Three-dimensional corrective osteotomy for cubitus varus deformity using patient-matched instruments.

Background: Various methods of two or three-dimensional (3D) corrective osteotomy for cubitus varus deformity have been reported. However, whether 3D correction of cubitus varus deformity is necessary is controversial because of technical difficulties and surgical complications. This study introduced 3D simulations and printing technology for corrective osteotomy against cubitus varus deformities. Moreover, recent studies on the application of these technologies were reviewed. Methods: The amount of 3D deformity was calculated based on the difference in 3D shape between the affected side and the contralateral normal side. Patient-matched instruments were created to perform the actual surgery as simulated. Further, a 3D corrective osteotomy was performed using patient-matched instruments for cubitus varus deformity in pediatric and adolescent patients. The humerus-elbow-wrist angle, tilting angle, and elbow ranges of motion were evaluated. Results: Humerus-elbow-wrist angle and tilting angle were corrected from -21° to 14° and from 30° to 43°, respectively, in the pediatric patient and from -18° to 10° and from 20° to 40°, respectively, in the adolescent patient. The elbow flexion and extension angles changed from 130° to 140° and from 20° to 10°, respectively, in the pediatric patient and from 120° to 130° and from 15° to 0°, respectively, in the adolescent patient. Conclusion: The 3D computer simulations and the use of patient-matched instruments for cubitus varus deformity are reliable and can facilitate an accurate and safe correction. These technologies can simplify the complexity of 3D surgical procedures and contribute to the standardization of treatment for cubitus varus deformity.

Cubitus varus deformity following paediatric supracondylar humeral fracture remodelling predominantly in the sagittal direction: A three-dimensional analysis of eighty-six cases.

PURPOSE: Three-dimensional (3D) capacity for remodelling in cubitus varus deformity (CVD) after paediatric supracondylar humeral fractures (PSHFs) remains unelucidated. This study investigated remodelling patterns after PSHFs by examining 3D deformity distribution over time after injury. METHODS: Computed tomography (CT) data of 86 patients with CVD after PSHFs were analysed. The 3D deformity angles in the sagittal, coronal, and axial directions were assessed and correlated with the duration between the age at injury and CT evaluation. For the subgroup analysis, we performed the same correlation analysis in a younger (< 8 years old) and an older group (≥ 8 years old); we categorized the duration into early (< 2 years), middle (≥ 2 to < 5 years), and late periods (≥ 5 years) and compared the deformity angles of each direction among the three groups. RESULTS: Sagittal deformity showed a moderate correlation with the duration of deformity (r = -0.54; P < 0.001), while coronal and axial deformities showed a negligible correlation. Sagittal deformity showed moderate correlations with the duration in the younger group (r = -0.62; P < 0.001) and weak correlations in the older group (r = -0.37; P = 0.091). In the sagittal direction, the deformity angle in the early period was significantly larger than those in the mid and late periods (P < 0.001). However, there were no significant differences among the three groups in the coronal and axial directions. CONCLUSION: Sagittal deformities in CVDs are capable of remodelling, especially in the early period and at a younger age, whereas coronal and axial deformities are less likely to undergo remodelling.

Hypotension after general anaesthesia induction using remimazolam or propofol in geriatric patients undergoing sevoflurane anaesthesia with remifentanil: a single-centre, double-blind, randomised controlled trial.

BACKGROUND: The occurrence of hypotension after induction of general anaesthesia is common in geriatric patients, and should be prevented to minimise perioperative complications. Compared with propofol, remimazolam potentially has a lower incidence of hypotension. This study aimed to compare the incidence of hypotension after general anaesthesia induction with remimazolam or propofol in geriatric patients. METHODS: This single-centre, double-blind, randomised trial enrolled 90 patients aged ≥80 yr who received general anaesthesia for scheduled surgery. Patients were randomised to receive remimazolam (12 mg kg-1 h-1) or propofol (0.025 mg kg-1 s-1) for anaesthesia induction, with remifentanil and sevoflurane. The presence or absence of hypertension on the ward served as the stratification factor. The incidence of hypotension after the induction of general anaesthesia, defined as a noninvasive mean arterial pressure of <65 mm Hg measured every minute from initiation of drug administration to 3 min after tracheal intubation, was the primary outcome. Subgroup analysis was performed for the primary outcome using preoperative ward hypertension, clinical frailty scale, Charlson Comorbidity Index, and age. RESULTS: Three subjects were excluded before drug administration, and 87 subjects were included in the analysis. The incidence of hypotension was 72.1% (31/43) and 72.7% (32/44) with remimazolam or propofol, respectively. No statistically significant differences (adjusted odds ratio, 0.96; 95% confidence interval, 0.37-2.46; P=0.93) were observed between groups. Subgroup analysis revealed no significant differences between groups. CONCLUSIONS: Compared with propofol, remimazolam did not reduce the incidence of hypotension after general anaesthesia induction in patients aged ≥80 yr. CLINICAL TRIAL REGISTRATION: UMIN000042587.

Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention in Patients With Multivessel Disease and Diabetes.

There is a scarcity of data on clinical outcomes after intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) in patients with multivessel disease and diabetes. The Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention study multivessel cohort was a prospective, multicenter, single-arm trial enrolling 1,021 patients who underwent multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified OPTIVUS criteria for optimal stent expansion. We compared the clinical outcomes between those patients with and without diabetes. The primary end point was a composite of death, myocardial infarction, stroke, or any coronary revascularization. There were 560 patients (54.8%) with diabetes and 461 patients (45.2%) without diabetes. The mean age was not different between the 2 groups (70.9 ± 9.7 vs 71.7 ± 10.4 years, p = 0.17). Patients with diabetes more often had chronic kidney disease and complex coronary artery disease, as indicated by the greater total number of stents and longer total stent length. The rate of meeting the OPTIVUS criteria was not different between the 2 groups (61.2% vs 60.7%, p = 0.83). The cumulative 1-year incidence of the primary end point was not different between the 2 groups (10.8% vs 9.8%, log-rank p = 0.65). After adjusting for confounders, the risk of diabetes relative to nondiabetes remained insignificant for the primary end point (hazard ratio 0.97, 95% confidence interval 0.65 to 1.44, p = 0.88). In conclusion, in patients who underwent multivessel IVUS-guided PCI and were managed with contemporary clinical practice, patients with diabetes had similar 1-year outcomes to patients without diabetes.

Contributions of endoscopic ultrasonography-guided tissue acquisition (EUS-TA) to the diagnostics of biliary stricture and gallbladder lesions.

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.

Retrograde Coronary Chronic Total Occlusion Intervention (JR-CTO) Score: From the Japanese CTO-PCI Expert Registry.

BACKGROUND: Despite the effectiveness of the retrograde approach for chronic total occlusion (CTO) lesions, there are no standardized tools to predict the success of retrograde percutaneous coronary intervention (PCI). OBJECTIVES: The objective of this study was to develop a prediction tool to identify CTO lesions that will achieve successful retrograde PCI. METHODS: This study evaluated data from 2,374 patients who underwent primary retrograde CTO-PCI and were enrolled in the Japanese CTO-PCI Expert Registry between January 2016 and December 2022 (NCT01889459). All observations were randomly assigned to the derivation and validation cohorts at a 2:1 ratio. The prediction score for guidewire failure in retrograde CTO-PCI was determined by assigning 1 point for each factor and summing all accrued points. RESULTS: The JR-CTO score (moderate-severe calcification, tortuosity, Werner collateral connection grade ≤1, and nonseptal collateral channel) demonstrated a C-statistic for guidewire failure of 0.72 (95% CI: 0.67-0.76) and 0.71 (95% CI: 0.64-0.77) in the derivation and validation cohorts, respectively. Patients with lower scores had higher guidewire and technical success rates and decreased guidewire crossing time and procedural time (P < 0.01). CONCLUSIONS: The JR-CTO (Japanese Retrograde Chronic Total Occlusion) score, a simple 4-item score that predicts successful guidewire crossing in patients undergoing retrograde CTO-PCI, has the potential to support clinical decision-making for the retrograde approach.

Burosumab vs conventional therapy in children with X-linked hypophosphatemia: results of the open-label, phase 3 extension period.

In a randomized, open-label phase 3 study of 61 children aged 1-12 years old with X-linked hypophosphatemia (XLH) previously treated with conventional therapy, changing to burosumab every 2 weeks (Q2W) for 64 weeks improved the phosphate metabolism, radiographic rickets, and growth compared with conventional therapy. In this open-label extension period (weeks 64-88), 21 children continued burosumab Q2W at the previous dose or crossed over from conventional therapy to burosumab starting at 0.8 mg/kg Q2W with continued clinical radiographic assessments through week 88. Efficacy endpoints and safety observations were summarized descriptively for both groups (burosumab continuation, n = 6; crossover, n = 15). At week 88 compared with baseline, improvements in the following outcomes were observed in the burosumab continuation and crossover groups, respectively: mean (SD) RGI-C rickets total score (primary outcome), +2.11 (0.27) and +1.89 (0.35); mean (SD) RGI-C lower limb deformity score, +1.61 (0.91) and +0.73 (0.82); and mean (SD) height Z-score + 0.41 (0.50) and +0.08 (0.34). Phosphate metabolism normalized rapidly in the crossover group and persisted in the continuation group. Mean (SD) serum alkaline phosphatase decreased from 169% (43%) of the upper limit of normal (ULN) at baseline to 126% (51%) at week 88 in the continuation group and from 157% (33%) of the ULN at baseline to 111% (23%) at week 88 in the crossover group. During the extension period, treatment-emergent adverse events (AEs) were reported in all 6 children in the burosumab continuation group and 14/15 children in the crossover group. The AE profiles in the randomized and extension periods were similar, with no new safety signals identified. Improvements from baseline in radiographic rickets continued in the extension period among children with XLH who remained on burosumab. Children who crossed over from conventional therapy to burosumab demonstrated a rapid improvement in phosphate metabolism and improved rickets healing over the ensuing 22 weeks.

Risk and Time-to-Onset of Acute Kidney Injury With Vancomycin Plus Piperacillin-tazobactam Combination: Analysis Using JADER.

BACKGROUND/AIM: Pharmacovigilance data and clinical studies have indicated a risk of acute kidney injury (AKI) associated with concomitant administration of vancomycin and piperacillin-tazobactam. However, no pharmacovigilance studies have evaluated time-to-onset and outcomes of AKI related to this combination. Therefore, this study used a pharmacovigilance database to investigate the incidence, time-to-onset, and outcomes of AKI in patients treated with intravenous vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics. PATIENTS AND METHODS: From data in the Japanese Adverse Drug Event Report (JADER) database, we calculated the reporting odds ratios (RORs) and 95% confidence intervals (CIs), time-to-onset, and outcomes of AKI following intravenous administration of vancomycin plus piperacillin-tazobactam or other antipseudomonal antibiotics and with other vancomycin regimens, including monotherapy. RESULTS: The JADER database contained 4,471 reports of intravenous vancomycin treatment, including 517 reports of AKI. The adjusted RORs (95%CIs) of AKI in cases with co-administration of intravenous vancomycin and piperacillin-tazobactam was 2.58 (2.06-3.24). The median time-to-onset for AKI in vancomycin plus piperacillin-tazobactam was 6.0 (interquartile range=3.0-10.3). Weibull shape parameter analysis showed that the pattern of onset of AKI in vancomycin plus piperacillin-tazobactam represented a wear out failure, predicting an increasing hazard with time. For the outcome of AKI, there was no significant difference between all vancomycin regimen and the piperacillin-tazobactam combination groups. CONCLUSION: Concomitant use of intravenous vancomycin and piperacillin-tazobactam may increase the incidence of AKI but may not affect the outcome. This combination does not necessarily have to be avoided, but long-term use is not advisable.

Igneous processes in the small bodies of the Solar System II: Small satellites and dwarf planets.

Evidence of hot and cold igneous processes has been reported in small satellites and dwarf planets of the Solar System. Olivine and pyroxenes were detected in the spectral bands of both small satellites and dwarf planets. The aqueously altered form of olivine and serpentine has been detected in the spectrums of Ceres and Miranda hinting at possible hydrothermal processes in their interiors. Once more, the ubiquitous distribution of 26Al in the planetary nebula, then evolving in the protoplanetary disk, contributed to the primordial widespread heating. Volcanism, or cryovolcanism, then developed only in those bodies where long-lived radiogenic elements, and/or tidal processes, were available.

Elderly Woman With No Autoimmune Disease With Aseptic Meningitis Caused by Celecoxib.

Nonsteroidal anti-inflammatory drug (NSAID)-induced aseptic meningitis (NIAM) is frequently reported in patients with autoimmune disease. Ibuprofen-induced NIAM is the most common case report of NIAM. We report a patient without autoimmune disease who developed NIAM following oral celecoxib administration. A literature review and survey of cases registered in the Japanese Adverse Drug Event Report (JADER) database is also provided. A 73-year-old woman with no autoimmune disease developed a headache the day after taking celecoxib, and NIAM was suspected. The headache resolved quickly following celecoxib discontinuation. Although lumbar puncture was not available in this case, bacterial or viral meningitis was negative, and NIAM could not be ruled out. This case involved an older adult patient without an autoimmune disease, with celecoxib as the causative NSAID. A literature review found numerous cases of autoimmune diseases in younger patients. To date, only one case of celecoxib-induced NIAM has been reported. Analysis of NIAM cases in JADER revealed an onset time of approximately three days. JADER analysis indicated that NIAM tended to occur immediately after administration, although the onset with cyclooxygenase-2 selective agents might be slower.

Relationships between acute generalized eruptive pustulosis, age, sex, primary disease, and prescription medications: Further analysis of the Japanese Adverse Drug Event Report database.

Background: Acute generalized eruptive pustulosis (AGEP) is a rare, but serious, drug-related adverse event. This study aimed to determine the relationships between AGEP and age, sex, primary disease, and prescription medications using a database of adverse drug events, namely, the Japanese Adverse Drug Event Report (JADER) database. Methods: In this retrospective observational study, we analyzed AGEP reports extracted from the JADER database based on the preferred term for AGEP (code 10048799). We evaluated the effects of causative drugs, underlying diseases, age, and sex. The association between AGEP and prescription drugs was analyzed using the reporting odds ratio and adjusted for covariates using multiple logistic regression. Association rule mining was performed to evaluate the correlation between each combination of factors and AGEP. Results: Between April 2004 and March 2023, 823,662 reports, including 869 reports on AGEP, were entered in the JADER database. The highest percentage of reports in each age group was in males aged <10 years, and clarithromycin was the most used drug in males aged <10 years. Nasopharyngitis was the most common reason for use, and Kawasaki disease was reported as a reason for use among males under 10 years of age, but not among females. Conclusions: In boys aged <10 years, attention should be paid to the occurrence of AGEP when prescribing clarithromycin and treating Kawasaki disease.

Two-year outcomes of endovascular therapy for femoropopliteal arterial lesions for patients with high bleeding risk.

The Academic Research Consortium (ARC) recently published a definition of patients at high bleeding risk (HBR) undergoing percutaneous coronary intervention. However, the prevalence of the ARC-HBR criteria in patients undergoing endovascular therapy (EVT) for femoropopliteal arterial lesions has not been thoroughly investigated. The study population comprised 165 patients undergoing initial EVT for femoropopliteal lesions between June 2018 and June 2020. They were divided into two groups according to the ARC-HBR criteria. The primary end point was a composite of all-cause death, Bleeding Academic Research Consortium type 3 or 5 bleeding, and target lesion revascularization (TLR) within 2 years of EVT. The 165 patients were divided into two groups: 125 (75.8%) patients at HBR (HBR group) and 40 (24.2%) patients at no HBR (non-HBR group). The cumulative incidence of the primary endpoint was significantly higher in the HBR group than in the non-HBR group (40.6% vs. 0%, log-rank p < 0.001). The HBR group had a significantly higher risk of all-cause death, major bleeding, and TLR than the non-HBR group (25.2% vs. 0%, log-rank p = 0.004, 13.9% vs. 0%, log-rank p = 0.047, 16.8% vs. 0%, log-rank p = 0.035). Most patients with peripheral artery disease were classified as HBR patients, and HBR patients were at higher risk of death, major bleeding, and TLR than non-HBR patients.

Genome sequence and cell biological toolbox of the highly regenerative, coenocytic green feather alga Bryopsis.

Green feather algae (Bryopsidales) undergo a unique life cycle in which a single cell repeatedly executes nuclear division without cytokinesis, resulting in the development of a thallus (>100 mm) with characteristic morphology called coenocyte. Bryopsis is a representative coenocytic alga that has exceptionally high regeneration ability: extruded cytoplasm aggregates rapidly in seawater, leading to the formation of protoplasts. However, the genetic basis of the unique cell biology of Bryopsis remains poorly understood. Here, we present a high-quality assembly and annotation of the nuclear genome of Bryopsis sp. (90.7 Mbp, 27 contigs, N50 = 6.7 Mbp, 14 034 protein-coding genes). Comparative genomic analyses indicate that the genes encoding BPL-1/Bryohealin, the aggregation-promoting lectin, are heavily duplicated in Bryopsis, whereas homologous genes are absent in other ulvophyceans, suggesting the basis of regeneration capability of Bryopsis. Bryopsis sp. possesses >30 kinesins but only a single myosin, which differs from other green algae that have multiple types of myosin genes. Consistent with this biased motor toolkit, we observed that the bidirectional motility of chloroplasts in the cytoplasm was dependent on microtubules but not actin in Bryopsis sp. Most genes required for cytokinesis in plants are present in Bryopsis, including those in the SNARE or kinesin superfamily. Nevertheless, a kinesin crucial for cytokinesis initiation in plants (NACK/Kinesin-7II) is hardly expressed in the coenocytic part of the thallus, possibly underlying the lack of cytokinesis in this portion. The present genome sequence lays the foundation for experimental biology in coenocytic macroalgae.

Simultaneous high-performance liquid chromatography analysis of anthraquinones in sicklepod sprouts with α-glucosidase inhibitory activity.

INTRODUCTION: Sicklepod [Cassia obtusifolia L. syn Senna obtusifolia (L.) H.S. Irwin & Barneby, Fabaceae] sprouts are promising ingredients with health-promoting benefits. Notwithstanding, the pharmacologically active compounds in sicklepod sprouts have not been studied or analysed in detail. OBJECTIVE: This study aimed to isolate and structurally identify phytochemicals showing α-glucosidase inhibitory activity in sicklepod sprouts and simultaneously quantify the compounds in the sprouts to determine the optimal cultivation method and germination time to maximise active compounds. METHOD: A simultaneous high-performance liquid chromatography-ultraviolet (HPLC-UV) method with high sensitivity and accuracy was developed and used to analyse time-dependent changes in anthraquinone content during sicklepod germination. RESULTS: Thirteen anthraquinones were isolated and identified, of which six-chrysoobtusin, emodin, 1-O-methyl-2-methoxychrysophanol, 7-O-methylobtusin, chrysophanol, and physcion-showed moderate α-glucosidase inhibitory activity. The maximum content of anthraquinones in a sprout was observed on Day 5 under both light and dark conditions. CONCLUSION: The findings of this study revealed that sicklepod sprouts which are promising functional food materials contain a variety of anthraquinones.

Elastic Banding Compression as a Novel Treatment to Maintain Hemodynamics in a Patient With Klippel-Trenaunay Syndrome.

Klippel-Trenaunay syndrome (KTS) is also associated with venous thrombosis originating from varicose veins in the lower extremities, pulmonary embolism, and pulmonary hypertension. This study describes the anesthetic management of laparoscopic cholecystectomy in a 54-year-old male KTS patient with orthostatic hypotension due to massive varicose veins in the lower extremities and pulmonary thromboembolism. Compressing the varicosities with an elastic bandage can maintain stable circulatory dynamics even under general anesthesia management to prevent position and insufflation-induced changes that can occur spontaneously.

A novel pathogenic variant in fibroblast growth factor 23 outside the furin-recognizing RXXR motif in an autosomal dominant hypophosphatemic rickets patient.

INTRODUCTION: Autosomal dominant hypophosphatemic rickets (ADHR) is caused by pathogenic variants in the fibroblast growth factor 23 (FGF23) gene, which plays a key role in the regulation of phosphorus metabolism. FGF23 has the RXXR motif recognized by furin, leading to cleavage between R179 and S180 and thereby inactivating the protein's function. Previously reported variants in FGF23 causing ADHR occurred only affecting residues R176 or R179, which are located in the RXXR motif, leading to impaired cleavage. Impairment of protein cleavage increases bioactive FGF23 levels, subsequently resulting in the development of ADHR. CASE PRESENTATION: A 13-year-old boy with ADHR with the appearance of rickets on bone radiographs as well as documented hypophosphatemia was found to have a novel S180I variant in the FGF23 gene. Unlike previously reported pathogenic variants, this novel variant was located outside the RXXR motif. Subsequently, western blotting showed that the S180I mutant was resistant to proteolysis than the wild-type, similar to pathogenic variants model mutant (R176Q/R179Q). CONCLUSION: The novel variant in FGF23 presented herein, found in a patient with ADHR, is the first pathogenic variant found outside the typical furin recognition sequence. It exhibits proteolysis resistance due to impaired cleavage.

An Infant Diagnosed With 22q11.2 Deletion Syndrome Following Frequent Apneic Attacks.

22q11.2 deletion syndrome (DS) is a microdeletion syndrome that pediatricians may encounter. It has a distinctive presentation and is often diagnosed based on a few characteristic symptoms. However, 22q11.2 DS with apnea as the initial symptom has never been reported. In this report, we describe the case of a one-month-old infant diagnosed with 22q11.2 DS due to apneic attacks. Early diagnosis of 22q11.2 DS is crucial because it enables appropriate intervention.

Post-renal Biopsy Retroperitoneal Haematoma Accompanied by Decreased Coagulation Factor XIII Levels in Immunoglobulin A Nephropathy.

Post-biopsy bleeding is the primary complication of renal biopsy. Retroperitoneal haematoma is a rare but severe bleeding complication; it commonly occurs among patients who have risk factors or vascular lesions. The bleeding risks in patients with immunoglobulin A (IgA) nephropathy (IgAN) have been discussed in the literature, but clinical data are lacking. Here, we report a case of a post-biopsy retroperitoneal haematoma accompanied by decreased coagulation factor XIII (FXIII) in a patient with IgAN. A 14-year-old male patient with haematuria and proteinuria but no bleeding or family history of bleeding underwent pre-renal biopsy evaluation that showed no coagulation abnormalities. He underwent percutaneous renal biopsy, and the histopathological diagnosis was IgAN. Five days after the biopsy, he presented with delayed bleeding from a retroperitoneal haematoma. During the workup for undiagnosed haemorrhagic diatheses, a mildly decreased FXIII level was discovered. This result suggested the possibility of bleeding complications associated with decreased FXIII. Some bleeding diatheses, including FXIII deficiency, cannot be evaluated in routine pre-biopsy coagulation tests. Mild FXIII deficiency can increase the risk of post-biopsy bleeding complications. Therefore, physicians should consider unevaluated haemorrhagic diatheses when a patient presents with major bleeding complications or delayed bleeding following renal biopsy without any known risk factors or vascular lesions.