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Introduction Three randomized controlled trials have resulted in extremely extensive application of the strategy of using neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) for patients with advanced epithelial ovarian cancer in Japan. This study aimed to evaluate the status and effectiveness of treatment strategies using NAC followed by IDS in Japanese clinical practice. Patients and methods We conducted a multi-institutional observational study of 940 women with Federation of Gynecology and Obstetrics (FIGO) stages III–IV epithelial ovarian cancer treated at one of nine centers between 2010 and 2015. Progression-free survival (PFS) and overall survival (OS) were compared between 486 propensity-score matched participants who underwent NAC followed by IDS and primary debulking surgery (PDS) followed by adjuvant chemotherapy. Results Patients with FIGO stage IIIC receiving NAC had a shorter OS (median OS: 48.1 vs. 68.2 months, hazard ratio [HR]: 1.34; 95% confidence interval [CI] 0.99–1.82, p = 0.06) but not PFS (median PFS: 19.7 vs. 19.4 months, HR: 1.02; 95% CI: 0.80–1.31, p = 0.88). However, patients with FIGO stage IV receiving NAC and PDS had comparable PFS (median PFS: 16.6 vs. 14.7 months, HR: 1.07 95% CI: 0.74–1.53, p = 0.73) and OS (median PFS: 45.2 vs. 35.7 months, HR: 0.98; 95% CI: 0.65–1.47, p = 0.93). Conclusions NAC followed by IDS did not improve survival. In patients with FIGO stage IIIC, NAC may be associated with a shorter OS.

Objectives RA is an autoimmune disease characterized by destructive polyarthritis. CD4+ T cells are pivotal to its pathogenesis, and our previous study revealed the expression of fibroblast growth factor receptor 1 (FGFR1) is modulated by MTX treatment in CD4+ T cells of RA patients; however, the roles of FGFR1 in CD4+ T cells in the pathogenesis of RA is unclear. Therefore, in this study, we aimed to characterize FGFR1-positive CD4+ T cells in RA patients. Methods The abundance of FGFR1-positive CD4+ T cells in peripheral blood and synovium was determined. Single-cell RNA sequencing (scRNA-seq) was performed on synovial CD4+ T cells to characterize FGFR1-positive cells. In addition, T cell activation status and cytokine production were determined using flow cytometry. Results The percentage of FGFR1-positive CD4+ T cells in the peripheral blood was higher in RA patients than in healthy controls (P =0.0035). They were also present in the synovium of active RA patients. The results of scRNA-seq revealed that peripheral Th (Tph) cells preferentially expressed FGFR1. Additionally, these FGFR1-positive Tph cells displayed a terminal effector cell phenotype. Consistent with this finding, FGFR1-positive CD4+ T cells in peripheral blood expressed IL-21 and IFN-γ. Conclusion Our study provides evidence that FGFR1 marks terminal effector Tph cells in patients with RA.

Anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (MDA5-DM) is frequently complicated with rapidly progressive-interstitial lung disease (RP-ILD). The prognosis of MDA5-DM with RP-ILD is mostly poor despite intensive treatment with a combination of high-dose glucocorticoids and single conventional immunosuppressants. It was reported that the triple therapy (high-dose glucocorticoids, cyclophosphamide and tacrolimus) was more effective than a combination of high-dose glucocorticoids and stepwise addition of immunosuppressants. In addition, the efficacy of tofacitinib 10 mg/day for MDA5-DM with RP-ILD refractory to the triple therapy was suggested. However, the effect of those therapies was evaluated only in comparison to the historical control. Moreover, more importantly, there are still refractory patients even if treated with those therapies. In this case series, we report six MDA5-DM cases with RP-ILD in which the dose of tofacitinib was increased from 10 mg to 20 mg/day due to poor response to the triple therapy, followed by tofacitinib 10 mg/day. Four of six patients improved after dose escalation of tofacitinib, while two non-responders died. All six patients developed at least one infection including five cases of cytomegalovirus reactivation, one pulmonary aspergillosis, one herpes zoster and one herpes simplex keratitis. These cases suggest that the dose escalation of tofacitinib can be an option for MDA5-DM patients refractory to 10 mg/day of tofacitinib and other immunosuppressants although the risk of infection is a concern. The risk–benefit balance of the dose escalation of tofacitinib should be carefully assessed in each case.

This prospective multi-central randomized phase II trial evaluated the efficacy and safety of oral Vitamin B12 500 μg/day replacement compared with oral Vitamin B12 1,500 μg/day in patients with Vitamin B12 deficiency after total gastrectomy for gastric cancer.Patients were randomly assigned to receive oral Vitamin B12 500 μg/day or Vitamin B12 1,500 μg/day in a 1:1 ratio with a minimization method. The primary endpoint was the incidence of a normal serum Vitamin B12 level at three months after treatment.From January 2018 to December 2021, 3 institutions collaborated with the present study, and 74 patients were registered from these 3 institutions. The study was prematurely closed due to poor accrual after reaching almost 50% of its goal. Among the 74 recruited patients, 36 were allocated to the Vitamin B12 500 μg/day arm and 38 to Vitamin B12 1,500 μg/day arm. The incidences of patients with a normal Vitamin B12 level at 3 months (serum Vitamin B12 level200 pg/ml) were 91.7% (33/36) in the Vitamin B12 500 μg/day arm and 100% (38/38) in the Vitamin B12 1,500 μg/day arm (p=0.3587). The types of clinical symptoms with Vitamin B12 deficiency that improved with Vitamin B12 treatment and the degree of improvement were also similar.Although the primary endpoint of the present study was not met, it was found that oral Vitamin B12 500 μg/day replacement is as effective and safe as oral Vitamin B12 1,500 μg/day replacement for Vitamin B12 deficiency.

We aimed to evaluate the induction, anesthesia, and cardiorespiratory effects of intramuscular (IM) anesthetic protocol with alfaxalone following premedication with low-dose medetomidine, butorphanol, or a combination of both (medetomidine–butorphanol) in dogs. Six healthy beagles were administered 1, 2.5, or 5 mg/kg alfaxalone IM following premedication with low-dose medetomidine (5 µg/kg; MA-IM), butorphanol (0.3 mg/kg; BA-IM), or medetomidine-butorphanol (5 µg/kg and 0.3 mg/kg, respectively; MBA-IM). Each dog received 9 treatments with minimum 7-day washout period between treatments. Dogs were allowed to breath room air during anesthetic induction. We attempted endotracheal intubation after alfaxalone administration. Alfaxalone produced a dose-dependent anesthetic effect in each anesthetic protocol. Intubation was achieved in 4 out of 6 dogs that received MA-IM and BA-IM with 2.5 mg/kg alfaxalone and in all dogs that received MBA-IM with 1, 2.5, and 5 mg/kg alfaxalone. The median durations [minimum–maximum] of accepting intubation were 79 [0–89], 97 [84–120], and 117 [84–217] min, respectively. Hypotension (mean arterial blood pressure

To compare the anesthetic effects after intravenous administration of alfaxalone or propofol without premedication, either alfaxalone (5 mg/kg) or propofol (10 mg/kg) was administered intravenously over 120 sec in 6 cats. Each cat received the alternate treatment at least a 7-day interval. Anesthetic effects (tolerance of intubation, behavior changes and neurodepressive score) and physiological parameters were evaluated. Both treatments produced a rapid loss of consciousness, no apnea, and physiological parameters were maintained within clinically acceptable ranges apart from transient hypoxemia. The degree of hypoxemia was greater after the propofol treatment compared with the alfaxalone treatment. During the recovery period, more adverse events (ataxia, muscular tremors) were observed after the alfaxalone treatment compared with the propofol treatment.

Difficulty in airway management during anesthesia was noted in a 10-year-old, castrated, male Pekingese dog and a 13-year-old male French Bulldog. They showed strong resistance during tracheal tube insertion through the subglottic lumen. Therefore, the airway was secured by using a small endotracheal tube or supraglottic airway device. Computed tomography scan revealed a markedly narrower vertical dimension of the cricoid cartilage compared to that seen in common brachycephalic breeds. Posterior glottis was relatively more accessible for translaryngeal intubation in the present cases. Our findings showed that brachycephalic airway syndrome may be associated with narrow cricoid cartilage. To the best of our knowledge, this is the first clinical case report of airway management during anesthesia in dogs with narrow cricoid cartilage.

Background: Problems associated with using inhalational anaesthesia are numerous in veterinary anaesthesia practice. Decreasing the amount of used inhalational anaesthetic agents and minimising of cardiorespiratory disorders are the standard goals of anaesthetists. Objective: This experimental study was carried out to investigate the sparing effect of intravenous tramadol, lidocaine, dexmedetomidine and their combinations on the minimum alveolar concentration (MAC) of sevoflurane in healthy Beagle dogs. Methods: This study was conducted on six beagle dogs. Sevoflurane MAC was determined by the tail clamp method on five separate occasions. The dogs received no treatment (control; CONT), tramadol (TRM: 1.5 mg kg(-1) intravenously followed by 1.3 mg kg(-1) h(-1)), lidocaine (LID: 2 mg kg(-1) intravenously followed by 3 mg kg(-1) h(-1)), dexmedetomidine (DEX: 2 mu g kg(-1) intravenously followed by 2 mu g kg(-1) h(-1)), and their combination (COMB), respectively. Cardiorespiratory variables were recorded every five minutes and immediately before the application of a noxious stimulus. Results: The COMB treatment had the greatest sevoflurane MAC-sparing effect (67.4 +/- 13.9%) compared with the other treatments (5.1 +/- 25.3, 12.7 +/- 14.3, and 40.3 +/- 15.1% for TRM, LID, and DEX treatment, respectively). The cardiopulmonary variables remained within the clinically acceptable range following COMB treatment, although the mean arterial pressure was higher and accompanied by bradycardia. Conclusions: Tramadol-lidocaine-dexmedetomidine co-infusion produced a remarkable sevoflurane MAC-sparing effect in clinically healthy beagle dogs and could result in the alleviation of cardiorespiratory depression caused by sevoflurane. Cardiorespiratory variables should be monitored carefully to avoid undesirable side effects induced by dexmedetomidine.

Electrochemical conversion of CO2 into fuels or chemical feedstocks is one of the most promising methods for solving the problems of both fossil fuel depletion and global warming. Herein, we report...

Outcomes of immune checkpoint inhibitor (ICI) rechallenge in NSCLC remain uncertain. This study estimated the safety and efficacy of ICI rechallenge and compared rechallenge benefit among different reasons of initial ICI discontinuation in NSCLC.PubMed, EMBASE, and Cochrane Library were searched for studies on NSCLC retreated with ICI. Immune-related adverse events (irAEs), overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) at initial ICI and rechallenge were analyzed.A total of 15 studies including 442 patients between 2018 and 2022 were eligible for meta-analysis. The incidence of grade 3 or 4 irAE was lower in rechallenge than initial ICI (8.6% versus 17.8%,ICI rechallenge had less severe toxicity than initial ICI treatment. Patients undergoing disease progression after ICI cessation or ICI discontinuation owing to irAE are more likely to benefit from ICI rechallenge in NSCLC.

Background The significance of blood culture for acute cholecystitis remains unclear. Methods A retrospective cohort study was conducted on patients who underwent emergency cholecystectomy at Hyogo Prefectural Amagasaki General Medical Center to examine the clinical impact of bloodstream infection (BSI), focusing on the association of BSI with bactibilia and severity grade based on the Tokyo guidelines 2018 (TG18). Results Among 177 patients included in the study, 32 had positive and 145 had negative BSI. Significant differences were observed between the positive and negative BSI in terms of age, body mass index (BMI), the American Society of Anesthesiologists physical status (ASA-PS) and TG18 severity score. The odds ratios of BSI for patients aged ≥72 years, with a BMI of ≤21.8, an ASA-PS of ≥3E, and grade III acute cholecystitis were 3.45, 3.23, 2.43 and 4.51, respectively. In the multivariate analysis, lower BMI and grade III were significantly associated with BSI with odds ratios of 2.53 (95% confidence interval: 1.07-6.21, P = .037) and 3.03 (95% confidence interval: 1.02-8.82, P = .041). Bacterial species that could not be isolated in the bile culture alone were identified in blood culture on 10 (38.5%) of 26 patients. Conclusions Bloodstream infection is associated with grade III acute cholecystitis. Blood culture enables the identification of bacteria that cannot be isolated in bile culture. Blood culture should be obtained for patients with grade III acute cholecystitis who undergo emergency cholecystectomy.

The Japan Atomic Energy Agency's accelerator-driven subcritical system (JAEA-ADS) proposes the reduction of nuclear waste through the transmutation of minor actinides. The JAEA-ADS drives a 30-MW proton beam to a spallation target to produce neutrons for a subcritical 800-MWth reactor. The beam must be transported from the end of the linear accelerator (linac) to the target located inside the reactor core with high beam power stability and low peak density to ensure beam window integrity, which is a primary concern for the ADS project. Additionally, the design of the beam transport to the target (BTT) must be compatible with the established reactor design, and the elements that comprise the BTT must facilitate the maintenance and replacement of the fuel and the beam window. To this end, a robust-compact BTT design was developed through massive multiparticle simulations. First, the beam optics was optimized to guarantee beam window feasibility requirements by providing a low peak density of less than 0.3 μA/mm2. Then, beam stability was evaluated and improved by a simultaneous application of input beam and element errors. The input beam errors were based on the beam degradation obtained by implementing fast fault compensation in the linac, which is a key strategy to attain high-reliability operation. The results show that the BTT design fulfills reactor and beam window requirements for JAEA-ADS.

In this paper, photovoltaics (PV) outputs are not only limited constantly but also controlled by bidirectional communications to compensate short period power fluctuations. In this case, if qualities of communication systems are not high, communication delays may not be ignored. The effect of communication delays is evaluated. If communication delays are not very small, a system reaches a stability limit, and a PV output may oscillate continuously. Then, a compensation method of them is proposed. The compensation method uses a disturbance observer. In this method, it is a merit that models of communication delays are not necessary and only a PV output model is necessary. It is found that the proposed method can compensate communication delays to some extent by simulating step responses. Furthermore, compensation of short period power fluctuations in a micro grid is considered by using the proposed method. Short period power fluctuation may be reduced by the compensation method of communication delays.

Background Delayed arterial hemorrhage after pancreaticoduodenectomy is a life-threatening complication. There are no reports about infected aneurysms of the superior mesenteric artery after pancreaticoduodenectomy without clinically relevant pancreatic fistula. Case presentation A 78-year-old woman with borderline resectable pancreatic ductal adenocarcinoma involving the superior mesenteric arterial nerve plexus underwent pancreaticoduodenectomy with en bloc resection of the superior mesenteric vein and the superior mesenteric arterial nerve plexus after neoadjuvant chemotherapy. On postoperative day 14, she had bacteremia and sudden fever with chills. During the postoperative course, macroscopic abscesses or distinct infectious signs, including pancreatic fistula or bile fistula, were not present, but pylephlebitis was observed. After the antimicrobial treatment course, the patient was discharged. After 17 days, she was hospitalized for melena. Contrast-enhanced computed tomography showed a ruptured aneurysm of the superior mesenteric artery into the small intestine without a major intraabdominal abscess. E. coli was isolated from blood cultures. The patient was diagnosed with a ruptured infected aneurysm of the superior mesenteric artery. She was treated successfully with a covered stent by the cardiology team. There was no recurrence of bleeding at the 4-month follow-up, and the stent was patent in all subsequent computed tomography scans. Conclusions Endovascular repair using a covered stent was effective in palliating acute bleeding from an infected aneurysm of the superior mesenteric artery.

Robenacoxib is a novel nonsteroidal anti-inflammatory drug approved for dogs. The present study aimed to evaluate influences of sevoflurane anesthesia on the distribution of robenacoxib in dogs. Ten healthy beagle dogs (1 to 11 years old, 9.3 to 14.3 kg body weight, 6 males and 4 females) were subcutaneously administered robenacoxib (2 mg/kg) under conscious condition or sevoflurane anesthesia inhaled a 1.3-fold predetermined individual minimum alveolar concentration of sevoflurane at a 28-day interval. The dogs under sevoflurane anesthesia were also mechanically ventilated and received fluid-therapy. On each occasion, serum samples were collected from the dogs before and at 5, 15, 30, 60, 120, 180, and 240 min after the robenacoxib administration. Serum robenacoxib concentration was measured by a liquid chromatography-tandem mass spectrometry. Maximum serum concentration of robenacoxib (C_) was 2.2 µg/ml [range: 1.2-4.6] (median [range: minimum-maximum]) and time of C_ (T_) was 90 min [range: 60-120] in the conscious dogs. In the sevoflurane-anesthetized dogs, the C_ significantly declined (1.3 µg/ml [range: 0.8-1.4], P=0.008) and T_ was delayed (120 min [range: 120-240], P=0.018) compared with those in the conscious dogs. The serum robenacoxib concentration at 240 min (C_) decreased to 0.5 µg/ml [range: 0.2-0.9] in the conscious dogs, while it remained higher in the sevoflurane-anesthetized dogs (1.0 µg/ml [range: 0.3-1.4], P=0.011). In conclusion, the anesthetic procedure with sevoflurane, mechanically ventilated, and received fluid-therapy might affect the pharmacokinetics of subcutaneously administered robenacoxib in dogs.

The anesthetic and cardiorespiratory effects of xylazine-alfaxalone combination were evaluated in calves. Six calves (age: 6–9 months old; weight: 114–310 kg) were anesthetized with intravenous alfaxalone 15 min after administration of intramuscular saline (0.5 ml/100 kg) or xylazine (0.1 mg/kg; 0.5 ml/100 kg of a 2% xylazine solution). Anesthesia induction was smooth and orotracheal intubation was achieved in all calves. The calves anesthetized with xylazine-alfaxalone required a smaller induction dose of alfaxalone (1.23 ± 0.17 mg/kg, P=0.010) and accepted endotracheal intubation for a significantly longer period (16.8 ± 7.2 min, P=0.022) than the calves anesthetized with alfaxalone alone (2.28 ± 0.65 mg/kg 7.3 ± 1.6 min). At 5 min after induction, tachycardia (heart rate: 166 ± 47 beats/min of heart rate), hypertension (mean arterial blood pressure: 147 ± 81 mmHg) and hypoxemia (partial pressure of arterial blood oxygen [PaO_2]: 43 ± 10 mmHg) were observed in the calves anesthetized with alfaxalone alone, whereas hypoxemia (PaO2: 47 ± 7 mmHg) and mild hypercapnia (partial pressure of arterial blood carbon dioxide: 54 ± 5 mmHg) were observed in the calves anesthetized with xylazine-alfaxalone. Premedication with xylazine provided a sparing effect on the induction dose of alfaxalone and a prolongation of anesthetic effect. Oxygen supplementation should be considered to prevent hypoxemia during anesthesia.

Spontaneous coronary artery dissection (SCAD) is rare, but it frequently presents as acute myocardial infarction. It is frequently fatal and most cases are diagnosed at autopsy. We herein present the case of a 65-year-old woman with ST-elevation and myocardial infarction due to SCAD. Optical coherence tomography (OCT) helped us to confirm the diagnosis. The information on the intravascular morphology provided by OCT imaging is much more detailed in comparison to that provided by coronary angiography (CAG) and intravascular ultrasound (IVUS).

For examining pig ovaries, which have complex structures, laparoscopy is a useful technique, but requires general anesthesia; therefore, it cannot be performed repeatedly within a short period of time. We report a transvaginal endoscopy-based technique for conducting ovarian examinations without general anesthesia. Sows were sedated in pig stalls. Using a colonoscope, the vaginal wall was punctured with a trocar. To avoid the trocar being caught in the broad ligament of the uterus or the connective tissue around the vagina, the trocar was inserted close to the external uterine os and between the 2:00 and 3:00 or the 9:00 and 10:00 positions (in a clockwise direction). Then, a urethroscope was inserted into the abdomen, and an examination was carried out after the ovaries had been moved towards the urethroscope camera via rectal palpation. This less invasive procedure may allow repeated examinations and will increase our understanding of ovarian dynamics in pigs.

Changes in stroke volume variation (SVV) and pulse pressure variation (PPV) in response to fluid infusion were experimentally evaluated during vecuronium infusion and sevoflurane anesthesia in 5 adult, mechanically ventilated, euvolemic, beagle dogs. Sequential increases in central venous pressure (CVP; 3–7[baseline], 8–12, 13–17, 18–22 and 23–27 mmHg) were produced by infusing lactated Ringer’s solution and 6% hydroxyethyl starch solution. Heart rate (beats/min), right atrial pressure (RAP, mmHg), pulmonary arterial pressure (PAP, mmHg), pulmonary capillary wedge pressure (PCWP, mmHg), transpulmonary thermodilution cardiac output (TPTDCO, l/min), stroke volume (SV, ml/beat), arterial blood pressure (ABP, mmHg), extravascular lung water (EVLW, ml), pulmonary vascular permeability index (PVPI, calculated), SVV (%), PPV (%) and systemic vascular resistance (SVR, dynes/sec/cm^5) were determined at each predetermined CVP range. Heart rate (P=0.019), RAP (P