Impact of Obesity on Timing of Tracheotomy: A Multi-institutional Retrospective Study.

OBJECTIVE: To examine the impact of increased body mass index (BMI) on (1) tracheotomy timing and (2) short-term surgical complications requiring a return to the operating room and 30-day mortality utilizing data from the Multi-Institutional Study on Tracheotomy (MIST). METHODS: A retrospective analysis of patients from the MIST database who underwent surgical or percutaneous tracheotomy between 2013 and 2016 at eight institutions was completed. Unadjusted and adjusted logistic regression analyses were used to assess the impact of obesity on tracheotomy timing and complications. RESULTS: Among the 3369 patients who underwent tracheotomy, 41.0% were obese and 21.6% were morbidly obese. BMI was associated with higher rates of prolonged intubation prior to tracheotomy accounting for comorbidities, indication for tracheotomy, institution, and type of tracheostomy (p = 0.001). Morbidly obese patients (BMI ≥35 kg/m2) experienced a longer duration of intubation compared with patients with a normal BMI (median days intubated [IQR 25%-75%]: 11.0 days [7-17 days] versus 9.0 days [5-14 days]; p < 0.001) but did not have statistically higher rates of return to the operating room within 30 days (p = 0.12) or mortality (p = 0.90) on multivariable analysis. This same finding of prolonged intubation was not seen in overweight, nonobese patients when compared with normal BMI patients (median days intubated [IQR 25%-75%]: 10.0 days [6-15 days] versus 10.0 days [6-15 days]; p = 0.36). CONCLUSION: BMI was associated with increased duration of intubation prior to tracheotomy. Although morbidly obese patients had a longer duration of intubation, there were no differences in return to the operating room or mortality within 30 days. LEVEL OF EVIDENCE: III Laryngoscope, 2024.

Factors Associated With Otolaryngologists Performing Tracheotomy.

Importance: Tracheotomies are frequently performed by nonotolaryngology services. The factors that determine which specialty performs the procedure are not defined in the literature but may be influenced by tracheotomy approach (open vs percutaneous) and other clinicodemographic factors. Objective: To evaluate demographic and clinical characteristics associated with tracheotomies performed by otolaryngologists compared with other specialists and to differentiate those factors from factors associated with use of open vs percutaneous tracheotomy. Design, Setting, and Participants: This multicenter, retrospective cohort study included patients aged 18 years or older who underwent a tracheotomy for cardiopulmonary failure at 1 of 8 US academic institutions between January 1, 2013, and December 31, 2016. Data were analyzed from September 2022 to July 2023. Exposure: Tracheotomy. Main Outcomes and Measures: The primary outcome was factors associated with an otolaryngologist performing tracheotomy. The secondary outcome was factors associated with use of the open tracheotomy technique. Results: A total of 2929 patients (mean [SD] age, 57.2 [17.2] years; 1751 [59.8%] male) who received a tracheotomy for cardiopulmonary failure (652 [22.3%] performed by otolaryngologists and 2277 [77.7%] by another service) were analyzed. Although 1664 of all tracheotomies (56.8%) were performed by an open approach, only 602 open tracheotomies (36.2%) were performed by otolaryngologists. Most tracheotomies performed by otolaryngologists (602 of 652 [92.3%]) used the open technique. Multivariable regression analysis revealed that self-reported Black race (odds ratio [OR], 1.89; 95% CI, 1.52-2.35), history of neck surgery (OR, 2.71; 95% CI, 2.06-3.57), antiplatelet and/or anticoagulation therapy (OR, 1.74; 95% CI, 1.29-2.36), and morbid obesity (OR, 1.54; 95% CI, 1.24-1.92) were associated with greater odds of an otolaryngologist performing tracheotomy. In contrast, history of neck surgery (OR, 1.36; 95% CI, 0.96-1.92), antiplatelet and/or anticoagulation therapy (OR, 0.80; 95% CI, 0.56-1.14), and morbid obesity (OR, 0.94; 95% CI, 0.74-1.19) were not associated with undergoing open tracheotomy when performed by any service, and Black race (OR, 0.56; 95% CI, 0.44-0.71) was associated with lesser odds of an open approach being used. Age-adjusted Charlson Comorbidity Index score greater than 4 was associated with greater odds of both an otolaryngologist performing tracheotomy (OR, 1.26; 95% CI, 1.03-1.53) and use of the open tracheotomy technique (OR, 1.48, 95% CI, 1.21-1.82). Conclusions and Relevance: In this study, otolaryngologists were significantly more likely than other specialists to perform a tracheotomy for patients with history of neck surgery, morbid obesity, and ongoing anticoagulation therapy. These findings suggest that patients undergoing tracheotomy performed by an otolaryngologist are more likely to present with complex and challenging clinical characteristics.

Clinicodemographic Predictors of Tracheotomy Tube Size and Decannulation: A Multiinstitutional Retrospective Cohort Study on Tracheotomy.

OBJECTIVE: We aimed to discern clinico-demographic predictors of large (≥8) tracheostomy tube size placement, and, secondarily, to assess the effect of large tracheostomy tube size and other parameters on odds of decannulation before hospital discharge. SUMMARY OF BACKGROUND DATA: Factors determining choice of tracheostomy tube size are not well-characterized in the current literature, despite evidence linking large tracheostomy tube size with posttracheotomy tracheal stenosis. The effect of tracheostomy tube size on timing of decannulation is also unknown, an important consideration given reported associations between endotracheal tube size and probability of failed extubation. METHODS: We collected information pertaining to patients who underwent tracheotomy at 1 of 10 U.S. health care institutions between 2010 and 2019. Tracheostomy tube size was dichotomized (≥8 and <8). Multivariable logistic regression models were fit to identify predictors of (1) large tracheostomy tube size, and (2) decannulation before hospital discharge. RESULTS: The study included 5307 patients, including 2797 (52.7%) in the large tracheostomy cohort. Patient height (odds ratio [OR] = 1.060 per inch; 95% confidence interval [CI] 1.041-1.070) and obesity (1.37; 95% CI 1.1891.579) were associated with greater odds of large tracheostomy tube; otolaryngology performing the tracheotomy was associated with significantly lower odds of large tracheostomy tube (OR = 0.155; 95% CI 0.131-0.184). Large tracheostomy tube size (OR = 1.036; 95% CI 0.885-1.213) did not affect odds of decannulation. CONCLUSIONS: Obesity was linked with increased likelihood of large tracheostomy tube size, independent of patient height. Probability of decannulation before hospital discharge is influenced by multiple patient-centric factors, but not by size of tracheostomy tube.

Immune-mediated diseases and subsequent risk of alopecia areata in a prospective study of US women.

INTRODUCTION: Alopecia areata (AA) is the most common form of immune-mediated hair loss. Studies have begun to establish the most frequent comorbid diseases of AA; however, results have been inconsistent with few prospective studies. METHODS: A total of 63,692 women in the Nurses' Health Study, 53-80 years, were prospectively followed from 2002 to 2014 to determine whether history of immune-mediated disease was associated with AA risk. Hazard ratios (HRs) and 95% confidence intervals (CIs) for AA in relation to immune-mediated conditions were computed using Cox proportional hazard models, adjusted for AA risk factors. RESULTS: 133 AA cases were identified during follow-up. Personal history of any immune-mediated disease was associated with increased AA risk (HR 1.72, 95% CI 1.24-2.37). History of systemic lupus erythematosus (HR 5.43, 95% CI 2.11-13.97), multiple sclerosis (HR 4.10, 95% CI 1.40-11.96), vitiligo (HR 3.13, 95% CI 1.08-9.10), psoriasis (HR 2.01, 95% CI 1.00-4.03), hypothyroidism (HR 1.88, 95% CI 1.30-2.71), and rheumatoid arthritis (HR 1.66, 95% CI 1.09-2.52) were associated with increased AA risk. History of inflammatory bowel disease or Graves' disease/hyperthyroidism was not significantly associated with AA risk. CONCLUSIONS: In this prospective study, personal history of immune-mediated diseases either individually or overall was associated with increased AA risk.

Synthetic lethality of cyclin-dependent kinase inhibitor Dinaciclib with VHL-deficiency allows for selective targeting of clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (CC-RCC) remains one of the most deadly forms of kidney cancer despite recent advancements in targeted therapeutics, including tyrosine kinase and immune checkpoint inhibitors. Unfortunately, these therapies have not been able to show better than a 16% complete response rate. In this study we evaluated a cyclin-dependent kinase inhibitor, Dinaciclib, as a potential new targeted therapeutic for CC-RCC. In vitro, Dinaciclib showed anti-proliferative and pro-apoptotic effects on CC-RCC cell lines in Cell Titer Glo, Crystal Violet, FACS-based cell cycle analysis, and TUNEL assays. Additionally, these responses were accompanied by a reduction in phospho-Rb and pro-survival MCL-1 cell signaling responses, as well as the induction of caspase 3 and PARP cleavage. In vivo, Dinaciclib efficiently inhibited primary tumor growth in an orthotopic, patient-derived xenograft-based CC-RCC mouse model. Importantly, Dinaciclib targeted both CD105+ cancer stem cells (CSCs) and CD105- non-CSCs in vivo. Moreover, normal cell lines, as well as a CC-RCC cell line with re-expressed von-Hippel Lindau (VHL) tumor suppressor gene, were protected from Dinaciclib-induced cytotoxicity when not actively dividing, indicating an effective therapeutic window due to synthetic lethality of Dinaciclib treatment with VHL loss. Thus, Dinaciclib represents a novel potential therapeutic for CC-RCC.

Mixed olfactory neuroblastoma and neuroendocrine carcinoma: An unusual case report and literature review.

BACKGROUND: The aim of the study was to present a case of mixed olfactory neuroblastoma (ONB) and carcinoma, an extremely rare tumor with only a few cases in the published literature. CASE DESCRIPTION: An otherwise healthy 27-year-old male presented with sinus complaints, headache, and unilateral eye discharge. Imaging and endoscopy revealed a mass presumed to represent a juvenile nasopharyngeal angiofibroma. Unexpectedly, the final pathology report revealed high grade mixed ONB and carcinoma. This tumor is the sixth and youngest documented patient with mixed ONB and carcinoma. CONCLUSION: Physicians should remain vigilant for the possibility of malignancy in their approach to nasal cavity masses, even in young otherwise healthy patients. Careful review of the immunohistopathology should also be taken, as mixed olfactory tumors such as these are aggressive, rare entities that require multidisciplinary oncologic care.

Racial characteristics of alopecia areata in the United States.

BACKGROUND: Epidemiologic studies on the association between race and alopecia areata (AA) are limited. OBJECTIVE: To characterize racial differences of AA in the United States. METHODS: Cross-sectional study of self-registered AA patients and noncases in the National Alopecia Areata Registry (NAAR). We evaluated odds of AA and its subtypes for 5 ethnic/racial groups using logistic regression. A sex-stratified analysis and a sensitivity analysis among dermatologist-confirmed cases were also performed. RESULTS: We identified 9340 AA patients and 2064 noncases. Compared with whites, African Americans had greater odds of AA (odds ratio, 1.77; 95% confidence interval, 1.37-2.28) and Asians had lower odds (odds ratio, 0.40; 95% confidence interval, 0.32-0.50) of AA. The results were consistent in AA subtypes, dermatologist-confirmed cases, and by sex. LIMITATIONS: Residual confounding due to limited number of covariates. Recall or recruitment bias not representative of the entire disease spectrum. Also, outcome misclassification was possible because not all AA cases in the registry were confirmed by dermatologists. CONCLUSION: Our findings suggest higher odds of AA in African Americans and lower odds in Asians compared with whites. Future studies examining racial disparity in AA from clinical and genetic perspectives are warranted for a better understanding of the disease pathogenesis.

Gluten intake and risk of psoriasis, psoriatic arthritis, and atopic dermatitis among United States women.

BACKGROUND: Associations between gluten intake and psoriasis, psoriatic arthritis, and atopic dermatitis are poorly understood. OBJECTIVE: To determine whether increased gluten intake is associated with incident psoriasis, psoriatic arthritis, and atopic dermatitis. METHODS: Cohort studies among women in Nurses' Health Study II. Food frequency questionnaires were used to calculate gluten content of participants' diet every 4 years (1991-2015 for psoriatic disease, 1995-2013 for atopic dermatitis). Disease outcomes were assessed by self-report and subsequently validated. Multivariable-adjusted Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals for the association between gluten intake (quintiles) and psoriasis, psoriatic arthritis, and atopic dermatitis. RESULTS: We included 85,185 participants in the psoriasis analysis, 85,324 in the psoriatic arthritis analysis, and 63,443 in the atopic dermatitis analysis. Increased gluten intake was not associated with any of the outcomes (all P for trend >.05). Comparing highest and lowest gluten intake quintiles, the multivariable hazard ratios (95% confidence intervals) were 1.15 (0.98-1.36) for psoriasis, 1.12 (0.78-1.62) for psoriatic arthritis, and 0.91 (0.66-1.25) for atopic dermatitis. LIMITATIONS: No assessment of a strictly gluten-free diet. CONCLUSIONS: Our findings do not support the amount of dietary gluten intake as a risk factor for psoriasis, psoriatic arthritis, or atopic dermatitis in adult women.

Targeting the RhoGTPase/ROCK pathway for the treatment of VHL/HIF pathway-driven cancers.

The loss of the von Hippel-Lindau (VHL) tumor-suppressor is a major driver of Clear Cell Renal Cell Carcinoma (CC-RCC) resulting in the stabilization and overactivation of hypoxia inducible factors (HIFs). ROCK1 is a well-known protein serine/threonine kinase which is recognized as having a role in cancer including alterations in cell motility, metastasis and angiogenesis. We recently investigated and identified a synthetic lethal interaction between VHL loss and ROCK1 inhibition in CC-RCC that is dependent on HIF overactivation. Increased expression and activity of both HIFs and ROCK1 occurs in many types of cancer supporting the potential therapeutic role of ROCK inhibitors beyond CC-RCC. We also discuss future research required to establish prognostic markers to predict tumor response to ROCK inhibitors.

A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

Targeting the Mevalonate Pathway Suppresses VHL-Deficient CC-RCC through an HIF-Dependent Mechanism.

Clear cell renal cell carcinoma (CC-RCC) is a devastating disease with limited therapeutic options available for advanced stages. The objective of this study was to investigate HMG-CoA reductase inhibitors, also known as statins, as potential therapeutics for CC-RCC. Importantly, treatment with statins was found to be synthetically lethal with the loss of the von Hippel-Lindau (VHL) tumor suppressor gene, which occurs in 90% of CC-RCC driving the disease. This effect has been confirmed in three different CC-RCC cell lines with three different lipophilic statins. Inhibition of mevalonate synthesis by statins causes a profound cytostatic effect at nanomolar concentrations and becomes cytotoxic at low micromolar concentrations in VHL-deficient CC-RCC. The synthetic lethal effect can be fully rescued by both mevalonate and geranylgeranylpyrophosphate, but not by squalene, indicating that the effect is due to disruption of small GTPase isoprenylation and not the inhibition of cholesterol synthesis. Inhibition of Rho and Rho kinase (ROCK) signaling contributes to the synthetic lethality effect, and overactivation of hypoxia-inducible factor signaling resulting from VHL loss is required. Finally, statin treatment is able to inhibit both tumor initiation and progression of subcutaneous 786-OT1-based CC-RCC tumors in mice. Thus, statins represent potential therapeutics for the treatment of VHL-deficient CC-RCC. Mol Cancer Ther; 17(8); 1781-92. ©2018 AACR.

Race and Alopecia Areata amongst US Women.

Few studies have examined the clinical epidemiology of alopecia areata (AA) in regard to patient race, and therefore, any disparities in incidence or prevalence of disease are largely unexplored. We sought to investigate potential racial disparities amongst two large cohorts of women. We conducted a cross-sectional analysis from the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII), wherein participants self-reported a diagnosis of AA. We determined odds ratios for AA by race in a multivariate analysis. Among 63,960 women from NHS and 88,368 women from NHSII with information on race and diagnosis of AA, we identified 418 and 738 cases of AA, respectively. In NHS, the multivariate-adjusted odds ratio for AA was 2.72 (95% confidence interval 1.61-4.61) amongst black women as compared with white women. In NHSII, the multivariate-adjusted odds ratio was 5.48 (95% confidence interval 4.10-7.32) amongst black as compared with white women. In a secondary analysis designating participants by Hispanic ethnicity, in NHSII the multivariate odds ratio was 1.94 (95% CI 1.24-3.02) in Hispanic compared with non-Hispanic white women. In this study, we found increased odds of AA based on self-reported race in black and Hispanic women as compared with white women. Further studies are needed to explore the mechanism of this racial disparity related to AA.

The Role of Micronutrients in Alopecia Areata: A Review.

Alopecia areata (AA) is a common, non-scarring form of hair loss caused by immune-mediated attack of the hair follicle. As with other immune-mediated diseases, a complex interplay between environment and genetics is thought to lead to the development of AA. Deficiency of micronutrients such as vitamins and minerals may represent a modifiable risk factor associated with development of AA. Given the role of these micronutrients in normal hair follicle development and in immune cell function, a growing number of investigations have sought to determine whether serum levels of these nutrients might differ in AA patients, and whether supplementation of these nutrients might represent a therapeutic option for AA. While current treatment often relies on invasive steroid injections or immunomodulating agents with potentially harmful side effects, therapy by micronutrient supplementation, whether as a primary modality or as adjunctive treatment, could offer a promising low-risk alternative. However, our review highlights a need for further research in this area, given that the current body of literature largely consists of small case-control studies and case reports, which preclude any definite conclusions for a role of micronutrients in AA. In this comprehensive review of the current literature, we found that serum vitamin D, zinc, and folate levels tend to be lower in patients with AA as compared to controls. Evidence is conflicting or insufficient to suggest differences in levels of iron, vitamin B12, copper, magnesium, or selenium. A small number of studies suggest that vitamin A levels may modify the disease. Though understanding of the role for micronutrients in AA is growing, definitive clinical recommendations such as routine serum level testing or therapeutic supplementation call for additional studies in larger populations and with a prospective design.

Estimated serum vitamin D status, vitamin D intake, and risk of incident alopecia areata among US women.

Studies have identified increased prevalence of vitamin D deficiency in patients with alopecia areata (AA), an autoimmune disease characterized by hair loss, but none have prospectively examined vitamin D status and incident AA. In 55,929 women in the Nurses' Health Study (NHS), we prospectively evaluated the association between estimated vitamin D status, derived from a prediction model incorporating lifestyle determinants of serum vitamin D, and self-reported incident AA. We evaluated dietary, supplemental, and total vitamin D intake as additional exposures. Using Cox proportional hazards models, we calculated age-adjusted and multivariate hazard ratios (HR) to evaluate risk of AA. We identified 133 cases of AA over a follow-up of 12 years. The age-adjusted HR between top vs. bottom quartiles for serum vitamin D score was 0.94 (95 % CI 0.60-1.48) and the corresponding multivariate HR was 1.08 (95 % CI 0.68-1.73). There was no significant association between dietary, supplemental, or total vitamin D intake and incident AA. This study does not support a preventive role for vitamin D in the risk of developing AA.

Comprehensive Assessment of the Psoriasis Patient (CAPP): A Report from the GRAPPA 2015 Annual Meeting.

Outcome measures for psoriasis severity are complex because of the heterogeneous presentation of the disease. At the 2015 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), members introduced the Comprehensive Assessment of the Psoriasis Patient (CAPP), a novel disease severity measure to more accurately assess the full burden of plaque psoriasis and subtypes, including inverse, scalp, nail, palmoplantar, and genital psoriasis. The CAPP is based on a 5-point physician's global assessment for 7 psoriasis phenotypes and incorporates visual analog scale-based, patient-derived, patient-reported outcomes. By quantifying disease effects of plaque psoriasis, 6 other psoriasis subtypes, as well as quality of life and daily function, the CAPP survey identifies a subset of psoriasis patients with moderate to severe psoriasis that would not be considered moderate to severe when assessed by the Psoriasis Area and Severity Index. The current version of CAPP is focused entirely on psoriasis. Feedback from our industry colleagues and collaborators has suggested that a psoriatic arthritis (PsA) measure may be important to include in the CAPP. At the 2015 GRAPPA meeting, we administered a survey to 106 GRAPPA members to determine whether a PsA measure should be included. A majority (74%) of respondents across all professions agreed that the CAPP should include a measure of PsA. Although responses varied widely on how PsA should be measured, a majority of the respondents reported that presence of PsA in both peripheral and axial joint assessment was important.

Rhizobium radiobacter: A Recently Recognized Cause of Bacterial Keratitis.

PURPOSE: To present the first reported cases of keratitis caused by Rhizobium radiobacter. METHODS: A retrospective review of an observational case series from 2 institutions. RESULTS: There were 4 cases of microbiologically proven R. radiobacter. Three of these patients were contact lens wearers. The patient in case 4 defaulted from follow-up after receipt of the culture result. Keratitis in the other cases resolved with variable clinical courses once culture-directed therapy was instituted. CONCLUSIONS: R. radiobacter is a member of the genus Rhizobium. It is a gram-negative bacillus and was previously identified as an opportunistic pathogen in nonophthalmic infections and in a few cases of endophthalmitis. To our knowledge, we have described the clinical presentation, management, and treatment outcomes of the first reported cases of keratitis caused by R. radiobacter.

Approaches to identifying synthetic lethal interactions in cancer.

Targeting synthetic lethal interactions is a promising new therapeutic approach to exploit specific changes that occur within cancer cells. Multiple approaches to investigate these interactions have been developed and successfully implemented, including chemical, siRNA, shRNA, and CRISPR library screens. Genome-wide computational approaches, such as DAISY, also have been successful in predicting synthetic lethal interactions from both cancer cell lines and patient samples. Each approach has its advantages and disadvantages that need to be considered depending on the cancer type and its molecular alterations. This review discusses these approaches and examines case studies that highlight their use.

Balloon cell nevi of the conjunctiva: Clinicopathologic correlation and literature review.

Balloon cell nevi are rare, benign melanocytic tumors that may involve the conjunctiva, choroid, and skin. In the ocular adnexa they typically present as raised and mobile hyperpigmented masses. Histologically, balloon cell nevi consist of large cells forming nests that usually lack melanin pigment. The balloon cells have a clear or vacuolated cytoplasm with centrally located nuclei. The vacuolated cytoplasm may be the result of defective melanin synthesis, with the accumulation of melanin precursors in premelanosomes. Balloon cells can resemble xanthoma cells, adipocytes, macrophages, sebaceous adenomas, melanoma with balloon cell changes, and metastatic renal cell carcinoma. Differentiating between these various entities via morphology and immunohistochemistry thus remains clinically significant. We report three cases of conjunctival balloon cell nevi and review the literature.