Providence St. Joseph Health Digital Commons
Not a member yet
12290 research outputs found
Sort by
Neoadjuvant PD-1 blockade in surgically resectable desmoplastic melanoma: cohort A of the phase 2 SWOG S1512 trial.
No full textThe phase 2 SWOG S1512 trial ( NCT02775851 ) was designed to evaluate the response to pembrolizumab (anti-PD-1) in individuals with desmoplastic melanoma. Here we report the results of cohort A of the trial, evaluating the pathological complete response (pCR) rate of neoadjuvant PD-1 blockade in surgically resectable desmoplastic melanoma. Secondary endpoints included clinical response rate, overall survival and toxicities. Twenty-eight eligible individuals with resectable desmoplastic melanoma received intravenous pembrolizumab (200 mg) every 3 weeks three times, followed by excision. Tissue samples before treatment, at 3-5 weeks after treatment initiation and at the time of surgery were reviewed. The primary endpoint of pCR rate by local pathological review was 71% (95% confidence interval, 51-87%; P \u3c 0.001), which met the prespecified endpoint. There were two (7%) grade 3 treatment-related adverse events. At three years of follow-up, four participants have died, none known to be from melanoma or adverse events. In conclusion, neoadjuvant pembrolizumab in individuals with resectable desmoplastic melanoma results in a high pCR rate with acceptable safety profile. Clinicaltrials.gov: NCT02775851
HCN channels reveal conserved and divergent physiology in supragranular pyramidal neurons in primate species.
No full textThe physiological properties of human and rodent neurons differ, yet the extent to which these differences reflect human specializations is often unclear. Compared with their rodent counterparts, human supragranular pyramidal neurons possess enriched Hyperpolarization-activated Cyclic Nucleotide-gated channel (HCN channel)-dependent intrinsic membrane properties and a related sensitivity to synaptic inputs containing delta/theta band frequencies. Here we test whether other primate species possess enriched HCN channel dependent membrane properties. We observe ubiquitous HCN1 subunit gene expression in supragranular glutamatergic neurons across New World Monkeys, Old-World Monkeys, and great apes in single nucleus RNA-sequencing datasets. Using Patch-seq recordings from acute and cultured brain slices, we describe robust HCN channel-dependent physiological properties in supragranular pyramidal neurons in a species of New-World monkey (Saimiri sciureus) and two species of Old-World Monkey (Macaca mulatta, Macaca nemestrina). In both human and macaque neocortex, HCN channel-related intrinsic properties increase in magnitude with increasing laminar depth, especially in the L2/3 IT_1 transcriptomic cell type. Within this type, HCN dependent properties are more pronounced in macaque than human neurons. These findings indicate that HCN channel-governed membrane properties and sensitivity to delta/theta band frequencies are roughly conserved in supragranular pyramidal neurons across at least 36 million years of primate evolution
Longitudinal multi-omic profiling of tissues and blood to track the molecular evolution of metastatic breast cancer
No full text
Signal or Noise? Evaluating the Clinical Relevance of BPA Overrides in Opioid Harm Reduction Protocols
No full text
4. Impacting nurse leader satisfaction and retention through standardized support and education.
No full textEffect of high elevation on deep vein thrombosis: a multicenter cohort study.
No full textBACKGROUND: Prior research explored the effect of elevation on deep vein thrombosis (DVT) but primarily examined injuries at elevations \u3c 1000 or \u3e4000 feet, excluding elevations in between, and focused on specific subsets of trauma patients. This study aimed to conduct a more detailed analysis of the relationship between elevation and DVT in all trauma admissions.
METHODS: This retrospective cohort study at four level I trauma centers included adult trauma patients (October 1, 2022 to October 1, 2023). Injury zip codes were used to define elevation. High-elevation (H-ELV) injuries (≥5000 feet) were compared with low-elevation (L-ELV) injuries (\u3c 5000 feet). Elevation was further categorized into 1000-foot increments. An alpha of \u3c 0.0001 defined statistical significance.
RESULTS: Of 8620 patients, 49% (4231) had L-ELV injuries and 51% (4389) had H-ELV injuries. Compared to patients with L-ELV injuries, those with H-ELV injuries were significantly older, had lower oxygen saturation and higher heart rate, suffered falls and sports injuries more often, and motor vehicle collisions less often, and had a higher rate of comorbidities, including alcohol use disorder and anticoagulant use. DVTs occurred significantly more often after H-ELV injuries than L-ELV injuries (1.9% vs. 0.5%, p\u3c 0.0001). For each 1000-foot increase in elevation, there was a corresponding 0.4% average increase in the rate of DVT (moderate R
CONCLUSIONS: Even after adjustment, H-ELV injuries were associated with 3.8 increased odds of developing a DVT compared with L-ELV injuries. There was a significant positive linear association between DVT and injury elevation, with the rate of DVT increasing with increasing elevation. This finding may suggest the need for enhanced screening or tailored DVT prophylaxis methods at higher elevation trauma centers to improve outcomes.
LEVEL OF EVIDENCE: Level IV
