Anti-neutrophil cytoplasmic antibodies (ANCA) in malaria

Various autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-myeloperoxidase (anti-MPO), anti-proteinase3 (anti-PR3) and anti-lactoferrin (anti-LF) antibodies were studied in 173 acute hospitalised patients suffering from malaria of which 160 patients had P. falciparum and remaining 13 had P. vivax infection. Standard methods like indirect immunofluorescence (IIF) microscopy along with Confocal microscopy and ELISA were used for identifying and quantifying the autoantibodies and IIF patterns on PMN and HL-60 cells were studied for ANCA classification. Also HEp-2 cells were used for ANA detection, while estimation of anti-dsDNA, AHA, anti-MPO, anti-PR3 and anti-LF were tested using ELISA. Sera from malaria patients showed prominent immunofluorescence staining patterns where 23.8% cases had ANA in P. falciparum group as compared to 15.4% in P. vivax group and ANCA was found to be present in 20% in P. falciparum and 15.4% in P. vivax group. An interesting observation was that, of the total ANCA positives, 59% had p-ANCA, 5.9% had c-ANCA and 44.1% of the cases showed the 'atypical' or X-ANCA pattern. When p-ANCA positivity was compared with c-ANCA positivity among these patients, a good statistical correlation was noted with OR = 16, chi 2 = 16.43, EF = 0.46 and p-value = 5.037E 0.5. ELISA showed 31.2% anti-MPO and 6.2% anti-PR3 in P. falciparum cases while the two ANCA positive cases in P. vivax had anti-MPO. Anti-LF was found to be present in 40.6% cases. Neither the P. falciparum nor P. vivax contained autoantibodies with specificities similar to the characteristic lupus autoantibodies such as double stranded DNA (dsDNA). ANCA positivity develops in some types of malarial infection also with the presence of various autoantibodies which is important from a clinical point of view and should be carefully evaluated in those geographic areas where malaria is endemic. It also alerts us to the fact, whether in cases of repeated malarial infections in susceptible individuals, vasculitic disorders, which through ANCA pathways develop, could lead to renal and other complications.     

Left Ventricular Remodeling after Late Revascularization Correlates with Baseline Viability

The ideal management of stable patients who present late after acute ST-elevation myocardial infarction (STEMI) is still a matter of conjecture. We hypothesized that the extent of improvement in left ventricular function after successful revascularization in this subset was related to the magnitude of viability in the infarct-related artery territory. However, few studies correlate the improvement of left ventricular function with the magnitude of residual viability in patients who undergo percutaneous coronary intervention in this setting.In 68 patients who presented later than 24 hours after a confirmed first STEMI, we performed resting, nitroglycerin-enhanced, technetium-99m sestamibi single-photon emission computed tomography–myocardial perfusion imaging (SPECT–MPI) before percutaneous coronary intervention, and again 6 months afterwards. Patients whose baseline viable myocardium in the infarct-related artery territory was more than 50%, 20% to 50%, and less than 20% were divided into Groups 1, 2, and 3 (mildly, moderately, and severely reduced viability, respectively). At follow-up, there was significant improvement in end-diastolic volume, end-systolic volume, and left ventricular ejection fraction in Groups 1 and 2, but not in Group 3.We conclude that even late revascularization of the infarct-related artery yields significant improvement in left ventricular remodeling. In patients with more than 20% viable myocardium in the infarct-related artery territory, the extent of improvement in left ventricular function depends upon the amount of viable myocardium present. The SPECT–MPI can be used as a guide for choosing patients for revascularization.     

Effectiveness of midurethral slings in recurrent stress urinary incontinence: a systematic review and meta-analysis

Introduction and hypothesis

Midurethral slings (MUS) are the gold standard primary procedure for the surgical treatment of stress urinary incontinence (SUI). There is no robust evidence on the success with MUS in the treatment of recurrent SUI. Our objective was to evaluate the effectiveness and complications of MUS in women with recurrent SUI by systematic review and meta-analysis of the literature.

Methods

A systematic literature search was carried out (up to August 2011) using relevant search terms in MEDLINE, EMBASE, CENTRAL and Google Scholar. Relevant randomised controlled trials (RCT) and prospective studies were selected and then analysed by two independent reviewers. Meta-analysis of cure stated in prospective cohort studies was performed with a random effects model using Stata 8.

Results

There was 1 randomised trial and 11 good quality prospective studies included in this systematic review. The overall subjective cure rate per meta-analysis of prospective cohort studies following MUS for recurrent SUI after any previous surgery was found to be 78.5?% [95?% confidence interval (CI) 69–88] at the follow-up of 29.72?±?29.49?months. The subjective cure rate following MUS after previous failed MUS was 73.3?% (95?% CI 55–97) at the follow-up of 15.7?±?7.7?months.

Conclusions

The studies report good cure rates of SUI after MUS surgery following previous incontinence surgery (62–100?%). There seems to be a lower cure rate with transobturator compared to the retropubic tape for recurrent SUI after previous surgery.     

Mesh fixation with a barbed anchor suture results in significantly less strangulation of the abdominal wall

Background  

Laparoscopic ventral hernia repair using an underlay mesh frequently requires suture fixation across the abdominal wall, which results in significant postoperative pain. This study investigates the utility of a novel mesh fixation technique to reduce the strangulation force on the abdominal wall.     

Single-site laparoscopic (SSL) cholecystectomy in human cadavers using a novel percutaneous instrument platform and a magnetic anchoring and guidance system (MAGS): reestablishing the “critical view”

Introduction  

SSL introduces ergonomic challenges while establishing the critical view during dissection of the Triangle of Calot (TOC). This study investigates the use of a novel percutaneous instrument platform and MAGS in performing SSL cholecystectomy with a technique that closely mimics four-port cholecystectomy.     

Mechanisms Involved in the Development and Healing of Diabetic Foot Ulceration

We examined the role of vascular function and inflammation in the development and failure to heal diabetic foot ulcers (DFUs). We followed 104 diabetic patients for a period of 18.4 ± 10.8 months. At the beginning of the study, we evaluated vascular reactivity and serum inflammatory cytokines and growth factors. DFUs developed in 30 (29%) patients. DFU patients had more severe neuropathy, higher white blood cell count, and lower endothelium-dependent and -independent vasodilation in the macrocirculation. Complete ulcer healing was achieved in 16 (53%) patients, whereas 13 (47%) patients did not heal. There were no differences in the above parameters between the two groups, but patients whose ulcers failed to heal had higher tumor necrosis factor-α, monocyte chemoattractant protein-1, matrix metallopeptidase 9 (MMP-9), and fibroblast growth factor 2 serum levels when compared with those who healed. Skin biopsy analysis showed that compared with control subjects, diabetic patients had increased immune cell infiltration, expression of MMP-9, and protein tyrosine phosphatase-1B (PTP1B), which negatively regulates the signaling of insulin, leptin, and growth factors. We conclude that increased inflammation, expression of MMP-9, PTP1B, and aberrant growth factor levels are the main factors associated with failure to heal DFUs. Targeting these factors may prove helpful in the management of DFUs.Diabetic foot ulcers (DFUs) are one of the most common and serious complications of diabetes and affects 15% of all diabetic patients, leading to >80,000 amputations per year in the U.S. and results in a high financial burden (1,2). Neuropathy, peripheral vascular disease, and reduced resistance to infection are recognized risk factors leading to the development of DFUs, which have all the characteristics of a chronic wound (3,4).In the current study, we have well characterized and prospectively followed-up a large number of diabetic patients, the majority of whom were at risk for developing foot ulceration. Our main hypothesis was that changes in the peripheral nerve function and the diabetes-associated proinflammatory state are related not only to the development of DFUs but also to wound-healing failure.     

Clinical Variability of Family Members with the C104R Mutation in Transmembrane Activator and Calcium Modulator and Cyclophilin Ligand Interactor (TACI)

Purpose

Common Variable Immunodeficiency Disorder (CVID) is a complex disorder that predisposes patients to recurrent and severe infections. The C104R mutation in the transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is the most frequent mutation identified in patients with CVID. We carried out a detailed immunological and molecular study in a family with a C104R mutation.

Methods

We have undertaken segregation analysis of a kindred with C104R mutations of the TACI gene. Detailed immunological and molecular investigations were carried out for this kindred and the clinical phenotype was compared to the genotype.

Results

Segregation analysis of our kindred showed that inheriting single or double copy of the C104R mutation does not consign an individual to CVID. All heterozygotes in the family were phenotypically different, ranging from asymptomatic to ill-health. A family member with a wild type TACI variant had CVID-related phenotype including IgA deficiency and type 1 diabetes. Interestingly, a family member with the homozygous C104R/C104R variant did not meet the criteria for CVID because he had excellent, albeit unsustained, vaccine responses to T cell dependent and T cell independent vaccine antigens despite profound hypogammaglobulinemia.

Conclusion

The C104R mutation does not correlate with the clinical phenotypes in this family.