CD4+CD25+ regulatory T cells mediate acquired transplant tolerance

The Holy Grail of clinical organ transplantation is the safe induction of allograft tolerance. Transplant tolerance has been successfully induced in animal models. Since T cells play a pivotal role in graft rejection, modulating T cell function has been the primary focus of studies aimed at inducing transplant tolerance. Rodent models of transplant tolerance induction include central deletion and peripheral mechanisms involving activation-induced cell death (AICD), anergy, immune deviation, and production of regulatory T cells. These mechanisms are not mutually exclusive. Although clonal deletion and anergy limit self-reactive T cells in the thymus, these mechanisms alone are not sufficient for controlling self-reactive T cells in the periphery. There is now evidence that the adult animal harbors two functionally distinct populations of CD4(+) T cells; one mediates autoimmune disease and the other dominantly inhibits it. The latter cells express CD4, CD25 and CTLA-4. These thymus-derived T cells have recently been shown to mediate the induction and maintenance of transplant tolerance. These CD4(+)CD25(+) T cells are similar in origin, phenotype, and function to those that maintain natural self-tolerance and T cell homeostasis in the periphery. Against this background, is it possible that alloantigen specific regulatory T cells might be generated and expanded ex vivo before organ transplantation and then infused to induce long-term tolerance, perhaps without the need for chronic immunosuppression?     

Endoscopic ligation of esophageal varices for prophylaxis of first bleeding in children and adolescents with portal hypertension: preliminary results of a prospective study

Background/purpose

Endoscopic variceal ligation (EVL) is effective in controlling rebleeding from esophageal varices in children, but there is no data on the use of EVL to prevent initial bleeding. The objective of this study was to prospectively evaluate the efficacy of EVL in preventing the first hemorrhage from esophageal varices in children.

Methods

Thirty-seven children with portal hypertension (22 liver cirrhosis, 15 portal vein thrombosis), aged 4 to 17 years (M = 9.5 ± 4.4 years) were included in the study. The criteria for inclusion were (1) no previous variceal bleeding; (2) the presence of esophageal varices classified grade II or more, and (3) their enlargement by at least I grade after 6 months of observation without endoscopic treatment or appearance of endoscopic signs of high bleeding risk. A Multi-Band Ligator was used, and 2 to 6 bands were fixed under general anesthesia during one procedure depending on the number and size of varices. Follow-up examinations were performed every 3 months, repeating the procedure if necessary. In total, 75 procedures of EVL were performed, from one to 5 in each patient

Results

Four patients underwent liver transplantation before eradication of varices. Two others were excluded from the observation because of lack of compliance to the protocol. Of the remaining 31 patients, eradication of varices was achieved in 28 children (90.3%) after 2.0 EVL sessions performed at 3-month intervals. The average time of follow-up after cessation of treatment is 16 months. No bleeding from varices occurred in any child during or after treatment. There were no differences in results between children with liver cirrhosis and portal vein thrombosis. Development of hypertensive gastropathy was observed in 2 children with one episode of bleeding. Recurrence of varices without bleeding occurred in 3 children after 12, 13, and 28 months from eradication.

Conclusions

The study results confirmed that endoscopic variceal ligation is a safe and highly effective procedure in children with portal hypertension, regardless of its etiology. Eradication of esophageal varices was followed by 16 months free of bleeding. Prolonged observation is mandatory to conclude if preventive EVL influences the natural history of disease and diminishes the risk of first bleeding onset.     

The pathomorphology of congenital spinal defects in relation to future clinical development of the disease]

The authors categorised congenital malformations of the spine into five different pathomorphologic groups basing on a series of 61 cases (age ranging from 1 to 50 years): defects of the vertebra, of the vertebral body, intervertebral synostosis, rib synostosis, and defects of the vertebral arch. A total of over 30 different kinds of malformations were obtained in this classification. In the analysed series 34 patients had a predominant kind of malformation, while in 27 cases mixed malformations were noted. These malformations lead to spine deformities: 21 cases with arch scoliosis, 15 cases with kyphoscoliosis, 13 cases with angular scoliosis and 12 cases with kyphosis. Deformities had a tendency to progress with age. In 20 patients neurological deficits (increased spasticity, spastic paresis, spastic and flaccid paralysis) increased after reaching skeletal maturity. Prognosis as to deformity regression was made difficult be the large variety of different pathomorphologic types of deformity. Only general patterns were visible e.g. a tendency to progress in cases were hemivertebra were found. In cases were more than one type of deformity was noted, growth balance of the spine was not a rule. On the contrary, even small mixed deformities of ten progressed. This paper indicates that most congenital deformities of the spine should be treated operatively, either to correct the deformity or to attain spine growth balance.     

When Surgical Resources are Severely Constrained,Who Receives Care? Determinants of Access to Orthopaedic Trauma Surgery in Uganda

Background

In low- and middle-income countries, the volume of traumatic injuries requiring orthopaedic intervention routinely exceeds the capacity of available surgical resources. The objective of this study was to identify predictors of surgical care for lower extremity fracture patients at a high-demand, resource-limited public hospital in Uganda.

Methods

Skeletally mature patients admitted with the intention of definitive surgical treatment of an isolated tibia or femur fractures to the national referral hospital in Uganda were recruited to participate in this study. Demographic, socioeconomic, and clinical data were collected through participant interviews at the time of injury and 6 months post-injury. Social capital (use of social networks to gain access to surgery), financial leveraging, and ethnicity were also included as variables in this analysis. A probit estimation model was used to identify independent and interactive predictors of surgical treatment.

Results

Of the 64 patients included in the final analysis, the majority of participants were male (83%), with a mean age of 40.6, and were injured in a motor vehicle accident (77%). Due to resource constraints, only 58% of participants received surgical care. The use of social capital and femur fractures were identified as significant predictors of receiving surgical treatment, with social capital emerging as the strongest predictor of access to surgery (p < 0.05).

Conclusion

Limited infrastructure, trained personnel, and surgical supplies rations access to surgical care. In this environment, participants with advantageous social connections were able to self-advocate for surgery where demand for these services greatly exceeded available resources.

     

Trends of lymphadenectomy in upper tract urothelial carcinoma (UTUC) patients treated with radical nephroureterectomy

Introduction

To evaluate temporal trends in the delivery and extent of lymphadenectomy (LND) in radical nephroureterectomy (RNU) performed in upper tract urothelial carcinoma (UTUC) patients.

Methods

We evaluated a multi institutional collaborative database composed by 1512 consecutive patients diagnosed with UTUC treated with RNU between 1990 and 2016. Year of surgery were grouped in five periods: 1990–1996, 1997–2002, 2003–2007, 2008–2012 and 2013–2016. Data about LND were available for all patients and numbers of nodes removed and positive were reported by dedicate uropathologists. The Mann–Whitney and Chi square tests were used to compare the statistical significance of differences in medians and proportions, respectively.

Results

Five hundred forty-five patients (36.0%) received a concomitant LND while 967 (64.0%) did not; 41.9% of open RNU patients received a concomitant LND compared to 24.4% of laparoscopic RNU patients. The rate of concomitant LND increased with time in the overall, laparoscopic and open RNU patients (all p?<?0.03). Patients treated with open RNU also had an increasing likelihood to receive an adequate concomitant LND (p?<?0.001) while those undergoing a laparoscopic approach did not (p?=?0.1). Patients treated with concomitant LND had a median longer operative time of 20 min (p?=?0.01). There were no differences in perioperative outcomes and complications between patients who received a concomitant LND and those who did not (p?>?0.1).

Conclusion

Although an increased trend was observed, most patients treated with RNU did not receive LND. Surgeons using a laparoscopic RNU were less likely to perform a concomitant LND, and when done, they remove less nodes.

     

Effect of the transdermal low-level laser therapy on endothelial function

The effect of low-level laser therapy (LLLT) on the cardiovascular system is not fully established. Since the endothelium is an important endocrine element, establishing the mechanisms of LLLT action is an important issue.The aim of the study was to evaluate the effect of transdermal LLLT on endothelial function.In this study, healthy volunteers (n?=?40, age?=?20–40 years) were enrolled. N?=?30 (14 female, 16 male, mean age 30?±?5 years) constituted the laser-irradiated group (LG). The remaining 10 subjects (6 women, 4 men, mean age 28?±?5 years) constituted the control group (CG). Participants were subjected to LLLT once a day for three consecutive days. Blood for biochemical assessments was drawn before the first irradiation and 24 h after the last session. In the LG, transdermal illumination of radial artery was conducted (a semiconductor laser λ?=?808 nm, irradiation 50 mW, energy density 1.6 W/cm² and a dose 20 J/day, a total dose of 60 J). Biochemical parameters (reflecting angiogenesis: vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiostatin; antioxidative status: glutathione (GSH) and the nitric oxide metabolic pathway: symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and l-arginine) were assessed. In the LG, a significant increase in GSH levels and considerable decrease in angiostatin concentration following the LLLT were observed. No significant differences in levels of the VEGF, FGF, SDMA, ADMA were observed.LLLT modifies vascular endothelial function by increasing its antioxidant and angiogenic potential. We found no significant differences in levels of the nitric oxide pathway metabolites within 24 h following the LLLT irradiation.     

The influence of idiopathic scoliosis on load distribution in the foot

Pedobarography is used more and more often in such fields as orthopaedics, traumatology, neurology, diabetology or rehabilitation. The aim of this work has been to evaluate the effects of right-side idiopathic thoracic scolioses and changes in angular values of physiological curvatures of the spine on sub-pedal pressure distribution. TWINN 99 software assisted PEL-38 measuring platform and Penny & Giles tensiometric electrogoniometre were used in the study which was carried out on the population of 30 girls with right-side idiopathic thoracic scoliosis. The girls exhibited a mild degree of scoliosis. The control was made up of a group of 30 healthy girls with no musculoskeletal system pathology. The girls in both groups were 10 years old. Measurements of spinal curvatures and distribution of sub-pedal pressure forces were carried out three times daily, always at the same time. The analysis of the results has shown that right-side idiopathic thoracic scoliosis leads to higher pressure being imposed on the halux and convex front part of the foot. Such pressure distribution stems from flattening of the thoracic kyphosis and enhancement of lumbar lordosis. The shift of the gravity centre to the front and to the right can as a result exacerbate the pathology not only in the foot, but also in the whole lower limb at the scoliotic side.     

Atrial septal defect in adults: echocardiography and cardiopulmonary exercise capacity associated with hemodynamics before and after surgical closure

The study aimed to evaluate pre and postoperative echocardiographic data and exercise capacity in relation to age and hemodynamics in adults with atrial septal defect (ASD). Fifty-two subjects with ASD (mean age: 38.6+/-15 years) were enrolled. Echocardiography and cardiopulmonary exercise test were performed before and a year after surgery. Pre and postoperative data were analyzed for the entire group and then compared in terms of age: <40 and >or=40 years, right ventricular systolic pressure (RVSP): 30 mmHg and pulmonary to systemic flow ratio (Qp/Qs): <2.5 and >or=2.5. After surgery right ventricle dimension decreased in all patients, although it remained significantly larger in patients over 40 years. There was a negative correlation between peak oxygen uptake and preoperative RVSP (r=-0.69, P<0.001). Exercise capacity improved irrespective of the age at surgery, preoperative RVSP and Qp/Qs, although it failed to normalize in patients with RVSP >30 mmHg. Adults with ASD benefit from surgical closure irrespective of the actual age at surgery. Patient's age at surgery and pulmonary hypertension crucially impact the results of surgical intervention. Early defect correction is therefore highly recommendable, specifically with a view to preventing the hemodynamic consequences of ASD.     

Sole Use of Dexmedetomidine Has Limited Utility for Conscious Sedation during Outpatient Colonoscopy

Background: This study evaluated the ability of dexmedetomidine to provide analgesia and sedation for outpatient colonoscopy, examining outcomes including cardiorespiratory variables, side effects, and discharge readiness.

Methods: Sixty-four patients were randomly assigned to one of three treatment regimens. In group D, patients received 1 [mu]g/kg dexmedetomidine over 15 min followed by an infusion of 0.2 [mu]g [middle dot] kg-1 [middle dot] h-1. Group P received meperidine (1 mg/kg) with midazolam (0.05 mg/kg), and group F received fentanyl (0.1-0.2 mg intravenous) on demand. The assessment included measurements of heart rate, blood pressure, oxygen saturation, respiratory rate, quality of sedation/analgesia, and an evaluation of the recovery time.

Results: The study was terminated before the planned 90 patients had been recruited because of adverse events in group D. In all groups, negligible hemoglobin oxygen saturation and respiratory rate variations were observed. In group D, there was a significantly larger decrease in heart rate (to approximately 40 beats/min in 2 of 19 cases) and blood pressure (to less than 50% of the initial value in 4 of 19 patients). Supplemental fentanyl was required in 47% of patients receiving dexmedetomidine to achieve a satisfactory level of analgesia (vs. 42.8% of patients in group P and 79.2% of patients in group F). Vertigo (5 patients), nausea/vomiting (5 patients), and ventricular bigeminy (1 patient) were observed only in group D. Time to home readiness was longest in group D (85 +/- 74, 39 +/- 21, and 32 +/- 13 min in groups D, P and F, respectively; P = 0.007).     

Interleukin-10 gene polymorphism in Parkinson's disease patients

BACKGROUND: The etiology of sporadic Parkinson's disease (PD) is not well established. Recent studies revealed that inflammatory processes might also play an important role in the pathogenesis of PD. We hypothesized that genetically determined differences in the immune response, especially in anti-inflammatory cytokines production, might influence the risk of sporadic PD development and/or onset. To prove this hypothesis, two DNA polymorphisms at IL-10 promoter (-1082 and -519) were examined in sporadic PD patients. METHODS: The study enrolled 341 patients with diagnosed idiopathic PD. All cases of secondary parkinsonism were excluded from the study. For the purpose of this study the patients were also divided into two subgroups: group 1: patients with onset of Parkinson's disease, i.e., <50 years of age (early onset) included 60 patients, as well as group 2: patients with onset of Parkinson's disease >50 years of age (late onset) comprising 281 subjects. Control samples were from 315 randomly selected healthy individuals from the same geographical region who were free from signs of parkinsonism as evaluated by consultant neurologists. PCR-RFLP methods were used for genotyping. RESULTS: No statistically significant differences between PD patients and controls were found in the frequency of a single locus (-1082, -519) of IL-10 promoter. Likewise, haplotype analysis did not demonstrate any significant differences between evaluated groups. The frequency of the evaluated IL-10 genotypes was also similar in EOPD and LOPD patients. CONCLUSIONS: Results from our study revealed that the IL-10 (-1082G>A, -592C>A) polymorphism is not a risk factor of sporadic Parkinson's disease in a Polish population.