A phase II study of carboplatin and paclitaxel in esophageal cancer.

BACKGROUND: This study was conducted to evaluate the efficacy and toxicity of combination carboplatin and paclitaxel in patients with esophageal cancer. MATERIALS AND METHODS: Thirty-five patients were enrolled. Patients were treated with paclitaxel 200 mg/m(2) intravenously (i.v.) over 3 h and carboplatin i.v. at an AUC of 5 mg/h/ml. Thirty-three patients were assessable for toxicity and objective response. RESULTS: A total of 166 treatment courses were administered with a median of five courses per patient. The objective response rate was 43% [90% confidence interval (CI) 0.3-0.58] by the intention-to-treat analysis. The median response duration was 2.8 months (90% CI 2.1-5.4). The median survival time was 9 months (90% CI 7-13.8) and the 1-year survival rate was 43% (90% CI 0.29-0.57). The major grade 3-4 toxicity observed was neutropenia, occurring in 17 patients (52%). There were no treatment-related deaths. CONCLUSIONS: The combination of carboplatin and paclitaxel is an moderately active and tolerable regimen in advanced esophageal cancer.     

Survival Outcomes of Adjuvant Chemotherapy in Elderly Patients with Stage III Colon Cancer

BackgroundThe survival impact of multi-agent (MAC) compared with single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study was to compare survival outcomes of MAC and SAC in this population utilizing the National Cancer Database (NCDB).Patients and MethodsPatients aged ≥70 years with pathological stage III CC diagnosed in 2004-2015 were identified in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify associations between MAC vs. SAC and overall survival (OS).ResultsAmong 41 707 elderly patients (≥70 years old) with stage III CC, about half (n = 20 257; 48.5%) received AC; the majority (n = 12 923, 63.8%) received MAC. The median age was 79 (range 70-90). The majority were female (n = 11 201, 55.3%), Caucasians (88%) and had moderately differentiated tumor grade (n = 12 619, 62.3%), tumor size >4 cm (11 785, 58.2%), and negative surgical margins (18 496, 91.3%). Low-risk stage III CC constituted 50.6% (n = 10 264) of the study population. High-risk stage III CC was associated with worse OS compared with low-risk disease (HR 0.35, 0.34-0.36, P < .001). Multi-agent chemotherapy was associated with a better 5-year OS compared with SAC (P < .001). High-risk stage III patients who received MAC vs. SAC had an OS of 4.2 vs. 3.4 years, respectively (P < .001). Low-risk stage III patients who received MAC vs. SAC had a median OS of 8.5 vs. 7 years (P < .001). In univariate and multivariable analyses, male sex, positive surgical margin, insurance and facility types, age, year of diagnosis, tumor size, and Charlson-Deyo score of >2 were associated with worse OS (P < .05).ConclusionsAny adjuvant chemotherapy has a trend of survival benefits. Multi-agent chemotherapy seems to have an enhanced benefit in the 70-75 age group. Multi-agent chemotherapy seemed to have similar efficacy as SAC in those aged >76 years.     

Role of local therapy in the management of patients with metastatic anal squamous cell carcinoma: a National Cancer Database study

BackgroundAbout 10–20% of patients with anal squamous cell carcinoma (SCCa) present with metastatic disease and are usually treated with systemic chemotherapy. However, primary tumor control is crucial as local failure is associated with significant morbidity. Using the largest cohort to date, we report the impact of local therapy on survival among patients with metastatic anal SCCa.MethodsData were collected from US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2015. Patients who did not receive palliative systemic chemotherapy were excluded from analysis. Univariate (UVA) and multivariable analyses (MVA) were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to evaluate the association between tumor/patient characteristics and overall survival (OS).ResultsA total of 1,160 patients were identified over the 12 years of study. Median age was 57 years. Majority were female (64.9%), non-Hispanic Whites (79.1%) and had Charlson-Deyo Score of 0 (83.6%). Most common metastatic sites were liver (25.9%), lung (11.6%) and bone (8.5%). More than 79% of the patients had received radiation to the primary site, and 10.4% underwent surgical resection for local control. Use of local therapy correlated closely with OS on MVA (HR 0.66; 0.55–0.79; P<0.001), with a 12-month and 5-year OS rates of 72.8% and 25.7% respectively, compared with 61.1% and 14.6% for patients treated with chemotherapy only. Poor prognostic factors included male gender (HR 1.44; 1.24–1.67; P<0.001), age >70 years (HR 1.28; 1.02–1.62; P=0.034), lack of health insurance (HR 1.32; 1.02–1.71; P=0.034), and cloacogenic zone location (HR 4.02; 1.43–11.30; P=0.008). There was no benefit from abdominoperineal resection (mOS =19.7 months; HR 1.05; 0.48–2.29; P=0.909), but both local resection of the primary (mOS =24.8 months, HR 0.48; 0.29–0.80; P=0.005) and palliative radiation (mOS =22.6 months; HR 0.66; 0.55–0.79; P<0.001) were associated with improved OS.ConclusionsIn addition to systemic therapy, resection of the primary tumor or palliative radiation improved OS in patients with anal SCCa. Patients unlikely to benefit from local control were those >70 years of age, male, lack of health insurance and cloacogenic carcinoma.     

Thirty-Day Post-Discharge Outcomes Following COVID-19 Infection

BackgroundThe clinical course of COVID-19 includes multiple disease phases. Data describing post-hospital discharge outcomes may provide insight into disease course. Studies describing post-hospitalization outcomes of adults following COVID-19 infection are limited to electronic medical record review, which may underestimate the incidence of outcomes.ObjectiveTo determine 30-day post-hospitalization outcomes following COVID-19 infection.DesignRetrospective cohort studySettingQuaternary referral hospital and community hospital in New York City.ParticipantsCOVID-19 infected patients discharged alive from the emergency department (ED) or hospital between March 3 and May 15, 2020.MeasurementOutcomes included return to an ED, re-hospitalization, and mortality within 30 days of hospital discharge.ResultsThirty-day follow-up data were successfully collected on 94.6% of eligible patients. Among 1344 patients, 16.5% returned to an ED, 9.8% were re-hospitalized, and 2.4% died. Among patients who returned to the ED, 50.0% (108/216) went to a different hospital from the hospital of the index presentation, and 61.1% (132/216) of those who returned were re-hospitalized. In Cox models adjusted for variables selected using the lasso method, age (HR 1.01 per year [95% CI 1.00–1.02]), diabetes (1.54 [1.06–2.23]), and the need for inpatient dialysis (3.78 [2.23–6.43]) during the index presentation were independently associated with a higher re-hospitalization rate. Older age (HR 1.08 [1.05–1.11]) and Asian race (2.89 [1.27–6.61]) were significantly associated with mortality.ConclusionsAmong patients discharged alive following their index presentation for COVID-19, risk for returning to a hospital within 30 days of discharge was substantial. These patients merit close post-discharge follow-up to optimize outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-06924-0.KEY WORDS: COVID-19, mortality, re-admission, discharge     

Reverse LISS plating for intertrochanteric Hip Fractures in elderly patients

Background  

Fractures of the intertrochanteric hip are common and the treatment of unstable fractures generally requires an operative approach. In elderly patients, osteoporosis makes internal fixation problematic and frequently contributes to failed fixation and poor clinical results. We have attempted to apply the Less Invasive Stabilization System (LISS) in reverse position for the repair of intertrochanteric hip fractures in elderly patients with osteoporotic bones. A retrospective review is presented of the cases of 28 elderly patients with stable and unstable fractures of the intertrochanteric hip treated using the reverse LISS.     

Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism

Heyerdahl S, Kase BF, Stake G. Skeletal maturation during thyroxine treatment in children with congenital hypothyroidism. Acta Prediatr 1994;83:618–22. Stockholm. ISSN 0803–5253
The aim of this investigation was to study if bone age development (assessed by the Greulich & Pyle atlas) was related to L-thyroxine treatment in 47 children with congenital hypothyroidism, treated early and according to general recommendations. In spite of frequent delay in skeletal maturation at diagnosis, the delay in mean bone age at a mean chronological age of 1.5 years was slight (0.5 months), and 30% of the variation in bone age SD score (SDS) at 1.5 years was accounted for by the dose of L-thyroxine and serum thyroxine during the first year. The children with a bone age within ± 1 SDS had a prescribed mean dose of L-thyroxine per kg body weight from 3 to 12 months of age of 5.4 ± 1.7 pg/kg/day, and their mean serum thyroxine concentration during the first year was 175 ± 29 nmol/l. We conclude that bone age at 1.5 years of age was positively correlated with the dose of L-thyroxine and the serum thyroxine concentration during the first year. This supports the general use of bone age assessments as a complement to other treatment variables in the follow-up of children with congenital hypothyroidism.     

Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and Oseltamivir by suppressing the expression of Carboxylesterases HCE1 and HCE2

Carboxylesterases constitute a class of enzymes that play important roles in the hydrolytic metabolism of drugs and other xenobiotics, patients with liver conditions such as cirrhosis show increased secretion of proinflammatory cytokines [e. g., interleukin-6 （IL- 6）] and decreased capacity of hydrolysis. In this sfudy, we provide a molecular explanation linking cytokine secretion directly to the decreased capacity of hydrolytic biotransformation. In both primary hepatocytes and HepG2 cells, treatment with IL-6 decreased the expression of human carboxylesterases HCE1 and HCE2 by as much as 60%. The decreased expression occurred at both mRNA and protein levels, and it was confirmed .by enzymatic assay. In cotransfection experiments, both HCE1 and HCE2 promoters were significantly repressed, and the repression was comparable with the decrease in HCE1 and HCE2 mRNA, suggesting that transrepression is responsible for the suppressed expression. In addition, pretreatment with IL-6 altered the cellular responsiveness in an opposite manner of overexpression of HCE1 and HCE2 toward various ester therapeutic agents （ e. g., clopidogrel）. Transfection of HCE1, for example, decreased the cytotoxicity induced by antithrombogenic agent clopidogrel, whereas pretreatment with IL-6 increased the cytotoxicity. Such a reversal was observed with other ester drugs, including anticancer agent irinotecan and anti-influenza agent oseltamivir. The altered cellular responsiveness was observed when drugs were assayed at sub-and low-micromolar concentrations, suggesting that suppressed expression of carboxylesterases by IL-6 has profound pharmacological consequences, particularly with those that are hvdrolvzed in an isoform-specific manner.     

7-溴乙氧苯四氢巴马汀对离体豚鼠工作心脏的作用

用Tris-丙酮酸钠液灌流离体豚鼠工作心脏,记录左室压的导管从左房灌流管插入,可使心脏有效工作时间达70min。用Tris-丙酮酸钠液加0.5%的氟碳液能使有效工作时间延长至90min。7-溴乙氧苯四氢巴马汀(7-bromoethyoxybenzene tetrahydropalmatine,EBP)及哌唑嗪0.1μmol/L对工作心脏各项指标均无显著影响。甲氧胺1μmol/L,多巴胺1μmol/L对LVP,ABF,T-CO等指标均有明显的药理作用。EBP 10μmol/L能对抗甲氧胺、多巴胺对上述指标的影响。