidaglabrata.

We report on a 64-year-old man with necrotizing pancreatitis related, invasive candidiasis, and candidemia. Despite a multidisciplinary management including antifungal therapy, endoscopic interventions and surgery, the patients' infection progressed and lead to colon perforation, retroperitoneal abscess formation, and polymicrobial bloodstream infections. Resistance to echinocandins in Candida glabrata further complicated the course. This report emphasizes the need for vigilant monitoring and exploring alternative therapeutic approaches for patients in critical conditions.

Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM.

Cryptococcosis is a major worldwide disseminated invasive fungal infection. Cryptococcosis, particularly in its most lethal manifestation of cryptococcal meningitis, accounts for substantial mortality and morbidity. The breadth of the clinical cryptococcosis syndromes, the different patient types at-risk and affected, and the vastly disparate resource settings where clinicians practice pose a complex array of challenges. Expert contributors from diverse regions of the world have collated data, reviewed the evidence, and provided insightful guideline recommendations for health practitioners across the globe. This guideline offers updated practical guidance and implementable recommendations on the clinical approaches, screening, diagnosis, management, and follow-up care of a patient with cryptococcosis and serves as a comprehensive synthesis of current evidence on cryptococcosis. This Review seeks to facilitate optimal clinical decision making on cryptococcosis and addresses the myriad of clinical complications by incorporating data from historical and contemporary clinical trials. This guideline is grounded on a set of core management principles, while acknowledging the practical challenges of antifungal access and resource limitations faced by many clinicians and patients. More than 70 societies internationally have endorsed the content, structure, evidence, recommendation, and pragmatic wisdom of this global cryptococcosis guideline to inform clinicians about the past, present, and future of care for a patient with cryptococcosis.

Quantification of midostaurin in plasma and serum by stable isotope dilution liquid chromatography-tandem mass spectrometry: Application to a cohort of patients with acute myeloid leukemia.

OBJECTIVES: Midostaurin is an oral multitargeted tyrosine kinase inhibitor for the treatment of acute myeloid leukemia (AML). Therapeutic drug monitoring of midostaurin may support its safe use when suspecting toxicity or combined with strong CYP3A4 inhibitors. METHODS: A stable isotope dilution liquid chromatography-tandem mass spectrometry method was developed and validated for the determination and quantification of midostaurin in human plasma and serum. Midostaurin serum concentrations were analyzed in 12 patients with FMS-like tyrosine kinase 3 (FLT3)-mutated AML during induction chemotherapy with cytarabine, daunorubicin, and midostaurin. Posaconazole was used as prophylaxis of invasive fungal infections. RESULTS: Linear quantification of midostaurin was demonstrated across a concentration range of 0.01-8.00 mg/L. Inter- and intraday imprecisions of the proposed method were well within ±10%. Venous blood samples were taken in nine and three patients in the first and second cycle of induction chemotherapy. Median (range) midostaurin serum concentration was 7.9 mg/L (1.5-26.1 mg/L) as determined in 37 independent serum specimens. CONCLUSION: In a real-life cohort of AML patients, interindividual variability in midostaurin serum concentrations was high, highlighting issues concerning optimal drug dosing in AML patients. A personalized dosage approach may maximize the safety of midostaurin. Prospective studies and standardization of analytical methods to support such an approach are needed.

Hybrid immunity to SARS-CoV-2 in patients with chronic lymphocytic leukemia.

OBJECTIVE: Preventing severe COVID-19 remains a priority globally, particularly in the immunocompromised population. As shown in healthy individuals, immunity against SARS-CoV-2 can be yielded by previous infection, vaccination, or both (hybrid immunity). The objective of this observation study was to investigate hybrid immunity in patients with chronic lymphocytic leukemia (CLL). METHODS/RESULTS: Blood samples of six patients with CLL were collected 55 days after fourth COVID-19 vaccination. All patients had a SARS-CoV-2 infection within 12 months before the second booster (fourth vaccination). SARS-CoV-2 spike receptor binding domain (RBD)-specific IgG antibodies were detectable in 6/6 (100.0%) CLL patients after four compared to 4/6 (66.7%) after three vaccinations. The median number of SARS-CoV-2 spike-specific T cells after repeated booster vaccination plus infection was 166 spot-forming cells (SFC) per million peripheral blood mononuclear cells. Overall, 5/5 (100%) studied patients showed a detectable increase in T cell activity. CONCLUSION: Our data reveal an increase of cellular and humoral immune response in CLL patients after fourth COVID-19 vaccination combined with SARS-CoV-2 infection, even in those undergoing B cell-depleting treatment. Patients with prior vaccination failure now show a specific IgG response. Future research should explore the duration and effectiveness of hybrid immunity considering various factors like past infection and vaccination rates, types and numbers of doses, and emerging variants.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

Tracheobronchopathia Osteochondroplastica - to Biopsy or not to Biopsy? A Relook at The Rare Disease.

BACKGROUND: Tracheobronchopathia osteochondroplastica (TPO) is a rare idiopathic disease involving the tracheobronchial tree. It is mostly an incidental finding with non-specific clinical manifestations. It has typical bronchoscopic, radiological features and biopsy is usually considered non-essential. The study aimed to determine whether biopsy makes a difference in the management of patients. METHODS: All patients diagnosed with TPO in our institution over 15 years (2005 to 2020) were included in this study. Their medical records, chest computed tomography (CT), and bronchoscopy reports were retrospectively reviewed, and data were analysed. All the CT images were reviewed by a senior chest radiologist. RESULTS: From the 20,000 bronchoscopies and 260,000 CT thorax images obtained, 28 cases were diagnosed as TPO based on either bronchoscopy or radiology or both. Among the 19 cases diagnosed through bronchoscopy, 16 underwent a biopsy. In addition to TPO features, biopsy showed additional diagnoses in 6 cases. In 9 cases, TPO was not initially diagnosed by CT but by bronchoscopy. In 8 patients, TPO was diagnosed incidentally on CT performed for other reasons. On follow-up with the treatment of underlying/co-existing concomitant aetiologies, clinical improvement was noted in all patients. None of them progressed to respiratory failure or airway obstruction until the last follow-up. CONCLUSION: Among patients who underwent bronchoscopic biopsy of TPO lesions, 38% had biopsy results showing an alternative aetiology, which led to changes in the treatment plan for all these patients. Hence, a bronchoscopic biopsy of TPO lesions should be performed to rule out other aetiologies.

Early combination therapy of COVID-19 in high-risk patients.

PURPOSE: Prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed in immunocompromised hosts. Early monotherapy with direct-acting antivirals or monoclonal antibodies, as recommended by the international guidelines, does not prevent this with certainty. Dual therapies may therefore have a synergistic effect. METHODS: This retrospective, multicentre study compared treatment strategies for corona virus disease-19 (COVID-19) with combinations of nirmatrelvir/ritonavir, remdesivir, molnupiravir, and/ or mABs during the Omicron surge. Co-primary endpoints were prolonged viral shedding (≥ 106 copies/ml at day 21 after treatment initiation) and days with SARS-CoV-2 viral load ≥ 106 copies/ml. Therapeutic strategies and risk groups were compared using odds ratios and Fisher's tests or Kaplan-Meier analysis and long-rank tests. Multivariable regression analysis was performed. RESULTS: 144 patients were included with a median duration of SARS-CoV-2 viral load ≥ 106 copies/ml of 8.0 days (IQR 6.0-15.3). Underlying haematological malignancies (HM) (p = 0.03) and treatment initiation later than five days after diagnosis (p < 0.01) were significantly associated with longer viral shedding. Prolonged viral shedding was observed in 14.6% (n = 21/144), particularly in patients with underlying HM (OR 3.5; 95% CI 1.2-9.9; p = 0.02). Clinical courses of COVID-19 were mild to moderate with only few adverse effects potentially related to combination treatment. CONCLUSION: Early combination treatment of COVID-19 effectively prevented prolonged viral shedding in 85.6% of cases. Considering the rapid viral clearance rates and low toxicity, individualized dual therapy approaches may be beneficial in high-risk patients.

Systematic discovery of neoepitope-HLA pairs for neoantigens shared among patients and tumor types.

The broad application of precision cancer immunotherapies is limited by the number of validated neoepitopes that are common among patients or tumor types. To expand the known repertoire of shared neoantigen-human leukocyte antigen (HLA) complexes, we developed a high-throughput platform that coupled an in vitro peptide-HLA binding assay with engineered cellular models expressing individual HLA alleles in combination with a concatenated transgene harboring 47 common cancer neoantigens. From more than 24,000 possible neoepitope-HLA combinations, biochemical and computational assessment yielded 844 unique candidates, of which 86 were verified after immunoprecipitation mass spectrometry analyses of engineered, monoallelic cell lines. To evaluate the potential for immunogenicity, we identified T cell receptors that recognized select neoepitope-HLA pairs and elicited a response after introduction into human T cells. These cellular systems and our data on therapeutically relevant neoepitopes in their HLA contexts will aid researchers studying antigen processing as well as neoepitope targeting therapies.

Association of program-specific variation in bariatric surgery volume for Medicaid patients and access to care: a tale of inequality?

BACKGROUND: Although patients with lower socioeconomic status are at higher risk of obesity, bariatric surgery utilization among patients with Medicaid is low and may be due to program-specific variation in access. Our goal was to compare bariatric surgery programs by percentage of Medicaid cases and to determine if variation in distribution of patients with Medicaid could be linked to adverse outcomes. METHODS: Using a state-wide bariatric-specific data registry that included 43 programs performing 97,207 cases between 2006 and 2020, we identified all patients with Medicaid insurance (n = 4780, 4.9%). Bariatric surgery programs were stratified into quartiles according to the percentage of Medicaid cases performed and we compared program-specific characteristics as well as baseline patient characteristics, risk-adjusted complication rates and wait times between top and bottom quartiles. RESULTS: Program-specific distribution of Medicaid cases varied between 0.69 and 22.4%. Programs in the top quartile (n = 11) performed 18,885 cases in total, with a mean of 13% for Medicaid patients, while programs in the bottom quartile (n = 11) performed 32,447 cases in total, with a mean of 1%. Patients undergoing surgery at programs in the top quartile were more likely to be Black (20.2% vs 13.5%, p < 0.0001), have diabetes (35.1% vs 29.5%, p < 0.0001), hypertension (55.1% vs 49.6%, p < 0.0001) and hyperlipidemia (47.6% vs 45.2%, p < 0.0001). Top quartile programs also had higher complication rates (8.4% vs 6.6%, p < 0.0001), extended length of stay (5.6% vs 4.0%, p < 0.0001), Emergency Department visits (8.1% vs 6.5%, p < 0.0001) and readmissions (4.7% vs 3.9%, p < 0.0001). Median time from initial evaluation to surgery date was also significantly longer among top quartile programs (200 vs 122 days, p < 0.0001). CONCLUSIONS: Bariatric surgery programs that perform a higher proportion of Medicaid cases tend to care for patients with greater disease severity who experience delays in care and also require more resource utilization. Improving bariatric surgery utilization among patients with lower socioeconomic status may benefit from insurance standardization and program-centered incentives to improve access and equitable distribution of care.

Phase 1b safety and pharmacokinetics of intravenous and oral fosmanogepix in patients with acute myeloid leukaemia and neutropenia.

OBJECTIVES: Fosmanogepix (APX001), a first-in-class, intravenous (IV) and oral (PO) antifungal prodrug, is being developed to treat invasive fungal diseases (IFDs). Manogepix (APX001A; active moiety) targets fungal glycosylphosphatidylinositol-anchored cell wall transfer protein 1, inhibiting cell wall synthesis causing loss of viability. This open-label, multicentre, Phase 1b study in patients with AML and neutropenia (absolute neutrophil count <500 cells/µL; >10 days) undergoing chemotherapy aimed to assess tolerability, safety and pharmacokinetics (PK) of IV and PO fosmanogepix. METHODS: Of 21 adult AML patients undergoing remission induction chemotherapy, 10 received IV fosmanogepix (600 mg; q24h) and 11 received oral fosmanogepix (500 mg; q24h) over 14 days, with a 28 day follow-up. Patients also received remission induction chemotherapy [sequential high-dose cytarabine and mitoxantrone (S-HAM) or 7 + 3 regimen] for AML and IFD prophylaxis (posaconazole). A two-compartmental PK model from previous studies in healthy volunteers was fitted to manogepix plasma data. RESULTS: Of 26 fosmanogepix-related adverse events (AEs; IV: 14; PO: 12) in 9 (42.9%) patients [IV: 5 (50%); PO: 4 (36.4%)], none were serious or resulted in fosmanogepix discontinuation. Most frequently occurring fosmanogepix-related AEs were Grade 1/2 nausea [four events in three patients (14.3%)]; vomiting, ALT increase, and delirium [two events; two patients (9.5%) each]. One patient experienced fosmanogepix-related Grade 3 hypertension. Dose-corrected geometric mean ratio of AUC (PO-to-IV) was 95%. Elimination half-lives (∼2 days) were consistent with prior studies in healthy volunteers. CONCLUSIONS: Fosmanogepix was safe and well tolerated in AML patients with neutropenia receiving remission induction chemotherapy. Safety and PK profiles were comparable to healthy volunteers.

Depression as a risk factor for adverse outcomes and increased healthcare utilization in bariatric surgery patients.

INTRODUCTION: Depression is strongly associated with obesity and is common among patients undergoing bariatric surgery. Little is known about the impact of depression on early postoperative outcomes or its association with substance use. METHODS: The Michigan Bariatric Surgery Collaborative is a statewide quality improvement program that maintains a large clinical registry. We evaluated patients undergoing primary Roux-en-Y gastric bypass or sleeve gastrectomy between 2017 and 2022. Patients self-reported symptoms of depression (PHQ-8) and use of alcohol (AUDIT-C), smoking, prescription opiates, and marijuana at baseline. Preoperative PHQ-8 scores stratified patients based on severity: no depression (0-4), mild (5-9), moderate (10-14), or severe (15-24). We compared 30-day outcomes and substance use between patients with and without depression. RESULTS: Among 44,301 patients, 30.8% had some level of depression, with 19.8% mild, 7.5% moderate, and 3.5% severe. Patients with depression were more likely to have an extended length of stay (LOS) (> 3 days) than those without depression (no depression 2.1% vs. severe depression 3.0%, p = 0.0452). There were no significant differences between no depression and severe depression groups in rates of complications (5.7% vs. 5.2%, p = 0.1564), reoperations (0.9%, vs. 0.8%, p = 0.7394), ED visits (7.7% vs. 7.8%, p = 0.5353), or readmissions (3.2% vs. 3.9%, p = 0.3034). Patients with severe depression had significantly higher rates of smoking (9.7% vs. 12.5%, p < 0.0001), alcohol use disorder (8.6% vs. 14.0%, p < 0.0001), opiate use (14.5% vs. 22.4%, p < 0.0001) and marijuana use (8.4%, vs. 15.5%, p = 0.0008). CONCLUSIONS: This study demonstrated that nearly one-third of patients undergoing bariatric surgery have depression, with over 10% in the moderate to severe range. There was a significant association between preoperative depressive symptoms and extended LOS after bariatric surgery, as well as higher rates of smoking and use of marijuana, prescription opiates and alcohol. There was no significant effect on adverse events or other measures of healthcare utilization.

Evaluating outcomes among surgeons who changed their technique for gastric bypass: a state-wide analysis from 2011 to 2021.

INTRODUCTION: Technical variation exists when performing the gastrojejunostomy during Roux-en-Y gastric bypass (RYGB). However, it is unclear whether changing technique results in improved outcomes or patient harm. METHODS: Surgeons participating in a state-wide bariatric surgery quality collaborative who completed a survey on how they perform a typical RYGB in 2011 and again in 2021 were included in the analysis (n = 31). Risk-adjusted 30-day complication rates and case characteristics for cases in 2011 were compared to those in 2021 among surgeons who changed their gastrojejunostomy technique from end-to-end anastomosis (EEA) to either a linear staple or handsewn anastomosis (LSA/HSA). In addition, case characteristics and outcomes among surgeons who maintained an EEA technique throughout the study period were assessed. RESULTS: A total of 15 surgeons (48.3%) changed their technique from EEA to LSA/HSA while 7 surgeons (22.3%) did not. Nine surgeons did LSA or HSA the entire period and therefore were not included. Surgeons who changed their technique had significantly lower rates of surgical complications in 2021 when compared to 2011 (1.9% vs 5.1%, p = 0.0015), including lower rates of wound complications (0.5% vs 2.1%, p = 0.0030) and stricture (0.1% vs 0.5%, p = 0.0533). Likewise, surgeons who did not change their EEA technique, also experienced a decrease in surgical complications (1.8% vs 5.8%, p < 0.0001), wound complications (0.7% vs 2.1%, p < 0.0001) and strictures (0.2% vs 1.2%, p = 0.0006). Surgeons who changed their technique had a significantly higher mean annual robotic bariatric volume in 2021 (30.0 cases vs 4.9 cases, p < 0.0001) when compared to those who did not. CONCLUSIONS: Surgeons who changed their gastrojejunostomy technique from circular stapled to handsewn demonstrated greater utilization of the robotic platform than those who did not and experienced a similar decrease in adverse events during the study period, despite altering their technique. Surgeons who chose to modify their operative technique may be more likely to adopt newer technologies.

The Austrian landscape of diagnostic capacity and access to treatment for invasive fungal infections.

INTRODUCTION: Immunosuppression after chemotherapy, stem cell transplantation or solid organ transplantation are the main risk factors for invasive fungal infections in Austria. Here, we aim to describe the status of laboratory mycology and the access to antifungal treatment in Austria. METHODS: Between October and November 2021, hospitals were contacted to participate in our online survey: www.clinicalsurveys.net/uc/IFI_management_capacity/. Centres were required to provide information on their institutional profile; self-assessment of burden of invasive fungal infections; access to microscopy, culture, serology, antigen detection and molecular testing; and availability of antifungal agents and therapeutic drug monitoring. RESULTS: Responses were collected from university hospitals and laboratories in Graz, Innsbruck, Linz and Vienna. The four hospitals can provide tertiary care and were highly specialised, including management of patients with severe immunosuppression. All sites consider the incidence of invasive fungal infections to be moderate. Access to microscopy, culture, serology, antigen detection and molecular testing is provided regardless of laboratory. The maximum capacity to identify fungi varies from institution to institution. All currently marketed antifungal agents are available at the four sites. CONCLUSION: Austria is currently well equipped to deal with the emerging threat of invasive fungal infections. However, hospitals may consider preparing for the potential endemicity of certain infections in the near future.