Repeat Low‐Trauma Fractures Occur Frequently Among Men and Women Who Have Osteopenic BMD

Fracture risk assessment based solely on BMD has limitations. Additional risk factors include the presence of a previous low‐trauma fracture. We sought to quantify the fracture burden attributable to first versus repeat fracture. We studied 2179 men and 5269 women, 50–90 yr of age, participating in the Canadian Multicentre Osteoporosis Study (CaMos). We included all low‐trauma fractures that occurred over 8 yr of follow‐up and classified these as either first or repeat clinical low‐trauma fracture based on lifetime fracture history. Analyses were further stratified by sex, age, BMD risk categories (normal, osteopenia, osteoporosis), and vertebral deformity status. There were 128 fractures in men and 577 fractures in women. About 25% of fractures in men and 40% in women were repeat fractures. Just over one half of first fractures occurred in those with osteopenic BMD (58% in men, 54% in women). Just under one half of repeat fractures also occurred in those with osteopenic BMD (42% in men, 47% in women). The incidence of repeat fracture was, in most cases, nearly double, but sometimes nearly quadruple, the incidence of first fracture within a given BMD risk category in both men and women. Repeat fractures contribute substantially to overall fracture burden, and the contribution is independent of BMD. Furthermore, those with a combination of prior low‐trauma fracture and another risk factor were at especially high risk of future fracture.     

Autoimmune responses against renal tissue proteins in long-term surviving allograft recipients

Major histocompatibility complex antigens (MHC) are classical targets of recipient responses to allotransplants. However, the role of an immune response directed against autologous graft tissue determinants is poorly defined. In this study, we investigated (i) whether autologous kidney tissue extract can induce an immune response to autologous kidney proteins in normal rats, and (ii) if a similar autologous response develops in the long-term surviving LEW.1A recipients of an MHC-mismatched LEW.1W kidney (RT1^u to RT1^a). LEW.1A rats immunized with allo- or syngeneic soluble kidney extracts developed a T-cell response to self antigens as shown by the frequency of specific IFN-γ-producing T cells from LEW.1A rats in the presence of extracts (ELISPOT). In contrast, they responded only marginally to dominant RT1^u determinants. The ELISPOT against fractions of soluble autologous kidney extracts separated by an FPLC gel-filtration system indicated a preferential response to megalin, a high molecular weight protein that has been shown to be involved in experimental Heymann nephritis. In a model of long-term kidney allograft survival by anti-CD28 administration, recipients also developed humoral but not cellular responses to megalin. Our data suggest that autoimmune processes develop in long-term surviving kidney allograft recipients.     

Laparoscopic Sleeve Gastrectomy as Revisional Procedure for Failed Gastric Banding and Vertical Banded Gastroplasty

Background  The problem of revision of failed gastric banding (GB) and vertical banded gastroplasty (VBG) procedures has become a common situation in bariatric surgery. Laparoscopic sleeve gastrectomy (LSG) has been recently used to revise failed restrictive procedures. The objective of this study is to evaluate the results of LSG as revisional procedure for failed GB and VBG. Methods  A prospective held database was questioned regarding patients' demographic, indication for revision, conversion to open surgery, morbidity, percentage of excess weight loss (%EWL), evolution of comorbidities, and need for a second procedure after LSG. Results  Forty-one patients, 34 women and seven men with a mean age of 42 years (range 19 to 63 years) and a mean body mass index at 49.9 kg/m² (range 35.9–63 kg/m²), underwent laparoscopic conversion of GB (36 patients) and VBG (five patients) into LSG. Indication for revisional surgery was insufficient weight loss in all the cases. All procedures were completed laparoscopically. There was no mortality and five patients (12.2%) developed complications (high leak, one patient; intra-abdominal abscess, three patients; and complicated incisional hernia, one patient). At a mean follow-up of 13.4 months, %EWL is on average 42.7% (range 4–76.1%). Six patients had a second procedure (four had laparoscopic duodenal switch, one had laparoscopic Roux-en-Y gastric bypass, and one had laparoscopic biliopancreatic diversion). Conclusion  Conversion of GB and VBG into LSG is feasible and safe. LSG is effective in the short term with a mean %EWL of 42.7% at 13.4 months. Long-term results of LSG as revisional procedure are awaited to establish its efficacy in the long term.     

Designing a workplace return-to-work program for occupational low back pain: an intervention mapping approach

Background  

Despite over 2 decades of research, the ability to prevent work-related low back pain (LBP) and disability remains elusive. Recent research suggests that interventions that are focused at the workplace and incorporate the principals of participatory ergonomics and return-to-work (RTW) coordination can improve RTW and reduce disability following a work-related back injury. Workplace interventions or programs to improve RTW are difficult to design and implement given the various individuals and environments involved, each with their own unique circumstances. Intervention mapping provides a framework for designing and implementing complex interventions or programs. The objective of this study is to design a best evidence RTW program for occupational LBP tailored to the Ontario setting using an intervention mapping approach.     

Late relapse of germ cell tumors

Objective  To assess the main characteristics of late relapsing malignant germ cell tumors (MGCTs). These tumors are rare and occur by definition 2 years or later after successful treatment. Methods  We present relevant literature on relapsing MGCT in order to highlight the following issues: incidence, impact of initial treatment on the subsequent risk of late relapse, treatment, and survival. Results  A pooled analysis of 5,880 patients with MGCT revealed late relapses in 119 of 3,704 (3.2%) and in 31 of 2,176 (1.4%) patients with non-seminoma and seminoma, respectively. The retroperitoneal space is the predominant site of relapse in both histological types. The initial treatment is important for the risk and localization of late relapses. Patients with single site teratoma are usually cured by surgery alone, whereas viable MGCT or teratoma with malignant transformation may require multimodal treatment with chemo- and/or radiotherapy as well as surgery. Surgery is the most important part in the treatment of late relapses. Salvage chemotherapy should, if feasible, be based on a representative biopsy. Five-year cancer-specific survival is above 50% in the recent large series and reaches 100% in case of single site teratoma. Conclusions  Treatment of late relapsing MGCT patients is challenging and should be performed in experienced centers only. Referral of late relapsing patients to high-volume institutions ensures the best chances of cure and enables multimodal treatment, and contributes to increased knowledge of tumor biology as well experience with the clinical course of these patients.     

Critical influence of natural regulatory CD25+ T cells on the fate of allografts in the absence of immunosuppression

BACKGROUND: Allografts are occasionally accepted in the absence of immunosuppression. Because naturally occurring CD4(+)CD25(+) regulatory T cells (natural CD25(+) Treg cells) have been shown to inhibit allograft rejection, we investigated their influence on the outcome of allografts in nonimmunosuppressed mouse recipients. METHODS: We compared survival times of male CBA/Ca skin grafts in female CBA/Ca recipients expressing a transgenic anti-HY T-cell receptor on a RAG-1(+/+) (A1[M]RAG+) or a RAG-1(-/-) (A1[M]RAG-) background. Depletion of natural CD25(+) Treg cells in A1[M]RAG+ mice was achieved by in vivo administration of the PC61 monoclonal antibody. The influence of natural CD25(+) Treg cells on the fate of major histocompatibility complex class II-mismatched (C57BL/6X bm12)F1 skin or bm12 heart transplants in C57BL/6 recipients was also assessed. Finally, we investigated the impact of natural CD25(+) Treg cells on the production of T-helper (Th)1 and Th2 cytokines in mixed lymphocyte cultures between C57BL/6 CD4(+) CD25(-) T cells as responders and bm12 or (C57BL/6X bm12)F1 antigen-presenting cells as stimulators. RESULTS: Male allografts were spontaneously accepted by female A1(M)RAG+ mice but readily rejected by female A1(M)RAG+ mice depleted of natural CD25(+) Treg cells by pretreatment with the PC61 monoclonal antibody. Depletion of CD25(+) Treg cells also enhanced eosinophil-determined rejection of (C57BL/6X bm12)F1 skin grafts or bm12 cardiac grafts in C57BL/6 recipients. Finally, natural CD25(+) Treg cells inhibited the production of interleukin (IL)-2, interferon-gamma, IL-5, and IL-13 in mixed lymphocyte culture in a dose-dependent manner. CONCLUSION: Natural CD25(+) Treg cells control Th1- and Th2-type allohelper T-cell responses and thereby influence the fate of allografts in nonimmunosuppressed recipients.     

Predictors of a favourable response to icodextrin in peritoneal dialysis patients with ultrafiltration failure

BACKGROUND AND AIMS: Icodextrin is a starch-derived glucose polymer that causes sustained ultrafiltration in long dwells in peritoneal dialysis. The aim of this study was to assess factors that were predictive of an increment in ultrafiltration following the introduction of icodextrin in patients with refractory fluid overload. METHODS: Thirty-nine patients (20 male/19 female, mean age 57.7 +/- 2.4 years) on peritoneal dialysis were enrolled in a prospective pretest/post-test, open-label study. All patients had symptomatic fluid overload refractory to fluid restriction (<800 mL/day), frusemide doses of 250 mg or more daily, optimization of dwell time and use of hypertonic dextrose. An icodextrin exchange was substituted for a 4.25% dextrose exchange for the long-dwell period. RESULTS: After 1 month, median (interquartile range) 24 h ultrafiltration volume increased by 500 mL (interquartile range: 50-1000). An increase in ultrafiltration volume correlated positively with the dialyate : plasma creatinine ratio at 4 h (r = 0.498, P = 0.001) and negatively with the ratio of dialysate glucose concentrations at 4 and 0 h (r = -0.464, P = 0.003). On multivariate regression analysis, high transporter status was predictive of a greater ultrafiltration response to icodextrin relative to dextrose peritoneal dialysis exchanges. Age, sex, race, peritoneal dialysis duration, peritoneal dialysis modality, diabetes mellitus, baseline albumin, and baseline ultrafiltration volume were not significantly correlated with the change in ultrafiltration volume. CONCLUSION: Icodextrin significantly augments ultrafiltration volumes in patients with refractory fluid overload. A high peritoneal membrane transporter status is the best predictor of a favourable ultrafiltration response to icodextrin.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy: a randomized controlled trial

Jean-Jacques Parienti, MD, DTM&H; Marina Thirion, MD; Bruno Mégarbane, MD, PhD; Bertrand Souweine, MD, PhD; Abdelali Ouchikhe, MD; Andrea Polito, MD; Jean-Marie Forel, MD; Sophie Marqué, MD; Benoît Misset, MD; Norair Airapetian, MD; Claire Daurel, MD; Jean-Paul Mira, MD, PhD; Michel Ramakers, MD; Damien du Cheyron, MD, PhD; Xavier Le Coutour, MD; Cédric Daubin, MD; Pierre Charbonneau, MD; for Members of the Cathedia Study Group

JAMA. 2008;299(20):2413-2422.

Context  Based on concerns about the risk of infection, the jugular site is often preferred over the femoral site for short-term dialysis vascular access.

Objective  To determine whether jugular catheterization decreases the risk of nosocomial complications compared with femoral catheterization.

Design, Setting, and Patients  A concealed, randomized, multicenter, evaluator-blinded, parallel-group trial (the Cathedia Study) of 750 patients from a network of 9 tertiary care university medical centers and 3 general hospitals in France conducted between May 2004 and May 2007. The severely ill, bed-bound adults had a body mass index (BMI) of less than 45 and required a first catheter insertion for renal replacement therapy.

Intervention  Patients were randomized to receive jugular or femoral vein catheterization by operators experienced in placement at both sites.

Main Outcome Measures  Rates of infectious complications, defined as catheter colonization on removal (primary end point), and catheter-related bloodstream infection.

Results  Patient and catheter characteristics, including duration of catheterization, were similar in both groups. More hematomas occurred in the jugular group than in the femoral group (13/366 patients [3.6%] vs 4/370 patients [1.1%], respectively; P = .03). The risk of catheter colonization at removal did not differ significantly between the femoral and jugular groups (incidence of 40.8 vs 35.7 per 1000 catheter-days; hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.62-1.16; P = .31). A prespecified subgroup analysis demonstrated significant qualitative heterogeneity by BMI (P for the interaction term < .001). Jugular catheterization significantly increased incidence of catheter colonization vs femoral catheterization (45.4 vs 23.7 per 1000 catheter-days; HR, 2.10; 95% CI, 1.13-3.91; P = .017) in the lowest tercile (BMI <24.2), whereas jugular catheterization significantly decreased this incidence (24.5 vs 50.9 per 1000 catheter-days; HR, 0.40; 95% CI, 0.23-0.69; P < .001) in the highest tercile (BMI >28.4). The rate of catheter-related bloodstream infection was similar in both groups (2.3 vs 1.5 per 1000 catheter-days, respectively; P = .42).

Conclusion  Jugular venous catheterization access does not appear to reduce the risk of infection compared with femoral access, except among adults with a high BMI, and may have a higher risk of hematoma.

Trial Registration  clinicaltrials.gov Identifier: NCT00277888

     

Starch digestibility modulation significantly improves glycemic variability in type 2 diabetic subjects: A pilot study

Background and aimsIn type 2 diabetes (T2D) patients, the reduction of glycemic variability and postprandial glucose excursions is essential to limit diabetes complications, beyond HbA1c level. This study aimed at determining whether increasing the content of Slowly Digestible Starch (SDS) in T2D patients’ diet could reduce postprandial hyperglycemia and glycemic variability compared with a conventional low-SDS diet.Methods and resultsFor this randomized cross-over pilot study, 8 subjects with T2D consumed a controlled diet for one week, containing starchy products high or low in SDS. Glycemic variability parameters were evaluated using a Continuous Glucose Monitoring System.Glycemic variability was significantly lower during High-SDS diet compared to Low-SDS diet for MAGE (Mean Amplitude of Glycemic Excursions, p < 0.01), SD (Standard Deviation, p < 0.05), and CV (Coefficient of Variation, p < 0.01). The TIR (Time In Range) [140–180 mg/dL[ was significantly higher during High-SDS diet (p < 0.0001) whereas TIRs ≥180 mg/dL were significantly lower during High-SDS diet. Post-meals tAUC (total Area Under the Curve) were significantly lower during High-SDS diet.ConclusionOne week of High-SDS Diet in T2D patients significantly improves glycemic variability and reduces postprandial glycemic excursions. Modulation of starch digestibility in the diet could be used as a simple nutritional tool in T2D patients to improve daily glycemic control.Registration numberin clinicaltrials.gov: NCT 03289494.