Hyperuricemia,Hypertension, and Chronic Kidney Disease: an Emerging Association

Uric acid is a product of purine metabolism and has been linked to gout and kidney calculi. Chronic kidney disease (CKD) and hypertension (HTN) are two major public health problems, and both are associated with increased risk of cardiovascular events. Emerging evidence suggests a pathogenic role of hyperuricemia in the development of HTN and CKD, in addition to progression of CKD, by inducing renal inflammation, endothelial dysfunction, and activation of the renin-angiotensin system. In addition, several epidemiological studies have linked hyperuricemia with an increased risk of HTN and CKD. A few clinical trials have assessed the use of uric acid-lowering therapies such as allopurinol and febuxostat in the management of HTN and delaying progression of CKD. To date, most of these trials are short-term with a small sample size; however, their results are encouraging and provide a rationale for larger randomized controlled trials to establish the role of uric acid-lowering therapies in the management of HTN, in addition to prevention of CKD progression and cardiovascular events.     

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 x 10(9)/L or more, or CNS-3 (5 or more leukocytes/microL with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lower-risk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% +/- 2.6% (SE); the 8-year rate was 78.6% +/- 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% +/- 0.8%, and that of isolated plus combined CNS relapse was 3.0% +/- 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% +/- 1.3% in the lower-risk patients who received a cumulative dose of 1.2 g/m(2) and 5.0% +/- 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m(2) (P = .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether.     

The Role of Tendon Transfers for Irreparable Rotator Cuff Tears

Purpose of Review

This review aims to describe the tendon transfer options for treating irreparable rotator cuff tears (RCTs). Options for transfer include latissimus dorsi and lower trapezius transfers for posterior-superior RCTs and pectoralis major and latissimus dorsi transfer for anterior-superior RCTs.

Recent Findings

While the latissimus dorsi tendon transfer has historically been performed for posterosuperior RCTs, the lower trapezius transfer is a more anatomic option and has demonstrated promising results in recent studies. Similarly, the pectoralis major transfer has historically been the tendon transfer of choice for anterosuperior RCTs. However, the latissimus dorsi tendon transfer has recently been shown to be a safe and anatomic tendon transfer for subscapularis insufficiency.

Summary

The treatment of irreparable RCTs involves complex decision making. Tendon transfer procedures can restore the glenohumeral joint force couples, allowing restoration of near-normal shoulder kinematics. Benefits include reliable pain relief, increased function, and increased strength. Proper selection of donor tendon is crucial, and the principles of tendon transfer procedures must be adhered to for maximal benefit.

     

The PROPKD Score: A New Algorithm to Predict Renal Survival in Autosomal Dominant Polycystic Kidney Disease

The course of autosomal dominant polycystic kidney disease (ADPKD) varies among individuals, with some reaching ESRD before 40 years of age and others never requiring RRT. In this study, we developed a prognostic model to predict renal outcomes in patients with ADPKD on the basis of genetic and clinical data. We conducted a cross-sectional study of 1341 patients from the Genkyst cohort and evaluated the influence of clinical and genetic factors on renal survival. Multivariate survival analysis identified four variables that were significantly associated with age at ESRD onset, and a scoring system from 0 to 9 was developed as follows: being male: 1 point; hypertension before 35 years of age: 2 points; first urologic event before 35 years of age: 2 points; PKD2 mutation: 0 points; nontruncating PKD1 mutation: 2 points; and truncating PKD1 mutation: 4 points. Three risk categories were subsequently defined as low risk (0–3 points), intermediate risk (4–6 points), and high risk (7–9 points) of progression to ESRD, with corresponding median ages for ESRD onset of 70.6, 56.9, and 49 years, respectively. Whereas a score ≤3 eliminates evolution to ESRD before 60 years of age with a negative predictive value of 81.4%, a score >6 forecasts ESRD onset before 60 years of age with a positive predictive value of 90.9%. This new prognostic score accurately predicts renal outcomes in patients with ADPKD and may enable the personalization of therapeutic management of ADPKD.     

Mediastinal fibrosis combined with Behçet's disease. Three case reports

PURPOSE: Intrathoracic manifestations other then vascular aneurysm and thrombosis are rare in the course of Beh?et's disease. Mediastinal fibrosis is also unusual. METHODS: Three cases of Beh?et's disease with initial mediastinal fibrosis are reported. Diagnosis means, pathogenic mechanisms and therapeutic modalities are also more precisely defined. RESULTS: Three male patients (21, 25 and 27 years of age, respectively) were hospitalized for progressive vena cava superior syndrome accompanied by mediastinal fibrosis demonstrated by MRI and/or CT scan which both showed infiltration of the mediastinal fat. Multiple calcifications were also present in one patient. Histology was performed in one case. Thrombosis of the vena cava superior and innominata veins was associated with fibrosis in all three cases. Thrombosis of venae subclavia and left jugularis was also present in one case. Other manifestations leading to the diagnosis of Beh?et's disease were demonstrated by the patient's history and, in one case, occurred on the fourth day of hospitalization. After initiation of a treatment including corticoids, anticoagulants and colchicine, the outcome was favorable in two cases. The third patient died. CONCLUSION: Mediastinal fibrosis combined with Beh?et's disease has rarely been described. However, it should be included in manifestations of the disease. The causative process which might be vasculitis has to be demonstrated.