Polysialylation and lipopolysaccharide‐induced shedding of E‐selectin ligand‐1 and neuropilin‐2 by microglia and THP‐1 macrophages

Microglia are tissue macrophages and mediators of innate immune responses in the brain. The protein‐modifying glycan polysialic acid (polySia) is implicated in modulating microglia activity. Cultured murine microglia maintain a pool of Golgi‐confined polySia, which is depleted in response to lipopolysaccharide (LPS)‐induced activation. Polysialylated neuropilin‐2 (polySia‐NRP2) contributes to this pool but further polySia protein carriers have remained elusive. Here, we use organotypic brain slice cultures to demonstrate that injury‐induced activation of microglia initiates Golgi‐confined polySia expression in situ. An unbiased glycoproteomic approach with stem cell‐derived microglia identifies E‐selectin ligand‐1 (ESL‐1) as a novel polySia acceptor. Together with polySia‐NRP2, polySia‐ESL‐1 is also detected in primary cultured microglia, in brain slice cultures and in phorbol ester‐induced THP‐1 macrophages. Induction of stem cell‐derived microglia, activated microglia in brain slice cultures and THP‐1 macrophages by LPS, but not interleukin‐4, causes polySia depletion and, as shown for stem cell‐derived microglia, a metalloproteinase‐dependent release of polySia‐ESL‐1 and polySia‐NRP2. Moreover, soluble polySia attenuates LPS‐induced production of nitric oxide and proinflammatory cytokines. Thus, shedding of polySia‐ESL‐1 and polySia‐NRP2 after LPS‐induced activation of microglia and THP‐1 macrophages may constitute a mechanism for negative feedback regulation. GLIA 2016 GLIA 2016;64:1314–1330     

Single-Incision Laparoscopic Cholecystectomy: Do Patients Care?

Introduction  

Single-incision approaches to laparoscopic cholecystectomy typically involve increasing the size of the umbilical incision and eliminating three smaller incisions, but it is not intuitive that patients would view this as a benefit. We hypothesize that when patient satisfaction with standard laparoscopic cholecystectomy is assessed, most dissatisfaction will be linked to the umbilical incision and, given the option, patients would actually wish to eliminate this incision.     

Secundum ASD closure using a right lateral minithoracotomy: five-year experience in 122 patients

BACKGROUND: Surgical closure of secundum atrial septal defect (ASD) is a standard procedure associated with very low mortality and morbidity. We evaluated outcomes in the era of catheter-based interventional closure and minimally invasive techniques. METHODS: From May 1996, February 2002, 177 patients with a body weight of more than 30 kg underwent surgical ASD closure. A right lateral minithoracotomy (LMT) was used in 122 patients and a conventional approach, in 55. Diagnoses included secundum ASD in 106 patients in the LMT group and 40 in the conventional group, sinus venosus ASD in 13 patients in each group, and status post interventional closure in 3 and 2 patients, respectively. Mean age was 37 +/- 17 years in the LMT group and 43 +/- 20 years, in the conventional group and mean body weight was 66 +/- 17 kg and 70 +/- 16 kg, respectively. In the LMT group, femoral cannulation was performed for cardiopulmonary bypass. RESULTS: Direct ASD closure was carried out in 67.2% of patients in the LMT group and 58.2% of those in the conventional group. The remaining patients had pericardial patch closure. There was one death: A patient in the conventional group who required explantation of an Amplatzer device because of infection died postoperatively. Average stay in the intensive care unit was 1.2 +/- 0.5 days. Two patients required reoperation for residual ASD after direct closure; 1 sustained a temporary neurological deficit that resolved completely. On postoperative echocardiography, a minimal residual shunt was seen in only 3 patients. All patients were in good clinical condition with improved functional status at discharge from the hospital. CONCLUSIONS: Secundum ASD closure by LMT has become as standard and safe an operation as the conventional technique and achieves good perioperative results and satisfactory long-term outcomes. Thus LMT is an attractive option for patients who are not suitable for closure using catheter-based devices.     

Mitral valve repair in patients with end stage cardiomyopathy: who benefits?

Objective: Patients with end stage cardiomyopathy frequently present with additional severe mitral regurgitation. We analyzed the outcome of mitral valve reconstruction in this high risk patient group. Methods: Sixty-six patients with significant mitral regurgitation and an ejection fraction (EF) below 30% (dilated CARDIOMYOPATHY=53, ischemic cardiomyopathy (ICM)=13) were retrospectively evaluated from 07/96 and 02/02. All received annuloplasty ring implantation and additional repair (n=4) if required. Mean follow-up was 28±18 months. Results: Mitral valve repair (MVR) was technically feasible in all patients. Intraoperative transesophageal echocardiography (TEE) revealed none (n=60) or only trivial (n=6) residual mitral regurgitation. Thirty day mortality was 6.1%. Actuarial survival after 1 and 5 years was 86±4 and 66±8%, respectively. During follow-up seven patients were transplanted due to lack of clinical improvement after 10±7 months (range 1–23). Echocardiography revealed a significant improvement in EF (25±10.5% pre-op, 34±15% post-op) and a slight decrease in left ventricular end-diastolic diameter (69±10 mm pre-op, 67±13 mm follow up). Patients were in NYHA functional -class 3 (median) preoperatively and in class 2 at long term-follow-up. Gender, left ventricular enddiastolic diameter, preoperative ejection fraction or type of surgical approach (sternotomy, right lateral minithoracotomy) had no significant influence on patient outcome. Patients with ICM or patients older than 60 years showed an increased risk for clinical events both early post-operatively and at long-term follow-up. Conclusion: MVR can be performed with low perioperative morbidity and mortality even in patients with advanced heart failure, modifying selection criteria for potential candidates may further improve long term outcome.     

Obese and non-obese hemodialysis patients have a similar prevalence of functioning arteriovenous fistula using pre-operative vein mapping

AIMS: The arteriovenous fistula (AVF) is the preferred hemodialysis access. Subset analyses of both the HEMO and DOPPS studies have shown that obese hemodialysis patients have a lower prevalence of functioning AVF. Doppler ultrasound may increase the prevalence of functioning AVF in obese subjects. PATIENTS AND METHODS: The effect of pre-operative vein mapping employed between 10/01/98 and 12/08/00 on the prevalence of functioning AVF in a single university hemodialysis program was studied. Preoperative ultrasound was performed to study venous and arterial systems on both arms. RESULTS: There were 50 obese patients, defined as bodymass index (BMI) > or = 27 kg/m2, and 130 patients with a lower BMI. The groups were similar in mean age and diabetes prevalence. The obese group had statistically significantly more females 34/50 versus 61/130 with p = 0.01. There was no statistically significant difference between the vein mapping parameters studied in the two BMI groups, including mean mid-forearm cephalic vein diameter, distal radial artery peak systolic velocity and subclavian vein patency. No obese patient required venography. There was no significant difference between the number of functioning AVF in both groups (22/50 obese, 48/130 lower BMI, p = 0.24). CONCLUSIONS: Pre-operative vein mapping is associated with a similar prevalence of functioning AVF in obese and lower BMI patients. Pre-operative ultrasound screening is a useful tool to promote AVF placement in obese patients.     

Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction

Recent studies using magnetic resonance spectroscopy have shown that decreased insulin-stimulated muscle glycogen synthesis due to a defect in insulin-stimulated glucose transport activity is a major factor in the pathogenesis of type 2 diabetes. The molecular mechanism underlying defective insulin-stimulated glucose transport activity can be attributed to increases in intramyocellular lipid metabolites such as fatty acyl CoAs and diacylglycerol, which in turn activate a serine/threonine kinase cascade, thus leading to defects in insulin signaling through Ser/Thr phosphorylation of insulin receptor substrate (IRS)-1. A similar mechanism is also observed in hepatic insulin resistance associated with nonalcoholic fatty liver, which is a common feature of type 2 diabetes, where increases in hepatocellular diacylglycerol content activate protein kinase C-epsilon, leading to reduced insulin-stimulated tyrosine phosphorylation of IRS-2. More recently, magnetic resonance spectroscopy studies in healthy lean elderly subjects and healthy lean insulin-resistant offspring of parents with type 2 diabetes have demonstrated that reduced mitochondrial function may predispose these individuals to intramyocellular lipid accumulation and insulin resistance. Further analysis has found that the reduction in mitochondrial function in the insulin-resistant offspring can be mostly attributed to reductions in mitochondrial density. By elucidating the cellular and molecular mechanisms responsible for insulin resistance, these studies provide potential new targets for the treatment and prevention of type 2 diabetes.     

Conversion of temporary hemodialysis catheters to permanent hemodialysis catheters: a retrospective study of catheter exchange versus classic de novo placement

Many clinicians believe that de novo access is required when converting temporary hemodialysis (HD) catheters to long-term or permanent catheters. However, since vascular access sites are at a premium in the dialysis patient, it is important to preserve existing central venous catheters and conserve future access sites. In this retrospective study, data from 94 patients referred to interventional radiology for placement of long-term, tunneled HD catheters between July 2001 and September 2002 were reviewed. The study group consisted of 42 patients in whom the temporary catheter was exchanged for a peel-away sheath and a tunneled catheter inserted using the existing venous access site. The control group included 52 patients who received traditional de novo placement of permanent catheters. Based on available follow-up data, we report a 100% technical success rate, with 72% patency at 30 days in the study group (n = 32; mean age 58 years). By comparison, de novo catheter placement (n = 35; mean age 59 years) yielded a 100% technical success rate, with 83% patency at 30 days. The overall infection rate was 0.30 per 100 catheter-days (total 3036 catheter-days) and 0.36 per 100 catheter-days (total 3295 catheter-days), respectively (chi2 = 0.64, p > or = 0.05). There was no incidence of exit site infection, tunnel infection, or florid sepsis in either group. Likewise, no stenosis or bleeding complication was noted. Thus conversion of a temporary HD catheter to a tunneled catheter using the same venous insertion site is safe, does not increase the risk of infection, and allows conservation of other central venous access sites.     

Comparison of outcomes of minimally invasive mitral valve surgery for posterior, anterior and bileaflet prolapse

Objective: We sought to compare the outcomes of minimally invasive mitral valve (MV) surgery for anterior (anterior mitral leaflet, AML), posterior (posterior mitral leaflet, PML) or bileaflet (BL) MV prolapse. Methods: Between August 1999 and December 2007, 1230 patients who presented with isolated AML (n = 156, 12.7%), isolated PML (n = 672, 54.6%) or BL (n = 402, 32.7%) MV prolapse underwent minimally invasive MV surgery. The preoperative mitral regurgitation (MR) grade was 3.3 ± 0.8, left ventricular ejection fraction (LVEF) was 62 ± 12% and mean age was 58.9 ± 13.0 years; 836 patients (68.0%) were male. Mean follow-up time was 2.7 ± 2.1 years, and the follow-up was 100% complete. Results: Overall, the MV repair rate was 94.0% (1156 patients). Seventy-four patients (6.0%) received MV replacement. MV repair for PML prolapse was accomplished in 651 patients (96.9%), for AML in 142 patients (91%) and for BL in 363 patients (90.3%). Repair techniques consisted predominantly of leaflet resection and/or implantation of neochordae, combined with ring annuloplasty. Concomitant procedures were tricuspid valve surgery (n = 56), atrial fibrillation ablation (n = 286) and closure of an atrial septal defect or patent foramen ovale (PFO) (n = 89). The overall duration of cardiopulmonary bypass was 127 ± 40 min and aortic cross-clamp time was 78 ± 33 min. The mean postoperative hospital stay was 11.6 ± 9.7 days for the overall group. Early echocardiographic follow-up revealed excellent valve function in the vast majority of patients, regardless of the repair technique, with a mean MR grade of 0.3 ± 0.5. For the overall group, 5-year survival rate was 87.3% (95% CI: 83.9–90.1) and 5-year freedom from cardiac reoperation rate was 95.6% (95% CI: 94.1–96.7). The log-rank test revealed no significant difference between the three groups regarding long-term survival or freedom from reoperation. Conclusions: Minimally invasive MV repair can be achieved with excellent results. Long-term outcomes and reoperation rates for AML prolapse are not significantly different from PML or BL prolapse.     

Indomethacin,ibuprofen and gentamicin administered during late stages of glomerulogenesis do not reduce glomerular number at 14 days of age in the neonatal rat

Premature neonates are frequently administered indomethacin, ibuprofen and gentamicin during the period of active glomerulogenesis. These drugs are known to have nephrotoxic effects, but the morphological effect of these drugs is unknown. The purpose of this study was to determine whether administration of these drugs during the late stages of glomerulogenesis in the rat has an effect on glomerular endowment. Rat pups were given, intraperitoneally, indomethacin, ibuprofen or indomethacin and gentamicin for the first 5 days of their postnatal life. The pups were killed at 14 days of age at completion of glomerulogenesis. The total number of glomeruli in the left kidney was determined by the physical disector/fractionator stereological technique. There was no difference between treatment groups in total number of glomeruli per kidney (P = 0.45). There were significantly fewer glomeruli per gram of kidney in those rat pups that had received indomethacin or ibuprofen (P < 0.0001). The reduction in the number of glomeruli per gram of kidney may indicate augmented growth of nephron tubules and/or collecting ducts, and/or be a consequence of oedema secondary to drug exposure. Further study is required to determine whether reduced glomerular number is seen in older animals or following exposure to these drugs at different time-points in kidney development.     

Does routine intraoperative cholangiography prevent bile duct transection?

Background The role of routine intraoperative cholangiography is controversial. The aim of this study was to assess the impact of routine intraoperative cholangiography on the incidence of common bile duct injuries, and to evaluate the operative outcome of laparoscopic cholecystectomy carried out in a major teaching hospital and review the literature.Methods Prospectively collected data on 3,145 laparoscopic cholecystectomies performed mainly by surgical trainees in the period 1990 to 2002 using routine intraoperative cholangiography with fluoroscopy were reviewed.Results The mean age of the study sample (65.6% male, 34.4% female) was 54 years, and 16.9% of the patients had clinical acute cholecystitis. The conversion rate to open cholecystectomy was 4.3%. Intraoperative cholangiography was attempted for 90.7% of the patients with a 95.9% success rate. Five patients (0.16%) had common bile duct injuries. Four injuries had occurred in the first 5 years. One injury (0.06%) had occurred after 1995. This injury was identified intraoperatively and repaired laparoscopically. Routine intraoperative cholangiography prevented one definite common bile duct transection.Conclusions In this series using routine intraoperative cholangiography, there was a low rate and severity of common bile duct injuries, with a high intraoperative recognition rate. There was no bile duct transection or major injury requiring common bile duct reconstruction. Although intraoperative cholangiography helped in the immediate identification of injuries and the institution of appropriate therapy, injury was not completely prevented.