Flexible, Phase-Transfer Catalyzed Approaches to 4-Substituted Prolines

A range of 4-substituted prolines can be rapidly synthesized from a protected glycine Schiff base in only four steps and in 27–55% overall yield. Phase transfer catalysis allows direct access to both enantiomeric series, and the relative stereochemistry at the 4-position is readily controlled (>10:1 dr) through the choice of hydrogenation conditions

Matched control analysis suggests R-CHOP followed by (R)-ICE may improve outcome in non-GCB DLBCL compared to R-CHOP

Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is considered the standard-of-care for patients with advanced-stage diffuse large B-cell lymphoma (DLBCL), despite findings that non-germinal center B-cell-like (non-GCB) patients have significantly worse outcome with this regimen. We evaluated the prognostic significance of baseline risk factors, including cell of origin (COO) classified by the Hans algorithm, within an alternative chemoimmunotherapy program. At Memorial Sloan Kettering Cancer Center (MSK), 151 patients with DLBCL received sequential R-CHOP induction and (R)-ICE (rituximab, ifosfamide, carboplatin, and etoposide) consolidation. Outcome analysis based on COO was validated with a propensity score matched cohort treated with R-CHOP from the Mayo Clinic component of the Molecular Epidemiology Resource (MER). Among the GCB (n=69) and non-GCB (n=69) patients at MSK, event-free survival (EFS) of non-GCB was superior to that of GCB (HR 0.53, 95% CI 0.29-0.98). Overall survival (OS) demonstrated an association in the same direction but was not statistically significant (HR 0.68, 95% CI 0.33-1.42). Propensity score matched patients from MSK (n=108) demonstrated a small attenuation in the HRs for EFS (HR 0.57, 95% CI 0.27-1.18) and OS (HR 0.76, 95% CI 0.33-1.79) and were no longer statistically significant. In contrast, the matched MER cohort (n=108) demonstrated an EFS association (HR 1.17, 95% CI 0.70-1.95) and OS association (HR 1.13, 95% CI 0.64-2.00) in the opposite direction, but were also not statistically significant. R-CHOP induction and (R)-ICE consolidation may overcome the negative prognostic impact of the non-GCB phenotype, per the Hans algorithm, and can be preferentially selected for this population

Ventilation and outcomes following robotic-assisted abdominal surgery : an international, multicentre observational study

Background: International data on the epidemiology, ventilation practice, and outcomes in patients undergoing abdominal robotic-assisted surgery (RAS) are lacking. The aim of the study was to assess the incidence of postoperative pulmonary complications (PPCs), and to describe ventilator management after abdominal RAS. Methods: This was an international, multicentre, prospective study in 34 centres in nine countries. Patients >= 18 yr of age undergoing abdominal RAS were enrolled between April 2017 and March 2019. The Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score was used to stratify for higher risk of PPCs (>= 26). The primary outcome was the incidence of PPCs. Secondary endpoints included the preoperative risk for PPCs and ventilator management. Results: Of 1167 subjects screened, 905 abdominal RAS patients were included. Overall, 590 (65.2%) patients were at increased risk for PPCs. Meanwhile, 172 (19%) patients sustained PPCs, which occurred more frequently in 132 (22.4%) patients at increased risk, compared with 40 (12.7%) patients at lower risk of PPCs (absolute risk difference: 12.2% [95% confidence intervals (CI), 6.8-17.6%]; P<0.001). Plateau and driving pressures were higher in patients at increased risk, compared with patients at low risk of PPCs, but no ventilatory variables were independently associated with increased occurrence of PPCs. Development of PPCs was associated with a longer hospital stay. Conclusions: One in five patients developed one or more PPCs (chiefly unplanned oxygen requirement), which was associated with a longer hospital stay. No ventilatory variables were independently associated with PPCs

Genomewide Clonal Analysis of Lethal Mutations in the Drosophila melanogaster Eye: Comparison of the X Chromosome and Autosomes

Using a large consortium of undergraduate students in an organized program at the University of California, Los Angeles (UCLA), we have undertaken a functional genomic screen in the Drosophila eye. In addition to the educational value of discovery-based learning, this article presents the first comprehensive genomewide analysis of essential genes involved in eye development. The data reveal the surprising result that the X chromosome has almost twice the frequency of essential genes involved in eye development as that found on the autosomes