Brain insulin resistance: an early risk factor for Alzheimer's disease development in Down syndrome

Down syndrome(DS) is the most frequent chromosomal abnormality that causes intellectual disability, resulting from the presence of an extra complete or segment of chromosome 21(HSA21)(Tramutola et al., 2020;Lanzillotta et al., 2021). Every year, approximately 6000 children are born with DS and most of them do not have an autonomous life.     

Side-to-side esophagojejunostomy during totally laparoscopic total gastrectomy for malignant disease: a multicenter study

Background  

Esophagojejunostomy (EJS) represents the most difficult steps during totally laparoscopic total gastrectomy (TLTG). Over the past few years, several techniques have been developed. This study aimed to evaluate the feasibility and surgical outcomes of the laparoscopic intracorporeal side-to-side EJS during TLTG used to treat malignant disease of the stomach.     

Chance of Cure Following Liver Resection for Initially Unresectable Colorectal Metastases: Analysis of Actual 5-Year Survival

Background

Survival with long-term follow-up following liver resection for unresectable colorectal liver metastases (CRLM) downsized by chemotherapy has rarely been reported. The aim of this study was to determine the chance of cure following liver resection for initially unresectable CRLM.

Methods

Between January 2000 and December 2009, 61 patients underwent hepatectomy for unresectable liver-only CRLM downsized after chemotherapy. Cure was defined as a recurrence-free interval of at least 5 years after primary hepatectomy.

Results

Resectability of CRLM was achieved after a mean number of 11 courses, and 42.6 % of patients underwent liver resection after ≥10 courses. Postoperative mortality was nil, and morbidity rate was 19.7 %. The 5- and 10-year actuarial overall survival rates were 42.6 and 16.0 %. Of 30 patients with a follow-up ≥5 years, 11 were alive, yielding a 5-year actual overall survival rate of 36.7 %, and 7 (23.3 %) were considered cured because they are alive without recurrence. On multivariate analysis, response to chemotherapy was the only independent predictor of both overall and disease-free survival.

Conclusions

Cure can be achieved in about 23 % of patients resected for initially unresectable CRLM downsized by chemotherapy. Liver resection can be safely performed in selected patients even after multiple courses of chemotherapy.     

Evaluation of the effects of multiple-dose activated charcoal on the absorption of orally administered salicylate in a simulated toxic ingestion model

The effects of multiple-dose activated charcoal administration on the absorption of orally administered salicylate were evaluated in a simulated overdose model. Thirteen adult volunteers were each given 24 81-mg aspirin tablets during a control phase, and during three randomized treatment periods the volunteers received 50 g activated charcoal for one, two, or three doses (separated by four hours). The control phase and treatment periods were separated by a one-week interval. Urine was collected for 48 hours to determine percent total salicylate excretion. Ten subjects completed all four phases of the study. Mean +/- SD percent recovery of salicylate from urine was: control, 91.0 +/- 6.12; one-dose charcoal, 68.3 +/- 12.46; two-dose charcoal, 65.9 +/- 13.48; and three-dose charcoal, 49.2 +/- 12.48. Each charcoal treatment significantly lowered the absorption of aspirin as compared with the control (P less than .01). There was no significant difference between one-dose and two-dose charcoal regimens. There was a statistically significant decrease in salicylate absorption with the three-dose charcoal regimen as compared to one-dose and two-dose regimens (P less than .01). We conclude that activated charcoal is effective in inhibiting absorption of orally administered salicylate, in a small-dose aspirin ingestion model, with a three-dose multiple charcoal regimen being superior to either single-dose or two-dose regimens.     

Docetaxel and oxaliplatin combination in second-line treatment of patients with advanced gastric cancer

Background In advanced gastric cancer few data are available on the efficacy or safety of new drug combination regimens after progression following first-line chemotherapy. Methods Patients with histologically confirmed advanced gastric cancer and Eastern Cooperative Oncology Group (ECOG) performance status (PS) less than 2, progressing after first-line chemotherapy, were eligible. Patients were treated with docetaxel 75 mg/m² on day 1 and oxaliplatin 80 mg/m² on day 2, every 3 weeks, until progression or unacceptable toxicity. Results Between May 2002 and April 2005, 38 patients were enrolled. Men accounted for 73.7% of the patients and the median age was 59 years. The primary tumor was not resected in 47.4% of the patients; the peritoneum was the most frequent metastatic site (60.5%). The first-line treatment was cisplatin, epirubicin, and infusional 5-fluorouracil (ECF) in 81.5% of the patients and cisplatin and infusional 5-fluorouracil (CF) in 15.7%. The median number of cycles was 4.3. The treatment was well tolerated, with no toxic deaths. National Cancer Institute (NCI) grade III-IV neutropenia was frequent (26.3%), but no febrile neutropenia was reported. Severe asthenia (15.7%) and severe nausea (15.7%) required dose reductions in 2 patients and treatment discontinuation in another. The overall response rate was 10.5%, and 18 patients (47.3%) experienced disease stabilization (7 of them with significant clinical benefit). Median time to progression was 4.0 months (range, 2–8 months) and median overall survival was 8.1 months (range, 3–26 months). Thirteen patients (34.2%) also received third-line chemotherapy, with an irinotecan-containing regimen, and their median overall survival was higher than that of the other patients (16.3 vs 6.0 months) Conclusion The combination of oxaliplatin and docetaxel shows only marginal activity as second-line treatment, but it has a good tolerability profile. This suggests that there is room for optimizing the schedule as well as for planning sequential treatments in gastric cancer.