Mcclellanlausen3501

The definition of "no tumor on ink" is generally applied for clear resection margin (RM) after breast-conserving surgery (BCS). However, few studies reported the effect of RM in the setting of neoadjuvant chemotherapy (NAC). We investigated the association between RM status and survival outcomes for those who underwent BCS after NAC for breast cancer.

We retrospectively reviewed the data of 2,803 patients who underwent BCS and whole-breast irradiation after NAC between January 2008 and December 2016 from three institutions in South Korea.

The 786 patients in the pathologic complete response group (R

) had significantly longer local recurrence-free survival (LRFS) than the 1,949 patients in clear or close RM and non-pCR group (R

) and the 68 patients in involved RM and non-pCR group (R

) (vs. R

, p = 0.001; vs. R

, p = 0.049). Patients in R

showed no benefit in LRFS compared to R

on both log-rank test (HR = 1.20; 95% C.I., 0.49-2.93; p = 0.692) and Cox regression analysis (HR = 2.05; 95% C.I., 0.64-6.58; p = 0.227). Subgroup analysis according to tumor subtypes revealed that there was no significant difference in LRFS, distant metastasis-free survival, and recurrence-free survival between the R

and R

group. Additionally, among 286 patients with pCR with residual ductal carcinoma in situ (DCIS) alone, RM status was not significantly associated with LRFS.

Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.

Clear RM of specimen does not have benefit on LRFS after NAC. Additionally, for the patients showing pCR with residual DCIS in the breast, margin involvement also did not affect the risk of local recurrence.Metoprolol, a selective β1-adrenoreceptor blocking agent used in the treatment of hypertension, angina, and heart failure, is primarily metabolized by the CYP2D6 enzyme, which catalyzes α-hydroxylation and O-desmethylation. As CYP2D6 is genetically highly polymorphic and the enzymatic activity differs greatly depending on the presence of the mutant allele(s), the pharmacokinetic profile of metoprolol is highly variable depending on the genotype of CYP2D6. The aim of study was to develop the physiologically based pharmacokinetic (PBPK) model of metoprolol related to CYP2D6 genetic polymorphism for personalized therapy with metoprolol. For PBPK modelling, our previous pharmacogenomic data were used. To obtain kinetic parameters (Km, Vmax, and CLint) of each genotype, the recombinant CYP enzyme of each genotype was incubated with metoprolol and metabolic rates were assayed. Based on these data, the PBPK model of metoprolol was developed and validated in different CYP2D6 genotypes using PK-Sim® software. As a result, the input values for various parameters for the PBPK model were presented and the PBPK model successfully described the pharmacokinetics of metoprolol in each genotype group. The simulated values were within the acceptance criterion (99.998% confidence intervals) compared with observed values. The PBPK model developed in this study can be used for personalized pharmacotherapy with metoprolol in individuals of various races, ages, and CYP2D6 genotypes.

The number of patients with primary Sjögren's syndrome (PSS) requiring total hip arthroplasty (THA) is expected to increase, but few studies have detailed their outcomes. The purpose of this study was to evaluate a THA cohort of patients with avascular necrosis of the femoral head (ANFH) who had PSS and to compare their outcomes with those of matched patients with osteoarthritis.

A case-control study using data from a single-institution arthroplasty registry was performed. Forty-two THAs in 32 patients undergoing THA with a diagnosis of PSS were identified and were matched with 84 THAs in 64 patients with osteoarthritis (12 ratio). Functional and health-related quality of life (QoL) evaluations were performed, and complications were recorded at the last follow-up. Logistic regression was used to determine factors associated with reaching the transfusion trigger of hemoglobin < 8g/dL (TT8) in PSS patients.

After a mean 5-year follow-up, both cohorts had similar hip function and health-related QoL outcilar to those of non-PSS patients. Improving preoperative Hb level can reduce the risk of transfusion. Key Points • THA significantly improved hip function and health-related quality of life in PSS patients with osteonecrosis of the femoral head. • Patients with PSS were more likely to reach the transfusion trigger and higher rates of incision complications after THA. • Improving preoperative Hb level can reduce the risk of transfusion for PSS patients who underwent THA.Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition, historically considered a predominantly male disease. However, increasing evidence suggests a more equal prevalence between men and women. Of the limited research conducted to date, it is apparent that gender differences exist in terms of time to diagnosis, treatment outcomes and health-related quality of life (HRQoL). Despite this, women are underrepresented in clinical trials and most studies do not stratify by gender to identify potential differences in terms of disease manifestations and treatment response. In this perspectives article, we reflect on the potential biological and social factors contributing to these differences and propose three key areas of education and research that should be prioritised in order to address the unmet needs of female patients with axSpA, namely (1) to identify ways to increase awareness of disease occurrence in female patients among healthcare professionals (HCPs), (2) to improve understanding of gender differences in disease manifestation and outcomes, and (3) to conduct gender-stratified clinical trials with a representative sample of female patients.Vascular calcification is an independent risk factor for acute cardiovascular events and a predictor of adverse prognosis; the abnormal fusion and degradation of autophagosomes and lysosomes are closely related to the calcification of VSMC and aortic AS plaque in ApoE-/- mice. Rab7 is a member of the Ras protein family and acts as a molecular switch in the fusion between autophagosomes and lysosomes. In this study, we found that the activation of the CD137-CD137L signal promoted calcification by inhibiting the expression and activity of Rab7, which regulates the degradation of autophagic cargo in vascular smooth muscle cells (VSMCs) and aortic atherosclerosis (AS) plaques in ApoE-/- mice. Knockdown of Rab7 impaired its tethering with the downstream molecule FYVE and coiled-coil containing 1 (FYCO1), which transports autophagosomes to lysosomes through microtubule motor kinesins and fuses with lysosomes to degrade the autophagic content. Overexpression of Rab7-alleviated calcification caused by the activation of the CD137 signaling pathway. In addition, FYCO1 knockdown promoted calcification even though the expression and activity of Rab7 were normal. Our results suggest that Rab7 is the target of CD137 signaling; Rab7 cannot interact with its downstream molecule FYCO1 when its activity and expression were inhibited by the activation of CD137 signaling pathway, thus inhibiting the autophagic degradation and promoting calcification.Heat stress during gametogenesis leads to spikelet sterility. To ascertain the role of female reproductive organ (pistil), two rice genotypes N22 and IR64 with contrasting heat stress responses were exposed to control (30 °C) and heat stress (38 °C and 40 °C) during megasporogenesis. Anatomical observations of ovule revealed greater disappearance of megaspore mother cell and nuclei at early stages, and during later stages mature embryo sac without female germ unit, improper positioning of nuclei, and shrunken embryo sac was observed in the sensitive IR64. Under heat stress, a decrease in sugar and starch, increase in H2O2 and malondialdehyde with lower antioxidant enzyme activities were recorded in pistils of both N22 and IR64. Lower accumulation of TCA cycle metabolites and amino acids were noticed in IR64 pistils under heat stress at gametogenesis, whereas N22 exhibited favorable metabolite profiles. At heading, however, N22 pistils had higher carbohydrate accumulation and better ROS homeostasis, suggesting higher recovery after heat stress exposure. In summary, the results indicate that heat stress during megasporogenesis leads to irreversible anatomical and physiological changes in pistil and alters metabolic signatures leading to increased spikelet sterility in rice. Mechanisms identified for enhanced heat tolerance in pistil can help in developing rice varieties that are better adapted to future hotter climate.A 77-year-old woman with obstructive jaundice due to pancreatic head tumor was admitted to our hospital for biliary drainage. Transpapillary biliary drainage was attempted using endoscopic retrograde cholangiopancreatography; however, the catheter could not be inserted into the bile duct. Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) was conducted using a 7-Fr plastic stent. Fever and cognitive dysfunction were observed 73 days after EUS-HGS. Abdominal-computed tomography (CT) showed a huge biloma and a liver abscess. On admission, an uncovered metal stent was applied to the biliary obstruction site of the distal bile duct using an antegrade stenting technique, and the plastic hepaticogastrostomy stent was substituted with a new one. On the second day, two double-pigtail plastic stents were inserted into the biloma, and one into the liver abscess. Head CT and magnetic resonance imaging revealed a brain abscess in the right cerebral frontal lobe. Serum white blood cell count and C-reactive protein level, and the state of consciousness, improved with antibiotic administration. Biloma and liver abscess almost disappeared on CT 38 days after admission. check details The brain abscess also improved, and the patient was discharged from the hospital 48 days after admission. Endoscopic ultrasound-guided biloma drainage is helpful because self-removal of the drainage tube and reduced activities of daily living are unlikely to occur.We report the use of indocyanine green (ICG) fluorescence for intraoperative diagnosis in two cases of strangulated ileus. We successfully preserved the bowel and avoided postoperative complications by detecting adequate perfusion and no necrosis in the intestine's strangulated regions. In the first case, enhanced computed tomography (CT) revealed a closed loop intestine, which showed poor contrast, and we performed laparotomy with ICG fluorescence. In the second case, the CT scan revealed bowel obstruction without ascites. We conservatively treated the patient with the insertion of a long tube. The patient's condition did not improve, and we performed laparotomy using ICG fluorescence. In both of these cases, the visual observation during laparotomy showed that the ileum had dark-red discoloration. We demonstrated perfusion and preserved the ileum by injecting 2.5 mg of ICG intravenously; fluorescence was observed in the dark-red ileum using the PINPOINT system (Novadaq, Kalamazoo, MI, US). Both patients recovered successfully after the surgery with no adverse events.