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.

Radiological characteristics of skeletal growth in neonates and infants with achondroplasia.

Achondroplasia (ACH) is the most common form of skeletal dysplasia characterized by a rhizomelic short stature. Radiological skeletal findings in pediatric and adult patients with ACH include short long bones, a relatively longer fibula compared to the tibia, a narrow lumbar interpedicular distance, and a hypoplastic iliac wing. Nonetheless, the characteristics of skeletal growth during the neonatal and infantile periods have scarcely been explored. Therefore, this retrospective study aimed to analyze the radiological skeletal growth during the neonatal and infantile periods in 41 Japanese patients with genetically confirmed ACH. The length of long bones in the upper and lower limbs and the lumbar interpedicular distances at L1 and L4 were measured. These parameters showed significant positive correlations with age. The upper segment-to-lower segment ratio in the lower limbs resembled the data of healthy controls from previous reports. The L1/L4 and fibula/tibia ratios increased with age, suggesting that some representative skeletal phenotypes of ACH were less distinct during the neonatal and infantile periods. In conclusion, for the first time, this study radiologically characterized skeletal growth during the neonatal and infantile periods of patients with genetically confirmed ACH.

Fifteen-Year Clinical Outcomes After Sirolimus-Eluting Stent Implantation.

BACKGROUND: Clinical outcomes after percutaneous coronary intervention have improved with the use of drug-eluting stents, but data beyond 10 years are limited. The purpose of this study was to evaluate the clinical outcomes of patients undergoing sirolimus-eluting stent implantation with follow-up beyond 10 years and to determine the impact of clinical and angiographic characteristics on long-term prognosis. METHODS AND RESULTS: The clinical outcomes of 885 patients who had undergone sirolimus-eluting stent implantation at a single institution were retrospectively reviewed. Primary endpoints included in the analysis were clinically driven target lesion revascularization (cTLR) and target lesion revascularization (TLR). Univariate and multivariate nominal logistic regression was used for data analysis. The incidence rates of cTLR and TLR beyond 10 years after sirolimus-eluting stent implantation were 16.4% and 36.8%, respectively, with cTLR tending to decrease beyond 10 years. Acute coronary syndrome was a predominant trigger for cTLR. Age, statin use, and stent restenosis emerged as predictors of cTLR within 10 years, but no significant predictors other than age were identified beyond 10 years. CONCLUSIONS: Events continue to occur beyond 10 years after sirolimus-eluting stent implantation, with a trend toward an increase in acute coronary syndromes. It is important to be vigilant about the occurrence of acute coronary syndromes during long-term follow-up.

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.

Analysis of the Medication Persistence Rate for and Adherence to Oral 5-Aminosalicylic Acid Preparations in Japanese Patients with Ulcerative Colitis: Study Using a Nationwide Claims Database.

INTRODUCTION: 5-aminosalicylic acid (5-ASA) is the first-line drug for the treatment of mild-to-moderate ulcerative colitis (UC). Three oral sustained-release formulations are often used. However, no unified view of their actual use in routine medical practice has been presented to date. METHODS: Using a health insurance claims database, we extracted patients with an initial diagnosis of mild-to-moderate UC during the period from December 1, 2017, to March 31, 2022. For the three types of oral 5-ASA formulation, we calculated and compared descriptive statistics of medication persistence rates (MPR), proportions of days covered (PDC), and adherence proportion (PDC ≥80%) in the extracted population. RESULTS: An oral 5-ASA formulation was used in combination with a topical preparation (cohort 1) in 899 patients, and oral 5-ASA was used alone (cohort 2) in 1,829 patients. In cohort 1, MPR at days 151-180 with concomitant use of topical formulation was significantly higher for the Multi Matrix System™ (MMX) formulation (65.2%) compared with that for pH-dependent formulation (51.7%, p < 0.025), while MPR tended to be higher for MMX than for the time-dependent formulation (56.4%, not significant). During days 151-180 after starting the oral formulation, MPR for MMX (66.7% and 65.8%) was higher than for pH-dependent (55.9% and 55.3%) and time-dependent (57.6% and 55.9%) formulations in cohorts 1 + 2 and 2, respectively. In cohort 1, there was a significant difference between MMX (68.3%) and pH-dependent (57.1%) formulations, but no significant difference was seen with time-dependent formulations (61.8%). In terms of the proportion of adherence until day 180, MMX was significantly better than the other formulations. CONCLUSION: The analyses of the three oral 5-ASA formulations suggested that both MPR and medication adherence were better for the MMX formulation than for time-dependent or pH-dependent formulations.

Female social dynamics as viewed from grooming networks in the Central Himalayan Langur (Semnopithecus schistaceus).

Enhanced survival and reproduction are associated with an individual's direct and indirect social connections with members of a group. Yet, the role of these connections is little known in a vast range of primate species. We studied female Central Himalayan Langur (CHL) to investigate the link between four specific attributes (dominance rank, age, genetic relatedness, and the presence of females carrying infants) and a female's direct and indirect social relationships. By analyzing grooming networks, we revealed different behavioral strategies: high-ranking females form relationships with many females (high degree), whereas females with dependent infants have strong relationships (high strength and eigenvector). Subadult females are important individuals that hold the social network together (high betweenness), while an immigrant female strategy is to integrate herself into the group by forming strong bonds with females who themselves have strong bonds (high eigenvector). Our study sheds light on how behavioral strategies shape female CHL grooming networks, which may help them to secure fitness and survival advantages.

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.

Simultaneous rapid detection of glycyrrhizin and sennoside A in Daiokanzoto samples by lateral flow immunoassay.

INTRODUCTION: Glycyrrhizin (GLY) and sennoside A (SA) are characteristic bioactive marker compounds of the Kampo medicine Daiokanzoto. Their accurate detection in blends of Rhei rhizoma and Glycyrrhizae radix of several species (4:1 or 4:2) is essential for quality control and to ensure therapeutic efficacy. A rapid, efficient assay can significantly facilitate their detection. OBJECTIVE: To establish a rapid qualitative assay for GLY and SA detection, a lateral flow immunoassay (LFA) was developed using specific monoclonal antibody (mAb) nanoparticles. METHODOLOGY: This assay harnesses the competitive binding of mAb nanoparticles to the immobilized analytes on test strips and free analytes in the samples. Two conjugates for detecting GLY and SA, GLY-bovine serum albumin and SA-human serum albumin, were separately immobilized on the test zones of LFA strips. The detection mechanism is reliant on the visual detection of color changes in the test zones. RESULTS: When GLY and SA were present in samples, they contended with the immobilized conjugates on the strip to bind with the mAb nanoparticles and produced distinct color patterns in the test zones. The limits of detection of the assay for GLY and SA were both 3.13 µg/mL. The capability of the LFA was substantiated using plant samples and Daiokanzoto, and its alignment with indirect competitive ELISA results was confirmed. CONCLUSION: The introduced LFA is a groundbreaking procedure that offers a rapid, straightforward, and sensitive method for simultaneously detecting GLY and SA in Daiokanzoto samples. It is instrumental in ensuring product quality.

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.

[Questionnaire Survey on Early-Stage Hepatocellular Carcinoma in Patients and Physicians].

We conducted an online questionnaire survey to investigate changes in well-being and anxiety in patients with hepatocellular carcinoma requiring repeated locoregional therapy(hepatectomy/ablation)and the differences between patients' and treating physicians' perceptions of what is important to patients when selecting treatment. Between December 2022 and January 2023, we collected responses from 162 patients and 115 physicians in Japan. Results showed no clinically significant changes in well-being over time. Patients experiencing recurrences and repeated locoregional therapy reported increased anxiety regarding"effectiveness of treatment"and"how to handle the disease."As"factors that patients consider important when receiving locoregional therapy,"many patients and physicians selected suppression of recurrence, prolonged survival, and safety; however, patients placed more importance on"reducing the number of locoregional therapies"as they repeatedly experienced recurrence and therapy. Regarding"information that patients consider important when selecting adjuvant therapy,""effectiveness of treatment"and"adverse effects of treatment"were important to both patients and physicians, while"maintaining a normal daily life"was more important in patients and"length of treatment"was more important in physicians. In conclusion, some factors are perceived by both physicians and patients as important when selecting treatment, but there is a gap in perception for other factors. Physicians and patients should discuss their opinions on what is important in treatment before deciding on a treatment strategy.

Development of an Organic Emitter Exhibiting Reverse Intersystem Crossing Faster than Intersystem Crossing.

In thermally activated delayed fluorescence (TADF)-based organic light-emitting diodes (OLEDs), acceleration of reverse intersystem crossing (RISC) and suppression of intersystem crossing (ISC) are demanded to shorten a lifetime of triplet excitons. As a system realizing RISC faster than ISC, inverted singlet-triplet excited states (iST) with a negative energy difference (ΔEST) between the lowest excited singlet and the lowest triplet states have been gathering much attention recently. Here, we have focused on an asymmetric hexa-azaphenalene (A6AP) core to obtain a new insight into iST. Based on A6AP, we have newly designed A6AP-Cz with the calculated ΔEST of -44 meV. The experimental studies of a synthesized A6AP-Cz revealed that the lifetime of delayed fluorescence (τDF) was only 54 ns, which was the shortest among all organic materials. The rate constant of RISC (kRISC=1.9×107 s-1) was greater than that of ISC (kISC=1.0×107 s-1). The negative ΔEST of A6AP-Cz was experimentally confirmed from 1) the kRISC and kISC (-45 meV) and 2) the temperature-dependent τDF. 3) The onsets of fluorescence and phosphorescence spectra at 77 K also supported the evidence of negative ΔEST (-73 meV). This study demonstrated the potential of A6AP as an iST core for the first time.

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.

Emotional journey of patients with specified intractable diseases in Japan.

This study aimed to depict the emotional journey of Japanese patients with specific intractable diseases facing challenges associated with a delayed diagnosis. Specifically, our focus was on elucidating the emotional journey of patients and identifying the unmet needs caused by a delayed diagnosis. We conducted a web-based survey targeting 179 patients with 11 specified intractable diseases. They reported their emotional states during each journey phase using a 10-point scale. The results revealed that the period from noticing bodily changes to clinic visits was characterized by the most negative emotional states. Furthermore, the patients experienced a gradual shift towards positive emotional states as they decided to complete a consultation at a specialized hospital. They reached their most positive emotional states when they received a definitive diagnosis, subsequent treatment, and care. The thematic classification of emotional changes at the time of definitive diagnosis showed that "relief" was the most prevalent emotion (41.9%), followed by "no change" (19.9%), "anxiety" (14.0%), "shock" (13.4%), and "resignation" (6.5%). Additionally, when classifying the thematic changes in emotions during the period of bodily changes and clinic visits, "frustration" was the most common (51.3%), followed by "fear and anxiety" (43.6%). Patients tended to be most psychologically distressed during the period leading up to the definitive diagnosis. These results reveal that patients with intractable diseases are seeking a fast and accurate diagnosis, and that achieving these is a key unmet need for the patients.

Demonstration of enhanced long-range cosmic time synchronization for wireless and secure dissemination of standard time.

Accurate traceability of time is prerequisite to the proper functioning of many necessary aspects of our modern life including making financial transactions, managing automated technology and navigating the transport of goods and human beings. One of the most reliable international time references is the Coordinated Universal Time (UTC) that can be distributed wirelessly in principle. However, this wireless option is currently limited to GPS and other global navigation satellite systems. GPS signals are weak and easily affected by environmental conditions. Moreover, since GPS signals are unencrypted, the possibility of a signal spoofing attack remains a continuous threat. Prior works showed the potential of the alternative wireless time synchronization technique called Cosmic Time Synchronization (CTS), in which, clocks are located 50 m apart were wirelessly synchronized with a sub-microsecond level accuracy, and its operation time was limited to 20 min. However, for the actual implementation of CTS to real-life situations, these distance and stability values are not sufficient. In this study, we constructed a dedicated CTS facility and conducted a long-haul (180 m) CTS demonstration. As a result, it was verified that this long-range CTS is capable of maintaining stable sub-microsecond time synchronization for 3 days with a granularity of 148.8 ns (SD) and an offset of 22.97 ns. Since the current version of CTS can now operate over an area that has been enlarged by more than one order of magnitude, it is possible to utilize for more diverse applications, and the application to a banking synchronization system is proposed. As a case study, it is shown that CTS now has the capability to offer wireless time synchronization service to large clusters of financial firms in large cities. With its accurate time dissemination (the metrological traceability to UTC), its reasonable cost, and its hack-proof, stable design, this latest CTS model has the capacity to improve the accuracy of timing for a wide variety of sectors.

Developments of a centimeter-level precise muometric wireless navigation system (MuWNS-V) and its first demonstration using directional information from tracking detectors.

Various positioning techniques such as Wi-Fi positioning system have been proposed to use in situations where satellite navigation is unavailable. One such system, the muometric positioning system (muPS), was invented for navigation which operates in locations where even radio waves cannot reach such as underwater or underground. muPS takes advantage of a key feature of its probe, cosmic-ray muons, which travel straightforwardly at almost a speed of light in vacuum regardless of the matter they traverse. Similar to other positioning techniques, muPS is a technique to determine the position of a client's muPS receiver within the coordinate defined by reference detectors. This can be achieved either by using time-of-flight (ToF) or angle of arrival (AoA) measurements. The latter configuration (AoA), called the Vector-muPS has recently been invented and the present paper describes the developments of the first prototype of a vector muometric wireless navigation system (MuWNS-V) with this new vector-muPS concept and its demonstration. With MuWNS-V, the reference tracker and the receiver ran wirelessly with fully independent readout systems, and a positioning accuracy of 3.9 cm (RMS) has been achieved. We also evaluated the outcome of measuring continuous indoor localization of a moving receiver with this prototype. Our results indicated that further improvements in positioning accuracy will be attainable by acquiring higher angular resolution of the reference trackers. It is anticipated that "sub-cm level" navigation will be possible for muPS which could be applied to many situations such as future autonomous mobile robot operations.

Hypoxia-inducible Factor Prolyl Hydroxylase Inhibitors and Hypothyroidism: An Analysis of the Japanese Pharmacovigilance Database.

BACKGROUND/AIM: Hypothyroidism induced by roxadustat, a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, was recently reported; however, information regarding roxadustat-associated hypothyroidism is still lacking. We explored the risk and time to onset of hypothyroidism associated with HIF-PH inhibitors using the Japanese Adverse Drug Event Report (JADER), a pharmacovigilance database. PATIENTS AND METHODS: The participants of this study were registered in the JADER database between April 2004 and March 2023. The association between HIF-PH inhibitors and hypothyroidism was evaluated using the reporting odds ratio (ROR) and information component (IC). We also calculated the period from the start of drug administration to the onset of hypothyroidism and determined the onset pattern using Weibull distribution. RESULTS: Roxadustat had positive signals for hypothyroidism among the HIF-PH inhibitors based on the ROR [31.03, 95% confidence interval (CI)=27.81-34.62] and IC (4.51, 95%CI=4.36-4.67) values, and a strong relationship was confirmed. In addition, the median time to roxadustat-associated hypothyroidism onset was 92 days, and over 50% of cases occurred within 100 days of starting treatment. Furthermore, the onset pattern was an early failure type. CONCLUSION: There is a possible association between roxadustat and hypothyroidism. Therefore, enhanced thyroid function testing within 100 days of treatment initiation may help detect roxadustat-associated hypothyroidism. However, further research is required to confirm these findings, considering study limitations using databases of spontaneous adverse event reports.

Successful treatment of a unique case of solitary primary iliopsoas abscess caused by Streptococcus dysgalactiae subspecies equisimilis: A case report.

RATIONALE: Iliopsoas abscess, mainly caused by Staphylococcus aureus, occurs via the bloodstream or spread from adjacent infected organs. Although a few cases regarding primary iliopsoas abscess caused by Streptococcus dysgalactiae subspecies equisimilis (SDSE) with accompanying disseminated foci have been reported to date, there has been no case report on solitary primary iliopsoas abscess caused by SDSE. PATIENT CONCERNS: An 85-year-old Japanese woman presented with worsening right hip pain and fever after an exercise. Hip computed tomography revealed a right iliopsoas abscess (iliac fossa abscess), and intravenous cefazolin was started as a treatment based on the creatinine clearance level on admission. DIAGNOSES: Blood cultures were positive for ß-hemolytic Lancefield group G gram-positive cocci arranged in long chains, which were identified as SDSE by matrix-assisted laser desorption/ionization. No other disseminated foci were found upon performing whole computed tomography and transthoracic echocardiography. The patient was diagnosed with an SDSE solitary iliopsoas abscess. INTERVENTIONS: The antimicrobial was appropriately switched to intravenous ampicillin on day 2, with the dosage adjusted to 2 g every 6 hours based on the preadmission creatinine clearance, followed by oral amoxicillin (1500 mg, daily). OUTCOMES: The abscess disappeared without drainage on day 39, and the patient remained disease-free without recurrence or sequelae during a 6-month follow-up period. LESSONS: SDSE can cause a solitary primary iliopsoas abscess, which can be successfully treated with an appropriate dose of antimicrobials without draining the abscess.

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.

Two Cases of Cardiovascular Adverse Events Following Subcutaneous Vosoritide Injection in Early Infancy.

Achondroplasia, characterized by short stature and skeletal abnormalities, is caused by a gain-of-function variant in the fibroblast growth factor receptor 3 gene. Vosoritide, a C-type natriuretic peptide analog, is an emerging treatment for achondroplasia that functions by promoting endochondral ossification. Vosoritide was approved for the treatment of achondroplasia in Europe and the United States in 2021, and in Japan, the following year. However, vosoritide is associated with a risk of hypotension and vomiting after subcutaneous injection due to its vasodilating effect. Herein, we present two cases of cardiovascular adverse events in infants following vosoritide injection. Case 1 involved a one-month-old female infant with achondroplasia who received the first subcutaneous injection of vosoritide 30 minutes after her last formula intake. Following injection, she developed transient symptomatic hypotension accompanied by vomiting. Although established guidelines recommend that injections be administered after approximately 30 minutes (Europe/Japan) or within one hour (USA) following the last feeding, an extended interval of 1.5 to two hours was required to prevent hypotension-associated vomiting. Case 2 involved a three-month-old female infant with achondroplasia. The first subcutaneous vosoritide injection was administered four hours after the last formula intake, and she subsequently developed prolonged compensated shock with marked tachycardia requiring intervention, including repetitive bolus saline injection. These cases indicate the need to monitor patients for cardiovascular adverse events following subcutaneous injection of vosoritide in early infancy.

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.