APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy

A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated MYH9, more recent analyses localized the strongest association within the neighboring APOL1 gene. In this replication study, we examined the six top-most associated variants in APOL1 and MYH9 in an independent cohort of African Americans with various nephropathies (44 with FSGS, 21 with HIVAN, 32 with IgA nephropathy, and 74 healthy controls). All six variants associated with FSGS and HIVAN (additive ORs, 1.8 to 3.0; P values 3 × 10(-2) to 5 × 10(-5)) but not with IgA nephropathy. In conditional and haplotype analyses, two APOL1 haplotypes accounted for virtually all of the association with FSGS and HIVAN on chromosome 22q13 (haplotype P value = 5.6 × 10(-8)). To assess the role of MYH9 deficiency in nephropathy, we crossbred Myh9-haploinsufficient mice (Myh9(+/-)) with HIV-1 transgenic mice. Myh9(+/-) mice were healthy and did not demonstrate overt proteinuria or nephropathy, irrespective of the presence of the HIV-1 transgene. These data further support the strong association of genetic variants in APOL1 with susceptibility to FSGS and HIVAN among African Americans.     

Use of external fixator in the postoperative management of sciatic nerve injuries

Immobilization of lower limb following neurorrhaphy for sciatic nerve injuries poses a difficult clinical situation both for the surgeon and for the patient. In this article, we describe a new technique for maintenance of lower limb in desired position of extension at hip and flexion of knee without application of spica cast using an external fixator. In this method, a spanning external fixator across the knee and hip joint is applied in the desired position following neurorrhaphy, and both joints are sequentially brought back to normal position. Clinical follow-up of 2 cases is also presented with preservation of range of motion at hip and knee joint as well as good functional outcome of nerve repair.     

Cardiac surgery in low birth weight infants: current outcomes

Low birth weight (LBW) is a risk factor for mortality in neonatal and infant heart surgery. The purpose of this study was to determine the contemporary outcomes and risk factors of cardiac surgery in low weight babies. The records of 75 consecutive infants weighing <2.5 kg having heart surgery were reviewed. The median weight was 2100 g (range 800-2500 g) and median age was 11 days (range 2-86 days). Half (n=38) of the infants were premature. Diagnoses included: arch obstruction (n=14), hypoplastic left heart syndrome (HLHS) (n=12), tetralogy of Fallot (ToF) or pulmonary atresia (PA)/ventricular septal defect (VSD) (n=11), transposition of the great arteries (TGA) (n=7), total anomalous pulmonary venous return (TAPVR) (n=5), and other (n=20). There were two early deaths. Follow-up was available on all infants with a median duration of 1320 days (range 6-3055 days). Cumulative Kaplan-Meier survival at one year was 90% [95% confidence interval (CI), 80-95%] and at five years was 88% (95% CI, 77-94%). Overall mortality amongst patients with genetic/chromosomal abnormalities was higher, 28% vs. 5.4% amongst patients without such abnormalities (P=0.008). Age, prematurity, preoperative mechanical ventilation, prostaglandins, non-cardiac organ dysfunction, extra-cardiac malformations, perioperative extracorporeal membrane oxygenation (ECMO), and type of procedure were not associated with significant differences in mortality. Cardiac surgery in LBW infants can be performed with low early and mid-term mortality. LBW infants with chromosomal/genetic anomalies have a higher risk.     

Infra-popliteal deep venous thrombi and the risk of symptomatic pulmonary embolism in hospitalized patients

Infra-popliteal veins include the tibial and peroneal veins, as well as the soleal and gastrocnemial veins collectively known as the calf muscle veins (CMVs). Acute infra-popliteal deep venous thrombi (DVTs) are often considered insignificant with regard to the risk of pulmonary embolism (PE). A retrospective review of 4035 consecutive lower extremity venous duplex scans were made in 3146 hospital patients at our Intersocietal Commission for the Accreditation of Vascular Laboratories (ICAVL)-accredited vascular lab. Seven hundred sixteen (17.7%) duplex scans were positive for acute DVTs, and 112 (2.8%) were associated with PEs. The breakdown of positive duplexes for acute DVTs was as follows: 202 (28.2%) isolated femoral-popliteal DVTs with PE in 23 (11.4%), 304 (42.5%) isolated infra-popliteal DVTs with PE in 24 (7.9%) and 210 (29.3%) multilevel DVTs involving both vein segments (femoral-popliteal and infra-popliteal) with PE in 38 (18.1%). Of the 304 isolated acute infra-popliteal DVTs, 207 (68.1%) were isolated CMV DVTs with evidence of PE in 12 (5.8%). No statistically significant difference (P = 0.27) in the risk of PE between isolated femoral-popliteal and isolated infra-popliteal DVTs was noted. A significant number of patients (5.8%) with isolated CMV DVTs developed PE. Lower limb venous scans for DVTs should evaluate the infra-popliteal veins. Hospitalized patients with infra-popliteal DVTs should receive anticoagulation.     

Antidiabetic and antioxidant potential of β-sitosterol in streptozotocin-induced experimental hyperglycemia

Background: Oxidative stress, produced under diabetic conditions, may cause tissue damage. Although several drugs are currently available for the treatment of diabetes, their continued use may cause unwanted side effects. The aim of the present study was to evaluate the antioxidant potential of β‐sitosterol (BS), a phytosterol from Solanum surattense, using an experimental model for diabetes‐induced oxidative damage. Methods: The effects of 21 days treatment with BS (10, 15 and 20 mg/kg, p.o.) on blood, serum, and tissue biochemical parameters were evaluated in control and streptozotocin‐induced diabetic rats. Nine experimental groups, including a control group, a diabetic group, and BS‐ and glibenclamide‐treated diabetic groups, were evaluated. Results: All three dose levels dose dependently resulted in decreases in glycated hemoglobin, serum glucose, and nitric oxide, with concomitant increases in serum insulin levels. Furthermore, treatment with BS doses also increased pancreatic antioxidant levels, with a concomitant decrease in thiobarbituric acid‐reactive substances. Conclusions: β‐Sitosterol has promising antidiabetic as well as antioxidant effects and may be considered in clinical studies for drug development.     

Modular Training in Laparoscopic Colorectal Surgery Maximizes Training Opportunities without Clinical Compromise

Background  

Laparoscopic surgery is increasingly proposed as the gold standard technique for colorectal resections and is offered to greater numbers of patients. To meet the rising service demands, more trainees and established consultants need to learn the technique. We sought to establish whether it is feasible and safe to train on a large proportion of patients without adversely affecting clinical outcome or smooth running of clinical service.