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Corynebacterium species are an important cause of granulomatous mastitis (GM). Although there have been worldwide reports of infections caused by Corynebacterium kroppenstedtii, few cases of C. tuberculostearicum GM have been reported. We conducted a retrospective study to investigate the clinical and microbiological characteristics of GM caused by Corynebacterium spp. between January 1, 2014, and May 31, 2024. During the study period, six patients with GM were identified, including four cases of C. kroppenstedtii GM and two cases of C. tuberculostearicum GM. All patients were female with a median age of 32 years (range: 18-50 years). All patients underwent surgical drainage and were treated with clarithromycin. The minimum inhibitory concentration (MIC) values for various antimicrobial agents, including azithromycin, clarithromycin, ciprofloxacin, clindamycin, and trimethoprim-sulfamethoxazole, were higher for C. tuberculostearicum than for C. kroppenstedtii. Additionally, MALDI-TOF MS and 16s rRNA gene sequencing accurately identified C. kroppenstedtii and C. tuberculostearicum. Accurate identification of lipophilic Corynebacterium spp. is important for antibiotic treatment selection. If clinicians suspect lipophilic Corynebacterium spp. infection, particularly GM, they should ask the microbiology laboratory to test for lipophilic Corynebacterium spp., Competing Interests: Declaration of competing interest The authors state that they have no conflict of interest., (Copyright © 2025 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

The effect of smoking on hypertensive disorders of pregnancy is a public concern. Recent evidence suggests that the risk of hypertensive disorders of pregnancy is influenced by the presence of uterine fibroids. We explored the association between maternal smoking exposure and the risk of hypertensive disorders of pregnancy in relation to the presence of uterine fibroids using data from Japan's largest birth cohort study. This study focused on first-time mothers, and the study population comprised 2752 and 35,294 first-time mothers with and without uterine fibroids, respectively. Hypertensive disorders of pregnancy was categorized as early-onset (before 34 weeks) and late-onset (after 34 weeks). Maternal smoking exposure was assessed by measuring the urinary cotinine concentration during the mid-trimester. Participants were classified into four quartiles based on their urinary cotinine levels as follows: Q1 (low concentration) to Q4 (high concentration). Multivariate analysis adjusted for potential confounders revealed that in women without uterine fibroids, the Q3 urinary cotinine level was associated with a modified risk of early-onset hypertensive disorders of pregnancy (adjusted odds ratio: 0.63, 95% confidence interval: 0.44-0.89). Conversely, for women with uterine fibroids, Q4 urinary cotinine level was associated with an increased risk of hypertensive disorders of pregnancy (adjusted odds ratio: 1.68, 95% confidence interval: 1.05-2.72). In conclusion, this study indicated that the impact of maternal smoking exposure varied based on the presence of uterine fibroids, underscoring the importance of personalized preconception care., Competing Interests: Compliance with ethical standards. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objective: Preeclampsia (PE) is a pregnancy-specific hypertensive disorder. Late-onset (Lo)-PE can cause serious complications in both the mother and child. This study aimed to explore biomarkers for elucidating the mechanisms underlying Lo-PE, via a metabolomic analysis of first-trimester maternal serum., Methods: This study was conducted at Fukushima Regional Center as an adjunct to Japan Environment and Children Study and included 12 patients with Lo-PE matched to 12 women with healthy pregnancies. Capillary electrophoresis-mass spectrometry-based quantitative analyses of charged metabolites were performed on first-trimester maternal serum samples., Results: Overall, 183 charged metabolites were identified. The peak area of glucosamine was significantly higher for the first-trimester sera of patients with Lo-PE than that for controls. Conversely, the peak area of serotonin was significantly decreased in the sera of patients with Lo-PE., Conclusions: During early pregnancy, glucosamine and serotonin levels in maternal serum may serve as early biomarkers for Lo-PE. As part of preconception care, pre-pregnancy dietary habits and mental health could potentially prevent Lo-PE onset.

Background/aim: Osimertinib is a well-tolerated first- or second-line treatment option for elderly patients with epidermal growth factor receptor mutation-positive advanced non-small cell lung cancer. However, the safety of osimertinib in elderly patients requires further investigation. Herein, we identified safety signals for various osimertinib-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database., Patients and Methods: Data from the JADER database from April 2004 to March 2023 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection for osimertinib-related AEs in elderly patients (≥70 years old) was determined using the relative elderly reporting odds ratio (ROR). For osimertinib-related AEs, we extracted 92 preferred terms (PTs) and nine standardized MedDRA queries (SMQs)., Results: Safety signals in elderly patients were detected for "Cardiomyopathy (PT)" and "Cardiomyopathy (SMQ)". The symptoms most frequently associated with "Cardiomyopathy (SMQ)" included "Ejection fraction decreased (PT)", "Cardiomyopathy (PT)", and "Stress cardiomyopathy (PT)". Notably, 53.7% of these outcomes were "Recovery" or "Remission". The median time to the onset of "Cardiomyopathy (SMQ)" in elderly patients was 85 days (range=2-537 days)., Conclusion: We demonstrated that patients ≥70 years potentially have increased osimertinib-related cardiomyopathy compared with patients <70 years. In the future, it is necessary to conduct research focusing on cardiomyopathy in elderly patients., Competing Interests: The Authors declare no conflicts of interest in relation to this study., (©2024 The Author(s). Published by the International Institute of Anticancer Research.)

Objectives: Hypertensive disorders of pregnancy (HDP) are a significant cause of morbidity and mortality. This study aimed to investigate whether preconception dietary fiber intake is associated with new-onset HDP., Study Design: We identified 84,873 (primipara, 33,712; multipara, 51,161) normotensive participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. The participants were subsequently categorized into five groups based on their preconception dietary fiber intake quintiles (Q1-Q5)., Main Outcome Measures: The main obstetric outcome was HDP, and the secondary obstetric outcomes included early-onset (Eo, <34 weeks)-HDP, late-onset (Lo, ≥34 weeks)-HDP, small for gestational age (SGA) births, and HDP with/without SGA., Results: Multiple logistic regression analysis showed that in primiparas, the risks of HDP, Lo-HDP, and HDP without SGA were lower in the Q5 group compared with the Q3 group (HDP: adjusted odds ratio [aOR] = 0.73, 95 % confidence intervals [95 % CI] = 0.58-0.93; Lo-HDP: aOR = 0.72, 95 % CI = 0.55-0.94; and HDP without SGA: aOR = 0.68, 95 % CI = 0.53-0.88). However, the risks of Eo-HDP and HDP with SGA were higher in the Q1 group compared with the Q3 group (Eo-HDP: aOR = 1.66, 95 % CI = 1.02-2.70; and HDP with SGA: aOR = 1.81, 95 % CI = 1.04-3.17). In multiparas, the risks of Lo-HDP and SGA were higher in the Q1 group compared with the Q3 group (Lo-HDP: aOR = 1.47, 95 % CI = 1.10-1.97; SGA: aOR = 1.17, 95 % CI = 1.02-1.35)., Conclusions: Preconception dietary fiber intake is beneficial in preventing HDP onset. Therefore, new recommendations should be considered to encourage higher dietary fiber intake as part of preconception care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Background: Older candidates for transcatheter aortic valve replacement (TAVR) frequently present with both cardiac and noncardiac comorbidities. There are few risk scores that evaluate a wide range of comorbidities., Methods: Patients who underwent TAVR for severe aortic stenosis were retrospectively evaluated. A new prediction model (Cardiac and nonCardiac Comorbidities risk score: 3C score) was determined based on coefficient in the multivariate Cox regression analysis for two-year all-cause mortality. C -statistics were assessed to compare the predictive abilities of the 3C score, the Charlson Comorbidities Index (CCI) score, the European System for Cardiac Operative Risk Evaluation (EuroSCORE) II, and the Model for End-stage Liver Disease eXcluding International normalized ratio (MELD-XI) score., Results: The present study included 226 patients (age, 86 ± 5 years; males, 38 %). The values of the CCI score, EuroSCORE II, and MELD-XI score were 2 (1-3), 3.36 (2.12-4.58), and 5.35 (3.05-8.55), respectively. Multivariate Cox regression analysis identified two cardiac (left ventricular ejection fraction [LVEF] <40 % [2 points]; pulmonary hypertension [1 point]) and three noncardiac comorbidities (hepatobiliary system impairment [3 points]; estimated glomerular filtration rate <30 ml/min/1.73 m 2 [1 point]; cachexia [1 point]). The C -statistics of the 3C score, EuroSCORE II, MELD-XI score, and CCI score were 0.767 (0.666-0.867), 0.610 (0.491-0.729), 0.580 (0.465-0.696), and 0.476 (0.356-0.596), respectively (p < 0.001)., Conclusions: Among cardiac and noncardiac comorbidities, special attention should be given to hepatobiliary system impairment and reduced LVEF in older patients following TAVR. The 3C score may contribute to the risk stratification., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Purpose: Minimally invasive glaucoma surgery is safer and effective surgical modality for patients with glaucoma. To compare the effect of axial length (AL) on the surgical outcomes of combined cataract surgery and ab interno trabeculotomy (phaco-LOT), a retrospective, non-randomized comparative study was performed., Methods: In total, 458 eyes of 458 open-angle glaucoma patients who underwent phaco-LOT and were followed-up without any intervention for at least 6 months were enrolled. All were divided into a long-AL group (AL ≥ 26.0 mm, 123 eyes) and a not-long-AL group (AL < 26.0 mm, 335 eyes). The principal outcomes were the changes in intraocular pressure (IOP) and medication scores. We also sought a correlation between postoperative IOP spike and hyphema., Results: Significant postoperative reductions in IOP and medication scores were apparent in all subjects. The IOP reductions were significant at all timepoints in the not-long-AL group, but not until 1 month postoperatively in the long-AL group, and the IOP change was significantly lower in the long-AL group from postoperative day 1 to 3 months. On subanalysis of subjects by age, the microhook used, the pre-operative IOP, and the medication score, a significantly higher incidence of IOP spike was observed in the long-AL group in weeks 1 and 2 (both p < 0.05), but this did not correlate with hyphema status, implying that a different mechanism was in play., Conclusion: Phaco-LOT was effective regardless of AL, but the postoperative IOP decrease was lower and the early postoperative incidence of IOP spike was higher in long-AL eyes., (© 2023. The Author(s).)

Objectives: Although risk factors for unsuccessful Maze procedure have been demonstrated, an appropriate patient selection is still controversial. In our institute, Maze procedure is indicated for those whom normal sinus rhythm (NSR) was reestablished by intraoperative direct cardioversion (DC) after ventricular unloading by total cardiopulmonary bypass. The purpose of this study was to evaluate the effectiveness of our indication criteria for Maze procedure in patients with mitral valve disease., Methods: Between October 2012 and October 2021, MAZE was indicated in 55 patients in whom normal sinus rhythm (NSR) was reestablished by intraoperative direct current cardioversion (DC). Three endpoints and predictors were examined: disappearance of atrial fibrillation (AF), NSR, and A-wave detection., Results: Restoration of NSR by intraoperative DC was confirmed in 43 patients, and these patients underwent MAZE. AF disappeared in 39 patients (90.7%), and F-wave ≥ 0.1 mV was a significant predictive factor (odds ratio (OR) 20.99, 95% CI 1.22-1079.06). NSR was reestablished in 36 patients (83.7%), and F-wave ≥ 0.1 mV (odds ratio 15.62, 95% CI 1.62-359.86) + AF history ≤ 3 years (OR 8.30, 95% CI 1.09-177.04) were significant predictors. A-wave detection was confirmed in 26 patients (60.5%), and left atrial diameter ≤ 55 mm was a significant predictor (OR 5.22, 95% CI 1.28-24.79)., Conclusions: Intraoperative DC after ventricular unloading resulted effective patient selection for concomitant Maze procedure. F-wave and AF history were predictive factor of electrical restoration of AF, and left atrial diameter was predictive factor of restoration of atrial function., (© 2024. The Author(s).)

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. Therefore, this study aimed to determine whether preconception dietary fiber intake is associated with PTB. This was a prospective cohort Japan Environmental and Children's Study (JECS). The study population comprised 85,116 singleton live-birth pregnancies from the JECS database delivered between 2011 and 2014. The participants were categorized into five groups based on their preconception dietary fiber intake quintiles (Q1 and Q5 were the lowest and highest groups, respectively). Multiple logistic regression analysis was performed to determine the association between preconception dietary fiber intake and PTB. Multiple logistic regression analysis revealed that the risk for PTB before 34 weeks was lower in the Q3, Q4, and Q5 groups than in the Q1 group (Q3: adjusted odds ratio [aOR] 0.78, 95% confidence interval [CI] 0.62-0.997; Q4: aOR 0.74, 95% CI 0.57-0.95; Q5: aOR 0.68, 95% CI 0.50-0.92). However, there was no significant difference between preconception dietary fiber intake and PTB before 37 weeks. In conclusion, higher preconception dietary fiber intake correlated with a reduced the risk for PTB before 34 weeks. Therefore, new recommendations on dietary fiber intake as part of preconception care should be considered.

Purpose: A higher body mass index (BMI) is associated with lower mortality in older patients following transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis. The current study aimed to investigate potential confounders of association between BMI and prognosis., Methods: The retrospective single-center study included consecutive patients following TAVR and excluded those in whom subcutaneous fat accumulation (SFA), visceral fat accumulation (VFA), and major psoas muscle (MPM) volume were not assessed by computed tomography. Cachexia was defined as a combination of BMI < 20 kg/m 2 and any biochemical abnormalities., Results: After 2 patients were excluded, 234 (age, 86 ± 5 years; male, 77 [33%]; BMI, 22.4 ± 3.8 kg/m 2 ; SFA, 109 (54-156) cm 2 ; VFA, 71 (35-115) cm 2 ; MPM, 202 (161-267) cm 3 ; cachexia, 49 [21%]) were evaluated. SFA and VFA were strongly correlated with BMI (ρ = 0.734 and ρ = 0.712, respectively), whereas MPM was weakly correlated (ρ = 0.346). Two-year all-cause mortality was observed in 31 patients (13%). Higher BMI was associated with lower mortality (adjusted hazard ratio [aHR], 0.86; 95% confidence interval [CI], 0.77-0.95). A similar result was observed in the multivariate model including SFA (aHR in an increase of 20 cm 2 , 0.87; 95% CI, 0.77-0.98) instead of BMI, whereas VFA was not significant. Cachexia was a worse predictor (aHR, 2.51; 95% CI 1.11-5.65)., Conclusions: Association of higher BMI with lower mortality may be confounded by SFA in older patients following TAVR. Cachexia might reflect higher mortality in patients with lower BMI., (© 2023. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

The right ventricular (RV) impairment can predict clinical adverse events in patients following transcatheter aortic valve replacement (TAVR) for severe aortic stenosis (AS). Limited reports have compared impact of the left ventricular (LV) and RV disorders. This retrospective study evaluated two-year major adverse cardiac and cerebrovascular events (MACCE) in patients following TAVR for severe AS. RV sphericity index was calculated as the ratio between RV mid-ventricular and longitudinal diameters during the end-diastolic phase. Of 239 patients, 2-year MACCE were observed in 34 (14%). LV ejection fraction was 58 ± 11%. Tricuspid annular plane systolic excursion (TAPSE) and RV sphericity index were 20 ± 3 mm and 0.36 (0.31-0.39). Although the univariate Cox regression analysis demonstrated that both LV and RV parameters predicted the outcomes, LV parameters no longer predicted them after adjustment. Lower TAPSE (adjusted hazard ratio per 1 mm, 0.84; 95% confidence interval, 0.75-0.93) and higher RV sphericity index (adjusted hazard ratio per 0.1, 1.94; 95% confidence interval, 1.17-3.22) were adverse clinical predictors. In conclusion, the RV structural and functional disorders predict two-year MACCE, whereas the LV parameters do not. Impact of LV impairment can be attenuated after development of RV disorders., (© 2024. The Author(s).)

Meniscal injury is a common cause of knee pain and functional impairment, often necessitating surgical intervention. Although magnetic resonance imaging (MRI) is frequently used for diagnosis, its accuracy is variable and may lead to false positives and negatives. To address these issues, needle arthroscopy has gained attention as a potential diagnostic alternative to MRI because of its immediate availability and ability to directly visualize intra-articular structures. This study aimed to assess the diagnostic capabilities of needle arthroscopy in comparison with MRI and diagnostic arthroscopy for meniscal injuries. Forty patients with suspected meniscal injuries requiring surgical treatment were enrolled between November 2017 and March 2019. A needle arthroscope with a 0.95-mm diameter was used to evaluate meniscal injuries. Three orthopaedic surgeons with approximately 10 years of experience independently evaluated the images from the needle arthroscopy, diagnostic arthroscopy, and preoperative MRI without any knowledge regarding patients' information. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each modality were used to compare the diagnostic accuracies. For lateral meniscus (LM) injuries, the sensitivity, specificity, PPV, and NPV of needle arthroscopy compared to diagnostic arthroscopy were 0.706, 0.852, 0.148, and 0.294, respectively. For medial meniscus (MM) injuries, the corresponding values were 0.889, 0.864, 0.136, and 0.111, respectively. In comparison, MRI had a lower sensitivity for LM injuries (0.588) and a higher sensitivity for MM injuries (1.0). The agreement between diagnostic arthroscopy and needle arthroscopy was moderate (kappa=0.517), while the agreements between diagnostic arthroscopy or needle arthroscopy and MRI were poor. Similar patterns were observed for the presence, location, and tear patterns of meniscal injuries. In conclusion, needle arthroscopy shows promise as an effective diagnostic modality for meniscal injuries, surpassing the limitations of MRI., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nakasa et al.)

Pseudomonas fulva is a Gram-negative rod that was isolated from Japanese paddy rice, and few cases of infections due to trauma, catheters, or contaminated infusion products have been reported. We report a case of P. fulva infection in an older patient who developed septic shock due to P. fulva during hospitalization after treatment for aspiration pneumonia. Since signs of infection were seen at the skin epidermal exfoliation site, which had been present since admission, this was considered to be the route of infection. The patient recovered on treatment with piperacillin. It was suggested that P. fulva can infect minor wounds in older individuals and lead to sepsis, even if the infection is not caused by a medical device or from severe trauma from an accident. This means that even small wounds, especially in older individuals, should be treated with caution, and a full body examination, including the skin, is essential even at the onset of sepsis. Although P. fulva has been identified as P. putida in many cases by conventional bacterial identification tests, it is expected that more cases will be accurately identified with the widespread use of polymerase chain reaction and mass spectrometry., Competing Interests: None., (© 2023 The Authors.)

Background: During anterior cruciate ligament (ACL) reconstruction, even when a posterior wall of the femoral bone tunnel is identified, computed tomography (CT) occasionally demonstrates a breach of the posterior femoral cortex of the femoral bone tunnel, i.e., posterior wall blowout, after ACL reconstruction (posterior wall blowout-like phenomenon). This study aimed to investigate the influence of the posterior wall blowout-like phenomenon on clinical outcomes after ACL reconstruction using hamstring tendon., Methods: A total of 105 patients who underwent CT examination two weeks after ACL reconstruction were enrolled. A cortical suspension device was used for femoral side fixation in all cases. Posterior wall was identified in all cases during the surgery. The side-to-side difference in anterior knee laxity, pivot shift test, Lysholm knee score, the International Knee Documentation Committee (IKDC) subjective form, and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were evaluated one year after the surgery. A second CT examination was performed 6-12 months after the surgery, if a posterior wall blowout-like phenomenon was identified in the first CT examination., Results: Two weeks after the surgery, 16 of the 105 patients showed a posterior wall blowout-like phenomenon. Twelve of the 16 cases demonstrated a regenerated posterior femoral cortex of the femoral bone tunnel on their second CT images. There were no significant differences between the posterior wall blowout-like phenomenon group and the normal posterior wall group in terms of a side-to-side difference in anterior knee laxity (0.4 ± 1.5 mm and 0.1 ± 1.6 mm, respectively), pivot shift test, Lysholm knee score, IKDC score, and KOOS at one year after surgery. The length and diameter of the femoral bone tunnel were not significantly different between the two groups., Conclusions: Posterior wall blowout-like phenomenon after ACL reconstruction using a cortical suspension device did not negatively influence clinical outcomes., Level of Evidence: III - retrospective comparative clinical study., Competing Interests: Declaration of competing interest The authors declare there are no conflicts of interest directly relevant to the content of this study., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: The aim of this study was to investigate the sectorized corneal thickness of eyes with corneal endothelial dysfunction using anterior-segment optical coherence tomography., Methods: We retrospectively collected anterior-segment optical coherence tomography data conducted before endothelial keratoplasty on 53 eyes of 53 patients with corneal endothelial dysfunctions including Fuchs endothelial corneal dystrophy, bullous keratopathy (BK) after trabeculectomy, and BK after laser iridotomy and from 18 normal eyes of 18 subjects. The imaging points were divided into 17 sectors. The mean for each sector was calculated and compared with the corresponding superior/inferior and temporal/nasal sectors., Results: In the normal eyes, the superior sectors were thicker than the inferior and the temporal sectors thinner than the nasal. In the diseased eyes, the superior sectors were thicker than the inferior in all subgroups; however, this tendency was no longer observed after the values were divided by the mean for the normal eyes. No significant differences were found on horizontal comparisons; however, after the values were divided by the mean for the normal eyes, the temporal sectors were thicker than the nasal. When comparing the values between the with-hole and the without-hole sides in the BK after laser iridotomy eyes, the sectors on the with-hole side were thicker than the other side., Conclusions: Corneal thickness of endothelial dysfunction was thicker in the superior sectors than the inferior but at a similar level to normal eyes. No significant differences were found for horizontal comparisons but, based on comparison with the normal eyes, the temporal sectors were thicker than the nasal., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Sialic acids (Sias) are often linked to galactose (Gal) residues by α2,6- and α2,3-linkages in glycans of glycoproteins. Sias are indispensable for vertebrate development, because organisms deficient in some enzymes in the Sia synthetic pathway are lethal during the development. However, it remains unknown if the difference of Siaα2,6Gal or α2,3Gal linkage has a critical meaning. To find a clue to understand significance of the linkage difference at the organism level, medaka was used as a vertebrate model. In embryos, Siaα2,6Gal epitopes recognized by Sambucus nigra lectin (SNA) and Siaα2,3Gal epitopes recognized by Maackia amurensis lectin (MAA) were enriched in the blastodisc and the yolk sphere, respectively. When these lectins were injected in the perivitelline space, SNA, but not MAA, impaired embryo body formation at 1 day post-fertilization (dpf). Most Siaα2,6Gal epitopes occurred on N-glycans owing to their sensitivity to peptide:N-glycanase. Of knockout-medaka (KO) for either of two β-galactoside:α2,6-sialyltransferase genes, ST6Gal I and ST6Gal II, only ST6Gal I-KO showed severe cardiac abnormalities at 7-16 dpf, leading to lethality at 14-18 dpf. Interestingly, however, these cardiac abnormalities of ST6Gal I-KO were rescued not only by forced expression of ST6Gal I, but also by that of ST6Gal II and the β-galactoside:α2,3-sialyltransferase IV gene (ST3Gal IV). Taken together, the Siaα2,6Gal linkage synthesized by ST6Gal I are critical in heart development; however, it can be replaced by the linkages synthesized by ST6Gal II and ST3Gal IV. These data suggest that sialylation itself is more important than its particular linkage for the heart development., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest regarding this manuscript., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The aim of this study was to determine the frequency of opioid-induced neurotoxicity (OIN) in cancer patients receiving oral controlled-release oxycodone and to define risk factors for OIN., Methods: This was a single-center, retrospective study of hospitalized adult cancer patients receiving oral controlled-release oxycodone between April 1, 2013, and April, 30, 2020. The onset of OIN within 30 days after oxycodone initiation in the study patients was investigated. OIN was defined as any of the following: delirium, hallucinations (visual or auditory), seizure, myoclonus, hyperesthesia, and excessive somnolence. Multivariate logistic regression analysis was performed to identify risk factors for OIN in patients receiving oxycodone., Results: In total, 520 patients were included in this study. The number of patients with OIN was 65 (12.5%). The median time until onset of OIN after oxycodone initiation was 7.5 days. Multivariate logistic regression analysis revealed that age ≥ 65 years (OR = 2.74, 95% CI [1.30-5.78], p = 0.008), total bilirubin ≥ 1.3 mg/dL (OR = 4.85, 95% CI [2.13-11.0], p < 0.001), and concomitant use of pregabalin or mirogabalin (OR = 3.11, 95% CI [1.47-6.61], p = 0.003) were significant independent risk factors for OIN., Conclusion: Age ≥ 65 years, liver dysfunction, and concomitant use of pregabalin or mirogabalin were independent risk factors for OIN in patients receiving oxycodone. Patients with these risk factors who are receiving oxycodone should be monitored for OIN, especially early in the administration of oxycodone., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We studied the association between operative timing and the feasibility of mitral valve (MV) repair in active infective endocarditis (IE)., Methods: Forty-nine active IE patients who underwent MV operation were classified according to operative timing: within 48 hours (Term I: n = 7), between 3 and 14 days (Term II: n = 22), and ≥15 days (Term III: n = 20). Patient profiles, operative outcomes, and feasibility of MV repair were evaluated. Complexity score and severity score were used to define the feasibility of MV repair depending on the extent of infected lesion and technical difficulties., Results: There were no differences in basic profile in the three groups. Rate of major complications was higher in Term I (86%) than II (41%, p = 0.031) and III (25%, p = 0.005). In-hospital mortality was also higher in Term I (43%) than II (9%, p = 0.039) and III (5%, p = 0.015). The three groups did not differ by feasibility of MV repair calculated by the two-score system or by frequency of MV repair (I: 57%, II: 59%, and III: 55%)., Conclusions: Morbidity and mortality were high in urgent cases. Feasibility of MV repair is associated with the extent of infected lesion and technical difficulties, and not with operative timing.

Aim: Hypertensive disorders of pregnancy (HDP) are a crucial cause of morbidity and mortality. We aimed to examine whether preconception carbohydrate intake is associated with new-onset HDP and small for gestational age (SGA) births., Methods: We identified 93 265 normotensive (primiparous, 37 387; multiparous, 55 878) participants from the Japan Environmental Children's Study database who delivered between 2011 and 2014. After excluding participants with multiple gestations, preconception hypertension, and insufficient data, primiparous and multiparous participants were categorized into five groups according to their preconception carbohydrate-intake quintiles (Q1 and Q5 were the lowest and highest groups, respectively). Multiple logistic regression analysis was performed to identify the effect of preconception carbohydrate intake on early (<34 weeks) and late-onset (≥34 weeks) HDP and the incidence of SGA births., Results: With the middle carbohydrate intake group (Q3) as a reference, the risk for late-onset HDP among multiparous women was higher in the Q5 group (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.02-1.69). The incidence of SGA births was higher in the Q1 group among both primiparous (aOR 1.16, 95% CI 1.01-1.33) and multiparous women (aOR 1.16, 95% CI 1.02-1.32)., Conclusions: Excessive carbohydrate intake increases the incidence of HDP in multiparous women, while low-carbohydrate intake increases the incidence of SGA births. New recommendations for preconception carbohydrate intake are required to prevent major HDP-related complications., (© 2022 Japan Society of Obstetrics and Gynecology.)

Objectives: The aneurysmal sac shrinkage has been reported as the strong predictor of favorable long-term outcome after endovascular aneurysm repair (EVAR). We evaluated the effects of perioperative and intraoperative factors on the aneurysm sac shrinkage. Methods: EVAR was performed for 296 patients during August 2009-December 2021. Nine patients with type Ia, Ib, or III; 69 patients with the sac diameter change less than 5 mm; and five patients with sac re-expansion after shrunk more than 5 mm were excluded. Thus, patients with sac shrinkage 5 mm or more (79 patients, shrinkage group) and with sac expansion 5 mm or more (18 patients) were included in this study. Antifibrinolytic therapy with tranexamic acid (TXA) 1500 mg/day for 6 months after EVAR was introduced in March 2013 and patent aortic side branches were coil embolized during EVAR since July 2015. Patients' background and patent aortic side branches at the end of EVAR were evaluated. Results: Univariate analysis for comparison between patients with sac shrinkage and sac expansion revealed that males (82.3% vs. 55.6%, p = 0.021), without antiplatelet therapy (40.5% vs. 66.7%, p = 0.044) and TXA (79.8% vs. 38.9%, p <0.001), were significantly associated with sac shrinkage. By multivariate analysis, the odds ratio of sac shrinkage was 11.7 for males, 0.1 for the patients on antiplatelet therapy, and 6.5 for the patient who received TXA. The patients with patent inferior mesenteric artery (IMA) were less in the shrinkage group (20.3% vs. 77.8%, p <0.001) and with two or less patent lumbar arteries (LAs) were more in the shrinkage group (82.3% vs. 33.3%, p < 0.001). The odd ratio of sac shrinkage was 7.8 for occluded IMA and 3.9 for two or less patent LAs. Conclusion: The possibility of sac shrinkage would be high for the patient with occluded IMA and two or less patent LA at the end of EVAR, and that patient received TXA after EVAR. (This is a translation of Jpn J Vasc Surg 2022; 31 : 291-297.)., (@ 2023 The Editorial Committee of Annals of Vascular Diseases.)

The purpose of the study was to investigate the number of examinations required to precisely predict the future central 10-degree visual field (VF) test and to evaluate the effect of fitting non-linear models, including quadratic regression, exponential regression, logistic regression, and M-estimator robust regression model, for eyes with glaucoma. 180 eyes from 133 open angle glaucoma patients with a minimum of 13 Humphrey Field Analyzer 10-2 SITA standard VF tests were analyzed in this study. Using trend analysis with ordinary least squares linear regression (OLSLR), the first, second, and third future VFs were predicted in a point-wise (PW) manner using a varied number of prior VF sequences, and mean absolute errors (MAE) were calculated. The number of VFs needed to reach the minimum 95% confidence interval (CI) of the MAE of the OLSLR was investigated. We also examined the effect of applying other non-linear models. When predicting the first, second, and third future VFs using OLSLR, the minimum MAE was obtained using VF1-12 (2.15 ± 0.98 dB), VF1-11 (2.33 ± 1.10 dB), and VF1-10 (2.63 ± 1.36 dB), respectively. To reach the 95% CI of these MAEs, 10, 10, and 8 VFs were needed for the first, second and third future VF predictions, respectively. No improvement was observed by applying non-linear regression models. As a conclusion, approximately 8-10 VFs were needed to achieve an accurate prediction of PW VF sensitivity of the 10-degree central VF., (© 2022. The Author(s).)

Bullous keratopathy (BK) is known to present with corneal edema and Descemet's folds, which can cause corneal astigmatism. However, no report quantitatively evaluated BK astigmatism by separating it into regular and irregular astigmatism. This study investigated the regular and irregular astigmatism of the anterior and posterior corneal surface with Fourier harmonic analysis and anterior segment optical coherence tomography. Preoperative data from 43 eyes of 41 BK patients who received corneal endothelial transplantation were compared with the data from 43 eyes of 43 subjects without corneal disease. Anterior and posterior cylinder power, central corneal thickness (CCT) and thinnest corneal thickness were significantly greater in BK. With Fourier harmonic analysis, BK eyes were found to have significantly larger anterior and posterior regular astigmatism, asymmetry component and higher-order irregularity. Asymmetry component and higher-order irregularity that accounted for the posterior irregular astigmatism increased as CCT increased in BK. Higher-order irregularity in the posterior cornea also positively correlated with worsening best corrected visual acuity. Subgroup analysis found significant correlations between CCT and posterior higher-order irregularity for intraocular surgery and laser iridotomy, but not Fuchs endothelial corneal dystrophy. This study has significance in that it revealed the characteristics of the corneal posterior irregular astigmatism of BK., (© 2022. The Author(s).)

Purpose: The detailed effects of age and systemic factors on intraocular pressure (IOP) have not been fully understood because of the lack of a large-scale longitudinal investigation. This study aimed to investigate the effect of various systemic factors on the longitudinal change of IOP., Methods: There were a total of 20,909 eyes of 10,471 subjects from a health checkup cohort that were followed up for systemic factors: (i) age at baseline, (ii) sex, (iii) time series body mass index (BMI), (iv) time series smoking habits, (v) time series systolic and diastolic blood pressures (SBP and DBP), and (vi) time series 19 blood examinations (all of the time series data was acquired at each annual visit), along with IOP annually for at least 8 years. Then the longitudinal effect of the systemic factors on the change of IOP was investigated., Results: IOP significantly decreased by -0.084 mm Hg/year. BMI, SBP, DBP, smoking habits, total triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and glycosylated hemoglobin A1c were not significantly associated with the change of IOP. Higher values of age, aspartate aminotransferase, hemoglobin, platelet, and calcium were suggested to be significantly associated with the decrease of IOP, whereas higher alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and female gender were significantly associated with the increase of IOP., Conclusions: Age, aspartate aminotransferase, hemoglobin, platelet, calcium, alanine aminotransferase, guanosine triphosphate, white blood cell count, red blood cell count, and gender were the systemic variables significantly associated with the change of IOP.

Objectives : Appropriateness of device selection, procedure protocol and aortic remodeling effects of entry closure (TEVAR) with stent-graft (SG) for patent false lumen type B aortic dissection (TBAD) were compared between the patients with narrow true lumen (narrow group) and those with aneurysmal dilated false lumen (aneurysmal group). Methods : Twenty-six patients with narrow true lumen (narrow group) and 20 patients with aneurysmal false lumen (aneurysmal group) were included in this study. In narrow group, straight SG was implanted from Zone 3 regardless the distance between the left subclavian artery and entry. In aneurysmal group, straight or taped SG was implanted with proximal landing zone length 20 mm or more. Thoracic aortic anatomy was evaluated by CT and aortic remodeling was defined as true lumen diameter ≥50% of the aortic diameter and occlusion of false lumen. Aorta related death, retrograde type A aortic dissection (RTAD), stentgraft induced new entry (SINE) and aortic maximum diameter enlargement 5 mm or more (aortic expansion) were included in the aortic event. Results : There was no procedure related complication in narrow group and 1 patient died due to aortic rupture in aneurysmal group, Type Ia endoleak by enhanced CT 7 days after TEVAR was detected in one patient in each group. Achievement of aortic remodeling was significantly better in narrow group. Aortic event occurred in only one patient in narrow group, in whom aortic expansion was observed. In aneurysmal group, aortic event occurred 12 patients (60%) and 2 RTAD, 5 SINE, and 8 aorta expansion were observed. Aortic event free rate was significantly better in narrow group. Conclusion : TEVAR procedure for the TBAD patients with narrow true lumen seemed to be appropriate, however, different TEVAR procedure or additional procedures would be required for those with aneurysmal dilated false lumen to obtain favorable outcomes. (This is secondary publication from Jpn J Vasc Surg 2021; 30: 347-357.)., Competing Interests: Conflicts of InterestThe authors of this study have no conflicts of interest to disclose., (© 2022 The Editorial Committee of Annals of Vascular Diseases.)

The purpose of this study was to evaluate corneal irregular astigmatism of patients with granular and lattice corneal dystrophy (GCD and LCD). 70 GCD, 35 LCD, and 81 control eyes were included. Anterior and posterior corneal topographic data obtained from anterior segment optical coherence tomography were expanded into four components via Fourier harmonic analysis. These components were compared with healthy eyes and the association between each component and best-corrected visual acuity (BCVA) was investigated. Anterior and posterior components increased in both GCD and LCD eyes. Anterior and posterior components of GCD2, anterior of LCD type 1 (LCD1), posterior of LCD type IIIA (LCD 3A), and type IV (LCD4) significantly increased. BCVA was significantly associated with anterior and posterior components in LCD eyes but not in GCD. The anterior components of LCD1, anterior and posterior of LCD3A, and posterior of LCD4 , were positively correlated with BCVA. As conclusions, in GCD eyes, anterior and posterior components differed from those of the control but BCVA was not significantly associated with them. In LCD eyes, the anterior and posterior components increased, and BCVA was significantly associated with the anterior and posterior components., (© 2022. The Author(s).)

Tendon is a fibrous connective tissue, that is, transmitting the forces that permit body movement. However, tendon/ligament biology is still not fully understood and especially, the role of miRNAs in tendon/ligament is sparse and uncharacterized in in vivo models. The objectives of this study were to address the function of DICER using mice with tendon/ligament-specific deletion of Dicer ( Dicer conditional knockout; cKO), and to identify key miRNAs in tendon/ligament. Dicer cKO mice exhibited hypoplastic tendons through structurally abnormal collagen fibrils with downregulation of tendon-related genes. The fragility of tendon did not significantly affect the tensile strength of tendon in Dicer cKO mice, but they showed larger dorsiflexion angle in gait compared with Control mice. We identified two miRNAs, miR-135a and miR-1247, which were highly expressed in the Achilles tendon of Control mice and were downregulated in the Achilles tendon of Dicer cKO mice compared with Control mice. miR-135a mimic increased the expression of tendon-related genes in injured Achilles tendon-derived fibroblasts. In this study, Dicer cKO mice exhibited immature tendons in which collagen fibrils have small diameter with the downregulation of tendon-related genes such as transcriptional factor, extracellular matrix, and miRNAs. Thus, DICER plays an important role in tendon maturation, and miR-135a may have the potential to become key miRNA for tendon maturation and healing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Omoto, Yimiti, Sanada, Toriyama, Ding, Hayashi, Ikuta, Nakasa, Ishikawa, Sano, Lee, Akimoto, Shukunami, Miyaki and Adachi.)

Optimal positive end-expiratory pressure (PEEP) can induce sustained lung function improvement. This prospective, non-randomized interventional study aimed to investigate the effect of individualized PEEP determined using electrical impedance tomography (EIT) in post-cardiac surgery patients (n = 35). Decremental PEEP trials were performed from 20 to 4 cmH2O in steps of 2 cmH2O, guided by EIT. PEEP levels preventing ventilation loss in dependent lung regions (PEEPONLINE) were set. Ventilation distributions and oxygenation before the PEEP trial, and 5 min and 1 h after the PEEPONLINE setting were examined. Furthermore, we analyzed the saved impedance data offline to determine the PEEP levels that provided the best compromise between overdistended and collapsed lung (PEEPODCL). Ventilation distributions of dependent regions increased at 5 min after the PEEPONLINE setting compared with those before the PEEP trial (mean ± standard deviation, 41.3 ± 8.5% vs. 49.1 ± 9.3%; p < 0.001), and were maintained at 1 h thereafter (48.7 ± 9.4%, p < 0.001). Oxygenation also showed sustained improvement. Rescue oxygen therapy (high-flow nasal cannula, noninvasive ventilation) after extubation was less frequent in patients with PEEPONLINE ≥ PEEPODCL than in those with PEEPONLINE < PEEPODCL (1/19 vs. 6/16; p = 0.018). EIT-guided individualized PEEP stabilized the improvement in ventilation distribution and oxygenation. Individual PEEP varies with EIT measures, and may differentially affect oxygenation after cardiac surgery.

Purpose: The objective of this study was to investigate factors that influence the prevalence of medial and lateral meniscal injuries at the time of anterior cruciate ligament (ACL) reconstruction in patients with ACL injuries., Methods: Patients with ACL injuries at 9 institutions were enrolled in this multicentre study. Age, sex, duration between injury and surgery, pivot shift test grade, anterior knee laxity determined using the Kneelax 3 arthrometer, and other variables were assessed by logistic regression analysis. Meniscal conditions were evaluated via arthroscopy., Results: In all, 830 patients were enrolled. The prevalence of medial and lateral meniscal tears was 32.0% (266 knees) and 26.5% (220 knees), respectively. Significant factors that influenced the prevalence of medial meniscal injuries were age [odds ratio (OR) 1.03; P = 0.000], side-to-side differences in instrumented anterior knee laxity before surgery (OR 1.12; P = 0.002), duration between injury and surgery (≥ 12 months) (OR 1.86; P = 0.023), and pivot shift test grade (OR 1.36; P = 0.014). Significant factors of lateral meniscal injury were side-to-side differences in anterior knee laxity before surgery (OR 1.12; P = 0.003) and the male sex (OR 1.50; P = 0.027)., Conclusion: Greater anterior knee laxity, age, a longer duration between injury and surgery, and a higher pivot shift test grade predicted medial meniscal injury. Greater anterior knee laxity and the male sex predicted lateral meniscal injury. In patients with ACL injuries, the importance of side-to-side differences in anterior knee laxity should be rediscovered from the viewpoint of meniscal conditions., Level of Evidence: Level III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

In this retrospective cohort study, we evaluated the efficacy of baricitinib in the treatment of coronavirus disease 2019 (COVID-19). Among 404 adult patients with COVID-19 who were admitted to our hospital between October 23, 2020, and July 31, 2021, 229 patients with respiratory failure were included. Among these, 41 patients in the baricitinib group and 41 patients in the control group were selected by propensity score matching to adjust for background factors. We compared the survival rates of the two groups at 30 and 60 days after admission. The 30-day survival rate was significantly higher in the baricitinib group than in the control group. However, there was no significant difference in 60-day survival in the two groups. Baricitinib may improve the early prognosis of patients with respiratory failure associated with COVID-19. However, efforts should be made to improve the long-term prognosis., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Aim: To evaluate the usefulness of the application of the clustering method to the trend analysis (sectorwise regression) in comparison with the pointwise linear regression (PLR)., Methods: This study included 153 eyes of 101 patients with open-angle glaucoma. With PLR, the total deviation (TD) values of the 10th visual field (VF) were predicted using the shorter VF sequences (from first 3 to 9) by extrapolating TD values against time in a pointwise manner. Then, 68 test points were stratified into 29 sectors. In each sector, the mean of TD values was calculated and allocated to all test points belonging to the sector. Subsequently, the TD values of the 10th VF were predicted by extrapolating the allocated TD value against time in a pointwise manner. Similar analyses were conducted to predict the 11th-16th VFs using the first 10 VFs., Results: When predicting the 10th VF using the shorter sequences, the mean absolute error (MAE) values were significantly smaller in the sectorwise regression than in PLR. When predicting from the 11th and 16th VFs using the first 10 VFs, the MAE values were significantly larger in the sectorwise regression than in PLR when predicting the 11th VF; however, no significant difference was observed with other VF predictions., Conclusion: Accurate prediction was achieved using the sectorwise regression, in particular when a small number of VFs were used in the prediction. The accuracy of the sectorwise regression was not hampered in longer follow-up compared with PLR., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The therapeutic potential of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) for various diseases and tissue repair is attracting attention. Here, EVs from conditioned medium of human bone marrow MSCs at passage 5 (P5) and passage 12 (P12) were analysed using mouse Achilles tendon rupture model and lectin microarray. P5 MSC-EVs accelerated Achilles tendon healing compared with P12 MSC-EVs. Fucose-specific lectin TJA-II was indicated as a glycan marker for therapeutic MSC-EVs. The present study demonstrated that early passaged MSC-EVs promote Achilles tendon healing compared with senescent MSC-EVs. Glycans on MSC-EVs might provide useful tools to establish a quality control and isolation system for therapeutic MSC-EVs in regenerative medicine., (© 2022 Federation of European Biochemical Societies.)

To evaluate the effects of the discontinuation of antithrombotic drugs on intraocular pressure (IOP) reduction and complications from ab interno trabeculotomy for patients with glaucoma. We performed a retrospective chart review on the data of patients treated with antithrombotic agents who have undergone ab interno trabeculotomy through Tanito microhook combined with cataract surgery at the Asahi General Hospital and the Tokyo University Hospital, with 6 months of follow-up. The patients were classified into two groups depending on whether they discontinued (AT-) or continued (AT+) antithrombotic therapy during the perioperative phase. The demographics, pre- and postoperative IOP, medication score, best-corrected visual acuity (BCVA), and postoperative complications were analyzed preoperatively and postoperatively at 1 week and 1-6 months. The series included 44 eyes from 44 Japanese patients. The AT- and AT+ groups included 21 eyes from 21 patients and 23 eyes from 23 patients, respectively. The decrease in IOP from the baseline at 1 week postoperative was significantly different between the two groups (p = 0.009), but there were no significant differences observed in the other visits. Hyphema and IOP spikes exceeding 30 mmHg occurred in 10% and 10% of AT- participants, and in 43% and 26% of AT+ participants, respectively. Hyphema and spikes with hyphema occurred more frequently in the AT+ than in the AT- group (p = 0.02 and p = 0.05). The number of patients who had spikes was not significantly different (p = 0.27). In trabeculotomy using the Tanito microhook®, discontinuing antithrombotic therapy had better IOP-lowering effects and less postoperative complications., Competing Interests: The authors have declared that no competing interests exist.

Objective: The midterm results of endovascular abdominal aortic aneurysm repair (EVAR) with aortic side branch coil embolization during EVAR was evaluated., Methods: Our center began coil embolization for all patent inferior mesenteric artery (IMA) and lumbar artery (LA) with an inner diameter more than 2.0 mm during EVAR since June 2015. When four or more LA were patent, coil embolization for LA with inner diameter 2.0 mm or less was done. EVAR without aortic side branches coil embolization was performed for 59 patients prior to June 2015 (control group) and 79 patients underwent EVAR with coil embolization during EVAR (coil group). The success rate of coil embolization for IMA and LA was evaluated in coil group. The frequency of type 2 endoleak (T2EL), freedom from aneurysm sac expansion (5 mm or more) rate and the rate of the aneurysm sac shrinkage (10 mm or more) were compared between the coil and control groups. Additionally, multiple logistic regression analysis for all patients was conducted to analyze whether IMA patency and the number of patent lumbar artery at the end of EVAR were the risk factors of the aneurysm sac expansion of 5 mm or more., Results: The success rate of IMA coil embolization was 96.4% and that of LA was 74.5%. Compared to the control group, the frequency of T2EL was significantly lower in coil group at 7 days (1.3% vs. 60.4%, P <0.0001) and at 6 months (2.1% vs 38.2%, P <0.0001) after EVAR. The freedom from aneurysm sac expansion rate was significantly better in the coil group at 5 years (100% in coil group and 65.2% in control group, P = 0.002). The rate of aneurysm sac shrinkage was significantly better in coil group (15.5% vs. 2.0% at 1 year, 42.8% vs. 6.3% at 2 years and 53.4% vs. 17.8% at 3 years, p = 0.0007). The risk of aneurysm sac expansion of 5 mm or more was estimated to be 11 times greater when the IMA was patent, and 4.9 times greater when 3 or more LAs were patent at the end of EVAR., Conclusion: When IMA was occluded and the number of patent LA became 2 or less by aortic side branch coil embolization during EVAR, favorable mid-term results were safely obtained and good long-term result could be expected with EVAR., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study is two-fold: (1) to describe the femoral reference point of the medial patellofemoral ligament (MPFL) on a virtual true lateral radiograph reconstructed from a three-dimensional computed tomography (3D-CT) image and (2) to compare this point with that of patients without patellofemoral instability and with Schöttle's point., Methods: A total of 26 consecutive patients (29 affected knees) with recurrent patellar dislocation (RPD), who underwent MPFL reconstruction were included in this study (4 males; 22 females; mean age, 24.0 years old). Using a true lateral 3DCT image, the MPFL femoral insertion was identified and marked with a 2-mm circle, and this image was reconstructed as a virtual true lateral radiograph. Following Schöttle's method, the point of intersection was described by their anterior-posterior and proximal-distal positions. As a control population, 29 age- and gender-matched patients with anterior cruciate ligament (ACL) injuries were also analysed., Results: The points in RPD patients were located significantly posterior (-2.5 ± 2.3 mm, p < 0.01) to the line representing an extension of the posterior cortex of the femur and distal (- 6.9 ± 2.4 mm, p < 0.01) to the posterior origin of the medial femoral condyle compared with those in the control population. The mean reference point of RPD patients was located in a 3.8-mm posterior and 4.4-mm distal position compared with Schöttle's point., Conclusions: An anatomical and radiographic femoral reference point of the MPFL on a true lateral virtual radiograph was described with our method. In patients with RPD, this reference point was identified to be more posterior and distal to Schöttle's point. More anatomical and individualized MPFL reconstruction will be secured using our method., Level of Evidence: Level IV., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

To compare the short-term surgical effectiveness and safety profile of trabeculotomy ab externo and ab interno with microhook in terms of the recovery of visual acuity. A retrospective chart review was performed on patients who underwent trabeculotomy combined with phacoemulsification and lens implantation at Asahi General Hospital, with 6 months of follow-up. The patients treated by trabeculotomy were classified into two groups depending on the surgical procedures: ab interno with Tanito microhook (TMH) and ab externo with rigid probe trabeculotome (LOT). The demographics, preoperative and postoperative intraocular pressure (IOP), number of medications (Med), best-corrected visual acuity (BCVA), surgical-induced astigmatism (SIA), and postoperative complications were analyzed at pre-operation, and 1 week and 1-6 months post-operation. Fifty-two eyes of 38 Japanese patients underwent TMH and 42 eyes of 32 patients underwent LOT. The decreases in IOP and Med from the baseline were significant at all time points in both groups (p < 0.001), but there were no significant differences between the two groups. BCVA improved significantly in TMH and LOT after the operation (p < 0.001). BCVA and SIA significantly improved, mostly at 1 week in TMH, compared with LOT (p = 0.02 and 0.003). Hyphema and IOP spike exceeding 30 mmHg (spike) occurred in 11% and 6% of participants in TMH, and 33% and 26% of participants in LOT, respectively. Hyphema and IOP spike occurred more frequently in the LOT than in the TMH group (p = 0.01 and 0.005). Ab interno trabeculotomy showed similar IOP-lowering effects as ab externo, but had less postoperative complications., (© 2021. The Author(s).)

Purpose: To investigate the relationship between biomechanical glaucoma factor (BGF) measured with Corvis ST and glaucomatous visual field (VF) progression, compared to corneal hysteresis (CH) measured with ocular response analyzer using a longitudinal dataset of primary open-angle glaucoma (POAG). The discriminative powers of BGF and CH were also compared using a cross-sectional dataset., Methods: The longitudinal dataset included 166 POAG eyes. The rate of VF change during the follow-up period was evaluated using the mean of 52 pointwise total deviations in the Humphrey 24-2 field test. Variables associated with the VF progression rate were identified from BGF, CH, age, baseline VF severity, and intraocular pressure during the VF follow-up period by identifying the optimal model. The cross-sectional dataset included 68 POAG eyes and 68 healthy eyes. Using this dataset, the area under the curve (AUC) values of the receiver-operating curve were compared between CH and BGF., Results: The optimal multivariate linear mixed model to describe the VF rate included age and CH, but not BGF. Between POAG and healthy eyes, CH was statistically different (P < 0.001), although this was not the case with BGF. The AUC values were 0.61 and 0.71 for BGF and CH, respectively (P = 0.027)., Conclusions: CH, but not BGF, was associated with VF progression in POAG patients under treatment. BGF was not useful to discriminate POAG between treated and normal eyes.

The aim was to establish and evaluate a new clustering method for visual field (VF) test points to predict future VF in retinitis pigmentosa. A Humphrey Field Analyzer 10-2 test was clustered using total deviation values from 858 VFs. We stratified 68 test points into 24 sectors. Then, mean absolute error (MAE) of the sector-wise regression with them (S1) was evaluated using 196 eyes with 10 VF sequences and compared to pointwise linear regression (PLR), mean sensitivity of total area (MS) and also another sector-wise regression basing on VF mapping for glaucoma (29 sectors; S2). MAE with S1 were smaller than with PLR when between the first-third and first-seventh VFs were used. MAE with the method were significantly smaller than those of S2 when between the first-sixth and first-ninth VFs were used. The MAE of MS was smaller than those with S1 only when first to 3rd and first to 4th VFs were used; however, the prediction accuracy became far larger than any other methods when larger number of VFs were used. More accurate prediction was achieved using this new sector-wise regression than with PLR. In addition, the obtained cluster was more useful than that for glaucoma to predict progression.

Purpose: To compare 12-month clinical results of spatula-shaped and dual-blade microhooks ab interno trabeculotomy with phacoemulsification., Study Design: Retrospective comparative study., Methods: We conducted a retrospective chart review of Japanese open-angle glaucoma patients who underwent ab interno trabeculotomy with phacoemulsification with a 12-month follow-up. Two types of trabecular hook were used: the spatula-shaped Tanito Trabeculotomy ab interno Micro-hook ® and the Kahook Dual Blade ® . Changes in intraocular pressure (IOP) and medication scores comprised the main outcome metrics. We also analyzed and compared patient demographics and the occurrence of complications., Results: Trabeculotomy was performed using a spatula-shaped hook in 17 eyes and a dual-blade hook in 15 eyes. Significant reductions in IOP (p < 0.001) and medication scores (p < 0.001) were noted in both groups after the 1-month time point. The percentage changes of IOP from baseline at each time point were not significantly different between groups, though there was a significant difference in medication scores at 12 months (p = 0.0192). Postoperative complications occurred similarly in both groups; one case in the dual-blade group required additional filtration surgery., Conclusions: Ab interno trabeculotomy with phacoemulsification was effective in lowering IOP both with spatula-shaped and with double-blade microhooks. At 12 months more medications were used postoperatively in the spatula-shaped microhook group; however, the reductions in the medication scores from baseline were statistically significant in both groups.

Objectives: Lupus enteritis (LE) is a rare but well-known gastrointestinal manifestation of systemic lupus erythematosus (SLE). This study was conducted to identify prognostic factors associated with poor responses in patients with LE., Methods: We consecutively registered patients diagnosed with LE between January 2009 and October 2019, and retrospectively compared their clinical characteristics based on whether they had good or poor responses to treatment., Results: A total of 13 patients (17 episodes) were included. The median age was 41 years, and 12 patients were female. A comparison of clinical characteristics between groups revealed similar computed tomography (CT) findings. However, serum CH50 levels were significantly lower in the poor response group (median [interquartile ranges (IQR)]; 29.2 [25.3-46.9] U/mL vs 19.3 [7.8-24.0] U/mL, p  = .0095). More patients in the poor response group had higher titers of anti-cardiolipin β2-glycoprotein I antibody (anti-CL β2GPI Ab) and were started on glucocorticoids (GCs) at moderate doses. In multivariable analysis, serum CH50 level was independently associated with poor response to induction therapy., Conclusion: Lower levels of CH50 at the time of initial treatment predicted inadequate treatment response in patients with LE.

Purpose: The effectiveness of Electronic Medication Packaging devices for monitoring drug adherence has been widely reported. However, conventional devices are expensive for routine use and cannot confirm whether the medication was administered. We aimed to determine, in a pilot and feasibility study, the impact of introducing a new medication support device, the Pletaal Assist System ® , to monitor and improve cilostazol adherence for stroke prevention at an outpatient clinic., Patients and Methods: We assessed consecutive patients treated with cilostazol for >3 months at our stroke outpatient clinic from January 2018 to March 2020. The adherence rate was assessed as follows: (the number of pills prescribed minus the number of remaining pills)/the number of pills prescribed. We compared the adherence rates before, during, and after Pletaal Assist System ® usage, respectively., Results: Overall, 25 patients (median age, 68.5 years; range, 51-86 years; male, 64%) were enrolled. All participants were prescribed cilostazol (100 mg) twice a day. There was no significant difference in the adherence rate among the three periods. However, in 10 patients with adherence rate below 100%, the adherence rate during Pletaal Assist System ® usage was higher than before usage (99.5% vs 95%, p=0.04), and the rate after using the Pletaal Assist System ® tended to be lower compared to the rate during usage (99.5% vs 96%, p=0.05)., Conclusion: Our preliminary evidence suggest that the Pletaal Assist System ® could further improve cilostazol adherence in outpatients with poor drug adherence and may reduce the risk of recurrent strokes by improving adherence of patients with a history of stroke., Competing Interests: The authors declare no conflicts of interest., (© 2021 Oura et al.)

We report a case of bilateral iridoschisis with corneal oedema and a quantitative evaluation of the changes in iridotrabecular and iridocorneal contact before and after cataract surgery and after Descemet stripping automated endothelial keratoplasty (DSAEK). A 76-year-old woman with iridoschisis and cataracts, previously managed with laser iridotomy, experienced progressive vision loss. The preoperative iridotrabecular contact (ITC) index measured by anterior segment optical coherence tomography was 23.6% in the right eye and 24.4% in the left eye. Preoperative corneal oedema in the right eye was more severe than that in the left eye. Cataract surgery, followed by DSAEK, was performed in the right eye and subsequently in the left eye. Her visual acuity improved postoperatively, and the corneal oedema of both eyes was treated successfully. Moreover, the ITC index improved in both eyes, to 4.7 and 6.9% after cataract surgery and to 0 and 0% after DSAEK in the right and left eyes, respectively. Staged cataract surgery and DSAEK were effective for endothelial decompensation caused by iridoschisis. Additionally, we confirm that iridotrabecular and iridocorneal contacts improved after both surgical procedures not only after cataract surgery but also after DSAEK. This case report showed the clinical usefulness of the ITC index in the detection of changes after different surgical procedures., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

Purpose: To evaluate the visual outcomes of vitrectomy for lamellar macular hole (LMH) and epiretinal membrane (ERM) foveoschisis and to investigate the prognostic factor for postoperative visual acuity., Methods: We retrospectively reviewed 15 LMH and 17 ERM foveoschisis eyes that had undergone a standard three-port pars plana vitrectomy with (12 eyes) or without (20 eyes) cataract surgery. Best-corrected visual acuity (BCVA) at postoperative three months and the final visit were compared to the preoperative measurements. We investigated the relationship between BCVA at the final visit and baseline parameters (age, preoperative BCVA, the presence of epiretinal proliferation [EP] and ellipsoid zone [EZ] disruption). The best explanatory variables for the final BCVA were investigated using the corrected Akaike information criterion (AICc) model selection., Results: The mean age was 67.2 years. The mean follow-up duration was 30.7 months. Fifteen of 32 examined eyes were diagnosed as LMH and 17 eyes as ERM foveoschisis. Twelve eyes in LMH had EP and 13 eyes showed the disruption of EZ integrity. In total, BCVA significantly improved at 3 months postoperatively (p = 0.0013). A significant improvement was observed in ERM foveoschisis (p = 0.0085) but not in LMH group (p = 0.071). Comparing the BCVA between the baseline and the final visit, significant improvements were observed in total, ERM foveoschisis and LMH group (p<0.001, p<0.001 and p = 0.026, respectively). The optimal model for BCVA at the final visit included preoperative BCVA and the presence of EZ disruption (p<0.001 and p<0.001, respectively)., Conclusion: Our results suggested that the final BCVA was dependent on preoperative BCVA and the presence of EZ disruption. Surgical indications might be warranted for LMHs with EZ disruption., Competing Interests: The authors have declared that no competing interests exist.

The purpose of the current study was to predict intraocular pressure (IOP) using color fundus photography with a deep learning (DL) model, or, systemic variables with a multivariate linear regression model (MLM), along with least absolute shrinkage and selection operator regression (LASSO), support vector machine (SVM), and Random Forest: (RF). Training dataset included 3883 examinations from 3883 eyes of 1945 subjects and testing dataset 289 examinations from 289 eyes from 146 subjects. With the training dataset, MLM was constructed to predict IOP using 35 systemic variables and 25 blood measurements. A DL model was developed to predict IOP from color fundus photographs. The prediction accuracy of each model was evaluated through the absolute error and the marginal R-squared (mR 2 ), using the testing dataset. The mean absolute error with MLM was 2.29 mmHg, which was significantly smaller than that with DL (2.70 dB). The mR 2 with MLM was 0.15, whereas that with DL was 0.0066. The mean absolute error (between 2.24 and 2.30 mmHg) and mR 2 (between 0.11 and 0.15) with LASSO, SVM and RF were similar to or poorer than MLM. A DL model to predict IOP using color fundus photography proved far less accurate than MLM using systemic variables.

The prevalence of an epiretinal membrane (ERM) was elucidated using a dataset from a health examination program database in Japan. From the cohort database, 5042 eyes of 2552 subjects were included. The presence of an ERM, cellophane macular reflex (CMR), or preretinal macular fibrosis (PMF) was detected using color fundus photographs, and crude and age-standardized prevalence were obtained. To further assess the possible risk factors of ERM, background parameters were compared between ERM+ and - groups, and multiple logistic regression analysis was performed. ERM was detected in fundus photographs of 275 eyes (eye-based prevalence of 5.5%) from 217 subjects (subject-based prevalence of 8.5%). CMR was detected in 169 eyes (3.4%) of 138 subjects (5.4%), and PMF was detected in 106 eyes (2.1%) of 97 subjects (3.8%). By univariate analyses, compared with ERM- eyes or subjects, higher Scheie's H grade ( p < 0.0001), S grade ( p < 0.0001), and glaucoma prevalence ( p = 0.0440) were found in ERM+ eyes, and older age ( p < 0.0001), more frequent histories of hypertension ( p = 0.0033) and hyperlipidemia ( p = 0.0441), and more frequent uses of medication for hypertension ( p = 0.0034) and hyperlipidemia ( p = 0.0074), shorter body height ( p = 0.0122), and higher systolic blood pressure ( p = 0.0078), and thicker intimal medial thickness ( p = 0.0318) were found in ERM+ subjects. By multivariate analyses, older age ( p < 0.0001, estimate = 0.05/year) was the only significant factor of ERM prevalence. Age-standardized prevalence of ERM was calculated to be 2.4%, 6.7%, and 13.3% for all ages, subjects older than 40 years, and subjects older than 65 years, respectively. We reported the prevalence of ERM and its subclasses in Japanese subjects. Since its prevalence is remarkably high in older subjects, an ERM can be seen as an important cause of visual impairment in Japan and in areas of the world where individuals live to an advanced age.

The purpose of the study was to evaluate the 12-month surgical outcome and prognostic factors of stand-alone ab interno trabeculotomy. The changes in the intraocular pressure (IOP) and medication score and the success rate of the surgery were analyzed. Thirty-four eyes of 29 patients with primary open-angle glaucoma (POAG; n = 16) or pseudoexfoliation glaucoma (PEG; n = 18) with a 12-month follow-up period were included in the study. The decreases in IOP and medication score from the baseline to the all-time-point were statistically significant (P < 0.001). The surgical success rates were 97.1%, 76.5%, and 44.0% at 3 months (90 days), 6 months (180 days), and 12 months (365 days), respectively. A mixed effect Cox model revealed that the type of glaucoma (POAG) was significantly associated with surgical failure (P = 0.044). Furthermore, the surgical success rate was significantly higher in eyes with PEG than it was in those with POAG (P = 0.019). Stand-alone ab interno trabeculotomy significantly lowered both the IOP and the medication score in patients with glaucoma, although almost one quarter of the cases needed additional glaucoma surgeries. The surgical success rate was significantly higher in eyes with PEG than it was in those with POAG., Competing Interests: The authors have declared that no competing interests exist.

Background: Medial meniscus extrusion (MME) leads to symptomatic knee osteoarthritis (OA) due to increased mechanical stress. MME increases with weight-bearing, and the difference in MME between non-weight-bearing and weight-bearing status (ΔMME) is a factor that causes greater MME. The lateral wedge insole (LWI) is an ideal approach for decreasing the amount of ΔMME associated with the reduction of medial loading stress in the early stage of knee OA. However, the effect of the LWI for 3 months on the ΔMME and its response to OA stage have not been elucidated., Objective: To investigate the effects of the LWI for 3 months on MME and the ΔMME in each stage of OA., Methods: Participants were divided into three groups: no intervention with the LWI (control group; n = 9) and intervention with the LWI in early OA (early OA group: Kellgren-Lawrence (K/L) stage = 2, n = 17) and late OA (late OA group: K/L stage > 2, n = 13). MME was evaluated using ultrasound, and the ΔMME was obtained as the difference in MME from non-weight-bearing and weight-bearing conditions. These measurements were performed at two time points: the initial office visit as a baseline and post-3 months., Results: The weight-bearing MME and ΔMME values post-3 months were significantly decreased compared with those at baseline in the early OA group but not in the control or late OA groups., Conclusions: The use of the LWI for 3 months decreased weight-bearing MME and ΔMME values, and its effectiveness was more pronounced in the early stage of knee OA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

A 33-year-old male with a history of bronchial asthma and allergic rhinitis was diagnosed with eosinophilic granulomatosis with polyangiitis (EGPA) eight years ago. The diagnosis was based on the presence of fever, remarkable eosinophilia, and painful digital ulcer. His signs and symptoms improved with a moderate dose of glucocorticoids. Thereafter, he was lost to follow-up, failing to attend any of the scheduled appointments. Three years later, he presented with painful digital gangrene on the lateral fold of the right ring fingernail and abdominal pain triggered by meals. Angiography showed multiple occlusions and severe stenoses of the peripheral arteries and coronary aneurysms, which confirmed the diagnosis of medium vessel vasculitis of the coronary and peripheral arteries due to flare up of EGPA. EGPA predominantly affects the small-sized vessels, but rarely the medium-sized vessels. Coronary vasculitis might occur asymptomatically, until the coronary stenosis becomes severe or myocardial infarction develops; hence, its prevalence is underestimated. In this case, a digital gangrene prompted us to perform a systemic angiography, leading to the diagnosis of coronary vasculitis. Careful observation for coronary lesions is necessary in patients with EGPA who develop digital gangrene.

Opioids are widely used for the treatment of moderate/severe pain in cancer and noncancer patients. In this study, we searched for safety signals for a wide variety of opioid-related adverse events (AEs) in elderly patients by disproportionality analysis using the Japanese Adverse Drug Event Report (JADER) database. Data from the JADER database from April 2004 to May 2018 were obtained from the Pharmaceuticals and Medical Devices Agency website. Safety signal detection of opioid-related AEs in elderly patients was defined using the relative elderly reporting odds ratio (ROR). Among the analyzed AEs, opioid-induced neurotoxicity (OIN) was assessed based on the time to onset using the Weibull shape parameter. The following safety signals were detected in elderly patients: respiratory depression, somnolence, hallucinations, akathisia and OIN. Fentanyl, tramadol, oxycodone and morphine exhibited a large relative elderly ROR for OIN. The median time to onset of OIN of transdermal fentanyl, oral tramadol, oral oxycodone and oral morphine was 13.5, 6, 9, and 6 d, respectively. These opioids were classified as early failure types using the Weibull distribution. Our results showed that elderly patients who are administered opioids should be closely monitored for AEs, such as respiratory depression, OIN and akathisia.

Background: The prenatal diagnosis of microhydranencephaly is important and needs to be distinguished from anencephaly, because unlike anencephaly, fetuses with microhydranencephaly can survive after birth. Herein, we report a case of microhydranencephaly that was diagnosed and distinguished from anencephaly prenatally., Case Presentation: The patient was an 18-year-old woman, 2 gravida nullipara, who presented at 15 weeks of gestation. Ultrasonography showed a normal biparietal diameter (BPD) and no major anomalies. At 23 weeks of gestation, an ultrasound examination revealed a BPD of 40 mm (-5.3 standard deviation, SD). At 29 weeks, anencephaly was suspected despite difficulty in visually examining the fetal head above the orbit. At 34 weeks, insertion of a metreurynter made it possible to observe the skull. Three-dimensional computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of the fetal skull, a prominent occipital bone, sloping forehead, marked microcephaly, cerebral loss, and excess cerebrospinal fluid. This allowed differentiation between microhydranencephaly and anencephaly. She delivered vaginally at 37 weeks, and the child had a birth weight of 2342 g and a head circumference of 24 cm (-5.4 SD). The baby's head was flat above the forehead, with a suspected partial head defect. The baby received desmopressin acetate due to central diabetes insipidus 6 months after birth., Conclusions: The use of multiple imaging modalities and physical manipulation of the fetal head are required to accurately differentiate between microhydranencephaly and anencephaly.