Gut permeability is associated with lower insulin sensitivity in youth with perinatally acquired HIV.

The relationships between alterations in the intestinal barrier, and bacterial translocation with the development of metabolic complications in youth with perinatally acquired HIV (YPHIV) have not been investigated. The PHACS Adolescent Master Protocol enrolled YPHIV across 15 U.S. sites, including Puerto Rico, from 2007 to 2009. For this analysis, we included YPHIV with HIV viral load 1000 c/ml or less, with at least one measurement of homeostatic assessment of insulin resistance (HOMA-IR) or nonhigh density lipoprotein (non-HDLc) between baseline and year 3 and plasma levels of intestinal fatty-acid binding protein (I-FABP), lipopolysaccharide-binding protein (LBP), and zonulin levels at baseline. We fit linear regression models using generalized estimating equations to assess the association of baseline log 10 gut markers with log 10 HOMA-IR and non-HDLc at all timepoints. HOMA-IR or non-HDLc was measured in 237, 189, and 170 PHIV at baseline, Yr2, and Yr3, respectively. At baseline, median age (Q1, Q3) was 12 years (10, 14), CD4 + cell count was 762 cells/µl (574, 984); 90% had HIV RNA less than 400 c/ml. For every 10-fold higher baseline I-FABP, HOMA-IR dropped 0.85-fold at baseline and Yr2. For a 10-fold higher baseline zonulin, there was a 1.35-fold increase in HOMA-IR at baseline, 1.23-fold increase in HOMA-IR at Yr2, and 1.20-fold increase in HOMA-IR at Yr3 in adjusted models. For a 10-fold higher baseline LBP, there was a 1.23-fold increase in HOMA-IR at baseline in the unadjusted model, but this was slightly attenuated in the adjusted model. Zonulin was associated with non-HDLc at baseline, but not for the other time points. Despite viral suppression, intestinal damage may influence downstream insulin sensitivity in YPHIV.

Brentuximab vedotin plus AVD for Hodgkin lymphoma: incidence and management of peripheral neuropathy in a multisite cohort.

Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is increasingly used for frontline treatment of stage III/IV classical Hodgkin lymphoma (cHL). Peripheral neuropathy (PN) was the most common and treatment-limiting side effect seen in clinical trials but has not been studied in a nontrial setting, in which clinicians may have different strategies for managing it. We conducted a multisite retrospective study to characterize PN in patients who received BV + AVD for newly diagnosed cHL. One hundred fifty-three patients from 10 US institutions were eligible. Thirty-four patients (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage, performance status, and comorbidities. PN was reported by 80% of patients during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of patients because of PN leading to BV discontinuation in 23%, dose reduction in 17%, and temporary hold in 4%. With a median follow-up of 24 months, PN resolution was documented in 36% and improvement in 33% at the last follow-up. Two-year progression-free survival (PFS) for the advanced-stage patients was 82.7% (95% confidence interval [CI], 0.76-0.90) and overall survival was 97.4% (95% CI, 0.94-1.00). Patients who discontinued BV because of PN did not have inferior PFS. In the nontrial setting, BV + AVD was associated with a high incidence of PN. In our cohort, which includes patients who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable.

Comparison of 2D Shear Wave Elastography, Transient Elastography, and MR Elastography for the Diagnosis of Fibrosis in Patients With Nonalcoholic Fatty Liver Disease.

OBJECTIVE. The aim of the present study was to compare the diagnostic accuracy of liver stiffness measurements (LSMs) obtained using MR elastography (MRE), transient elastography (TE), and 2D shear wave elastography (SWE) in patients with biopsy-proven nonalcoholic fatty liver disease (NAFLD). SUBJECTS AND METHODS. We prospectively enrolled 62 adult subjects (mean age [± SD], 50 ± 13 years; 58% women; body mass index [weight in kilograms divided by the square of height in meters], 35 ± 7). Two-dimensional SWE, MRE, and TE were performed at a mean of 105 ± 86 days after liver biopsy. The area under the ROC curve (AUROC) values and 95% CIs for the corresponding LSMs (expressed in kilopascals) were calculated, with significant fibrosis (Metavir liver fibrosis score, F2-F4) and advanced fibrosis (F3-F4) used as outcome measures. Pairwise comparisons of AUROC values were conducted using the DeLong test. Statistical significance was set at p < 0.05. RESULTS. For the 62 subjects, valid LSMs were obtained for 57 subjects with the use of 2D SWE, for 59 subjects with TE, for 59 subjects with MRE, and for 54 subjects with all three modalities combined. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of significant fibrosis were 0.80 (0.67-0.92), 0.77 (0.64-0.89), and 0.85 (0.74-0.95), respectively. The AUROC values (95% CIs) of 2D SWE, TE, and MRE for the diagnosis of advanced fibrosis were 0.89 (0.80-0.98), 0.86 (0.77-0.95), and 0.95 (0.89-1.00), respectively. Pairwise comparisons revealed similar diagnostic accuracy for significant fibrosis (2D SWE vs MRE, p = 0.431; 2D SWE vs TE, p = 0.317; and MRE vs TE, p = 0.052) and advanced fibrosis (2D SWE vs MRE, p = 0.348; 2D SWE vs TE, p = 0.293; and MRE vs TE, p = 0.059). CONCLUSION. For patients with biopsy-proven NAFLD, 2D SWE, MRE and TE exhibited comparable and very good to excellent diagnostic accuracy for advanced fibrosis and comparable but lower accuracy for significant fibrosis.

Changes in insulin sensitivity over time and associated factors in HIV-infected adolescents.

OBJECTIVE: To compare prevalence of insulin resistance between perinatally HIV-infected (PHIV+) and perinatally HIV-exposed, but uninfected adolescents (PHEU), determine incidence of and contributory factors to new and resolved cases of insulin resistance in PHIV+, and evaluate glucose metabolism. DESIGN: Cross-sectional design for comparison of prevalence among PHIV+ and PHEU. Longitudinal design for incidence and resolution of insulin resistance among PHIV+ at risk for these outcomes. METHODS: The source population was adolescents from pediatric HIV clinics in the United States and Puerto Rico participating in the Pediatric HIV/AIDS Cohort Study, an ongoing prospective cohort study designed to evaluate impact of HIV infection and its treatment on multiple domains in preadolescents and adolescents. Insulin resistance was assessed by homeostatic model assessment of insulin resistance. Those with incident insulin resistance underwent 2-h oral glucose tolerance test and HbA1c. Baseline demographic, metabolic, and HIV-specific variables were evaluated for association with incident or resolved insulin resistance. RESULTS: Unadjusted prevalence of insulin resistance in PHIV+ was 27.3 versus 34.1% in PHEU. After adjustment for Tanner stage, age, sex, and race/ethnicity, there was no significant difference between groups. Factors positively associated with developing insulin resistance included female sex, higher BMI z score, and higher waist circumference; those associated with resolving insulin resistance included male sex and lower BMI z score. CONCLUSION: Prevalence of insulin resistance in PHIV+ and PHEU was substantially higher than that reported in HIV-uninfected nonoverweight youth, but similar to that in HIV-uninfected obese youth. Factors associated with incident or resolved insulin resistance among PHIV+ were similar to those reported in HIV-negative obese youth. However, a contributory role of HIV infection and/or its treatment to the incident risk of insulin resistance cannot be excluded.

Mental health training experiences among Haitian healthcare workers post-earthquake 2010.

BACKGROUND: After the 2010 earthquake in Haiti, the large number of persons with major limb damage, amputations, shock, trauma, anxiety and depression placed a severe strain on mental health (MH) services. PURPOSE: This qualitative study describes the impact and acceptability of a Mental Health Training Program (MHTP) implemented in the north of Haiti after the earthquake. METHODS: A total of 113 healthcare workers (HCWs) participated in a training program designed to build local MH care capacity. The training curriculum draws on literature related to MH and the impact of the Haiti earthquake. Two focus groups were conducted with 16 HCWs; discussions centred on the personal and professional impact and acceptability of the training program. DISCUSSION: Results demonstrated that the MHTP changed the HCWs' perceptions about MH issues and provided them with the knowledge and skills to respond to growing community MH needs. Acceptability of the MHTP was related to the content covered, to the delivery mode of the content and to the cultural appropriateness of the program. CONCLUSIONS: Disasters of different types will continue to occur and to impact MH in communities around the world. MH training will allow nurses to quickly and effectively respond to disasters. A coordinated emergency plan that is subject to frequent review, rehearsal and evaluation is also essential.

Nodule size is an independent predictor of malignancy in mutation-negative nodules with follicular lesion of undetermined significance cytology.

BACKGROUND: In thyroid nodule fine-needle aspiration (FNA) cytology, the atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) category has a 5-15% malignancy risk that increases to 85-99% when mutation testing for BRAF, RAS, RET/PTC, or PAX8/PPARγ is positive. However, negative testing does not exclude malignancy. The study objective was to identify clinical and imaging features that predict cancer in mutation-negative AUS/FLUS thyroid nodules. METHODS: All patients were reviewed (April 2007 to April 2009) who had AUS/FLUS cytology, negative prospective molecular testing of FNA, and histopathology. RESULTS: Of the 230 nodules, 12 (5.2%) were malignant in 11 of 190 patients, and known clinical risk factors for thyroid cancer did not predict malignancy. On preoperative imaging, ≥1 suspicious ultrasound feature was identified in 33% of nodules and occurred regardless of histology (P = .23). Malignant mutation-negative AUS/FLUS nodules were larger than benign nodules (mean maximum diameter, 33.6 vs 24.0 mm; P = .007). On multivariate analysis, nodule size remained an independent predictor of malignancy (odds ratio, 1.043; P = .018). We observed no malignancies in 88 mutation-negative AUS/FLUS nodules <18.5 mm. CONCLUSION: Size is an independent predictor of malignancy in mutation-negative AUS/FLUS nodules and the risk increased 4.3% with every millimeter increase in nodule size. Selected patients with small, mutation-negative AUS/FLUS thyroid nodules may be managed with ultrasound surveillance in lieu of thyroidectomy.

Hematopoietic stem cell transplantation for complete IFN-gamma receptor 1 deficiency: a multi-institutional survey.

OBJECTIVES: To evaluate the outcome of hematopoietic stem cell transplantation (HSCT) in a series of patients with inherited complete IFN-gamma receptor 1 (IFNgammaR1) deficiency. STUDY DESIGN: We report 8 patients who received altogether 11 HSCT from family donors, including 10 HLA-identical (5 siblings and 5 relatives) and 1 HLA-haplo-identical donors. Five grafts were T-cell depleted, and conditioning regimens varied in intensity. RESULTS: Four patients died within 8 months after HSCT. Two of these deaths were due to specific complications related to mycobacterial infection. There was no or very low (2%) donor cell engraftment in 2 survivors. Only 2 patients are in full remission of mycobacterial disease 5 years after HSCT. These are the only patients who received non-T-cell-depleted grafts from an HLA-identical sibling after a fully myeloablative conditioning regimen. CONCLUSIONS: HSCT can lead to prolonged remission of mycobacterial disease in children with complete IFNgammaR1 deficiency. However, optimal control of mycobacterial infection before HSCT and the use of a non-T-cell-depleted transplant from an HLA-identical sibling after a fully myeloablative conditioning regimen are recommended.

Growth hormone treatment in children with familial dysautonomia.

OBJECTIVE: To assess experience with growth hormone (GH) therapy in patients with familial dysautonomia (FD). Study design Of 580 patients with FD registered at the Dysautonomia Center at New York University Medical Center, 13 patients (8 males, 5 females) aged 1.10 to 15.10 years received GH treatment. GH doses ranged from 0.2 to 0.3 mg/kg/wk; one patient received 0.14 mg/kg/wk. Information regarding auxologic data, skeletal age, pubertal status, and spinal deformity before and after GH therapy was obtained from center records and treating endocrinologists. Growth velocity was analyzed before and during GH treatment at 0 to 6 months, 6 to 12 months, 1 to 2 years, and >2 years. RESULTS: Before GH therapy, growth velocity was <5 cm/y in 10 patients and 5 to 6 cm/y in three patients. In the first six months of GH therapy, growth velocity exceeded pretreatment rates in all but one patient; 10 patients achieved an annualized growth rate >7 cm/y. Six of nine patients treated for more than one year grew >5 cm/y. Less than optimal treatment responses were attributed to poor compliance, intercurrent illness, scoliosis, or advanced puberty. CONCLUSION: The data demonstrate that GH treatment in patients with FD may increase growth velocity, at least in the short term. This experiential data supports a future prospective study.

Simultaneous development of pheochromocytomas in prepubertal siblings with von Hippel-Lindau syndrome.

We report 2 siblings with a known von Hippel-Lindau mutation who simultaneously developed asymptomatic pheochromocytomas at significantly younger ages than are typically seen in this setting.

Sheepskin bedding and the sudden infant death syndrome. New Zealand Cot Death Study Group.

We carried out a nationwide case-control study, comparing 393 case patients with sudden infant death syndrome (SIDS) with 1592 control subjects, in order to examine sheepskin bedding as a risk factor. Sheepskin use was similar for case patients and control subjects (both, 42%; adjusted odds ratio [OR] = 1.28; 95% CI = 0.92, 1.79). Sheepskin use among the control subjects was associated with socioeconomic advantage. The relative risk for SIDS with sheepskin use was significantly increased in the infants placed prone to sleep (adjusted OR = 1.70; 95% CI = 1.08, 2.67), but not for infants placed in the supine or lateral position (adjusted OR = 0.82; 95% CI = 0.45, 1.48). An interaction between sheepskin use and bed sharing was also found. Sheepskin use was associated with a decreased risk of SIDS among infants sharing beds (adjusted OR = 0.61; 95% CI = 0.38, 0.99), but an increased risk among infants not bed sharing (adjusted OR = 2.25; 95% CI = 1.32, 3.86). We conclude that if an infant needs to be placed prone to sleep for medical reasons, a sheepskin should not be used as underbedding. However, for infants placed supine to sleep, sheepskins are not associated with an increased risk of SIDS.

Advances in the treatment of metastatic colorectal cancer.

Colorectal cancer is the second leading cause of cancer-related deaths in men and women in the United States. In 1997, it is estimated that 131,200 new cases of colorectal cancer will be diagnosed and 54,900 deaths will occur due to the disease. Although the tumor is localized at the time of diagnosis and resection with curative intent is possible in approximately 75% of patients, more than a third will develop disease recurrence. Consequently, almost half of all patients with colorectal cancer will die of metastatic disease.

Worldwide variations in prevalence of symptoms of allergic rhinoconjunctivitis in children: the International Study of Asthma and Allergies in Childhood (ISAAC).

BACKGROUND: As part of the International Study of Asthma and Allergies in Childhood (ISAAC), prevalence surveys were conducted among representative samples of school children from locations in Europe, Asia, Africa, Australia, North and South America. SUBJECTS: 257,800 children aged 6-7 years from 91 centres in 38 countries, and 463,801 children aged 13-14 years from 155 centres in 56 countries. METHODS: Written symptom questionnaires were translated from English into the local language for self-completion by the 13-14-year-olds and completion by the parents of the 6-7-year-olds. Rhinitis was described as a problem with sneezing, or a runny, or blocked nose when you (your child) DID NOT have a cold or the flu. Additional questions were asked about rhinitis associated with itchy-watery eyes, interference with activities and a history of hay fever ever. RESULTS: The prevalence of rhinitis with itchy-watery eyes ("rhinoconjunctivitis") in the past year varied across centres from 0.8% to 14.9% in the 6-7-year-olds and from 1.4% to 39.7% in the 13-14-year-olds. Within each age group, the global pattern was broadly consistent across each of the symptom categories. In centres of higher prevalence there was great variability in the proportion of rhinoconjunctivitis labelled as hay fever. The lowest prevalences of rhinoconjunctivitis were found in parts of eastern Europe, south and central Asia. High prevalences were reported from centres in several regions. CONCLUSION: These results suggest substantial worldwide variations in the prevalence and labelling of symptoms of allergic rhinoconjunctivitis which require further study. These differences, if real, may offer important clues to environmental influences on allergy.