Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high‐, and low‐impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome‐wide association study (GWAS)‐implicated BMD variants. We used dual‐energy X‐ray absorptiometry to estimate femoral neck, total hip, and spine areal‐BMD and total body less head (TBLH) bone mineral content (BMC) Z‐scores. The BMD genetic score was negatively associated with each bone Z‐score (eg, TBLH‐BMC: estimate = –0.03, p = 1.3 × 10^?6). Total PA was positively associated with bone Z‐scores; these associations were driven by time spent in high‐impact PA (eg, TBLH‐BMC: estimate = 0.05, p = 4.0 × 10^?10) and were observed even for children with lower than average bone Z‐scores. We found no evidence of PA‐adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA‐genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH‐BMC in males (p interaction = 7.1 × 10^?5), where PA was associated with higher TBLH‐BMC Z‐score among the BMD‐lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10^?9). In conclusion, the beneficial effect of PA on bone, especially high‐impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS‐implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.     

Influence of preservation solution on the isolation and culture of human hepatocytes from liver grafts

A major problem for the isolation and transplantation of hepatocytes is the lack of resources for obtaining viable hepatocytes. Improving this situation would enhance hepatic cell transplantation programs. Our objective was to evaluate the influence of the preservation solutions used during organ retrieval on the quality of hepatocytes isolated from liver tissue. We compared the results of the collagenase perfusion technique for isolation of hepatocytes in human livers flushed with University of Wisconsin (UW) and Celsior preservation solutions. Yield (number of viable cells per gram of tissue), cellular viability, efficiency of cells to attach to culture plates and form a monolayer, and drug metabolizing competence of the hepatocytes were measured. Successful isolation was achieved in 63% of the procedures using the UW solution and 100% of the procedures using the Celsior solution. In the UW group, significantly lower cell viability (38 +/- 41% vs. 79 +/- 14%, p < 0.05), yield of cells (4.0 +/- 5.2 x 10(6) vs. 8.2 +/- 5.6 x 10(6) cells/g, p < 0.05), and protein content at 24 h of culture (0.6 +/- 0.6 vs. 1.2 +/- 0.3 mg protein per plate, p < 0.05) than in Celsior solution were found. However, similar values of P450 activities were found in both groups. The more successful isolation, better yield, and higher cell viability obtained from human liver grafts preserved in Celsior solution, in comparison to UW solution, suggest Celsior solution as the most appropriate for preserving cadaveric hepatic tissue to be used for hepatocyte harvesting.     

Cáncer de vesícula biliar en un hospital comarcal

Objectives

To assess the management of gallbladder cancer (GBC) in our region.

Material and methods

Data on 372 patients who underwent cholecystectomy were identified from our database (January 2003 to February 2008) and 6 patients were found to have GBC.

Results

Four patients had incidental carcinoma, one case was preoperatively suspected, and one patient presented with jaundice and locally advanced neoplasia. The incidence was 2 per 100,000 inhabitants per year; incidental carcinoma in 1.1% of cholecystecomies. The ultrasonography showed multilithiasis in 2 patients, sludge and neoplasia in 1, gallstones more than 3 cm in 2, and tumor mass only in 1 case. T stage: 1 case of T0 (in situ), 1 of T1, 2 of T2 and one T4. Incidental carcinomas were reoperated on when a T2 was established: 2 underwent lymphadenectomy and cystic stump resection, 1 segmentectomy IVb-V and lymphadenectomy. In the preoperative suspected neoplasia a cholecystectomy, lymphadenectomy, and partial hepatic gallbladder bed resection was initially performed.

Conclusions

GBC has a low incidence but it will be found in 1% of cholecystectomies. There is no adjuvant treatment and T-based surgical treatment is the is the only opportunity to reach cure in those patients. A national GBC database would be helpful in the publication of national guidelines for this disease.     

Estudio epidemiológico de la anemia preoperatoria en pacientes sometidos a cirugía oncológica en España. Estudio RECIRON

Introduction

Anaemia is common in oncology patients who are going to have surgery for tumour resection. Allogenic blood transfusion has been associated with a greater incidence of postoperative complications. The aim of this study is to analyse current clinical practice as regards the preoperative treatment and conditions of these patients in Spain.

Material and method

This is an epidemiological observational study which included 472 patients from different hospitals. The data included in the clinical history was analysed: tumour location, preoperative laboratory tests, functional situation (Karnofsky index [KI]), anaemia treatment and transfusions given since the diagnosis.

Results

As regards the tumour location, 181 were urological (38.3%), 161 digestive system (34.1%), and 130 gynaecological (27.5%). The time from the initial diagnosis until surgical intervention was 6.2±6 weeks, and 19.1±23 days from the anaesthetist visit to the surgical operation. The mean pre-operative haemoglobin (Hb) was 13.1±2 g/dl. The anaemia was treated in 12.9% of the patients and 15% (69 patients) received a transfusion before surgery. A total of 28.1% patients had a KI≤80. The lowest preoperative haemoglobin levels are associated with the lowest KI.

Conclusions

Anaemia is present in a high percentage of oncology patients who are going to be surgically treated. Preoperative blood transfusion is the most common treatment. It was observed that there is sufficient preoperative time to be able to improve preparation of the patient for surgery.     

Molecular subtypes of breast cancer: metabolic correlation with 18F-FDG PET/CT

Purpose

To determine whether the metabolic features of breast tumours differ among molecular subtypes.

Methods

This prospective study included 168 women diagnosed with locally advanced breast cancer. PET/CT was requested in the initial staging before neoadjuvant treatment (multicentre study, FISCAM grant). All patients underwent an ¹⁸F-FDG PET/CT scan with a dual time-point acquisition. Both examinations (PET-1 and PET-2) were evaluated qualitatively and semiquantitatively with calculation of SUVmax (SUV-1 and SUV-2, respectively), and the percentage variation in the SUVs and retention indexes (RI) between PET-1 and PET-2 in the breast tumour were calculated. Biological prognostic parameters, including the steroid receptor status, HER-2 expression, proliferation rate (Ki-67) and grading, were determined from primary tumour tissue. Tumour subtypes were classified following the recommendations of the 12th International Breast Conference, by immunohistochemical surrogates as luminal A, luminal B-HER2(?), luminal B-HER2(+), HER2(+) or basal. Metabolic semiquantitative parameters and molecular subtypes were correlated.

Results

Of the 168 tumours, 151 were classified: 16 were luminal A, 53 were luminal B-HER2(?), 29 were luminal B-HER2(+), 18 were HER2(+) and 35 were basal. There were significant differences between SUV-1 and SUV-2 and the different subtypes, with higher SUVs in HER2(+) and basal tumours. No significant differences were found with respect to RI.

Conclusion

Semiquantitative metabolic parameters showed statistically significant differences among the molecular subtypes of the tumours evaluated. Therefore, there seems to be a relationship between molecular and glycolytic phenotypes.     

Multiparametric monitoring of ischemia-reperfusion in rat kidney: effect of ischemic preconditioning

BACKGROUND: Microelectrode technology is a promising tool for monitoring kidney ischemia and the changes induced by its therapeutic management. Ischemic preconditioning, that is, brief ischemic periods before sustained ischemia, has been shown to protect several organs, including the kidney, from ischemia-reperfusion injury. We tested whether the effect of preconditioning could be appraised by real-time measurement of parameters representative of tissue hypoxia. METHODS: In a sample of pentobarbital-anesthetized and mechanically ventilated rats, we studied the effect of renal ischemic preconditioning (10-min ischemia and 10-min reflow interval) on subsequent ischemia-reperfusion (45 min and 60 min). Renal tissue electrical impedance, extracellular pH, and potassium concentration [K+] were measured continuously by implanted microelectrodes. RESULTS: Ischemia induced an early, rapid rise in extracellular potassium and impedance module, followed by a phase of slower increase, whereas pH decreased rapidly, reaching a plateau. Preconditioning treatment did not cause significant changes in interstitial pH and [K+] but increased ischemic tissue impedance. During reperfusion, the three variables recovered progressively; however, after a decline, electrical impedance showed a clear postischemic increase. This rise was suppressed by preconditioning. CONCLUSIONS: Real-time measurement of any of the three parameters showed capability for early detection of ischemia. In contrast with findings in myocardial tissue, preconditioning in the kidney did not increase potassium cell loss during ischemia or improve ischemic acidosis or tissue impedance. Electrical impedance increased for a second time during reperfusion, indicating the presence of a postischemic cellular edema; concealing this episode was the most noticeable effect of the preconditioning treatment.     

Physical fitness effect on bone mass is mediated by the independent association between lean mass and bone mass through adolescence: a cross-sectional study

We studied 278 adolescents (169 females) aged 13.0–18.5 years to elucidate whether an independent effect of physical fitness and lean mass in the differences between male and female bones can be detected. Lean and fat masses and bone mineral content (BMC) were measured with DXA. Physical fitness was evaluated with six different tests included in the EUROFIT test battery (flexibility, isometric, dynamic and endurance strength, speed, and cardiovascular fitness). To test the independent relationship between physical fitness and bone mass, multiple regression analysis was applied, including lean mass, age, and Tanner development as covariates. The males had a 43% lower fat mass and 40% and 16% higher lean mass and total BMC compared with the females (all P < 0.05). After adjustment for differences in body size and lean mass, the females exhibited a 7.4% higher BMC than the males (P < 0.05). The multiple regression analysis showed that lean mass had an independent relationship with bone mass (P < 0.001), explaining 67% of the total variance in whole-body BMC. In males, change in R ² was 0.658 for hand grip and 0.035–0.151 for the rest of physical fitness-related variables; but 0.019–0.042 in females (all P–0.001); however, the independent relationships between physical fitness and bone disappeared after controlling for lean mass. In conclusion, it is likely the differences between male and female in bone mass could be explained by differences in lean mass and physical fitness.     

Ultrasound guidance for lateral midfemoral sciatic nerve block: a prospective, comparative, randomized study

Block of the sciatic nerve at the midfemoral level is usually performed using nerve stimulation techniques. We investigated the efficacy of ultrasound, combined with nerve stimulation, to locate and block the sciatic nerve at the lateral midfemoral level compared to nerve stimulation alone. Sixty-one patients scheduled for foot and ankle surgery were enrolled in this prospective, randomized study. Thirty patients underwent a lateral block of the sciatic nerve at the midfemoral level guided by ultrasound (group US) and 31 patients received the block without ultrasound (group ES). Once an adequate motor response was obtained using nerve stimulation, 35 mL of ropivacaine 0.5% was administered. The main end-points of the study were: number of attempts to obtain an adequate motor response, success rate of nerve location at the first attempt, quality and duration of both sensory and motor blocks, and anesthetic distribution. The success of sciatic nerve location at the first attempt was significantly more frequent in the US group than in the ES group (76.6% versus 41.9%; P < 0.001). The quality of the sensory block and the tolerance to the pneumatic tourniquet were also significantly better in the US group (P < 0.01). We conclude that ultrasound combined with nerve stimulation improved the quality of the sensory block and the tolerance to the pneumatic tourniquet, reducing the number of attempts to perform sciatic nerve block at the midfemoral level.     

Endoluminal treatment for traumatic aortic rupture. Case report and literature review

Traumatic rupture of the thoracic aorta is a near-lethal event presenting on-scene mortality rates of 80% and 60-80% perioperatively with an overall survival rate of 15%. Conventional treatment includes thoracotomy with aortic clamping and aortic replacement but this implies high complication and mortality rates with extended inpatient care. Endoluminal treatment has recently become an attractive treatment option with advantages such as lower death and complication rates as well as shorter inpatient care. We present an 18-year-old female victim of a frontal automobile crash who presented mediastinal enlargement and underwent CT evaluation confirming pericardial effusion, left hemothorax and a contained traumatic rupture of the thoracic aorta. She was sent to our hospital where aortography was performed identifying the injury, and a preperitoneal left iliac artery approach was made to insert a Medtronic Talent 24F endograft. Under fluoroscopic guidance the graft was placed below the subclavian ostium. There was no endoleak after the procedure. A left iliac-femoral bypass was performed and a chest tube was inserted. The patient was managed in the ICU, being later operated by reconstructive and orthopedic surgeons for injuries related to the initial trauma. The patient was released from the hospital on the 10th postoperative day after a satisfactory evolution. We present also a brief review of recent articles.     

Parametric uncertainty and disturbance attenuation in the suboptimal control of a non‐linear electrochemical process

The optimal control of the hydrogen evolution reactions is attempted for the regulation and change of set‐point problems, taking into account that model parameters are uncertain and I/O signals are corrupted by noise. Bilinear approximations are constructed, and their dimension eventually increased to meet accuracy requirements with respect to the trajectories of the original plant. The current approximate model is used to evaluate the optimal feedback through integration of the Hamiltonian equations. The initial value for the costate is found by solving a state‐dependent algebraic Riccati equation, and the resulting control is then suboptimal for the electrochemical process. The bilinear model allows for an optimal Kalman–Bucy filter application to reduce external noise. The filtered output is reprocessed through a non‐linear observer in order to obtain a state‐estimation as independent as possible from the bilinear model. Uncertainties on parameters are attenuated through an adaptive control strategy that exploits sensitivity functions in a novel fashion. The whole approach to this control problem can be applied to a fairly general class of non‐linear continuous systems subject to analogous stochastic perturbations. All calculations can be handled on‐line by standard ordinary differential equations integration software. Copyright © 2007 John Wiley & Sons, Ltd.