Publications

The purpose of this study was to estimate the prevalence of occupational noise exposure and risk factors of occupational noise-induced hearing loss (NIHL) in Hispanic/Latino adults included in the baseline wave of the Hispanic Community Health Study/Study of Latinos collected from 2008 to 2011. Sequential multiple linear regression modeled the relationship between occupational NIHL (defined as a 3-, 4-, 6-kHz pure-tone average [PTA]) and occupation type, self-reported noise exposure, cardiovascular disease (CVD) risk score, and hearing protective device (HPD) use. The final model controlled for sex, age, and recreational noise exposure. Among 12,851 included participants, approximately 40% (n = 5036) reported occupational noise exposure "Sometimes" (up to 50% of the time) or "Frequently" (75-100% of the time). In the final fitted model, longest-held occupation and CVD risk were associated with poorer hearing. Specifically, those in non-skilled, service, skilled, and military/police/other job categories had between 2.07- and 3.29-dB worse PTA than professional/office workers. Additionally, a shift in the CVD risk score category from low to medium was associated with a 2.25- and 8.20-dB worse PTA for medium and high CVD risk, respectively. Age and sex were also significantly associated with poorer hearing, such that men presented with 6.08 dB worse PTA than women, and for every one-year increase in age, PTA increased by 0.62 dB (ps < .001). No interactions were seen between noise*sometimes or frequent exposure to other ototoxic agents and PTA (ps = .33 & .92, respectively). The prevalence of occupational noise exposure was high in this cross-sectional investigation of adults from Hispanic/Latino backgrounds. Findings contribute to the extant literature by demonstrating that risk factors for occupational NIHL in adults from varying Hispanic/Latino backgrounds are consistent with those of other previously studied groups.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts and assess the risk of AD and survival among >30 million de-identified subjects with normal oral health (n = 31,418,814) and poor oral health (n = 1,232,751). There was a greater than two-fold increase in AD risk in the poor oral health cohort compared to the normal oral health group (risk ratio (RR): 2.363, (95% confidence interval: 2.326, 2.401)). To reduce potential bias, we performed retrospective propensity score matching for age, gender, and multiple laboratory measures. After matching, the cohorts had no significant differences in survival probability. Furthermore, when comparing multiple oral conditions, diseases related to tooth loss were the most significant risk factor for AD (RR: 3.186, (95% CI: 3.007, 3.376)). Our results suggest that oral health may be important in AD risk, regardless of age, gender, or laboratory measures. However, more large-scale cohort studies are necessary to validate these findings and further evaluate links between oral health and AD.

Background  Timely performed Neurointervention procedures in patients with neurovascular disorders save them from mortality and lifelong morbidity, in addition to relieving the immense economic and social burden associated with these diseases. Materials and Methods  We retrospectively reviewed data of neurointerventions performed in our hospital from November 2019 till March 2021. Patient age, sex, diagnosis, preoperative, and postoperative imaging findings were collected and analyzed. Types of procedures, success/failure, procedure-related and procedure-unrelated complications were noted and described. Results  Total 161 procedures were done (diagnostic n = 89, therapeutic n = 72). Among the 72 cases of therapeutic procedures, angiographic success was noted in 60 cases, partial success was noted in 5 cases (RR grade 3 occlusion) and failure was noted in 7 cases [mechanical thrombectomy (n = 2), coiling (n = 1), flow diverter (n = 1), Caroticocavernous fistula (n = 1), cerebral Arteriovenous malformation (n = 2)]. Among therapeutic cases (n = 72), patient outcome was categorized as improved (with mRS 0-2 at discharge) in 64 cases (60 neurointerventions, 4 converted to surgery), morbidity in form of weakness was noted in 2 cases, mortality was noted in 8 cases. There were no hemorrhagic complications due to rupture or dissection. Ischemic complications were noted in form of thromboembolic complications in three cases and vessel occlusion (delayed MCA occlusion) in one case. Conclusion  With recent efforts by medical associations and governments to provide access to these lifesaving, disability averting neuro-interventions, it's important to recognize and define challenges in implementation of neuro-intervention services. In this article, we share our early experience in establishing a neurointervention facility in a backward region of a low-middle income country.

Studying the interactions within protein structures can inform about the details of how proteins of various types interact and aggregate. Empirical contact potentials have proven to be extremely important in the evaluation of individual modeled protein structures, but have found few applications to protein-protein interactions. In part, this is caused by a lack of properly formulated potentials with a proper reference state. Since the comparisons are made between different bound structures, the proper reference state should take into account other contacts. Therefore, a preferred reference state should be defined with respect to a given residue type interacting with an average residue instead of interacting with solvent as typically is used in derivation of statistical contact potentials. Here, a two-stage procedure for generating and evaluating interacting protein pairs is described, and an example of E-cadherin interactions is shown.

Background and study aims  Post-ERCP pancreatitis (PEP) is a common adverse event in high-risk patients. Current intervention known to reduce the incidence and severity of PEP include pancreatic duct stent placement, nonsteroidal anti-inflammatory drugs per rectum, and intravenous (IV) fluids. We compared aggressive normal saline (NS) vs aggressive lactated Ringer's (LR) infusion for the prevention of PEP in high-risk patients undergoing ERCP. Patients and methods  Patients were randomized to receive either an aggressive infusion of NS or LR. The infusion was started at a rate of 3 mL/kg/hr and continued throughout the ERCP procedure. A 20 mL/kg bolus was given at the end of the procedure, then continued at a rate of 3 mL/kg/hr. Results  A total of 136 patients were included in our analysis. The incidence of PEP was 4 % (3/72 patients) in the LR group versus 11 % (7/64 patients) in the NS group resulting in a relative risk (RR) of 0.38 (95 % confidence interval [CI] 0.10 to 1.42; P  = 0.19). The relative risk reduction (RRR) was 0.62 (95 % CI -0.41 to 0.90) along with an absolute risk reduction (ARR) of 0.07 (95 % CI -0.025 to 0.17) and an number needed to treat of 15 (95 % CI -41 to 6). Conclusions  To our knowledge, this is the first study comparing aggressive IV NS to aggressive IV LR in high-risk patients. The incidence of PEP was lower in the group receiving an aggressive LR infusion (4 %) compared to NS infusion (11 %). However, the difference was not statistically significant likely due to poor accrual thereby impacting the power of the study.

Chimeric antigen receptor T-cell therapy (CAR-T) is a major advance in managing aggressive relapsed or refractory B-cell lymphomas; however, relapses are frequent and pose a major therapeutic challenge. There is substantial variability across transplantation and cellular therapy programs in assessing and managing post-CAR-T failures. The American Society for Transplantation and Cellular Therapy Committee on Practice Guidelines conducted an online cross-sectional survey between August 2021 and October 2021 to determine the U.S. lymphoma and transplantation and cellular therapy physicians' practice patterns for the detection and diagnosis of CAR-T failure, as well as management strategies for diffuse large B-cell lymphoma in this particular setting. E-mail surveys were sent to 901 potential participants, of which 174 (19%) completed the survey. Responders were mainly White (51.2%), male (70.7%), and with >10 years of practice experience (51.2%). Overall, 87% of the responders were affiliated with university/teaching centers; 54.6% had general oncology practices, and 45.4% had lymphoma-focused transplantation/cellular therapy practices. The most common periods to perform surveillance scans were at 3 months and 12 months after CAR-T infusion. Overall, 88.5% of responders would often or always consider a biopsy to confirm relapse and 89% would routinely check for the persistence of the antigen targeted by the CAR (e.g., CD19 in the case of CD19 CAR-T). The most popular first salvage regimen for relapse or progression was an alternate CAR-T therapy (dual or alternate target) regardless of CD19 positivity. Twenty-seven percent of responders chose this regimen for CD19 positive relapse, whereas 31% of responders did so for CD19 negative relapse. Overall, 88.5% of responders favored consolidative allogeneic hematopoietic cell transplantation after response to salvage, whereas 51.2% of physicians would consider autologous hematopoietic cell transplantation in transplantation-naïve patients. There is substantial cross-center variation in surveillance, diagnosis, and management of CAR-T failure. Prospective clinical trials evaluating novel agents in this setting are urgently needed to identify best management strategies.

Approximately 15-20% of chronic myeloid leukemia (CML) patients fail tyrosine kinase inhibitor (TKI) therapy secondary to resistance or intolerance. In the pre-TKI era, front-line allogeneic hematopoietic cell transplantation (allo- HCT) represented the standard approach for patients with chronic phase-CML (CP-CML) who were deemed fit to tolerate the procedure and had a human leukocyte antigen compatible donor available. Currently, CP-CML patients are eligible for allo-HCT only if they fail more than one TKI and/or are intolerant to the drug. We performed a systematic review/meta-analysis of the available literature to assess the evidence regarding allo-HCT efficacy in CP-CML patients. Data from eligible studies were extracted in relation to benefits (overall survival [OS], progression-free survival, disease-free survival [DFS], complete remission [CR], and molecular response [MR]) and harms (nonrelapse mortality [NRM], relapse, and acute and chronic graft-versus-host disease), and stratified by age into adult and pediatric groups. For adult allo-HCT recipients, the pooled OS, DFS, CR and, MR were 84% [95% confidence interval (CI) 59-99%], 66% (95% CI 59-73%), 56% (95% CI 30-80%), and 88% (95% CI 62-98%), respectively. Pooled NRM and relapse were 20% (95% CI 15-26%) and 19% (95% CI 10-28%), respectively. For the pediatric group, the OS rate was reported in one study and was 91% (95% CI 72-99%). Our results suggest that allo-HCT is an effective treatment for TKI-resistant or TKI-intolerant CP-CML. Post-transplant strategies are still needed to further mitigate the risk of relapse.

We present a case of a 54-year-old male with spinal epidural lipomatosis who had associated flow voids on magnetic resonance imaging with dilated intrathecal vessels. During spinal angiogram, 20s DynaCT (flat panel catheter angiotomography) was utilized to demonstrate the intrathecal engorged veins. Venous engorgement of epidural venous plexus has been previously described in epidural lipomatosis; however, dilated intrathecal perimedullary veins have not been demonstrated by imaging. We have described the utility of flat panel catheter angiotomography in understanding venous disorders in such patients.

Although tacrolimus and sirolimus (TAC/SIR) is an accepted graft-versus-host disease (GVHD) prophylaxis regimen following allogeneic hematopoietic cell transplantation (HCT), toxicity from this regimen can lead to premature discontinuation of immunosuppression. There are limited studies reporting outcomes and subsequent treatment of patients with TAC/SIR intolerance. This study was conducted to assess the outcomes of patients with TAC/SIR intolerance and guide their subsequent management. We retrospectively analyzed transplantation outcomes of consecutive adult patients at Moffitt Cancer Center who underwent allogeneic HCT with TAC/SIR as GVHD prophylaxis between 2009 and 2018. TAC/SIR intolerance was defined as discontinuation of either TAC or SIR due to toxicity before post-transplantation day +100. A total of 777 patients met the inclusion criteria. The median duration of follow-up was 22 months (range, 0.2 to 125 months). Intolerance occurred in 13% (n = 104) of the patients at a median of 30 days (range, 5 to 90 days). The most common causes of intolerance were acute kidney injury (n = 53; 51%), thrombotic microangiopathy (n = 31; 28%), and veno-occlusive disease (n = 23; 22%). The cumulative incidence of grade II-IV acute GVHD at 100 days was 50% (95% CI, 39% to 64%) in the TAC/SIR-intolerant patients and 25% (95% CI, 22% to 29%) in patients tolerant to this regimen (P < .0001). In multivariate analyses, the incidence of grade II-IV 4 acute GVHD was significantly higher in the TAC/SIR-intolerant patients (hazard ratio [HR], 2.40; 95% CI, 1.59 to 3.61; P < .0001). Similarly, in multivariate analyses, the TAC/SIR-intolerant patients had a higher incidence of chronic GVHD (HR, 1.48; 95% CI, 1.03 to 2.12; P = .03). The nonrelapse mortality (NRM) at 1 year was 47% (95% CI, 38% to 59%) in the TAC/SIR-intolerant patients and 12% (95% CI, 10% to 15%) in those tolerant to the regimen (P < .0001). The 2-year relapse-free survival was 35% (95% CI, 25% to 44%) in the TAC/SIR-intolerant patients and 60% (95% CI, 57% to 65%) in the TAC/SIR-tolerant patients (HR, 2.30; 95% CI, 1.61 to 3.28; P < .0001). Intolerance stratified by early (≤30 days) versus late (31 to 100 days) significantly affected the cumulative incidence of acute GVHD at 75% (early; 95% CI, 59% to 94%) versus 33% (late; 95% CI, 21% to 50%) (P = .001), as well as the cumulative incidence of NRM at 61% (early; 95% CI, 48% to 77%) versus 35% (late; 95% CI, 24% to 51%) (P = .006). Most patients who developed TAC/SIR intolerance were switched to an alternative 2-drug regimen (71 of 104; 68%), most commonly mycophenolate mofetil in addition to continuing TAC or SIR (68 of 71; 96%). Overall, TAC/SIR intolerance was associated with poorer outcomes. Early intolerance contributed to a higher risk of acute GVHD, increased NRM, and inferior survival. Patients with early intolerance were often switched to an alternative agent, and patients with late intolerance tended to be continued on single-drug therapy without substitution. The use of single-drug versus 2-drug regimens after intolerance did not appear to affect outcomes. Management strategies to mitigate the risks of intolerance are warranted.

INTRODUCTION: Women make up 15% of the total number of practicing gastroenterology (GI) physicians in the US. Despite this disparity, only 33% of the current GI fellows are female. Increasing female GIs is a major goal of all four GI societies. It is known that gender disparity exists in the field of gastroenterology, and women are underrepresented in the leadership ranks and trainee level at academic programs. Whether an increase in female leadership in academic medicine is associated with an increase in female program directors and trainees is unknown. The aim of this study was to assess this relationship in GI.

MATERIALS AND METHODS: Data were collected via a standardized protocol from all 173 US gastroenterology fellowship programs up until October 2018 from program websites and supplemented by online surveys completed by program coordinators. Any missing information was collected by calling the program coordinators. Data were collected on gender and academic rank of the program director, associate program director, division chief, chair of medicine, program size, academic center affiliation, number, and academic rank of female faculty and geographic region. The association was assessed using a Chi-square test or independent samples t test.

RESULTS: In leadership positions, men were listed as comprising 86% of chairs, 82% of division chiefs, 76% of program directors and 63% of associate program directors. Forty-three percent of programs did not have female representation at any leadership level. The presence of a female program director or female associate program director was associated with an increase in the number of female fellows (4.03 vs 3.20; p = 0.076; 4.26 vs 3.36; p = 0.041), respectively. Overall, the presence of a female in any leadership position led to an increase in the number of female fellows (4.04 females vs 2.87 females; p = 0.007) enrolled in a program. If a GI division chief was male, the program director was more likely to be male as well (81% male vs. 18.8% female). Conversely, having a female division chief was likely to lead to a more equitable program director representation, 54% female to 48% male (p value < 0.0001, OR 5.03 95% CI 2.04-12.3). Furthermore, if either the internal medicine department chair or GI chief was female, the proportion of female program directors increased to 41% as compared to 19% if both were male (p value < 0.0001, OR 2.99 95% CI 1.34-6.6).

CONCLUSION: Women are significantly underrepresented in the number of practicing gastroenterologists, at all levels of leadership in GI fellowship programs, and at the fellow level. Increasing the number of women in fellowship leadership positions is associated with an increase in female program directors and trainees. Per our knowledge, this is the first study to examine the relationship between female leadership in fellowship programs and the gender of trainees. Increasing female representation in leadership positions would not only address current gender disparity, but it may also increase the number of female future GI trainees.