Macronutrient-differential dietary pattern impacts on body weight, hepatic inflammation, and metabolism.

Introduction: Obesity is a multi-factorial disease frequently associated with poor nutritional habits and linked to many detrimental health outcomes. Individuals with obesity are more likely to have increased levels of persistent inflammatory and metabolic dysregulation. The goal of this study was to compare four dietary patterns differentiated by macronutrient content in a postmenopausal model. Dietary patterns were high carbohydrate (HC), high fat (HF), high carbohydrate plus high fat (HCHF), and high protein (HP) with higher fiber. Methods: Changes in body weight and glucose levels were measured in female, ovariectomized C57BL/6 mice after 15 weeks of feeding. One group of five mice fed the HCHF diet was crossed over to the HP diet on day 84, modeling a 21-day intervention. In a follow-up study comparing the HCHF versus HP dietary patterns, systemic changes in inflammation, using an 80-cytokine array and metabolism, by untargeted liquid chromatography-mass spectrometry (LCMS)-based metabolomics were evaluated. Results: Only the HF and HCHF diets resulted in obesity, shown by significant differences in body weights compared to the HP diet. Body weight gains during the two-diet follow-up study were consistent with the four-diet study. On Day 105 of the 4-diet study, glucose levels were significantly lower for mice fed the HP diet than for those fed the HC and HF diets. Mice switched from the HCHF to the HP diet lost an average of 3.7 grams by the end of the 21-day intervention, but this corresponded with decreased food consumption. The HCHF pattern resulted in dramatic inflammatory dysregulation, as all 80 cytokines were elevated significantly in the livers of these mice after 15 weeks of HCHF diet exposure. Comparatively, only 32 markers changed significantly on the HP diet (24 up, 8 down). Metabolic perturbations in several endogenous biological pathways were also observed based on macronutrient differences and revealed dysfunction in several nutritionally relevant biosynthetic pathways. Conclusion: Overall, the HCHF diet promoted detrimental impacts and changes linked to several diseases, including arthritis or breast neoplasms. Identification of dietary pattern-specific impacts in this model provides a means to monitor the effects of disease risk and test interventions to prevent poor health outcomes through nutritional modification.

Long-term Outcomes of the Kono-S Anastomosis: A Multicenter Study.

BACKGROUND: Postoperative recurrence remains a significant problem in Crohn's disease, and the mesentery is implicated in the pathophysiology. The Kono-S anastomosis was designed to exclude the mesentery from a wide anastomotic lumen, limit luminal distortion and fecal stasis, and preserve innervation and vascularization. OBJECTIVE: To review postoperative complications and long-term outcomes of the Kono-S anastomosis in a large series of consecutive unselected patients with Crohn's disease. DESIGN: Retrospective study of prospectively collected patients. SETTINGS: Four tertiary referral centers. PATIENTS: Consecutive patients with Crohn's disease who underwent resection with Kono-S anastomosis between May 2010 and June 2022. INTERVENTIONS: Extracorporeal handsewn Kono-S anastomosis. MAIN OUTCOME MEASURES: Postoperative outcomes and recurrence defined as endoscopic, clinical, laboratory, or surgical, including endoscopic, intervention. RESULTS: A total of 262 consecutive patients (53.4% male) were included. The mean duration of disease at surgery was 145.1 months. One hundred thirty-five patients (51.5%) had previous abdominal surgery for Crohn's disease. Forty-four patients (17%) were actively smoking and 150 (57.3%) were on biologic therapy. Anastomotic failure occurred in 4 (1.5%), with 2 patients requiring reoperation (0.7%). Sixteen patients had postoperative surgical site infection (6.1%). With a median follow-up of 49.4 months, 20 patients (7.6%) were found to have surgical recurrence. In the multivariate analysis, perianal disease (OR = 2.83, p = 0.001), urgent/emergent surgery (OR = 3.23, p = 0.007), and postoperative use of steroids (OR = 2.29, p = 0.025) were associated with increased risk of overall recurrence. LIMITATIONS: Retrospective study and variability of perioperative medical therapy. CONCLUSIONS: This study showed very low postoperative complication rates despite the complexity of the patient population. There was a low rate of surgical recurrence, likely due to the intrinsic advantages of the anastomotic configuration and the low rate of postoperative septic complications. In experienced hands, the Kono-S anastomosis is a safe technique with very promising short- and long-term results. Randomized controlled trials are underway to validate this study's findings. See Video Abstract . RESULTADO A LARGO PLAZO DE LA ANASTOMOSIS KONOS UN ESTUDIO MULTICNTRICO: ANTECEDENTES:La recurrencia posoperatoria sigue siendo un problema importante en la enfermedad de Crohn y el mesenterio está implicado en la fisiopatología. La anastomosis Kono-S fue diseñada para excluir el mesenterio de una anastomosis amplia, limitar la distorsión luminal y la estasis fecal y preservar la inervación y vascularización.OBJETIVO:Revisar las complicaciones posoperatorias y los resultados a largo plazo de la anastomosis Kono-S en una gran serie de pacientes consecutivos no seleccionados con enfermedad de Crohn.DISEÑO:Estudio retrospectivo de pacientes recolectados prospectivamente.ESCENARIO:Cuatro centros de referencia terciarios.PACIENTES:Pacientes consecutivos con enfermedad de Crohn sometidos a resección con anastomosis Kono-S entre mayo de 2010 y junio de 2022.INTERVENCIONES:Anastomosis Kono-S extracorpórea manual.PRINCIPALES MEDIDAS DE RESULTADO:Resultados posoperatorios y recurrencia definidos como endoscópicos, clínicos, de laboratorio o quirúrgicos, incluida la intervención endoscópica.RESULTADOS:Se incluyeron un total de 262 pacientes consecutivos (53,4% varones). La duración media de la enfermedad al momento de la cirugía fue de 145,1 meses. Ciento treinta y cinco pacientes (51,5%) habían tenido cirugía abdominal previa por enfermedad de Crohn. Cuarenta y cuatro pacientes (17%) eran fumadores activos y 150 (57,3%) estaban en tratamiento biológico. Se produjo filtración anastomótica en 4 (1,5%) y 2 pacientes requirieron reoperación (0,7%). Dieciséis pacientes tuvieron infección postoperatoria del sitio quirúrgico (6,1%). Con una mediana de seguimiento de 49,4 meses, se encontró que 20 pacientes (7,6%) tuvieron recurrencia quirúrgica. En el análisis multivariado, la enfermedad perianal (OR = 2,83, p = 0,001), la cirugía urgente/emergente (OR = 3,23, p = 0,007), el uso postoperatorio de esteroides (OR = 2,29, p = 0,025) se asociaron con un mayor riesgo de recurrencia general.LIMITACIÓN:Estudio retrospectivo. Variabilidad del tratamiento médico perioperatorio.CONCLUSIONES:Nuestro estudio mostró tasas de complicaciones postoperatorias muy bajas a pesar de la complejidad de la población de pacientes. Hubo una baja tasa de recurrencia quirúrgica, probablemente debido a las ventajas intrínsecas de la configuración anastomótica y la baja tasa de complicaciones sépticas posoperatorias. En manos experimentadas, la anastomosis Kono-S es una técnica segura con resultados muy prometedores a corto y largo plazo. Se están realizando estudios randomizados controlados para validar nuestros hallazgos. (Traducción-Dr. Felipe Bellolio ).

Perioperative Management of Patients Undergoing Total Pancreatectomy with/without Islet Cell Autotransplantation: A Single Center Experience.

Total pancreatectomy (TP) and islet cell autotransplantation (IAT) are complex operations that require intensive postoperative monitoring with standardized protocols. There are few studies detailing immediate perioperative management. The purpose of this study was to describe the perioperative management of post-pancreatectomy patients in the first week following surgery to guide clinicians in addressing salient points from different organ systems. This is a retrospective cohort review of prospectively collected data from September 2017 to September 2022 at a single institution, including patients 16 years and older who underwent TP or TPIAT for chronic pancreatitis. Patients were maintained on a heparin drip (TPIAT), insulin drip, and ketamine infusion. Primary outcomes were complications in the first 5 days following surgery and ICU length of stay (LOS). Secondary outcomes included overall LOS and mortality. Of 31 patients, 26 underwent TPIAT, and 5 underwent TP. Median ICU LOS was five days (IQR 4-6). The most common immediate postoperative complications were reintubation [n = 5 (16%)] and bleeding [n = 2 (6%)]. Median insulin drip use was 70 h (IQR 20-124). There was no mortality. Patients were extubated quickly and progressed well on the protocol. Immediate postoperative complications were generally minor and without long-term effects.

Clinical trial-identified inflammatory biomarkers in breast and pancreatic cancers.

Breast cancer and pancreatic cancer are two common cancer types characterized by high prevalence and high mortality rates, respectively. However, breast cancer has been more well-studied than pancreatic cancer. This narrative review curated inflammation-associated biomarkers from clinical studies that were systematically selected for both breast and pancreatic cancers and discusses some of the common and unique elements between the two endocrine-regulated malignant diseases. Finding common ground between the two cancer types and specifically analyzing breast cancer study results, we hoped to explore potential feasible methods and biomarkers that may be useful also in diagnosing and treating pancreatic cancer. A PubMed MEDLINE search was used to identify articles that were published between 2015-2022 of different kinds of clinical trials that measured immune-modulatory biomarkers and biomarker changes of inflammation defined in diagnosis and treatment of breast cancer and pancreatic cancer patients. A total of 105 papers (pancreatic cancer 23, breast cancer 82) were input into Covidence for the title and abstract screening. The final number of articles included in this review was 73 (pancreatic cancer 19, breast cancer 54). The results showed some of the frequently cited inflammatory biomarkers for breast and pancreatic cancers included IL-6, IL-8, CCL2, CD8+ T cells and VEGF. Regarding unique markers, CA15-3 and TNF-alpha were two of several breast cancer-specific, and CA19 and IL-18 were pancreatic cancer-specific. Moreover, we discussed leptin and MMPs as emerging biomarker targets with potential use for managing pancreatic cancer based on breast cancer studies in the future, based on inflammatory mechanisms. Overall, the similarity in how both types of cancers respond to or result in further disruptive inflammatory signaling, and that point to a list of markers that have been shown useful in diagnosis and/or treatment method response or efficacy in managing breast cancer could potentially provide insights into developing the same or more useful diagnostic and treatment measurement inflammatory biomarkers for pancreatic cancer. More research is needed to investigate the relationship and associated inflammatory markers between the similar immune-associated biological mechanisms that contribute to breast and pancreatic cancer etiology, drive disease progression or that impact treatment response and reflect survival outcomes.

Impact of the hepatoselective glucokinase activator TTP399 on ketoacidosis during insulin withdrawal in people with type 1 diabetes.

AIMS: To determine the effect of TTP399, a hepatoselective glucokinase activator, on the risk of ketoacidosis during insulin withdrawal in individuals with type 1 diabetes (T1D). MATERIALS AND METHODS: Twenty-three participants with T1D using insulin pump therapy were randomized to 800 mg TTP399 (n = 12) or placebo (n = 11) for 7 to 10 days. After the treatment period, an insulin withdrawal test (IWT) was performed, during which insulin pumps were removed to induce ketogenesis. The IWT was stopped after 10 hours or if blood glucose reached >399 mg/dL [22.1 mmol/L], if beta-hydroxybutyrate (BHB) was >3.0 mmol/L, or for patient discomfort. The primary endpoint was the proportion of participants who reached BHB concentrations of 1 mmol/L or greater. RESULTS: During the 7- to 10-day treatment period, mean fasting plasma glucose was significantly reduced ( -27.6 vs. -4.4 mg/dL [-1.5 vs. -0.2 mmol/L]; P = 0.03) and there were fewer adverse events, including hypoglycaemia, in the TTP399-treated arm. During the IWT, no differences were observed between TTP399 and placebo in mean serum BHB concentration, mean duration of IWT, or BHB at termination of IWT. However, serum bicarbonate was numerically higher and urine acetoacetate was quantitatively lower in the TTP399-treated participants. As a result of higher bicarbonate values, none of the TTP399-treated participants met the prespecified criteria for diabetic ketoacidosis (DKA), defined as BHB >3 mmol/L and serum bicarbonate <18 mEq/L, compared to 42% of placebo-treated participants. CONCLUSIONS: When used as an adjunctive therapy to insulin, TTP399 improves glycaemia without increasing hypoglycaemia in individuals with T1D. During acute insulin withdrawal, TTP399 did not increase BHB concentrations and decreased the incidence of DKA.