Malignancy incidences by glycemic control among diabetic patients

Background: The aim of this study was to evaluate the difference in malignancy incidence by evaluating time-dependent HbA1c levels among diabetic patients in a longitudinal study. Methods: We conducted a retrospective longitudinal study at large academic hospital, Tokyo, Japan, from 2006 to 2016. We included all diabetic patients who were 50 years or older and who underwent health check-ups at the Center for Preventive Medicine. Those patients with a prior history of malignancies were excluded. We categorized patients into five groups on the basis of HbA1c measurements: 8.5%. Our primary outcome was the development of any types of malignancy. Longitudinal analyses by a mixed effect model with time-dependent HbA1c levels were applied in order to take into account fluctuations in HbA1c levels within the same patient. Results: In total, 2729 participants were included in this study, where the mean age was 62.6 (standard deviation (s.d.): 7.8) and 2031 (74.4%) were male. The mean disease duration of diabetes was 7.6 (s.d.: 7.6) years, and 1688 (61.8%) were prescribed medications. Median follow-up was 1443.5 (interquartile range (IQR): 2508) days and 376 (13.8%) developed malignancies. Compared to the reference range of HbA1c (5.5–6.4%), the odds ratios for developing malignancies among the other HbA1c level groups were similar and not statistically different (OR: 0.98, 95% CI:0.31–3.15 (for HbA1c 8.5%)). Conclusion: In our study, there was no association between glycemic control and the development of future malignancies. Compared to very strictly controlled HbA1c levels, both excessive control and good or bad control had a statistically similar risk of developing malignancies

EFFICACY OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C ： A COOPERATIVE STUDY IN ELEVEN HOSPITALS

We investigated the influences of liver histology，serum levels of hepatitis C virus (HCV) and HCV genotypes on responsiveness to interferon (IFN) therapy in 342 patients with chronic hepatitis C. Either 9 million units (MU) of lymphoblastoid alpha IFN or 3 MU of recombinant IFN-alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three groups on the basis of the results of polymerase chain reaction (PCR) assay detecting HCV-RNA in serum. Complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment，partial response (PR) as HCV elimination for a limited period，non-response (NR) as continuously positive for HCV-RNA in serum. Quantitation of pre-treament HCV-RNA amount in serum was determined by competitive PCR assay in 47 patients. HCV genotyping was performed in 114 patients by PCR with genotype-specific primers. CR was obtained in 97 patients (28.4%)，PR in 104 (30.4%) and NR in 141 (41.2%). IFN responses，represented by CR/PR/NR，were 15/18/11 in 44 patients with chronic persistent hepatitis (CPH)，72/65/73 in 210 patients with chronic aggressive hepatitis (CAH) 2a，and 10/21/57 in 88 patients with CAH2b. CR rate was lower in patients with CAH2b (11.4%) compared to those with CPH (34.1%) or CAH2a (34.3%). Averages of pre-treatment serum HCV-RNA amount (copies/50μl) were 10³·⁵⁵ in 13 CRs，10⁴·⁵⁶ in 17 PRs，and 10⁵·⁹⁵ in 17 NRs. There was a positive correlation between pre-treatment HCV-RNA levels and IFN unresponsiveness. HCV genotyping in 114 patients revealed that HCV type Ⅰ infection was observed in one，type Ⅱ in 94，type Ⅲ in 11，type Ⅳ in 6 and mixed (types Ⅱ and Ⅳ) in 2 patients，and their IFN responses (CR/PR/NR) were 0/0/1，28/26/40，3/5/3，1/3/2 and 0/1/1，respectively

Treatment for recurrence after esophagectomy

Background : With regard to the recurrence of esophageal cancer after surgery, the prognosis has improved with the progress of multimodal perioperative treatment. In this study, the recurrence pattern, treatment method, and prognosis of recurrent cases following esophageal cancer surgery were retrospectively examined. Materials and Methods : Three hundred seven patients with histologically proven squamous cell carcinoma, adenocarcinoma, and others were enrolled in the study. With respect to clinicopathologic factors and recurrence patterns, recurrence risk factors, recurrence period, treatment for recurrence, and prognosis were investigated. Results : Ninety two percent of all recurrent cases were observed within two years after radical esophagectomy. Locoregional recurrence, distant recurrence, and mixed recurrence were observed in 38 (35%), 56 (51%), and 16 (14%) cases, respectively. Patients with lymph node metastasis showed a significantly longer survival in comparison to those with metastasis to other organs (p = 0.0032). When analyzed using the treatment method, patients who underwent surgery (only surgery or additional postoperative chemotherapy) exhibited better survival in comparison to those who underwent other treatments. Discussion : Detailed and strict follow-up within two years are necessary in cases with deeper than muscular invasion, cases with extensive lymph node metastasis, or cases with lymphatic or vascular invasion

Anatomy-based prediction method for determining ipsilateral lung doses in postoperative breast radiation therapy assisted by diagnostic computed tomography images

Background: This study aimed to investigate whether ipsilateral lung doses (ILDs) could be predicted by anatomical indexes measured using diagnostic computed tomography (CT) prior to the planning stage of breast radiation therapy (RT). Materials and methods: The thoracic diameters and the length of lines drawn manually were measured on diagnostic CT images. The parameters of interest were the skin maximum lung distance (sMLD), central lung distance (CLD), Haller index (HI), and body mass index (BMI). Lung dose-volume histograms were created with conformal planning, and the lung volumes receiving 5–40 Gy (V5–V40) were calculated. Linear regression models were used to investigate the correlations between the anatomical indexes and dose differences and to estimate the slope and 95% confidence intervals (CIs). Results: A total of 160 patients who had undergone three-dimensional conformal RT after breast-conserving surgery were included. Univariable analysis revealed that the sMLD (p < 0.001), CLD (p < 0.001), HI (p = 0.002), and BMI (p < 0.001) were significantly correlated with the V20. However, multivariable analysis revealed that only the sMLD (slope: 0.147, p = 0.001, 95% CI: 0.162–0.306) and CLD (0.157, p = 0.005, 0.048–0.266) were strongly correlated with the V20. The p-value for the sMLD was the lowest among the p-values for all indexes, thereby indicating that the sMLD had the best predictive power for ILD. Conclusions: sMLD and CLD are anatomical markers that can be used to predict ILD in whole breast RT. An sMLD > 20.5 mm or a CLD > 24.3 mm positively correlated with a high ILD.

Using spin to understand the formation of LIGO's black holes

With the detection of four candidate binary black hole (BBH) mergers by the Advanced LIGO detectors thus far, it is becoming possible to constrain the properties of the BBH merger population in order to better understand the formation of these systems. Black hole (BH) spin orientations are one of the cleanest discriminators of formation history, with BHs in dynamically formed binaries in dense stellar environments expected to have spins distributed isotropically, in contrast to isolated populations where stellar evolution is expected to induce BH spins preferentially aligned with the orbital angular momentum. In this work we propose a simple, model-agnostic approach to characterizing the spin properties of LIGO's BBH population. Using measurements of the effective spin of the binaries, which is LIGO's best constrained spin parameter, we introduce a simple parameter to quantify the fraction of the population that is isotropically distributed, regardless of the spin magnitude distribution of the population. Once the orientation characteristics of the population have been determined, we show how measurements of effective spin can be used to directly constrain the underlying BH spin magnitude distribution. Although we find that the majority of the current effective spin measurements are too small to be informative, with LIGO's four BBH candidates we find a slight preference for an underlying population with aligned spins over one with isotropic spins (with an odds ratio of 1.1). We argue that it will be possible to distinguish symmetric and anti-symmetric populations at high confidence with tens of additional detections, although mixed populations may take significantly more detections to disentangle. We also derive preliminary spin magnitude distributions for LIGO's black holes, under the assumption of aligned or isotropic populations

Immune Responses following Stereotactic Body Radiotherapy for Stage I Primary Lung Cancer

Purpose. Immune responses following stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) were examined from the point of view of lymphocyte subset counts and natural killer cell activity (NKA). Patients and Methods. Peripheral blood samples were collected from 62 patients at 4 time points between pretreatment and 4 weeks post-treatment for analysis of the change of total lymphocyte counts (TLC) and lymphocyte subset counts of CD3 + , CD4 + , CD8 + , CD19 + , CD56 + , and NKA. In addition, the changes of lymphocyte subset counts were compared between patients with or without relapse. Further, the correlations between SBRT-related parameters and immune response were analyzed for the purpose of revealing the mechanisms of the immune response. Results. All lymphocyte subset counts and NKA at post-treatment and 1 week post-treatment were significantly lower than pre-treatment ( < 0.01). No significant differences in the changes of lymphocyte subset counts were observed among patients with or without relapse. The volume of the vertebral body receiving radiation doses of 3 Gy or more (VV 3 ) significantly correlated with the changes of nearly all lymphocyte subset counts. Conclusions. SBRT for stage I NSCLC induced significant immune suppression, and the decrease of lymphocyte subset counts may be associated with exposure of the vertebral bone marrow

A VCP modulator, KUS121, as a promising therapeutic agent for post-traumatic osteoarthritis

京大開発の薬剤「KUS121」の変形性膝関節症への効果を確認 --外傷性変形性関節症の治療薬として臨床応用へ--. 京都大学プレスリリース. 2020-12-17.Post-traumatic osteoarthritis (PTOA) is a major cause which hinders patients from the recovery after intra-articular injuries or surgeries. Currently, no effective treatment is available. In this study, we showed that inhibition of the acute stage chondrocyte death is a promising strategy to mitigate the development of PTOA. Namely, we examined efficacies of Kyoto University Substance (KUS) 121, a valosin-containing protein modulator, for PTOA as well as its therapeutic mechanisms. In vivo, in a rat PTOA model by cyclic compressive loading, intra-articular treatments of KUS121 significantly improved the modified Mankin scores and reduced damaged-cartilage volumes, as compared to vehicle treatment. Moreover, KUS121 markedly reduced the numbers of TUNEL-, CHOP-, MMP-13-, and ADAMTS-5-positive chondrocytes in the damaged knees. In vitro, KUS121 rescued human articular chondrocytes from tunicamycin-induced cell death, in both monolayer culture and cartilage explants. It also significantly downregulated the protein or gene expression of ER stress markers, proinflammatory cytokines, and extracellular-matrix-degrading enzymes induced by tunicamycin or IL-1β. Collectively, these results demonstrated that KUS121 protected chondrocytes from cell death through the inhibition of excessive ER stress. Therefore, KUS121 would be a new, promising therapeutic agent with a protective effect on the progression of PTOA