Mixed histiocytic neoplasms: A multicentre series revealing diverse somatic mutations and responses to targeted therapy.

Histiocytic neoplasms are diverse clonal haematopoietic disorders, and clinical disease is mediated by tumorous infiltration as well as uncontrolled systemic inflammation. Individual subtypes include Langerhans cell histiocytosis (LCH), Rosai-Dorfman-Destombes disease (RDD) and Erdheim-Chester disease (ECD), and these have been characterized with respect to clinical phenotypes, driver mutations and treatment paradigms. Less is known about patients with mixed histiocytic neoplasms (MXH), that is two or more coexisting disorders. This international collaboration examined patients with biopsy-proven MXH with respect to component disease subtypes, oncogenic driver mutations and responses to conventional (chemotherapeutic or immunosuppressive) versus targeted (BRAF or MEK inhibitor) therapies. Twenty-seven patients were studied with ECD/LCH (19/27), ECD/RDD (6/27), RDD/LCH (1/27) and ECD/RDD/LCH (1/27). Mutations previously undescribed in MXH were identified, including KRAS, MAP2K2, MAPK3, non-V600-BRAF, RAF1 and a BICD2-BRAF fusion. A repeated-measure generalized estimating equation demonstrated that targeted treatment was statistically significantly (1) more likely to result in a complete response (CR), partial response (PR) or stable disease (SD) (odds ratio [OR]: 17.34, 95% CI: 2.19-137.00, p = 0.007), and (2) less likely to result in progression (OR: 0.08, 95% CI: 0.03-0.23, p < 0.0001). Histiocytic neoplasms represent an entity with underappreciated clinical and molecular diversity, poor responsiveness to conventional therapy and exquisite sensitivity to targeted therapy.

Human herpesvirus 6 (HHV-6) associated permanent hyponatremia in umbilical cord blood transplant recipient.

Long-term neurocognitive deficits after human herpesvirus-6 (HHV-6) infection are common in stem-cell transplant recipients, but SIADH (Syndrome of inappropriate antidiuretic hormone secretion) with persistent hyponatremia is rare. A 51-year-old woman presented with somnolence, hyponatremia (121 mmol/L) and HHV-6 viremia (80,330 copies/ml) on day +22 post umbilical cord blood transplant (UCBT). With waterrestriction, tolvaptan and combination of foscarnet and ganciclovir, patient's hyponatremia and HHV-6 viremia improved. On day +94 UCBT, hyponatremia and HHV-6 viremia recurred. Foscarnet was restarted and continued until day +269 UCBT due to multiple HHV-6 recurrences with persistent hyponatremia. At day +712, patient remains on water-restriction, tolvaptan for continuous hyponatremia from SIADH.

Usefulness of Timed Up and Go (TUG) Test for Prediction of Adverse Outcomes in Patients Undergoing Thoracolumbar Spine Surgery.

BACKGROUND: Spine surgery rates have increased and the high postoperative morbidity in these patients result in increased costs. Consequently, it is essential to identify patients at risk of adverse outcomes. OBJECTIVE: To assess whether preoperative Timed Up and Go (TUG) test performance can predict high-grade postoperative complications. METHODS: A prospective cohort study of patients undergoing elective thoracolumbar spine surgery in a tertiary care hospital between 2017 and 2018. Patients were assessed preoperatively and assigned to the slow-TUG group if unable to perform or test performance time was ≥18.4 s. Primary outcome: high-grade postoperative complications. Secondary outcomes: overall complications, length of stay (LOS), discharge to healthcare facility, readmission and emergency department (ED) presentation. Patients were followed-up until 6 wk after surgery. RESULTS: One hundred three patients (mean age 62.95 ± 10.97 yr) were enrolled. Slow-TUG group were more likely to be classified as American Society of Anaesthesiology (ASA) class 3 (74.1% vs 47.4%, P = .02), non-independent (25.9% vs 5.3%, P < .01), and frail (92.3% vs 42.1%, P < .01). TUG was an independent predictor of high-grade complications (adjusted odds ratio (OR): 4.97, 95% CI: 1.18-22.47), overall complications (OR: 3.77, 95% CI: 1.33-11.81), discharge to a skilled-nursing facility (OR: 3.2, 95% CI: 1.00-10.70), readmission within 6 wk of surgery (OR: 9.14, 95% CI: 2.39-41.26) and LOS (adjusted incident rate ratio (IRR): 1.45, 95% CI: 1.16-1.80). CONCLUSION: Compared to traditional risk factors, TUG is an important predictor of adverse postoperative outcomes and may be used preoperatively to identify high-risk thoracolumbar surgery patients.