Effects of oral administration of nonselective Trk inhibitor on bladder overactivity in rodent models of prostatic inflammation.

BACKGROUND: Our research focused on the assessment of the impact of systemic inhibition of Trk receptors, which bind to nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), on bladder hypersensitivity in two distinct rodent models of prostatic inflammation (PI). METHODS: Male Sprague-Dawley rats were divided into three groups (n = 6 each): the control group (no PI, vehicle administration), the untreated group (PI, vehicle administration), and the treated group (PI, nonselective Trk inhibitor, GNF 5837, administration). PI in rats was induced by a intraprostatic injection of 5% formalin. Posttreatment, we carried out conscious cystometry and a range of histological and molecular analyses. Moreover, the study additionally evaluated the effects of a nonselective Trk inhibitor on bladder overactivity in a mouse model of PI, which was induced by prostate epithelium-specific conditional deletion of E-cadherin. RESULTS: The rat model of PI showed upregulations of NGF and BDNF in both bladder and prostate tissues in association with bladder overactivity and inflammation in the ventral lobes of the prostate. GNF 5837 treatment effectively mitigated these PI-induced changes, along with reductions in TrkA, TrkB, TrkC, and TRPV1 mRNA expressions in L6-S1 dorsal root ganglia. Also, in the mouse PI model, GNF 5837 treatment similarly improved bladder overactivity. CONCLUSIONS: The findings of our study suggest that Trk receptor inhibition, which reduced bladder hypersensitivity and inflammatory responses in the prostate, along with a decrease in overexpression of Trk and TRPV1 receptors in sensory pathways, could be an effective treatment strategy for male lower urinary tract symptoms associated with PI and bladder overactivity.

Criteria for immediate extubation after pediatric liver transplantation in a single pediatric liver transplant center in Japan.

Immediate extubation (IE) following liver transplantation (LT) has become the standard practice, even for pediatric patients. However, no preoperative or postoperative case selection protocols for IE are currently available. We have developed selection criteria for IE following pediatric LT. The aim of this study is to assess the safety and effectiveness of these selection criteria and anesthetic management protocol implemented in our hospital for IE after pediatric LT. METHOD: This was a retrospective study. The records of all cases undergoing LT in our center from January 2016 to December 2020 were collected. We excluded cases > 18 years old at the time of LT. Enrolled cases were divided into two groups: cases with immediate extubation (IE) or without immediate extubation (NIE). We compared preoperative conditions, intraoperative management, and postoperative courses. Finally, we classified NIE group patients into cases extubated at postoperative day 1 (early; E-NIE) and others (delayed; D-NIE) and compared their underlying diseases and postoperative courses. RESULTS: In the IE group, there were 81 cases, while the NIE group consisted of 185 cases. All patients in the IE group were successfully extubated without any instances of re-intubation due to respiratory failure. Within the E-NIE group, comprising 130 cases, all patients were ultimately extubated without the need for tracheostomy. However, in the D-NIE group, which encompassed 53 cases, seven patients required tracheostomy. CONCLUSION: In our center, the implementation of our anesthesia management protocol and the use of pre/postoperative case selection criteria have allowed for the safe practice of IE following pediatric LT. However, it should be noted that patients who cannot be extubated by Postoperative Day 1 (POD1) may be at an increased risk of requiring a tracheostomy. When contemplating IE, it is crucial to take into account the disease-specific physiological aspects and surgical site situations.

Impact of preoperative bloodstream infection on outcomes of pediatric liver transplant recipients treated for acute liver failure.

BACKGROUND: Acute liver failure (ALF) is a component of multisystem organ failure that causes severe liver dysfunction in patients without underlying chronic liver disease. The patients with ALF are prone to have infections, including bacteremia. However, studies of the infectious impact for post liver transplantation (LT) in pediatric ALF are limited. We aimed to evaluate our current practice for pediatric LT cases of ALF with preoperative bacteremia. METHODS: The records of all patients under 18 years old undergoing LT for ALF in our center from November 2005 to December 2021 were collected. They were divided into two groups: those with a preoperative bloodstream infection (BSI) and those without (NBSI). We compared the preoperative status and also reviewed the details of the BSI group. Intraoperative course and postoperative outcomes were also compared. RESULTS: There were 19 BSI patients and 66 NBSI patients. One BSI case was detected on the day of LT. This patient had no changes in vital signs and general condition. After evaluation and therapeutic intervention by pediatric infectious disease specialists, LT was performed on the same day. Five cases developed septic shock at the time of detection of BSI. All BSI patients were in stable condition on the operation day with proper interventions. There were no significant differences in mortality and hospital stay between both groups. CONCLUSIONS: LT might be able to be performed for pediatric ALF even with positive blood cultures. In addition, appropriate therapeutic intervention by specialists and patient's stable condition before LT are essential.

How the brain can be trained to achieve an intermittent control strategy for stabilizing quiet stance by means of reinforcement learning.

The stabilization of human quiet stance is achieved by a combination of the intrinsic elastic properties of ankle muscles and an active closed-loop activation of the ankle muscles, driven by the delayed feedback of the ongoing sway angle and the corresponding angular velocity in a way of a delayed proportional (P) and derivative (D) feedback controller. It has been shown that the active component of the stabilization process is likely to operate in an intermittent manner rather than as a continuous controller: the switching policy is defined in the phase-plane, which is divided in dangerous and safe regions, separated by appropriate switching boundaries. When the state enters a dangerous region, the delayed PD control is activated, and it is switched off when it enters a safe region, leaving the system to evolve freely. In comparison with continuous feedback control, the intermittent mechanism is more robust and capable to better reproduce postural sway patterns in healthy people. However, the superior performance of the intermittent control paradigm as well as its biological plausibility, suggested by experimental evidence of the intermittent activation of the ankle muscles, leaves open the quest of a feasible learning process, by which the brain can identify the appropriate state-dependent switching policy and tune accordingly the P and D parameters. In this work, it is shown how such a goal can be achieved with a reinforcement motor learning paradigm, building upon the evidence that, in general, the basal ganglia are known to play a central role in reinforcement learning for action selection and, in particular, were found to be specifically involved in postural stabilization.

Triglyceride/high-density lipoprotein cholesterol ratio may be a better index of cardiometabolic risk in women than in men in Japan.

BACKGROUND AND AIMS: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts. METHODS AND RESULTS: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis. CONCLUSION: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations.

Association of Higher N-3 Polyunsaturated Fatty Acid Consumption and Aerobic Exercise with Lower Neutrophil-to-Lymphocyte Ratio: Implications of Anti-Atherosclerotic Effect of Fish Consumption.

INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker. METHODS: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey. RESULTS: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits. CONCLUSION: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk.

Anesthesia management in a child with mucopolysaccharidosis and toxic epidermal necrolysis: A case report.

Toxic epidermal necrolysis and mucopolysaccharidosis are both rare diseases that pose significant airway maintenance challenges to anesthesiologists. In this report, we describe the anesthesia management in a 4-year-old male with mucopolysaccharidosis type II who developed toxic epidermal necrolysis and presented for ophthalmic surgical procedures. Combined use of propofol and ketamine with the support of high-flow nasal oxygen enabled adequate analgesia and sedation while maintaining spontaneous ventilation and airway patency. The strategy presented in this report may contribute to enhancing the safety of sedation in spontaneously breathing children with abnormal airways.

A randomized, double-blind, dose-controlled study of the use of dexmedetomidine alone for procedural sedation of children and adolescents undergoing MRI scans.

BACKGROUND: Dexmedetomidine is a selective α2-adrenergic agonist originally approved for sedation of adults in the intensive care unit and subsequently approved for procedural sedation in adults undergoing medical procedures. Dexmedetomidine is widely used off-label for procedural sedation in children. AIMS: To evaluate efficacy and safety of monotherapy dexmedetomidine for magnetic resonance imaging procedural sedation of children ≥1month-<17years across three ascending doses. METHODS: Randomized, double-blind, dose-ranging study of procedural sedation recruited patients at USA and Japanese sites from February 2020 to November 2021. Patients were stratified into Cohort A (≥1month-<2years) or Cohort B (≥2-<17years). Cohort A loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.0 mcg/kg/1.0 mcg/kg/h, and 1.5 mcg/kg/1.5 mcg/kg/h. Cohort B loading doses/maintenance infusions: 0.5 mcg/kg/0.5 mcg/kg/h, 1.2 mcg/kg/1.0 mcg/kg/h, and 2.0 mcg/kg/1.5 mcg/kg/h. Primary endpoint was percentage of overall patients completing MRI without rescue propofol at the high versus low dose. Key secondary endpoint was percentage in each age cohort who did not require propofol at the high versus low dose. RESULTS: One hundred twenty-two patients received high- (n = 38), middle- (n = 42), or low-dose (n = 42) dexmedetomidine. A greater percentage completed MRI without propofol rescue, while receiving high- versus low-dose dexmedetomidine (24/38 [63.2%] vs. 6/42 [14.3%]) (odds ratio: 10.29, 95% confidence interval: 3.47-30.50, p < .001). Similar results were seen in both age cohorts. The most common adverse events were bradypnea, bradycardia, hypertension, and hypotension, and the majority were of mild-to-moderate severity. CONCLUSIONS: Dexmedetomidine was well tolerated. The high dose was associated with meaningfully greater efficacy compared with lower doses. Based on these results, the recommended starting dose for procedural sedation in children ≥1month-<2years is loading dose 1.5 mcg/kg/maintenance infusion 1.5 mcg/kg/h; children ≥2-<17years is loading dose 2.0 mcg/kg/maintenance infusion 1.5 mcg/kg/h.

Aortic valve area index values of Trifecta implants correlate with energy loss and increased valve stress.

Biological valves are becoming more frequently used in aortic valve replacement. While several reports have evaluated the performance of biological valves, echocardiography studies during exercise stress remain scarce. Furthermore, no current reports compare rate changes in the aortic valve area of biological valves under increased exercise load. Here, we performed exercise stress echocardiography in patients after AVR with Trifecta or Inspiris valves and compared the rates of change in aortic valve areas (AVA). In addition, hydrodynamic analysis at rest was conducted with four-dimensional flow magnetic resonance imaging (4D-flow MRI). Exercise stress echocardiography was performed in seven Trifecta and seven Inspiris patients who underwent AVR at our hospital while 4D flow MRI was performed in all but two Trifecta cases. Comparing the percentage change in AVA when loaded to 25 W versus at rest, Trifecta was greater than Inspiris (28.7 ± 36.0 vs - 0.8 ± 12.4%). The smaller AVA at rest was considered causative for this. Meanwhile, Trifecta systolic energy loss in the prosthetic valve segment on 4D-flow MRI (97.5 ± 35.9 vs 52.7 ± 25.3 mW) was higher than Inspiris. The opening of the Trifecta valve was considered to be restricted at rest and this may reflect the current reports of early valve degradation requiring reoperation. Taken together, we observed that the Trifecta design may promote faster wear due to higher valve stress.

Higher frequency of fish intake and healthy lifestyle behaviors may be associated with a lower platelet count in Japan: Implication for the anti-atherosclerotic effect of fish intake.

BACKGROUND: Habitual fish intake and healthier lifestyles are associated with a lower risk of atherosclerotic cardiovascular disease (ASCVD). Higher platelet counts (PLCs) are reportedly associated with higher ASCVD events. We aimed to investigate the association between fish intake and lifestyle with PLCs. METHODS: We conducted a cross-sectional study in a cohort of 9329 participants (average age: 46.9 ± 12.9 years; 58.9% men) with no history of ASCVD registered at the Health Planning Center of Nihon University Hospital in 2019. RESULTS: The average fish intake frequency was 2.15 ± 1.28 days/week. As fish intake frequency increased (0, 1, 2, 3, 4, 5, 6, and 7 days), PLC decreased significantly (p < 0.0001). Multivariable logistic regression analysis showed that higher fish intake frequency tended to be a determinant of lower PLC. Aerobic exercise habits and sleep duration were independent negative determinants of PLC. Cigarette smoking habits were a positive independent determinant of PLC. Furthermore, with increasing fish intake frequency, the proportion of participants with habitual aerobic exercise, non-smoking habits, and longer sleep duration increased (p < 0.0001 for all). Higher n-3 polyunsaturated fatty acid (n-3 PUFA), calculated based on data from the Japanese National Health and Nutrition Survey, intake was associated with a lower PLC. CONCLUSION: Higher fish intake and healthier lifestyle behaviors may be comprehensively associated with lower PLCs. The intake of N-3 PUFA with anti-inflammatory effects, rich in fish, may also be related to the lower PLC. This association may explain the preventive effects of fish intake on ASCVD risk.

Habitual fish consumption and healthy lifestyle behaviours may be associated with higher total serum bilirubin level and anti-inflammatory activity: a cross-sectional study.

Habitual fish consumption and a healthy lifestyle are associated with lower atherosclerotic CVD (ASCVD) risk. Mildly elevated bilirubin, an end product of Hb metabolism, may be associated with anti-inflammatory effects, suppressing ASCVD risk. No data exist on the relationship between fish consumption, total serum bilirubin (TSB) and inflammation in clinical settings. We conducted a cross-sectional study between April 2019 and March 2020 in a cohort of 8292 participants (average age, 46·7 (sd 12·9) years and 58·9 % men) with no history of ASCVD and TSB concentrations < 2·0 mg/dl. Multiple stepwise regression analysis showed Hb concentrations were a solid positive determinant of TSB concentrations (ß = 0·302, P< 0·0001). Fish consumption (ß = 0·025, P= 0·019) and aerobic exercise (ß = 0·021, P= 0·043) were statistically weak but significantly positive determinants of TSB concentrations. Cigarette smoking negatively affected TSB concentrations (ß = −0·104, P< 0·0001). Moreover, with increasing fish consumption, the proportion of participants with a habit of cigarette smoking decreased, and that of participants who engaged in aerobic exercises increased (P< 0·0001 for both). Furthermore, as TSB concentrations increased, the leukocyte counts and C-reactive protein concentrations decreased (P< 0·0001 for both). In conclusion, despite the lesser relevance given to TSB concentrations than Hb concentrations, higher fish consumption and healthier lifestyle behaviours related to fish consumption habits may be additively or synergistically associated with higher TSB concentrations and anti-inflammatory activity, leading to attenuated ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.

Successful pediatric liver transplantation case with a positive SARS-CoV-2 test at the time of transplant.

AIM: We report a successful liver transplantation (LT) in a child with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. CASE PRESENTATION: A 3-year-old female patient with decompensated cirrhosis due to Alagille syndrome underwent a split LT with a left lateral segment graft. She had a history of SARS-CoV-2 infection 4 months before LT. She was exposed to SARS-CoV-2 after the decision for organ acceptance. We repeatedly confirmed the negative SARS-CoV-2 test by polymerase chain reaction (PCR) before LT. Liver transplantation was carried out in the negative pressure operational theater with full airborne, droplet, and contact precautions as the patient was considered to be within the incubation period of SARS-CoV-2. The SARS-CoV-2 PCR test became positive in the nasopharyngeal swab specimen at the operation. Remdesivir, the antiviral treatment, was held off due to potential hepatotoxicity and no exacerbation of COVID-19. She received tacrolimus and low-dose steroids per protocol. She remained SARS-CoV-2 positive on postoperative days (PODs) 1, 2, and 5. The presence of antibodies for SARS-CoV-2 at LT was confirmed later. On POD 53, she was discharged without any symptomatic infection. CONCLUSION: This case demonstrated that a positive SARS-CoV-2 result was not an absolute contraindication for a life-saving LT. Liver transplantation could be safely performed in a pediatric patient with asymptomatic COVID-19 and S-immunoglobulin G antibodies for SARS-CoV-2.

Prognostic risk stratification based on left ventricular mechanical dyssynchrony in patients at low or intermediate risk of major cardiac events using the J-ACCESS risk model.

There have been no reports on prognostic prediction and risk stratification based on stress phase bandwidth (SPBW), or a left ventricular (LV) mechanical dyssynchrony index, in patients with known or suspected stable coronary artery disease (CAD) at low or intermediate risk of major cardiac events (MCEs) using the J-ACCESS risk model. We retrospectively investigated 4,996 consecutive patients with known or suspected CAD who underwent rest 201Tl and stress 99mTc-tetrofosmin electrocardiogram (ECG)-gated single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) and followed up for 3 years to confirm their prognosis. MCE risk over 3 years was estimated using an equation based on that used in the J-ACCESS study. The composite endpoint was the onset of MCEs consisting of cardiac death, non-fatal myocardial infarction (MI), and severe heart failure requiring hospitalization. SPBW was calculated by phase analysis with the Heart Risk View-F software and its normal upper limit was set to 38°. Based on the estimated 3-year incidence of MCEs obtained from the J-ACCESS risk model, 4,123 of the 4,996 consecutive patients were classified as low (n = 2,653) or intermediate risk (n = 1,470) and they were analyzed for follow-up. During the follow-up, 153 patients experienced MCEs: cardiac death (n = 38), non-fatal MI (n = 45), and severe heart failure (n = 70). The results of the multivariate analysis showed age, estimated glomerular filtration rate (eGFR), stress LV ejection fraction, and stress SPBW to be independent predictors of MCEs. The actual 3-year MCE rate in patients at intermediate risk was significantly higher than in those at low risk (6.7% vs. 2.1%, P < 0.0001). However, the actual 3-year MCE rate in patients with abnormal SPBW (> 38°) was 4.0% and 9.2% in low- and intermediate-risk patients, respectively, which corresponded to intermediate and high risk. Kaplan-Meier analysis also showed significant risk stratification by normal SPBW values for both low- and intermediate-risk patients. LV mechanical dyssynchrony assessed with ECG-gated SPECT MPI is useful for risk stratification of known or suspected stable CAD patients at low or intermediate risk of MCEs and may help identify higher risk patients who could not be identified as being at risk based on J-ACCESS risk assessment.

Anesthesia management protocol for liver transplantation as treatment for ornithine transcarbamylase deficiency.

BACKGROUND: Ornithine transcarbamylase deficiency is an X-linked genetic disorder that induces accumulation of ammonia in the liver and is the most common urea cycle disorder. The clinical manifestation of ornithine transcarbamylase deficiency is hyperammonemia that causes irreversible neurological damage. Liver transplantation is a curative therapy for ornithine transcarbamylase deficiency. The aim of this study is to suggest, from our previous experience, an anesthesia management protocol of liver transplantation for ornithine transcarbamylase deficiency, particularly focused on liver transplantation for cases with uncontrolled hyperammonemia. METHOD: We retrospectively reviewed our anesthesia-related experience in all cases of liver transplantation for ornithine transcarbamylase deficiency in our center. RESULTS: Twenty-nine liver transplantation cases for ornithine transcarbamylase deficiency were found between November 2005 and March 2021 in our center. Of these, 25 cases were stable through the perioperative period. However, 2 cases with carrier donor graft had hyperammonemia after liver transplantation. Another two cases had uncontrolled hyperammonemia before liver transplantation, even with continuous hemodialysis. They underwent life-saving liver transplantation. Their metabolic status stabilized after the anhepatic phase. CONCLUSION: Liver transplantation for cases with uncontrolled hyperammonemia can be performed with proper management. Second, liver transplantation with carrier donors should be avoided because of the risk of postoperative recurrence.

Low billing rates for pediatric sedation fee on magnetic resonance imaging.

BACKGROUND: The 2018 revision of social insurance in Japan allows additional fees to be calculated for pediatric magnetic resonance imaging (MRI) that must be performed under sedation. The number and trend of actual claims since this revision was established is unknown. The aim of this study to investigate the use of the additional fees and any regional differences in the use. METHODS: To analyze the claims of additional fees for pediatric sedated MRI after the fiscal year (FY) 2018, the actual claims in inpatient and outpatient practice was analyzed using publicly-available data from the Ministry of Health, Labour and Welfare (MHLW). We analyzed the calculation rate for all MRI scans. Annual changes in the actual number and calculation rate were analyzed. The ratio of the number of additional fees to the overall number of pediatric radiological procedures was used to examine the geographic disparity. RESULTS: The number of calculations from FY 2018 to FY 2020 was available. In FY 2020, only 1347 additional fees were calculated, corresponding to 0.35% of the total number of MRI scans. The number of fees showed a decreasing trend. Most cases were in the 0-4 year age group; however, there were a few cases in the 10-14 year age group without such a decrease. The relative number of calculations by prefecture showed an up to 14-fold disparity. CONCLUSIONS: The requirements for sedation for pediatric MRI are strict, but they are not fully utilized. Measures such as relaxing the requirements for the fee are needed to make MRI-related sedation safer.

Impact of the hospital volume and setting on postoperative complications of surgery for gastroenterological cancers in a regional area of Western Japan.

PURPOSE: A research subgroup was established by the Japanese Society of Gastroenterological Surgery to improve the health care quality in the Chushikoku area of Western Japan. METHODS: The records of four surgical procedures were extracted from the Japanese National Clinical Database and analyzed retrospectively to establish the association between hospital characteristics, defined using a combination of hospital case-volume and patients' hospital travel distance, and the incidences of perioperative complications of ≥ Grade 3 of the Clavien-Dindo classification after gastroenterological surgery. RESULTS: This study analyzed 11,515 cases of distal gastrectomy for gastric cancer, 4,705 cases of total gastrectomy for gastric cancer, 4,996 cases of right hemicolectomy for colon cancer, and 5,243 cases of lower anterior resection for rectal cancer, with composite outcome incidences of 5.6%, 10.2%, 5.5%, and 10.7%, respectively. After adjusting for patient characteristics and surgical procedures, no association was identified between the hospital category and surgical outcomes. CONCLUSION: The findings of our study of the Chushikoku region did not provide positive support for the consolidation and centralization of hospitals, based solely on hospital case volume. Our grouping was unique in that we included patient travel distance in the analysis, but further investigations from other perspectives are needed.

Efficacy of neoadjuvant chemoradiotherapy followed by pancreatic resection for older patients with resectable and borderline resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The benefit of preoperative treatment followed by pancreatic resection in older patients with pancreatic ductal adenocarcinoma (PDAC) remains unclear. In this retrospective analysis of prospectively collected data, we evaluated the significance and safety of preoperative treatment followed by curative resection for older PDAC patients. METHODS: We evaluated 122 patients with resectable and borderline resectable PDAC who received neoadjuvant chemoradiotherapy (NACRT) followed by curative resection between 2009 and 2019. Changes in the prognostic nutritional indices during NACRT, surgical outcomes, and prognosis were compared between older (≥75 years, n = 44) and younger patients (<75 years, n = 78). RESULTS: The completion rate, adverse event rate, changes in prognostic nutritional indices during NACRT, and prognosis were similar between the groups. In multivariate analysis, an elevated C-reactive protein/albumin ratio (CRP/Alb) ≥ 33.1% during NACRT (p = 0.035) and no postoperative adjuvant chemotherapy (p = 0.041) were identified as significant predictors of overall survival. CONCLUSIONS: NACRT followed by pancreatic resection could be safely performed in older patients, with a similar prognosis as that of younger patients, despite an increased frequency of postoperative complications. Elevated CRP/Alb during NACRT and no postoperative adjuvant chemotherapy were poor prognostic factors for older patients.

[Infective Endocarditis Caused by Abiotrophia defectiva Required Double-valve Replacement Using the Manouguian Procedure].

A 39-year-old man was presented with infective endocarditis caused by Abiotrophia defectiva. Transesophageal echocardiography revealed extensive vegetation and destruction extending from the aortic valve to the aortic-mitral curtain and mitral valve accompanied by severe regurgitation of the aortic and mitral valves. After removal of vegetation, double-valve replacement were performed with double patch and mechanical prosthesis using the manouguian procedure.

Prediction of local tumor control and recurrence-free survival in patients with pancreatic cancer undergoing curative resection after neoadjuvant chemoradiotherapy.

BACKGROUND AND OBJECTIVES: There is little data on the correlation between the reduction in fluorodeoxyglucose positron emission tomography (FDG-PET) radioactive accumulation and carbohydrate antigen 19-9 (CA19-9) levels with pathological tumor responses (PTRs) and prognosis after neoadjuvant chemoradiotherapy (NACRT) for patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: This study was a retrospective analysis of prospectively collected data from 102 patients with resectable (R-) and borderline resectable (BR-) PDAC who received NACRT, followed by curative resection. Data were prospectively collected and compared between the responders and nonresponders to NACRT. RESULTS: Patients with 60% or more reduction in maximum standardized uptake value (SUVmax) on FDG-PET, with 75% or more reduction in CA19-9 levels, or with 50%-100% of tumor cells destroyed due to NACRT had significantly better recurrence-free survival (RFS) than each of the nonresponders (p = 0.028, <0.001, and 0.022, respectively). The reduction rates of SUVmax and CA19-9 levels were correlated with PTR. The combined evaluation of these biomarkers reflected RFS. CONCLUSIONS: Reduction rates of FDG uptake and CA19-9 levels were preoperative predictors of pathological response to NACRT. These biomarkers of local response had prognostic value in R-PDAC and BR-PDAC. The combined evaluation of these biomarkers allowed for reliable prediction of RFS after surgery.

Inadequate sleep duration may attenuate the anti-inflammatory effects of fish consumption in a healthy Japanese population: a cross-sectional study.

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (ß = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (ß = 0·059, P < 0·0001) or cigarette smoking (ß = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (ß = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (ß = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6­7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.