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.

Spinal Tuberculosis and Cold Abscess without Known Primary Disease: Case Report and Review of the Literature.

Extrapulmonary tuberculosis (TB) is uncommon but not rare. Bone and joint involvement constitute about 10% of extrapulmonary TB cases, with the spine being the most frequently affected site. Spinal TB patients typically present with back pain but other constitutional or pulmonary symptoms may be absent, rendering the diagnosis difficult. This case explores challenges in the diagnosis of spinal TB. We report a case of a 39-year-old woman presenting with vague back swelling for many years. Imaging revealed osteomyelitis of the spine but initial studies and cultures were negative for Mycobacterium tuberculosis. The diagnosis was confirmed weeks later when cultures demonstrated Mycobacterium tuberculosis. Considering the severe complications of untreated spinal TB including paraplegia and need for surgical intervention, high suspicion is critical in early diagnosis.

Epidemiology and risk factors for isolation of Escherichia coli producing CTX-M-type extended-spectrum ß-lactamase in a large U.S. Medical Center.

A case-case-control study was conducted to identify independent risk factors for recovery of Escherichia coli strains producing CTX-M-type extended-spectrum ß-lactamases (CTX-M E. coli) within a large Southeastern Michigan medical center. Unique cases with isolation of ESBL-producing E. coli from February 2010 through July 2011 were analyzed by PCR for blaCTX-M, blaTEM, and blaSHV genes. Patients with CTX-M E. coli were compared to patients with E. coli strains not producing CTX-M-type ESBLs (non-CTX-M E. coli) and uninfected controls. Of 575 patients with ESBL-producing E. coli, 491 (85.4%) isolates contained a CTX-M ESBL gene. A total of 319 (84.6%) patients with CTX-M E. coli (282 [74.8%] CTX-M-15 type) were compared to 58 (15.4%) non-CTX-M E. coli patients and to uninfected controls. Independent risk factors for CTX-M E. coli isolation compared to non-CTX-M E. coli included male gender, impaired consciousness, H2 blocker use, immunosuppression, and exposure to penicillins and/or trimethoprim-sulfamethoxazole. Compared to uninfected controls, independent risk factors for isolation of CTX-M E. coli included presence of a urinary catheter, previous urinary tract infection, exposure to oxyimino-cephalosporins, dependent functional status, non-home residence, and multiple comorbid conditions. Within 48 h of admission, community-acquired CTX-M E. coli (n = 51 [16%]) and non-CTX-M E coli (n = 11 [19%]) strains were isolated from patients with no recent health care contacts. CTX-M E. coli strains were more resistant to multiple antibiotics than non-CTX-M E. coli strains. CTX-M-encoding genes, especially bla(CTX-M-15) type, represented the most common ESBL determinants from ESBL-producing E. coli, the majority of which were present upon admission. Septic patients with risk factors for isolation of CTX-M E. coli should be empirically treated with appropriate agents. Regional infection control efforts and judicious antibiotic use are needed to control the spread of these organisms.