Design and rationale of penn medicine healthy heart, a randomized trial of effectiveness of a centrally organized approach to blood pressure and cholesterol improvement among patients at elevated risk of atherosclerotic cardiovascular disease.

RATIONALES: Atherosclerotic Cardiovascular Disease (ASCVD) is the leading cause of morbidity and mortality in the United States. Suboptimal control of hypertension and hyperlipidemia are common factors contributing to ASCVD risk. The Penn Medicine Healthy Heart (PMHH) Study is a randomized clinical trial testing the effectiveness of a system designed to offload work from primary care clinicians and improve patient follow-through with risk reduction strategies by using a centralized team of nonclinical navigators and advanced practice providers, remote monitoring, and bi-directional text messaging, augmented by behavioral science engagement strategies. The intervention builds on prior nonrandomized evaluations of these design elements that demonstrated significant improvement in patients' systolic blood pressure and LDL Cholesterol (LDL-C). PRIMARY HYPOTHESIS: Penn Medicine Healthy Heart will significantly improve systolic blood pressure and LDL-C compared to usual care over the 6 months of this intervention. DESIGN: Randomized clinical trial of Penn Medicine Healthy Heart in patients aged 35-80 years at elevated risk of ASCVD whose systolic blood pressure and LDL-C are not well controlled. The intervention consists of 4 modules that address blood pressure management, lipid management, nutrition, and smoking cessation, offered in a phased approach to give the participant time to learn about each topic, adopt any recommendations, and build a relationship with the care team. SITES: University of Pennsylvania Health System at primary care practices located in inner-city urban and rural/semi-rural areas. PRIMARY OUTCOMES: Improvement in systolic blood pressure and LDL-C. SECONDARY OUTCOMES: Cost-effectiveness analyses are planned to evaluate the health care costs and health outcomes of the intervention approach. An implementation evaluation is planned to understand factors influencing success of the intervention. ESTIMATED ENROLLMENT: 2,420 active patients of Penn Medicine primary care practices who have clinical ASCVD, or who are at elevated risk for ASCVD, and who are (a) not on statins or have LDL-C >100 despite being on statins and (b) had systolic blood pressure >140 at 2 recent ambulatory visits. ENROLLMENT DATES: March 2024-March 2025. The intervention will last 6 months with a 12-month follow-up to determine whether its effects persist. CURRENT STATUS: Enrolling (1,240 enrolled as of August 15, 2024) CLINICAL TRIAL REGISTRATION: NCT06062394.

Review article: strategies for the management of chronic unremitting ulcerative colitis.

BACKGROUND: Chronic active ulcerative colitis (UC) is associated with significant morbidity, loss of productivity, increased colorectal cancer risk and cost. Up to 18% of patients suffer chronic active disease, with 30% requiring colectomy at 10 years. The management remains challenging given the relatively few clinical trials in this area. AIM: To summarise the evidence regarding optimal management strategies for patients with chronic active UC of differing disease extents and degrees of treatment refractoriness. METHOD: A literature search using the PubMed and Medline databases was performed. No time limit was set on article publication for inclusion. RESULTS: The principles of management should focus on confirming disease activity, exclusion of alternative diagnoses, adherence and treatment escalation. Infliximab and topical tacrolimus are options in refractory proctitis, although the evidence for these therapies is limited. Both infliximab and adalimumab are effective in corticosteroid-refractory disease, although the proportions of patients achieving corticosteroid-free remission remain modest (24% at 30 weeks and 16.9% at 8 weeks respectively). Alternatives include ciclosporin and tacrolimus, and possibly methotrexate. Colectomy often leads to an improved quality of life; medical strategies unlikely to provide durable corticosteroid-free remission should not be pursued. CONCLUSIONS: No current pharmacological treatment delivers mucosal healing in the majority of patients. Newer treatments such as vedolizumab and tofacitinib may represent valuable future therapies. Available medical options should be discussed with patients at every step of their management, with an honest appraisal of the evidence. Surgery should always be considered in patients with chronic refractory disease of any extent.

Splenomegaly, cardiomegaly, and osteoporosis in a child with Gaucher disease.

A 15-month-old girl, born to the consanguineous parents, was referred with the sign of massive splenomegaly associated with thrombocytopenia and anemia. Plasma Chitotriosidase estimation was carried out as a screening test and was found to be normal with reduced activity of ß-glucosidase in leucocytes suggestive of Gaucher disease. At the age of 4 years, severe osteoporosis and cardiomegaly with pulmonary congestion were observed in the child. Molecular analysis for GBA gene has revealed homozygous status for L444P (c.1448C) in the proband, whereas parents and two elder sisters were found to be heterozygote. Prenatal study during the fourth pregnancy was carried out from cultured chorionic villi for ß-glucosidase, which was in the carrier range. Further confirmation of the carrier status was carried out from amniotic fluid DNA and was found to be heterozygous for L444P (c.1448C) in the GBA gene. This case demonstrates that children with the sign of splenomegaly with anemia and thrombocytopenia need to be screened for Gaucher disease, and molecular study can further help to confirm the heterozygous status, where prenatal study by enzyme investigation demonstrate heterozygous condition.

Manometric studies of the human pylorus.

The human gastroduodenal junction was investigated by means of simultaneous measurements of pressure and potential difference between skin and mucosa. An accurate and circumferentially sensitive miniature transducer assembly failed to reveal a zone of elevated pressure at the gastroduodenal junction of 8 fasting, healthy, young subjects. Additional studies were carried out with a six-lumen perfused catheter system, in which three of the pressure-transmitting catheters had openings arranged circumferentially at the same axial level. Measurements of pressure and potential difference were obtained basally during intraduodenal infusion of hydrochloric acid and after intraduodenal instillation of olive oil. In only 1 of 10 subjects was a tonic elevation in pressure recorded simultaneously by all three leads at the gastroduodenal junction. The normal human pylorus, therefore, is not reliably demonstrable as a high pressure zone.

Inhibition of Chlamydia pneumoniae replication in HEp-2 cells by interferon-gamma: role of tryptophan catabolism.

Interferon-gamma (IFN-gamma) induces tryptophan catabolism in HEp-2 cells, possibly via stimulation of host cell indoleamine-2,3-dioxygenase activity, in a dose-dependent (12.5-1600 U/mL) fashion after 24 h, resulting in a 99% conversion to its metabolites at 1600 U/mL. Replication of Chlamydia pneumoniae isolates A-03 and BAL-16 was inhibited in HEp-2 cells following treatment with 50 and 100 U/mL IFN-gamma, respectively; however, addition of excess L-tryptophan (200 microg/mL) to monolayers infected with C. pneumoniae resulted in unrestricted growth of both isolates up to 1600 U/mL IFN-gamma. C. pneumoniae could be recovered from IFN-gamma-treated monolayers, indicating the potential for this bacterium to undergo an altered life cycle, in vitro, analogous to that described in detail for Chlamydia trachomatis. The ability of C. pneumoniae to persist in host tissue despite an immunologic response would be an important attribute in order to cause or exacerbate chronic infections.

Relative concentrations of individual nonsulfated bile acids in the serum and bile of patients with cirrhosis.

The relative concentrations of individual nonsulfated bile acids were determined in samples of serum and bile obtained simultaneously from 16 patients with biopsy-proven alcoholic cirrhosis. A highly significant (P less than 0.001) correlation was found between the fasting relative concentrations of each of the three major bile acids (cholic, chenodeoxycholic, and deoxycholic) in serum and bile. This relationship persisted after manipulation of bile acid pools produced by feeding of individual bile acids. We conclude that the relative concentrations of individual nonsulfated bile acids in serum accurately reflect those in bile and that measurement of individual serum bile acids may be used for screening and serial determination purposes. In particular, low levels of biliary deoxycholate can be reliably predicted by serum measurements.

Radiation-induced intestinal pseudoobstruction.

A case of intestinal pseudoobstruction occurring 30 yr after radiation therapy is described. Mechanical causes of obstruction were excluded by laparotomy. Histology of full-thickness sections of the small bowel revealed vascular ectasia and sclerosis, serosal fibrosis, neuronal proliferation within the submucosa, and degeneration of the muscle fibers of the circular layer of the muscularis propria. On the basis of the clinical and histologic findings we conclude that, in this patient, intestinal pseudoobstruction was due to muscular and neuronal injury from abdominal irradiation.