Gorgas Hospital was a U.S. Army hospital in Panama City, Panama, named for Army Surgeon General William C. Gorgas (1854–1920).Built on the site of an earlier (1882) French hospital called L'Hospital Notre Dame de Canal, it was originally (1904) christened Ancon Hospital by the Americans. It was originally built of wood but was rebuilt in concrete in 1915 by Samuel Hitt. It was renamed Gorgas Hospital in 1928.Gorgas Hospital is located on Ancon Hill. It was managed by the U.S. Army for most of the 20th century but is now, in accordance with the Torrijos-Carter Treaties (1977), in Panamanian hands. Since October 1999, it has been home to the Instituto Oncologico Nacional..
636 Background: Upper Tract Urothelial Carcinoma (UTUC) presents a challenging prognosis even after Radical Nephroureterectomy (RNU), and postoperative renal insufficiency further limits the options for adjuvant therapy. The efficacy of neoadjuvant chemotherapy for UTUC remains uncertain as past studies have not shown satisfactory results and have mostly been retrospective. There is an urgent need for a more promising regimen. This phase II study aims to investigate the efficacy and safety of a combination of chemotherapy (Gemcitabine/Cisplatin) and PD-1 inhibitor (Toripalimab) as neoadjuvant treatment (NT) in UTUC patients. Methods: We planned to enroll 34 UTUC patients with either cT1N0M0 (high grade) or cT2-3N0M0, confirmed by ureterorenoscopy biopsy and imaging. The treatment regimen included three or four cycles of NT (Gemcitabine, 800mg/m 2 , days 1 and 8/Cisplatin, 60mg/m 2 , day 1/Toripalimab, 240mg, day 1 of a 21-day cycle), followed by RNU and pelvic lymphadenectomy. The primary outcome was the pathological complete response (pCR) rate, with secondary outcomes including significant downstaging (≤pT1) rate, disease control rate (DCR), and safety. Results: To date, 17 patients have been accrued since August 1st, 2020, and recruitment is ongoing. Fifteen patients have completed treatments and were preliminarily analyzed, with two patients still undergoing treatment. The median age was 66.0 years, with 53.3% being male. The majority of patients had unifocal tumors, with a median maximum diameter of 2.8cm (0.4-5.8). All patients experienced obstructed hydronephrosis. Clinical T staging was confirmed by multi-parameter MRI, indicating two T2 and thirteen T3 patients. Ureterorenoscopy biopsy revealed 13 high-grade and two low-grade urothelial carcinoma patients. All patients were classified as high-risk UTUC. Twelve patients completed 4 cycles, and three underwent 3 cycles. The median interval time from initiation of NT to RNU and from the end of NT to RNU was 18.3 (11.4-22.7) weeks and 6.3 (0.1-11.6) weeks respectively. The pCR rate was 20.0% (3/15), the ≤pT1 rate was 53.3% (8/15), and the DCR was 100%. No grade 4-5 chemotherapy-related adverse events were recorded, but 26.7% (4/15) experienced grade 2 myelosuppression, 20% (3/15) grade 3, and 6.7% (1/15) grade 4. Two patients experienced immune-related adverse events after 4 cycles, including hypothyroidism (grade 2) and adrenal insufficiency (grade 2). No surgery-related complications or readmissions within one month were reported. With a median follow-up of 25.6 months, all patients remained alive and tumor-free. Conclusions: Preliminary analyses suggest that the combination of chemotherapy and a PD-1 inhibitor as NT exhibits promising pCR rate for UTUC. The treatment was manageable in terms of safety, with immune-related adverse events potentially leading to prolonged treatment periods. Clinical trial information: NCT04099589 .
We aimed to characterize the outcomes of patients with severe meningoencephalitis requiring intensive care. We conducted a prospective multicenter international cohort study (2017–2020) in 68 centers across 7 countries. Eligible patients were adults admitted to the intensive care unit (ICU) with meningoencephalitis, defined by an acute onset of encephalopathy (Glasgow coma scale (GCS) score ≤ 13), a cerebrospinal fluid pleocytosis ≥ 5 cells/mm3, and at least two of the following criteria: fever, seizures, focal neurological deficit, abnormal neuroimaging, and/or electroencephalogram. The primary endpoint was poor functional outcome at 3 months, defined by a score of three to six on the modified Rankin scale. Multivariable analyses stratified on centers investigated ICU admission variables associated with the primary endpoint. Among 599 patients enrolled, 589 (98.3 ≤ 3 (OR 2.23, 95
The multicancer early detection (MCED) test has the potential to enhance current cancer-screening methods. We evaluated a new MCED test that analyzes plasma cell-free DNA using genetic- and fragmentomics-based features from whole-genome sequencing. The present study included an internal validation cohort of 3,021 patients with cancer and 3,370 noncancer controls, and an independent cohort of 677 patients with cancer and 687 noncancer individuals. The results demonstrated an overall sensitivity of 87.4%, specificity of 97.8% and tissue-of-origin prediction accuracy of 82.4% in the independent validation cohort. Preliminary results from a prospective study of 3,724 asymptomatic participants showed a sensitivity of 53.5% (predominantly early stage cancers) and specificity of 98.1%. These findings indicate that the MCED test has strong potential to improve early cancer detection and support clinical decision-making.
BACKGROUND:Glecirasib, an inhibitor of Kirsten rat sarcoma viral oncogene homolog glycine-to-cysteine substitution at codon 12 (KRAS G12C), has exhibited clinical activity in non-small-cell lung cancer (NSCLC) and colorectal cancer (CRC). Here, we investigated the efficacy and safety of glecirasib in patients with pancreatic ductal adenocarcinoma (PDAC) and other solid tumors (excluding NSCLC and CRC) that rarely harbor the KRAS G12C mutation but for which effective treatment options remain limited. METHODS:We conducted and analyzed two open-label, phase I/II trials in adult patients with KRAS G12C mutant solid tumors, in which glecirasib was administered orally. The two trials had similar eligibility criteria and endpoints but differed in the regions of patient recruitment. We performed a pooled analysis of all patients, excluding NSCLC and CRC, from both trials. The primary endpoint in the pooled population was objective response rate (ORR). Efficacy and safety were assessed in patients who received at least one dose of glecirasib. RESULTS:As of June 30, 2024, the pooled analysis included 54 patients who were treated with glecirasib: 32 PDACs, 8 biliary tract cancers (BTCs), 4 small intestinal cancers, 3 gastric cancers, 2 appendiceal cancers, and 5 other tumors. At baseline, 24 received ≥ two prior lines of systemic therapy. Of the 53 efficacy-evaluable patients, the confirmed ORR was 50.9% (95% confidence interval [CI], 36.8%-64.9%), with an ORR of 46.9% (95% CI, 29.1%-65.3%) in PDAC patients. Among other solid tumors, ORR was 71.4% (5/7) in BTC, 100% (4/4) in small intestinal cancer, and 66.7% (2/3) in gastric cancer. Median progression-free survival and median overall survival were 6.9 and 10.8 months, respectively, in the overall population, and 5.5 and 10.8 months, respectively, in patients with PDAC. Treatment-related adverse events (TRAEs) of any grade occurred in 94.4% patients, with grade ≥ 3 TRAEs in 27.8%. No fatal TRAEs or TRAEs leading to treatment discontinuation occurred. CONCLUSIONS:Glecirasib showed promising efficacy and was well tolerated in patients with PDAC and other advanced solid tumors (beyond NSCLC and CRC), warranting further expedited clinical development in this patient population. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05009329 and NCT05002270.
BACKGROUND:The response to ruxolitinib after 6 months (RR6) model allows early identification of ruxolitinib-treated myelofibrosis (MF) patients with poorer overall survival (OS); however, it is less applicable to lower-risk patients. METHODS:To further explore this, the authors performed a subanalysis of the "RUX-MF" study (NCT06516406) with an aim to validate the RR6 and to develop a score specific for intermediate-1 DIPSS/MYSEC-PM risk patients. RESULTS:Among the 776 evaluable patients, 34.4%, 47.8%, and 17.8% were at low, intermediate, and high RR6 risk, with 5-year OS of 64.1%, 51.8%, and 44.5%, respectively (p < .001). In the 428 intermediate-1 patients, the RR6 model did not discriminate between intermediate and low-risk patients (5-year OS: 74.4% vs. 72.0%, p = .24). The intermediate-1 specific RR6 (iRR6) model was therefore developed by incorporating new variables: underdosed ruxolitinib with respect to platelet count at one or more time points (hazard ratio [HR], 3.91; p < .001), absence of palpable spleen reduction by ≥50% at 6 months (HR, 1.45; p = .02), and red blood cell transfusion requirement at all time points (HR, 1.85; p = .01). The iRR6 model stratified patients into three risk categories: low (score 0, 20.3%), intermediate (score 1-2, 45.8%), and high-risk (score >2, 33.9%), with 5-year OS of 84.8%, 76.4%, and 56.6%, respectively (p < .0001). The iRR6 model was validated in a cohort of 95 intermediate-1 risk patients from the Moffitt Cancer Center, yielding stratification into the same three risk categories, with 5-year OS of 83.3% (low-risk), 71.7% (intermediate-risk), and 54.5% (high-risk) (p = .01). CONCLUSIONS:The iRR6 model provides a more refined tool for the identification of intermediate-1 MF patients who may benefit from early therapy shift.
