Hamiltoncrowell9317

Germline pathogenic variants in the DNA mismatch repair genes (MMR) MLH1, MSH2, MSH6, and PMS2, are causative of Lynch syndrome (LS). However, many of the variants mapping outside the invariant splice site positions (IVS ± 1, IVS ± 2) are classified as variants of unknown significance (VUS). Three such variants (MLH1 c.588+5G>C, c.588+5G>T and c.677+5G>A) were identified in 8 unrelated LS families from Argentina, Brazil and Chile. Herein, we collected clinical information on these families and performed segregation analysis and RNA splicing studies to assess the implication of these VUS in LS etiology. Pedigrees showed a clear pattern of variant co-segregation with colorectal cancer and/or other LS-associated malignancies. Tumors presented deficient expression of MLH1-PMS2 proteins in 7/7 of the LS families, and MSI-high status in 3/3 cases. Moreover, RNA analyses revealed that c.588+5G>C and c.588+5G>T induce skipping of exon 7 whereas c.677+5G>A causes skipping of exon 8. In sum, we report that the combined clinical findings in the families and the molecular studies provided the evidences needed to demonstrate that the three MLH1 variants are causative of LS and to classify c.588+5G>C and c.677+5G>A as class 5 (pathogenic), and c.588+5G>T as class 4 (likely-pathogenic). Our findings underline the importance of performing clinical and family analyses, as well as RNA splicing assays in order to determine the clinical significance of intronic variants, and contribute to the genetic counseling and clinical management of patients and their relatives.The author would like to correct the names for the below co-authors in the online published article.PURPOSE Although several trials have confirmed the treatment efficacy of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) from endemic area of China, little is known about the best regime for induction chemotherapy in non-endemic region. This study compared the treatment effect of Gemcitabine and cisplatin (GP) versus docetaxel and cisplatin (TP) followed by concurrent chemoradiotherapy in locoregionally advanced NPC from non-endemic area of China. MATERIALS AND METHODS A total of 196 locoregionally advanced NPC patients were enrolled in this study, with 142 and 54 patients in TP and GP followed by concurrent chemoradiotherapy groups. The primary endpoint was treatment response of induction chemotherapy. The secondary endpoints included disease-free survival. The Kaplan-Meier method was used to evaluate the efficacy between treatment groups. RESULTS The median follow-up time was 45.5 months (range 6-60.5 months). During induction chemotherapy course, GP contributed higher treatment response rate than TP (68.1% vs. 47.1%, p = 0.007). Patients in GP group had better DFS and LRFS than those in TP group (3-year and 5-year DFS, 86.8% and 82.5% vs. 71.7% and 68%, p = 0.036; 3-year and 5-year LRFS, 96.2% and 96.2% vs. 90.5% and 82.8%, p = 0.03). No significant difference of adverse events was observed between two treatment groups in the whole course. CONCLUSION This study suggested that GP followed by CCRT was better than TP followed by CCRT in improving survival outcomes of locoregionally advanced NPC patients from non-endemic area of China.PURPOSE This study aimed to evaluate the prevalence of preoperative anemia and impacts of anemia and transfusion on survival in patients undergoing surgery for colorectal cancer. METHODS This study included patients who underwent surgery for primary colorectal cancer between 2011 and 2012. The influence of preoperative anemia and postoperative transfusion on recurrence-free survival and overall survival were retrospectively investigated. Anemia was defined as hemoglobin level less then  13 g/dL in males and less then  12 g/dL in females. The primary outcome was the prevalence of preoperative anemia in patients with colorectal cancer. Secondary outcomes included preoperative anemia management, postoperative 30-day mortality and morbidity, tumor recurrence, and overall survival. RESULTS Among a total of 1899 patients, 823 patients (43.3%) were anemic preoperatively, and 264 patients (13.9%) received postoperative transfusions. Postoperative transfusion was associated with 30-day postoperative complications (OR = 1.514, 95% CI = 1.020 ~ 2.247) but not preoperative anemia (OR = 1.143, 95% CI, 0.811 ~ 1.611). UC2288 molecular weight Preoperative anemia (HR = 1.459, 95% CI = 1.104 ~ 1.929) and postoperative transfusion (HR = 1.566, 95% CI = 1.089 ~ 2.252) were significantly associated with worse recurrence-free survival in multivariable analysis. Preoperative anemia (HR = 1.572, 95% CI = 1.274 ~ 1.940) and postoperative transfusion (HR = 1.381, 95% CI = 1.076 ~ 1.773) were significant independent risk factors for worse overall survival. CONCLUSIONS Preoperative anemia and postoperative transfusion were associated with worse survival in patients undergoing surgery for colorectal cancer. An alternative therapy to treat anemia and reduce transfusions should be introduced to improve oncologic outcomes.PURPOSE To evaluate the impact of local soaking of the autografts with vancomycin during anterior cruciate ligament (ACL) reconstruction on postoperative infection rates. METHODS Between 2003 and 2014 (first study period), 1,242 patients underwent ACL reconstruction using autografts, without soaking them in vancomycin solution, while between 2014 and 2019 (second study period) all ACL autografts in 593 patients were soaked in a 5-mg/ml vancomycin solution, in a territory University Hospital. The same standard treatment of perioperative IV antibiotics was applied in both groups. RESULTS Postoperative septic arthritis occurred in seven out of 1,242 patients (0.56%) during the first study period. Bone patellar tendon bone autograft was used in 311 (25%) patients, and hamstring tendon autograft was used in the rest 931 (75%) of the study population during this period. All infected cases were male and had a hamstrings graft implanted. There were no postoperative infections (0%) in 593 ACL reconstructions during the second study period.