Elevated Myl9 reflects the Myl9-containing microthrombi in SARS-CoV-2-induced lung exudative vasculitis and predicts COVID-19 severity.

The mortality of coronavirus disease 2019 (COVID-19) is strongly correlated with pulmonary vascular pathology accompanied by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-triggered immune dysregulation and aberrant activation of platelets. We combined histological analyses using field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy analyses of the lungs from autopsy samples and single-cell RNA sequencing of peripheral blood mononuclear cells to investigate the pathogenesis of vasculitis and immunothrombosis in COVID-19. We found that SARS-CoV-2 accumulated in the pulmonary vessels, causing exudative vasculitis accompanied by the emergence of thrombospondin-1-expressing noncanonical monocytes and the formation of myosin light chain 9 (Myl9)-containing microthrombi in the lung of COVID-19 patients with fatal disease. The amount of plasma Myl9 in COVID-19 was correlated with the clinical severity, and measuring plasma Myl9 together with other markers allowed us to predict the severity of the disease more accurately. This study provides detailed insight into the pathogenesis of vasculitis and immunothrombosis, which may lead to optimal medical treatment for COVID-19.

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

AIM: We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. MATERIALS AND METHODS: This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. RESULTS: Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. CONCLUSIONS: There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Volume-Outcome Relationships for Intra-Aortic Balloon Pump in Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a major scenario for the use of an intra-aortic balloon pump (IABP), particularly when complicated by cardiogenic shock, although the utilization of mechanical circulatory support devices varies widely per hospital. We evaluated the relationship, at the hospital level, between the volume of IABP use and mortality in AMI.Methods and Results: Using a Japanese nationwide administrative database, 26,490 patients with AMI undergoing primary percutaneous coronary intervention (PCI) from 154 hospitals were included in this study. The primary endpoint was the observed-to-predicted in-hospital mortality ratio. Predicted mortality per patient was calculated using baseline variables and averaged for each hospital. The associations among PCI volume for AMI, observed and predicted in-hospital mortality, and observed and predicted IABP use were assessed per hospital. Of 26,490 patients, 2,959 (11.2%) were treated with IABP and 1,283 (4.8%) died during hospitalization. The annualized number of uses of IABP per hospital in AMI was 4.5. In lower-volume primary PCI centers, IABP was more likely to be underused than expected, and the observed-to-predicted in-hospital mortality ratio was higher than in higher-volume centers. CONCLUSIONS: A lower annual number of IABP use was associated with an increased mortality risk at the hospital level, suggesting that IABP use can be an institutional quality indicator in the setting of AMI.

A prediction model of abnormal acid reflux in gastroesophageal reflux disease.

BACKGROUND AND AIM: The measurement of esophageal acid exposure time (AET) using combined multichannel intraluminal impedance-pH (MII-pH) tests is the gold standard for diagnosing gastroesophageal reflux disease (GERD). However, this catheter-based 24-h test can cause considerable patient discomfort. Our aim is to identify factors affecting AET and to develop a scoring model for predicting AET abnormalities before conducting the MII-pH test. METHODS: Of the 366 patients who underwent MII-pH test at two facilities in Japan and Vietnam, 255 patients who also had esophagogastroduodenoscopy and high-resolution manometry were included in this study. Logistic regression analysis was conducted using risk factors for AET > 6% identified from a derivation cohort (n = 109). A scoring system predicting AET > 6% was then constructed and externally validated with a separate cohort (n = 146). RESULTS: Three variables were derived from the prediction model: male gender, Hill grades III-IV, and weak mean distal contractile integrals. Based on these scores, patients were classified into low (0 point), intermediate (1-3 points), and high (4 points) risk groups. The probabilities of having an AET > 6% were 6%, 34%, and 100% for these groups, respectively. A score of < 1 excluded patients with abnormal AET, with a negative predictive value of 93.8% in the derivation cohort and 80.0% in the validation cohort. CONCLUSIONS: We derived and externally validated a prediction model for abnormal AET. This system could assist in guiding the appropriate treatment strategies for GERD.

Franseen needle in endobronchial ultrasound-guided transbronchial needle aspiration: a phase II prospective study.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has been used to diagnose and stage lung cancer. Acquire™ Pulmonary and Expect™ Pulmonary dedicated EBUS-TBNA needles were introduced as the Franseen and Lancet needles, respectively. It is still unclear whether the Franseen or Lancet needles yield a higher quality specimen especially focusing on next-generation sequencing-based molecular testing. METHODS: A single-center, prospective study performed at the Chiba University Hospital randomly assigned patients to two groups: Group A, wherein the first and second EBUS-TBNA were performed using Lancet and Franseen needles, respectively, and Group B, wherein the first and second EBUS-TBNA were performed using Franseen and Lancet needles, respectively. Each specimen was compared and analyzed pathologically. The primary outcome was the histological tissue area except blood clot and the cellularity of each sample. We also examined the success rate of molecular testing. RESULTS: Twelve patients who underwent EBUS-TBNA between November 2022 and February 2023 were enrolled in this study. The tissue area of the specimens obtained by the Franseen and Lancet needles was 13.3 ± 6.4 mm2 and 10.6 ± 6.3 mm2, respectively (P = .355). The tumor cellularity in the specimens obtained using the Franseen and Lancet needles was 54.0 ± 30.3 and 46.2 ± 36.3%, respectively (P = .608). The success rate of molecular testing using the single-pass sample by Franseen needle was 85.7 and 57.1% by Lancet needle. No serious complications were reported. CONCLUSIONS: The Franseen needle tended to show a greater amount of specimen with higher tumor cellularity than the Lancet needle which may contribute higher success rate of molecular testing. Further studies must be conducted to validate the results of this study. KEY FINDINGS: What is known and what is new?  What is the implication, and what should change now?

Comparison of the effect of surgical versus transcatheter aortic valve replacement on the development of postoperative acute kidney injury.

Acute kidney injury (AKI) frequently occurs after cardiac surgery. Recently, transcatheter aortic valve implantation (TAVI), a less invasive option for aortic stenosis (AS), has been increasingly performed, particularly in elderly patients. We retrospectively investigated and compared the incidence and risk factors of postoperative AKI in patients who underwent surgical aortic valve replacement (SAVR) and TAVI. This was a retrospective single-center study. Seven days postoperatively, data were obtained from medical records. Patients were classified into SAVR and TAVI groups based on age, according to the policy of the Japanese Circulation Society. A total of 155 patients underwent surgery for AS between January 2020 and December 2021. Variables included age, sex, risk score, preoperative left ventricular ejection fraction, hypertension, and renal dysfunction. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes criteria. A total of 33 SAVR and 79 TAVI procedures were included in this study. The incidences of AKI in the SAVR and TAVI groups were 45.5% and 43.0%, respectively. No significant differences existed between the two groups. Weight (p = 0.0392) and pre-renal dysfunction (p = 0.0308) affected the incidence of AKI in the SAVR group, whereas no such variables were identified in the TAVI group. Within the current age-based treatment selection criteria for AS, no significant difference in the incidence of AKI was observed between the two procedures.Although preoperative renal function may be associated with postoperative AKI, further studies are required to select the optimal surgical procedure for patients with renal dysfunction.

Variability in sonographic anterior drawer test measurements of the ankle: Experienced versus beginner examiners.

BACKGROUND: This study aimed to clarify the variability in the measurements of stress sonography of the ankle and determine the effects of examiner experience on the measurements. METHODS: Twenty examiners (10 experienced and 10 beginners) were included in the study. Each examiner performed stress ultrasonography on a patient with a chronic anterior talofibular ligament injury and a patient with an intact ligament using the reverse anterior drawer method. Changes in ligament length before versus after stress were determined. The same 20 examiners performed ultrasonography on two other patients with an injured or intact ATFL using the anterior drawer method. The length change values and variance were compared between the groups using t-tests and F-tests. RESULTS: Using the reverse anterior drawer method, the change in the anterior talofibular ligament length was 3.3 mm (range, 2.2-4.8 mm) in the experienced group and 2.7 mm (0.0-4.1 mm) in the beginner group for the ligament injured patient. The length changes for the patient with intact anterior talofibular ligament were 0.5 mm (0.1-0.9 mm) and 0.4 mm (-0.1-1.5 mm) in the experienced and beginner groups, respectively. There were no significant intergroup differences in measurement amount (P = 0.37) or variance (P = 0.72). Similarly, using the anterior drawer method, no significant differences between the groups were found in measurement amount or variance. CONCLUSION: The quantitative evaluation of stress sonography of the ankle was variable regardless of examiner experience or stress method, particularly in patients with an anterior talofibular ligament injury. The amount of variability appeared to be unacceptably large for clinical application. Our study results highlight the need for technical standardization.

Assessment of pre-extubating recurrent laryngeal nerve palsy using ultrasound in postoperative patients with esophageal cancer: a prospective observational study.

PURPOSE: Ultrasound performed after extubation has been suggested to be useful for the diagnosis of recurrent laryngeal nerve (RLN) paralysis. However, the use of ultrasound for this purpose before extubation has not been examined. The aim of this study was to examine the versatility (interrater reliability) and usefulness of ultrasound for evaluating the movement of vocal cords before extubation. METHODS: The subjects were 30 patients who underwent radical surgery for esophageal cancer from August 2020 to December 2021. An experienced examiner performed an ultrasound examination before and after elective extubation on the day after surgery to evaluate RLN paralysis and record videos. Bronchoscopy was then performed to make a definite diagnosis. Three anesthetists blinded to the diagnosis also evaluated the cases using the videos, and the versatility of the examination was determined using a kappa test. RESULTS: The diagnostic accuracies of the examiner and three anesthetists were 76.7%, 50.0%, 53.3%, and 46.7%, respectively, and the kappa coefficients for the examiner with the anesthetists were 0.310, 0.502, and 0.169, respectively. The sensitivity, specificity, positive predictive value and negative predictive value for diagnosis of RLN paralysis by the examiner using ultrasound before extubation were 0.57, 0.95, 0.80, and 0.87, respectively. CONCLUSION: These results indicate a lack of versatility of the ultrasound examination based on the low kappa coefficients. However, with an experienced examiner, ultrasound can serve as a non-invasive examination that can be performed before extubation with high accuracy and specificity for diagnosis of postoperative RLN paralysis.

Protocolized oxytocin infusion for elective cesarean delivery: a retrospective before-and-after study.

PURPOSE: To elucidate the clinical impact of the novel oxytocin protocol using a syringe pump with a stratified dose compared with the conventional practice of putting oxytocin into the bag. METHODS: This is a retrospective cohort study. We collected the data of the patients who underwent elective cesarean delivery under neuraxial anesthesia between June 2019 and May 2020. The patients were allocated to two groups according to oxytocin administration methods; the control group (the attending anesthesiologist put oxytocin 5-10 units in the infusion bag and adjusted manually after childbirth) and the protocol group (the oxytocin protocol gave oxytocin bolus 1 or 3 units depending on the PPH risk, followed by 5 or 10 unit h-1 via a syringe pump). We compared the total amount of oxytocin within 24 h postpartum, estimated blood loss, and adverse clinical events within 24 h postpartum between the two groups. RESULTS: During the study period, 262 parturients were included. Oxytocin doses of intraoperative and postoperative were significantly lower in the protocol group (9.7 vs. 11.7 units, intraoperative, 15.9 vs. 18 units, postoperative). The subgroup analyses showed that the impact was more remarkable in the low PPH risk than in the high PPH risk. The multivariate linear regression analyses also confirmed the difference. The groups had no significant difference in blood loss, requirement of additional uterotonics, and other adverse events. CONCLUSIONS: Our oxytocin infusion protocol significantly reduced oxytocin requirements in elective cesarean delivery under neuraxial anesthesia without increasing blood loss. However, we could not find other clinical benefits of the novel protocol.

The effect of assisted reproductive technology on postpartum bleeding: hormonal cycle frozen embryo transfer might increase blood loss.

BACKGROUND: Among assisted reproductive technologies, frozen thawed embryo transfer (FET) is associated with increased blood loss at delivery. Anesthesiologists need to be aware of new factors that affect postpartum blood loss. This study investigated whether FET cycles with or without hormonal support affect the amount of postpartum bleeding. METHODS: We conducted a retrospective cohort study of patients admitted for delivery at a single university hospital between January 2015 and December 2018. Patients were divided into no-assisted reproductive technology (No-ART), hormonal cycle FET (HC-FET) and natural cycle FET (NC-FET) group. The primary outcome was the amount of blood loss after delivery (median [interquartile range]), which was compared among the three groups. Multiple regression analysis was performed to investigate the factors affecting blood loss. RESULTS: Between 2015 and 2018, 3187 women delivered neonates. In vaginal delivery, postpartum blood loss in the HC-FET group (1060 [830] g) was significantly greater than in the NC-FET group (650 [485] g, P = 0.001) and in the No-ART group (590 [420] g P < 0.001). Multiple linear regression analysis showed that HC-FET (P < 0.001) was one of the independent factors for the amount of bleeding. In cesarean delivery, the HC-FET group had more blood loss than the No-ART group (910 [676] g vs. 784 [524] g, P = 0.039). However, HC-FET was not an independent factor for postpartum blood loss. CONCLUSIONS: The HC-FET group had more blood loss than the No-ART group for both vaginal and cesarean deliveries. Furthermore, HC-FET was an independent factor that increased postpartum blood loss in vaginal deliveries.

Long-term course of gastric submucosal tumors: growth speed and size-increasing factors.

BACKGROUND AND AIMS: Gastric submucosal tumors (SMTs) are treated or monitored according to GI stromal tumor guidelines, but the adequacy of the guidelines has not been thoroughly examined. We investigated the long-term course of gastric SMTs to determine the validity of guideline-based follow-up methods and the factors contributing to their size increase. METHODS: This study included gastric SMTs diagnosed as GI mesenchymal tumors (GIMTs) by using EUS and followed up with EUS. The percentage and speed of GIMT enlargement and factors associated with the enlargement were investigated by using the Cox proportional hazards model. RESULTS: From January 1994 to May 2022, a total of 925 gastric SMTs were evaluated with EGD, and 231 SMTs were diagnosed as GIMTs. Of the 231 GIMTs, 145 were examined by EUS more than twice and were followed up for >6 months. The mean ± standard deviation follow-up period was 5.20 ± 4.04 years (range, 0.5-17.3 years), with 39 (26.9%) of 145 GIMTs increasing in size with a mean doubling time of 3.60 ± 3.37 years. A multivariate analysis of factors influencing tumor growth revealed that irregular extraluminal borders were an increasing factor (hazard ratio, 3.65; 95% confidence interval, 1.26-10.52), initial tumor size ≤9.5 mm (hazard ratio, .23; 95% confidence interval, 0.07-0.77) was a nonincreasing factor, and GIMTs with calcification (n = 13) did not increase in size. CONCLUSIONS: Tumor growth in gastric GIMTs <9.5 mm in diameter and/or with calcification is rare. Follow-up intervals for these lesions could be extended.

Factors affecting severity of pressure ulcers: Impact of number of medications.

Polypharmacy, which refers to the situation of a patient taking more medications than is clinically necessary, has become a major problem in recent years. Although the effects of medications on pressure ulcers have been reported, there are no reports on the impact of the total number of medications on pressure ulcers. The purpose of this study was to investigate the effect of number of medications on the severity of pressure ulcers. Participants included 94 patients who were admitted to Chiba University Hospital with pressure ulcers between April 2013 and March 2021. Univariate analysis identified ulcer depth, weight loss and anticoagulant use to be factors that contributed to the severity of pressure ulcers. Multiple regression analysis was performed for six variables, namely, the number of medications, ulcer depth, weight loss and anticoagulant use, as well as diabetes status and total serum protein level, which have been reported to be associated with pressure ulcers in previous studies. The following independent risk factors were identified: weight loss (ß 0.207, 95% confidence interval [CI] 0.700-3.193; p = 0.003), anticoagulant use (ß 0.161, 95% CI 0.271-3.088; p = 0.020) and ulcer depth (ß 0.719, 95% CI 7.172-10.329; p < 0.001). The number of medications was not a significant factor. This study revealed that the number of medications a patient is taking does not affect the severity of pressure ulcers. The findings should provide useful information for the management of pressure ulcers.

Effects of the combination of atomoxetine and oxybutynin in Japanese patients with obstructive sleep apnoea: A randomized controlled crossover trial.

BACKGROUND AND OBJECTIVE: The possibility of combination therapy with atomoxetine (ATO) and oxybutynin (OXY) has been suggested for obstructive sleep apnoea (OSA). However, the effectiveness of this treatment remains uninvestigated in Japanese OSA patients. Therefore, we performed a randomized, crossover, phase II, single-centre prospective trial to examine the effects of ATO-OXY therapy in Japanese OSA patients. METHODS: In total, 17 OSA patients participated in this study. The effects of one night of 80-mg ATO plus 5-mg OXY administration were compared with those of no medication administered before sleep. The primary and secondary outcomes comprised the apnoea-hypopnoea index (AHI) and nadir SpO2 , SpO2 drop time and sleep architecture, respectively. The safety endpoints included drug side effects and adverse events. RESULTS: The values of AHI, nadir SpO2 , 3% oxygen desaturation index (ODI), 4% ODI, and SpO2 drop time of <90% did not significantly differ between patients receiving ATO-OXY administration and no medication. Sleep architecture exhibited a significant change: ATO-OXY increased sleep stage N1 (p < 0.0001) and decreased stage N2 (p = 0.03), rapid eye movement (p < 0.0001) and sleep efficiency (p = 0.02). However, the subanalysis demonstrated an obvious decrease in AHI in five responder patients. Total sleep time and basal sleep efficiency tended to be lower in the responders compared with nonresponders (p = 0.065). No patients experienced severe adverse events or side effects. CONCLUSION: Overall, ATO-OXY therapy does not reduce AHI in Japanese OSA patients, although AHI was decreased in a proportion of patients. Future studies for identifying treatment response group characteristics are warranted.

Characteristics and comparative study of thoracolumbar spine injury and dislocation fracture due to tertiary trauma.

PURPOSE: Thoracolumbar spine injury is frequently seen with high-energy trauma but dislocation fractures are relatively rare in spinal trauma, which is often neurologically severe and requires urgent treatment. Therefore, it is essential to understand other concomitant injuries when treating dislocation fractures. The purpose of this study is to determine the differences in clinical features between thoracolumbar spine injury without dislocation and thoracolumbar dislocation fracture. METHODS: We conducted an observational study using the Japan Trauma Data Bank (2004-2019). A total of 734 dislocation fractures (Type C) and 32,382 thoracolumbar spine injuries without dislocation (Non-type C) were included in the study. The patient background, injury mechanism, and major complications in both groups were compared. In addition, multivariate analysis of predictors of the diagnosis of dislocation fracture using logistic regression analysis were performed. RESULTS: Items significantly more frequent in Type C than in Non-type C were males, hypotension, bradycardia, percentage of complete paralysis, falling objects, pincer pressure, accidents during sports, and thoracic artery injury (P < 0.001); items significantly more frequent in Non-type C than in Type C were falls and traffic accidents, head injury, and pelvic trauma (P < 0.001). Logistic regression analysis showed that younger age, male, complete paralysis, bradycardia, and hypotension were associated with dislocation fracture. CONCLUSION: Five associated factors were identified in the development of thoracolumbar dislocation fractures. LEVEL OF EVIDENCE: III.

Comparison between neonatal outcomes of labor and delivery with labor neuraxial analgesia and without analgesia: A propensity score-matched study.

AIM: This single-center observational study aimed to investigate the association between labor neuraxial analgesia (LNA) and neonatal outcomes. METHODS: We conducted a retrospective cohort study at a tertiary perinatal center and included all vaginal deliveries performed between November 2015 and December 2021. Obstetric and neonatal outcomes were compared between deliveries with LNA (LNA group) and without analgesia (control group). Propensity score (PS) matching was used for statistical analysis. RESULTS: We included 2343 singleton deliveries performed in 1367 nulliparous and 976 multiparous women, in whom LNA was induced in 352 and 178 deliveries, respectively. After PS matching, the nulliparous LNA group had a significantly higher incidence of Apgar scores <7 at 1 (7.1% vs. 3.6%, p = 0.0139) and 5 min (2.3% vs. 0.7%, p = 0.0397) and meconium staining (29.8% vs. 23.2%, p = 0.0272) than the nulliparous control group. Other neonatal outcomes, including umbilical artery pH and neonatal intensive care unit admission rate, were comparable between the nulliparous LNA and control groups. No significant differences in neonatal outcomes were seen in multiparous women. Regarding fetal heart rate abnormalities, severe late deceleration (4.8% vs. 1.7%, p = 0.0036) and severe prolonged deceleration (17.0% vs. 11.9%, p = 0.0224) were more common in the nulliparous LNA group than in the nulliparous control group, and the multiparous LNA group exhibited more severe variable deceleration (21.3% vs. 14.3%, p = 0.0485) than the multiparous control group. CONCLUSION: Our findings suggest that LNA is associated with short-term adverse neonatal and obstetric outcomes in vaginal deliveries. LNA should be performed with precautionary measures and adequate medical resources.

Do standardization of the procedure reduce measurement variability of the sonographic anterior drawer test of the ankle?

BACKGROUND: In quantitative ankle stress sonography, different examiners use different techniques, which may cause measurement variability. This study aimed to clarify whether standardizing stress sonography techniques reduces variability in the quantitative measurement of anterior talofibular ligament length change. METHODS: Fourteen examiners with a mean ultrasound experience of 8.7 years participated in this study. Each examiner performed stress ultrasonography of the ankle using their preferred method on one patient with an intact anterior talofibular ligament (Patient 1) and on two patients with chronic ankle instability (Patient 2 and 3). Changes in the ligament length between the resting and stressed positions were determined. A consensus meeting was then conducted to standardize the sonographic technique, which was used by the examiners during a repeat stress sonography on the same patients. The variance and measured values were compared between the preferred and standardized techniques using F-tests and paired t-tests, respectively. RESULTS: At a consensus meeting, a sonographic technique in which the examiner pushed the lower leg posteriorly against the fixed foot was adopted as the standardized technique. In Patient 1, the change in the anterior talofibular ligament length was 0.4 (range, -2.3-1.3) mm and 0.6 (-0.6-1.7) mm using the preferred and standardized techniques, respectively, with no significant difference in the variance (P = 0.51) or the measured value (P = 0.52). The length changes in Patient 2 were 2.0 (0.3-4.4) mm and 1.7 (-0.9-3.8) mm using the preferred and standardized techniques, respectively. In Patient 3, the length changes were 1.4 (-2.7-7.1) mm and 0.7 (-2.0-2.3) mm. There were no significant differences between the techniques in either patient group. CONCLUSION: Variability in the quantitative measurement of ankle stress sonography was not reduced despite the standardization of the technique among examiners. Hence, comparing the measured values between different examiners should be avoided.

Guided parent-delivered cognitive behavioural therapy for Japanese children and parents: a single-arm uncontrolled study.

BACKGROUND: Guided parent-delivered cognitive behavioural therapy (GPD-CBT) is an effective low-intensity treatment for childhood anxiety disorder in Western countries and can increase access to evidence-based psychological therapies. AIM: This study aimed to examine its feasibility in a Japanese sample. METHOD: Twelve children with anxiety disorders and their parents participated in the study, and ten children and parents completed the program. Participants were assessed at pre-, post- and one-month follow-up using a diagnostic interview for anxiety disorders, self- and parent-report measures for anxiety, depression, parental behaviour, and parental anxiety. RESULTS: Four children (40% of completers) were free from their primary diagnoses immediately following the brief treatment, and seven children (70%) at the one-month follow-up. Changes in disorder severity, child and parent reported anxiety symptoms, and child reported depression symptoms were consistent with those found in Western trials of GPD-CBT and of Japanese trials of more intensive CBT for child anxiety disorders that involves both the child and the parent. Moderate increases were also found in child reported parental autonomy behaviours; however, there were only small changes in parent self-reported anxiety. CONCLUSION: These results support the potential of GPD-CBT to increase access to evidence-based treatments for anxiety disorders in Japanese children.

Epidemiological characteristics in serotype 24 paediatric invasive pneumococcal disease according to an 11-year population-based study in Japan.

After the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), serotype replacement has occurred in Japan, and serotype 24 has become the most common serotype in paediatric invasive pneumococcal disease (IPD). To understand the characteristics of serotype 24-IPD in Japanese children in the post-PCV13 era, we conducted a retrospective study in children aged ≤15 years from 2010 to 2020 using a database of paediatric IPD surveillance in Chiba prefecture, Japan. We identified a total of 357 IPD cases and collected clinical information on 225 cases (24: 32 cases, non-24: 193 cases). Compared with the non-serotype 24-IPD, serotype 24-IPD was independently related to be <2 years of age [odds ratio (OR) 3.91, 95% confidence interval (CI) 1.47-10.44; P = 0.0064] and bacteremia (OR 2.28, 95% CI 1.01-5.13; P = 0.0475), as a result of the multivariate regression analysis. We also conducted a bacterial analysis, and the isolates of serotype 24-IPD had tendencies of PCG-susceptible (24: 100.0%, non-24: 61.3%; P < 0.0001) and macrolide-resistance (24: 100.0%, non-24: 87.3%; P = 0.0490). Their multilocus sequence typing was mostly ST2572 and the variants, which were unique to Japan. This tendency might have been a result of the progress made in the Japanese PCV13 immunisation programme.

Carbon-ion radiotherapy versus radiofrequency ablation as initial treatment for early-stage hepatocellular carcinoma.

AIM: Carbon-ion radiotherapy (C-ion RT) has shown potential as a curative treatment for patients with hepatocellular carcinoma (HCC). However, no reports have compared the effectiveness of C-ion RT and radiofrequency ablation (RFA). This study aimed to compare clinical outcomes between C-ion RT and RFA for patients with early-stage HCC. METHODS: Medical records of consecutive patients with HCC (single lesion ≤5 cm or two to three lesions ≤3 cm) who received either C-ion RT or RFA as initial treatment were retrospectively reviewed. Propensity score matching (PSM) was used to adjust for clinical factors between both groups. RESULTS: A total of 560 patients were included, among whom 69 and 491 received C-ion RT and RFA, respectively. After PSM (C-ion RT, 54 patients; RFA, 95 patients), both groups were well balanced. Carbon-ion radiotherapy had significantly lower cumulative intrasubsegmental recurrence rate after PSM compared to RFA (p = 0.004) (2-year, 12.6% vs. 31.7%; 5-year, 15.5% vs. 49.6%, respectively). However, no significant difference in cumulative local recurrence rate, stage progression-free survival, or overall survival (OS) was observed between both groups. In the RFA group, 6 of 491 patients (1.2%) showed grade 3 adverse events, whereas no grade 3 or higher adverse events were observed in the C-ion RT group. CONCLUSION: Carbon-ion radiotherapy provided a lower cumulative intrasubsegmental recurrence rate, but a comparable cumulative local recurrence rate, stage progression-free survival, and OS compared to RFA. Thus, C-ion RT appears to be one of the effective treatment options for early-stage HCC when RFA is deemed not indicated.

Efficacy and Safety of Propranolol Gel for Infantile Hemangioma: A Randomized, Double-Blind Study.

We aimed to evaluate the efficacy and safety of propranolol gel at various concentrations with infantile hemangiomas after proliferative phases. We designed a single-center, randomized, double-blind, dose-dependent trial with placebo control and randomized patients to receive propranolol gel at 0, 1, or 5%, twice daily for 24 weeks. The primary efficacy endpoint was the percentage change in redness of the tumors. Safety endpoints were skin characteristics changes and systemic symptoms. We made two comparisons to evaluate the superiority of 1 and 5% propranolol gels against placebo for primary endpoint analysis and used the t-test to compare parents' satisfaction with these treatments. Initially, 19 patients were enrolled, but 8 were excluded from the analysis. We were underpowered to answer the question of efficacy. In the per-protocol set, we found similar results for the redness percentage change among the patients on placebo, 1 and 5% gel. However, the difference in redness before and after treatment suggested a slight decreasing trend of lesion's redness as the propranolol concentration increased. The difference in parents' satisfaction between the placebo and 5% propranolol gel groups was significant (p = 0.08). We observed no serious adverse events. We did not find an obvious dose-dependent effect for the propranolol gel treatment against infantile hemangiomas after the proliferative phase. However, external applications twice daily were less burdensome for parents and led to good compliances. It had a favorable safety profile in Japanese pediatric patients with infantile hemangiomas.