Kombucha tea as an anti-hyperglycemic agent in humans with diabetes - a randomized controlled pilot investigation.

Introduction: Kombucha is a popular fermented tea that has attracted considerable attention due, in part, to its suggested health benefits. Previous results from animal models led us to hypothesize kombucha may reduce blood sugar levels in humans with diabetes. The objective of this pilot clinical study was to evaluate kombucha for its anti-hyperglycemic activities in adults with diabetes mellitus type II. Methods: The study was organized as a prospective randomized double-blinded crossover study at a single-center urban hospital system. Participants (n = 12) were instructed to consume either a kombucha product or a placebo control (each 240 mL) for 4 weeks. After an 8-week washout period, participants consumed the alternate product. Fasting blood glucose levels were self-determined at baseline and at 1 and 4 weeks during each treatment period. Secondary health outcomes, including overall health, insulin requirement, gut health, skin health, mental health, and vulvovaginal health were measured by questionnaire at the same time points. The kombucha microbiota was assessed by selective culturing and 16S rRNA gene (bacteria) and ITS (fungi) sequencing. Fermentation end products were assessed by HPLC. Statistical significance of changes in fasting blood glucose was determined using paired, two-tailed student's t-tests. Results: Kombucha lowered average fasting blood glucose levels at 4 weeks compared to baseline (164 vs. 116 mg/dL, p = 0.035), whereas the placebo did not (162 vs. 141 mg/dL, p = 0.078). The kombucha microbiota, as assessed by cultural enumeration, was mainly comprised of lactic acid bacteria, acetic acid bacteria, and yeast, with each group present at about 106 colony forming units (CFU)/mL. Likewise, 16S rRNA gene sequencing confirmed that lactic acid and acetic acid bacteria were the most abundant bacteria, and ITS sequencing showed Dekkera was the most abundant yeast. The primary fermentation end products were lactic and acetic acids, both less than 1%. Ethanol was present at 1.5%. Discussion: Although this pilot study was limited by a small sample size, kombucha was associated with reduced blood glucose levels in humans with diabetes. Larger follow-up studies are warranted. Clinical trial registration: ClinicalTrials.gov, identifier NCT04107207.

Efficacy of partial spraying of SumiShield, Fludora Fusion and Actellic against wild populations of Anopheles gambiae s.l. in experimental huts in Tiassalé, Côte d'Ivoire.

From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy.

Clinical and Histopathologic Features of 35 Patients Treated for Colorectal Peritoneal Metastases Who Survived 5 Years.

BACKGROUND: Currently, patients with a limited extent of peritoneal metastases from colon and rectal cancer are treated by cytoreductive surgery combined with perioperative chemotherapy performed at experienced centers. OBJECTIVE: To statistically evaluate features that may impact survival of ≥5 years. These data are used in the risk/benefit analyses performed by the multidisciplinary team. DESIGN: This was a retrospective review of a prospective database. SETTINGS: This single-institution study was conducted at an academic center. PATIENTS: All patients who had biopsy-proven colon or rectal peritoneal metastases treated by systemic chemotherapy, complete cytoreductive surgery, and perioperative surgery were included. MAIN OUTCOME MEASURES: The primary outcomes measured were the clinical-, histologic-, and treatment-related features that had an impact on 5-year survival. RESULTS: From 131 patients who had complete cytoreduction, 35 patients (26.7%) were identified as 5-year survivors. The median survival time was 27 months. The median age was 50.5 (range, 25-80) years. By univariant analysis, an absence of lymph node involvement at the time of primary colorectal cancer resection (HR 1.899 [95% CI, 1.064-3.388]; p = 0.03), complete or near-complete response to neoadjuvant chemotherapy (HR 0.251 [95% CI, 0.092-0.684]; p = 0.007), peritoneal cancer index ≤17 (HR 0.509 [95% CI, 0.329-0.788]; p = 0.002), complete visible resection of disease indicated by the completeness of cytoreduction score of 0 (HR 0.412 [95% CI, 0.224-0.756]; p = 0.004), and well-differentiated tumor (HR 0.34 [95% CI, 0.157-0.737]; p = 0.006) were significantly associated with ≥5 years survival. LIMITATIONS: Limitations include its retrospective nature, unmeasured confounders, and data from a single institution. CONCLUSIONS: The tumor biology as revealed by lymph node status and tumor differentiation plus extent of disease as measured by the response to neoadjuvant chemotherapy, peritoneal cancer index, and no visible residual disease indicated a favorable outcome. See Video Abstract at http://links.lww.com/DCR/C62 . CARACTERSTICAS CLNICAS E HISTOPATOLGICAS EN PACIENTES TRATADOS POR METASTASIS PERITONEALES DE ORGEN COLORECTAL Y QUE SOBREVIVIERON AOS: ANTECEDENTES:Actualmente, los pacientes con extensión limitada de metástasis peritoneales de orígen colorectal son tratados mediante cirugía citorreductora asociada con una quimioterapia peri-peratoria realizadas en centros experimentados.OBJETIVO:Estúdio y evaluación estadística de las características que puedan impactar en la sobrevida de los pacientes a 5 años o más. Se utilizaron estos datos en el análisis de riesgo /beneficio realizados por un equipo multidisciplinario.DISEÑO:Revisión retrospectiva de una base de datos prospectiva.AJUSTES:Estudio realizado en una sola institución académica.PACIENTES:Todos aquellos que presentaban metástasis peritoneales de orígen colorectal, comprobadas por biopsia y tratadas con quimioterapia sistémica, cirugía peri-operatoria y citorreductora completas.MEDIDAS DE RESULTADO PRINCIPALES:Las medidads de resultados primarios fueron las características clínicas, histológicas y relacionadas con el tratamiento que tuvieron un impacto en la sobrevida a 5 años.RESULTADOS:De 131 pacientes que tuvieron una cirugía de citorreducción completa, 35 pacientes (26, 7%) fueron identificados como sobrevivientes a 5 años. La mediana de sobrevida fué de 27 meses. Se identificarion 16 varones. La mediana de edad fue de 50, 5 años con un rango de 25 a 80 años. Según análisis univariante, la ausencia de compromiso de los ganglios linfáticos en el momento de la resección del cáncer colorrectal primario (HR 1,899 (1,064, 3,388) p = 0,03), la respuesta completa o casi completa al tratamiento neoadyuvante con quimioterapia (HR 0,251 (0,092, 0,684) p = 0,007), el índice de cáncer peritoneal ≤17 (HR 0,509 (0,329, 0,788) p = 0,002), la resección completa y visible de la enfermedad indicada por la puntuación de citorreducción de 0 (HR 0,412 (0,224), 0,756) p = 0,004) y los tumores bien diferenciados (HR 0,34 (0,157, 0,737) p = 0,006) se asociaron significativamente con 5 o más años de sobrevida.LIMITACIONES:El estudio se encontró limitado por su naturaleza retrospectiva, por la no medida de factores de confusión y por los datos provenientes de una sola institución.CONCLUSIONES:La biología tumoral demostrada según el estado de los ganglios linfáticos y la diferenciación tumoral, agregada a la extensión de la enfermedad medida por la respuesta a la quimioterapia neoadyuvante, el índice de cáncer peritoneal y la ausencia visible de enfermedad residual, demostraron un resultado favorable. Consulte Video Resumen en http://links.lww.com/DCR/C62(Traducción-Dr. Xavier Delgadillo ).

Persistent Disparities in Access to Elective Colorectal Cancer Surgery After Medicaid Expansion Under the Affordable Care Act: A Multistate Evaluation.

BACKGROUND: Despite their higher incidence of colorectal cancer, ethnoracial minority and low-income patients have reduced access to elective colorectal cancer surgery. Although the Affordable Care Act's Medicaid expansion increased screening of colonoscopies, its effect on disparities in elective colorectal cancer surgery remains unknown. OBJECTIVE: This study assessed the effects of Medicaid expansion on elective colorectal cancer surgery rates overall and by race-ethnicity and income. DESIGN: Using the 2012 to 2015 State Inpatient Databases, a retrospective cohort study was conducted. SETTINGS: State Inpatient Databases from 3 expansion states (Maryland, New Jersey, and Kentucky) and 2 nonexpansion states (Florida and North Carolina) were used. PATIENTS: This study examined 22,304 adult patients aged 18 to 64 years who underwent colorectal cancer surgery. MAIN OUTCOME MEASURES: Using interrupted time series analysis, the effect of Medicaid expansion on the odds of elective colorectal cancer surgery was assessed. RESULTS: Elective vs nonelective surgery rates remained unchanged overall (70.2% vs 70.7%, p = 0.63) and in ethnoracial minorities in expansion states (whites from 72.8% to 73.8% pre to post, p = 0.40 and non-white from 64.0% to 63.1% pre to post, p = 0.67). There was an instantaneous increase in odds of elective surgery in expansion vs nonexpansion states at policy implementation (adjusted OR 1.37; 95% CI, 1.05-1.79; p = 0.02), but it subsequently decreased (combined adjusted OR 0.95; 95% CI, 0.92-0.99; p = 0.03). Elective surgery rates were also unchanged among ethnoracial minorities (instantaneous changes in expansion states, combined effect 1.06; pre-trend 1.01 vs post-trend 0.98) and low-income persons in expansion states (pre-trend 1.03 vs post-trend 0.97) (for all, p > 0.1). LIMITATIONS: The study was limited to 5 states. Although patients may have increased access to cancer screening services and surgery after expansion, the State Inpatient Databases only provide information on patients who underwent surgery. CONCLUSIONS: Despite gains in screening, Medicaid expansion was not associated with reductions in known ethnoracial or income-based disparities in elective colorectal cancer surgery rates. Expanding access to colorectal cancer surgery for underserved populations likely requires attention to provider and health system factors contributing to persistent disparities. See Video Abstract at http://links.lww.com/DCR/C217 . DISPARIDADES PERSISTENTES EN EL ACCESO A LA CIRUGA ELECTIVA DEL CNCER COLORRECTAL DESPUS DE LA EXPANSIN DE MEDICAID EN VIRTUD DE LA LEY DEL CUIDADO DE SALUD A BAJO PRECIO UNA EVALUACIN MULTIESTATAL: ANTECEDENTES: A pesar de su mayor incidencia de cáncer colorrectal, los pacientes de minorías etnoraciales y de bajos ingresos tienen un acceso reducido a la cirugía electiva de cáncer colorrectal. Aunque la expansión de Medicaid de la Ley del Cuidado de Salud a Bajo Precio aumentó las colonoscopias de detección, aún se desconoce su efecto sobre las disparidades en la cirugía electiva de cáncer colorrectal.OBJETIVO: Este estudio evaluó los efectos de la expansión de Medicaid en las tasas de cirugía electiva de cáncer colorrectal en general y por raza, etnia e ingresos.DISEÑO: Utilizando las bases de datos estatales de pacientes hospitalizados de 2012-2015, se realizó un estudio de cohorte retrospectivo.CONFIGURACIÓN: Se utilizaron bases de datos estatales de pacientes hospitalizados de tres estados en expansión (Maryland, Nueva Jersey, Kentucky) y dos estados sin expansión (Florida, Carolina del Norte).PACIENTES: Este estudio examinó a 22,304 pacientes adultos de 18 a 64 años que se sometieron a cirugía de cáncer colorrectal.RESULTADO PRINCIPAL: Mediante el análisis de series de tiempo interrumpido, se evaluó el efecto de la expansión de Medicaid en las probabilidades de cirugía electiva de cáncer colorrectal.RESULTADOS: Las tasas de cirugía electiva frente a no electiva permanecieron sin cambios en general (70,2% frente a 70,7%, p = 0,63) y en las minorías etnoraciales en los estados de expansión (blancos del 72,8% al 73,8 % antes y después, p = 0,40 y no blancos del 64,0% al 63,1% pre a post, p = 0,67). Hubo un aumento instantáneo en las probabilidades de cirugía electiva en los estados de expansión frente a los de no expansión en la implementación de la política (OR ajustado 1,37, IC del 95%, 1,05-1,79, p = 0,02), pero disminuyó posteriormente (OR ajustado combinado 0,95, 95% IC, 0,92-0,99, p = 0,03). Las tasas de cirugía electiva también se mantuvieron sin cambios entre las minorías etnoraciales (cambios instantáneos en los estados de expansión, efecto combinado 1,06; antes de la tendencia 1,01 frente a la postendencia 0,98) y las personas de bajos ingresos en los estados de expansión (antes de la tendencia 1,03 frente a la postendencia 0,97; para todos, p > 0,1).LIMITACIONES: El estudio se limitó a cinco estados. Si bien los pacientes pueden tener un mayor acceso a los servicios de detección de cáncer y la expansión posterior a la cirugía, la base de datos de pacientes hospitalizados del estado solo brinda información sobre los pacientes que se sometieron a cirugía.CONCLUSIONES: A pesar de los avances en la detección, la expansión de Medicaid no se asoció con reducciones en las disparidades etnoraciales o basadas en los ingresos conocidas en las tasas de cirugía electiva de cáncer colorrectal. Ampliar el acceso a la cirugía del cáncer colorrectal para las poblaciones desatendidas probablemente requiera atención a los factores del proveedor y del sistema de salud que contribuyen a las disparidades persistentes. Consulte el Video Resumen en http://links.lww.com/DCR/C217 . (Traducción-Dr. Yesenia.Rojas-Khalil ).

Scribes with PGY-1 Residents on Inpatient Medicine Teams: Effect on Time Spent in Meaningful Work.

Background: The high documentation demands and limited time in direct patient care in the first year of internal medicine residency represent concerns for burnout and low job satisfaction in this important year of training. Objective: To assess the effect of scribes on the time PGY-1 residents spent on various work tasks. Methods: Participants were 24 PGY-1 internal medicine residents on two inpatient medicine teams at one site for 6 months (September 2019-February 2020). Residents were assigned a scribe during the first or second 2 weeks of a 4-week rotation and had no scribe for the other 2 weeks. Time study observers documented resident work activities. Residents ranked the meaningfulness of work activities via survey at the end of each 2-week period. Results: Of 24 residents, 18 (75%) completed the survey at both time points. Residents ranked patient care as the most meaningful and EHR work as the least meaningful work activity. EHR work claimed the largest percentage of time, with or without a scribe (mean, 33.2% and 39%, respectively). With a scribe, residents spent significantly less time (-5.8%, P < 0.0001) in EHR work and significantly more time (1.3%, P = 0.0267) in direct patient care and coordinating patient care (3.0%, P < 0.0001). Conclusions: The presence of a scribe with PGY-1 internal medicine residents on inpatient teams resulted in a significantly greater percentage of total work time spent in work they considered most meaningful and a significantly lower percentage of total work time in work they considered least meaningful.

Benefit of Outpatient Musculoskeletal Medicine Experience Early in Physical Medicine and Rehabilitation Residency.

ABSTRACT: Musculoskeletal care for persons with disabilities is an important competency in physical medicine and rehabilitation training. The optimal timing of musculoskeletal medicine rotations in the physical medicine and rehabilitation residency curriculum is unknown. The objective of this study is to determine whether outpatient experience in musculoskeletal medicine increases resident use of musculoskeletal examination skills in the inpatient setting. An eight-item multiple-choice questionnaire was administered monthly to 19 physical medicine and rehabilitation residents rotating on inpatient services inquiring about number and types of musculoskeletal examinations performed on each inpatient rotation. Seventy-one surveys were collected with a 90% response rate. Significant increases were noted in number of knee examinations and shoulder examinations performed on inpatient rotations after residents completed 2 mos of outpatient musculoskeletal medicine. Most postgraduate year 2 residents (76%) felt that they would perform more musculoskeletal examinations on their inpatient rotations if they had more outpatient musculoskeletal experience at that point in their training. The results suggest that outpatient musculoskeletal experience increases resident use of musculoskeletal examination skills in the inpatient setting. Earlier outpatient musculoskeletal experience in combination with a greater focus on teaching musculoskeletal examination skills in the inpatient setting can support residents in learning how to provide comprehensive musculoskeletal care to individuals with disabilities.

Mental health impact of COVID-19 pandemic on therapists at an inpatient rehabilitation facility.

BACKGROUND: Healthcare workers have faced extraordinary work-related stress in the face of the COVID-19 pandemic. Physical therapy, occupational therapy, and speech-language pathology providers at inpatient rehabilitation facilities may represent a distinct at-risk subgroup for work-related stress during the pandemic due to the usual nature of their job duties, including close physical contact and extended treatment times. OBJECTIVE: To evaluate the impact of the COVID-19 pandemic on work-related stress and occurrence of depression and anxiety in physical therapists, occupational therapists, and speech-language pathologists during the first surge of COVID-19 hospitalizations. DESIGN: Cross-sectional survey. SETTING: Academic, freestanding inpatient rehabilitation facility. PARTICIPANTS: Survey responses were collected from 38 therapists. INTERVENTION: A 26-item electronic questionnaire containing a mix of multiple-choice and open-ended questions. MAIN OUTCOME MEASURES: Positive screens for depression or anxiety as measured by the Patient Health Questionnaire-9 (PHQ-9) and the General Anxiety Disorder 7-item (GAD-7) scale, respectively. RESULTS: Seven individuals (19%) scored at or above the clinically significant cutoff of 10 on each the PHQ-9 and GAD-7, corresponding to increased risk for depression and anxiety. Therapists younger than 30 years old had significantly higher GAD-7 scores compared to therapists between 30-39 years old (p < .05). Occupational stress was attributed to a number of causes including concerns for health and safety, unpredictable changes in hospital protocols and work assignments, acquisition of additional work duties, concerns about the ability to provide high-quality patient care in a restricted environment, and the psychological toll of caring for patients with or recovering from COVID-19. CONCLUSION: This cross-sectional survey highlights the impact of the COVID-19 pandemic on occupational stress and mental health of therapists working at an inpatient rehabilitation facility during the first surge of COVID-19 hospitalizations. This research may help institutions identify at-risk individuals who may benefit from support and guide policy changes to resolve potentially modifiable factors at a systems level.

The interplay of inflammation and coagulation in COVID-19 Patients receiving extracorporeal membrane oxygenation support.

OBJECTIVE: Bleeding and thrombosis are common complications during Extracorporeal Membrane Oxygenation (ECMO) support for COVID-19 patients. We sought to examine the relationship between inflammatory status, coagulation effects, and observed bleeding and thrombosis in patients receiving venovenous (VV) ECMO for COVID-19 respiratory failure. STUDY DESIGN: Cross-sectional cohort study. SETTINGS: Quaternary care institution. PATIENTS: The study period from April 1, 2020, to January 1, 2021, we included all patients with confirmed COVID-19 who received VV ECMO support. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Thirty-two patients were supported with VV ECMO during the study period, and 17 patients (53%) survived to hospital discharge. The ECMO nonsurvivors mean lactate dehydrogenase (LDH) levels were markedly elevated in comparison to survivors (1046 u/L [IQR = 509, 1305] vs 489 u/L [385 658], p = 0.003). Platelet/fibrinogen dysfunction, as reflected by the low Maximum Amplitude (MA) on viscoelastic testing, was worse in nonsurvivors (65.25 mm [60.68, 67.67] vs 74.80 mm [73.10, 78.40], p = 0.01). Time-group interaction for the first seven days of ECMO support, showed significantly lower platelet count in the nonsurvivors (140 k/ul [103, 170] vs 189.5 k/ul [ 146, 315], p < 0.001) and higher D-dimer in (21 µg/mL [13, 21] vs 14 µg/mL [3, 21], p < 0.001) in comparison to the survivors. Finally, we found profound statistically significant correlations between the clinical markers of inflammation and markers of coagulation in the nonsurvivors group. The ECMO nonsurvivors experienced higher rate of bleeding (73.3% vs 35.3%, p = 0.03), digital ischemia (46.7% vs 11.8%, p = 0.02), acute renal failure (60% vs 11.8%, p = 0.01) and bloodstream infection (60% vs 23.5%, p = 0.03). CONCLUSION: The correlation between inflammation and coagulation in the nonsurvivors supported with VV ECMO could indicate dysregulated inflammatory response and worse clinical outcomes.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

BACKGROUND: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients. METHODS: This is a retrospective study of patients who underwent LT between 2015 and 2018 at Medstar Georgetown Transplant Institute. Patients with prolonged hospitalization post-LT (>90 days), death within 90 days post-LT, and re-transplants were excluded. RESULTS: Two hundred and ninety seven patients were transplanted, among 29% for indications of ALD. ALD patients were younger (52 vs. 56 years), more likely to be male (76% vs. 61%), Caucasian (71% vs. 44%), have higher MELD (28.8±8.8 vs. 25±8.8), and psychiatric disease than non-ALD patients (P < .05). There was no difference in pre-LT use of opioids, tobacco, marijuana, or illicit drugs between ALD and non-ALD patients. Pre-LT opioid use (OR = 11.7, P < .001), ALD (OR = 2.5, P = .01), and MELD score (OR = .95, P = .02) independently predicted 90-day p-LTOU. CONCLUSIONS: ALD, pre-LT opioid use, and MELD score independently predict p-LTOU. Special attention should be paid to identify post-LT prolonged opioid use in ALD patients.

Prevalence of pelvic floor disorders, associations of endocrine therapy, and surgical intervention among breast cancer survivors.

INTRODUCTION AND HYPOTHESIS: To evaluate prevalence of pelvic floor disorders, association of endocrine therapy with pelvic floor disorders, and rates of pelvic floor surgery among breast cancer survivors compared to matched controls without history of cancer. METHODS: This is a retrospective, cohort study using electronic medical record data from a ten-hospital regional healthcare system. A total of 19,483 women diagnosed with breast cancer between January 2008 and April 2020 were propensity score matched to 19,483 women without a history of cancer. Medical charts were abstracted for ICD-9 and ICD-10 codes for pelvic floor disorders, use of endocrine therapy, and CPT codes for pelvic floor surgeries and procedures. RESULTS: Overall, the prevalence of pelvic floor disorders was lower among breast cancer survivors (8.8% vs. 22.6%, p < 0.001), and mean time to development of pelvic floor disorders among breast cancer survivors was 3 years. Selective estrogen receptor modulators and aromatase inhibitors were associated with pelvic organ prolapse and stress urinary incontinence, while estrogen antagonists were associated with urge urinary incontinence and lower urinary tract symptoms. Women with breast cancer had similar or higher rates of pelvic floor surgery compared to matched controls. CONCLUSIONS: Rates of pelvic floor disorders were lower among breast cancer survivors compared to controls but rates of surgical intervention did not differ and were higher for some conditions among breast cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Screening for these disorders should be considered as part of routine survivorship care.

Changes in Thyroid Metabolites after Liothyronine Administration: A Secondary Analysis of Two Clinical Trials That Incorporated Pharmacokinetic Data.

We examined relationships between thyroid hormone (TH) metabolites in humans by measuring 3,5-diiodothyronine (3,5-T2) and 3-iodothyronamine (3-T1AM) levels after liothyronine administration. In secondary analyses, we measured 3,5-T2 and 3-T1AM concentrations in stored samples from two clinical trials. In 12 healthy volunteers, THs and metabolites were documented for 96 h after a single dose of 50 mcg liothyronine. In 18 patients treated for hypothyroidism, levothyroxine therapy was replaced by daily dosing of 30-45 mcg liothyronine. Analytes were measured prior to the administration of liothyronine weekly for 6 weeks, and then hourly for 8 h after the last liothyronine dose of the study. In the weekly samples from the hypothyroid patients, 3,5-T2 was higher by 0.033 nmol/L with each mcg/dL increase in T4 and 0.24 nmol/L higher with each ng/dL increase in FT4 (p-values = 0.007, 0.0365). In hourly samples after the last study dose of liothyronine, patients with T3 values higher by one ng/dL had 3-T1AM values that were lower by 0.004 nmol/L (p-value = 0.0473); patients with 3,5-T2 higher by one nmol/L had 3-T1AM values higher by 2.45 nmol/L (p-value = 0.0044). The positive correlations between weekly trough levels of 3,5-T2 and T4/FT4 during liothyronine therapy may provide insight into 3,5-T2 production, possibly supporting some production of 3,5-T2 from endogenous T4, but not from exogenous liothyronine. In hourly sampling after liothyronine administration, the negative correlation between T3 levels and 3-T1AM, but positive correlation between 3,5-T2 levels and 3-T1AM could support the hypothesis that 3-T1AM production occurs via 3,5-T2 with negative regulation by T3.

Prognostic factors for overall survival in malignant ureteral obstruction.

INTRODUCTION: To identify prognostic factors for overall survival (OS) in patients with malignant ureteral obstruction (MUO) from gynecologic malignancy (GM), with the goal of improving patient selection for urinary diversion. MATERIALS AND METHODS: Retrospective review of 126 patients with MUO from GM at two academic centers from 2011-2019. Factors related to OS identified by Cox regression proportional hazard model. In patients with incomplete survival data (n = 30), hospice was used as a surrogate for death. Multivariate models and receivers operating characteristics (ROC) curves were created for hemoglobin and albumin values. RESULTS: Overall median survival was 6.2 months. On univariate analysis, age at diagnosis, Charlson Comorbidity Index (CCI) ≥ 8, advanced clinical stage, ascites, pleural effusion, albumin, and hemoglobin were associated with poor OS. OS was higher for those receiving ureteral stenting as compared with no intervention. There was no survival difference based on hydronephrosis grade, stent failure (SF), or creatinine at the time of intervention. On multivariate analysis, albumin < 2.85 g/dL and hemoglobin < 9.6 g/dL were predictive of poor OS. CONCLUSIONS: OS in patients with MUO due to GM is poor. Several prognostic factors for poor survival including low serum albumin and hemoglobin were identified. Ureteral stenting was associated with improved OS compared to observation, but selection bias likely contributed to this result. Additional studies are needed to clarify this finding. These data can be utilized to counsel patients regarding outcomes after urinary diversion in the setting of MUO and perhaps avoid additional procedures in some of these patients who will not derive meaningful benefit.

Immunotherapy-Associated Hypothyroidism: Comparison of the Pre-Existing With De-Novo Hypothyroidism.

Background: Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism. Methods: A retrospective analysis was conducted using patients who received immunotherapy between 2010-2019 within a multicenter hospital system. Participants were separated in three groups-those with pre-existing hypothyroidism, those who developed primary hypothyroidism and those with hypophysitis within a year of their first immunotherapy. Serial effects of immunotherapy on thyroid function tests (TFTs) and levothyroxine dosing were evaluated. Results: 822 patients were screened, with 85 determined to have pre-existing hypothyroidism, 48 de-novo primary hypothyroidism and 12 de-novo hypophysitis. All groups displayed fluctuations in TFTs around weeks 6-8 of treatment. In the pre-existing hypothyroidism group, the levothyroxine dose was higher at 54 weeks than at baseline with the difference showing a trend towards statistical significance (p=0.06). The observed mean levothyroxine dose was significantly lower than the mean calculated weight-based dose for all groups. This finding was most clinically significant for the de-novo hypophysitis group (mean difference: -58.3 mcg, p<0.0001). The mean 0.9 mcg/kg levothyroxine dose at week 54 for the de-novo hypophysitis group was statistically lower than the other groups (p=0.009). Conclusion: It is reasonable to screen with TFTs every 4 weeks, and space out TFTs surveillance to every 12 weeks after week 20. Our findings suggest a more conservative approach for levothyroxine dosing in those developing de-novo hypothyroidism, especially hypophysitis, such as initiating at 0.9-1.2 mcg/kg.

Can Clinical Response Predict Pathologic Response Following Neoadjuvant Chemoradiation for Esophageal Cancer?

OBJECTIVES: Approximately 20-40% of patients with locally advanced esophageal cancer will achieve a pathologic complete response (ypCR) following neoadjuvant chemoradiotherapy (nCRT). Predicting ypCR based on a clinical complete response (ycCR) has been a challenge. This study assessed the correlation between ycCR and ypCR, as determined from esophagectomy specimens. METHODS: Patients undergoing esophagectomy following nCRT at three major institutions between 2005 and 2018 were reviewed. Restaging, including PET/CT, endoscopy with biopsy, and esophageal ultrasound (EUS), was performed to determine ycCR. RESULTS: Six hundred sixty patients were included, with 93.3% with esophageal adenocarcinoma histology. Six hundred fifty-eight of these patients underwent PET, 304 EUS, and 584 underwent a biopsy. Following nCRT, 148 (22.4%) were found to have a ypCR. Only 12/32 (37.5%) determined to have a ycCR were found to have a ypCR, while 136/628 (21.6%) with a non-ycCR were found to have a ypCR (p 0.075). Individual modality PPV was 28% for PET, 54% for EUS, and 26% for biopsy. When PET was combined with EUS, 168 reports were concordant and the PPV of ypCR was 50%, though the number of patients was low (1/2). With all 3 re-staging modalities combined, the PPV and NPV both rose to 100%. CONCLUSIONS: Current restaging tools cannot reliably predict ypCR after nCRT. While multimodal restaging appears to be a more accurate predictor of ypCR than any testing modality alone, patients cannot reliably be advised to avoid an esophagectomy on the assumption that ycCR predicts ypCR at this time.

National evaluation of patterns and predictors of underuse of multimodal therapy for high-risk extremity soft tissue sarcoma.

BACKGROUND: Treatment of high-risk extremity soft tissue sarcomas remains widely varied. Despite growing support for a multimodal approach for treatment of these rare and aggressive neoplasms, its dissemination remains underused. This national study aimed to evaluate variations in treatment patterns and uncover factors predictive of underuse of multimodal therapy in high-risk extremity soft tissue sarcomas. METHODS: The 2010 to 2015 National Cancer Database was used to evaluate trends in 3 common treatment patterns: surgery alone, surgery + adjuvant therapy, and neoadjuvant therapy + surgery. Demographic-, sarcoma-, hospital-, and treatment-level factors of 6,725 surgically treated patients with stage II or III intermediate- to high-grade extremity soft tissue sarcomas were evaluated by types of treatment modality. Stepwise multivariable logistic regression was performed to identify factors predictive of each treatment modality. RESULTS: When compared to surgery alone (34.6%) and adjuvant therapy (41.2%), use of neoadjuvant therapy + surgery for high-risk extremity soft tissue sarcomas remained low (25.3%). However, time trend analysis demonstrated that neoadjuvant therapy + surgery has significantly increased by 7% per year, whereas surgery alone decreased by 4% every year (P < .05 for both). Factors predictive of surgery alone were older age, nonprivate insurance, increasing travel distance, and multimorbidity (P < .05). Conversely, factors associated with neoadjuvant therapy + surgery were private insurance, higher education, and care at academic or high-volume institutions (for all, P < .05). Tumor-related factors predictive for neoadjuvant therapy + surgery included size <5 cm and higher-grade tumors (P < .05). CONCLUSION: Adoption of multimodality therapy for high-risk extremity soft tissue sarcomas remains low and gradual in the United States. Dissemination of multimodality therapy will require attention to access and hospital factors to maximize these therapies for high-risk extremity soft tissue sarcomas.

Thrombotic and Clinical Outcomes in Patients with Hematologic Malignancy and COVID-19.

BACKGROUND: Venous thromboembolism (VTE) is a common complication in acute COVID-19 and those with hematologic malignancy (HM) may be at an even higher risk. We performed a retrospective analysis of patients with history of HM and acute COVID-19 to evaluate thrombotic and clinical outcomes. METHODS: Patients with COVID-19 were identified by positive SARS-CoV-2 PCR test. Our primary endpoints were rate of VTE and CVA in patients with HM compared to the general population (GP). Secondary outcomes included composite thrombotic events (CVA + VTE), COVID-19 fatality, respiratory support, ICU admission rates, and length of ICU stay RESULTS: A total of 833 patients were evaluated, 709 in the GP cohort, 124 patients in the HM cohort. CVA was more prevalent in the HM cohort (5.4% vs. 1.6%, P = .011). Rates of VTE were numerically higher for the HM cohort (8.0% vs. 3.6%, P = .069). The composite thrombotic rate was increased in the HM cohort (13.4% vs. 5.2%, P = .005). Patients with HM had a higher inpatient fatality rate (35.5% vs. 11.3%, P < .001), required more respiratory support (74.6% vs. 46.5%, P < .001) and had a higher rate of ICU admission (31.9% vs. 12.1%, P = .001). CONCLUSION: Our data demonstrated an increased rate of composite thrombotic (CVA + VTE) outcomes, indicating HM patients with acute COVID-19 are at increased risk of thrombosis. Irrespective of disease status, HM patients also have significantly increased need for intensive care, respiratory support, and have higher fatality rates.

Risk factors for bleeding hepatocellular adenoma in a United States cohort.

BACKGROUND & AIMS: Known risk factors for hepatocellular adenoma (HCA) bleeding are size >5 cm, growth rate, visible vascularity, exophytic lesions, ß-catenin and Sonic Hedgehog activated HCAs. Most studies are based on European cohorts. The objective of this study is to identify additional risk factors for HCA bleeding in a US cohort. METHODS: Retrospective chart review was performed on patients diagnosed with HCA on magnetic resonance imaging (n = 184) at an academic tertiary institution. Clinical, pathological, and imaging data were collected. Primary outcomes measured were HCA bleeding and malignancy. Statistical analysis was performed with SAS 9.4 using Chi-Square, Fisher's exact test, sample t test, non-parametric Wilcoxon test, and logistic regression. RESULTS: After excluding patients whose pathology showed focal nodular hyperplasia and non-adenoma lesions, follow-up data were available for 167 patients. 16% experienced microscopic or macroscopic bleeding and 1.2% had malignancy. HCA size predicted bleeding (P < .0001) and no patients with lesion size <1.8 cm bled. In unadjusted analysis, hepatic adenomatosis (≥10 lesions) trended towards 2.8-fold increased risk of bleeding. Of patients with a single lesion that bled, 77% bled from a lesion >5 cm. In patients with multiple HCAs that bled, 50% bled from lesions <5 cm. In patients with multiple adenomas, size (P = .001) independently predicted bleeding and hepatic steatosis trended towards increased risk of bleeding (P = .05). CONCLUSIONS: In a large US cohort, size predicted increased risk of HCA bleeding while hepatic adenomatosis trended towards increased risk of bleeding. In patients with multiple HCAs, size predicted bleeding and hepatic steatosis trended toward increased risk of bleeding.

A New Reality for Multiple Myeloma Renal Failure: US Data Report on Kidney Transplant Outcomes.

INTRODUCTION: Describe graft and overall survival outcomes in multiple myeloma (MM) patients who underwent kidney transplant (KT) compared to the general KT population. PATIENTS AND METHODS: The Organ Procurement and Transplantation Network/National United Network for Organ Sharing (OPTON/UNOS) database was analyzed from 1988 to 2019 with R 4.00 and the 2013-2017 United States Renal Data System (USRDS) was surveyed for incidence and mortality of MM ESRD. RESULTS: USRDS analysis revealed 961 patients diagnosed with ESRD due to MM on average annually, accounting for 0.8% of the ESRD population. Without KT, 44.4% of MM patients died in the first year of renal replacement initiation. OPTON/UNOS analysis identified 218 MM KT patients, compared to 490,089 patients without MM. There was no difference in graft survival between MM KT and the general population (P-value = .13, HR = 1.19 [0.95, 1.49], 95% CI). Median graft survival in MM KT was 2683 days (7.4 years). KT patients with MM had a higher risk for death (P-value = <.0001, HR = 1.83 [1.41, 2.37], 95% CI), and median overall survival was 3076 days (8.4 years). Survival difference was lost when comparing patients ≥50 years (P-value = .42, HR = 1.14 [0.83, 1.56], 95% CI). CONCLUSION: Patients with MM renal failure who underwent KT had equivalent graft and age-matched overall survival compared to the general KT population. Therefore select patients with MM renal failure have potential for excellent KT outcomes, should be considered for transplantation when feasible, and should not be excluded from KT based on a history of MM.

COVID-19 Outcomes in a US Cohort of Persons Living with HIV (PLWH).

Reported coronavirus disease 2019 (COVID-19) outcomes in persons living with HIV (PLWH) vary across cohorts. We examined clinical characteristics and outcomes of PLWH with COVID-19 compared with a matched HIV-seronegative cohort in a mid-Atlantic US healthcare system. Multivariate logistic regression was used to explore factors associated with hospitalization and death/mechanical ventilation among PLWH. Among 281 PLWH with COVID-19, the mean age was 51.5 (SD 12.74) years, 63% were male, 86% were Black, and 87% had a HIV viral load <200 copies/mL. Overall, 47% of PLWH versus 24% (p < 0.001) of matched HIV-seronegative individuals were hospitalized. Rates of COVID-19 associated cardiovascular and thrombotic events, AKI, and infections were similar between PLWH and HIV-seronegative individuals. Overall mortality was 6% (n = 18/281) in PLWH versus 3% (n = 33/1124) HIV-seronegative, p < 0.0001. Among admitted patients, mortality was 14% (n = 18/132) for PLWH and 13% (n = 33/269) for HIV-seronegative, p = 0.75. Among PLWH, hospitalization associated with older age aOR 1.04 (95% CI 1.01, 1.06), Medicaid insurance aOR 2.61 (95% CI 1.39, 4.97) and multimorbidity aOR 2.98 (95% CI 1.72, 5.23). Death/mechanical ventilation associated with older age aOR 1.06 (95% CI 1.01, 1.11), Medicaid insurance aOR 3.6 (95% CI 1.36, 9.74), and multimorbidity aOR 4.4 (95% CI 1.55, 15.9) in adjusted analyses. PLWH were hospitalized more frequently than the HIV-seronegative group and had a higher overall mortality rate, but once hospitalized had similar mortality rates. Older age, multimorbidity and insurance status associated with more severe outcomes among PLWH suggesting the importance of targeted interventions to mitigate the effects of modifiable inequities.

Impact of COVID-19 pandemic on emergency department substance use screens and overdose presentations.

BACKGROUND: The COVID-19 pandemic can exacerbate underlying substance use disorder and has impacted this vulnerable population in a variety of ways. There are limited data regarding how this pandemic has impacted emergency department (ED) patient presentations. METHODS: We extracted data on ED visits from the electronic health record (EHR) of a large healthcare system in the Washington, DC/Baltimore, MD metropolitan area. The dataset includes data from 7 hospitals on ED visits between 11/1/2019-6/30/2020. The health system utilizes a validated screening program for substance use, Screening, Brief Intervention, and Referral to Treatment (SBIRT), for ED patients who are clinically stable and willing to complete screening. We evaluated trends in patients with a positive SBIRT screen and those presenting with a clinical diagnosis of acute alcohol or substance intoxication/overdose before (11/1/19-2/29/2020-pre) and during the first wave of the COVID pandemic (3/1/2020-6/30/2020-post). Data were described using descriptive statistics. Bivariate analyses were conducted using chi-square test and two-sample t-tests. Interrupted time series analysis was used to evaluate the changes in the weekly trends with the start of the pandemic. RESULTS: There were 107,930 screens performed in the EDs during the study period (61,961 pre, 45,969 post). The population was primarily African American (64.7%) and female (57.1%). Positive SBIRT screens increased from 12.5% to 15.8% during COVID (p < 0.001). Alcohol intoxication presentations increased as a proportion of positive screens from 12.6% to 14.4% (p = 0.001). A higher percentage of screened patients reported problem drinking (AUDIT score ≥ 7) during the pandemic (2.4% pre vs 3.2% post, p < 0.001). Substance intoxication/overdoses among all screened increased from 2.1% to 3.1% (p < 0.001) and as a percentage of positive screens during the pandemic (16.8% to 20%, p < 0.001). The proportion of opioid vs. non-opioid overdoses remained unchanged before (67%) and during the pandemic (64%, p = 0.33). DISCUSSION: There was an increase in the proportion of positive SBIRT screens and visits for acute overdoses and intoxication during the first wave of the COVID-19 pandemic. Additional research should focus on mitigation strategies to address substance use during this vulnerable time.