Sodium–glucose cotransporter 2 inhibitors reduce day-to-day glucose variability in patients with type 1 diabetes

Aims/IntroductionSodium–glucose cotransporter 2 inhibitors (SGLT2i) are used worldwide because of their multiple benefits for patients with type 2 diabetes. The purpose of this study was to determine the efficacy and safety of SGLT2i in patients with type 1 diabetes.Materials and MethodsPatients with type 1 diabetes who had been treated with SGLT2i for >12 weeks were included in this retrospective observation study. We recorded the changes in body mass, insulin dose, blood and urine test data, and adverse events. The changes in day‐to‐day glucose variability, as the primary end‐point, was evaluated using the interquartile range (P25/P75) of the ambulatory glucose data obtained using continuous glucose monitoring.ResultsA total of 51 patients (37 women; mean age 52.7 years) were included. Glycated hemoglobin and body mass significantly decreased by 0.4% and 1.6 kg, respectively. The total required insulin dose decreased by 9.4% (42.7 ± 26.6–38.7 ± 24.3 units/day). Continuous glucose monitoring data were obtained from 30 patients. P25/P75 decreased by 17.6 ± 20.7% during SGLT2i treatment (P < 0.001). The percentage of time per day within the target glucose range of 70–180 mg/dL significantly increased (from 42.2 to 55.5%, P < 0.001), without an increase in the percentage of time spent in the hypoglycemic range (<70 mg/dL). Urinary ketone bodies were detected in four patients (7.8%), but none developed ketoacidosis.ConclusionsSGLT2i improved day‐to‐day glucose variability and time in the target glucose range, without increasing frequency of hypoglycemia, in patients with type 1 diabetes, and reduced glycated hemoglobin, body mass and the required insulin dose.     

Changes in Medical Students’ Attitudes Towards End-of-Life Decisions Across Different Years of Medical Training

BACKGROUND  Decisions to forgo life-sustaining medical treatments in terminally ill patients are challenging, but ones that all doctors must face. Few studies have evaluated the impact of medical training on medical students’ attitudes towards end-of-life decisions and none have compared them with an age-matched group of non-medical students. OBJECTIVE  To assess the effect of medical education on medical students’ attitudes towards end-of-life decisions in acutely ill patients. DESIGN  Cross-sectional study. PARTICIPANTS  Four hundred and two students at The Chinese University of Hong Kong. MEASUREMENTS  Completion of a questionnaire focused on end-of-life decisions. MAIN RESULTS  The number of students who felt that cardiopulmonary resuscitation must always be provided was higher in non-medical students (76/90 (84%)) and medical students with less training (67/84 (80%) in year 1 vs. 18/67 (27%) in year 5) (p < 0.001). Discontinuing life-support therapy was more accepted among senior medical students compared to junior medical and non-medical students (27/66 (41%) in year 5 vs. 18/83 (22%) in year 1 and 20/90 (22%) in non-medical students) (p = 0.003). An unexpectedly large proportion of non-medical students (57/89 (64%)) and year 1 medical students (42/84 (50%)) found it acceptable to administer fatal doses of drugs to patients with limited prognosis. Euthanasia was less accepted with more years of training (p < 0.001). When making decisions regarding limitation of life-support therapy, students chose to involve patients (98%), doctors (92%) and families (73%) but few chose to involve nurses (38%). CONCLUSIONS  Medical students’ attitudes towards end-of-life decisions changed during medical training and differed significantly from those of non-medical students.     

Acute myocardial infarction associated with systemic lupus erythematosus documented by coronary arteriograms

A 19-year-old man with untreated systemic lupus erythematosus had an acute myocardial infarction. A coronary arteriogram five hours after the onset of symptoms revealed total occlusion of the left anterior descending coronary artery. Reperfusion was achieved by coronary thrombolytic therapy with urokinase. Four weeks later, a coronary arteriogram showed only minimal luminal irregularities at the original site of occlusion, where significant reduction in diameter could be induced by ergonovine maleate. This case suggests that coronary arterial involvement in systemic lupus erythematosus may be related to coronary arterial spasm.     

Altered platelet alpha 2 adrenoreceptor in acute myocardial infarction and its relation to plasma catecholamine concentrations.

Changes in platelet alpha 2 adrenoreceptors and their relation to plasma catecholamine concentrations were studied in 11 patients with acute transmural myocardial infarction. A radiolabelled alpha 2 adrenoreceptor antagonist, [3H]-yohimbine, was used to assay alpha 2 adrenoreceptors on platelet membranes, and plasma catecholamine concentrations were measured by high performance liquid chromatography. The number of platelet alpha 2 adrenoreceptors, the dissociation constant, and plasma noradrenaline and adrenaline concentrations were studied 6.6 (3.3) (mean (SD)) hours after the onset of acute myocardial infarction and one month later. The mean (SD) number of adrenoreceptors increased significantly from 94.5 (50.5) fmol/mg protein immediately after infarction to 157.0 (65.7) fmol/mg protein one month later. The dissociation constant, however, did not change significantly (4.33 (1.40) nmol/l vs 4.37 (1.22) nmol/l). Raised noradrenaline (5.60 (4.37) nmol/l) and adrenaline (0.28 (0.14) nmol/l) concentrations had fallen significantly to normal values (1.21 (0.67) and 0.09 (0.05) nmol/l respectively) a month after infarction. The decrease in the number of alpha 2 adrenoreceptors soon after infarction may be beneficial because such a change will reduce the strength of various reactions to catecholamines, such as vasoconstriction.     

Long-Term Survival in Patients with Locally Advanced Colon Cancer After <Emphasis Type="Italic">En Bloc</Emphasis> Pancreaticoduodenectomy and Colectomy

Purpose  Surgical indications for colon cancer directly invading the pancreas head are controversial. Methods  Between 1957 and 2007, a total of 12 patients (8 men) underwent pancreaticoduodenectomy combined with right hemicolectomy for colon cancer involving the pancreas head. Results  Mean age was 58 (range, 34–77) years. Fistula formation was observed in five patients (41 percent) preoperatively. Tumor involvement was duodenum only (n = 4), duodenum/pancreas (n = 3), stomach/pancreas (n = 1), duodenum/stomach (n = 2), duodenum/liver (n = 1), and pancreas only (n = 1). Only one postoperative death was encountered. Histologic examination showed malignant invasion to the pancreas head in nine cases (75 percent). Overall one-year, three-year and, five-year survival rates after surgery were 75, 66, and 55 percent, respectively. Five patients (41 percent) survived for more than ten 10 years. Conclusions  Pancreaticoduodenectomy for advanced colon cancer invading the pancreas or duodenum provides favorable long-term survival. Supported by a Grant-in-Aid for Basic Research to Dr. Akio Saiura from the Ministry of Education, Culture, Sports, Science and Technology. Reprints are not available.     

The role of lipid peroxidation in individuals with autism spectrum disorders

Metabolic Brain Disease - The role of malondialdehyde-modified low-density lipoprotein (MDA-LDL), an oxidized LDL, in the pathophysiology of autism spectrum disorder (ASD) is unclear. We studied...     

Delayed renal dysfunction after total body irradiation in pediatric malignancies

The purpose of this study was to retrospectively evaluate the incidence of delayed renal dysfunction after total body irradiation (TBI) in long-term survivors of TBI/hematopoietic stem cell transplantation (HSCT). Between 1989 and 2006, 24 pediatric patients underwent TBI as part of the conditioning regimen for HSCT at Chiba University Hospital. Nine patients who survived for more than 5 years were enrolled in this study. No patient had any evidence of renal dysfunction prior to the transplant according to their baseline creatinine levels. The median age at the time of diagnosis was 6 years old (range: 1–17 years old). The follow-up period ranged from 79–170 months (median: 140 months). Renal dysfunction was assessed using the estimated glomerular filtration rate (eGFR). The TBI dose ranged from 8–12 Gy delivered in 3–6 fractions over 2–3 d. The patients were treated with linear accelerators in the supine position, and the radiation was delivered to isocentric right–left and left–right fields via the extended distance technique. The kidneys and the liver were not shielded except in one patient with a left adrenal neuroblastoma. No patient required hemodialysis. The eGFR of four patients (44.4%) progressively decreased. The remaining patients did not demonstrate any eGFR deterioration. Only one patient developed hypertension. By evaluating the changes in eGFR, renal dysfunction among long-term survivors of TBI/HSCT could be detected. Our results suggested that the TBI schedule of 12 Gy in 6 fractions over three consecutive days affects renal function.     

Alpha‐actinin‐4 (ACTN4) gene amplification is a predictive biomarker for adjuvant chemotherapy with tegafur/uracil in stage I lung adenocarcinomas

Although adjuvant tegafur/uracil (UFT) is recommended for patients with completely resected stage I non‐small‐cell lung cancer (NSCLC) in Japan, only one‐third of cases has received adjuvant chemotherapy (ADJ) according to real‐world data. Therefore, robust predictive biomarkers for selecting ADJ or observation (OBS) without ADJ are needed. Patients who underwent complete resection of stage I lung adenocarcinoma with or without adjuvant UFT were enrolled. The status of ACTN4 gene amplification was analyzed by FISH. Statistical analyses to determine whether the status of ACTN4 gene amplification affected recurrence‐free survival (RFS) were carried out. Formalin‐fixed, paraffin‐embedded samples from 1136 lung adenocarcinomas were submitted for analysis of ACTN4 gene amplification. Ninety‐nine (8.9%) of 1114 cases were positive for ACTN4 gene amplification. In the subgroup analysis of patients aged 65 years or older, the ADJ group had better RFS than the OBS group in the ACTN4‐positive cohort (hazard ratio [HR], 0.084, 95% confidence interval [CI], 0.009‐0.806; P = .032). The difference in RFS between the ADJ group and the OBS group was not significant in ACTN4‐negative cases (all ages: HR, 1.214; 95% CI, 0.848‐1.738; P = .289). Analyses of ACTN4 gene amplification contributed to the decision regarding postoperative ADJ for stage I lung adenocarcinomas, preventing recurrence, improving the quality of medical care, preventing the unnecessary side‐effects of ADJ, and saving medical costs.     

Reduced area of the normal lung on high-resolution computed tomography predicts poor survival in patients with lung cancer and combined pulmonary fibrosis and emphysema

Background

This study aimed to determine the radiologic predictors and clarify the clinical features related to survival in patients with combined pulmonary fibrosis and emphysema (CPFE) and lung cancer.