Single fibers of skeletal muscle as a novel graft for cell transplantation to the heart

OBJECTIVE: Skeletal myoblast transplantation is a promising alternative to treat heart failure. A single fiber, the minimal functional unit of skeletal muscle, retains skeletal myoblasts beneath the basal lamina. When surrounding muscle is injured, myoblasts migrate from the fiber into the damaged area to regenerate muscle. We hypothesized that such isolated fibers could be used as an efficient vehicle to deliver myoblasts into damaged myocardium, resulting in improved cardiac function. METHODS: Living single fibers of rat skeletal muscle were isolated, and their behavior was characterized in vitro. Single fibers were injected into the myocardium (at 4 sites, each receiving a single fiber) of rats in 2 models of heart failure induced either by means of doxorubicin administration or left coronary artery occlusion. RESULTS: Skeletal myoblasts dissociated from an isolated single fiber, proliferated, and differentiated into multinucleated myotubes in vitro. Within 3 days after grafting in vivo, original fibers provided putative myoblasts and disappeared. At 4 weeks, discrete loci consisting of several multinucleated myotubes were observed. Furthermore, single-fiber transplantation significantly improved cardiac function compared with the control treatment in either doxorubicin-treated hearts (maximum dP/dt, 4013.9 +/- 96.1 vs 3603.1 +/- 102.3 mm Hg/s; minimum dP/dt, -2313.7 +/- 75.1 vs. -2057.1 +/- 52.4 mm Hg/s) or ischemic hearts (maximum dP/dt, 3905.6 +/- 103.0 vs 3572.6 +/- 109.7 mm Hg/s; minimum dP/dt, -2336.1 +/- 69.7 vs -2106.4 +/- 74.2 mm Hg/s). CONCLUSION: Single-fiber transplantation acts as a vehicle for delivering putative skeletal myoblasts that appear to differentiate into myotubes within the myocardium. This was associated with improved function of failing hearts, suggesting its efficacy as a novel graft for cellular cardiomyoplasty.     

Long-term outcomes following laparoscopic adjustable gastric banding: Postoperative psychological sequelae predict outcome at 5-year follow-up

Background: NICE guidelines state that patients with psychological contra-indications should not be considered for bariatric surgery, including Laparoscopic Adjustable Gastric Banding (LAGB) surgery as treatment of morbid obesity, although no consistent correlation between psychiatric illness and long-term outcome in LAGB has been established. This is to our knowledge the first study to evaluate long-term outcomes in LAGB for a full range of DSM-IV defined psychiatric and eating disorders, and forms part of a research portfolio developed by the authors aimed at defining psychological predictors of bariatric surgery in the short-, medium- and long-term.^1,2 Methods: Case notes of 37 subjects operated on between April 1997 and June 2000, who had undergone structured clinical interview during pre-surgical assessment to yield diagnoses of mental and eating disorders according to DSM-IV criteria were analyzed according to a set of operationally defined criteria. Statistical analysis was carried out to compare those with a poor outcome and those considered to have a good outcome in terms of psychiatric profile. Results: In this group of mainly female, Caucasian subjects, ranging in age from 27 to 60 years, one-third were diagnosed with a mental disorder according to DSM-IV criteria. The development of postoperative DSM-IV defined binge eating disorder (BED) or depression strongly predicted poor surgical outcome, but pre-surgical psychiatric factors alone did not. Conclusion: Although pre-surgical psychiatric assessment alone cannot predict outcome, an absence of preoperative psychiatric illness should not reassure surgeons who should be mindful of postoperative psychiatric sequelae, particularly BED. The importance of providing an integrated biopsychosocial model of care in bariatric teams is highlighted.     

Hemodialysis vascular access modifies the association between dialysis modality and survival

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.     

Postnatal HIV transmission in breastfed infants of HIV‐infected women on ART: a systematic review and meta‐analysis

Introduction : To systematically review the literature on mother‐to‐child transmission in breastfed infants whose mothers received antiretroviral therapy and support the process of updating the World Health Organization infant feeding guidelines in the context of HIV and ART. Methods : We reviewed experimental and observational studies; exposure was maternal HIV antiretroviral therapy (and duration) and infant feeding modality; outcomes were overall and postnatal HIV transmission rates in the infant at 6, 9, 12 and 18 months. English literature from 2005 to 2015 was systematically searched in multiple electronic databases. Papers were analysed by narrative synthesis; data were pooled in random effects meta‐analyses. Postnatal transmission was assessed from four to six weeks of life. Study quality was assessed using a modified Newcastle‐Ottawa Scale (NOS) and GRADE. Results and discussion : Eleven studies were identified, from 1439 citations and review of 72 abstracts. Heterogeneity in study methodology and pooled estimates was considerable. Overall pooled transmission rates at 6 months for breastfed infants with mothers on antiretroviral treatment (ART) was 3.54% (95% CI: 1.15–5.93%) and at 12 months 4.23% (95% CI: 2.97–5.49%). Postnatal transmission rates were 1.08 (95% CI: 0.32–1.85) at six and 2.93 (95% CI: 0.68–5.18) at 12 months. ART was mostly provided for PMTCT only and did not continue beyond six months postpartum. No study provided data on mixed feeding and transmission risk. Conclusions : There is evidence of substantially reduced postnatal HIV transmission risk under the cover of maternal ART. However, transmission risk increased once PMTCT ART stopped at six months, which supports the current World Health Organization recommendations of life‐long ART for all.     

Use of perioperative cardiac medical therapy among patients undergoing coronary artery bypass graft surgery

BACKGROUND: Previous studies have demonstrated that cardiac medical therapy is associated with improved clinical outcomes in noncardiac surgery. However, the use of these agents among patients undergoing coronary artery bypass graft (CABG) remains poorly understood. METHODS: We described the in-hospital medication use among 2,389 consecutive patients who underwent CABG at three North American hospitals. Demographic, clinical, and medication use information was extracted from resource and cost accounting systems at each hospital. We examined use of aspirin, angiotensin-converting-enzyme (ACE) inhibitors, beta blockers, and statins during the following seven in-hospital periods: admission, presurgery, the day before surgery, the day of surgery, the day after surgery, postsurgery, and discharge. RESULTS: Medication use throughout hospitalization was low among patients undergoing CABG. Use of ACE inhibitors and statins on the day of surgery was <10%, while aspirin and beta blocker use on the day of surgery was 43.0% and 42.9%, respectively. The use of cardiac medical therapy at hospital discharge was also low (ACE inhibitors: 23.0%; aspirin: 74.9%; beta blockers: 58.9%; and statins: 28.2%). The use of cardiac medical therapy at discharge appeared to increase over time. CONCLUSION: In-hospital cardiac medical therapies are underused among patients undergoing CABG. This is particularly true at discharge, where the benefits of these agents for secondary prevention are well established.     

Age affects outcomes in chronic kidney disease

Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD.     

Adiponectin in renal disease: relationship to phenotype and genetic variation in the gene encoding adiponectin

BACKGROUND: The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with end-stage renal disease (ESRD). Adiponectin is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD. METHODS: In a cohort of 204 (62% males) ESRD patients aged 52 +/- 1 years the following parameters were studied: presence of CVD, body composition, plasma adiponectin (N= 107), cholesterol, triglycerides, HDL-cholesterol, serum leptin, high-sensitivity C-reactive protein (hs-CRP), urinary albumin excretion (UAE), and single-nucleotide polymorphisms (SNPs) in the apM1 gene at positions -11391, -11377, 45, and 276. Thirty-six age- (52 +/- 2 years) and gender-matched (64% males) healthy subjects served as control subjects. RESULTS: Markedly (P < 0.0001) elevated median plasma adiponectin levels were observed in ESRD patients (22.2 microg/mL), especially type 1 diabetic patients (36.8 microg/mL), compared to control subjects (12.2 microg/mL). Log plasma adiponectin correlated to visceral fat mass (R=-0.29; P < 0.01) and Log hs-CRP (R=-0.26; P < 0.01). In a stepwise (forward followed by backward) multiple regression model only type-1 diabetes (P < 0.001) and visceral fat mass (P < 0.05) were independently associated with plasma adiponectin levels. The adiponectin gene -11377 C/C genotype was associated with a lower prevalence of CVD (25 vs. 42%) compared to the G/C genotype. CONCLUSION: The present cross-sectional study demonstrates that, whereas genetic variations seem to have a minor impact on circulating adiponectin levels, lower visceral fat mass and type 1 diabetes mellitus are associated with elevated plasma adiponectin levels in ESRD patients. Furthermore, low levels of adiponectin are associated with inflammation in ESRD.     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.