Citations

Response to a drug often differs widely among individual patients. This variability is frequently observed not only with respect to effective responses but also with adverse drug reactions. Matching patients to the drugs that are most likely to be effective and least likely to cause harm is the goal of effective therapeutics. Pharmacogenomics (PGx) holds the promise of precision medicine through elucidating the genetic determinants responsible for pharmacological outcomes and using them to guide drug selection and dosing. Here we survey the US landscape of research programs in PGx implementation, review current advances and clinical applications of PGx, summarize the obstacles that have hindered PGx implementation, and identify the critical knowledge gaps and possible studies needed to help to address them.

A “perineal” branch of the sciatic nerve has been visualized during surgery, but there is currently no description of this nerve branch in the literature. Our study investigates the presence and frequency of occurrence of perineal innervation by the sciatic nerve and characterizes its anatomy in the posterior thigh. Fifteen cadavers were obtained for dissection. Descriptive results were recorded and analyzed statistically. Twenty‐one sciatic nerves were adequately anatomically preserved. Six sciatic nerves contained a perineal branch. Five sciatic nerves had a branch contributing to the perineal branch of the posterior femoral cutaneous (PFC) nerve. In specimens with adequate anatomical preservation, the perineal branch of the sciatic nerve passed posterior to the ischial tuberosity in three specimens and posterior to the conjoint tendon of the long head of biceps femoris and semitendinosus muscles (conjoint tendon) in one. In specimens in which the perineal branch of the PFC nerve received a contribution from the sciatic nerve, the branch passed posterior to the sacrotuberous ligament in one case and posterior to the conjoint tendon in three. Unilateral nerve anatomy was found to be a poor predictor of contralateral anatomy (Cohen's kappa = 0.06). Our study demonstrates for the first time the presence and frequency of occurrence of the perineal branch of the sciatic nerve and a sciatic contribution to the perineal branch of the PFC nerve. Clinicians should be cognizant of this nerve and its varying anatomy so their practice is better informed. Clin. Anat. 31:357–363, 2018. © 2018 Wiley Periodicals, Inc.

OBJECTIVEThe sciatic nerve, particularly its peroneal division, is at risk for injury during total hip arthroplasty (THA), especially when a posterior approach is used. The majority of the morbidity results from the loss of peroneal nerve–innervated muscle function. Approximately one-third of patients recover spontaneously. The objectives of this study were to report the outcomes of distal decompression of the peroneal nerve at the fibular tunnel following sciatic nerve injury secondary to THA and to attempt to identify predictors of a positive surgical outcome.METHODSA retrospective study of all patients who underwent peroneal decompression for the indication of sciatic nerve injury following THA at the Mayo Clinic or Washington University School of Medicine in St. Louis was performed. Patients with less than 6 months of postoperative follow-up were excluded. The primary outcome was dorsiflexion strength at latest follow-up. Univariate and multivariate logistic regression analyses were performed to assess the ability of the independent variables to predict a good surgical outcome.RESULTSThe total included cohort consisted of 37 patients. The median preoperative dorsiflexion grade at the time of peroneal decompression was 0. Dorsiflexion at latest follow-up was Medical Research Council (MRC) ≥ 3 for 24 (65%) patients. Dorsiflexion recovered to MRC ≥ 4− for 15 (41%) patients. In multivariate logistic regression analysis, motor unit potentials in the tibialis anterior (OR 19.84, 95% CI 2.44–364.05; p = 0.004) and in the peroneus longus (OR 8.68, 95% CI 1.05–135.53; p = 0.04) on preoperative electromyography were significant predictors of a good surgical outcome.CONCLUSIONSAfter performing peroneal nerve decompression at the fibular tunnel, 65% of the patients in this study recovered dorsiflexion strength of MRC ≥ 3 at latest follow-up, potentially representing a significant improvement over the natural history.

Bioprostheses are prone to structural valve degeneration, resulting in limited long-term durability. A significant challenge when comparing the durability of different types of bioprostheses is the lack of a standardized terminology for the definition of a degenerated valve. This issue becomes especially important when we try to compare the degeneration rate of surgically inserted and transcatheter bioprosthetic valves. This document, by the VIVID (Valve-in-Valve International Data), proposes practical and standardized definitions of valve degeneration and provides recommendations for the timing of clinical and imaging follow-up assessments accordingly. Its goal is to improve the quality of research and clinical care for patients with deteriorated bioprostheses by providing objective and strict criteria that can be utilized in future clinical trials. We hope that the adoption of these criteria by both the cardiological and surgical communities will lead to improved comparability and interpretation of durability analyses.

OBJECTIVEThe natural history of complete spinal cord injury (SCI) is poorly studied. The classically quoted rate of improvement or conversion for patients with American Spinal Injury Association (ASIA) grade A (ASIA A) injuries is 15%–20%; however, data supporting this rate are very limited. In this paper, the authors conducted a meta-analysis of modern data reporting on ASIA A patients and evaluated factors affecting the natural history of the disease.METHODSThe authors conducted a systematic literature review of all randomized clinical trials (RCTs) and observational studies of patients with traumatic SCI. The Embase, MEDLINE, PubMed, Scopus, CINAHL, and Cochrane databases were reviewed for all studies reporting on SCI and published after 1992. A meta-analysis was conducted using the DerSimonian and Laird (random-effects) model with a summary odds ratio analysis.RESULTSEleven RCTs and 9 observational studies were included in the final analysis. Overall, the 20 included studies reported on 1162 patients with ASIA A injuries. The overall conversion rate was 28.1%, with 327 of 1162 patients improving to at least ASIA B. The overall rate of conversion noted in cervical spine injuries was 33.3%, whereas that in thoracic injuries was 30.6%. Patients undergoing early surgery had a higher rate of conversion (46.1%) than patients undergoing late surgery (25%) (OR 2.31, 95% CI 1.08–4.96, p = 0.03).CONCLUSIONSThe overall rate of conversion of ASIA A SCIs from pooled data of prospective trials and observational series is 28.1%. This rate of conversion is higher than what is reported in the literature. Early surgery is predictive of a higher conversion rate. However, there are not enough data to provide conclusions pertaining to the efficacy of biological and medical therapies.

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N -acetyl-β- d -glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation–Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C. Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300–815 mg), which induced a urine output of 8425 mL (interquartile range, 6341–10 528 mL) over the 72-hour intervention period. Levels of N -acetyl-β- d -glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P >0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (−8.7 ng/mg; interquartile range, −169 to 35 ng/mg; P <0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin ( P =0.21), N -acetyl-β- d -glucosaminidase ( P =0.46), or kidney injury molecule 1 ( P =0.22). Increases in neutrophil gelatinase-associated lipocalin, N -acetyl-β- d -glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69–0.91; P =0.001). Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

Background: Statin dose guidelines for patients with peripheral artery disease (PAD) are largely based on coronary artery disease and stroke data. The aim of this study is to determine the effect of statin intensity on PAD outcomes of amputation and mortality. Methods: Using an observational cohort study design and a validated algorithm, we identified patients with incident PAD (2003–2014) in the national Veterans Affairs data. Highest statin intensity exposure (high-intensity versus low-to-moderate–intensity versus antiplatelet therapy but no statin use) was determined within 1 year of diagnosis of PAD. Outcomes of interest were lower extremity amputations and death. The association of statin intensity with incident amputation and mortality was assessed with Kaplan-Meier plots, Cox proportional hazards modeling, propensity score–matched analysis, and sensitivity and subgroup analyses, as well, to reduce confounding. Results: In 155 647 patients with incident PAD, more than a quarter (28%) were not on statins. Use of high-intensity statins was lowest in patients with PAD only (6.4%) in comparison with comorbid coronary/carotid disease (18.4%). Incident amputation and mortality risk declined significantly with any statin use in comparison with the antiplatelet therapy–only group. In adjusted Cox models, the high-intensity statin users were associated with lower amputation risk and mortality in comparison with antiplatelet therapy–only users (hazard ratio, 0.67; 95% confidence interval, 0.61–0.74 and hazard ratio, 0.74; 95% confidence interval, 0.70–0.77, respectively). Low-to-moderate–intensity statins also had significant reductions in the risk of amputation and mortality (hazard ratio amputation, 0.81; 95% confidence interval, 0.75– 0.86; hazard ratio death, 0.83; 95% confidence interval, 0.81–0.86) in comparison with no statins (antiplatelet therapy only), but effect size was significantly weaker than the high-intensity statins ( P <0.001). The association of high-intensity statins with lower amputation and death risk remained significant and robust in propensity score–matched, sensitivity, and subgroup analyses. Conclusions: Statins, especially high-intensity formulations, are underused in patients with PAD. This is the first population-based study to show that high-intensity statin use at the time of PAD diagnosis is associated with a significant reduction in limb loss and mortality in comparison with low-to-moderate–intensity statin users, and patients treated only with antiplatelet medications but not with statins, as well.

What's already known about this topic? LUTO is a rare but life‐threatening condition affecting the fetus and child in which prenatal therapy is currently being offered but remains controversial. A recent RCT comparing this treatment to post‐natal treatment in selected cases failed to come to robust conclusions due to under‐recruitment. So, the controversy persists. What does this study add? In this debate, 2 renown experts in the field develop their arguments pro and against shunting for all LUTO cases based on the current literature and a long‐standing clinical experience in the field of fetal therapy.