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Background Anti-programmed cell death 1 antibodies (PD-1 Abs) are widely used for advanced melanoma, but information on the efficacy of anti-PD-1 Abs is limited in the Asian population. There remains an unmet need to improve the therapeutic effects of anti-PD-1 Ab-treatment, particularly in patients with melanoma who are refractory to anti-PD-1 Abs. The aim of this study was to evaluate anti-PD-1 Ab-treatment in combination with TM5614 (a plasminogen activator inhibitor-1 inhibitor) in patients with unresectable melanoma. Methods The TM5614-MM study was a multicentre, open-label, single-arm, phase II clinical trial to evaluate the efficacy and safety of nivolumab in combination with TM5614 in patients with advanced, unresectable malignant melanoma recruited at seven Japanese institutes between 13 September 2021 and 31 March 2023. Patients with metastatic or unresectable melanoma previously treated with anti-PD-1 Abs were enrolled. Nivolumab 480 mg was administered intravenously every 4 weeks for 8 weeks, while TM5614 was administered orally at a dose of 120 mg (0–4 weeks) and 180 mg once daily (5–8 weeks). The primary endpoint was the overall response rate after 8 weeks of concomitant use of TM5614. Results Thirty-nine patients were enrolled, and 34 patients were included in the anti-PD-1 Ab-refractory cohort. The overall response rate at 8 weeks was 25.9% (95% confidence interval 12.9–44.9%, P = 0.027) in 27 patients who were anti-PD-1 Ab-refractory based on investigator assessment in the protocol per set cohort. Seven patients discontinued treatment owing to progressive disease or adverse events. Treatment-related grade 3 or higher adverse events occurred in 3 of 39 patients (7.7%) in the intention-to-treat cohort. Conclusions TM5614 in combination with nivolumab is well tolerated and effective in anti-PD-1 Ab-refractory unresectable melanoma. [ABSTRACT FROM AUTHOR]

To determine the characteristics of pediatric patients 0-19 years of age who died after onset of SARS-CoV-2 infection in Japan during January 1-September 30, 2022, we reviewed multiple sources. We identified 62 cases, collected detailed information from medical records and death certificates, and conducted interviews, resulting in 53 patients with detailed information for our study. Among 46 patients with internal causes of death (i.e., not external causes such as trauma), 15% were <1 year of age, 59% had no underlying disease, and 88% eligible for vaccination were unvaccinated. Nonrespiratory symptoms were more common than respiratory symptoms. Out-of-hospital cardiac arrest affected 46% of patients, and time from symptom onset to death was <7 days for 77%. Main suspected causes of death were central nervous system abnormalities (35%) and cardiac abnormalities (20%). We recommend careful follow-up of pediatric patients after SARS-CoV-2 infection during the first week after symptom onset, regardless of underlying diseases. [ABSTRACT FROM AUTHOR]

Aims: p16 is a sensitive surrogate marker for transcriptionally active high‐risk human papillomavirus (HR‐HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect. Methods and results: We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR‐HPV infection by mRNA in‐situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR‐HPV was detected in 83 of 108 ECA cases (77%), including five HPV‐associated adenocarcinomas in situ and 78 invasive HPV‐associated adenocarcinomas. All 83 HPV‐positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV‐independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV‐independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR‐HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR‐HPV infection correlated with better prognosis among invasive ECAs. Conclusions: The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR‐HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy. [ABSTRACT FROM AUTHOR]

Background: Increased levels of plasminogen activator inhibitor-1 (PAI-1) in tumors have been found to correlate with poor clinical outcomes in patients with cancer. Although abundant data support the involvement of PAI-1 in cancer progression, whether PAI-1 contributes to tumor immune surveillance remains unclear. The purposes of this study are to determine whether PAI-1 regulates the expression of immune checkpoint molecules to suppresses the immune response to cancer and demonstrate the potential of PAI-1 inhibition for cancer therapy. Methods: The effects of PAI-1 on the expression of the immune checkpoint molecule programmed cell death ligand 1 (PD-L1) were investigated in several human and murine tumor cell lines. In addition, we generated tumor-bearing mice and evaluated the effects of a PAI-1 inhibitor on tumor progression or on the tumor infiltration of cells involved in tumor immunity either alone or in combination with immune checkpoint inhibitors. Results: PAI-1 induces PD-L1 expression through the JAK/STAT signaling pathway in several types of tumor cells and surrounding cells. Blockade of PAI- 1 impedes PD-L1 induction in tumor cells, significantly reducing the abundance of immunosuppressive cells at the tumor site and increasing cytotoxic T-cell infiltration, ultimately leading to tumor regression. The anti-tumor effect elicited by the PAI-1 inhibitor is abolished in immunodeficient mice, suggesting that PAI-1 blockade induces tumor regression by stimulating the immune system. Moreover, combining a PAI-1 inhibitor with an immune checkpoint inhibitor significantly increases tumor regression. Conclusions: PAI-1 protects tumors from immune surveillance by increasing PDL1 expression; hence, therapeutic PAI-1 blockade may prove valuable in treating malignant tumors. [ABSTRACT FROM AUTHOR]

Epoxy fatty acid formation during heating was estimated using triolein (OOO) and trilinolein (LLL). Epoxy octadecanoic acids were found in heated OOO, while epoxy octadecenoic acids were found in heated LLL. The content of epoxy fatty acids increased with heating time, and trans-epoxy fatty acids were formed significantly more than cis-epoxy fatty acids. A comparison between OOO and LLL indicated that epoxy fatty acid formation was higher in the OOO than that in the LLL. Heating tests in the presence of α-tocopherol suggested that the formation of epoxy fatty acids could be suppressed by antioxidants. [ABSTRACT FROM AUTHOR]

Background: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. Case presentation: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5–S disc degeneration. L5–S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. Conclusions: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root. [ABSTRACT FROM AUTHOR]

Guangnanmycin A is a recently discovered congener of the well‐known antitumor drug lead leinamycin; its macrolactam ring, however, is even more strained than that of the parent compound. The first synthetic foray towards this challenging target is reported, which relies on molybdenum‐catalyzed macrocyclization by ring closing alkyne metathesis (RCAM) followed by ruthenium‐catalyzed redox isomerization of the propargyl alcohol thus formed; the resulting enone enabled the introduction of the yet missing exo‐methylene group by a modified Peterson olefination. The signature disulfide moiety of guangnanmycin A was installed by strain‐driven thia‐Michael addition followed by conversion of the thioether thus formed into an unsymmetric disulfide with the aid of (methylthio)dimethylsulfonium tetrafluoroborate and MeSSMe. While this sequence furnished racemic guangnanmycin A alcohol in good overall yield, the final oxidation to the corresponding acid failed, most likely because of the exceptional sensitivity of the strained scaffold. [ABSTRACT FROM AUTHOR]

Guangnanmycin A is a recently discovered congener of the well‐known antitumor drug lead leinamycin; its macrolactam ring, however, is even more strained than that of the parent compound. The first synthetic foray towards this challenging target is reported, which relies on molybdenum‐catalyzed macrocyclization by ring closing alkyne metathesis (RCAM) followed by ruthenium‐catalyzed redox isomerization of the propargyl alcohol thus formed; the resulting enone enabled the introduction of the yet missing exo‐methylene group by a modified Peterson olefination. The signature disulfide moiety of guangnanmycin A was installed by strain‐driven thia‐Michael addition followed by conversion of the thioether thus formed into an unsymmetric disulfide with the aid of (methylthio)dimethylsulfonium tetrafluoroborate and MeSSMe. While this sequence furnished racemic guangnanmycin A alcohol in good overall yield, the final oxidation to the corresponding acid failed, most likely because of the exceptional sensitivity of the strained scaffold. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluated the efficacy and safety of transvaginal approach combined intracavitary and interstitial brachytherapy (IC/IS BT) assisted by transrectal ultrasound (TRUS) for treatment of locally advanced cervical cancer (LACC). Materials and Methods: A total of 30 patients of LACC treated with external beam radiotherapy and IC/IS BT via transvaginal approach assisted by transrectal ultrasound were observed retrospectively. The 2-year local control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan–Meier method. Late adverse events were also evaluated to assess the safety of IC/IS BT. Results: The median follow-up period was 22 months. The 2-year LC, PFS, and OS were 90%, 61%, and 82%, respectively. We observed no critical complications related to the IC/IS BT technique. Late adverse events of grade 3 or more included one case of grade 4 colon perforation. Conclusion: Our patient series demonstrated that radiotherapy combined with transvaginal approach, TRUS-assisted IC/IS BT achieves favorable local control and safety for LACC. [ABSTRACT FROM AUTHOR]

Background Although many human papillomavirus (HPV)–targeted therapeutic vaccines have been examined for efficacy in clinical trials, none have been translated into clinical use. These previous agents were mostly administered by intramuscular or subcutaneous injection to induce systemic immunity. We investigated the safety and therapeutic efficacy of an HPV-16 E7-expressing lacticaseibacillus -based oral vaccine. Methods In a double-blind, placebo-controlled, randomized trial, a total of 165 patients with HPV-16–positive high-grade cervical intraepithelial neoplasia 2 and 3 were assigned to orally administered placebo or low, intermediate, or high doses of IGMKK16E7 (lacticaseibacillus paracasei expressing cell surface, full-length HPV-16 E7). In the 4 groups, IGMKK16E7 or placebo was administered orally at weeks 1, 2, 4, and 8 postenrollment. The primary outcomes included histopathological regression and IGMKK16E7 safety. Results In per-protocol analyses, histopathological regression to normal (complete response) occurred in 13 (31.7%) of 41 high-dose recipients and in 5 (12.5%) of 40 placebo recipients (rate difference = 19.2, 95% confidence interval [CI] = 0.5 to 37.8). In patients positive for HPV-16 only, the clinical response rate was 40.0% (12 of 30) in high-dose recipients and 11.5% (3 of 26) in recipients of placebo (rate difference = 28.5, 95% CI = 4.3 to 50.0). There was no difference in adverse events that occurred in the high-dose and placebo groups (P  = .83). The number of HPV-16 E7–specific interferon-γ producing cells within peripheral blood increased with level of response (stable disease, partial, and complete responses; P  = .004). The regression to normal (complete response) rates among recipients with high levels of immune response were increased in a dose-dependent manner. Conclusion This trial demonstrates safety of IGMKK16E7 and its efficacy against HPV-16–positive cervical intraepithelial neoplasia 2 and 3. IGMKK16E7 is the first oral immunotherapeutic vaccine to show antineoplastic effects. Trial registration jRCT2031190034. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the optimal sodium hypochlorite solution (NaOCl) concentration to effectively remove the root canal biofilm without stimulating periradicular inflammation using coronal laser‐activated irrigation (CLAI). To compare the efficacy of different NaOCl concentrations combined with CLAI in removing the biofilm, an in vivo intraradicular biofilm rat model was used. Root canals were irrigated using an Er:YAG laser with either 5% or 0.5% NaOCl. Biofilm removal efficacy of CLAI was compared to that of conventional needle irrigation using scanning electron microscopy (SEM) and quantitative polymerase chain reaction (qPCR). Histological observation of CLAI‐associated periradicular inflammation was also conducted. In both the 5% and 0.5% CLAI groups, SEM observation showed the opening of the dentin tubules and biofilm removal. qPCR analysis indicated that the residual bacteria counts after cleaning were significantly lower in the 5% and 0.5% CLAI groups than in the conventional needle irrigation and positive control groups (Tukey test, p < 0.05), and no significant difference was observed between the 5% and 0.5% CLAI groups (p > 0.05). Periapical inflammation in the 5% CLAI group revealed the most severe, including significant neutrophilic and lymphocytic infiltration with abscess formation, while only mild vasodilation was observed in the 0.5% CLAI group. CLAI can remove the biofilm independently of chemical action, which avoids the risks associated with high NaOCl concentrations. Therefore, this root canal irrigation technique ensures safety and effectiveness, promising to contribute to new treatment strategies intended to remove intraradicular biofilm. [ABSTRACT FROM AUTHOR]

The first prophylactic vaccine against human papillomavirus (HPV) 16 and HPV18 was licensed in Japan in 2009. HPV vaccine effectiveness against high‐grade cervical lesions has been demonstrated among young Japanese women, but evidence of its effects on invasive cervical cancer (ICC) is lacking. Using data from two different cancer registries, we compared recent trends of new ICC cases by age group using Poisson regression analysis. We also analyzed time trends in HPV16/18 prevalence among 1414 Japanese women aged <40 years newly diagnosed with ICC in the past decade. Based on the population‐based cancer registry, the incidence of ICC among young women aged 20–29 years showed a significant decline from 3.6 to 2.8 per 100 000 women‐years during 2016–2019, but no similar decline was observed for older age groups (p < 0.01). Similarly, using data from the gynecological cancer registry of the Japan Society of Obstetrics and Gynecology, the annual number of ICCs among women aged 20–29 years also decreased from 256 cases to 135 cases during 2011–2020 (p < 0.0001). Furthermore, a declining trend in HPV16/18 prevalence in ICC was observed only among women aged 20–29 years during 2017–2022 (90.5%–64.7%, p = 0.05; Cochran–Armitage trend test). This is the first report to suggest population‐level effects of HPV vaccination on ICC in Japan. Although the declining trend in HPV16/18 prevalence among young women with ICC supports a causal linkage between vaccination and results from cancer registries, further studies are warranted to confirm that our findings are attributable to vaccination. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) with near‐infrared (NIR) fluorescence imaging is used for lymphatic mapping. However, binding of ICG to blood proteins like serum albumin can shorten its retention time in sentinel lymph nodes (SLNs). Here, we investigated the efficacy and safety of a new fluorescence tracer comprising phytate and liposome (LP)‐encapsulated ICG. Coadministration of phytate with LP containing phosphatidic acid promotes chelation mediated by Ca2+ in bodily fluids to enhance SLN retention. Uniformly sized LPs (100 nm) encapsulating ICG under conditions that minimized fluorescence self‐quenching during storage were produced. We analyzed the behavior of the new tracer (ICG‐phytate‐LP) and control tracers (ICG and ICG‐LP) in the lymphatic flow of mice in terms of lymph node retention time. We also tested lymphatic flow and safety in pigs that have a more human‐like lymphatic system. LPs encapsulating stabilized ICG were successfully prepared. Mixing LP with phytate in the presence of Ca2+ increased both the particle size and negative surface charge. In mice, ICG‐phytate‐LP had the best lymph node retention, with a fluorescence intensity ratio that increased over 6 h and then decreased slowly over the next 24 h. In pigs, administration of ICG and ICG‐phytate‐LP resulted in no death or weight loss. There were no obvious differences between blood test results for the ICG and ICG‐phytate‐LP groups, and the overall safety was good. ICG‐phytate‐LP may be a useful new tracer for gynecological cancers that require time for lymph node identification due to a retroperitoneal approach. [ABSTRACT FROM AUTHOR]

Objective: To examine the significant events experienced by initial trainees during community medicine training, evaluate their impact on community medicine practice, and support improvements in rural community medicine training. Results: Three faculty teachers independently evaluated the reports of 25 residents who had completed a four-week community medicine training in a rural area to analyze major events. The reports were analyzed using topics from the Model Core Curriculum for Medical Education that relate to rural medicine. The most frequently reported items were identified as follows: Primary care: 9 (36.0%); integrated community care systems: 8 (32.0%); medical care in the local community: 7 (28.0%); home health care and systems, patient-physician relationship, and end-of-life medical treatment and care: 6 each (24.0%). Reports from residents describing events related to home health care and systems and end-of-life medical treatment and care were related to more than one item. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study. Purpose: This research aimed to assess the clinical outcomes of patients with traumatic cervical spine dislocation who underwent closed reduction employing our approach. Overview of Literature: Bedside closed reduction is the quickest procedure for repairing traumatic cervical spine dislocations; nevertheless, it also possesses the risk of neurological deterioration. Methods: For closed reduction, the patient's head was elevated on a motorized bed, the cervical spine was placed at the midline, traction of 10 kg was applied, the motorized bed was gradually returned to a flat position, the head was lifted off the bed, and the cervical spine was slowly adjusted to a flexed position. The weight of traction was elevated by 5-kg increments until the positional shift was attained. Subsequently, the bed was gradually tilted while traction was applied again to return the cervical spine to the midline position. Results: Of the 43 cases of cervical spine dislocation, closed reduction was carried out in 40 cases, of which 36 were successful. During repositioning, three patients experienced a temporary worsening of their neck pain and neurological symptoms that enhanced when the cervical spine was flexed. Closed reduction was conducted while the patient was awake; nevertheless, sedation was needed in three cases. Among the 24 patients whose pretreatment paralysis had been characterized by American Spinal Injury Association Impairment Scale (AIS) grades A--C, seven patients (29.2%) demonstrated an enhancement of two or more AIS grades at the last observation. Conclusions: Our closed reduction approach safely repaired traumatic cervical spine dislocations. [ABSTRACT FROM AUTHOR]

Background: Single-blind 9 case comparative studies were conducted to evaluate salivary fluoride concentrations following toothbrushing using experimental toothpaste containing surface pre-reacted glass-ionomer (S-PRG) fillers. Preliminary tests were conducted in order to determine the volume of usage as well as the concentrations (wt %) of S-PRG filler. Based on the results given these experiments, we compared the salivary fluoride concentrations following toothbrushing with 0.5 g of 4 different types of toothpastes: 5 wt % S-PRG filler, 1400 ppm F AmF (amine fluoride), 1500 ppm F NaF (sodium fluoride), and MFP (monofluorophosphate) containing toothpaste. Methods: Of the 12 participants, 7 participated in the preliminary study and 8 in the main study. All participants brushed their teeth using the scrubbing method for 2 min. At first, 1.0 and 0.5 g of 20 wt % S-PRG filler toothpastes were used to compare, then followed by 0.5 g of 0 (control), 1, and 5 wt % S-PRG toothpastes, respectively. The participants spat out once and rinsed with 15 mL of distilled water for 5 s. Saliva was collected for 3 min each at different time intervals of 0 (baseline), 5, 10, 15, 30, 60, 120, and 180 min after the rinsing. Fluoride concentrations were determined using a fluoride electrode, and the area under the salivary clearance – time curve (AUC: ppm‧min) of each toothpaste was calculated as the salivary fluoride retention. The main study was then conducted to evaluate the salivary fluoride concentrations as well as the AUC value using 0.5 g of 5 wt % S-PRG filler toothpaste, followed by NaF, MFP, and AmF toothpastes. Results: Since there were no statistical differences between using 1.0 and 0.5 g of 20 wt % S-PRG toothpastes in salivary fluoride concentrations as well as the AUC value throughout the 180 min measurement, the volume was set as 0.5 g for the following studies. Concentrations of 5 and 20 wt % S-PRG toothpastes retained 0.09 ppm F or more in saliva even after 180 min. No statistical differences were seen in the salivary fluoride concentrations at any time intervals as well as the AUC value between 5 and 20 wt % S-PRG toothpastes. Based on these results, the concentration of 5 wt % S-PRG toothpaste was used for the main comparative study. MFP toothpaste resulted in by far the lowest salivary fluoride concentrations (0.06 ppm F at 180 min) and the AUC value (24.6 ppm‧min), whereas 5 wt % S-PRG toothpaste (0.15 ppm F at 180 min, 92.3 ppm‧min) displayed retention on par with AmF toothpaste which appeared to result in higher values (0.17 ppm F at 180 min, 103 ppm‧min), compared to NaF toothpaste (0.12 ppm F at 180 min, 49.3 ppm‧min). Conclusions: The salivary fluoride concentrations following toothbrushing with 0.5 g of 5 wt % S-PRG filler containing toothpaste showed retention similar to the best performing 1400 ppm F AmF toothpaste even 180 min after toothbrushing. [ABSTRACT FROM AUTHOR]

Background: Adult spinal deformity has a substantially debilitating effect on older people's physical and mental health. However, the impact of sagittal malalignment on locomotive syndrome (LS), sarcopenia, and physical function in community-dwelling older women has not yet been clarified. This study aimed to investigate the association between these factors in community-dwelling middle aged and older women. Methods: A total of 361 women were recruited from participants performing aquatic exercises in a rural area of Japan. The body mass index, skeletal muscle mass index, trunk muscle mass, spinal inclination angle (SIA), grip strength, timed up-and-go test (TUG), maximum stride of the participants, and one-leg standing time were measured. Low back pain (LBP)- and health-related quality of life (HRQOL) were evaluated using the Oswestry Disability Index (ODI) and the Short-Form 8 questionnaire. Associations between the global sagittal alignment using SIA and investigating parameters were analyzed. Results: The prevalence of sarcopenia was 3.6%. The prevalence of LS (stages 1, 2, and 3) was 43.8% (158 of 361), and the number of participants in each LS stage was 203 (stage 0), 95 (stage 1), 28 (stage 2), and 35 (stage 3). The SIA was significantly correlated with the 25-question geriatric locomotive function scale (r′ = 0.292, p < 0.001), ODI (r′ = 0.267, p < 0.001), and TUG (r′ = 0.453, p < 0.001) after adjusting for age. In the receiver-operating characteristic curve analysis, the cutoff values of SIA for LS ≥ stage 2 and ODI ≥ 20% were 5°. Conclusions: LBP-related QOL and physical performance were significantly associated with global sagittal alignment. Global sagittal alignment was correlated with the three-stage category of LS. The spinal inclination of 5° was a cutoff value to predict exacerbation of mobility function and HRQOL status. [ABSTRACT FROM AUTHOR]

It is well-known that poly(2-methoxyethyl acrylate) (PMEA) exhibits excellent blood compatibility and various investigations have examined the underlying mechanism of this compatibility in terms of the water structure in PMEA and/or inherent PMEA properties. However, information regarding the dynamic properties of the PMEA remains limited. This study was performed to clarify the effect of water molecules on the structure and dynamic properties of hydrated PMEA by comparing dry PMEA using temperature-variable 13C nuclear magnetic resonance spectroscopy (13C-NMR) with a solution probe at 15 –45 °C. Hydration changed the chemical shift values of the four carbons in the PMEA side chain (−COOCH2CH2OCH3). Investigations of spin-lattice relaxation times and resonance peak widths showed that hydration increased PMEA mobility and the side chain mobility markedly changed at approximately 30 °C, especially in dry PMEA. [ABSTRACT FROM AUTHOR]

Background: Intrathecal baclofen therapy can substantially improve symptoms in most patients with severe spasticity due to traumatic spinal cord injury, multiple sclerosis, or cerebral paresis. To the best of our knowledge, decompression surgeries at the intrathecal catheter insertion site in patients with a preexisting intrathecal pump for drug delivery have not been reported. Case presentation: We report the case of a 61-year-old Japanese man with lumbar spinal stenosis who underwent intrathecal baclofen therapy. We performed decompression for lumbar spinal stenosis at the intrathecal catheter insertion site during intrathecal baclofen therapy. The yellow ligament was removed by partial resection of the lamina under a microscope to avoid damage to the intrathecal catheter. The dura mater was distended. No obvious cerebrospinal fluid leakage was observed. Postoperatively, lumbar spinal stenosis symptoms improved, and spasticity remained well controlled with intrathecal baclofen therapy. Conclusions: This is the first reported case of lumbar spinal stenosis decompression at an intrathecal catheter insertion site during intrathecal baclofen therapy. Preoperative preparation is necessary, as the intrathecal catheter may be replaced during surgery. We performed surgery without removing or replacing the intrathecal catheter, taking care not to damage the spinal cord by migrating the intrathecal catheter. [ABSTRACT FROM AUTHOR]

Hepatitis E virus (HEV) is an emerging causative agent of acute hepatitis. To clarify the epidemiology of HEV and characterize the genetic diversity of the virus in Japan, nationwide enhanced surveillance and molecular characterization studies of HEV in Japan were undertaken from 2014 to 2021. In total, 2770 hepatitis E cases were reported, of which 88% were domestic cases, while only 4.1% represented cases following infection abroad. In addition, 57% of domestic infections occurred in males aged in their 40s–70s. For domestic cases, infection via pork meat consumption continued to be the most reported route. Analysis of the 324 sequences detected between 2016 and 2021 showed that the majority of domestic HEV strains belong to Genotype 3a (G3a) and G3b. In contrast, six of eight cases of G1 HEV reflected infection abroad. Our results suggest that HEV is circulating widely in Japan, with genotypes G3a and G3b being most prevalent. Continued surveillance is necessary to monitor future trends and changes in the epidemiology of HEV in Japan. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) enhance antitumoral immune mechanisms and are used to treat various types of solid tumors including those that are microsatellite instability (MSI)-high. Uterine endometrial cancer is one of the most frequent tumor types that shows MSI-high, and, consequently, opportunities to use ICIs for endometrial cancer treatment are increasing. While using ICIs, it is important to monitor and manage various immune-related adverse events (irAEs). Here, we report two cases of secondary adrenal insufficiency during treatment of endometrial cancer with pembrolizumab. Both cases showed appetite loss and general fatigue after the 6th or 12th cycle of pembrolizumab. They were admitted to our hospital because of remarkable hyponatremia. Both cases showed no adrenocorticotropic hormone (ACTH) or cortisol response to CRH loading tests. Other pituitary hormone levels were normal, and MRI revealed no sign of hypophysitis in either patient. They were diagnosed with secondary adrenal insufficiency due to isolated ACTH deficiency and recovered soon after the administration of hydrocortisone and hydration. Thus, we should be aware of irAEs with the use of ICIs. In particular, adrenocortical insufficiency is sometimes lethal without appropriate treatment. Because the clinical symptoms are fatigue, appetite loss, and nausea, patients might be misjudged to have symptoms related to cancer. Checking serum morning cortisol before ICIs use and monitoring serum sodium levels could provide clues to diagnose secondary adrenal insufficiency. [ABSTRACT FROM AUTHOR]

Background: Flavanone 3-hydroxylase (F3H), a key enzyme in the flavonoid biosynthetic pathway, plays an important role in the regulation of flavonols and anthocyanidins accumulation. Citrus fruit is a rich source of flavonoids with varied flavonoid compositions among different varieties. To date, the study on F3H is limited in citrus, and its roles in regulating flavonoid accumulation in citrus fruit are still unclear. Results: In this study, we isolated a CitF3H from three different citrus varieties, Satsuma mandarin (Citrus unshiu Marc.), Ponkan mandarin (C. reticulata Blanco) and blood orange 'Moro' (C. sinensis Osbeck). Functional analysis showed that CitF3H encoded a functional flavanone 3-hydroxylase. It catalyzed the hydroxylation of naringenin to yield dihydrokaempferol, which was a precursor of anthocyanins in flavonoid biosynthetic pathway. In the juice sacs, CitF3H was differentially expressed among the three citrus varieties, and its expression level was positively correlated with the accumulation of anthocyanins during the ripening process. In the juice sacs of Satsuma mandarin and Ponkan mandarin the expression of CitF3H kept constant at an extremely low level, and no anthocyanin was accumulated during the ripening process. In contrast, the expression of CitF3H increased rapidly along with the accumulation of anthocyanin in the juice sacs of blood orange 'Moro' during the ripening process. In addition, we found that blue light irradiation was effective to up-regulate the expression of CitF3H and improve anthocyanin accumulation in the juice sacs of blood orange 'Moro' in vitro. Conclusion: CitF3H was a key gene regulating anthocyanin accumulation in the juice sacs of citrus fruit. The results presented in this study will contribute to elucidating anthocyanin biosynthesis in citrus fruit, and provide new strategies to improve the nutritional and commercial values of citrus fruit. [ABSTRACT FROM AUTHOR]

Objective: To apply the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system to all patients who underwent trachelectomy in our previous study and to update the oncologic and obstetric results. Methods: We retrospectively reviewed the medical records of patients in whom abdominal trachelectomy was attempted between June 2005 and September 2021. The FIGO 2018 staging system for cervical cancer was applied to all patients. Results: Abdominal trachelectomy was attempted for 265 patients. Trachelectomy was converted to hysterectomy in 35 patients, and trachelectomy was completed successfully in 230 (conversion rate: 13%). Applying the FIGO 2018 staging system, 40% of the patients who underwent radical trachelectomy had stage IA tumors. Among 71 patients who had tumors measuring =2 cm, 8 patients were classified as stage IA1 and 14 as stage IA2. Overall recurrence and mortality rates were 2.2% and 1.3%, respectively. One hundred twelve patients attempted to conceive after trachelectomy; 69 pregnancies were achieved in 46 patients (pregnancy rate: 41%). Twenty-three pregnancies ended in first-trimester miscarriage, and 41 infants were delivered between gestational weeks 23 and 37; 16 were deliveries at term (39%) and 25 were premature deliveries (61%). Conclusion: This study suggested that patients judged to be ineligible for trachelectomy and patients receiving overtreatment will continue to appear using the current standard eligibility criteria. With the revisions to the FIGO 2018 staging system, the preoperative eligibility criteria for trachelectomy, which were based on the FIGO 2009 staging system and tumor size, should be changed. [ABSTRACT FROM AUTHOR]

Although the identification of late adolescents with subthreshold depression (StD) may provide a basis for developing effective interventions that could lead to a reduction in the prevalence of StD and prevent the development of major depressive disorder, knowledge about the neural basis of StD remains limited. The purpose of this study was to develop a generalizable classifier for StD and to shed light on the underlying neural mechanisms of StD in late adolescents. Resting-state functional magnetic resonance imaging data of 91 individuals (30 StD subjects, 61 healthy controls) were included to build an StD classifier, and eight functional connections were selected by using the combination of two machine learning algorithms. We applied this biomarker to an independent cohort (n = 43) and confirmed that it showed generalization performance (area under the curve = 0.84/0.75 for the training/test datasets). Moreover, the most important functional connection was between the left and right pallidum, which may be related to clinically important dysfunctions in subjects with StD such as anhedonia and hyposensitivity to rewards. Investigation of whether modulation of the identified functional connections can be an effective treatment for StD may be an important topic of future research. [ABSTRACT FROM AUTHOR]

Objective: To analyze the effects of in‐person attendance at an academic conference held during the Covid‐19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid‐19 virus. Methods: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7. Results: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in‐person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167–0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229–0.690, p = 0.0010]). Conclusion: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in‐person attendance at the congress. [ABSTRACT FROM AUTHOR]

Background: There is increasing evidence that diagnostic salivary tests measuring inflammatory biomarkers are being developed to assess inflammatory status for early detection, prevention, and progression of periodontal disease. Therefore, the aim of the present study was to investigate and identify the salivary biomarker that can predict the inflammatory status of periodontal disease. Methods: A total of 36 patients (28 women and 8 men) with an average age of 57 years were investigated. Unstimulated saliva was collected from the recruited subjects and analyzed using SillHa, a saliva-testing device that measures bacteria count, saliva buffer capacity, acidity, leukocyte esterase, protein, and ammonia. Periodontal parameters were then obtained by clinical examination and initial periodontal therapy was performed. Data obtained with SillHa were compared with clinical periodontal parameters at baseline, re-examination (three months from baseline), and final examination (six months from re-examination). Results: Leukocyte esterase activity in saliva measured by SillHa; BOP and PCR measured by clinical examination showed a significant difference between baseline and final examination and between re-examination and final examination. Patients in the lower median group (group 1) had a significant difference in leukocyte esterase activity between baseline and final examination and re-examination and final examination. In addition, patients in Group 1 had significantly lower BOP between baseline and final examination. While patients in the higher median group (group 2) showed a modest decrease in leukocyte esterase activity, which was significant only between baseline and final examination, no significant changes were observed concerning BOP. Furthermore, the associated systemic disease was observed in 30% and 81.2% of group 1 and 2 patients, respectively. Conclusion: The results suggest that leukocyte esterase activity in saliva measured by SillHa could serve as a reliable diagnostic marker for monitoring inflammatory status in periodontal disease. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the prevalence of locomotive syndrome (LS) and related musculoskeletal diseases [osteoarthritis (OA), lumbar spondylosis, and spinal alignment] in Type 2 diabetes mellitus (DM) patients. Methods: Clinical data were collected from 101 patients (55 males; 46 females) admitted to our hospital for diabetes education from October 2018 to April 2021. Patients underwent full-spine and whole-legs standing radiography and physical measurements (10-m walking and grip strength tests and three LS risk tests). Results: The estimated prevalence of LS was 86.1% (Stage 1: 44.5%, Stage 2: 41.6%), lumbar spondylosis was 11.9%, and hip, knee, and ankle OA were 16.9%, 51.5%, and 12.9%, respectively. Multiple logistic regression analysis identified grip strength [odds ratio (OR) = 0.89, confidence interval (CI) = 0.83-0.94], diabetic retinopathy (OR = 5.85, CI = 1.64-20.78), knee OA (OR = 3.34, CI = 1.11-10.02), and a sagittal vertical axis >40 mm (OR = 3.42, CI = 1.13-10.39) as significantly associated risk factors for worsening LS in Type 2 DM patients. Conclusions: This study clarified the epidemiological indicators of LS and associated factors in DM patients. Exercise therapy and DM management are effective strategies to reduce the occurrence and progression of LS. [ABSTRACT FROM AUTHOR]

Objective To assess the longitudinal changes in nailfold videocapillaroscopy (NVC) in patients expressing myositis-specific autoantibodies [anti-aminoacyl-tRNA synthetase (ARS), anti-transcriptional intermediary factor 1 (TIF1), and anti-melanoma differentiation-associated gene 5 (MDA5)]. Methods This study was performed retrospectively, at a single site, on an observational cohort. Seventy-one idiopathic inflammatory myopathy patients were included (25 patients expressed anti-MDA5 Abs, 24 patients expressed anti-TIF1 Abs, and 22 patients expressed anti-ARS Abs). NVC findings included giant, enlarged, and reduced capillaries, haemorrhages, capillary ramification, disorganization of the vascular array, and capillary loss. NVC findings were compared from baseline to after disease activity stabilization. Results The frequency of enlarged capillaries at baseline was different among the three groups, and was significantly higher in patients with anti-TIF1 Abs compared with those with anti-ARS Abs (88% vs 55%, P  < 0.05). Reduced capillaries were significantly increased in patients with anti-TIF1 Abs compared with those with anti-MDA5 (96% vs 44%, P  < 0.0001) or anti-ARS Abs (96% vs 50%, P  < 0.0005). Both enlarged and reduced capillaries improved after stabilization in patients with anti-MDA5 Abs (P  < 0.0001 and P  < 0.05, respectively). These improvements were not observed in patients expressing anti-TIF1 and anti-ARS Abs. However, a significant reduction in haemorrhages was observed in all three groups (P  < 0.0001 for each group). Conclusions The results of this study demonstrate that longitudinal changes in NVC findings may vary depending on myositis-specific Ab expression. Therefore, it is crucial to assess individual NVC findings separately, as each finding may impact disease activity in a different manner. [ABSTRACT FROM AUTHOR]

The obturator nerve originates from the lumbar plexus and innervates sensation in the thigh and movement of the adductor muscle group of the hip. Reports on physical therapy for patients with obturator nerve injuries have been limited due to insufficient injuries, and there have been no reports on rehabilitation after neurotmesis. Furthermore, there are no reports on the status of activities of daily living (ADL) and details of physical therapy in patients with paralysis of the adductor muscle group. In this study, we reported on a patient with adductor paralysis due to obturator neurotmesis, including the clinical symptoms, characteristics of ADL impairment, and effective movement instruction. The patient is a woman in her 40's who underwent laparoscopic total hysterectomy, bilateral adnexectomy, and pelvic lymph node dissection for uterine cancer (grade-2 endometrial carcinoma). During pelvic lymph node dissection, she developed an obturator nerve injury. She underwent nerve grafting during the same surgery by the microsurgeon. Donor nerve was the ipsilateral sural nerve with a 3-cm graft length. Due to obturator nerve palsy, postoperative manual muscle test results were as follows: adductor magnus muscle, 1; pectineus muscle, 1; adductor longs muscle, 0; adductor brevis muscle, 0; and gracilis muscle, 0. On postoperative day 6, the patient could independently perform ADL; however, she was at risk of falling toward the affected side when putting on and taking off her shoes while standing on the affected leg. The patient was discharged on postoperative day 8. Through this case, we clarified the ADL impairment of a patient with adductor muscle palsy following obturator neurotmesis, and motion instruction was effective as physical therapy for this disability. This case suggests that movement instruction is important for acute rehabilitation therapy for patients with hip adductor muscle group with obturator neurotmesis. [ABSTRACT FROM AUTHOR]

Mitochondria are indispensable in maintaining hematopoietic stem cells (HSCs), and mitochondrial complex II (MCII) has been recognized as a key component of HSCs. However, the physiological role of MCII on long-term hematopoiesis and hematopoietic reconstitution capacity remains unknown. Hence, this study evaluated the impact of MCII dysfunctions on long-term HSC maintenance and hematopoietic homeostasis among conditional transgenic mice with a missense mutation in the succinate dehydrogenase complex subunit C gene (SdhcV69E). HSCs collected from SdhcV69E mice had a higher reactive oxygen species (ROS) accumulation and DNA damage in response to mitochondrial activation. Via the aging stress response, MCII dysfunctions caused decreased white blood cell count with myeloid-skewing property, macrocytic anemia, and thrombocytosis. Moreover, the HSCs of aged SdhcV69E mice exhibited greater ROS accumulation and lower membrane potential. Transplantation-induced replicative stress also caused premature senescent hematopoiesis. Furthermore, accelerated ROS accumulation and profound DNA damage in HSCs were observed in the SdhcV69E-derived cell recipients. The long-term hematopoietic reconstitution capacity was remarkably impaired in HSCs from the SdhcV69E-derived cell recipients. Taken together, MCII plays an essential role in long-term hematopoiesis, and MCII dysfunctions with aging or replicative stresses caused excessive ROS accumulation and DNA damage in HSCs, leading to premature senescence. Graphical Abstract [ABSTRACT FROM AUTHOR]

A foodborne outbreak related to milk cartons served in school lunches occurred in June 2021, which involved more than 1,800 cases from 25 schools. The major symptoms were abdominal pain, diarrhoea, vomiting, and fever. Although major foodborne toxins and pathogens were not detected, a specific Escherichia coli strain, serotype OUT (OgGp9):H18, was predominantly isolated from milk samples related to the outbreak and most patients tested. The strains from milk and patient stool samples were identified as the same clone by core genome multilocus sequence typing and single-nucleotide polymorphism analysis. The strain was detected in milk samples served for two days related to the foodborne outbreak at a rate of 69.6% and levels of less than ten most probable number/100 mL but not on days unrelated to the outbreak. The acid tolerance of the strain for survival in the stomach was similar to that of enterohaemorrhagic E. coli O157:H7, and the same inserts in the chu gene cluster in the acid fitness island were genetically revealed. The pathogenicity of the strain was not clear; however, it was indicated that the causative pathogen was atypical diarrhoeagenic E. coli OUT (OgGp9):H18. [ABSTRACT FROM AUTHOR]

Purpose: This study compared concentric–eccentric coupled (CON-ECC), concentric-only (CON), and eccentric-only (ECC) resistance training of the elbow flexors for their effects on muscle strength and hypertrophy. Methods: Non-resistance-trained young adults were assigned to one of the four groups: CON-ECC (n = 14), CON (n = 14) and ECC (n = 14) training groups, and a control group (n = 11) that had measurements only. The training group participants performed dominant arm elbow flexor resistance training in extended elbow joint angles (0°–50°) twice a week for 5 weeks. The total training volume (dumbbell weight × number of contractions) in CON-ECC (5745 ± 1020 kg) was double of that in CON (2930 ± 859 kg) and ECC (3035 ± 844 kg), because 3 sets of 10 contractions were performed for both directions in CON-ECC. Maximum voluntary isometric (MVC-ISO), concentric (MVC-CON), and eccentric contraction (MVC-ECC) torque of the elbow flexors and biceps brachii and brachialis muscle thickness (MT) were measured at baseline, and 3–9 days post-last training session. Results: No significant changes in any measures were evident for the control group. The CON-ECC and ECC groups showed increases (P < 0.05) in MVC-ISO (12.0 ± 15.7% and 11.3 ± 10.8%, respectively) and MVC-ECC torque (12.5 ± 18.3%, 16.2 ± 11.0%) similarly. Increases in MVC-CON torque (P < 0.05) were evident for the CON-ECC (17.5 ± 13.5%), CON (10.5 ± 12.8%), and ECC (14.2 ± 10.4%) groups without a significant difference among groups. MT increased (P < 0.01) after CON-ECC (10.6 ± 5.4%) and ECC (9.7 ± 7.2%) similarly, but not significantly after CON (2.5 ± 4.8%). Conclusions: ECC training increased muscle strength and thickness similarly to CON-ECC training, despite the half training volume, suggesting that concentric contractions contributed little to the training effects. [ABSTRACT FROM AUTHOR]

Although foam rolling interventions with and without vibration have been used to increase flexibility in the field of sports, their effects on passive and active properties remain unclear. Hence, this study aimed to investigate the effects of foam rolling interventions on range of motion (ROM), shear elastic modulus, plantarflexor muscle strength, and jump performance. This randomized, controlled, crossover study included 16 healthy male subjects who visited the laboratory 3 times (control condition, foam rolling condition, and vibration foam rolling condition), each with an interval of >72 hours. In both foam rolling and vibration foam rolling conditions, subjects were instructed to perform 60-second bouts of intervention for 3 sets, with 30-second rest between each set. In the vibration foam rolling condition, the intensity of vibration was set at a frequency of 48 Hz. Dorsiflexion (DF) ROM, shear elastic modulus, plantar flexor muscle strength, and drop jump height were determined before and after the rolling intervention. Our results showed a similar increase in dorsiflexion range of motion (p < 0.01, d = 0.51; p < 0.01, d = 0.65, respectively) and passive torque at dorsiflexion range of motion (p = 0.02, d = 0.51 and p < 0.01, d = 0.65, respectively) after foam rolling and vibration foam rolling. Medial gastrocnemius shear elastic modulus decreased only after vibration foam rolling (p < 0.01, d = 0.44). No significant main effects of time were observed in maximal voluntary isometric contraction torque (F = 2.0, p = 0.15, ηp² = 0.119) and drop jump height (F = 1.5, p = 0.24, ηp² = 0.091) after both interventions. Maximal voluntary concentric contraction torque showed a significant main effect of time (F = 7.59, p = 0.02, ηp² = 0.336). However, only after foam rolling, the maximal voluntary concentric contraction torque significantly decreased (p = 0.01, d = 0.39). Our results suggest that vibration foam rolling effectively alters passive muscle properties without decreasing muscle strength and performance. [ABSTRACT FROM AUTHOR]

Background: The purpose of the current study was to investigate factors related to morphological changes in the masseter muscle after preoperative orthodontic treatment in patients with skeletal class III dentofacial deformities for analysis of muscle changes and malocclusions. Methods: Twenty female patients with dentofacial deformities were included in the study. Computed tomography was performed before and after preoperative orthodontic treatment, and the lengths, widths, and cross-sectional areas of the masseter muscles were measured. Changes in these parameters were evaluated, and factors related to changes in masseter muscle area after preoperative orthodontic treatment were analyzed. Results: The lengths, widths, and areas of masseter muscles were significantly smaller after preoperative orthodontic treatment. Smaller masseter muscle area was significantly associated with changes in overbite and pretreatment values of SNA angle. Conclusions: Atrophy of the masseter muscle during preoperative orthodontic treatment was greater in patients with increased open bite due to improved dental compensation in patients with skeletal class III dentofacial deformities with maxillary retraction. [ABSTRACT FROM AUTHOR]

Aim: Westernization of lifestyle has increased the numbers of patients with endometrial cancer and obesity. This study aimed to compare the clinical outcomes of robotic‐assisted surgery according to whether patients are obese, morbidly obese, or nonobese. Methods: Sixty‐three patients with endometrial cancer who underwent robotic‐assisted surgery between March 2014 and June 2022 were categorized according to whether they had a body mass index (BMI) <30 (group A, nonobese, n = 40), ≥30 and <35 (group B, obese, n = 13), or ≥35 (group C, morbidly obese, n = 10). Operation time, blood loss, perioperative complications, and recurrence rate were investigated. Results: Conversion to laparotomy was required in one case in group A and one in group C. There was no difference in total operation time, time for setting (including trocar installation and docking of the da Vinci robot), console time, or time for wound closure between the groups; however, there was a significant between‐group difference in the total time for setting and wound closure. There was no significant difference in blood loss or complications between the groups. Three patients in group A and two in group B received adjuvant treatment; none have shown evidence of recurrent disease during a mean observation time of 21 months (range, 2–29). Two cases in group A and one in group B had recurrence during a mean observation time of 38 months (range, 19–46). Conclusion: Patients with endometrial cancer who are obese can be treated safely by robotic‐assisted surgery with a low risk of complications and few relapses. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the influence of sex, age, and quadrivalent vaccination history on adverse reactions (ARs) to influenza vaccines and the relationship between the occurrence of ARs and the risk of influenza infection. Study participants were employees of three hospitals in the Hyogo Prefecture, Japan, who received the influenza vaccine in 2019. Data were collected using questionnaires. The main factors were age, sex, and history of influenza vaccination as a control. The primary outcomes were the incidence of local and systemic ARs attributable to the vaccine and positive influenza cases among the participants during the influenza season. Logistic regression was used to calculate the odds ratio (OR) and 95% confidence interval (CI). Among the 1493 participants, 80% experienced either local or systemic ARs. ARs were less common among men than among women (OR: 0.28, 95% CI: 0.21–0.37) and less common among those aged ≥60 years (OR: 0.48, 95% CI: 0.26–0.89). ARs were significantly more likely to occur in those with a history of influenza vaccination (OR: 1.96, 95% CI: 1.15–3.33). Those who had ARs, notably localized ones, were significantly more likely to incur influenza infection. Individuals who report ARs to influenza vaccination should strictly adopt non-pharmaceutical preventive measures in the hospital, community settings, and at home. [ABSTRACT FROM AUTHOR]

Ovarian low-grade serous carcinoma (LGSC) is usually a slow growing tumor with a relatively good prognosis. However, LGSC that have relapsed are highly resistant to chemotherapy, and there is currently no established treatment for them in contrast to high-grade serous carcinoma (HGSC). Here, we first review the literature on this topic and then describe a case of LGSC that relapsed and responded to Gemcitabine and Bevacizumab. The patient was a 37-year-old nulliparous woman who had undergone three cycles of topotecan after initial surgery at age 28.5 years as well as three months later during a disease-free interval. Intraperitoneal dissemination was observed and laparoscopic biopsy was performed. Histopathological examination revealed LGSC, and genetic testing revealed mutations in the neurofibromatosis type 1 (NF1) and TP53 genes. The mass of the disseminated lesion subsequently increased overall, and subileus was observed. The patient was treated, but the operation was incomplete. Postoperatively, Gemcitabine and Bevacizumab therapy was started. After six cycles, tumor markers became negative and Positron Emission Tomography-CT (PET-CT) showed decreased tumor activity. There were 20 cycles without any symptoms. LGSC is often resistant to anticancer drugs, but Gemcitabine and Bevacizumab therapy was able to suppress the lesions and symptoms in this case. With these findings, future genomic testing may assist in the treatment strategy for cases of LGSC recurrence, which are considered to be less likely to respond to anticancer drugs. Comprehensive genetic analysis will hopefully lead to the molecular mechanism of carcinogenesis for more effective and targeted therapies. [ABSTRACT FROM AUTHOR]

Aim: A maxillary left central incisor had been traumatised and undergone incorrect repositioning, causing apical fenestration of the cortical bone and patient discomfort. The aim of this case report was to evaluate the use of cone beam computed tomography (CBCT) in the diagnosis and treatment evaluation of lateral luxation injuries. Materials and methods: CBCT was used to accurately image and diagnose the lateral luxation. The tooth was root canal treated, orthodontically repositioned and aesthetically restored with resin composite. Results: Root canal treatment resolved the periapical pathology, and orthodontic treatment brought the tooth back into an anatomically appropriate position, with regeneration of labial cortical bone and complete resolution of patient discomfort. The 15-month follow-up was uneventful and the tooth was in good condition, both clinically and radiographically. Conclusion: CBCT providing detailed three-dimensional images of teeth and surrounding tissues was a promising tool for the management of lateral luxation injury. [ABSTRACT FROM AUTHOR]

Background: The major complication of renal biopsy is bleeding. Infection is an extremely rare complication of percutaneous renal biopsy, providing sterile techniques are used and bowel perforation does not occur. However, the questionnaire included in the Kidney Biopsy Guidebook 2020 in Japan reported that antibiotic prophylaxis was administered to patients undergoing percutaneous renal biopsy at 61% of 170 adult institutions and 57% of 54 pediatric institutions. The objective of this study is to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy.Methods: Patients aged ≥15 years who are scheduled to undergo percutaneous renal biopsy are eligible for inclusion in the study. Three hundred and sixty-four patients will be recruited at 6 hospitals. The patients will be randomly assigned at a 1:1 ratio to receive either a single dose of intravenous cefazolin (1 g) or no antibiotic prophylaxis. The primary outcome is the number of patients that exhibit positive urine cultures (>105 colony-forming units/ml) 3 or 4 days after the renal biopsy, or at which point the patients are diagnosed with pyelonephritis until 3 or 4 days after the renal biopsy. The secondary outcomes are the number of patients who are diagnosed with pyelonephritis within 30 days after the renal biopsy, the number of patients who are diagnosed with puncture site infections within 30 days after the renal biopsy, the number of patients who are diagnosed with an infection other than pyelonephritis or a puncture site infection within 30 days after the renal biopsy, and the number of patients who experience cefazolin-induced side effects.Discussion: This randomized controlled trial aims to show the non-inferiority of not administering antibiotic prophylaxis for percutaneous renal biopsy. If this study shows that antibiotic prophylaxis is not needed, it would help to ensure patient safety and prevent the development of antibiotic-resistant bacteria.Trial Registration: UMIN Clinical Trials Registry (UMIN-CTR) UMIN000042378 . Registered on 7 Nov 2020. [ABSTRACT FROM AUTHOR]

Background: Marfan syndrome (MFS) is a systemic disorder of connective tissues caused by insufficient elastic fiber formation that leads to structural weakness and results in various tissue disorders, including cardiovascular and periodontal disease. Notably however, the risk of periodontal disease in MFS patients affected by an aortic aneurysm or dissection has not yet been clarified. Methods: We investigated the periodontal condition in the following three groups: MFS patients diagnosed with an aortic aneurysm or dissection with a planned aortic surgery (MFS surgery), MFS patients who had already undergone aortic surgery (MFS post-surgery) and healthy control patients (Healthy). The periodontal condition of all of these patients was evaluated at their first visit, reassessed again at two-month after the first visit, and evaluated again at a six-month follow-up after the reassessment. Results: A total of 14 participants, 3 MFS surgery patients, 4 MFS post-surgery patients and 7 healthy control volunteers were examined. Saliva examinations revealed no significant differences between any of the groups at the first visit, reassessment, or follow-up. Interestingly, the MFS surgery cases showed a higher BOP and PISA at the first visit and follow-up compared with the other groups. In contrast, the MFS surgery patients showed an improvement in their LVDd and EF values, both markers of cardiac function, at the reassessment and follow-up compared with the first visit. Conclusions: MFS associated with an aortic aneurysm or dissection leads to a higher risk of periodontal disease, indicating the need for more frequent oral hygiene maintenance in these patients. In addition, MFS patients who undergo frequent professional cleaning of their teeth show a lower onset of cardiovascular disease, suggesting that professional oral hygiene in these cases contributes to a healthier condition. [ABSTRACT FROM AUTHOR]