Continued Diabetes Remission Despite Weight Recurrence: Gastric Bypass Long-Term Metabolic Benefit.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) demonstrates high rates of type 2 diabetes mellitus (T2DM) remission, a phenomenon hypothesized to be mediated mainly by weight loss. Compared with procedures that do not bypass the proximal small intestines, such as sleeve gastrectomy (SG), RYGB exhibits weight loss-independent intestinal mechanisms conducive to T2DM remission. We investigated continued diabetes remission (CDR) rates despite weight recurrence (WR) after RYGB compared with an SG cohort. STUDY DESIGN: A retrospective review of patients who underwent successful primary RYGB or SG with a BMI value of 35 kg/m 2 or more and a preoperative diagnosis of T2DM was performed. Patients with less than 5 years of follow-up, absence of WR, or lack of T2DM remission at nadir weight were excluded. After selecting the optimal procedure for glycemic control, rates of CDR were then stratified into WR quartiles and compared. RESULTS: A total of 224 RYGB and 46 SG patients were analyzed. The overall rate of CDR was significantly higher in the RYGB group (75%) compared with the SG group (34.8%; p < 0.001). The odds of T2DM recurrence were 5.5 times higher after SG compared with RYGB. Rates of CDR were stratified into WR quartiles (85.5%, <25%; 81.7%, 25% to 44.9%; 63.2%, 45% to 74.9%; and 60%, >75%). Baseline insulin use, higher preoperative glycosylated hemoglobin, and longer preoperative duration of T2DM were associated with T2DM recurrence, whereas WR was not. CONCLUSIONS: T2DM remission rates after RYGB are maintained despite WR, arguing for a concurrent weight loss-independent metabolic benefit likely facilitated by bypassing the proximal small intestine.

MBSAQIP database: are the data reliable?

BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database collects data from all accredited centers in the US. A prior study showed data quality issues limiting use of up to 20% of the 2015 database. OBJECTIVES: To evaluate the completeness and data quality (internal validity, accuracy, and consistency) of the MBSAQIP database between 2015 and 2019. SETTING: United States. METHODS: All subsets of data from the MBSAQIP Participant User Data File (PUDF) were compiled into one main file. Completeness, internal validity, accuracy, and consistency were evaluated. Completeness was determined via missing values. Internal validity was assessed using the percentage of patients with a body mass index (BMI) < 30 kg/m2 who underwent primary bariatric surgery. Accuracy was evaluated using reported versus calculated BMI. Consistency was assessed using the percentage of patients with a gain of >5 or a loss of >20 units of BMI change in 30 days. Effects across years were assessed using a chi-squared test. RESULTS: Missing data for age, BMI, and ASA was consistently low (<2.5%) with no significant difference across years. Only .02% of patients who underwent a primary bariatric procedure had a reported BMI <30 kg/m2. The mean difference between reported versus calculated BMI was -.02 units. A maximum of .33% of patients gained >5 units of BMI, and a maximum of .85% of patients lost > 20 units of BMI in early follow-up. CONCLUSIONS: While the MBSAQIP is a database with acceptable data quality and minimal changes from 2015-2019, ongoing efforts are needed to improve data.

Primary hyperparathyroidism in patients with multiple endocrine neoplasia type 1: Impact of genotype and surgical approach on long-term postoperative outcomes.

BACKGROUND: Protein-truncating germline pathogenic variants in the N- and C-terminal exons (2, 9, and 10) of the MEN1 gene may be associated with aggressive pancreatic neuroendocrine tumors. However, the impact of these variants on parathyroid disease is poorly understood. We sought to investigate the effects of genotype and surgical approach on clinical phenotype and postoperative outcomes in patients with multiple endocrine neoplasia type 1 (MEN1)-related primary hyperparathyroidism. METHODS: We identified patients with MEN1 evaluated at our institution from 1985 to 2020 and stratified them by genotype, (truncating variants in exons 2, 9, or 10, or other variants), and index surgical approach, (less-than-subtotal parathyroidectomy [

Type 2 diabetes remission after Roux-en-Y gastric bypass: a multicentered experience with long-term follow-up.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is associated with short- and mid-term type 2 diabetes (T2D) remission. Long-term outcomes and predictive parameters associated with remission following RYGB have not been well elucidated. OBJECTIVE: Determining the overall long-term T2D remission rates following RYGB and identifying predictive variables associated with remission. SETTING: Multicentered study including patients who underwent RYGB at 3 tertiary referral centers for bariatric surgery. METHODS: We performed a retrospective cohort study between 2008-2017 to allow a minimum of 5 years of follow-up. We evaluated long-term T2D remission rates and annual T2D clinical and metabolic parameters up to 14 years after surgery. Predictors of remission were assessed using multivariate logistic regression. Patients were divided into 4 groups based on quartiles of total body weight loss percentage (%TBWL) to compare remission rates between groups. RESULTS: A total of 815 patients were included (68.9% female, age 52.1 ± 11.5 yr; body mass index 45.1 ± 7.7 kg/m2) with a follow-up of 7.3 ± 3.8 years. Remission was demonstrated in 51% of patients. Predictors of remission included pre-operative duration of diabetes, baseline HbA1C, insulin use prior to surgery, number of antidiabetic medications and %TBWL (all P < .01). Remission rates were proportionally associated with %TBWL quartile (Q1, 40.9%; Q2, 52.7%; Q3, 53.1%; Q4, 56.1%) (P = .02). CONCLUSIONS: Longer duration and higher severity of T2D were negatively associated with remission while higher %TBWL had a positive association. A significant proportion of patients in all quartiles experienced long-term remission after RYGB with a greater likelihood of remission correlated with greater weight loss.

Selective Deep Lobe Parotidectomy vs Total Parotidectomy for Patients With Benign Deep Lobe Parotid Tumors.

Importance: Limited literature exists on surgical outcomes after selective deep lobe parotidectomy (SDLP) with preservation of superficial lobe for patients with benign deep lobe tumors. Objective: To compare the following factors for SDLP vs total parotidectomy for patients with benign tumors in the deep lobe: postoperative complications, including facial nerve paresis or paralysis, Frey syndrome, first bite syndrome, cosmetic defect, sialocele formation, and wound infection; and tumor control and recurrence. Design, Setting, and Participants: This case series included 273 adults who underwent SDLP (n = 177) or total parotidectomy (n = 96) at a single tertiary care institution for benign parotid tumors located in the deep lobe or deep lobe and parapharynx from January 1, 2000, to December 31, 2020. Exposure: Selective deep lobe parotidectomy vs total parotidectomy. Main Outcomes and Measures: Incidence of postoperative complications and tumor recurrence. Results: Among 273 patients (SDLP, 177 [65%]; 122 women [69%]; median age at surgery, 58 years [IQR, 46-67 years]; total parotidectomy, 96 [35%]; 57 women [59%]; median age at surgery, 59 years [IQR, 40-68 years]), the most common tumor was pleomorphic adenoma (SDLP, 128 of 177 [72%]; total parotidectomy, 62 of 96 [65%]). An abdominal dermal fat graft was less commonly performed for patients who underwent SDLP than those who underwent total parotidectomy (2 of 177 [1%] vs 20 of 96 [21%]; difference, -20% [95% CI, -28% to -11%]). The rate of great auricular nerve preservation was higher in the SDLP group than in the total parotidectomy group (84 of 102 [82%] vs 20 of 34 [59%]; difference, 24% [95% CI, 5%-42%]). No meaningful difference in length of hospital stay was found. The percentage of patients with House-Brackmann grade I immediately after surgery was 48% (85 of 177) in the SDLP group and 21% (20 of 96) in the total parotidectomy group (difference, 28% [95% CI, 16%-40%]). There were no clinically meaningful differences in rates of hematoma, sialocele, seroma, ear numbness, wound infection, or unplanned return to emergency department or operating room. The SDLP group reported a lower rate of Frey syndrome than the total parotidectomy group (1 of 137 [1%] vs 12 of 78 [15%]; difference, -15% [95% CI, -23% to -7%]), as well as a lower rate of facial contour defect (28 of 162 [17%] vs 25 of 84 [30%]; difference, -13% [95% CI, -24% to -1%]) and a higher rate of first bite syndrome (34 of 148 [23%] vs 7 of 78 [9%]; difference, 14% [95% CI, 5%-23%]). The percentage of patients with House-Brackmann grade I at their first follow-up visit was 67% (118 of 177) in the SDLP group compared with 49% (47 of 96) in the total parotidectomy group (difference, 17% [95% CI, 4%-30%]). There was no clinically meaningful difference in House-Brackmann grade after 1 year. Conclusions and Relevance: Findings of this case series study suggest that SDLP can be considered an effective and even superior technique for management of benign tumors in the deep parotid lobe. Advantages associated with SDLP include reduction in need for reconstruction for facial contour defect and reduction in complications, such as immediate facial nerve weakness and Frey syndrome. The incidence of first bite syndrome was higher in the SDLP group. Tumor control was not compromised by SLDP.

Singing Voice Concern in Tertiary Laryngology Practice.

OBJECTIVES: To determine the prevalence and characteristics of patients who identify singing voice as a primary concern when presenting with general voice complaints to a voice clinic. METHODS: Data were collected from medical records on demographics, medical history, laryngoscopy exam, diagnosis, and subsequent treatments; and from self-report questionnaires including the Voice Handicap Index-10 (VHI-10) and clinical voice questionnaire. RESULTS: A total of 17% of patients presenting to a voice clinic with general voice problems who completed a VHI-10 identified singing voice as a primary concern. Compared to the reference cohort, patients concerned about singing voice report greater handicap on several questions of the VHI-10, particularly in personal and social life impact, loss of income, unpredictability of vocal clarity, subjective upset, and subjective handicap. Those concerned with singing voice were also more concerned about their vocal problem, and both more likely to be recommended voice therapy and participate in voice therapy despite no statistical differences in categorical diagnoses. CONCLUSIONS: When considering both professional and recreational singers, voice concerns occurred in 17% of the cohort under study. Patients with singing voice concerns are accounted for largely by recreational singers, who remain poorly characterized in the literature. We underscore the importance of sensitivity and responsivity to the needs of this group of patients.

Diagnostic Delay in Human Papillomavirus Negative Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Failure to recognize symptoms of non-human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV(-)OPSCC) at presentation can delay diagnosis and treatment. We aim to identify patient factors and provider practice patterns that delay presentation and care in HPV(-)OPSCC. METHODS: Retrospective review at a tertiary care center. Patients with HPV(-)OPSCC receiving treatment from 2006 to 2016. Patients were excluded if their date of symptom onset or diagnosis was unknown after thorough review of the electronic medical record or their tissue was not tested for HPV or p16. Clinical data, workup, and care timelines were abstracted. Univariate and multivariable linear regressions were performed to determine associations between patient and provider factors and delays in care. RESULTS: Of 70 included patients, 52 (74%) were male and mean age was 60.5 (SD = 9.0). Median time to diagnosis was 69 days (IQR = 32-127 days), with a median latency of 30 days (IQR = 12-61 days) from symptom onset to first presentation and 19.5 days (IQR = 4-46 days) from the first presentation to diagnosis. Most patients visited at least 2 providers (n = 52, 74%) before diagnosis. Evaluation by 3 or more providers prior to diagnosis was associated with significant delays in diagnosis of nearly a year (357.7 days, p < 0.001) and being treated or prescribed analgesia prior to diagnosis was significantly associated with delays in diagnosis (p = 0.004) on univariate regression analysis. CONCLUSIONS: Delays in care related to evaluations by multiple providers and misdiagnosis prolonged time to diagnosis in HPV(-)OPSCC. Improved patient and provider education is necessary to expedite the diagnosis of HPV(-)OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1394-1401, 2023.

Feasibility of At-Home Virological and Serological Testing for SARS-CoV-2 in Children.

Longitudinal virological and serological surveillance is essential for understanding severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) transmission among children but requires increased test capacity. We assessed the uptake of serial at-home testing in children (2-17 years) via mailed SARS-CoV-2 antibody and molecular tests. Completion rates demonstrated the feasibility and sustainability of at-home testing across age groups.

From crisis to opportunity in a big data study: barriers and facilitators in a national web-based COVID-19 surveillance study.

Context: In March 2020 a COVID-19 Community Research Partnership (CRP) surveillance study was launched. We describe the barriers and facilitators to recruitment and retention during enrollment of >12,000 participants. Objective: To describe the barriers and facilitators to recruitment and retention while collecting daily syndromic and serologic data in a virtual setting. Methods: Key communication strategies designed to proactively enhance participation and retention were: Set up of a study call center; FAQs were emailed to participants and placed on the study webpage; preemptive messaging for getting started after enrollment, updating addresses, and in-home testing were designed; Later setup of a central call center for National team; design and implementation of national messaging for large scale in-home serological testing. Setting and Participants: Healthcare System linked to Six other National study sites. Healthcare system employees and patients, North Carolina residents and bordering counties. Atrium enrolled >12,000 participants, with over 65,000 participants enrolled nationally. Results: Key barriers: missing email communications, incorrectly entered participant information, participant fatigue due to longevity of study, use and return of serology kits. Facilitators: developing appropriate tailored messaging, preemptive communication for pending and failed validations, and development of "Unsubscribe" or "Paused" statuses. Proactive strategies kept the "Pending" enrollment below 10% and "Failed Validation" below 1% of total enrollees. The "Unsubscribe" option allowed withdraw rates to stay below 1% while the unsubscribe rate stayed below 10%. Tailored messaging supported the return of ~79% of test kits with ~43% of missing kits recovered. Conclusions: Large participant enrollment and data accrual resulted in the need for creative approaches to trouble shooting "big data" challenges associated with the rapid start-up of a high enrolling COVID -19 surveillance study. Preemptive messaging and anticipating participants' needs enhanced enrollment, participation and retention.

Venous thromboembolism incidence and risk factors in non-small cell lung cancer patients receiving first-line systemic therapy.

BACKGROUND: There are limited data on venous thromboembolism (VTE) incidence and predictive factors in non-small cell lung cancer (NSCLC) across first-line therapies. OBJECTIVE: To evaluate VTE incidence rates and identify predictive factors in NSCLC patients receiving first-line systemic therapies, including immune checkpoint inhibitors (ICIs). PATIENTS/METHODS: This is a single institution retrospective study of adult NSCLC patients who received first-line treatment, including chemotherapy, ICIs (pembrolizumab, nivolumab, atezolizumab, avelumab, and durvalumab), and/or targeted therapies (TTs) (erlotinib, gefitinib, afatinib, osimertinib, crizotinib, alectinib, ceritinib). Risk factors included Khorana score, cancer stage, central venous catheter, pacemaker, comorbidities, and prior VTE. The primary objective - cumulative incidence of VTE at 6- and 12-months by treatment group - was compared using Gray's test. Univariable and multivariable competing risk analyses were used to identify predictors. RESULTS: Of 1587 evaluable patients, 53% were male, 79% white, 18% black, median age was 66; 58% had adenocarcinoma, 32% squamous cell carcinoma, and 47% metastatic disease; 1043 received chemotherapy, 171 ICIs, 157 chemotherapy plus concomitant ICI, 107 chemotherapy and durvalumab maintenance, and 109 TTs. The 6-month cumulative incidence of VTE by treatment type was 5.0%, 7.6%, 9.9%, 9.4%, and 11.1%; 12-month incidence was 6.5%, 9.0%, 12.8%, 12.2%, and 13.1% per arm, respectively (p = 0.01). Treatment type (p = 0.034) and nicotine dependence (p = 0.048) were significantly associated with time to VTE in multivariable analyses. CONCLUSION: Treatment type and smoking status were predictive of time to VTE in NSCLC patients receiving various first-line therapies. Cumulative incidence was highest in those receiving TTs and combination chemotherapy plus ICI.

A State Census of Unsubmitted Sexual Assault Kits: Comparing Forensic DNA Testing Outcomes by Geographic and Population Density Characteristics.

A growing number of U.S. cities and states have large numbers of unsubmitted sexual assault kits (SAKs) in police property facilities. Prior research conducted in large urban cities has found that testing these kits yields a sizable number of DNA profiles that meet FBI eligibility for upload to the national criminal DNA database CODIS (Combined DNA Index System) and uploaded profiles return a substantial number of matches to existing criminal profiles in CODIS. It is unknown whether these findings are unique to large urban cities with high crime rates. The purpose of current study was to document forensic testing outcomes from a state census of previously unsubmitted SAKs, which included large urban-suburban centers, as well as smaller cities and rural counties. We inventoried all previously unsubmitted SAKs in Michigan (N = 3422 SAKs) and submitted all kits for forensic DNA testing. A total of n = 1239 SAKs had a DNA profile that met eligibility for upload into CODIS (36.2% unconditional, 56.5% conditional CODIS eligible rate) and n = 585 SAKs yielded a CODIS Hit (17.1% unconditional, 47.2% conditional CODIS hit rate). These rates are consistent with studies from urban areas suggesting approximately half of SAKs tested yield a CODIS profile and approximately half of those uploaded profiles yield a hit. We compared SAK forensic testing outcomes by geographic and population density characteristics, and although rates were often higher in larger metropolitan areas, the obtained rates in micropolitan and rural areas suggest testing is warranted in smaller jurisdictions as well.

Acute Myocardial Infarction in Patients with Paraplegia: Characteristics, Management, and Outcomes.

BACKGROUND: Cardiovascular disease has become a leading cause of death for patients with paraplegia. Acute myocardial infarction in patients with paraplegia has not been described in the literature. This study investigates clinical features, management strategies, and outcomes of these patients. METHODS: Acute myocardial infarction in patients with or without paraplegia was identified in the New York State Inpatient Database between 2007 and 2013. Clinical comorbidities, management strategies and their associated outcomes were compared using propensity score-matching analysis. RESULTS: Among 402,569 patients with acute myocardial infarction, 1400 had a concomitant diagnosis of paraplegia. Compared with those without, patients with paraplegia were younger, more likely to be black, and had a higher prevalence of hypertension, anemia, congestive heart failure, coagulopathy, and depression, but a lower prevalence of diabetes, hyperlipidemia, obesity, chronic lung disease, and renal failure. Patients with paraplegia were more likely to receive medical therapy without a diagnostic cardiac catheterization than those without (83.7% vs 64.5%, P < .001). Nine percent of patients with paraplegia received revascularization, which was significantly lower than that without paraplegia. In terms of the clinical outcome, patients with paraplegia had higher in-hospital mortality than those without (22.4% vs 16.8%, P < .001). Among the patients with paraplegia, the subcohort that received revascularization had lower in-hospital mortality (9.5% vs 22.0%, P < .01), had shorter length of stay (13.0 vs 16.9 days, P =.08), and higher hospital charges ($130,079 vs $92,125, P < .001) than those without revascularization. Furthermore, the paraplegic subcohort underwent coronary artery bypass grafting that was associated with higher in-hospital mortality (21.7% vs 1.7%, P < .001), longer length of stay (24.8 vs 14.2 days, P < .001), and higher hospital charges ($231,323 vs $144,449, P < .01) than subcohort that received percutaneous coronary intervention. CONCLUSIONS: Acute myocardial infarction patients with concomitant paraplegia had distinct clinical characteristics and comorbidity profiles; were less likely to receive revascularization therapy; and had higher in-hospital mortality. Acute myocardial infarction patient with paraplegia who underwent revascularization were associated with better clinical outcomes, in particular, those who were treated with percutaneous coronary intervention had significantly lower in-hospital mortality than those treated with coronary artery bypass grafting.

Kaiso directs the transcriptional corepressor MTG16 to the Kaiso binding site in target promoters.

Myeloid translocation genes (MTGs) are transcriptional corepressors originally identified in acute myelogenous leukemia that have recently been linked to epithelial malignancy with non-synonymous mutations identified in both MTG8 and MTG16 in colon, breast, and lung carcinoma in addition to functioning as negative regulators of WNT and Notch signaling. A yeast two-hybrid approach was used to discover novel MTG binding partners. This screen identified the Zinc fingers, C2H2 and BTB domain containing (ZBTB) family members ZBTB4 and ZBTB38 as MTG16 interacting proteins. ZBTB4 is downregulated in breast cancer and modulates p53 responses. Because ZBTB33 (Kaiso), like MTG16, modulates Wnt signaling at the level of TCF4, and its deletion suppresses intestinal tumorigenesis in the Apc(Min) mouse, we determined that Kaiso also interacted with MTG16 to modulate transcription. The zinc finger domains of Kaiso as well as ZBTB4 and ZBTB38 bound MTG16 and the association with Kaiso was confirmed using co-immunoprecipitation. MTG family members were required to efficiently repress both a heterologous reporter construct containing Kaiso binding sites (4×KBS) and the known Kaiso target, Matrix metalloproteinase-7 (MMP-7/Matrilysin). Moreover, chromatin immunoprecipitation studies placed MTG16 in a complex occupying the Kaiso binding site on the MMP-7 promoter. The presence of MTG16 in this complex, and its contributions to transcriptional repression both required Kaiso binding to its binding site on DNA, establishing MTG16-Kaiso binding as functionally relevant in Kaiso-dependent transcriptional repression. Examination of a large multi-stage CRC expression array dataset revealed patterns of Kaiso, MTG16, and MMP-7 expression supporting the hypothesis that loss of either Kaiso or MTG16 can de-regulate a target promoter such as that of MMP-7. These findings provide new insights into the mechanisms of transcriptional control by ZBTB family members and broaden the scope of co-repressor functions for the MTG family, suggesting coordinate regulation of transcription by Kaiso/MTG complexes in cancer.