A molecularly integrated grade for meningioma

BackgroundMeningiomas are the most common primary intracranial tumor in adults. Clinical care is currently guided by the World Health Organization (WHO) grade assigned to meningiomas, a 3-tiered grading system based on histopathology features, as well as extent of surgical resection. Clinical behavior, however, often fails to conform to the WHO grade. Additional prognostic information is needed to optimize patient management.MethodsWe evaluated whether chromosomal copy-number data improved prediction of time-to-recurrence for patients with meningioma who were treated with surgery, relative to the WHO schema. The models were developed using Cox proportional hazards, random survival forest, and gradient boosting in a discovery cohort of 527 meningioma patients and validated in 2 independent cohorts of 172 meningioma patients characterized by orthogonal genomic platforms.ResultsWe developed a 3-tiered grading scheme (Integrated Grades 1-3), which incorporated mitotic count and loss of chromosome 1p, 3p, 4, 6, 10, 14q, 18, 19, or CDKN2A. 32% of meningiomas reclassified to either a lower-risk or higher-risk Integrated Grade compared to their assigned WHO grade. The Integrated Grade more accurately identified meningioma patients at risk for recurrence, relative to the WHO grade, as determined by time-dependent area under the curve, average precision, and the Brier score.ConclusionWe propose a molecularly integrated grading scheme for meningiomas that significantly improves upon the current WHO grading system in prediction of progression-free survival. This framework can be broadly adopted by clinicians with relative ease using widely available genomic technologies and presents an advance in the care of meningioma patients.     

Scope and limitations of limb-sparing surgery in childhood sarcomas

The authors reviewed 43 children with high-grade sarcomas of bone and soft tissue who underwent surgery during the past 9 years. Twenty-six patients had osteosarcoma, 7 had Ewing sarcoma, and 10 had soft tissue sarcomas. Patients ranged in age from 4 months to 13 years. Mean follow-up period was 6 years. The feasibility of resection, results of local resection, and failure of local disease control were reviewed. Limb salvage was feasible in 81% of patients. Of the 35 patients undergoing limb salvage, margins were considered adequate in 88% and inadequate in 12%. Limb-sparing resection was not feasible in 19% of patients. Five patients (four with metastatic disease at presentation) did not undergo surgery and were given palliative care; three other patients underwent amputation. The decision of whether to proceed with limb salvage surgery must depend on the aggressiveness of the underlying tumor, its stage, the feasibility of obtaining tumor-free resection margins, and the response to neoadjuvant therapy.     

Double level Chance-type fractures of spine in ankylosing spondylitis

Chance fractures are usually associated with seat belt injuries. Mechanism is always related to flexion-distraction at vertebral level. Double level Chance-type fractures have rarely been reported in published literature. We presented such a fracture at D10 and L3 level in a 38-year-old patient with ankylosing spondylitis. Management was done with posterior decompression and short segment fixation separately.     

An iatrogenic proximal radioulnar synostosis: a case report and review of literature

The most common cause of proximal radioulnar synostosis in adults is traumatic, usually after forearm fractures. Disabling complications are mainly loss of rotatory movements of the forearm. Various surgical procedures have been described in the literature to end up in forearm synostosis as a complication. We here presented a rare case of proximal forearm synostosis following a common but improper surgical technique for an olecranon fracture complicated by implant infection. The synostosis was treated by resection and fascia lata interposition graft.     

Renal sarcoidosis presenting as acute kidney injury with granulomatous interstitial nephritis and vasculitis

Among the various renal manifestations of sarcoidosis, granulomatous inflammation confined to the tubulointerstitial compartment is the most commonly reported finding. We present the case of a 66-year-old man with acute kidney injury, hypercalcemia, mild restrictive pulmonary disease, and neurologic signs of parietal lobe dysfunction. Kidney biopsy showed diffuse interstitial inflammation with noncaseating granulomas that exhibited the unusual feature of infiltrating the walls of small arteries with destruction of the elastic lamina, consistent with granulomatous vasculitis. The findings of granulomatous interstitial nephritis on kidney biopsy, hypercalcemia, and possible cerebral and pulmonary involvement in the absence of other infectious, drug-induced, or autoimmune causes of granulomatous disease established the diagnosis of sarcoidosis. Pulse methylprednisolone followed by maintenance prednisone therapy led to improvement in kidney function, hypercalcemia, and neurologic symptoms. Vasculocentric granulomatous interstitial nephritis with granulomatous vasculitis is a rare and under-recognized manifestation of renal sarcoidosis.     

Abolition of endocrine dimorphism in hyperthyroid males? An argument for the positive feedback effect of hyperoestrogenaemia on LH secretion

Our aim was (i) to investigate the hypothalamo-hypophyseal-gonadal axis in hyperthyroid Indian males, (ii) to rule out the modulatory role of adrenal steroids on it and (iii) to determine if the simultaneous rise in oestradiol and luteinising hormone (LH) in hyperthyroid males is due to a positive feedback action of oestradiol on pituitary LH release. Age- and BMI-matched men were divided into two groups, I, euthyroid subjects (n = 17) and II, hyperthyroid patients (n = 12) on the basis of their thyroid hormone levels. Serum levels of thyroid-stimulating hormone, triiodothyronine, thyroxine, LH, follicle-stimulating hormone (FSH), prolactin, E(2), T, P(4), sex hormone binding globulin and dehydroepiandrosterone sulphate (DHEAS) were assayed. Mean levels of T and E(2) were approximately two times higher in group II in comparison with group I. DHEAS levels were similar in both groups ruling out any adrenal involvement. Mean serum LH level was 2.6 folds higher in group II in comparison with group I. Mean serum levels of FSH were higher in group II, it was marginally nonsignificant. On the basis of these and previous observations, we hypothesise that endocrinological dimorphism in human male and female is not rigid; a sustained rise in serum oestradiol probably induces a positive feedback action on pituitary leading to elevated gonadotrophin levels.     

How can we utilize livers from advanced aged donors for liver transplantation for hepatitis C?

Advanced age donors have inferior outcomes of liver transplantation for Hepatitis C (HCV). Aged donors grafts may be transplanted into young or low model for end stage liver disease (MELD) patients in order to offset the effect of donor age. However, it is not well understood how to utilize liver grafts from advanced aged donors for HCV patients. Using the UNOS database, we retrospectively studied 7508 HCV patients who underwent primary liver transplantation. Risk factors for graft failure and graft survival using advanced aged grafts (donor age ≥ 60 years) were analyzed by Cox hazards models, donor risk index (DRI) and organ patient index (OPI). Recipient's age did not affect on graft survival regardless of donor age. Advanced aged grafts had significant inferior survival compared to younger aged grafts regardless of MELD score (P < 0.0001). Risk factors of HCV patients receiving advanced aged grafts included donation after cardiac death (DCD, HR: 1.69) and recent hospitalization (HR: 1.43). Advanced aged grafts showed significant difference in graft survival of HCV patients with stratification of DRI and OPI. In conclusion, there was no offsetting effect by use of advanced aged grafts into younger or low MELD patients. Advanced aged grafts, especially DCD, should be judiciously used for HCV patients with low MELD score.