Citations

The appropriate target for BP in patients with CKD and hypertension remains uncertain. We report prespecified subgroup analyses of outcomes in participants with baseline CKD in the Systolic Blood Pressure Intervention Trial. We randomly assigned participants to a systolic BP target of <120 mm Hg (intensive group; n =1330) or <140 mm Hg (standard group; n =1316). After a median follow-up of 3.3 years, the primary composite cardiovascular outcome occurred in 112 intensive group and 131 standard group CKD participants (hazard ratio [HR], 0.81; 95% confidence interval [95% CI], 0.63 to 1.05). The intensive group also had a lower rate of all-cause death (HR, 0.72; 95% CI, 0.53 to 0.99). Treatment effects did not differ between participants with and without CKD ( P values for interactions ≥0.30). The prespecified main kidney outcome, defined as the composite of ≥50% decrease in eGFR from baseline or ESRD, occurred in 15 intensive group and 16 standard group participants (HR, 0.90; 95% CI, 0.44 to 1.83). After the initial 6 months, the intensive group had a slightly higher rate of change in eGFR (−0.47 versus −0.32 ml/min per 1.73 m 2 per year; P <0.03). The overall rate of serious adverse events did not differ between treatment groups, although some specific adverse events occurred more often in the intensive group. Thus, among patients with CKD and hypertension without diabetes, targeting an SBP<120 mm Hg compared with <140 mm Hg reduced rates of major cardiovascular events and all-cause death without evidence of effect modifications by CKD or deleterious effect on the main kidney outcome.

AbstractBackgroundWe report the accumulated experience with ventral intermediate nucleus deep brain stimulation for medically refractory orthostatic tremor.MethodsData from 17 patients were reviewed, comparing presurgical, short‐term (0‐48 months), and long‐term (≥48 months) follow‐up. The primary end point was the composite activities of daily living/instrumental activities of daily living score. Secondary end points included latency of symptoms on standing and treatment‐related complications.ResultsThere was a 21.6% improvement (P = 0.004) in the composite activities of daily living/instrumental activities of daily living score, which gradually attenuated (12.5%) in the subgroup of patients with an additional long‐term follow‐up (8 of 17). The latency of symptoms on standing significantly improved, both in the short‐term (P = 0.001) and in the long‐term (P = 0.018). Three patients obtained no/minimal benefit from the procedure.ConclusionsDeep brain stimulation of the ventral intermediate nucleus was, in general, safe and well tolerated, yielding sustained benefit in selected patients with medically refractory orthostatic tremor. © 2017 International Parkinson and Movement Disorder Society

The failure of the polycystins (PCs) to function in primary cilia is thought to be responsible for autosomal dominant polycystic kidney disease (ADPKD). Primary cilia integrate multiple cellular signaling pathways, including calcium, cAMP, Wnt, and Hedgehog, which control cell proliferation and differentiation. It has been proposed that mutated PCs result in reduced intracellular calcium, which in turn upregulates cAMP, protein kinase A (PKA) signaling, and subsequently other proliferative signaling pathways. However, the role of PKA in ADPKD has not been directly ascertained in vivo, although the expression of the main regulatory subunit of PKA in cilia and other compartments (PKA-RIα, encoded by PRKAR1A) is increased in a mouse model orthologous to ADPKD. Therefore, we generated a kidney-specific knockout of Prkar1a to examine the consequences of constitutive upregulation of PKA on wild-type and Pkd1 hypomorphic ( Pkd1 RC ) backgrounds. Kidney-specific loss of Prkar1a induced renal cystic disease and markedly aggravated cystogenesis in the Pkd1 RC models. In both settings, it was accompanied by upregulation of Src, Ras, MAPK/ERK, mTOR, CREB, STAT3, Pax2 and Wnt signaling. On the other hand, Gli3 repressor activity was enhanced, possibly contributing to hydronephrosis and impaired glomerulogenesis in some animals. To assess the relevance of these observations in humans we looked for and found evidence for kidney and liver cystic phenotypes in the Carney complex, a tumoral syndrome caused by mutations in PRKAR1A. These observations expand our understanding of the pathogenesis of ADPKD and demonstrate the importance of PRKAR1A highlighting PKA as a therapeutic target in ADPKD.

Vascularized toe joint transfer for finger proximal interphalangeal joint reconstruction can result in sub-optimal arc of motion and extension lag due to inappropriate intercalated bony segment length. We investigated the impact of intercalated segment length on passive arc of motion and extension lag of the reconstructed proximal interphalangeal joint. Cadaveric intercalated joint grafts were harvested from lesser toes and transferred to cadaveric fingers. The pre-determined finger proximal interphalangeal joint defect size was 2 cm. Three different intercalated segment lengths were inserted and resulting proximal interphalangeal joint arc of motion and extension lag were measured. The average arc of motion of finger proximal interphalangeal joints was 81° and 54° for toe proximal interphalangeal joints. Long intercalated segments had an average arc of motion of 30° with 32° extension lag. Equal-length intercalated segments had an average 49° arc of motion with 15° extension lag. Short intercalated segments had an average arc of motion of 71° with 8° extension lag. Shorter intercalated segments provide the greatest reduction in extension lag.

Hypermobility may be associated with decreased lower extremity proprioception, which in turn may increase injury risk. The prevalence of hypermobility in dancers varies across studies, but joint hypermobility appears to be more common in dancers than in the general population. The purpose of this study was to determine how hypermobility affects eyes-closed single-limb balance as an indirect measure of proprioception in dancers. The secondary aim was to compare hypermobility and balance across dancer affiliation groups. Data were collected from 45 professional dancers, 11 collegiate modern dancers, 227 student dancers, and 15 pre-professional dancers during routine dance screens. Dancer hypermobility status was assessed via an eight-point Beighton-Horan Laxity test. Single-limb balance time, in seconds, was assessed in parallel position with the eyes closed. Hypermobile (HM) and non-hy-permobile (NHM) dancers showed very similar balance times (HM median: 36.5 seconds; NHM median: 33.0 seconds; p = 0.982). Hypermobility was not significantly different between dancer affiliation groups (p = 0.154): 47% in ballet academy students, 27% in collegiate modern dancers, 62% in pre-professional dancers, and 36% in professional dancers. The student, pre-professional, and professional ballet dancers all demonstrated longer balance times than the collegiate modern dancers; however, this difference was only significant between the professional ballet dancers and collegiate modern dancers (p = 0.026). Dancers demonstrated a higher prevalence of hypermobility than what has been reported for the general population. Joint hypermobility did not affect eyes-closed single-limb balance time. Future studies are needed to determine if joint hypermobility affects more sensitive measures of proprioception and risk of injury.