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Koki Tsuchiya,1 Koji Ishikawa,1 Soji Tani,1 Yusuke Oshita,2 Takuma Kuroda,1 Ryo Yamamura,1 Haruka Emori,1 Hiroshi Maruyama,1 Akira Matsuoka,1 Yoshifumi Kudo,1 Toshiyuki Shirahata,1 Tomoaki Toyone,1 Takashi Nagai,1 Katsunori Inagaki11Department of Orthopaedic Surgery, Showa University School of Medicine, Tokyo 142-8666, Japan; 2Department of Orthopaedic Surgery, Yamanashi Red Cross Hospital, Yamanashi, JapanAbstract: Discontinuation of denosumab during osteoporosis treatment leads to rapid loss of bone mineral density and induces a bone turnover rebound effect. Previous studies have reported analysis based on dual-energy X-ray absorptiometry scanning (DXA). Here, we report the first case involving analysis of three-dimensional bone mineral density and bone strength, measured by quantitative computed tomography (QCT) after discontinuation of denosumab. An 82-year-old woman who discontinued denosumab because of patient’s wish was administered the fifth dose after a gap of 14 months. Her bone mineral density evaluated by DXA and QCT, bone strength, and bone turnover marker levels showed significant rebound phenomenon. The levels of the cortical parameters of the hip were also decreased indicating an increased risk of femoral fractures after denosumab interruption. Our case highlights the increased risk of fractures after discontinuation of denosumab. Therefore, denosumab must be used judiciously without interruption in the dosage schedule.Keywords: lumbar spine, femoral neck, bone turnover markers, cortical bone, biomechanical analysis

This study examined the impact of the COVID-19 pandemic on men's ice hockey in Kanagawa prefecture. We investigated the number and type of penalties and injuries that occurred in men's ice hockey league games in Kanagawa between September 2018 and March 2023. In total, data from 734 games were analyzed, and data were compared between seasons. The average number of penalties per game was 5.93 in the 2018-2019 season, 5.66 in the 2019-2020 season, 4.96 in 2020-2021, and 4.40 in 2021-2022, 4.64 in the 2022-2023 season, indicating that the number of penalties decreased during the COVID-19 pandemic. However, the number of penalties involving the stick increased. Injuries during games also increased during the COVID-19 pandemic, from 0 in the 20182019 (175 games) and 2019-2020 (191 games) seasons to 1 case in the 2020-2021 (73 games) season, 6 cases in the 2021-2022 (119 games) season and 2 cases in the 2022-2023 (176 games) season. The increased number of injuries observed may have been due to the closure of ice rinks by the state of emergency, which restricted on-ice training. As players avoided contact to prevent the spread of COVID-19, penalties caused by contact play decreased, whereas those involving sticks increased. [ABSTRACT FROM AUTHOR]

In the use of anti-inflammatory compounds, sustained serum levels are thought to be related to drug efficacy. This study shows that frequent clinical administration of indomethacin can result in sustained serum levels of the drug and that food and antacid may have important modifying effects on serum indomethacin concentrations. After oral ingestion by fasting subjects, indomethacin rapidly appeared in the serum, usually reaching peak concentrations in 30 to 90 minutes. Food delayed and decreased the mean peak level; antacid delayed the peak and slightly enhanced subsequent concentrations. With multiple dose schedules plateau levels were reached after 24 hours. When a total daily dose of 150 mg was given as 25 mg every 4 hours peak concentrations were the same but fluctuations were smaller and average concentrations were higher than with a dosage of 50 mg every 8 hours. [ABSTRACT FROM PUBLISHER]

Abstract Background Bacteria integrate numerous environmental stimuli when generating cellular responses. Increasing numbers of examples describe how one two-component system (TCS) responds to signals detected by the sensor of another TCS. However, the molecular mechanisms underlying this phenomenon remain poorly defined. Results Here, we report a connector-like factor that affects the activity of the CpxR/CpxA two-component system in Salmonella enterica serovar Typhimurium. We isolated a clone that induced the expression of a cpxP-lac gene fusion from a high-copy-number plasmid pool of random Salmonella genomic fragments. A 63-amino acid protein, CacA, was responsible for the CpxA/CpxR-dependent activation of the cpxP gene. The CpxR-activated genes cpxP and spy exhibited approximately 30% and 50% reductions in transcription, respectively, in a clean cacA deletion mutant strain in comparison to wild-type. From 33 response regulator (RR) deletion mutants, we identified that the RssB regulator represses cacA transcription. Substitution mutations in a conserved -10 region harboring the RNA polymerase recognition sequence, which is well conserved with a known RpoS -10 region consensus sequence, rendered the cacA promoter RpoS-independent. The CacA-mediated induction of cpxP transcription was affected in a trxA deletion mutant, which encodes thioredoxin 1, suggesting a role for cysteine thiol-disulfide exchange(s) in CacA-dependent Cpx activation. Conclusions We identified CacA as an activator of the CpxR/CpxA system in the plasmid clone. We propose that CacA may integrate the regulatory status of RssB/RpoS into the CpxR/CpxA system. Future investigations are necessary to thoroughly elucidate how CacA activates the CpxR/CpxA system.

In Japan, priority of sewage works implementation has gradually beengiven to smaller communities. Sewage treatment processes for small communities must meet several requirements such as low construction and O-M cost, easy O-M, stable performance, and in some locations nitrogen and/or phosphorus removal as well as BOD and SS removal. With a view to achieving these requirements, the authors have been developinga novel anaerobic/aerobic filter process for simultaneous removal ofBOD, SS and nitrogen. In this process, an upflow anaerobic filter isfollowed by a nitrification tank using entrapped immobilized nitrifier pellets and an aerobic filter for the polishing process. In order to demonstrate this novel process in the field, a pilot plant with a capacity of 1.75 m3/d was installed in an existing sewage treatment plant near Tokyo in January, 1996. The target effluent qualities are BOD and T-N less than 10 mg/l respectively and SS less than5 mg/l. The pilot plant study has shown that the overall treatment performance of 96--97% in SS and BOD removal and 74--75% in T-N removal has been stably obtained under the conditions of 5.5 h in total retention time, recycling ratio of 3, and 25 to 250% in load variation. (c) 1997 IAWQ. Published by Elsevier Science Ltd. [ABSTRACT FROM AUTHOR]

Background: Endovascular therapy (EVT) with devices such as drug-coated balloons (DCBs) and drug-eluting stents (DESs) for atherosclerotic disease in the femoropopliteal (FP) artery has been established. However, EVT using drug-based devices for chronic limb-threatening ischemia (CLTI) remains challenging. The optimal device for FP lesions in patients with CLTI remains unknown. This study compared the clinical efficacy of DCB and DES in patients with CLTI and FP lesions., Methods and Results: This retrospective single-center study included 539 consecutive patients (562 lesions) treated with EVT between January 2018 and December 2022; 166 patients with CLTI and Rutherford Class 5 or 6 wounds underwent EVT with DCB or DES. Clinical outcomes were compared between 53 pairs after propensity score matching. There were no significant differences between the DCB and DES groups in the incidence of complete wound healing without death or major amputation (84.8% vs. 80.2%, respectively; P=0.99), primary patency (69.4% vs. 75.6%, respectively; P=0.65), and freedom from target lesion revascularization at 1 year (78.6% vs. 78.0%, respectively; P=0.92). Multivariate analysis showed that complete wound healing at 1 year is negatively associated with hemodialysis and Wound, Ischemia, and foot Infection Stage 4, but positively associated with Global Limb Anatomic Staging System FP Grade 3 or 4., Conclusions: No significant differences in clinical outcomes were found between DCB and DES for patients with CLTI and FP lesions.

The prognostic implications of cardiac troponin elevation after percutaneous coronary intervention (PCI) with atherectomy have not been established. The aim of this study was to investigate the incidence of periprocedural myocardial injury (PMI) and its association with cardiovascular events in patients with severely calcified lesions who underwent PCI with atherectomy. The study analyzed 346 patients (377 lesions) who underwent PCI with atherectomy between January 2018 and December 2021. Peak post-PCI high-sensitivity cardiac troponin (hs-cTn) was measured. The primary outcome was target lesion failure (TLF), a composite of cardiovascular death, target vessel myocardial infarction, and clinically driven target lesion revascularization. A lesion-based analysis was conducted to assess the association of PMI with TLF up to 5 years after PCI. Increase of hs-cTn was seen with 362 lesions (96%), and significant PMI, defined as hs-cTn increase ≥70 × upper reference limit, was seen with 83 lesions (22%). Significant PMI was associated with a significantly greater risk of TLF (adjusted hazard ratio 1.93, 95% confidence interval 1.12 to 3.30, p = 0.017), primarily driven by an increased risk of cardiovascular death (adjusted hazard ratio 5.29, 95% confidence interval 1.46 to 19.16, p = 0.011). In conclusion, hs-cTn increase was frequently observed in patients who underwent PCI with atherectomy, and significant PMI was associated with an increased risk of TLF and cardiovascular death., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The efficacy of guideline-directed medical therapy (GDMT) in the elderly remains unclear. This study evaluated the impact of GDMT (aspirin or a P2Y 12 inhibitor, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, β-blocker, and statin) at discharge on long-term mortality in elderly patients with acute myocardial infarction (AMI) who had undergone percutaneous coronary intervention (PCI)., Methods and results: Of 2,547 consecutive patients with AMI undergoing PCI in 2009-2020, we retrospectively analyzed 573 patients aged ≥80 years. The median follow-up period was 1,140 days. GDMT was prescribed to 192 (33.5%) patients at discharge. Compared with patients without GDMT, those with GDMT were younger and had higher rates of ST-segment elevation myocardial infarction and left anterior descending artery culprit lesion, higher peak creatine phosphokinase concentration, and lower left ventricular ejection fraction (LVEF). After adjusting for confounders, GDMT was independently associated with a lower cardiovascular death rate (hazard ratio [HR] 0.35; 95% confidence interval [CI] 0.16-0.81), but not with all-cause mortality (HR 0.77; 95% CI 0.50-1.18). In the subgroup analysis, the favorable impact of GDMT on cardiovascular death was significant in patients aged 80-89 years, with LVEF <50%, or with an estimated glomerular filtration rate ≥30 mL/min/1.73 m 2 ., Conclusions: GDMT in patients with AMI aged ≥80 years undergoing PCI was associated with a lower cardiovascular death rate but not all-cause mortality.

Background: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time., Aims: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated., Methods: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa., Results: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00])., Conclusions: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Background: Plaque characteristics associated with effective intravascular lithotripsy (IVL) treatment of calcification have not been investigated. This study identified calcified plaque characteristics that favor the use of IVL., Methods and results: Optical coherence tomography (OCT) was performed in 16 calcified lesions in 16 patients treated with IVL and coronary stenting. Cross-sectional OCT images in 262 segments matched across pre-IVL, post-IVL, and post-stenting time points were analyzed. After IVL, 66 (25%) segments had calcium fracture. In multivariable analysis, calcium arc (odds ratio [OR] 1.22; 95% confidence interval [CI] 1.13-1.32; P<0.0001), superficial calcification (OR 6.98; 95% CI 0.07-55.57; P=0.0182), minimum calcium thickness (OR 0.66; 95% CI 0.51-0.86; P=0.0013), and nodular calcification (OR 0.24; 95% CI 0.08-0.70; P=0.0056) were associated with calcium fracture. After stenting, stent area was larger for segments with fracture (8.0 [6.9-10.6] vs. 7.1 [5.2-8.9] mm 2 ; P=0.004)., Conclusions: Post-IVL calcium fracture is more likely in calcified lesions with lower thickness, a larger calcium arc, superficial calcification, and non-nodular calcification, leading to a larger stent area.

Background and Objectives: Intradiscal injection of Condoliase (chondroitin sulfate ABC endolyase), a glycosaminoglycan-degrading enzyme, is employed as a minimally invasive treatment for lumbar disc herniation (LDH) and represents a promising option between conservative treatment and surgical intervention. Since its 2018 approval in Japan, multiple single-site trails have highlighted its effectiveness, however, the effect of LDH types, and influences of patient age, sex, etc., on treatment success remains unclear. Moreover, data on teenagers and elderly patients has not been reported. In this retrospective multi-center study, we sought to classify prognostic factors for successful condoliase treatment for LDH and assess its effect on patients < 20 and ≥70 years old. Materials and Methods: We reviewed the records of 137 LDH patients treated through condoliase at four Japanese institutions and assessed its effectiveness among different age categories on alleviation of visual analog scale (VAS) of leg pain, low back pain and numbness, as well as ODI and JOA scores. Moreover, we divided them into either a “group-A” category if a ≥50% improvement in baseline leg pain VAS was observed or “group-N” if VAS leg pain improved <50%. Next, we assessed the differences in clinical and demographic distribution between group-A and group-N. Results: Fifty-five patients were classified as group-A (77.5%) and 16 patients were allocated to group-N (22.5%). A significant difference in Pfirrmann classification was found between both cohorts, with grade IV suggested to be most receptive. A posterior disc angle > 5° was also found to approach statical significance. In all age groups, average VAS scores showed improvement. However, 75% of adolescent patients showed deterioration in Pfirrmann classification following treatment. Conclusions: Intradiscal condoliase injection is an effective treatment for LDH, even in patients with large vertebral translation and posterior disc angles, regardless of age. However, since condoliase imposes a risk of progressing disc degeneration, its indication for younger patients remains controversial.

Background: Whether a coronary lesion with discordant fractional flow reserve (FFR) and non-hyperemic pressure ratios (NHPRs) causes myocardial ischemia remains unclear. This study investigates the prevalence of myocardial ischemia as assessed by myocardial perfusion scintigraphy (MPS) in coronary lesions with discordant FFR and instantaneous wave-free ratio (iFR), and, additionally, other NHPRs: resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and resting Pd/Pa., Methods: A total of 484 coronary arteries in 295 patients with stable coronary artery disease that underwent MPS and invasive physiological pressure measurements were categorized into four groups (FFR+/NHPR+, FFR+/NHPR-, FFR-/NHPR+, and FFR-/NHPR-) using the respective cut-off values of FFR ≤ 0.80, iFR ≤ 0.89, RFR ≤ 0.89, dPR < 0.89, and Pd/Pa ≤ 0.92. The proportions of MPS-derived myocardial ischemia in a relevant myocardial territory were compared between the four groups., Results: In total, 175 (36%), 61(13%), 35(7%) and 213(44%) vessels were classified into FFR+/iFR+, FFR+/iFR-, FFR-/iFR+ and FFR-/iFR- groups, respectively. The FFR+/iFR+ group had the highest proportion of MPS-derived ischemia (70%), followed by the FFR+/iFR- group (38%), the FFR-/iFR+ group (23%), and the FFR-/iFR- group (10%) (P < 0.001). Similar proportions of MPS-derived ischemia were found when RFR. (70%, 34%, 24%, and 10%, P < 0.001), dPR (70%, 38%, 26%, and 10%, P < 0.001), and Pd/Pa (70%, 31%, 22%, and 10%, P < 0.001) were used in place of iFR., Conclusions: The prevalence of MPS-derived myocardial ischemia in coronary lesions with discordance between FFR and NHPRs is lower than those with concordantly positive FFR and NHPRs, but higher than those with concordantly negative FFR and NHPRs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD., (© 2022 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

Background: Percutaneous coronary intervention (PCI) of heavily calcified lesions remains challenging. This study examined whether calcified lesion preparation is better with an ablation-based than balloon-based technique. Methods and Results: Results of lesion preparations with and without atherectomy devices were compared in 121 patients undergoing optical coherence tomography (OCT)-guided PCI of heavily calcified lesions. Lesion preparation was performed with the ablation-based technique in 59 patients (atherectomy group) and with the balloon-based technique in 62 patients (balloon group). Lower grades of angiographic coronary dissections (National Heart, Lung, and Blood Institute [NHLBI] classification) occurred in the atherectomy than balloon group (atherectomy group: none, 33%; NHLBI A, 59%; B, 8%; C, 0%; D, 0%; balloon group: none, 1%; NHLBI A, 24%; B, 58%; C, 15%; D, 2%). On OCT, a large dissection was less common (49% vs. 90%; P<0.001) and calcium fractures were more frequent (75% vs. 18%; P<0.001) in the atherectomy than balloon group. In multivariable analyses, the ablation-based technique was associated with a lower grade of angiographic coronary dissection (adjusted odds ratio [aOR] 0.04; 95% confidence interval [CI] 0.01-0.12; P<0.001), a lower incidence of OCT-detected large dissection (aOR 0.09; 95% CI 0.03-0.30; P<0.001), and a higher incidence of OCT-detected calcium fracture (aOR 18.19; 95% CI 6.45-58.96; P<0.001). Conclusions: The ablation-based technique outperformed the balloon-based technique in the lesion preparation of heavily calcified lesions., Competing Interests: Y.S. has received lecture fees from Abbott Japan. The remaining authors have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022, THE JAPANESE CIRCULATION SOCIETY.)