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With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier UMIN000007636.

With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier UMIN000007636.Prolonged chest tube drainage is one of the most common postoperative complications of pulmonary resections; it is related to complications such as residual pleural spaces or continuous alveolar air leaks. We retrospectively evaluated the efficacy of artificial intraoperative pneumoperitoneum in the treatment of such complications after lung resections. The presence of a residual space associated with prolonged air leaks can be difficult to treat, exposes the patient to a high risk of infection, prolongs hospitalization, and in some cases mandates reoperation. Between October 2016 and March 2020, four patients underwent pneumoperitoneum. The obliteration of the pleural cavity and the absence of air leaks were observed in 3 patients; only 1 patient was discharged with a Heimlich valve. Artificial intraoperative pneumoperitoneum is a safe and simple procedure. It decreases the duration of chest drainage and of the hospital stay; however, further studies are needed to corroborate our data. The learning curve for this technique may be relatively short.

Falling insulin requirements often lead to considerations of whether a pregnancy can continue safely or if delivery is indicated.

To evaluate prevalence and predictors of falling insulin requirements in pregnant women with preexisting diabetes delivering preterm and to explore the relationship to fetal asphyxia and neonatal morbidity.

A prospective cohort study of 101 consecutive singleton pregnant women with preexisting diabetes delivering preterm < 37 weeks (68 type 1 and 33 type 2 diabetes) where the prevalence of falling insulin requirements (≥20%) before delivery was recorded.

In total, 27% (27/101) experienced falling insulin requirements of median 30% (interquartile range 24-40) before delivery. In all women with type 1 diabetes, the prevalence was 37% (25/68), whereas it was 43% (24/56) in those with indicated preterm delivery and 6% (2/33) among women with type 2 diabetes. In women with type 1 diabetes and indicated preterm delivery, falling insulin requirements were first identified at 34nly reflects variations in normal physiology needs further investigation.

Diabetic kidney disease is a major burden among diabetic patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) were shown to reduce renal outcomes in clinical trials and real-world studies. However, head-to-head comparisons with individual classes of glucose-lowering agents warranted further investigation.

This work aimed to investigate the associations between SGLT2is use vs dipeptidyl peptidase-4 inhibitors (DPP4is) use and 4 renal outcomes end-stage renal disease (ESRD), albuminuria, acute renal failure (ARF), and the rate of estimated glomerular filtration rate (eGFR) change using a territory-wide electronic medical database in Hong Kong.

For this retrospective cohort study, the "prevalent new-user" design was adopted to account for previous exposure to study drugs. Propensity score matching was used to balance baseline characteristics. Electronic health data of type 2 diabetes patients using SGLT2is and DPP4is between 2015 and 2018 were collected.

The matched cohort consisted of 6333 SGLT2is users and 25 332 DPP4is users, with a median follow-up of 3.8 years. Compared to DPP4is, SGLT2is use was associated with lower risks of ESRD (hazard ratio [HR] 0.51; 95% CI, 0.42-0.62; P < .001) and ARF (HR 0.59; 95% CI, 0.48-0.73; P < .001), and a slower decline in eGFR. AZD4547 The associations remained statistically significant among patients with or without rapid eGFR decline and patients who added or switched to SGLT2is from DPP4is. The association with albuminuria was inconsistent across analyses.

Compared to DPP4is, SGLT2is use was associated with reduced risks of ESRD and ARF, and a slower eGFR decline in a real-world setting. The associations remained statistically significant in patients with or without preindex rapid eGFR decline.

Compared to DPP4is, SGLT2is use was associated with reduced risks of ESRD and ARF, and a slower eGFR decline in a real-world setting. The associations remained statistically significant in patients with or without preindex rapid eGFR decline.The hepatic transcription factor forkhead box O1 (FOXO1) is a critical regulator of hepatic and systemic insulin sensitivity. Previous work by our group and others demonstrated that genetic inhibition of FOXO1 improves insulin sensitivity both in genetic and dietary mouse models of metabolic disease. Mechanistically, this is due in part to cell nonautonomous control of adipose tissue insulin sensitivity. However, the mechanisms mediating this liver-adipose tissue crosstalk remain ill defined. One candidate hepatokine controlled by hepatic FOXO1 is fibroblast growth factor 21 (FGF21). Preclinical and clinical studies have explored the potential of pharmacological FGF21 as an antiobesity and antidiabetic therapy. In this manuscript, we performed acute loss-of-function experiments to determine the role of hepatocyte-derived FGF21 in glucose homeostasis and insulin tolerance both in control and mice lacking hepatic insulin signaling. Surprisingly, acute deletion of FGF21 did not alter glucose tolerance, insulin tolerance, or adipocyte lipolysis in either liver-specific FGF21KO mice or mice lacking hepatic AKT-FOXO1-FGF21, suggesting a permissive role for endogenous FGF21 in the regulation of systemic glucose homeostasis and insulin tolerance in mice. In addition, these data indicate that liver FOXO1 controls glucose homeostasis independently of liver-derived FGF21.

The purpose of this study was to develop and validate a cochlear implant (CI)-specific parenting stress measure using the FDA Guidance on Patient-Reported Outcomes (2009).

The development and psychometric validation of the Parenting Stress-CI module for both the Early Childhood (EC; 0-5 years) and School-Age (SA; 6-12 years) versions are reported in this article. Instrument development consisted of qualitative interviews with parents of children with CIs (EC N = 19; SA N = 21), content analysis, item development, and cognitive testing of the instrument. Last, we conducted the psychometric validation (EC N = 72; SA N = 64), including analyses of internal consistency, test-retest reliability (∼2 weeks between administrations; N = 24), and convergent validity with the Parenting Stress Index-4 (PSI-4).

The final EC version includes 15 questions, and the SA version includes 8 questions. Both the EC and SA versions had strong reliability (EC α = .88; SA α = .85), with all items significantly correlated with the overall module (r = .43-.80). Both versions also had strong test-retest reliability (r = .99, p < .001). Last, analyses of convergent validity demonstrated significant correlations with the PSI-4 Total Stress scale for both Parenting Stress-CI versions (EC r = .66, p < .00; SA r = .45, p < .001).

The Parenting Stress-CI modules are reliable and valid condition-specific parenting stress instruments for parents of children with CIs ages 0-12 years, filling a significant gap in the literature. These fully validated instruments can be used to assess parental needs for support and guide the development of targeted, family centered interventions.

The Parenting Stress-CI modules are reliable and valid condition-specific parenting stress instruments for parents of children with CIs ages 0-12 years, filling a significant gap in the literature. These fully validated instruments can be used to assess parental needs for support and guide the development of targeted, family centered interventions.Neutrophils are key players during host defense and sterile inflammation. Neutrophil dysfunction is a characteristic feature of the acquired immunodeficiency during kidney disease. We speculated that the impaired renal clearance of the intrinsic purine metabolite soluble uric acid (sUA) may account for neutrophil dysfunction. Indeed, hyperuricemia (HU, serum UA of 9-12 mg/dL) related or unrelated to kidney dysfunction significantly diminished neutrophil adhesion and extravasation in mice with crystal- and coronavirus-related sterile inflammation using intravital microscopy and an air pouch model. This impaired neutrophil recruitment was partially reversible by depleting UA with rasburicase. We validated these findings in vitro using either neutrophils or serum from patients with kidney dysfunction-related HU with or without UA depletion, which partially normalized the defective migration of neutrophils. Mechanistically, sUA impaired β2 integrin activity and internalization/recycling by regulating intracellular pH and cytoskeletal dynamics, physiological processes that are known to alter the migratory and phagocytic capability of neutrophils. This effect was fully reversible by blocking intracellular uptake of sUA via urate transporters. In contrast, sUA had no effect on neutrophil extracellular trap formation in neutrophils from healthy subjects or patients with kidney dysfunction. Our results identify an unexpected immunoregulatory role of the intrinsic purine metabolite sUA, which contrasts the well-known immunostimulatory effects of crystalline UA. Specifically targeting UA may help to overcome certain forms of immunodeficiency, for example in kidney dysfunction, but may enhance sterile forms of inflammation.Bruton tyrosine kinase (BTK) inhibitor is an established treatment for relapsed/refractory (R/R) mantle cell lymphoma (MCL). Zanubrutinib, a highly selective BTK inhibitor, is approved for patients with MCL who have received ≥1 prior therapy. We report the long-term safety and efficacy results from the multicenter, open-label, phase 2 registration trial of zanubrutinib. Patients (n = 86) received oral zanubrutinib 160 mg twice daily. The primary endpoint was the overall response rate (ORR), assessed per Lugano 2014. After a median follow-up of 35.3 months, the ORR was 83.7%, with 77.9% achieving complete response (CR); the median duration of response was not reached. Median progression-free survival (PFS) was 33.0 months (95% confidence interval [CI], 19.4-NE). The 36-month PFS and overall survival (OS) rates were 47.6% (95% CI, 36.2-58.1) and 74.8% (95% CI, 63.7-83.0), respectively. The safety profile was largely unchanged with extended follow-up. Most common (≥20%) all-grade adverse events (AEs) were neutrophil count decreased (46.5%), upper respiratory tract infection (38.4%), rash (36.0%), white blood cell count decreased (33.7%), and platelet count decreased (32.6%); most were grade 1/2 events. Most common (≥10%) grade ≥3 AEs were neutrophil count decreased (18.6%) and pneumonia (12.8%). Rates of infection, neutropenia, and bleeding were highest in the first 6 months of therapy and decreased thereafter. No cases of atrial fibrillation/flutter, grade ≥3 cardiac AEs, second primary malignancies, or tumor lysis syndrome were reported. After extended follow-up, zanubrutinib demonstrated durable responses and a favorable safety profile in R/R MCL. The trial is registered at ClinicalTrials.gov as NCT03206970.