Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 patients with MPN, including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4 (5.8%) of 69 patients receiving JAK1/2 inhibition compared with 2 (0.36%) of 557 with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 patients with MPN. Considering primary myelofibrosis only (N = 216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) vs 1 (0.54%) of 185 control patients. Lymphomas were of aggressive B-cell type, extranodal, or leukemic with high MYC expression in the absence of V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a preexisting B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in mice: 16 of 24 mice developed a spontaneous myeloid hyperplasia with the concomitant presence of aberrant B cells. Transplantations of bone marrow from diseased mice unmasked the outgrowth of a malignant B-cell clone evolving into aggressive B-cell leukemia-lymphoma. We conclude that JAK/STAT1 pathway inhibition in myelofibrosis is associated with an elevated frequency of aggressive B-cell lymphomas. Detection of a preexisting B-cell clone may identify individuals at risk.

The prevalence of PTSD in cardiac arrest survivors is high. Besides younger age, neither clinical factors nor the use of sedation and analgesia were associated with development of PTSD.

Background/Aims: In hemodialysis and hemodiafiltration patients, the plasma sodium (PNa) measured before dialysis can be regarded as the sodium setpoint. By the end of dialysis, the PNa typically approximates the prescribed dialysate sodium (DNa), the difference between DNa and PNa being considered the sodium gradient. We determined the relationship between setpoint, gradient and pre- to postdialysis PNa change (delta PNa), and studied associations with dialysis-related variables. Methods: Cohort study. Measurements from 132 patients during 12 consecutive treatments included PNa and DNa concentrations, pre- to postdialysis body weight and predialysis systolic blood pressure. Results: Sodium setpoints were normally distributed (137.9 ± 2.4 mmol/l), DNa prescriptions were non-normally distributed (138.9 ± 1.8 mmol/l). The sodium gradient correlated strongly with delta PNa (r = 0.76, p < 0.001). Both sodium gradient and delta PNa correlated with relative interdialytic weight gain (IDWG; r = 0.25, p = 0.004, and r = 0.44, p < 0.001, respectively), but not with predialysis systolic blood pressure. These correlations were consistent after exclusion of patients with urine volume >500 ml/day and patients undergoing sodium profiling, and increased after exclusion of patients with hemodiafiltration protocols. Predictors for having higher relative IDWG (≧2.8%) were delta PNa concentrations ≧0 mmol/l and younger age. Predictors for having a delta PNa concentration ≧0 mmol/l were lower sodium setpoints, higher DNa prescriptions, use of Nikkiso machines, sodium profiling and younger age. Patients with positive delta PNa despite negative gradients were significantly younger, used more Nikkiso machines and presented with higher IDWG. Conclusion: IDWG correlated with the sodium gradient and more strongly with delta PNa, suggesting the need for studying other outcomes, such as morbidity and mortality.

Setting: Department of Surgery of a 2500-bed university hospital.Patients: Consecutive eligible patients who underwent stoma closure were selected from a local registry containing 30 219 patients. The medical records of 587 adult patients were reviewed according to a predefined extraction form. Patients with additional, unrelated surgical interventions or younger than 18 years were excluded. Follow-up was complete for all included patients. Main Outcome Measures:The primary outcome variable was 30-day mortality; the secondary outcome variable was presence of surgery-related complications within 30 days. Results:We analyzed 533 patients with stoma closure between 1993 and 2001. The overall stoma closurerelated mortality rate was 3% (15 patients); the overall stoma closure-related surgical complications rate was 20% (107 patients). Wound infections (9%) and anastomotic leakage (5%) were the most common surgical complications. Age was the only significant risk factor for survival (P = .02). Use of a soft silicone drain for intraperitoneal drainage (odds ratio, 1.62 [95% confidence interval, 1.07-2.45]; P =.03) was the only significant risk factor for complications. In patients with carcinoma as the primary disease (odds ratio, 0.61 [95% confidence interval, 0.40 to 0.93]; P =.02), we observed significantly fewer complications. Conclusions:We found considerable mortality and complications after stoma closure. Apart from age, we could not identify any predictor for mortality in patients with stoma closure. Randomized studies are needed to determine whether certain types of drains influence outcome.

The combination of a liver recipient with worsening Delta-MELD and a potential donor with at least two EDC should be avoided.