Methylenetetrahydrofolate reductase homozygosis and low-density lipoproteins in patients with genotype 1 chronic hepatitis C

Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 μg/L vs 12.5 ± 5.8 μg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.     

Laparoscopic repair for recurrent incisional hernias: a single institute experience of 10 years

Purpose

The treatment of recurrent incisional hernias (RIH) has been associated with unsatisfactory postoperative (PO) morbidity and high failure rates. The aim of this study is to retrospectively investigate our single-center experience of laparoscopic repair (LR) for RIH.

Methods

The case records of 69 patients with RIH who underwent LR in our institution between January 2002 and November 2011 were reviewed. The operative technique has been standardized and provides onlay placement of an ePTFE mesh fixed with titanium tacks. Patients’ demographic data and comorbidities, intraoperative course, PO complications and recurrences at follow-up were systematically collected and analyzed. The influence of defect’s size and obesity variables on clinical outcomes was also investigated.

Results

The mean operative time was 147.6 ± 71.2 min and mean hospital stay was 5.8 ± 1.8 days. No conversion occurred while five intraoperative complications (7.2 %) were recorded: three bowel injuries treated by laparoscopic sutures, one omentum bleeding and one epigastric vessel lesion. PO mortality was null, while overall morbidity was 13 % (9 patients) with a prevalence of seroma lasting over 8 weeks in six patients (8.7 %). Along a mean follow-up of 41 months (range 6–119), recurrence rate was 5.7 % (4 patients). Univariate analysis for width of defects and BMI showed no significant influence on patients’ outcomes.

Conclusions

Surgical treatment for RIH remains controversial because of lack in literature of specific studies on this topic. Morbid obesity and large defects have been often associated with technical difficulties and worse results. Our 10 years’ experience with LR provided satisfactory results in terms of PO morbidity and recurrence rate, despite any kind of patient selection.     

Long-term outcome and need of re-operation in gastro-esophageal reflux surgery in children

Background

Fundoplication is considered a mainstay in the treatment of gastro-esophageal reflux. However, the literature reports significant recurrences and limited data on long-term outcome.

Aims

To evaluate our long-term outcomes of antireflux surgery in children and to assess the results of redo surgery.

Methods

We retrospectively analyzed all patients who underwent Nissen fundoplication in 8 consecutive years. Reiterative surgery was indicated only in case of symptoms and anatomical alterations. A follow-up study was carried out to analyzed outcome and patients’ Visick score assessed parents’ perspective.

Results

Overall 162 children were included for 179 procedures in total. Median age at first intervention was 43 months. Comorbidities were 119 (73 %), particularly neurological impairments (73 %). Redo surgery is equal to 14 % (25/179). Comorbidities were risk factors to Nissen failure (p = 0.04), especially children suffering neurological impairment with seizures (p = 0.034). Follow-up datasets were obtained for 111/162 = 69 % (median time: 51 months). Parents’ perspectives were excellent or good in 85 %.

Conclusions

A significant positive impact of redo Nissen intervention on the patient’s outcome was highlighted; antireflux surgery is useful and advantageous in children and their caregivers. Children with neurological impairment affected by seizures represent significant risk factors.

     

Molecular aspects of a novel HLA-A*02 allele (A*0297): the first HLA class I allele mutated at codon 232

We describe a new HLA-A*02 allele, identified in a cord blood unit and in her mother. Nucleotide sequence analysis showed the presence of a new HLA-A*02 allele identical to HLA-A*02010101 except for a non-synonymous nucleotide exchange in exon 4 modifying codon 232 from GAG (Glu) to GAC (Asp). No other human leucocyte antigen class I allele sequenced so far shows this triplet at codon 232. The amino acid exchange affects a position that is part of the membrane proximal domain of class I major histocompatibility complex (MHC), designated alpha 3, and involved in the interaction with CD8 molecule. Using molecular modelling approach, the interactions between different subunits of the native and mutated forms of MHC-I resulted in relevant changes.     

Adhesion of platelets to surface-bound fibrinogen under flow

After platelet activation, fibrinogen mediates platelet-platelet interactions leading to platelet aggregation. In addition, fibrinogen can also function as a cell adhesion molecule, providing a substratum for adhesion of platelets and endothelial cells. In this report, we studied the adhesion of platelets to surface-immobilized fibrinogen under flow in different shear rates. Heparinized whole blood containing mepacrine-labeled platelets was perfused for two minutes at various wall shear rates from 250 to 2,000 s-1 in a parallel plate flow chamber. The number of adherent fluorescent platelets was quantitated every 15 seconds with an epifluorescent videomicroscope and digital image processing system. When compared with platelet adhesion and aggregation seen on glass surfaces coated with type I bovine collagen, a significant increase in platelet adhesion was observed on immobilized fibrinogen up to wall shear rates of 800 s-1. The adherent platelets formed a single layer on fibrinogen-coated surfaces. Under identical conditions, no significant adhesion was observed on fibronectin- or vitronectin-coated surfaces. Although platelet adhesion to collagen was substantially inhibited by the platelet inhibitors prostaglandin E1 and theophylline, these inhibitors had no effect on platelet adhesion to fibrinogen. Platelets adhered to recombinant homodimeric wild-type (gamma 400-411) fibrinogen, but not to the recombinant homodimeric gamma' variant of fibrinogen. Platelet adhesion to recombinant fibrinogen with RGD to RGE mutations at positions alpha 95-97 and alpha 572-574 was similar to that with plasma-derived fibrinogen. These results show that platelets adhere to fibrinogen-coated surfaces under moderate wall shear rates, that the interaction is mediated by the fibrinogen 400-411 sequence at the carboxy-terminus of the gamma chain, and that the interaction is independent of platelet activation and the RGD sequences in the alpha chain.     

The development of cellular immunity to Epstein-Barr virus after allogeneic bone marrow transplantation

Epstein-Barr virus-induced lymphoproliferative disease (EBV-LPD) is a potentially lethal complication during the first 6 months after allogeneic bone marrow transplantation (BMT). To determine whether deficiencies of EBV-specific cellular immunity contribute to EBV-LPD susceptibility and distinguish patients at risk, we performed limiting dilution analysis to quantify anti-EBV cytotoxic T-lymphocyte precursor (CTLp) frequencies in 26 recipients of unmodified or T-cell-depleted (TCD) grafts from EBV-seropositive donors. At 3 months post-BMT (n = 26), only five patients had EBV CTLp frequencies in the range of seropositive normal controls, irrespective of the type of transplant administered. By 6 months post-BMT, 9 of 13 patients tested had EBV CTLp frequencies within the normal range. The time period in which these patients had deficient cellular immunity to EBV corresponds to the period in which we have observed EBV-LPD in most prior patients. One patient with a low EBV CTLp frequency at 4 months post-BMT developed an EBV-LPD. Within 2 weeks of receiving an infusion of donor peripheral blood mononuclear cells (PBMC) providing less than 1,200 EBV- specific cytotoxic T-cell precursors, populations of EBV-specific CTL in the circulation were restored to levels detected in normal seropositive adults. Concurrently, the patient achieved a regression of the EBV-LPD, which has been sustained without further therapy. These studies indicate that recipients of both unmodified and TCD marrow grafts have profound deficiencies of EBV-specific T cell-mediated immunity early posttransplant, and that the period of risk for EBV-LPD closely corresponds to this interval of severe deficiency. Treatment of one patient with EBV-LPD with marrow donor-derived PBMC induced a rapid expansion of EBV-specific cytotoxic T-cell populations that occurred contemporaneously with the clinical regression of disease.     

对产前母体苯巴比妥给药以预防针对新生儿和胎儿溶血病的婴儿换血

胎儿和新生儿溶血病(HDFN)可导致严重的围产期疾病,包括高胆红素血症及其引起的核黄疸。血红素分子解离为胆红素并产生免疫介导的溶血。它与白蛋白结合后转运到肝细胞,再由尿苷二磷酸葡萄糖醛酸转移酶(UGT)酶家族作用而葡萄糖醛酸化。对于人类,这种代谢途径中主要的酶是胆红素-     

Risk factors for prolonged air leak and need for intervention following lung resection

 Open in a separate windowOBJECTIVESProlonged air leak (PAL; >5 days) following lung resection is associated with postoperative morbidity. We investigated factors associated with PAL and PAL requiring intervention.METHODSRetrospective review of all patients undergoing lobectomy, segmentectomy or wedge resection from 2016 to 2019 at our institution. Bronchoplastic reconstructions and lung-volume reduction surgeries were excluded. Incidence and risk factors for PAL and PAL requiring intervention were evaluated.RESULTSIn total, 2384 patients were included. PAL incidence was 5.4% (129/2384); 22.5% (29/129) required intervention. PAL patients were more commonly male (56.6% vs 39.7%), older (mean age 69 vs 65 years) and underwent lobectomy or thoracotomy (all P < 0.001). Patients with PAL had longer length of stay (9 vs 3 days), more discharge needs and increased odds of complication (all P < 0.050).Twenty-nine patients required intervention (9 chest tubes; 4 percutaneous drains; 16 operations). In 50% of operative interventions, an air leak source was identified; however, the median time from intervention to resolution was 13 days. Patients requiring intervention had increased steroid use, lower diffusion capacity for carbon monoxide and twice the length of stay versus PAL patients (all P < 0.050).On univariable analysis, forced expiratory volume in 1 s (FEV1) <40%, diffusion capacity for carbon monoxide <50%, steroid use and albumin <3 had increased odds of intervention (P < 0.050).CONCLUSIONSAge, gender and operative technique were related to PAL development. Patients with worse forced expiratory volume in 1 s or diffusion capacity for carbon monoxide, steroid use or poor nutrition were less likely to heal on their own, indicating a population that could benefit from earlier intervention.