The effect of frailty and age on outcomes in elective paraesophageal hernia repair.

Introduction: Paraesophageal hernia repair (PEHR) is a safe and effective operation. Previous studies have described risk factors for poor peri-operative outcomes such as emergent operations or advanced patient age, and pre-operative frailty is a known risk factor in other major surgery. The goal of this retrospective cohort study was to determine if markers of frailty were predictive of poor peri-operative outcomes in elective paraesophageal hernia repair.

Interventions to Improve Surveillance for Hepatocellular Carcinoma in High-Risk Patients: A Scoping Review.

Purpose: Hepatocellular carcinoma (HCC) is most often a sequela of chronic liver disease or chronic hepatitis B infection. Among high-risk patients, surveillance for HCC every 6 months is recommended by international guidelines. However, rates of HCC surveillance are suboptimal (11-64%).

mTORC1 regulates a lysosome-dependent adaptive shift in intracellular lipid species.

The mechanistic target of rapamycin complex 1 (mTORC1) senses and relays environmental signals from growth factors and nutrients to metabolic networks and adaptive cellular systems to control the synthesis and breakdown of macromolecules; however, beyond inducing de novo lipid synthesis, the role of mTORC1 in controlling cellular lipid content remains poorly understood. Here we show that inhibition of mTORC1 via small molecule inhibitors or nutrient deprivation leads to the accumulation of intracellular triglycerides in both cultured cells and a mouse tumor model. The elevated triglyceride pool following mTORC1 inhibition stems from the lysosome-dependent, but autophagy-independent, hydrolysis of phospholipid fatty acids.

Improving Access and Quality of Care for Kidney Stone Patients in an Underserved Community.

There is a call to improve Medicaid patient access to health care, enhance quality and outcomes of care, and reduce overall financial burden. We sought to build a comprehensive kidney stone program to help patients navigate through the acute and preventive aspects of stone disease by increasing multidisciplinary referrals and compliance with recommendations and decreasing no-show rates at first follow-up and repeat stone encounters after initial evaluation. A collaborative multidisciplinary program was established at our single institution consisting of urology, nephrology, and dietary specialists to be piloted over a 3-year period.

Reciprocal effects of mTOR inhibitors on pro-survival proteins dictate therapeutic responses in tuberous sclerosis complex.

mTORC1 is aberrantly activated in cancer and in the genetic tumor syndrome tuberous sclerosis complex (TSC), which is caused by loss-of-function mutations in the TSC complex, a negative regulator of mTORC1. Clinically approved mTORC1 inhibitors, such as rapamycin, elicit a cytostatic effect that fails to eliminate tumors and is rapidly reversible. We sought to determine the effects of mTORC1 on the core regulators of intrinsic apoptosis.

Incidental splenosis discovered during robotic assisted radical prostatectomy: A case report.

Splenosis refers to the benign heterotopic auto transplantation of splenic tissue that most commonly arises following traumatic rupture of the spleen. It is most often associated with traumatic rupture of the spleen. While often asymptomatic, splenosis can mimic malignancy and may lead to unnecessary biopsy, chemotherapy, and surgery.

Patient-, Provider-, and System-Level Barriers to Surveillance for Hepatocellular Carcinoma in High-Risk Patients in the USA: a Scoping Review.

Purpose: Hepatocellular carcinoma has a dismal prognosis, except in patients diagnosed early who are candidates for potentially curative therapies. Most HCC cases develop in patients with chronic liver disease. Therefore, expert society guidelines recommend surveillance every 6 months with ultrasound with or without serum alpha-fetoprotein for high-risk patients.

Colonic intussusception masquerading as diverticulitis: a case report of a 31 year old diagnosed with colorectal carcinoma after multiple presentations to the ED for episodes of acute diverticulitis.

Colonic intussusception is a rare occurrence in adults, with few reported cases in the literature. Patients often present with nonspecific and vague symptoms leading to diagnostic challenges and delayed treatment. Given the high incidence of underlying malignancy associated with cases of adult intussusception, it is important for clinicians to be able to recognize and coordinate appropriate follow-up.

IMPDH inhibitors for antitumor therapy in tuberous sclerosis complex.

Recent studies in distinct preclinical tumor models have established the nucleotide synthesis enzyme inosine-5'-monophosphate dehydrogenase (IMPDH) as a viable target for antitumor therapy. IMPDH inhibitors have been used clinically for decades as safe and effective immunosuppressants. However, the potential to repurpose these pharmacological agents for antitumor therapy requires further investigation, including direct comparisons of available compounds.

mTORC1 Couples Nucleotide Synthesis to Nucleotide Demand Resulting in a Targetable Metabolic Vulnerability.

The mechanistic target of rapamycin complex 1 (mTORC1) supports proliferation through parallel induction of key anabolic processes, including protein, lipid, and nucleotide synthesis. We hypothesized that these processes are coupled to maintain anabolic balance in cells with mTORC1 activation, a common event in human cancers. Loss of the tuberous sclerosis complex (TSC) tumor suppressors results in activation of mTORC1 and development of the tumor syndrome TSC.

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function.

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction.

BMI1 induces an invasive signature in melanoma that promotes metastasis and chemoresistance.

Melanoma can switch between proliferative and invasive states, which have identifying gene expression signatures that correlate with good and poor prognosis, respectively. However, the mechanisms controlling these signatures are poorly understood. In this study, we identify BMI1 as a key determinant of melanoma metastasis by which its overexpression enhanced and its deletion impaired dissemination.