Effects of Total Parenteral Nutrition on Serum Osmolality and Patent Ductus Arteriosus.

BACKGROUND: The persistence of high serum osmolality in the early postnatal period is a risk for developing patent ductus arteriosus (PDA). Early aggressive nutrition (EAN), involving total parenteral nutrition (TPN), by which enough concentrations of glucose and amino acids are administered intravenously, is recommended postnatally to improve the neurological prognosis in preterm infants. However, the effects of EAN involving TPN on serum osmolality and the development of a PDA have not been adequately studied. OBJECTIVES: Thus, in this study, we aimed to investigate the impact of TPN on serum osmolality and determine whether increased serum osmolality could be associated with a higher incidence of PDA in preterm infants. METHODS: In this single-center retrospective observational study, preterm infants born at <28 weeks of gestation who had been admitted to our neonatal intensive care unit (NICU) before (pre-TPN period) and after the introduction of TPN (post-TPN) were included. We reviewed the medical records of these patients, compared the changes in serum osmolality from birth to five days after birth, the clinical background, and the incidence of PDA between these two periods, and analyzed the risk factors. Additionally, the factors affecting the serum osmolality in very preterm infants were examined. The patients who met the intervention criteria of our NICU and received a cyclooxygenase (COX) inhibitor, Indacin® (Nobelpharma, Tokyo, Japan), within seven days after birth were classified as PDA+; those who could not be identified to have PDA flow by echo and did not receive a COX inhibitor were classified as PDA-. RESULTS: The postnatal day and serum sodium (Na+) were statistically significantly correlated with a higher serum osmolality. Serum osmolality remained statistically significantly higher in the PDA+ cohort compared with the PDA- cohort after the first day of life. However, no statistically significant differences were observed in serum osmolality after 24 hours of age, weeks of gestational age, birth weight, or incidence of PDA between the pre- and post-TPN periods. The results of the multiple logistic regression analyses revealed that the increased serum osmolality correlated with PDA development. CONCLUSIONS: In this study, the serum Na+ statistically significantly correlated with a higher serum osmolality. Moreover, the increased serum osmolality correlated with PDA development. Thus, the prevention of hypernatremia might reduce the incidence of PDA. Nonetheless, the findings in this study revealed that no statistically significant differences in serum osmolality were observed between the pre-and post-TPN periods, indicating that TPN had little effect on serum osmolality.

Bovine respiratory syncytial virus enhances the attachment of Trueperella pyogenes to cells.

In cattle, bovine respiratory syncytial virus (BRSV) is associated with secondary bacterial infections; however, the mechanisms of the interaction between BRSV and bacteria are unclear. Trueperella pyogenes (T. pyogenes) causes pneumonia in cattle and is involved in secondary infections following viral infections. In this study, we evaluated the effect of BRSV infection on the adhesion of T. pyogenes to BRSV-infected cells. BRSV infection significantly enhanced the adhesion of T. pyogenes to cells in a multiplicity of infection- and time-dependent manner. The BRSV-mediated change in the adhesion of T. pyogenes was widely observed in various cell types and bacterial strains. The results from the gentamicin protection assay showed that BRSV infection did not affect the intracellular invasion ability of T. pyogenes. Furthermore, adhesion assays conducted using BRSV G protein-expressing cells and anti-BRSV G antibodies revealed that the increased adhesion of T. pyogenes to cells was mediated by the G protein of BRSV. In addition, immunofluorescence assay revealed the colocalization of BRSV G protein and T. pyogenes. Thus, BRSV infection can potentially lead to bovine respiratory disease complex by promoting the adhesion of T. pyogenes to the infected cells.

Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study.

OBJECTIVE: In this study, we collected data over 8 years (2012-2019) from the Japan Society of Obstetrics and Gynecology (JSOG) tumor registry to determine the status of endometrial cancer in Japan, and analyzed detailed clinicopathological factors. METHODS: The JSOG maintains a tumor registry that gathers information on endometrial cancer treated at the JSOG-registered institutions. Data from the patients whose endometrial cancer treatment was initiated from 2012 to 2019 were analyzed retrospectively. RESULTS: A total of 82,969 patients with endometrial cancer underwent treatment from 2012 to 2019. Chemotherapy alone or in combination with hormonal therapy is more common among endometrial cancer patients under 40 years compared with those over 40 years. The number of patients with endometrial cancer, treated with laparoscopic or robot-assisted surgery was observed to have increased yearly. Small cell carcinomas and undifferentiated carcinomas were more likely to be diagnosed at an advanced stage. Lymphadenectomy was most commonly performed for stage IIIC2 disease, whereas positive peritoneal washing cytology was most common for stage IVB and serous carcinoma. CONCLUSION: Multi-year summary reports provided detailed clinicopathological information regarding endometrial cancer that could not be obtained in a single year. These reports were useful in understanding treatment strategies and trends over time based on age, histology, and stage.

TP53 signature predicts pathological complete response after neoadjuvant chemotherapy for breast cancer: Observational and confirmational study using prospective study cohorts.

The TP53 signature is considered a predictor of neoadjuvant chemotherapy (NAC) response and prognostic factor in breast cancer. The objective of this study was to confirm TP53 signature can predict pathological complete response (pCR) and prognosis in cohorts of breast cancer patients who received NAC in prospective studies. Development cohorts (retrospective [n = 37] and prospective [n = 216] cohorts) and validation cohorts (NAC administered prospective study cohorts [n = 407] and retrospective perioperative chemotherapy (PC)-naïve, hormone receptor (HrR)-positive cohort [PC-naïve_HrR+ cohort] [n = 322]) were used. TP53 signature diagnosis kit was developed using the development cohorts. TP53 signature predictability for pCR and the relationship between recurrence-free survival (RFS), overall survival (OS), and the TP53 signature were analyzed. The pCR rate of the mutant (mt) signature group was significantly higher than that of the wild-type (wt) signature group (odds ratio, 5.599; 95 % confidence interval = 1.876-16.705; P = 0.0008). The comparison of the RFS and OS between the HrR+ and HER2- subgroup of the NAC cohort and of the PC-naïve_HrR+ cohort indicated that the RFS and OS benefit of NAC was greater in the mt signature group than in the wt signature group. From post hoc analyses, the RFS and OS benefit from adding capecitabine to FEC+T as NAC might be observed only in the mt signature group. The TP53 signature can predict the pCR after NAC, and the RFS and OS benefit from NAC may be greater in the mt signature group than in the wt signature group.

Cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry during continuous intravenous infusion of a combination solution of xylazine, butorphanol, and propofol in calves.

General anesthesia in calves is easier to perform under field conditions, total intravenous anesthesia (TIVA) than using inhalation anesthesia. In the present study, cardiopulmonary function, anesthetic effects, quality of arousal, hematology, and blood biochemistry were assessed during continuous infusion of a combination solution of 0.01% xylazine, 0.001% butorphanol, and 0.2% propofol (XBP) at doses of 6 (G6; 10 µg/kg/min xylazine, 1 µg/kg/min butorphanol, 200 µg/kg/min propofol) and 9 mL/kg/h (G9; 15 µg/kg/min xylazine, 1.5 µg/kg/min butorphanol 300 µg/kg/min propofol). For both groups, five castrated Holstein calves received intravenous injections of xylazine (0.2 mg/kg) and propofol (2 mg/kg), followed by a continuous infusion of XBP for 60 min to maintain anesthesia. Respiratory management consisted of tracheal intubation followed by spontaneous inhalation of pure oxygen. Cardiopulmonary, anesthesia, hematology, and blood biochemistry variables were assessed at rest (baseline) and every 5 or 15 min after the start of the XBP infusion. Quality of arousal was assessed based on the swallowing reflex recovery time from the stop of XBP infusion, and the sternal position time and standing time after atipamezole administration. XBP produced adequate sedation, analgesia, and muscle relaxation in all calves and maintained stable anesthesia for 60 min. As XBP infusion time passed, rectal temperature and heart rate became lower, and mean arterial blood pressure increased. In both groups, hematologic and blood biochemical effects were mild. The quality of arousal was not different, and all calves were standing. The results of the present study suggested that XBP is useful for TIVA in calves.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODS AND RESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

English version of Japanese Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) issued by the Japan Society of Clinical Oncology.

The Japan Society of Clinical Oncology Clinical Practice Guidelines 2022 for gastrointestinal stromal tumor (GIST) have been published in accordance with the Minds Manual for Guideline Development 2014 and 2017. A specialized team independent of the working group for the revision performed a systematic review. Since GIST is a rare type of tumor, clinical evidence is not sufficient to answer several clinical and background questions. Thus, in these guidelines, we considered that consensus among the experts who manage GIST, the balance between benefits and harms, patients' wishes, medical economic perspective, etc. are important considerations in addition to the evidence. Although guidelines for the treatment of GIST have also been published by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), there are some differences between the treatments proposed in those guidelines and the treatments in the present guidelines because of the differences in health insurance systems among countries.

Epididymitis with Pasteurella multocida isolated from two male Japanese Black beef calves.

Two male Japanese Black calves developed an enlarged scrotum and testis. Orchiectomy was performed and pus was collected during surgery. After removal of the testis, bacteriological and histopathological examinations were conducted to investigate the cause and confirm the diagnosis. Based on the results obtained, both cases were diagnosed with epididymitis caused by an infection with Pasteurella multocida. This is the first study to show that P. multocida causes epididymitis in male calves. Further studies are required to clarify the details underlying the infection of calves with P. multocida.

Surgical treatment of bovine nasal granuloma and an allergological exploration.

Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.

Combination of oligo-fractionated irradiation with nivolumab can induce immune modulation in gastric cancer.

BACKGROUND: Tumor-associated antigen (TAA)-specific CD8(+) T cells are essential for nivolumab therapy, and irradiation has been reported to have the potential to generate and activate TAA-specific CD8(+) T cells. However, mechanistic insights of T-cell response during combinatorial immunotherapy using radiotherapy and nivolumab are still largely unknown. METHODS: Twenty patients included in this study were registered in the CIRCUIT trial (ClinicalTrials.gov, NCT03453164). All patients had multiple distant metastases and were intolerance or had progressed after primary and secondary chemotherapy without any immune checkpoint inhibitor. In the CIRCUIT trial, eligible patients were treated with a total of 22.5 Gy/5 fractions/5 days of radiotherapy to the largest or symptomatic lesion prior to receiving nivolumab every 2 weeks. In these 20 patients, T-cell responses during the combinatorial immunotherapy were monitored longitudinally by high-dimensional flow cytometry-based, multiplexed major histocompatibility complex multimer analysis using a total of 46 TAAs and 10 virus epitopes, repertoire analysis of T-cell receptor ß-chain (TCRß), together with circulating tumor DNA analysis to evaluate tumor mutational burden (TMB). RESULTS: Although most TAA-specific CD8(+) T cells could be tracked longitudinally, several TAA-specific CD8(+) T cells were detected de novo after irradiation, but viral-specific CD8(+) T cells did not show obvious changes during treatment, indicating potential irradiation-driven antigen spreading. Irradiation was associated with phenotypical changes of TAA-specific CD8(+) T cells towards higher expression of killer cell lectin-like receptor subfamily G, member 1, human leukocyte antigen D-related antigen, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain, CD160, and CD45RO together with lower expression of CD27 and CD127. Of importance, TAA-specific CD8(+) T cells in non-progressors frequently showed a phenotype of CD45RO(+)CD27(+)CD127(+) central memory T cells compared with those in progressors. TCRß clonality (inverted Pielou's evenness) increased and TCRß diversity (Pielou's evenness and Diversity Evenness score) decreased during treatment in progressors (p=0.029, p=0.029, p=0.012, respectively). TMB score was significantly lower in non-progressors after irradiation (p=0.023). CONCLUSION: Oligo-fractionated irradiation induces an immune-modulating effect with potential antigen spreading and the combination of radiotherapy and nivolumab may be effective in a subset of patients with gastric cancer.