Citations

AbstractETV6 mutations are rare but recurrent somatic events in myeloid neoplasms and are negatively prognostic in myelodysplastic syndrome. We set out to examine the clinical and molecular characteristics of patients undergoing investigation for myeloid neoplasms, found to have deleterious ETV6 mutations. ETV6 mutations occurred in 33 of 5793 (0.6%) cases investigated and predominantly in high‐risk disease entities including MDS with increased blasts, primary myelofibrosis and AML, myelodysplasia‐related. In three cases, isolated iso (17q) karyotype was concurrently detected, an otherwise rare karyotype in myeloid neoplasms. ETV6 mutations were frequently subclonal and never occurred as an isolated abnormality with ASXL1 (n = 22, 75%), SRSF2 (n = 14, 42%) and SETBP1 (n = 11, 33%) the predominant co‐mutations. Restricting to patients with MDS, higher rates of ASXL1, SETBP1, RUNX1 and U2AF1 mutations occurred in ETV6 mutated cases, relative to a consecutive control cohort with wild‐type ETV6. The median OS of the cohort was 17.5 months. This report highlights the clinical and molecular associations of somatic ETV6 mutations in myeloid neoplasms, suggests their occurrence as a later event, and proposes further translational research questions for their role in myeloid neoplasia.

AbstractObjectiveAdrenal schwannomas and juxta‐adrenal schwannomas are rare tumours. We aimed to summarise their clinical, biochemical and imaging characteristics.DesignSingle‐centre retrospective study of eligible patients between 1995 and 2022.Patients and MeasurementsPatients with a histopathologic diagnosis of adrenal or juxta‐adrenal schwannoma.ResultsTwenty‐four patients were diagnosed with either primary adrenal schwannoma (8, 33%) or juxta‐adrenal schwannoma (16, 67%). Most tumours (21, 88%) were discovered incidentally on imaging. All tumours were unilateral, with 15 (62%) on the left and 9 (38%) on the right. At diagnosis, the median tumour size was 4 cm (range, 2–13 cm). Adrenal schwannomas were smaller when compared to juxta‐adrenal schwannomas (median of 3.1 cm [range, 2–9 cm] vs. 4.6 cm [range, 2.3–13.3 cm], p = .037). On imaging, the tumours were round or oval in shape in 16 (70%), lobulated in 7 (30%), solid in 15 (68%), solid‐cystic in 7 (32%), heterogeneous in 14 (61%) and homogeneous in 9 (39%). The median unenhanced computed tomography attenuation was 30 Hounsfield units (HU) (range, 12–38 HU). Of the 20 patients who underwent complete hormonal testing, all had nonfunctioning tumours. There was no recurrence or new tumour development in our cohort.ConclusionsAdrenal and juxta‐adrenal schwannomas are nonfunctioning benign tumours that present with indeterminate radiographic features, including large tumour size and increased unenhanced CT attenuation. We did not find an imaging phenotype that was diagnostic of schwannoma. The diagnosis of this rare tumour is based on biopsy or resection.

Current validated hidradenitis suppurativa (HS) severity assessment tools are time-consuming and impractical in fast-paced, ambulatory clinic settings. This study evaluated the construct validity of the most severe or ‘worst’ area local Hidradenitis suppurativa Activity and Severity Index-Revised (W-HASI-R) as a novel target area assessment tool for clinical setting use. W-HASI-R had strong association with the International Hidradenitis Suppurativa Severity Score System and abscess and nodule count, moderate association with Hurley stage and HS physician global assessment and weak, negative association with reverse-scored Dermatology Quality Life Index. The resulting data suggest that W-HASI-R may be an option as an efficient target area assessment tool for fast-paced, ambulatory settings.

The purpose of this study was to evaluate the effect of rapid weight loss on static balance and functional mobility among excessively obese patients undergoing Laparoscopic Adjustable Gastric Banding (LAGB) surgery. Subjects (8 females; BMI >35 kg/m2) underwent baseline measurements before LAGB surgery, followed by subsequent evaluations at 6 weeks, 12 weeks, and 24 weeks during the follow-up appointments. During each evaluation, various assessments were conducted, including measurements of anthropometry such as body weight, height, hip and waist circumference, as well as functional tests for static balance, 10-meter walk, and timed get-up-and-go. There were statistically significant changes in weight, BMI, waist circumference, hip circumference, abdominal circumference, waist-hip ratio, static sway eyes open, timed up-and-go, 10-meter walk, and steps in 10-meter walk test values (p<0.001) between the baseline and the postoperative measurements. However static sway values under eyes closed condition were not statistically significant. In the 24-week follow-up, the weight loss, reduction in abdominal circumference, increase in walking speed against time and step count, and recovery in functional movements were shown to persist. Also, reduction in static balance surface oscillation confirmed the improvement of balance control.

Contrast-induced acute kidney injury (CI−AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI−AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI−AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI−AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI−AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI−AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI−AKI is crucial to uncover molecular targets for the prevention of CI−AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI−AKI and elaborate the biomarkers that are used to detect early-stage CI−AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI−AKI.

Key Points Hepatorenal syndrome type 1 (HRS-1) is an often fatal, but potentially reversible, kidney failure in patients with decompensated cirrhosis. Treatment with terlipressin in patients with HRS-1 is associated with a reduction in the need for RRT. Background Hepatorenal syndrome type 1 (HRS-1)—also known as hepatorenal syndrome-AKI (HRS-AKI)—is a rapidly progressing and usually fatal, but potentially reversible, kidney failure occurring in patients with decompensated cirrhosis. A large proportion of patients with HRS-1 require renal replacement therapy (RRT). Terlipressin demonstrated efficacy in reversing HRS and improving renal function in patients with HRS-1 in three phase III, randomized, clinical trials (RCTs; i.e. , OT-0401, REVERSE, and CONFIRM). However, these RCTs were not designed to evaluate the effect of terlipressin on the requirement of RRT. In this study, the effect of terlipressin on RRT requirements in the pooled phase III patient population was assessed. Methods For this retrospective analysis, data from patients who participated in the OT-0401, REVERSE, and CONFIRM studies were integrated in the largest-to-date randomized database ( N =608). Results The need for RRT was significantly decreased in patients in the terlipressin group versus the placebo group by day 30 (28.1% versus 35.9%, respectively; P = 0.040) and day 60 (30.1% versus 37.9%, respectively; P = 0.045) in the pooled population and also postliver transplantation (LT) at day 60 (20.5% versus 40.3%, respectively; P = 0.008) and day 90 (25.3% versus 43.1%, respectively; P = 0.018). More patients were alive and RRT-free by day 90 in the overall population (36.9% versus 28.5%; P = 0.030) and among patients who received an LT (60.0% versus 39.7%; P = 0.010). Random assignment to receive terlipressin was an independent positive predictor of avoidance of RRT ( P = 0.042); while higher baseline serum creatinine (sCr) level and Child-Pugh scores were negatively associated with RRT avoidance ( P < 0.001 and P = 0.040, respectively). Conclusions Terlipressin decreased the requirement of RRT compared with placebo among patients with HRS-1, including those receiving LT. A lower sCr level at the beginning of therapy was associated with avoidance of RRT.

Summary: The tibial nerve is bound tightly to the posterior tibial artery in the tarsal tunnel where expansion capacity is limited. Therefore, the nerve may be vulnerable to, and damaged by chronic pulsatile trauma from an atypically positioned overriding artery, labeled “punched-nerve syndrome”. In this article, we present a 49-year-old woman who presented with two months of severe burning pain in the left medial ankle and sole of the foot without antecedent trauma. Neurological examination identified dysesthetic sensation to light touch in the left medial sole of the foot, and both active and passive dorsiflexion worsened the painful paresthesia. Nerve conduction studies demonstrated a reduced left medial plantar mixed nerve action potential amplitude, 50% less than the right. High-resolution ultrasound (HRUS) showed an increased left tibial nerve cross-sectional area of 26 mm2 (normal <22.3 mm2) at the level of the ankle with side-to-side difference of 6 mm2 (normal <5.7 mm2). The distal tibial nerve and its medial plantar branch were atypically positioned immediately deep to the left posterior tibial artery and abnormally flattened with focal enlargement of the nerve on longitudinal view. Dynamic analysis demonstrated the nerve being compressed with each pulsation of the tibial artery immediately above. Active dorsiflexion of the ankle narrowed the space underneath the flexor retinaculum resulting in further compression of the nerve against the artery. In conclusion, HRUS as an adjunct to electrophysiological studies identified punched-nerve arterial compression as an etiology of tarsal tunnel syndrome.

OBJECTIVES: To investigate whether a novel acute care multipatient viewer (AMP), created with an understanding of clinician information and process requirements, could reduce time to clinical decision-making among clinicians caring for populations of acutely ill patients compared with a widely used commercial electronic medical record (EMR). DESIGN: Single center randomized crossover study. SETTING: Quaternary care academic hospital. SUBJECTS: Attending and in-training critical care physicians, and advanced practice providers. INTERVENTIONS: AMP. MEASUREMENTS AND MAIN RESULTS: We compared ICU clinician performance in structured clinical task completion using two electronic environments—the standard commercial EMR (Epic) versus the novel AMP in addition to Epic. Twenty subjects (10 pairs of clinicians) participated in the study. During the study session, each participant completed the tasks on two ICUs (7–10 beds each) and eight individual patients. The adjusted time for assessment of the entire ICU and the adjusted total time to task completion were significantly lower using AMP versus standard commercial EMR (–6.11; 95% CI, –7.91 to –4.30 min and –5.38; 95% CI, –7.56 to –3.20 min, respectively; p < 0.001). The adjusted time for assessment of individual patients was similar using both the EMR and AMP (0.73; 95% CI, –0.09 to 1.54 min; p = 0.078). AMP was associated with a significantly lower adjusted task load (National Aeronautics and Space Administration-Task Load Index) among clinicians performing the task versus the standard EMR (22.6; 95% CI, –32.7 to –12.4 points; p < 0.001). There was no statistically significant difference in adjusted total errors when comparing the two environments (0.68; 95% CI, 0.36–1.30; p = 0.078). CONCLUSIONS: When compared with the standard EMR, AMP significantly reduced time to assessment of an entire ICU, total time to clinical task completion, and clinician task load. Additional research is needed to assess the clinicians’ performance while using AMP in the live ICU setting.