The SAGES MASTERS program bariatric surgery pathway selects 10 seminal publications on adjustable gastric banding.

BACKGROUND: Bariatric surgery is one of the clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, and laparoscopic adjustable gastric banding (LAGB) is one of the three anchoring bariatric procedures. To improve surgeon lifelong learning, the Masters Program seeks to identify sentinel articles of each of the 3 bariatric anchoring procedures. In this article, we present the top 10 articles on LAGB. METHODS: A systematic literature search of papers on LAGB was completed, and publications with the most citations and citation index were selected and shared with SAGES Metabolic and Bariatric Surgery Committee members for review. The individual committee members then ranked these papers, and the top 10 papers were chosen based on the composite ranking. RESULTS: The top 10 sentinel publications on LAGB contributed substantially to the body of literature related to the procedure, whether for surgical technique, novel information, or outcome analysis. A summary of each paper including expert appraisal and commentary is presented here. CONCLUSION: These seminal articles have had significant contribution to our understanding and appreciation of the LAGB procedure. Bariatric surgeons should use this resource to enhance their continual education and acquisition of specialized skills.

Disparities in clinical trial participation in ovarian cancer: A real-world analysis.

BACKGROUND: Significant disparities exist in clinical trial participation in non-gynecologic cancers, but little is known about disparities in ovarian cancer trial participation. Our objective was to examine patient, sociodemographic (race/ethnicity, insurance), cancer, and health system factors associated with clinical trial participation in ovarian cancer. METHODS: We conducted a retrospective cohort study of patients with epithelial ovarian cancer diagnosed from 2011 to 2021, using a real-world electronic health record derived database, representing around 800 sites of care in US academic and community practices. We used multivariable Poisson regression modeling to analyze the association of ever participating in an ovarian cancer clinical drug trial with patient, sociodemographic, health system, and cancer factors. RESULTS: Of the 7540 patients with ovarian cancer, 5.0% (95% CI 4.5-5.5) ever participated in a clinical drug trial. Patients of Hispanic or Latino ethnicity were 71% less likely to participate in clinical trials (RR 0.29, 95% CI 0.13-0.61) than non-Hispanic patients, and patients whose race was unknown or other than Black or White were 40% less likely to participate in clinical trials (RR 0.68, 95% CI 0.52-0.89). Patients who had Medicaid insurance were 51% less likely (RR 0.49, 95% CI 0.28-0.87) and those with Medicare were 32% (RR 0.48-0.97) less likely to participate in clinical trials than privately-insured patients. CONCLUSION: In this national cohort study, only 5% of patients with ovarian cancer participated in clinical drug trials. Interventions are needed to decrease race, ethnicity, and insurance disparities in clinical trial participation.

Ovarian morphology and follicular dynamics associated with ovarian aging in Bos indicus beef cows.

This study characterizes the ovarian volume, antral follicle count (AFC), and ovarian dynamics of cows at different ages. Nellore cows (Bos taurus indicus) were used in two experiments. In Experiment 1, 57 lactating cows ranging in age from 3 to 23 years had their estrous cycle synchronized based on progesterone/estradiol treatments. The ovaries were scanned by ultrasound to record ovarian volume and AFC prior to follicle aspiration (AFC1). A second AFC (AFC2) was performed 5 days later to count only the growing antral follicles. In Experiment 2, six long-lived (14- to 23-year-old) and three young (4- to 8-year-old) non-lactating cows were submitted to daily ovarian scanning ultrasound during an interovulatory interval. Blood samples were collected during the estrous cycle to assess serum progesterone concentration. Data were analyzed using Student's t-test, ANOVA, and regression analysis tests. In Experiment 1, there were more (P < 0.05) antral follicles in AFC1 (31.4 ± 3.5) than in AFC2 (22.6 ± 2.4). In AFC1, the volume of the right ovary (6.03 ± 0.5 cm3) was greater (P < 0.01) than that of the left one (4.53 ± 0.4 cm3), although the AFC did not differ between the two ovaries (15.3 ± 1.8 and 16.3 ± 1.8, respectively). In both AFC1 and AFC2, there was a decline in the number of antral follicles as the age of the cow increased (P < 0.01). Ovarian volume (average of both ovaries) was related (P < 0.01) with AFC (R² = 0.1499) and cow age (R² = 0.0911). In Experiment 2, young and old cows under the age of 20 had a pattern of follicular growth waves, while cows over 20 years old did not have waves of follicular growth. The progesterone profiles and corpus luteum size during the estrous cycle did not differ between the groups. In conclusion, although cows had increased ovarian volume and decreased follicular population as they age, the follicular growth pattern and corpus luteum functionality appear to be unaffected by age.

Occupational Exposure to Pesticides as a Risk Factor for Sleep Disorders.

Inadequate sleep has been linked to a variety of impairments in bodily functions, including endocrine, metabolic, higher cortical function, and neurological disorders. For this reason, the aim of this study was to analyze the link between occupational pesticide exposure and sleep health among farmers in Almeria. A cross-sectional study was conducted among a population living on the coast of Almeria (southeastern Spain), where about 33,321 hectares of land are used for intensive agriculture in plastic greenhouses. A total of 380 individuals participated in the study: 189 greenhouse workers and 191 control subjects. The participants were contacted during their annual scheduled occupational health survey. Data on sleep disturbances were collected using the Spanish version of the Oviedo Sleep Questionnaire. Agricultural workers were found to be at a significantly higher risk of insomnia, especially among those who did not wear protective gloves (OR = 3.12; 95% C.I. = 1.93-3.85; p = 0.04) or masks (OR = 2.43; 95% C.I. = 1.19-4.96; p = 0.01). The highest risk of insomnia related to pesticide applicators was observed in those who did not wear a mask (OR = 4.19; 95% C.I. = 1.30-13.50; p = 0.01) or goggles (OR = 4.61; 95% C.I. = 1.38-10.40; p = 0.01). This study supports previous findings indicating an increased risk of sleep disorder in agricultural workers exposed to pesticides at work.

Independent association of preoperative Hill grade with gastroesophageal reflux disease 2 years after sleeve gastrectomy.

BACKGROUND: The sleeve gastrectomy (SG) is associated with postoperative gastroesophageal reflux disease (GERD). Higher endoscopic Hill grade has been linked to GERD in patients without metabolic surgery. How preoperative Hill grade relates to GERD after SG is unknown. OBJECTIVE: To explore the relationship between preoperative Hill grade and GERD outcomes 2 years after SG. SETTING: Academic hospital, United States. METHODS: All patients (n = 882) undergoing SG performed by 5 surgeons at a single academic institution from January 2015 to December 2019 were included. Complete data sets were available for 360 patients, which were incorporated in analyses. GERD was defined as the presence of a diagnosis in the medical record accompanied by pharmacotherapy. Patients with GERD postoperatively (n = 193) were compared with those without (n = 167). Univariable and multivariable analyses were conducted to explore independent associations between preoperative factors and GERD outcomes. RESULTS: The presence of any GERD increased at the postoperative follow-up of 25.2 (3.9) months compared with preoperative values (53.6% versus 41.1%; P = .0001). Secondary GERD outcomes at follow-up included de novo (41.0%), persistent (33.1%), resolved (28.4%), worsened (26.4%), and improved (12.2%) disease. Postoperative endoscopy and reoperation for GERD occurred in 26.4% and 6.7% of the sample. Patients with GERD postoperatively showed higher prevalence of Hill grade III-IV (32.6% versus 19.8%; P = .0062) and any hiatal hernia (HH) (36.3% versus 25.1%; P = .0222) compared with patients without postoperative GERD. Frequencies of gastritis, esophagitis A or B, duodenitis, and peptic ulcer disease were similar between groups. Higher prevalence of preoperative GERD (54.9% versus 25.1%; P < .0001), obstructive sleep apnea (66.8% versus 54.5%; P = .0171), and anxiety (25.4% versus 15.6%; P = .0226) was observed in patients with postoperative GERD compared with those without it. Baseline demographics, weight, other obesity-associated diseases, whether an HH was repaired at index SG, and follow-up length were statistically similar between groups. After adjusting for collinearity, preoperative GERD (odds ratio [OR] = 3.6; 95% confidence interval [CI], 2.2-5.7; P < .0001) and Hill grade III-IV (OR [95% CI]: 1.9 [1.1-3.1]; P = .0174) were independently associated with the presence of any GERD postoperatively. The preoperative presence of an HH >2 cm and whether an HH was repaired at index SG showed no independent association with GERD at follow-up. CONCLUSIONS: More than 50% of patients experienced GERD 2 years after SG. Preoperative GERD confers the highest risk for GERD postoperatively. Hill grade III-IV is independently associated with GERD after SG. Whether a hiatal hernia repair was performed did not influence GERD outcomes. Preoperative esophagogastroduodenoscopy should be obtained before SG and Hill grade routinely captured and used to counsel patients about the risk of postoperative GERD after this procedure. Hill grade may help guide the choice of metabolic operation.

Sleeve gastrectomy morphology and long-term weight-loss and gastroesophageal reflux disease outcomes.

BACKGROUND: The relationship between sleeve gastrectomy (SG) morphology and long-term weight-loss and gastroesophageal reflux disease (GERD) outcomes is unknown. METHODS: All patients (n = 268) undergoing SG performed by 3 surgeons at a single academic institution from January 1, 2010 to December 31, 2012 were included. Long-term weight-loss and GERD outcomes were available for 90 patients which were incorporated in analyses. SG morphology was determined from postoperative day 1 upper gastrointestinal series (UGIS) available from 50 patients. Images were independently categorized using previously published methodology as Dumbbell (38%), Lower Pouch (22%), Tubular (26%), or Upper Pouch (14%) by Radiologist and Surgeon. Radiologist categorization was used when disagreement occurred (8%). Univariable analyses were conducted to explore potential associations between SG morphology, weight loss, and GERD outcomes. RESULTS: Follow-up was 8.2 ± 0.9 years. Population characteristics included age of 45.1 ± 10.8 years, female sex in 83.3%, and hiatal hernia repair (HHR) performed at index SG in 17.8%. Surgeons did not preferentially achieve a specific SG morphology. Changes from preoperative obesity and associated diseases comprised body mass index (BMI) (49.5 ± 7.6 vs. 39.2 ± 9.4 kg/m2; p < 0.0001), diabetes mellitus (30.0 vs. 12.2%; p = 0.0006), hypertension (70.0 vs. 54.4%; p = 0.0028), hyperlipidemia (42.2 vs. 24.2%;p = 0.0017), obstructive sleep apnea (41.1 vs. 15.6%; p < 0.0001), osteoarthritis (48.9 vs. 13.3%; p < 0.0001), back pain (46.5 vs. 28.9%; p = 0.0035), and medications (4.8 ± 3.3 vs. 3.7 ± 3.5; p < 0.0001). Dumbbell SG morphology was associated with lesser reduction in BMI at follow-up (--6.8 ± 7.2 vs. -12.4 ± 8.3 kg/m2; p = 0.0196) while greater BMI change was appreciated with Lower Pouch SG shape (-16.9 ± 9.9 vs. -8.4 ± 6.8 kg/m2; p = 0.0017). GERD was more prevalent at follow-up than baseline (67.8 vs. 47.8%; p < 0.0001). GERD-specific outcomes included de novo (51.1%), persistent (27.9%), worsened (58.1%), and resolved (14.0%) disease. Ten patients underwent reoperation for refractory GERD with SG morphology corresponding to Dumbbell (n = 5) and Upper Pouch (n = 1) for those with available UGIS. Univariable analyses showed that patients with GERD experienced a larger reduction in BMI compared with patients without GERD (-11.8 ± 7.7 vs. -7.0 ± 5.1 kg/m2; p = 0.0007). Patient age, surgeon, morphology category, and whether a HHR was done at index SG were not associated with the presence of any, de novo, or worsened GERD. Female sex was associated with worsened GERD (96.0 vs. 4.0%; p = 0.0455). Type of calibration device, distance from staple line to pylorus, and whether staple line reinforcement was used were not associated with SG morphology classification. CONCLUSION: This is the first study assessing the impact of SG morphology on long-term weight loss and GERD. Our data suggest an association between SG morphology and long-term weight loss but not with GERD outcomes. Current technical standards may be limited in reproducing the same SG morphology. This information may help guide the technical optimization and standardization of SG. Surgeons did not favor a specific SG morphology (1). Our results signal to a relationship between radiographic assessment of SG morphology and long-term weight-loss outcomes with Dumbbell classification correlated with lesser reduction in BMI (2a) and Lower Pouch morphology associated with superior weight loss (2b). SG, sleeve gastrectomy; BMI, body mass index.

Conversion of gastric sleeve to Roux-en-Y gastric bypass: overall outcomes and predictors of below-average weight loss.

BACKGROUND: Conversion of sleeve gastrectomy (SG) to Roux-en-Y gastric bypass (RYGB) has been utilized to promote further weight loss, but results are variable in available literature. OBJECTIVES: To evaluate outcomes of SG to RYGB conversion for weight loss and to identify predictors of below-average weight loss. SETTING: University-affiliated hospital, United States. METHODS: Chart review was performed of our patients who underwent SG to RYGB conversion from November 1, 2013, to November 1, 2020. Primary outcomes were below-average percent excess weight loss (%EWL) at 1 and 2 years. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for preconversion demographics to evaluate their relationship to the primary outcome. RESULTS: Sixty-two patients underwent conversion from SG to RYGB with weight loss as a goal. One-year data was available for 47 patients. The average %EWL at 1 year was 41.5%. Twenty-six patients had below-average %EWL at 1 year. Interval to conversion <2 years (OR = 4.41, 95% CI [1.28,15.17], P = .019) and preconversion body mass index (BMI) >40 (OR = 4.00, 95% CI [1.17,13.73], P = .028) were statistically significant predictors of below-average 1-year %EWL. Two-year data was available for 36 patients. The average %EWL at 2 years was 30.8%. Seventeen patients had below-average %EWL at 2 years. Evaluated demographics were not statistically significant predictors of below-average 2-year %EWL. CONCLUSIONS: Following SG to RYGB conversion, %EWL outcomes are lower at 1 year (41.5%) and 2 years (30.8%) than reported values for primary RYGB. Interval to conversion <2 years and preconversion BMI >40 are predictors of below-average 1-year weight loss after conversion.

Disección coronaria espontánea posterior a envenenamiento por escorpión / Spontaneous coronary artery dissection following scorpion poisoning

Resumen Hombre de 44 años que acude al servicio de urgencias posterior a picadura de escorpión. Presentaba parestesias, dolor toracoabdominal y náuseas. Desde el momento del ingreso presentó dolor torácico atípico, dolor abdominal epigástrico de intensidad leve, asociado a náuseas. Se realizó electrocardiograma que no evidenció alteraciones. La troponina fue elevada, por lo que se llevó a cuidado intensivo y se inició manejo antiisquémico, corroborando posteriormente en la angiografía una disección coronaria tipo 1 en el ramus intermedio como causante de su evento coronario. El paciente recibió un vial de suero antiescorpiónico en primer nivel de atención y posteriormente se indicó manejo con betabloqueante, antiagregación con ácido acetilsalicílico y clopidogrel, con disminución progresiva de sus síntomas. Es egresado asintomático. Se reporta un caso de infarto agudo de miocardio tipo 2 por disección coronaria posterior a una picadura de escorpión, del cual no hay casos reportados previamente en el mundo.

Abstract A 44-year-old man was admitted to the emergency department after a scorpion sting. He presented paresthesia, thoracoabdominal pain and nausea. From the moment of admission, he presented atypical chest pain, epigastric abdominal pain of mild intensity, associated with nausea. An ECG was taken that did not show alterations, troponin was elevated, he was admitted to intensive care unit, management was initiated, subsequently corroborating in the angiography, a type 1 coronary artery dissection in the intermediate ramus as the cause of coronary event. The patient received a vial of antiscorpionic serum in the first level of care, later treatment with beta-blocker, antiaggregation with acetylsalicylic acid and clopidogrel was indicated, with progressive reduction of his symptoms. He is an asymptomatic graduate. A case of type 2 acute myocardial infarction due to coronary dissection after a scorpion sting is reported, there are no previously reported cases in the world.

Malignant hypercalcemia at a national referral center. A retrospective analysis

Malignant hypercalcemia is the most frequent endocrinological emergency in cancer. The factors related to its occurrence have not been evaluated, nor are there any related studies in Colombia. Objective: to determine the factors associated with the onset of malignant hypercalcemia (MH) in patients hospitalized at Instituto Nacional de Cancerología (2014-2019). Design: a retrospective analytical case-control study Population: 230 cases of adults with cancer and calcium corrected for albumin equal to or greater than 10.5 mg/dL and 223 controls of cancer patients with normal corrected calcium (8.5 to 10.4 mg/ dL) were included. Squamous cell carcinoma was used as the pairing variable. Analysis: univariate and bivariate analyses between the variables and the occurrence of MH were conducted to determine association, and raw ORs were calculated. Depending on their statis tical significance (p<0.05), they were included in the logistic regression for multivariate analysis and to rule out bias. Results: the median calcium for cases: 12.98 mg/dL (11.64-14.42) vs. 9.4 mg/dL (9.02-9.74) (p < 0.0001). The two groups were similar in age and sex. There was more metastasis in the cases (60.0% vs. 39.91%) (p< 0.0001). Altogether, 54.34% of the cases developed neurological symp toms. The median hospital stay was 16 days (IQR 9-27) vs. 9 days (IQR 6-17) for the controls (p< 0.0001), and inpatient deaths occurred in 48.70% vs. 16.59% (p < 0.0001). The following showed an association with MH: normal albumin, OR 0.41 (95% CI 0.29-0.55); a Karnofsky Index greater than or equal to 70, OR 0.98 (95% CI 0.97-0.99); and metastasis, OR 1.87 (95% CI 1.23-2.84). (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2555).

La hipercalcemia maligna es la urgencia endocrinológica en cáncer más frecuente, los factores relacionados a su presentación no han sido evaluados, ni hay estudios relacionados en Colombia. Objetivo: determinar los factores asociados a la presentación de hipercalcemia maligna (HM), en pacientes hospitalizados en el Instituto Nacional de Cancerología (2014-2019). Diseño: estudio analítico retrospectivo de casos y controles. Población: se incluyeron 230 casos de adultos con cáncer y calcio corregido por albúmina mayor e igual a 10.5 mg/dL y 223 controles de pacientes oncológicos con calcio corregido normal (8.5 a 10.4 mg/dL), se usó el carcinoma escamocelular como variable pareadora. Análisis: para establecer asociación se realizó el análisis univariado y bivariado entre las variables y la presentación de HM, se calcularon OR crudos, según significancia estadística (p<0.05) fueron incluidas en regresión logística para el análisis multivariado y excluir sesgos. Resultados: mediana de calcio en los casos: 12.98 mg/dL (11.64-14.42) vs. 9.4 mg/dL (9.02-9.74) (p < 0.0001). Los dos grupos presentaron edad y sexo similares. Hubo mayor proporción de metástasis en los casos (60.0% vs. 39.91%) (p < 0.0001). El 54.34% de los casos desarrolló síntomas neuro lógicos. La mediana de estancia hospitalaria fue de 16 días (RIC 9-27) vs. nueve días (RIC 6-17) para los controles (p < 0.0001) y la muerte intrahospitalaria se presentó en el 48.70% vs. 16.59% (p < 0.0001). Demostraron asociación con HM: albúmina normal OR 0.41 (IC 95% 0.29-0.55), índice de Karnofsky mayor o igual 70 OR 0.98 (IC95% 0.97-0.99) y presencia de metástasis OR 1.87 (IC 95% 1.23-2.84). (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2555).

Cardio-renal benefits of sacubitril/valsartan in patients with advanced chronic kidney disease: experience in daily clinical practice.

BACKGROUND: The association between cardiac complications, such as heart failure (HF), and chronic kidney disease (CKD) is well known. In this study, we examined the effectiveness and safety of treatment with neprilysin inhibition in patients with advanced chronic kidney disease (stage 3b-4). METHODS: This single-centre, longitudinal, retrospective study of 31 months duration involved consecutive patients with CKD and HF with a reduced ejection fraction (HFrEF) who started treatment with sacubitril/valsartan. Glomerular filtration rate (GFR), cardiovascular risk factors, proteinuria, potassium, echocardiographic parameters and admissions for heart failure were analysed. RESULTS: The study comprised 25 patients with a median age of 73.2 ± 5.9 years. The most frequent aetiology of heart failure was ischemic heart disease. The median GFR was 29.4 ± 8.3 ml/min/1.73 m2 and the left ventricular ejection fraction (LVEF) 36.4 ± 8.9%. The GFR improved after initiating the treatment (F = 3.396, p = 0.019), as did the LVEF at one year of follow-up (p = 0.018). The number of visits to the emergency department for heart failure was also reduced. No patients needed to start renal replacement therapy. CONCLUSIONS: This study shows that sacubitril/valsartan may play a beneficial role in patients who have advanced CKD and HFrEF, with a satisfactory safety profile.

Phase I, multicenter, open-label study of intravenous VCN-01 oncolytic adenovirus with or without nab-paclitaxel plus gemcitabine in patients with advanced solid tumors.

BACKGROUND: VCN-01 is an oncolytic adenovirus (Ad5 based) designed to replicate in cancer cells with dysfunctional RB1 pathway, express hyaluronidase to enhance virus intratumoral spread and facilitate chemotherapy and immune cells extravasation into the tumor. This phase I clinical trial was aimed to find the maximum tolerated dose/recommended phase II dose (RP2D) and dose-limiting toxicity (DLT) of the intravenous delivery of the replication-competent VCN-01 adenovirus in patients with advanced cancer. METHODS: Part I: patients with advanced refractory solid tumors received one single dose of VCN-01. Parts II and III: patients with pancreatic adenocarcinoma received VCN-01 (only in cycle 1) and nab-paclitaxel plus gemcitabine (VCN-concurrent on day 1 in Part II, and 7 days before chemotherapy in Part III). Patients were required to have anti-Ad5 neutralizing antibody (NAbs) titers lower than 1/350 dilution. Pharmacokinetic and pharmacodynamic analyses were performed. RESULTS: 26% of the patients initially screened were excluded based on high NAbs levels. Sixteen and 12 patients were enrolled in Part I and II, respectively: RP2D were 1×1013 viral particles (vp)/patient (Part I), and 3.3×1012 vp/patient (Part II). Fourteen patients were included in Part III: there were no DLTs and the RP2D was 1×1013 vp/patient. Observed DLTs were grade 4 aspartate aminotransferase increase in one patient (Part I, 1×1013 vp), grade 4 febrile neutropenia in one patient and grade 5 thrombocytopenia plus enterocolitis in another patient (Part II, 1×1013 vp). In patients with pancreatic adenocarcinoma overall response rate were 50% (Part II) and 50% (Part III). VCN-01 viral genomes were detected in tumor tissue in five out of six biopsies (day 8). A second viral plasmatic peak and increased hyaluronidase serum levels suggested replication after intravenous injection in all patients. Increased levels of immune biomarkers (interferon-γ, soluble lymphocyte activation gene-3, interleukin (IL)-6, IL-10) were found after VCN-01 administration. CONCLUSIONS: Treatment with VCN-01 is feasible and has an acceptable safety. Encouraging biological and clinical activity was observed when administered in combination with nab-paclitaxel plus gemcitabine to patients with pancreatic adenocarcinoma. TRIAL REGISTRATION NUMBER: NCT02045602.

When the Donor Surprises You: A Case Report.

The possibility of transplanting a graft from a cadaveric donor with unknown membranous nephropathy (MN) has been described in the literature. We present the case of 2 patients who received their first kidney transplant (KT) from a 27-year-old male donor with no relevant medical history. The first recipient was a 50-year-old man with stage 5 chronic kidney disease secondary to diabetic kidney disease. Two biopsies were performed; the first was performed on day +9 because of impaired renal function coinciding with high levels of tacrolimus, and vacuolization of the arteriolar walls was observed with no other findings; the second was performed on day +13 because of creatinine stagnation, and methenamine silver staining showed multiple cavities and isolated spikes. Immunofluorescence revealed contiguous granular positivity in capillary walls for IgG and C4d, and immunohistochemistry showed contiguous parietal positivity for IgG4, compatible with donor membranous glomerulopathy. Anti-phospholipase-2 receptor (PLA2R) antibodies were negative. The second-year biopsy showed persistence of stage 1 MN, without proteinuria. The second recipient was a 38-year-old man with hypertension and unknown stage 5 chronic kidney disease who experienced immediate kidney function post-KT. In the protocol kidney biopsy 3 months post-KT, data consistent with stage 1 membranous glomerulopathy were also observed. Anti-PLA2R antibodies were negative, and proteinuria did not increase. The second-year protocol biopsy showed no MN data.

Decrease in CD14++CD16+ Monocytes in Low-Immunological-Risk Kidney Transplant Patients with Subclinical Borderline Inflammation.

We determined the association between CD14++CD16+ monocytes and subclinical infiltrates that do not reach the histological threshold for rejection (≥Banff IA). We studied low-immunological-risk kidney-transplant recipients in a clinical trial (NCT02284464; EudraCT 2012-003298-24) whose protocol biopsy in the third month showed no significant changes or borderline lesions (BL). Flow cytometry was used to analyze the percentage of CD14++CD16+ monocytes in peripheral blood (PB) and blood from a fine-needle-aspiration biopsy (FNAB). A protocol biopsy was performed in 81 low-immunological-risk patients, of whom 15 were excluded (BK polyomavirus and rejection). The 28 (42.4%) with borderline lesions had significantly low levels of CD14++CD16+ in PB compared to patients with normal biopsies (7.9 ± 5.4 vs. 13.0 ± 12.8; p = 0.047). Patients without significant changes had similar percentages of CD14++CD16+ monocytes in the graft blood (GB) and FNAB blood. The percentage of these monocytes in the patients with an interstitial infiltrate, however, increased significantly in the FNAB blood compared to the GB: 16.9 ± 16.6 vs. 7.9 ± 5.4; p = 0.006. A difference of 50% in CD14++CD16+ in the GB versus the PB was a significant risk factor (p = 0.002) for BL, increasing the risk seven times. A decrease in CD14++CD16+ in the PB could be associated with the recruitment of these cells to the graft tissue in cases of subclinical BL inflammatory infiltrates below the threshold for rejection.

Changes in the plasma lipidome of healthy subjects after coffee consumption reveal potential cardiovascular benefits: A randomized controlled trial.

Lipid metabolism dysregulation is associated with cardiovascular disease (CVD) risk. Specific oxidized lipids are recognized CVD biomarkers involved in all stages of atherosclerosis, including foam cell formation. Moderate coffee intake is positively associated with cardiovascular health. A randomized, controlled (n = 25) clinical trial was conducted in healthy subjects to assess the changes in lipid species relevant to CVD (main inclusion criteria: coffee drinkers, nonsmokers, with no history and/or diagnosis of chronic disease and not consuming any medications). Volunteers consumed a coffee beverage (400 mL/day) containing either 787 mg (coffee A; n = 24) or 407 mg (coffee B; n = 25) of chlorogenic acids for eight weeks. We measured the total plasma levels of 46 lipids, including fatty acids, sterols, and oxysterols, at baseline and after eight weeks and assessed the effects of chlorogenic and phenolic acids, the major coffee antioxidants, in an in vitro foam cell model via targeted lipidomics. At baseline (n = 74), all participants presented oxysterols and free fatty acids (FFAs) (CVD risk markers), which are closely correlated to among them, but not with the classical clinical variables (lipid profile, waist circumference, and BMI). After eight weeks, the control group lipidome showed an increase in oxysterols (+7 ± 10%) and was strongly correlated with FFAs (e.g., arachidonic acid) and cholesteryl ester reduction (-13 ± 7%). Notably, the coffee group subjects (n = 49) had increased cholesteryl esters (+9 ± 11%), while oxysterols (-71 ± 30%) and FFAs (-29 ± 26%) decreased. No differences were found between the consumption of coffees A and B. Additionally, coffee antioxidants decreased oxysterols and regulated arachidonic acid in foam cells. Our results suggest that coffee consumption modulates the generation of oxidized and inflammatory lipids in healthy subjects, which are fundamental during CVD development. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer.

BACKGROUND: In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. METHODS: We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. RESULTS: We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. CONCLUSIONS: Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient's progression and therapeutic response.

Características de pacientes atendidos en dos clínicas de anticoagulación de Colombia / Characteristics of patients in two anticoagulation clinics in Colombia

Resumen Objetivo: Establecer las características demográficas, clínicas y terapéuticas de los pacientes anticoagulados atendidos en las clínicas de anticoagulación del Hospital Universitario Fundación Santa Fe de Bogotá (HUFSFB) y del Hospital Universitario San Vicente Fundación Medellín (HUSVF), en los años 2015 y 2016. Método: Se realizó un estudio descriptivo, retrospectivo y transversal. La población de referencia la conformaron los pacientes atendidos en las clínicas de anticoagulación del HUSVF y el HUFSFB en el periodo comprendido entre marzo de 2015 y marzo de 2016. La información se tomó de los registros clínicos de ambos hospitales y para el análisis se utilizó estadística descriptiva. Resultados: Se evaluaron 502 pacientes en las dos clínicas de anticoagulación, con una edad promedio de 64 años en el HUFSFB y de 61 años en el HUSVF. La principal indicación de anticoagulación fue fibrilación o flutter auricular en el HUSVF (46.5%) y enfermedad tromboembólica venosa en el HUFSFB (69.7%). El 100% de los pacientes del HUSVF fueron anticoagulados con warfarina, frente a solo el 23% de los del HUFSFB; el tiempo en rango terapéutico fue del 69% en el HUFSFB y del 55% en el HSVF. Se presentó retrombosis en tres pacientes en cada una de las instituciones, y los eventos de sangrado fueron 7 (3,8%) en el HUFSFB y 30 (9,3%) en el HUSVF. Conclusiones: Las diferencias administrativas entre las dos instituciones se ven reflejadas en los resultados obtenidos. Existe, ligada al sistema de salud de nuestro país, una gran diferencia en la población, las enfermedades y el acceso a los servicios y a los medicamentos.

Abstract Objective: To establish the demographic, clinical and therapeutic characteristics of the anticoagulated patients treated at the anticoagulation clinics of Fundación Santa Fe de Bogotá (HUSVF) and Hospital Universitario San Vicente Fundación Medellin (HUFSFB), between 2015 and 2016. Method: A transversal retrospective descriptive study was carried out. The reference population consist in patients treated in the anticoagulation clinics of the HUSVF in Medellin and the HUFSFB in Bogotá between March 2015 to 2016. The information was taken from the clinical records of both hospitals and descriptive statistics were used for the data analysis. Results: A total of 502 patients were evaluated in both anticoagulation clinics. Patients' average age in HUFSFB was 64 years while in HUSVF was 61; the main pathology that required anticoagulation was the fibrillation/auricular flutter in HUSVF (46,5%) and venous thromboembolic disease in HUFSFB (69.7%). 100% of HUSVF patients are anticoagulated using warfarin and only 23% of those in HUFSFB; the time in therapeutic range (TTR) was 69% in HUFSFB and 55% in HSVF. Re-thrombosis was presented in 3 patients in each of the institutions and the bleeding events were 7 (3.8%) in HUFSFB and 30 (9.3%) in HUSVF. Conclusions: The administrative differences between the two institutions are reflected in the results obtained; there is a great difference in the population, pathologies, access to services and medicines, linked to the health system of our country.

Factors associated with completion of patient surveys 1 year after bariatric surgery.

BACKGROUND: Patient-reported outcomes (PRO) obtained from follow-up survey data are essential to understanding the longitudinal effects of bariatric surgery. However, capturing data among patients who are well beyond the recovery period of surgery remains a challenge, and little is known about what factors may influence follow-up rates for PRO. OBJECTIVES: To assess the effect of hospital practices and surgical outcomes on patient survey completion rates at 1 year after bariatric surgery. SETTING: Prospective, statewide, bariatric-specific clinical registry. METHODS: Patients at hospitals participating in the Michigan Bariatric Surgery Collaborative are surveyed annually to obtain information on weight loss, medication use, satisfaction, body image, and quality of life following bariatric surgery. Hospital program coordinators were surveyed in June 2017 about their practices for ensuring survey completion among their patients. Hospitals were ranked based on 1-year patient survey completion rates between 2011 and 2015. Multivariable regression analyses were used to identify associations between hospital practices, as well as 30-day outcomes, on hospital survey completion rankings. RESULTS: Overall, patient survey completion rates at 1 year improved from 2011 (33.9% ± 14.5%) to 2015 (51.0% ± 13.0%), although there was wide variability between hospitals (21.1% versus 77.3% in 2015). Hospitals in the bottom quartile for survey completion rates had higher adjusted rates of 30-day severe complications (2.6% versus 1.7%, respectively; P = .0481), readmissions (5.0% versus 3.9%, respectively; P = .0157), and reoperations (1.5% versus .7%, respectively; P = .0216) than those in the top quartile. While most hospital practices did not significantly impact survey completion at 1 year, physically handing out surveys during clinic visits was independently associated with higher completion rates (odds ratio, 13.60; 95% confidence interval, 1.99-93.03; P =.0078). CONCLUSIONS: Hospitals vary considerably in completion rates of patient surveys at 1 year after bariatric surgery, and lower rates were associated with hospitals that had higher complication rates. Hospitals with the highest completion rates were more likely to physically hand surveys to patients during clinic visits. Given the value of PRO on longitudinal outcomes of bariatric surgery, improving data collection across multiple hospital systems is imperative.

VCN-01 disrupts pancreatic cancer stroma and exerts antitumor effects.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is characterized by dense desmoplastic stroma that limits the delivery of anticancer agents. VCN-01 is an oncolytic adenovirus designed to replicate in cancer cells with a dysfunctional RB1 pathway and express hyaluronidase. Here, we evaluated the mechanism of action of VCN-01 in preclinical models and in patients with pancreatic cancer. METHODS: VCN-01 replication and antitumor efficacy were evaluated alone and in combination with standard chemotherapy in immunodeficient and immunocompetent preclinical models using intravenous or intratumoral administration. Hyaluronidase activity was evaluated by histochemical staining and by measuring drug delivery into tumors. In a proof-of-concept clinical trial, VCN-01 was administered intratumorally to patients with PDAC at doses up to 1×1011 viral particles in combination with chemotherapy. Hyaluronidase expression was measured in serum by an ELISA and its activity within tumors by endoscopic ultrasound elastography. RESULTS: VCN-01 replicated in PDAC models and exerted antitumor effects which were improved when combined with chemotherapy. Hyaluronidase expression by VCN-01 degraded tumor stroma and facilitated delivery of a variety of therapeutic agents such as chemotherapy and therapeutic antibodies. Clinically, treatment was generally well-tolerated and resulted in disease stabilization of injected lesions. VCN-01 was detected in blood as secondary peaks and in post-treatment tumor biopsies, indicating virus replication. Patients had increasing levels of hyaluronidase in sera over time and decreased tumor stiffness, suggesting stromal disruption. CONCLUSIONS: VCN-01 is an oncolytic adenovirus with direct antitumor effects and stromal disruption capabilities, representing a new therapeutic agent for cancers with dense stroma. TRIAL REGISTRATION NUMBER: EudraCT number: 2012-005556-42 and NCT02045589.

Oxylipin regulation by phenolic compounds from coffee beverage: Positive outcomes from a randomized controlled trial in healthy adults and macrophage derived foam cells.

Oxylipins are considered biomarkers related to cardiovascular diseases (CVDs). They are generated in vivo via the oxygenation of polyunsaturated fatty acids as a result of oxidative stress and inflammation. Oxylipins are involved in vascular functions and are produced during foam cell formation in atherogenesis. Additionally, the consumption coffee is associated with the regulation on a particular oxylipin group, the F2t-isoprostanes (F2t-IsoPs). This function has been attributed to the chlorogenic acids (CGAs) from the coffee beverage. Considering the anti-inflammatory and antioxidant properties of CGAs, we evaluated the effects of two types of coffee that provided 787 mg CGAs/day (Coffee A) and 407 mg CGAs/day (Coffee B) by reducing 35 selected oxylipins in healthy subjects. Furthermore, we assessed the effect of CGAs on the cellular proatherogenic response in foam cells by using an oxidized LDL (oxLDL)-macrophage interaction model. After eight weeks of coffee consumption, the contents of 12 urine oxylipins were reduced. However, the effect of Coffee A showed a stronger decrease in IsoPs, dihomo-IsoPs, prostaglandins (PGs) and PG metabolites, probably due to its higher content of CGAs. Neither of the two coffees reduced the levels of oxLDL. Moreover, the in vitro oxylipin induction by oxLDL on foam cells was ameliorated by phenolic acids and CGAs, including the inhibition of IsoPs and PGs by caffeoylquinic and dicaffeoylquinic acids, respectively, while the phenolic acids maintained both antioxidant and anti-inflammatory activities. These findings suggest that coffee antioxidants are strong regulators of oxylipins related to CVDs. The clinical trial was registered on the International Clinical Trials Registry Platform, WHO primary registry (RPCEC00000168).