What is the impact of immunosuppressive treatment on the post-transplant renal osteopathy?

Although glucocorticoid therapy is considered to be the main pathogenic factor, a consistent body of evidence suggests that other immunosuppressants might also play an important role in the development of the post-transplant renal osteopathy (PRO) through their pleiotropic pharmacological effects. Glucocorticoids seem to induce osteoclasts’ activity suppressing the osteoblasts while data regarding other immunosuppressive drugs are still controversial. Mycophenolate mofetil and azathioprine appear to be neutral regarding the bone metabolism. However, the study analyzing any independent effect of antimetabolites on bone turnover has not been conducted yet. Calcineurin inhibitors (CNIs) induce trabecular bone loss in rodent, with contradictory results in renal transplant recipients. Suppression of vitamin D receptor is probably the underlying mechanism of renal calcium wasting in renal transplant recipients receiving CNI. In spite of an increased 1,25(OH)2 vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss. More efforts should be invested to determine the role of CNI in PRO. In particular, data regarding the role of mammalian target of rapamycin inhibitors (mTORi), such as sirolimus and everolimus, in the PRO development are still controversial. Rapamycin markedly decreases bone longitudinal growth as well as callus formation in experimental models, but also lowers the rate of bone resorption markers and glomerular filtration in clinical studies. Everolimus potently inhibits primary mouse and human osteoclast activity as well as the osteoclast differentiation. It also prevents the ovariectomy-induced loss of cancellous bone by 60 %, an effect predominantly associated with a decreased osteoclast-mediated bone resorption, resulting in a partial preservation of the cancellous bone. At present, there is no clinical study analyzing the effect of everolimus on bone turnover in renal transplant recipients or comparing sirolimus versus everolimus impact on bone, so only general conclusions could be drawn. Hence, the use of mTORi might be useful in patients with PRO due to their possible potential to inhibit osteoclast activity which might lead to a decreased rate of bone resorption. In addition, it should be also emphasized that they might inhibit osteoblast activity which may lead to a decreased bone formation and adynamic bone disease. Further studies are urgently needed to solve these important clinical dilemmas.     

Microvascular osteoseptocutaneous radial flap in reconstruction of mandible following war injury

BACKGROUND: Vascularized osteoseptocutaneous radial flap is commonly used in the reconstruction of composite bony and soft tissue defects of the lower third of the face due to the outstanding quality of its cutaneous component. The aim was to evaluate the primary and overall success in the reconstruction of mandibular defects, following war injuries, with vascularized osteoseptocutaneous radial flap. METHODS: At the Department of Maxillofacial Surgery of the Military Medical Academy Belgrade, there were eight patients with this kind of defect following war injury, and the mandible was reconstructed with a vascularized osteoseptocutaneous radial flap. Bony compartment of the graft was harvested as up to 11 cm long segment of radial circumference. RESULTS: The localization and structure of the defect, features of a harvested compound graft, the procedure of the reestablishment of the mandibular continuity was presented as well as immediate and late complications during the consolidation period, and the primary successful reconstruction in 87.5% of the patients. CONCLUSION: The primary and overall success in the mandibular defects reconstruction with a vascularized osteoseptocutaneous radial flap was equal or even better than those presented in the literature on the reconstruction of the similar defects after tumor resections.     

Paternal origin of der(X)t(X;6) in a girl with trisomy 6p and unbalanced t(6;10) mosaicism in her mother

We present a case of trisomy for the whole short arm of chromosome 6 in a 3-year-old girl with moderate mental retardation, mild facial dysmorphism, short stature, failure to thrive, and no abnormalities of the visceral organs. Cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed a 46, X, der(X)t(X;6)(q22; p11.1) karyotype. The derived X was late replicating with variable spreading of X chromosome inactivation onto the translocated 6p. A normal karyotype was observed in the father, while the mother presented 46,XX/46,XX, der(10)t(6;10)(p11;p11). The mother is a mosaic with unbalanced t(6;10) in 4.7% of cells. To the best of our knowledge, this unusual mosaicism has not yet been reported. In this family the short arm of chromosome 6 was involved in an unbalanced rearrangement with chromosome X in the proband and with chromosome 10 in the mother. In order to study the mechanism of the formation of t(X;6) in the girl we performed DNA polymorphism analysis. These investigations revealed that chromosomes X and 6 involved in the rearrangement are of paternal origin. Our patient exhibits only discrete facial features characteristic of partial trisomy 6p. We suggest that mild phenotypic expression be probably due to X chromosome inactivation spreading onto the translocated 6p. This report show that combined cytogenetic, FISH, and molecular analysis of chromosomal aberrations are necessary for the understanding of the mechanism of formation, parental origin, and genetic counseling.     

Impaired regulation of calcium excretion in kidney transplant recipients

Disorders of mineral metabolism and hypercalcemia are frequent in kidney transplant recipients. Calcium to creatinine (Ca/Cr) clearance ratio was used as a criterion to distinguish between different calcium metabolism disorders. The study comprised 91 (53 men, 38 women) kidney recipients aged 23-70 years, with creatinine clearance (CrCl) >60 ml/min. The following parameters related to mineral metabolism were measured in serum: iPTH, total alkaline phosphatase (tALP), telopeptide (bone degradation marker, CTX), 25(OH)D(3), total and ionized calcium, Ca(++), Pi, creatinine (Cr). Creatinine and Ca were also determined in urine, as well as Ca/Cr clearance ratio. According to the Ca/Cr clearance ratio, patients were divided into three groups as follows: <0.01 (found in disorders caused by reduced calcium-sensing receptor sensitivity, N = 30), 0.01-0.02 (normal value, N = 45), and >0.02 (found in hyperparathyroidism, N = 16). In the group of patients with Ca/Cr clearance ratio <0.01, seven patients had hypercalcemia, and four patients had hypercalcemia and elevated iPTH. It seems that impairment of renal calcium excretion may occur in kidney transplant recipients with good kidney function. Inappropriately low calciuria and impaired sensitivity of calcium-sensing receptor may be pathogenetic factors causing hypercalcemia in kidney transplant recipients.     

Morbidly Obese are Ghrelin and Leptin Hyporesponders with Lesser Intragastric Balloon Treatment Efficiency

Background

Ghrelin and leptin recently emerged as the most influential neuroendocrine factors in the pathophysiology of obesity. The said peptides act in reciprocity and are responsible for regulation of appetite and energy metabolism. Intragastric balloons acquired worldwide popularity for obesity treatment. However, the roles of ghrelin and leptin in intragastric balloon treatment were still not systematically studied.

Methods

A prospective single-center study included 43 Caucasians treated with BioEnterics intragastric balloon, with age range of 18?C60, and divided to non-morbid (body mass index cutoff 40 kg/m²) or morbid type of obesity, with 12 months follow-up. Serum hormonal samples were taken from fasting patients and kept frozen until analyses.

Results

Significant differences were observed in anthropometrics and there were no differences between genders or comorbidities. The baseline weight for non-morbid vs. morbid was 104 kg (90?C135) vs. 128.5 kg (104?C197). Weight loss was statistically different between the studied groups during the study course with a median control weight at 6 months of 92 kg (72?C121) vs. 107 kg (84?C163), p?<?0.001. Treatment was successful for 18 (94.7%) vs. 16 (66.7%) patients, p?=?0.026. Ghrelin varied from 333.3 to 3,416.8 pg/ml and leptin from 1.7 to 61.2 ng/ml, with a statistically significant time-dependent relationship. A significant difference (p?=?0.04) with emphasized ghrelin peak was found in the 3rd month of treatment for non-morbidly obese subjects.

Conclusions

The importance of ghrelin and leptin in treatment-induced changes was reaffirmed. Ghrelin hyper-response in non-morbidly obese subjects characterized greater short-term treatment efficiency and landmarked an inclination to weight regain. The results suggest a potential pattern of individualization between obese patients according to body mass index towards intragastric balloon or bariatric surgery. Further studies are needed in order to get better insights in the pathophysiologic mechanisms of obesity.     

Preoperative and perioperative management of patients with pericardial diseases

Hemodynamic instability is the major concern in surgical patients with pericardial diseases, since general anesthesia and positive pressure ventilation may precipitate cardiac tamponade. In advanced constriction diastolic impairment and myocardial fibrosis/atrophy may cause low cardiac output during and after surgery. Elective surgery should be postponed in unstable patients with pericardial comorbidities. Pericardial effusion should be drained percutaneously (in local anesthesia) and pericardiectomy performed for constrictive pericarditis before any major surgical procedure. In emergencies, volume expansion, catecholamines, and anesthetics keeping cardiac output and systemic resistance should be applied. Etiology of pericardial diseases is an important issue is the preoperative management. Patients with neoplastic pericardial involvement have generally poor prognosis and any elective surgical procedure should be avoided. For patients with acute viral or bacterial infection or exacerbated metabolic, uremic, or autoimmune diseases causing significant pericardial effusion, surgery should be postponed until the causative disorder is stabilized and signs of pericarditis have resolved.