Citations

ObjectivesMicrovascular free tissue transfer is routinely used for reconstructing midface defects in patients with malignancy, however, studies regarding reconstructive outcomes in invasive fungal sinusitis (IFS) are lacking. We aim to describe outcomes of free flap reconstruction for IFS defects, determine the optimal time to perform reconstruction, and if anti‐fungal medications or other risk factors of an immunocompromised patient population affect reconstructive outcomes.MethodsRetrospective review of reconstruction for IFS (2010–2022). Age, BMI, hemoglobin A1c, number of surgical debridements, and interval from the last debridement to reconstruction were compared between patients with delayed wound healing versus those without. Predictor variables for delayed wound healing and the effect of time on free flap reconstruction were analyzed.ResultsTwenty‐seven patients underwent free flap reconstruction for IFS. Three patients were immunocompromised from leukemia and 21 had diabetes mellitus (DM). Patients underwent an average of four surgical debridements for treatment of IFS. The interval from the last IFS debridement to flap reconstruction was 5.58 months (±5.5). Seven flaps (25.9%) had delayed wound healing. A shorter interval of less than 2 months between the last debridement for IFS and reconstructive free flap procedure was associated with delayed wound healing (Fisher Exact Test p = 0.0062). Other factors including DM, BMI, HgA1c, and bone reconstruction were not associated with delayed wound healing.ConclusionPatients with maxillectomy defects from IFS can undergo microvascular‐free flap reconstruction with good outcomes while on anti‐fungal medication. Early reconstruction in the first 2 months after the last IFS debridement is associated with delayed wound healing.Level of Evidence4 Laryngoscope, 134:1642–1647, 2024

ABSTRACTObjectivesWe aimed to investigate the gender-based differences in idiopathic inflammatory myopathies (IIMs), with a particular focus on patient-reported outcomes, utilizing the data obtained through the international COVID-19 vaccination in autoimmune disease e-survey.MethodsPatient-reported outcomes including fatigue, pain, and physical function were extracted from the COVID-19 vaccination in autoimmune disease database and compared between genders, adjusting for demographics and IIM subgroups by multivariable analysis. Inclusion body myositis (IBM) was analysed separately because of the substantial differences in outcomes.ResultsA total of 1197 complete responses from patients with IIMs as of 31 August 2021 were analysed. Seventy percent were women. Women were younger (58 [48–68] vs. 69 [58–75] years old, median [interquartile range], P < .001) and were more likely to suffer from autoimmune multimorbidity, defined as three or more autoimmune diseases in an individual patient (11.4% vs. 2.8%, P < .001). In non-IBM IIMs, fatigue visual analogue scale scores were higher in women (5 [3–7] vs. 4 [2–6], median [interquartile range], P = .004), whereas no significant gender-based differences were noted in IBM. Multivariable analysis in non-IBM IIMs revealed that women, residence in high-income countries, overlap myositis, and autoimmune multimorbidity were independently associated with increased fatigue.ConclusionsWomen with IIMs suffer from autoimmune multimorbidity and experience increased fatigue compared to men.

Abstract Objective To assess healthcare costs and healthcare resource utilization (HCRU) among adult patients who newly initiated erenumab in the United States. Methods This retrospective, non‐interventional analysis included adult patients (aged ≥18 years) newly initiating erenumab and who had three consecutive monthly claims for erenumab (11/1/2017–9/1/2019) from the Komodo Health database. Outcomes included migraine‐related and all‐cause costs, use of other preventive/acute migraine medications, and HCRU. All outcomes were compared during the 180‐day pre‐ versus the 180‐day post‐index periods. Cost outcomes were also assessed for longer periods including post‐index Days 91–270 and monthly mean post‐index costs for the longest time of continuous insurance enrollment. Results Overall, 1839 patients with migraine were included for analysis. Compared to the 180‐day pre‐index period, an increase in total migraine‐related costs (+$2639; p < 0.0001), migraine‐related prescription costs (+$3435, p < 0.0001), all‐cause total costs (+$2977; p < 0.001), and all‐cause prescription costs (+$4102; p < 0.0001) were observed during the 180‐day post‐index period after adjusting for covariates. Conversely, reduction in migraine‐related medical costs (−$896; p < 0.0001), and significantly lower odds of migraine‐related emergency room visits (odds ratio [OR] 0.60, 95% confidence interval [CI] 0.44–0.82; p = 0.001), migraine‐related office visits (OR 0.58, 95% CI 0.53–0.64; p < 0.0001), and migraine‐related neurologist visits (OR 0.69, 95% CI 0.63–0.75; p < 0.0001) were observed during the 180‐days post‐index period. There were significant decreases in the odds of having overall preventive migraine medications (OR 0.81, 95% CI 0.75–0.87; p < 0.0001), acute‐migraine medications (OR 0.92, 95% CI 0.85–1.00; p = 0.038), and triptan (OR 0.79, 95% CI 0.73–0.85; p < 0.0001) during the 180‐day post‐index period. Sensitivity analyses on cost outcomes found no statistically significant differences in pre‐index migraine‐related costs compared to post‐index migraine‐related costs when assessing longer post‐index follow‐up periods. Conclusion Initiation of therapy with a novel treatment is often associated with an increase in overall healthcare costs due to the entrance costs associated with novel therapy. For a chronic condition such as migraine, cost versus health benefits should be evaluated over a long period (e.g., ≥2 years) to better understand the true benefits of therapy. Data from this study suggest that the entrance cost for erenumab, the primary driver of the high post‐index prescription costs gets mitigated by reduced medical costs over long‐term follow‐up. The results indicate better disease management in adult patients with migraine, which should be an important consideration for both patients and payors, as these findings have shown an offset between migraine‐related prescription and medical costs.

ImportanceSystematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.ObjectiveTo assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.ExposureTreatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.Main Outcomes and MeasuresMain outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.ResultsOf 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).Conclusions and RelevanceIn this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.

For precision in clinical oncology practice, detection of tumor-derived peptides and proteins in urine offers an attractive and noninvasive alternative for diagnostic or screening purposes. In this study, we report comparative quantitative proteomic profiling of urine samples from patients with gastric cancer and healthy controls using tandem mass tags-based multiplexed mass spectrometry approach. We identified 1504 proteins, of which 246 were differentially expressed in gastric cancer cases. Notably, ephrin A1 (EFNA1), pepsinogen A3 (PGA3), sortilin 1 (SORT1), and vitronectin (VTN) were among the upregulated proteins, which are known to play crucial roles in the progression of gastric cancer. We also found other overexpressed proteins, including shisa family member 5 (SHISA5), mucin like 1 (MUCL1), and leukocyte cell derived chemotaxin 2 (LECT2), which had not previously been linked to gastric cancer. Using a novel approach for targeted proteomics, SureQuant, we validated changes in abundance of a subset of proteins discovered in this study. We confirmed the overexpression of vitronectin and sortilin 1 in an independent set of urine samples. Altogether, this study provides molecular candidates for biomarker development in gastric cancer, and the findings also support the promise of urinary proteomics for noninvasive diagnostics and personalized/precision medicine in the oncology clinic.

Abstract Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score &lt;90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Abstract Perturbations of the mucosal immune system and the microbiota can lead to allergic disorders with a lifelong impact. With up to 90% of cases diagnosed by age 6, atopic dermatitis represents a unique allergic disorder during early life. Diagnosis of atopic dermatitis is associated with an increased risk for other allergic disorders throughout life. The opportunistic fungal species Candida albicans is often found as part of a dysbiotic microbiota and its presence is associated with increased risk of atopy. While adult mice are unable to be stably colonized with C. albicans without the use of antibiotics, we have found that mice exposed to C. albicans prior to weaning maintain long term colonization in the gut and on the skin. In mice colonized in early life with C. albicans in the GI tract, FoxP3+ T cells were significantly decreased post-weaning in the mesenteric lymph node as well as in the small intestine and colon lamina propria. Colonization by C. albicans resulted in an increased Th17 response, with increased RORγt+ and c-Maf+ T cells in the colon lamina propria. In a clinical observation study, we found C. albicans colonization in the intestine of prematurely born infants, suggesting colonization of the human GI tract with C. albicans may frequently occur. As the microbiota develops with age, the presence of C. albicans may impact the normal course of increasing complexity and diversity in this ecosystem. The establishment of regulatory T cells in early life is vital to maintaining tolerance to commensal organisms throughout life; this disruption in regulatory T cells potentially links colonization by C. albicans to the development of atopy and allergic responses. Supported by grants from Mayo Clinic Center for Individualized Medicine

Abstract We identified the lowest composition necessary to generate a vaccination adjuvant that promotes a Treg response following immunization in mice and named it “complete tolerogenic adjuvant.” This novel adjuvant may allow us to utilize the well-established “antigen plus adjuvant” method of vaccination to induce Treg cell-mediated antigen-specific immunosuppression. The minimal composition is dexamethasone, rapamycin, and monophosphoryl lipid A with the following mass ratios: 8:20:3. We have demonstrated why immunosuppressive and immunogenic substances are both required for the formation of genuine adjuvants for Treg cells by dissecting the roles of each of these components during vaccination. Currently, research is ongoing in our group to begin to assess the usefulness of this adjuvant for antigen immunization in murine models of human autoimmune/inflammatory diseases. Specifically, we are evaluating the tolerogenic efficacy of this adjuvant for vaccination regimen targeting the apolipoprotein B antigen, using the ApoE−/− mouse model of atherosclerosis. These studies are expected to help drive the development of further, perhaps more effective, complete tolerogenic adjuvants that could be used to create a plethora of new, novel vaccines for treating immunological illnesses. Master program and NIH grant

Abstract Introduction Low creatinine to cystatin-C ratio (Cr/Cys-C) may be a biomarker for low-muscle mass. Furthermore, low Cr/Cys-C is associated with decreased overall survival (OS), but to date, has not been examined in patients with renal cell carcinoma (RCC). Our objective is to evaluate associations between low Cr/Cys-C ratio and OS and recurrence-free survival (RFS) in patients with RCC treated with nephrectomy. Methods We performed a retrospective review of patients with RCC treated with nephrectomy. Patients with end-stage renal disease and less than 1-year follow up were excluded. Cr/Cys-C was dichotomized at the median for the cohort (low vs. high). OS and RFS for patients with high versus low Cr/Cys-C were estimated with the Kaplan-Meier method, and associations with the outcomes of interest were modeled using Cox proportional Hazards models. Associations between Cr/Cys-C and skeletal muscle mass were assessed with correlations and logistic regression. Results A total of 255 patients were analyzed, with a median age of 64. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). Low Cr/Cys-C was associated with age, female sex, Eastern Cooperative Oncology Group Performance Status ≥1, TNM stage, and tumor size. Kaplan-Meier and Cox regression analysis demonstrated an association between low Cr/Cys-C and decreased OS (HR = 2.97, 95%CI, 1.12-7.90, P =0.029) and RFS (HR = 3.31, 95%CI, 1.26-8.66, P = .015). Furthermore, a low Cr/Cys-C indicated a 2-3 increase in risk of radiographic sarcopenia. Conclusions Lower Cr/Cys-C is associated with inferior oncologic outcomes in RCC and, pending validation, may have utility as a serum biomarker for the presence of sarcopenia in patients with RCC treated with nephrectomy.