Charlson Co‐morbidity Index and albumin significantly associated with fracture risk in peritoneal dialysis patients

Published literature on fracture in dialysis patients seldom addressed the effect of co‐morbidity and malnutrition. In this study, we reported the incidence and risk factors for fracture in peritoneal dialysis patients. Peritoneal dialysis patients who had fractures between 2006 and 2011 were recruited. Demographic data, details of fracture, Charlson Co‐morbidity Index (CCI) and biochemical parameters were also collected. Non‐fracture controls, matched for age, gender and duration of dialysis, were also recruited at ratio 1:1 for fracture risk analysis. The incidence of fracture was 1 in 37 patient‐years. The commonest site of fracture was neck of femur (n = 16, 55.2%). Twenty‐four patients (82.8%) developed fracture after slip and fall injury. Eight out of 17 self‐ambulatory patients (47.1%) became non‐ambulatory after fracture. Infection was the commonest complication during hospitalization. Univariant analysis demonstrated high CCI (P = 0.001), hypoalbuminaemia (P < 0.001), loss of self autonomy (P = 0.006) and non‐ambulatory state (P = 0.011) significantly associated with increased fracture risk. However, only CCI (odds ratio (OR) 1.373, P = 0.028) and albumin (OR 0.893, P = 0.025) increased fracture risk significantly on multivariant analysis. Bone profile and parathyroid hormone were not significant risk factors. To conclude, fracture associated with adverse outcome in peritoneal dialysis patients. High CCI score and hypoalbuminaemia significantly increase risk of fracture.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Optimizing dose and scheduling of filgrastim (granulocyte colony- stimulating factor) for mobilization and collection of peripheral blood progenitor cells in normal volunteers [see comments]

To define an optimal regimen for mobilizing and collecting peripheral blood progenitor cells (PBPC) for use in allogeneic transplantation, we evaluated the kinetics of mobilization by filgrastim (recombinant met- human granulocyte colony-stimulating factor [r-metHuG-CSF]) in normal volunteers. Filgrastim was injected subcutaneously for up to 10 days at a dose of 3 (n = 10), 5 (n = 5), or 10 micrograms/kg/d (n = 15). A subset of volunteers from each dose cohort underwent a 7L leukapheresis on study day 6 (after 5 days of filgrastim). Granulocyte-macrophage colony-forming cell (GM-CFC) numbers in the blood were maximal after 5 days of filgrastim; a broader peak was evident for CD34+ cells between days 4 and 6. The 95% confidence intervals (CI) for mean number of PBPC per milliliter of blood in the three dose cohorts overlapped on each study day. However, on the peak day, CD34+ cells were significantly higher in the 10 micrograms/kg/d cohort than in a pool of the 3 and 5 micrograms/kg/d cohorts. Mobilization was not significantly influenced by volunteer age or sex. Leukapheresis products obtained at the 10 micrograms/kg/d dose level contained a median GM-CFC number of 93 x 10(4)/kg (range, 50 x 10(4)/kg to 172 x 10(4)/kg). Collections from volunteers receiving lower doses of filgrastim contained a median GM- CFC number of 36 x 10(4)/kg (range, 5 x 10(4)/kg to 204 x 10(4)/kg). The measurement of CD34+ cells per milliliter of blood on the day of leukapheresis predicted the total yield of PBPC in the leukapheresis product (r = .87, P < .0001). Assuming a minimum GM-CFC requirement of 50 x 10(4)/kg (based on our experience with autologous PBPC transplantation), all seven leukapheresis products obtained at the 10 micrograms/kg/d dose level were potentially sufficient for allogeneic transplantation purposes. We conclude that in normal donors, filgrastim 10 micrograms/kg/d for 5 days with a single leukapheresis on the following day is a highly effective regimen for PBPC mobilization and collection. Further studies are required to determine whether PBPC collected with this regimen reliably produce rapid and sustained engraftment in allogeneic recipients.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet

Imbalances in gut microbiota composition during ulcerative colitis (UC) indicate a role for the microbiota in propagating the disorder. Such effects were investigated using in vitro batch cultures (with/without mucin, peptone or starch) inoculated with faecal slurries from healthy or UC patients; the growth of five bacterial groups was monitored along with short-chain fatty acid (SCFA) production. Healthy cultures gave two-fold higher growth and SCFA levels with up to ten-fold higher butyrate production. Starch gave the highest growth and SCFA production (particularly butyrate), indicating starch-enhanced saccharolytic activity. Sulphate-reducing bacteria (SRB) were the predominant bacterial group (of five examined) for UC inocula whereas they were the minority group for the healthy inocula. Furthermore, SRB growth was stimulated by peptone presumably due to the presence of sulphur-rich amino acids. The results suggest raised SRB levels in UC, which could contribute to the condition through release of toxic sulphide.     

Epidemiology of tuberculosis and HIV coinfections in Singapore, 2000–2014

Cross‐matching of records between Singapore's tuberculosis and HIV registries showed that 3.3% of individuals with tuberculosis (TB) were coinfected with HIV (2000?2014), the TB incidence among individuals with HIV infection was 1.65 per 100 person‐years, and 53% of coinfections were diagnosed within 1 month of each other. The findings supported joint prevention programmes for early diagnosis and treatment.     

图形翻转视觉诱发电位在视神经管减压后视神经损伤不同时期的变化特征

目的:观察视神经损伤动物模型在损伤后和不同时期视神经管减压后视觉诱发电位的变化,了解创伤性视神经损伤的手术时机与疗效的关系。方法:实验于2005-03/05在解放军南京军区南京总医院动物实验中心完成。①实验分组:30只新西兰白兔随机分为正常对照组、术后2d减压组、术后7d减压组、术后14d减压组、术后不减压组,每组6只。②造模:除正常对照组外,其余各组在视神经孔中塞入一细端为2mm直径的圆锥软硅胶,阻塞视神经孔,造成视神经的挤压伤。③指标检测:采用图形翻转视觉诱发电位检测损伤前、损伤后1h、减压前1h、减压后2周视功能变化,记录NPN曲线主波(P波)的绝对潜伏期、绝对波幅。正常对照组仅采集一组数据作为对照。结果:30只实验动物均进入结果分析。①正常对照组家兔图形翻转视觉诱发电位检查均引出典型NPN波型曲线,视神经挤压伤后1hNPN波形低阔扁平,P波潜伏期延长,波幅降低。②P波潜伏期:术后2d减压组减压后短于减压前[(71.25±8.51),(86.47±14.28)ms,P<0.05];术后7d减压组减压前后比较差异无显著性(P>0.05);术后14d减压组减压后明显长于减压前[(158.73±15.16),(116.35±17.13)ms,P<0.05]。术后2d减压组和术后7d减压组短于术后不减压组(P<0.01)。术后7,14d减压组和术后不减压组明显长于正常对照组(P<0.01)。③P波波幅:术后2d减压组减压后高于减压前[(5.25±0.78),(4.42±0.42)μV,P<0.05]。术后2d减压组减压后低于术后7d减压组、术后14d减压组(P<0.01),术后14d减压组低于术后7d减压组(P<0.05);术后7d减压组、术后14d减压组、术后不减压组低于正常对照组(P<0.01)。结论:神经元继发性损伤是视功能进行性下降的重要原因,视神经减压术有利于减轻视神经间接损伤,较早期(损伤后48h以内)减压可阻止轴突继发性损伤,避免视功能进一步下降,并在一定程度上逆转视功能的损害。     

One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -     

Enhanced recovery pathway in adult patients undergoing thoracolumbar deformity surgery

BACKGROUND CONTEXTEnhanced recovery (ERAS) pathways can help hospitals maximize the incentives of bundled payment models while maintaining high-quality patient care. A key component of an enhanced recovery pathway is the ability to predictably reduce inpatient length of stay, as this is a critical component of the cost equation.PURPOSETo determine the efficacy of an enhanced recovery pathway on reducing length of stay after thoracolumbar adult deformity surgery.STUDY DESIGNSingle surgeon retrospective review of prospectively-collected data.PATIENT SAMPLEForty adult deformity patients who underwent ≥5 levels of fusion to the pelvis (two to L5) with a single surgeon before and after implementation of an ERAS pathway.METHODSThe pathway involved participation by anesthesiology, hospital medicine, and physical therapy, and was designed to achieve goals previously associated with decreased LOS (eg, EBL<1200 mL, procedure time <4.5 hours, avoidance of ICU postoperatively, and mobilization POD0-1). Patients were propensity-score matched 1:1 to a historical cohort (enhanced recovery [ER] and historical [H] cohorts), based on demographics, medical comorbidities, radiographic alignment parameters, and surgical factors. Outcomes were compared to determine the effect of the enhanced recovery pathway. Primary outcomes included LOS and 90-day complications and readmissions.RESULTSAfter matching, gender, BMI, ASA class, preoperative opioid dependence, day of surgery, sagittal alignment parameters, rate of revision surgery, three-column osteotomies, and interbody fusions were comparable between the cohorts (p>.05). In the ER cohort, there was reduced EBL (920±640 vs. 1437±555, p=.004) and no ER patient went to the ICU immediately following surgery, compared with 30% of H patients (p=.022). The ER cohort also had a greater number of patients ambulating by POD1 compared to the H cohort (100% vs. 55%, p=.010). ER patients had a shorter LOS (4.5±1.3 vs. 7.3±4.4 days, p=.010). A 90-day readmission and complications were comparable between the cohorts (p>.05).CONCLUSIONSThe creation of an ERAS pathway for patients undergoing thoracolumbar adult deformity surgery reduced length of stay without negatively affecting short-term morbidity and complications. Given the specificity of this pathway to a single surgeon and hospital, the resources and staffing changes that were instrumental in creating the pathway may not be generalizable to other centers.