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AbstractWe report a two‐generation family with four females harboring an 8.5Mb heterozygous deletion of 5q15‐q21.2 who present with dysmorphic craniofacial features and speech delay. We hypothesize haploinsufficiency of CHD1 to be contributing to the clinical features observed in this family.

Abstract Aims Calmodulinopathies are rare life-threatening arrhythmia syndromes which affect mostly young individuals and are, caused by mutations in any of the three genes (CALM 1–3) that encode identical calmodulin proteins. We established the International Calmodulinopathy Registry (ICalmR) to understand the natural history, clinical features, and response to therapy of patients with a CALM-mediated arrhythmia syndrome. Methods and results A dedicated Case Report File was created to collect demographic, clinical, and genetic information. ICalmR has enrolled 74 subjects, with a variant in the CALM1 (n = 36), CALM2 (n = 23), or CALM3 (n = 15) genes. Sixty-four (86.5%) were symptomatic and the 10-year cumulative mortality was 27%. The two prevalent phenotypes are long QT syndrome (LQTS; CALM-LQTS, n = 36, 49%) and catecholaminergic polymorphic ventricular tachycardia (CPVT; CALM-CPVT, n = 21, 28%). CALM-LQTS patients have extremely prolonged QTc intervals (594 ± 73 ms), high prevalence (78%) of life-threatening arrhythmias with median age at onset of 1.5 years [interquartile range (IQR) 0.1–5.5 years] and poor response to therapies. Most electrocardiograms (ECGs) show late onset peaked T waves. All CALM-CPVT patients were symptomatic with median age of onset of 6.0 years (IQR 3.0–8.5 years). Basal ECG frequently shows prominent U waves. Other CALM-related phenotypes are idiopathic ventricular fibrillation (IVF, n = 7), sudden unexplained death (SUD, n = 4), overlapping features of CPVT/LQTS (n = 3), and predominant neurological phenotype (n = 1). Cardiac structural abnormalities and neurological features were present in 18 and 13 patients, respectively. Conclusion Calmodulinopathies are largely characterized by adrenergically-induced life-threatening arrhythmias. Available therapies are disquietingly insufficient, especially in CALM-LQTS. Combination therapy with drugs, sympathectomy, and devices should be considered.

BACKGROUNDTransfusion‐related acute lung injury (TRALI) is a serious complication of blood transfusion and is among the leading causes of transfusion‐related morbidity and mortality in most developed countries. In the past decade, the pathophysiology of this potentially life‐threatening syndrome has been increasingly elucidated, large cohort studies have identified associated patient conditions and transfusion risk factors, and preventive strategies have been successfully implemented. These new insights provide a rationale for updating the 2004 consensus definition of TRALI.STUDY DESIGN AND METHODSAn international expert panel used the Delphi methodology to develop a redefinition of TRALI by modifying and updating the 2004 definition. Additionally, the panel reviewed issues related to TRALI nomenclature, patient conditions associated with acute respiratory distress syndrome (ARDS) and TRALI, TRALI pathophysiology, and standardization of reporting of TRALI cases.RESULTSIn the redefinition, the term “possible TRALI” has been dropped. The terminology of TRALI Type I (without an ARDS risk factor) and TRALI Type II (with an ARDS risk factor or with mild existing ARDS) is proposed. Cases with an ARDS risk factor that meet ARDS diagnostic criteria and where respiratory deterioration over the 12 hours before transfusion implicates the risk factor as causative should be classified as ARDS. TRALI remains a clinical diagnosis and does not require detection of cognate white blood cell antibodies.CONCLUSIONSClinicians should report all cases of posttransfusion pulmonary edema to the transfusion service so that further investigation can allow for classification of such cases as TRALI (Type I or Type II), ARDS, transfusion‐associated circulatory overload (TACO), or TRALI or TACO cannot distinguish or an alternate diagnosis.

Background Blood flow restriction (BFR) therapy is an innovative rehabilitative program that enables patients to increase strength at a fraction of the weight typically necessary in endurance exercises. Therefore, we conducted a pilot study evaluating patient outcomes with a BFR therapy program for closed management after a distal radius fracture compared to a traditional rehabilitation protocol. Literature review A randomized-controlled study was conducted comparing a standardized hand therapy rehabilitation protocol alone to a combined protocol with the use of BFR therapy in patients who were initially treated with closed reduction and short arm cast immobilization for a displaced distal radius fracture between May 1, 2015 and August 1, 2016. BFR therapy was performed with a restrictive tourniquet applied to the upper brachium, performing the same strengthening exercises as the control group but with the restrictive tourniquet in place. Clinical assessment was conducted at 6, 10, and 14 weeks from the date of initial cast immobilization. Outcome measures collected included wrist range of motion; grip strength; pinch strength; visual analogue scale for pain with activity and at rest; patient-rated wrist evaluation (PRWE) scores; and disabilities of the arm, shoulder, and hand scores. Results Thirteen patients were enrolled and randomized between the BFR (n = 6) and control (n = 7) groups. The BFR group noted significantly greater reduction in pain with activity compared to the control group after 8 weeks of therapy (Δ −4.0 vs. −2.3, p = 0.03). Similarly, patients in the BFR group displayed greater reduction in PRWE scores compared to the control group after 8 weeks of BFR therapy (Δ −57.9 vs. 30.8, p = 0.01). The two groups did not demonstrate any significant difference in radiographic outcomes at any time point or throughout the course of the study. All patients tolerated the BFR therapy program and there were no complications. Clinical relevance The addition of BFR therapy to the rehabilitative program after closed management of a distal radius fracture is safe, well tolerated by patients, without any deleterious effects on radiographic outcomes. This pilot study noted that BFR therapy in patients with nonoperative distal radius fractures may result in a larger reduction in pain with activity and greater improvement in overall self-perceived function.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cutaneous melanoma have been significantly revised over the past few years in response to emerging data on immune checkpoint inhibitor therapies and BRAF-targeted therapy. This article summarizes the data and rationale supporting extensive changes to the recommendations for systemic therapy as adjuvant treatment of resected disease and as treatment of unresectable or distant metastatic disease.