SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery.

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: a phase 3 Children's Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial.

Sirolimus has activity against acute lymphoblastic leukemia (ALL) in xenograft models and efficacy in preventing acute graft-versus-host disease (aGVHD). We tested whether addition of sirolimus to GVHD prophylaxis of children with ALL would decrease aGVHD and relapse. Patients were randomized to tacrolimus/methotrexate (standard) or tacrolimus/methotrexate/sirolimus (experimental). The study met futility rules for survival after enrolling 146 of 259 patients. Rate of Grade 2-4 aGVHD was 31% vs 18% (standard vs experimental, P = .04), however, grade 3-4 aGVHD was not different (13% vs 10%, P = .28). Rates of veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) were lower in the nonsirolimus arm (9% vs 21% VOD, P = .05; 1% vs 10% TMA, P = .06). At 2 years, event free survival (EFS) and overall survival (OS) were 56% vs 46%, and 65% vs 55% (standard vs experimental), respectively (P = .28 and .23). Multivariate analysis showed increased relapse risk in children with ≥0.1% minimal residual disease (MRD) pretransplant, and decreased risk in patients with grades 1-3 aGVHD (P = .04). Grades 1-3 aGVHD were associated with improved EFS (P = .02), whereas grade 4 aGVHD and extramedullary disease at diagnosis led to inferior OS. Although addition of sirolimus decreased aGVHD, survival was not improved. This study is registered with ClinicalTrials.gov as #NCT00382109.

Roux-en-Y Gastric Bypass Increases Glycemic Variability and Time in Hypoglycemia in Patients With Obesity and Prediabetes or Type 2 Diabetes: A Prospective Cohort Study.

OBJECTIVE: Roux-en-Y gastric bypass (RYGB) is an established treatment for type 2 diabetes and obesity. The study objective was to establish RYGB's effects on glycemic variability (GV) and hypoglycemia. RESEARCH DESIGN AND METHODS: This was a prospective observational study of 10 participants with obesity and prediabetes or type 2 diabetes who underwent RYGB. Patients were studied before RYGB (Pre) and 1 month, 1 year, and 2 years postsurgery with continuous glucose measurement (CGM). A mixed-meal test (MMT) was conducted at Pre, 1 month, and 1 year. RESULTS: After RYGB, mean CGM decreased (at 1 month, 1 year, and 2 years), and GV increased (at 1 year and 2 years). Five of the 10 participants had a percent time in range (%TIR) <3.0 mmol/L (54 mg/dL) greater than the international consensus target of 1% at 1 or 2 years. Peak glucagon-like peptide-1 (GLP-1) and glucagon area under the curve during MMT were positively and negatively associated, respectively, with contemporaneous %TIR <3.0 mmol/L. CONCLUSIONS: Patients undergoing RYGB are at risk for development of postbariatric hypoglycemia due to a combination of reduced mean glucose, increased GV, and increased GLP-1 response.

Hepatitis C: a public health response in Kansas.

The hepatitis C (HCV) infection prevalence in Kansas is concentrated in populations with increased risk factors for acquiring the virus. Testing the appropriate population and providing counseling and medical referral to these high risk individuals is accomplished by offering HCV testing at HIV Counseling and Testing sites across the state. Such public health programs along with the medical community allow the at risk populations of Kansas an opportunity to improve their health and decrease the spread of HCV

Diarrheal illnesses: a public health perspective.

Diarrheal illnesses remain among the leading causes of morbidity in the United States. Approximately five million diarrheal cases occur annually (Chin, 2000; Ostroff & Leduc, 2000), with an estimated incidence of one diarrheal episode per person per year (Aranda-Michel & Giannella, 1999). Though the causes of diarrheal illnesses vary, infectious agents account for a majority of cases (Aranda-Michel & Giannella, 1999; Chin, 2000; Ostroff & Leduc, 2000). Most diarrhea-causing infectious agents are transmitted through food, water, or person-to-person via the fecal-oral route and are the cause of numerous diarrheal outbreaks. The risk for exposure to such pathogens within the general population is universal; however, persons in pediatric, geriatric, and other immunocompromised populations are at increased risk for subsequent illness and complications (Centers for Disease Control and Prevention, 2001; Ostroff & Leduc, 2000). Moreover, many persons with diarrheal illness do not seek medical care and self-treat with over-the-counter antidiarrheal agents, which have potentially serious side effects among high-risk individuals. The public health impact of diarrheal illness is apparent and emphasizes the need for early diagnosis and appropriate treatment, timely notification of illness with public health implications, and coordination between healthcare professionals and public health officials to prevent and control the spread of infection.

Preliminary report: the effect of a 6-month dietary glycemic index manipulation in addition to healthy eating advice and weight loss on arterial compliance and 24-hour ambulatory blood pressure in men: a pilot study.

We aimed to determine whether altering dietary glycemic index (GI) in addition to healthy eating and weight loss advice affects arterial compliance and 24-hour blood pressure (BP), both coronary heart disease (CHD) risk factors. Middle-aged men with at least 1 CHD risk were randomized to a 6-month low-GI (LGI) or high-GI (HGI) diet. All were advised on healthy eating and weight loss. They were seen monthly to assess dietary compliance and anthropometrics. Carotid-femoral pulse wave velocity (PWV), fasting blood lipid profile, and glucose and insulin concentrations were measured at baseline and at months 3 and 6. Six-hour postprandial glucose and insulin responses and 24-hour ambulatory BP were also assessed at baseline and month 6. Thirty-eight subjects (HGI group, n = 16; LGI group, n = 22) completed the study. At month 6, groups differed in dietary GI, glycemic load, and carbohydrate intake (P < .001). Fasting insulin concentration and insulin resistance (calculated by homeostatic model assessment) were lower in the LGI than the HGI group (P < .01). The reduction in total cholesterol and 24-hour BP was bigger in the LGI than the HGI group (P < .05); and only the LGI group had significant reductions (P < .05) in PWV, low-density lipoprotein cholesterol, and triacylglycerol concentration. There were no differences in postprandial glucose or insulin responses between the groups. The results suggest that an LGI diet may be more beneficial in reducing CHD risk, including PWV and 24-hour BP, even in the setting of healthy eating and weight loss; and thus, further study is warranted.