Efficacy and safety of romosozumab: a meta-analysis of placebo-controlled trials.

INTRODUCTION: We aimed to comprehensively compile placebo-controlled trials on the efficacy and safety of romosozumab (210 mg, subcutaneously, once monthly) in postmenopausal women and men with osteoporosis. MATERIALS AND METHODS: PubMed, Google Scholar, and ClinicalTrials.gov were searched for relevant placebo-controlled trials (as of January 1, 2024). Percent change in bone mineral density (BMD), falls, fractures, and adverse events (AEs) after drug administration were collected. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: Six trials (7990 patients; follow-up period, 6-12 months) were included. Compared with placebo, romosozumab significantly increased lumbar spine BMD (MD = 12.69; 95% CI 11.10-14.29), total hip BMD (MD = 4.42; 95% CI 3.03-5.80), and femoral neck BMD (MD = 3.99; 95% CI 2.42-5.57) at 12 months. Romosozumab significantly decreased falls (RR = 0.80; 95% CI 0.68-0.93) and major osteoporotic fractures (RR = 0.37; 95% CI 0.25-0.54), but increased injection-site reactions (RR = 1.83; 95% CI 1.46-2.30) within 12 months. No significant differences were observed in other AEs (including cardiovascular AEs) within 12 months. CONCLUSION: Romosozumab treatment resulted in a significant BMD gain, reduced falls and major osteoporotic fractures. It was generally well-tolerated, including the cardiovascular aspects. However, clinicians should consider the occurrence of minor AEs (e.g., injection-site reactions).

A well-managed case of discontinuous anorectal injury caused by a personal watercraft treated by combining surgery and colonoscopy.

Background: Anorectal injury caused by personal watercraft (PWC)-related trauma is rare. However, PWC accidents have increased recently, and since patients tend to be younger, treatment strategies should consider anal function preservation in addition to saving lives. Case Presentation: A 30-year-old female patient who fell into the water when a PWC suddenly accelerated and injured her perineum with a forceful water jet was transported to our hospital. On examination, she was diagnosed with a traumatic rectal perforation with intraperitoneal findings and an anorectal injury. Emergency surgery, which involved direct suturing, temporary colostomy with intraoperative endoscopy for the rectal perforation, and anorectal reconstruction, was performed. The patient was discharged on postoperative day 19 without complications, and the colostomy was closed 5 months postoperatively. Conclusion: We encountered a case of multiple noncontinuous anorectal injuries due to a PWC accident that was successfully treated using a combination of surgery and intraoperative endoscopy.

Biodegradation of nitenpyram (neonicotinoid insecticide) by endophytic bacterium, Bacillus thuringiensis strain NIT-2, isolated from neonicotinoid-treated plant samples.

Nitenpyram (neonicotinoid insecticide) is commonly used for crop protection from pests. Currently, due to its widespread use, the nitenpyram accumulation in the environment is anticipated to be high. Hence, the removal of nitenpyram residue from the environment is essential. However, the biodegradation of nitenpyram by endophytes is still unreported. Therefore, we aimed to isolate and identify a bacterial strain capable of degrading nitenpyram. We isolated approximately 300 endophytic strains from Brassica rapa var. perviridis that had been exposed to different neonicotinoid insecticides. After 14 days of incubation, a bacterial strain, NIT-2, with nitenpyram degradation capability (approximately 65%) was found. Via 16S rRNA gene sequencing, the strain was identified as Bacillus thuringiensis. In addition, metabolites, 2-[N-(6-chloro-3-pyridylmethyl)-N-ethyl]amino-2-methyliminoacetic acid, N-(6-chloro-3-pyridilmethyl)-N-ethyl-N-methylformamidine (CPMF), and N-(6-chloro-3-pyridilmethyl)-N-ethylformamide (CPF), were identified during the degradation. Moreover, CPMF and CPF were further degraded 71% and 18%, respectively by NIT-2. Thus, B. thuringiensis strain NIT-2 is the first reported endophytic bacterium capable of degrading nitenpyram.

Denosumab vs. bisphosphonates in primary osteoporosis: a meta-analysis of comparative safety in randomized controlled trials.

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12-24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34-0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03-4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07-2.41), more infections (RR = 1.14; 95% CI 1.02-1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08-2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31-0.93), and less abdominal pain (RR = 0.44;95% CI 0.22-0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results.

Surgical and Oncological Outcomes of Wedge Resection Versus Segment 4b + 5 Resection for T2 and T3 Gallbladder Cancer: a Meta-Analysis.

BACKGROUND: Liver resection is the standard operative procedure for patients with T2 and T3 gallbladder cancers (GBC). However, the optimal extent of hepatectomy remains unclear. METHODS: We conducted a systematic literature search and meta-analysis to assess the safety and long-term outcomes of wedge resection (WR) vs. segment 4b + 5 resection (SR) in patients with T2 and T3 GBC. We reviewed surgical outcomes (i.e., postoperative complications and bile leak) and oncological outcomes (i.e., liver metastasis, disease-free survival (DFS), and overall survival (OS)). RESULTS: The initial search yielded 1178 records. Seven studies reported assessments of the above-mentioned outcomes in 1795 patients. WR had significantly fewer postoperative complications than SR, with an odds ratio of 0.40 (95% confidence interval, 0.26 - 0.60; p < 0.001), although there were no significant differences in bile leak between WR and SR. There were no significant differences in oncological outcomes such as liver metastases, 5-year DFS, and OS. CONCLUSIONS: For patients with both T2 and T3 GBC, WR was superior to SR in terms of surgical outcome and comparable to SR in terms of oncological outcomes. WR that achieves margin-negative resection may be a suitable procedure for patients with both T2 and T3 GBC.

Catalog of 525 sprites observed over Japan from September 2016 to March 2021.

We present a catalog of 525 sprites detected over the Sea of Japan and a northeast part of the Pacific Ocean from Sagamihara between September 2016 and March 2021. We analyze the morphology of 525, estimate the location of 441, and calculate the accurate top height of 15 sprites. More than half of our samples occurred in winter, while only 11% were in summer. In terms of morphology, 52% to 60% column type sprites took place in spring, autumn, and winter, while only 15.5% in summer. Therefore, summer thunderstorms are more likely to produce sprites with complex structures like carrots. Furthermore, sprites in summer are almost all located on the main island of Japan, and their spatial distributions are significantly different from the other seasons. Finally, from the perspective of the time distribution, the number of sprites is the largest at 1:00 JST. In addition, the morphology of sprites tends to be simple (e.g., a column type) at midnight JST.

Survival Rate of 3-unit Fixed Partial Dentures Replacing First Molars: A Retrospective Cohort Study.

Fixed partial dentures (FPDs) made of 12% Au-Pd alloy are covered under Japan's national health insurance system. The survival rate of such 3-unit fixed FPDs remains unknown, however. The purpose of this retrospective study was to assess their survival rate in the replacement of first molars. A total of 140 FPDs were included, and the endpoint was removal of an FPD. During the observation period, 43 FPDs were removed. The FPD survival rate was 70.2% at 10 yr, 58.2% at 15 yr, and 42.1% at 20 yr according to the Kaplan-Meier method. The estimated mean survival period was 19.4 yr. The main reasons for FPD loss were dental caries (27.9%), separation from the abutment tooth (18.6%), and pulpitis (18.6%). Single factor analysis using the log-rank test showed that two factors influenced FPD survival: a smaller gonial angle and deep pockets around the abutment teeth. This effect was not statistically significant in either case, however (p>0.05). The present results suggest that the prevention of caries and of the separation of the dentures from the abutment teeth are important factors in the long-term survival of FPDs.

Isolation of a Novel Endophytic Bacillus Strain Capable of Transforming Pentachlorophenol and Structure Determination of Pentachlorophenol Phosphate Using Single-Crystal X-ray Diffraction.

A novel approach for the remediation of upland soils contaminated with pentachlorophenol (C6HCl5O; PCP) (1), a fungicide, wood perservative, and herbicide, through the exploitation of plant-endophytic bacteria may overcome the existing issues in bioaugmentaion and phytoremidiation. In this study, we isolated the endophytic Bacillus sp. strain PCP15 and determined its metabolite of PCP (1). This strain degraded 8.03 µmol L-1 PCP (1) within 24 h and generated the novel metabolite PCP phosphate (3). The PCP15 strain showed nearly complete growth inhibition of 20 µmol L-1 PCP (1). In contrast, PCP15 showed resistance to PCP phosphate (3), indicating that the phosphorylation of PCP, which has never previously been reported in organisms, contributed to the detoxification of PCP (1) in bacterial cells. Our results show the potential for practical application of this strain in hybrid remediation of PCP (1)-contaminated soils and reveal a novel PCP (1) detoxification mechanism in organisms.

Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model.

INTRODUCTION: Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. METHODS AND RESULTS: Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. CONCLUSION: TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

Mechanisms of aerobic dechlorination of hexachlorobenzene and pentachlorophenol by Nocardioides sp. PD653.

We sought to elucidate the mechanisms underlying the aerobic dechlorination of the persistent organic pollutants hexachlorobenzene (HCB) and pentachlorophenol (PCP). We performed genomic and heterologous expression analyses of dehalogenase genes in Nocardioides sp. PD653, the first bacterium found to be capable of mineralizing HCB via PCP under aerobic conditions. The hcbA1A2A3 and hcbB1B2B3 genes, which were involved in catalysing the aerobic dechlorination of HCB and PCP, respectively, were identified and characterized; they were classified as members of the two-component flavin-diffusible monooxygenase family. This was subsequently verified by biochemical analysis; aerobic dechlorination activity was successfully reconstituted in vitro in the presence of flavin, NADH, the flavin reductase HcbA3, and the HCB monooxygenase HcbA1. These findings will contribute to the implementation of in situ bioremediation of HCB- or PCP-contaminated sites, as well as to a better understanding of bacterial evolution apropos their ability to degrade heavily chlorinated anthropogenic compounds under aerobic conditions.

[The Role of Pharmacists in AST in Large Hospitals and Their Training].

Since 1997, Chubu Rosai Hospital has been establishing the proper use of various antibacterial drugs through the activities of an infection control team (ICT), introduction of a notification system for specific antibacterial drug use, and intervention of ward pharmacists for individual cases. There is no infectious disease department, and we have been working closely with each other on multiple occupations. As an initiative, we established the Nagoya Southern Infection Countermeasures Meeting in 2006 and conducted antimicrobial use and resistance (AUR) surveys to promote the proper use of antimicrobial agents within the area. In April 2018, we formed an antimicrobial stewardship team (AST) and initiated activities. In addition, an AST pharmacist can share the AST results with the ward pharmacist, for proper use of antibacterial drugs and for early monitoring of infectious disease treatment and appropriate intervention, thus improving the efficiency of the ward pharmacist's work. This program will also lead to the development of training programs for the younger generation of pharmacists.

Survival Rate of Removable Partial Dentures with Mandibular Bilateral Free End Saddle: A Retrospective Study.

The purpose of this study was to investigate the survival of removable partial dentures with a mandibular bilateral free end saddle (BFES) and abutment teeth in a clinical setting. Only mandibular dentures with a BFES were included (10 or fewer present teeth, and fewer than 4 occlusal units). The endpoints were replacement of denture and loss of abutment teeth. A total of 128 dentures and 595 abutment teeth were analyzed. Nineteen dentures had to be replaced during the observation period (mean duration: 11.4±6.9 years; range: 3 to 36 years). According to Kaplan-Meier analysis, the survival rate was 93.2% at 10 years and 68.6% at 20 years. The estimated mean survival period was 27.8 years. Single-factor analysis using the log-rank test showed that no factor investigated had a significant influence. The main reason for denture replacement was loss of abutment teeth (47.4%). The survival rate of the abutment teeth was 91.3% at 10 years and 77.3% at 20 years. The analysis revealed 4 significant risk factors: male sex (hazard ratio [HR]: 1.78); premolars (HR: 1.67); a lower number of abutment teeth (HR: 3.24); and history of endodontic treatment (HR: 2.79). The removable partial dentures with a mandibular BFES in this study lasted over 20 years, and their survival was influenced by loss of abutment teeth. Dentures are used continuously over long periods of time and should therefore be designed to allow easy adjustment when abutment teeth are lost.

Echocardiographic Assessments for Peripartum Cardiac Events in Pregnant Women with Low-Risk Congenital Heart Disease.

This retrospective cohort study aimed to explore the relationship between temporal changes in the cardiac function and peripartum cardiac events in pregnant women with low-risk congenital heart disease.We performed echocardiography at early and late pregnancy and postpartum in 76 pregnant women with low-risk congenital heart disease, and compared echocardiographic parameters between subjects with and without peripartum cardiac events. Median age at delivery was 27 (range, 24-31) years. The ZAHARA and CARPREG II scores suggested that most women were found to be at low-risk for pregnancy. Fifteen subjects had cardiac events that included heart failure in 10, arrhythmia in 4, and pulmonary hypertension in one subject. The left ventricular and atrial volumes significantly increased from early pregnancy toward late pregnancy, and the E/A ratio and global longitudinal strain significantly decreased from early pregnancy toward late pregnancy. The left atrial volume (67 [53-79] versus 45 [35-55] mL, P = 0.002) and plasma brain natriuretic peptide level (58 [36-123] versus 34 [18-48] pg/mL, P = 0.026) at late pregnancy were significantly higher in subjects with cardiac events than in those without cardiac events.An increase in the left atrial volume followed by mild left ventricular diastolic dysfunction is related to peripartum cardiac events in women with congenital heart disease who are at low risk for cardiac events during pregnancy.

Thoracic esophageal injury due to a neck stab wound: a case report.

BACKGROUND: Traumatic esophageal injury leads to severe complications such as mediastinitis, pyothorax, and tracheoesophageal fistula. Although prompt diagnosis and treatment are required, there are no established protocols to guide diagnosis or treatment. In particular, thoracic esophageal injury tends to be diagnosed later than cervical esophageal injury because it has few specific symptoms. We report a case of thoracic esophageal injury caused by a cervical stab wound; the patient was stabbed with a sharp blade. CASE PRESENTATION: A 74-year-old woman was attacked with a knife while sleeping at home. The patient was taken to the emergency room with an injury localized to the left section of her neck. She was suspected of a left jugular vein and recurrent laryngeal nerve injury from cervical hematoma and hoarseness. On the day following the injury, computed tomography revealed a thoracic esophageal injury. Emergency surgery was performed for an esophageal perforation and mediastinal abscesses. Although delayed diagnosis resulted in suture failure, the patient was able to resume oral intake of food a month later following enteral feeding with a gastrostomy. Esophageal injuries due to sharp trauma are rare, and most are cervical esophageal injuries. There are very few reports on thoracic esophageal injuries. CONCLUSIONS: The possibility of thoracic esophageal injury should always be considered when dealing with neck stab wounds, particularly those caused by an attack.

Laparoscopic appendectomy during the second trimester of a twin pregnancy.

Acute appendicitis during pregnancy may lead to increased maternal and fetal risks. Laparoscopic appendectomy is commonly performed during pregnancy. Compared with open appendectomy in pregnant women, laparoscopic appendectomy has shown non-inferior safety for pregnancy outcomes and superior safety for surgical outcomes. Over the last few decades, the occurrence of twin pregnancy has been increasing. Performing an operation on a patient with a twin pregnancy is more difficult than with a singleton pregnancy. Only a few operations of this kind have been reported. Here, we present a case of a 20-week twin pregnant woman who presented with acute appendicitis. Laparoscopic appendectomy was performed, and no maternal complications occurred. This report contributes to discussions on the safety of the laparoscopic approach for appendicitis during twin pregnancies.

Review of the health benefits of habitual consumption of miso soup: focus on the effects on sympathetic nerve activity, blood pressure, and heart rate.

High salt intake increases blood pressure, and dietary salt intake has been clearly demonstrated to be associated with hypertension incidence. Japanese people consume higher amounts of salt than Westerners. It has been reported that miso soup was one of the major sources of daily salt intake in Japanese people. Adding salt is indispensable to make miso, and therefore, in some cases, refraining from miso soup is recommended to reduce dietary salt intake. However, recent studies using salt-sensitive hypertensive models have revealed that miso lessens the effects of salt on blood pressure. In other word, the intake of miso dose not increase the blood pressure compared to the equivalent intake of salt. In addition, many clinical observational studies have demonstrated the absence of a relationship between the frequency of miso soup intake and blood pressure levels or hypertension incidence. The mechanism of this phenomenon seen in the subjects with miso soup intake has not been fully elucidated yet. However, in basic studies, it was found that the ingredients of miso attenuate sympathetic nerve activity, resulting in lowered blood pressure and heart rate. Therefore, this review focused on the differences between the effects of miso intake and those of the equivalent salt intake on sympathetic nerve activity, blood pressure, and heart rate.

Biochemical characterization of NADH:FMN oxidoreductase HcbA3 from Nocardioides sp. PD653 in catalyzing aerobic HCB dechlorination.

Nocardioides sp. PD653 genes hcbA1, hcbA2, and hcbA3 encode enzymes that catalyze the oxidative dehalogenation of hexachlorobenzene (HCB), which is one of the most recalcitrant persistent organic pollutants (POPs). In this study, HcbA1, HcbA2, and HcbA3 were heterologously expressed and characterized. Among the flavin species tested, HcbA3 showed the highest affinity for FMN with a K d value of 0.75±0.17 µM. Kinetic assays revealed that HcbA3 followed a ping-pong bi-bi mechanism for the reduction of flavins. The K m for NADH and FMN was 51.66±11.58 µM and 4.43±0.69 µM, respectively. For both NADH and FMN, the V max and k cat were 2.21±0.86 µM and 66.74±5.91 sec-1, respectively. We also successfully reconstituted the oxidative dehalogenase reaction in vitro, which consisted of HcbA1, HcbA3, FMN, and NADH, suggesting that HcbA3 may be the partner reductase component for HcbA1 in Nocardioides sp. PD653.

[A Case of Advanced Esophagogastric Junction Cancer Responding to Combined Modality Therapy].

The patient was a 75-year-old man with advanced esophagogastric junction cancer.He received 2 courses of neoadjuvant chemotherapy with DCS followed by lower esophagectomy and total gastrectomy via the left thoracoabdominal approach. Pathological examination revealed EGJ adenocarcinoma(pT3N4M0, pStage Ⅳa).He was followed up after the surgery and was diagnosed with pulmonary portal lymph node and No.1 07 node recurrences 4 years and 8 months after the surgery, respectively.He received 2 courses of TS-1 monotherapy and chemoradiotherapy, resulting in a complete response(CR).He has remained in CR until June 2019.

Effect of water-extractive components from funazushi, a fermented crucian carp, on the activity of fibrinolytic factors.

BACKGROUND: Japanese fermented foods, including funazushi, have have been studied insufficiently. Related research into fermented products has led to the hope that they might have positive effects on blood circulation, including anti-thrombosis effects. The possible antithrombotic effects of funazushi on the fibrinolytic system were examined. RESULTS: The administration of extracts from funazushi increased the activity of plasmin and tissue plasminogen activators in the fibrinolytic system but decreased the activity of plasminogen activator inhibitor type-1 (PAI-1). This decrease was positively correlated with the decreased plasma triglyceride levels. Funazushi extract directly inhibited PAI-1 activity in vitro despite alimentary enzyme digestion, although direct PAI-1 inhibition was not observed in an extract from salted crucian carp. CONCLUSION: These results suggest that funazushi extracts are closely involved in the antithrombotic effects of the fibrinolytic system, and that they exert their effect through a reduction in PAI-1 activity. The findings also indicate that fermentation processing is necessary to achieve the antithrombotic effects of funazushi. © 2020 Society of Chemical Industry.

Survival rate of removable partial dentures with complete arch reconstruction using double crowns: a retrospective study.

OBJECTIVES: The purpose of this study was to clinically investigate double-crown-retained removable partial dentures (DRPDs) and abutment teeth at dental clinics. MATERIALS AND METHODS: Only cases with complete arch reconstruction were included. Endpoints were replacement of denture and loss of abutment tooth. A total of 213 dentures with 1030 abutment teeth were analyzed. RESULTS: During the observation period, 32 dentures were replaced. The mean observation period was 12.7 (± 6.6) years (range 3 to 36). By the Kaplan-Meier method, survival rate at 10 years was 94.7% and at 20 years was 70.8%. Estimated mean survival period was 27.1 years. Cox regression analysis showed that risk factor for replacement was good occlusion as indicated by Eichner index groups A to B3 (HR 2.81). The main reason for denture replacement was loss of abutment teeth. Survival rate of abutment teeth at 10 years was 83.8% and at 20 years was 66.3%. The analysis revealed six risk factors: male gender (HR 1.76), age range 65-89 years (HR 1.51), posterior teeth (HR 1.60), higher number of present teeth in opposite jaw (HR 1.69), lower number of abutment teeth (HR 1.76), and short inner crown (HR 2.28). CONCLUSION: DRPDs last over 20 years, making them a durable investment in one's oral health; their survival is influenced by loss of abutment teeth. CLINICAL RELEVANCE: In cases where there are few teeth remaining in a jaw, DRPDs represent a suitable treatment that makes use of the remaining teeth, even if the abutment teeth are non-vital.