Local delivery of platelet-derived factors mitigates ischemia and preserves ovarian function through angiogenic modulation: A personalized regenerative strategy for fertility preservation.

As the most prominent and ideal modality in female fertility preservation, ovarian tissue cryopreservation, and transplantation often confront the challenge of ischemic damage and follicular loss from avascular transplantation. To surmount this impediment, we engineered a novel platelet-derived factors-encapsulated fibrin hydrogel (PFH), a paradigmatic biomaterial. PFH encapsulates autologous platelet-derived factors, utilizing the physiological blood coagulation cascade for precise local delivery of bioactive molecules. In our study, PFH markedly bolstered the success of avascular ovarian tissue transplantation. Notably, the quantity and quality of follicles were preserved with improved neovascularization, accompanied by decreased DNA damage, increased ovulation, and superior embryonic development rates under a Low-concentration Platelet-rich plasma-derived factors encapsulated fibrin hydrogel (L-PFH) regimen. At a stabilized point of tissue engraftment, gene expression analysis mirrored normal ovarian tissue profiles, underscoring the effectiveness of L-PFH in mitigating the initial ischemic insult. This autologous blood-derived biomaterial, inspired by nature, capitalizes on the blood coagulation cascade, and combines biodegradability, biocompatibility, safety, and cost-effectiveness. The adjustable properties of this biomaterial, even in injectable form, extend its potential applications into the broader realm of personalized regenerative medicine. PFH emerges as a promising strategy to counter ischemic damage in tissue transplantation, signifying a broader therapeutic prospect. (197 words).

Two-year clinical outcome of patients with mildly reduced ejection fraction after acute myocardial infarction: insights from the prospective KAMIR-NIH Registry.

Background: Left ventricular ejection fraction (LVEF) is a crucial prognostic indicator of acute myocardial infarction (AMI). However, there is a lack of studies on the clinical characteristics and prognosis of patients with mildly reduced ejection fraction (EF) after AMI. Methods: We categorized 6,553 patients with AMI from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) between November 2011 and December 2015 into three groups based on their EF, as assessed by echocardiography during index hospitalization: reduced EF (LVEF ≤40%), mildly reduced EF (LVEF 41%-49%), and preserved EF (LVEF ≥50%). The primary outcome was all-cause death within 2 years. The secondary outcomes included myocardial infarction (MI), revascularization, and patient-oriented composite endpoint (POCE), which was defined as a composite of all-cause death, any MI, or revascularization. Results: Of the total 6,553 patients, 884 (13.5%) were classified into the reduced EF group, 1,749 (26.7%) into the mildly reduced EF group, and 3,920 (59.8%) into the preserved EF group. Patients with mildly reduced EF exhibited intermediate mortality (reduced EF, 24.7%; mildly reduced EF, 8.3%; preserved EF, 4.6%; p < 0.0001), MI (3.9% vs. 2.7% vs. 2.6%; p < 0.0046), and POCE (33.0% vs. 15.6% vs. 12.4%; p < 0.0001) rates, albeit closer to those of the preserved EF. After adjustment for demographics, risk factors, admission status, and discharge medications, patients with mildly reduced EF showed a lower risk of all-cause death than those with reduced EF (mildly reduced EF group as a reference: HR, 1.74; 95% CI, 1.40-2.18; p < 0.001), but it did not differ significantly from those with preserved EF (HR, 0.94; 95% CI, 0.75-1.18; p = 0.999). Conclusions: Over a 2-year follow-up period, patients with AMI and mildly reduced EF demonstrated better prognoses than those with reduced EF, but did not differ significantly from those with preserved EF. Clinical Trial Registration: cris.nih.go.kr, identifier: KCT-0000863.

Predictors of success in left bundle branch area pacing with stylet-driven pacing leads: a multicenter investigation.

Purpose: Although left bundle branch area pacing (LBBAP) is an emerging conduction system pacing modality, it is unclear which parameters predict procedural success and how many implant attempts are acceptable. This study aimed to assess predictors of successful LBBAP, left bundle branch (LBB) capture, and factors associated with the number of LBBAP implant attempts. Methods: This retrospective observational multicenter study was conducted in Korea. LBBAP was attempted in 119 patients; 89.3% of patients had bradyarrhythmia (atrioventricular block 82.4%), and 10.7% of patients had heart failure (cardiac resynchronization therapy) indication. Procedural success and electrophysiological and echocardiographic parameters were evaluated. Results: The acute success rate of lead implantation in LBBAP was 95.8% (114 of 119 patients) and that of LBB capture was 82.4% (98 of 119 patients). Fewer implant attempts were associated with LBBAP success (three or fewer vs. over three times, p = 0.014) and LBB capture (three or fewer vs. over three times, p = 0.010). In the multivariate linear regression, the patients with intraventricular conduction delay (IVCD) required a greater number of attempts than those without IVCD [estimates = 2.33 (0.35-4.31), p = 0.02], and the larger the right atrial (RA) size, the more the attempts required for LBBAP lead implantation [estimates = 2.08 (1.20-2.97), p < 0.001]. Conclusion: An increase in the number of implant attempts was associated with LBBAP procedural failure and LBB capture failure. The electrocardiographic parameter IVCD and the echocardiographic parameter RA size may predict the procedural complexity and the number of lead implant attempts for LBBAP.

Clinical effect of prophylactic pegfilgrastim in patients with newly diagnosed acute lymphoblastic leukemia who receive intensive chemotherapy.

BACKGROUND: Using granulocyte colony-stimulating factor (G-CSF) after completing chemotherapy reduces the duration of neutropenia and infections. However, the efficacy and safety of prophylactic pegfilgrastim in acute lymphoblastic leukemia (ALL) patients have not yet been evaluated after intensive cytotoxic chemotherapy compared to the daily G-CSF. This study aimed to evaluate the efficacy of pegfilgrastim for ALL patients who received intensive chemotherapy compared with a short-acting G-CSF. PATIENTS AND METHODS: Clinical data of 145 patients treated with hyper-CVAD, modified VPDL/VPD, or KALLA 1406/1407 regimen were retrospectively evaluated. Pegfilgrastim or the short-acting G-CSF was selected according to the clinician's discretion. Patients not receiving pegfilgrastim were treated with the short-acting G-CSF. RESULTS: The median age of enrolled patients was 45 years. Sixty newly diagnosed ALL patients were treated with hyper-CVAD regimen, while KALLA and VPDL regimens were administered to 39 and 46 patients, respectively. Among the 60 patients treated with hyper-CVAD, 20 patients received pegfilgrastim. Patients who received pegfilgrastim had a significantly shorter duration of neutropenia and hospitalization and reduced incidence of severe infections compared to patients receiving the short-acting G-CSF. Consistent results were also confirmed in an analysis targeting only patients who achieved remission during hyper-CVAD induction therapy. There was no significant difference in neutrophil recovery ability and hospitalization duration when the daily short-acting G-CSF was used prophylactically after completing hyper-CVAD, KALLA, and VPDL regimens as induction therapy. CONCLUSION: Using pegfilgrastim after hyper-CVAD therapy was more effective than the short-acting G-CSF in terms of infection, neutropenia recovery, and hospitalization in patients with newly diagnosed ALL.

Structural Insights into Alterations in the Substrate Spectrum of Serine-ß-Lactamase OXA-10 from Pseudomonas aeruginosa by Single Amino Acid Substitutions.

The extensive use of ß-lactam antibiotics has led to significant resistance, primarily due to hydrolysis by ß-lactamases. OXA class D ß-lactamases can hydrolyze a wide range of ß-lactam antibiotics, rendering many treatments ineffective. We investigated the effects of single amino acid substitutions in OXA-10 on its substrate spectrum. Broad-spectrum variants with point mutations were searched and biochemically verified. Three key residues, G157D, A124T, and N73S, were confirmed in the variants, and their crystal structures were determined. Based on an enzyme kinetics study, the hydrolytic activity against broad-spectrum cephalosporins, particularly ceftazidime, was significantly enhanced by the G157D mutation in loop 2. The A124T or N73S mutation close to loop 2 also resulted in higher ceftazidime activity. All structures of variants with point mutations in loop 2 or nearby exhibited increased loop 2 flexibility, which facilitated the binding of ceftazidime. These results highlight the effect of a single amino acid substitution in OXA-10 on broad-spectrum drug resistance. Structure-activity relationship studies will help us understand the drug resistance spectrum of ß-lactamases, enhance the effectiveness of existing ß-lactam antibiotics, and develop new drugs.

Cediranib and Olaparib Combination Compared With Cediranib or Olaparib Alone, or Chemotherapy in Platinum-Resistant or Primary Platinum-Refractory Ovarian Cancer: NRG-GY005.

PURPOSE: We assessed the efficacy of cediranib, olaparib, and cediranib/olaparib compared with standard-of-care chemotherapy (SOC) in platinum-resistant or platinum-refractory epithelial ovarian cancer (PROC). PATIENTS AND METHODS: NRG-GY005 is an open-label, four-arm, phase II/III superiority trial enrolling patients with high-grade serous/endometrioid PROC and one to three previous therapies. Key exclusion criteria included previous receipt of poly(ADP-ribose) polymerase inhibitor or receipt of antiangiogenic therapy in the recurrent setting. Treatment arms (SOC [once weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin], cediranib, olaparib, or cediranib/olaparib) were equally randomized. A preplanned interim futility analysis on the basis of progression-free survival (PFS) selected treatment arms to advance to phase III. PFS and overall survival (OS) were phase III coprimary end points, with hierarchical testing of PFS followed by OS to preserve type 1 error control, designed to have 90% power for a 0.625 PFS hazard ratio (HR). OS was tested after PFS in the multiple hierarchical testing procedure. Secondary end points included objective response rate (ORR) and patient-reported outcomes. RESULTS: Five hundred sixty-two eligible patients were enrolled for phase II/III. Three arms met PFS criteria to carry forward to phase III (SOC, cediranib/olaparib, and cediranib). Median PFS was 3.4, 5.2, and 4 months with SOC, cediranib/olaparib, and cediranib, respectively, with a median follow-up duration of 42.2 months. PFS HR estimates for cediranib/olaparib and cediranib (v SOC) were 0.796 (98.3% CI, 0.597 to 1.060) and 0.972 (98.3% CI, 0.726 to 1.300), respectively. Median OS was 13.6, 12.8, and 10.5 months, and of 443 patients with measurable disease, ORR was 8.6%, 24.7%, and 13.1% for SOC, cediranib/olaparib, and cediranib, respectively. No new safety signals were identified. In patients receiving cediranib/olaparib, no statistically significant difference was observed on the NFOSI-DRS-P subscale compared with SOC (98.3% CI, -1.3 to 1.5, P = .8725). CONCLUSION: The cediranib-containing arms demonstrated clinical activity on the basis of PFS but were not superior compared with SOC.

One-shot manufacturable soft-robotic pump inspired by embryonic tubular heart.

Soft peristaltic pumps, which use soft ring actuators instead of mechanical pistons or rollers, offer advantages in transporting liquids with non-uniform solids, such as slurry, food, and sewage. Recent advances in 3D printing with flexible thermoplastic polyurethane (TPU) present the potential for single-step fabrication of these pumps, distinguished from handcrafted, multistep traditional silicone casting methods. However, because of the relatively high hardness of TPU, TPU-based soft peristaltic pumps contract insufficiently and thus cannot perform as well as silicone-based ones. Improving the performance is crucial for fully automated, one-step manufactured soft pumps to lead to industrial use. This study aims to enhance TPU-based soft pumps through bioinspired design. Specifically, it proposed a design inspired by embryonic tubular hearts, in contrast to previous studies that mimicked digestive tracts. The new design facilitated long-axis stretching of an elliptical lumen during non-concentric contractile motion, akin to embryonic tubular hearts. The design was optimized for ring actuators and pumps 3D-printed with shore hardness 85A TPU filament. The ring actuator achieved over 99% lumen closure with the best designs. The soft pumps transported water at flow rates of up to 218 ml/min and generated a maximum discharge pressure of 355 mmHg, comparable to the performance of blood pumps used in continuous renal replacement therapy. .

Establishing the Foundations of Emotional Intelligence in Care Companion Robots to Mitigate Agitation Among High-Risk Patients With Dementia: Protocol for an Empathetic Patient-Robot Interaction Study.

BACKGROUND: An estimated 6.7 million persons are living with dementia in the United States, a number expected to double by 2060. Persons experiencing moderate to severe dementia are 4 to 5 times more likely to fall than those without dementia, due to agitation and unsteady gait. Socially assistive robots fail to address the changing emotional states associated with agitation, and it is unclear how emotional states change, how they impact agitation and gait over time, and how social robots can best respond by showing empathy. OBJECTIVE: This study aims to design and validate a foundational model of emotional intelligence for empathetic patient-robot interaction that mitigates agitation among those at the highest risk: persons experiencing moderate to severe dementia. METHODS: A design science approach will be adopted to (1) collect and store granular, personal, and chronological data using Personicle (an open-source software platform developed to automatically collect data from phones and other devices), incorporating real-time visual, audio, and physiological sensing technologies in a simulation laboratory and at board and care facilities; (2) develop statistical models to understand and forecast the emotional state, agitation level, and gait pattern of persons experiencing moderate to severe dementia in real time using machine learning and artificial intelligence and Personicle; (3) design and test an empathy-focused conversation model, focused on storytelling; and (4) test and evaluate this model for a care companion robot (CCR) in the community. RESULTS: The study was funded in October 2023. For aim 1, architecture development for Personicle data collection began with a search for existing open-source data in January 2024. A community advisory board was formed and met in December 2023 to provide feedback on the use of CCRs and provide personal stories. Full institutional review board approval was received in March 2024 to place cameras and CCRs at the sites. In March 2024, atomic marker development was begun. For aim 2, after a review of open-source data on patients with dementia, the development of an emotional classifier was begun. Data labeling was started in April 2024 and completed in June 2024 with ongoing validation. Moreover, the team established a baseline multimodal model trained and validated on healthy-person data sets, using transformer architecture in a semisupervised manner, and later retrained on the labeled data set of patients experiencing moderate to severe dementia. In April 2024, empathy alignment of large language models was initiated using prompt engineering and reinforcement learning. CONCLUSIONS: This innovative caregiving approach is designed to recognize the signs of agitation and, upon recognition, intervene with empathetic verbal communication. This proposal has the potential to have a significant impact on an emerging field of computational dementia science by reducing unnecessary agitation and falls of persons experiencing moderate to severe dementia, while reducing caregiver burden. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55761.

Suppressing Hole Accumulation Through Sub-Nanometer Dipole Interfaces in Hybrid Perovskite/Organic Solar Cells for Boosting Near-Infrared Photon Harvesting.

The potential of hybrid perovskite/organic solar cells (HSCs) is increasingly recognized owing to their advantageous characteristics, including straightforward fabrication, broad-spectrum photon absorption, and minimal open-circuit voltage (VOC) loss. Nonetheless, a key bottleneck for efficiency improvement is the energy level mismatch at the perovskite/bulk-heterojunction (BHJ) interface, leading to charge accumulation. In this study, it is demonstrated that introducing a uniform sub-nanometer dipole layer formed of B3PyMPM onto the perovskite surface effectively reduces the 0.24 eV energy band offset between the perovskite and the donor of BHJ. This strategic modification suppresses the charge recombination loss, resulting in a noticeable 30 mV increase in the VOC and a balanced carrier transport, accompanied by a 5.0% increase in the fill factor. Consequently, HSCs that achieve power conversion efficiency of 24.0% is developed, a new record for Pb-based HSCs with a remarkable increase in the short-circuit current of 4.9 mA cm-2, attributed to enhanced near-infrared photon harvesting.

Relapse risk factors and clinical characteristics of idiopathic inflammatory myopathies in 105 patients.

OBJECTIVE: To identify the risk factors for relapse of idiopathic inflammatory myopathies (IIMs). METHODS: Patients who were newly diagnosed with IIMs and underwent muscle biopsy between 2000 and 2017 at Asan Medical Center were retrospectively reviewed. The relapse of IIMs was defined as the recurrence of muscle or cutaneous manifestations with a ≥50% increase in glucocorticoid dosage after reaching the low-dose glucocorticoid phase with clinically significant improvement. The factors associated with the relapse of IIMs were investigated by Cox proportional hazards analysis. RESULTS: Of 105 patients with IIMs, relapse was observed in 65 patients (62%). The titer of antinuclear antibody (ANA) was higher in the relapse group than in the non-relapse group (P = 0.033). Multivariable analysis showed that the relapse of IIMs was significantly associated with histopathologic features consistent with IIMs (hazard ratio [HR], 1.69; 95% confidence interval [CI], 1.01-2.83, P = 0.045) and the use of immunosuppressants before relapse (HR, 0.50; 95% CI, 0.29-0.86, P = 0.013). Doubling of ANA titer was also associated with relapse, albeit without statistical significance (HR, 1.13; 95% CI, 1.00-1.27, P = 0.052). CONCLUSION: In patients with IIMs, the use of immunosuppressants had a significant negative association with relapse. Administering immunosuppressants from the early period during the initial glucocorticoid tapering phase may be useful in reducing the risk of relapse in patients with IIMs. Key Points • Since idiopathic inflammatory myopathies (IIMs) have a low prevalence, it is poorly understood which factors are associated with the relapse of IIMs. • In this study, about two-thirds of 105 patients with IIMs experienced a relapse of IIMs. • The risk of relapse in patients with IIMs was negatively associated with the use of immunosuppressants during glucocorticoid tapering and low-dose glucocorticoid phase. • Even in less severe cases, the use of immunosuppressants might be a good option for the management of IIMs.

Age at menarche by birth cohort: A pooled analysis of half a million women in Asia.

OBJECTIVES: To evaluate changes in the age at menarche in Asian populations. STUDY DESIGN: Retrospective cohort study. METHODS: We included 548,830 women from six countries in Asia. The data were sourced from 20 cohorts participating in the Asia Cohort Consortium (ACC) and two additional cohort studies: Japan Multi-institutional Collaborative Cohorts (J-MICC), and Japan Nurse Health Study (JNHS) with data on age at menarche. Joinpoint regression was used to evaluate changes in age at menarche by birth year and by country. RESULTS: The study includes data from cohorts in six Asian countries namely, China, Iran, Japan, Korea, Malaysia and Singapore. Birth cohorts ranged from 1873 to 1995. The mean age of menarche was 14.0 years with a standard deviation (SD) of 1.4 years, ranged from 12.6 to 15.5 years. Over 100 years age at menarche showed an overall decrease in all six countries. China showed a mixed pattern of decrease, increase, and subsequent decrease from 1926 to 1960. Iran and Malaysia experienced a sharp decline between about 1985 and 1990, with APC values of -4.48 and -1.24, respectively, while Japan, South Korea, and Singapore exhibited a nearly linear decline since the 1980s, notably with an APC of -3.41 in Singapore from 1993 to 1995. CONCLUSIONS: Overall, we observed a declining age at menarche, while the pace of the change differed by country. Additional long-term observation is needed to examine the contributing factors of differences in trend across Asian countries. The study could serve as a tool to strengthen global health campaigns.

Epidemiological and Clinical Characteristics of Women Living with HIV in Korea.

BACKGROUND: While Korea maintains a low prevalence of human immunodeficiency virus (HIV), the number of newly diagnosed cases has been steadily rising, reaching approximately 1,000 annually in recent years. The 2022 annual report from the Korea Disease Control and Prevention Agency revealed that women living with HIV (WLWH) constitute 6.4% of the total confirmed people living with the HIV population, totaling 1,219 individuals. Despite this, only a few studies have focused on WLWH in Korea. This study aims to analyze the epidemiological and clinical characteristics of WLWH in Korea. MATERIALS AND METHODS: We retrospectively collected data by reviewing the medical records of all WLWH who visited 10 urban referral hospitals across Korea between January 2005 and May 2023. RESULTS: A total of 443 WLWH were enrolled in this study. The predominant risk exposure was heterosexual contact, with 235 (53%) participants either married or cohabiting with a male partner at their initial clinic visit. Among the participants, 334 (77.7%) were Korean, 27 (6.1%) were Southeast Asian, and 19 (4.3%) were African. Antiretroviral therapy was initiated by 404 WLWH (91.2%). We observed 118 pregnancies in WLWH following their HIV diagnosis, resulting in 78 live births (66.1%), 18 induced abortions (15.2%), 10 pre-viable fetal losses (8.5%), and four stillbirths (3.4%). Over a cumulative follow-up duration of 3,202.1 years, the incidence rates of breast and cervical cancers were both 2.18 per 1,000 person-years. Additionally, the incidence rates of pelvic inflammatory disease, cervical intraepithelial neoplasm (above grade II), and osteoporosis were 4.67, 11.21, and 13.39 per 1,000 patient-years, respectively. CONCLUSION: This is the first multicenter study to investigate the clinical and epidemiological characteristics of WLWH in Korea. The incidence and prevalence of diseases in women, including breast cancer, cervical cancer, and chronic comorbidities, are high in WLWH in Korea; therefore, further research and efforts are needed to manage these diseases.

Mll4 regulates postnatal palate growth and midpalatal suture development.

MLL4, also known as KMT2D, is a histone methyltransferase that acts as an important epigenetic regulator during various organogenesis programs. Mutations in the MLL4 gene are the major cause for Kabuki syndrome, a human developmental disorder that involves craniofacial birth defects, including anomalies in the palate. The purpose of this study was to investigate the role of Mll4 and the underlying mechanisms in the development and growth of the palate. We generated a novel conditional knockout (cKO) mouse model with tissue-specific deletion of Mll4 in the palatal mesenchyme. By using micro-computed tomography (CT), histology, cell mechanism assays, and gene expression analysis approaches, we examined the development and growth of the palate in the Mll4 -cKO mice. Gross intra-oral examination at adult stages showed that Mll4 -cKO mice had defects along the midline of the palate, which included disrupted rugae pattern and widened midpalatal suture. Micro-CT-based skeletal analysis in the adult mice revealed that the overall palate width was decreased in the Mll4 -cKO mice. By using whole-mount and histological staining approaches at perinatal stages, we identified that the midline defects started to appear as early as 1 day prior to birth, manifesting initially as a widened midpalatal suture, accompanied by increased cell apoptosis in the suture mesenchyme cells. Genome-wide analysis of mRNA expression in the midpalatal suture tissue showed that Mll4 is essential for timely expression of major genes for cartilage development, such as Col2a1 and Acan , at birth. These results were validated through immunofluorescence staining, confirming that the expression of chondrogenic markers Sox9 and Col2a1 were markedly decreased, whereas that of the osteogenic marker Runx2 remained unchanged, in the midpalatal suture of the Mll4 -cKO mice. Indeed, time-course histological analysis during postnatal palate growth revealed retardation in the development of the suture cartilage in the Mll4 -cKO mice. In parallel, time-course micro-CT analysis during postnatal palatogenesis confirmed a transverse growth deficit in the palate of the Mll4 -cKO mice. Taken together, our results show that Mll4 is essential for timely occurrence of key cellular and molecular events that lead to proper midpalatal suture development and palate growth.

Peer-to-Peer Human Milk Sharing Through Social Media Groups: The Experiences of Women Donors and Recipients in Hong Kong.

AIM: To explore the lived experience of donors and recipients involved in peer-to-peer human milk donation. DESIGN: An exploratory descriptive qualitative study. METHOD: Semi-structured interviews were conducted between November 2022 and April 2023. A total of 50 women consisting of 34 donors and 16 recipients were recruited using purposive sampling from specific social media groups in Hong Kong that focus on breast milk donation and sharing. Data were analysed based on thematic analysis. RESULTS: Five key themes were identified in this study: Motivation; Milk sharing as a social act; Not a Norm; Recommendation to formal milk banks; and Formal donation as the preferred route. CONCLUSION: The findings indicate informal milk sharing is seen as an inferior alternative to formal milk donation systems. The establishment of formal milk banks is viewed as a way to address the shortcomings of informal sharing. IMPLICATIONS FOR THE PROFESSION: The findings have implications for the healthcare field, particularly in improving the experiences of those involved in informal milk sharing. The insights gained from the experiences of informal milk sharers can directly inform and enhance the services provided by formal milk banks. IMPACT: Given the growing prevalence of online informal milk sharing, healthcare professionals should enhance their understanding of this practice. However, the practice has remained understudied, particularly in Asian region. This study brings together the experiences of both milk donors and recipients, providing a comprehensive view on the phenomenon. REPORTING METHOD: The Standards for Reporting Qualitative Research (SRQR). PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Correlation between the etiology of severe hearing loss and endolymphatic hydrops.

PURPOSE: This study aimed to investigate correlation between the presence of endolymphatic hydrops(EH) and factors such as causes of hearing loss, patient age, duration of deafness, and results of vestibular function tests. METHODS: We retrospectively reviewed medical charts of 128 ears of cochlear implantees who were not considered relevant to Meniere's disease. RESULTS: When comparing group with genetic variants of GJB2, SLC26A4, LMX1A and other genetic mutation group, the proportion of vestibular EH and cochlear EH found in group with genetic variants of GJB2, SLC26A4, LMX1A was significantly higher than group with other genetic etiology (p < 0.01) or the group with all the other causes of hearing loss (p < 0.01). The rate of vestibular and cochlear EH detection was higher in younger patients (41.5% and 35.4%) than in older patients (25.4% and 20.6%). A higher ratio of vestibular and cochlear EH was observed in patients with a longer duration of deafness (37.5% and 31.3%) than those with a shorter duration of deafness (29.7% and 25.0%). The group with vestibular EH showed a higher incidence of abnormal findings in the caloric test (42.9%) than the group without vestibular EH (28.2%). CONCLUSION: Patients with genetic variants of GJB2, SLC26A4, LMX1A, younger patients, those with longer deaf durations showed a higher prevalence of vestibular and cochlear EH, implying EH appears to be formed as a developmental disorder in association with a certain set of genetic variants, rather than a phenotypic marker as a result of severe to profound hearing loss.

Validation of the Scoliosis Japanese Questionnaire-27 in Korean patients with adolescent idiopathic scoliosis.

We sought to evaluate the reliability and validity of the Korean adaptation of the Scoliosis Japanese Questionnaire-27 (SJ-27). This involved translating the English SJ-27 into Korean and back-translating it, followed by completing all stages of the cross-cultural adaptation process. Subsequently, the Korean SJ-27, along with the validated Scoliosis Research Society-22 (SRS-22) questionnaire, was administered to 140 consecutive idiopathic scoliosis patients wearing a brace. Reliability was determined using kappa statistics to assess agreement for each item, the intraclass correlation coefficient (ICC), and Cronbach's α. Construct validity was established by comparing responses on the SJ-27 with those on the SRS-22 using Pearson's correlation coefficient. All items showed kappa statistics indicating agreement above 0.6. The SJ-27 demonstrated excellent test-retest reliability (ICC=0.91). Internal consistency measured by Cronbach's α was very good (α = 0.898). The Korean version of the SJ-27 exhibited significant correlations with both the total score and individual domain scores of the SRS-22. The adapted Korean SJ-27 was effectively translated and showed acceptable measurement properties, making it suitable for assessing outcomes in Korean-speaking patients with idiopathic scoliosis.

Mortality in elderly Parkinson's disease patients with long-term care needs: A nationwide population-based study in Korea.

BACKGROUND: The effects of long-term care insurance (LTCI) in reducing medical costs and utilization among older adults have been reported. This study aims to investigate the mortality in patients with Parkinson's disease (PD) requiring LTCI and its relationships with economic status. METHODS: This study was conducted using the database of the Korean National Health Insurance Service (NHIS)-Senior Cohort between 2008 and 2019. A total of 5937 patients with PD were included. Hazard ratios (HRs) of mortality associated with LTCI were estimated using a Cox regression model. Potential confounders such as demographics and comorbidities were adjusted. RESULTS: Out of 5937 PD patients, 821 required LTCI, and 5116 did not. Compared to PD patients without LTCI, PD patients with LTCI were older and exhibited a higher comorbidity burden. The overall incidence rate of mortality was 18.63 per 100 person-years in PD patients with LTCI. PD patients requiring LTCI were associated with an increased HR of 3.61 (95 % CI = 3.13-4.16) for mortality compared to PD patients not eligible for LTCI. Low-income status with LTCI was associated with the highest mortality risk (HR = 4.54, 95 % CI = 3.38-6.09), compared to middle-income status (HR = 3.47, 95 % CI = 2.64-4.61) and high-income status (HR = 3.53, 95 % CI = 2.91-4.91). CONCLUSIONS: Our study suggests that older PD patients requiring LTCI with low economic status have a higher risk of death. Continuous policy efforts to reduce the mortality risk in this group are needed.

Prediction of prognosis in supramalleolar osteotomy with or without additional fibula osteotomy by approaching a biomechanical study: a finite element analysis.

Supramalleolar osteotomy (SMO) is a representative procedure to restore a malalignment in the varus ankle deformity by shifting the concentrated pressure on the medial ankle joint to the lateral area. Additionally, fibula osteotomy (FO) is selectively selected and performed according to the surgeon's preference. However, it is controversial whether FO is effective in shifting the abnormal pressure from the medial to the lateral area on the ankle joint. Some cadaveric studies have been performed to prove this. However, it is difficult to consistently reconstruct amount of the varus ankle deformities angle in cadavers and to guarantee reliable contact pressure between the ankle joint. Thus, the aim of this study was predicted and quantitatively compared a peak pressure between single SMO and SMO with FO procedure by using a finite element analysis as a powerful biomechanical tool to those limitations of cadaveric study. This study reconstructed total 4 3D foot and ankle models including a normal and pre-op model and 2 post-op models. The pre-op model was modified by assigning 10° varus tilting corresponding to stage 3b in the classification of varus ankle osteoarthritis based on the validated normal model. Also, the post-op models were reconstructed by applying single SMO and SMO with FO, respectively. All of the models were assumed as one-leg standing position and to mimic smooth ankle joint motion. Peak contact pressure change was predicted at the medial ankle joint by using computational simulation. As a result, 2 post-op models showed a remarkably peak pressure reduction by up to 5.5 times on the medial tibiotalar joint. However, a comparison between single SMO and SMO with FO model showed no appreciable differences. In conclusion, this study predicted that single SMO may be as effective as SMO with FO in reducing peak contact pressure on the medial tibiotalar joint in varus ankle osteoarthritis.

Pembrolizumab or placebo with chemoradiotherapy followed by pembrolizumab or placebo for newly diagnosed, high-risk, locally advanced cervical cancer (ENGOT-cx11/GOG-3047/KEYNOTE-A18): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: At the first interim analysis of the phase 3 ENGOT-cx11/GOG-3047/KEYNOTE-A18 study, the addition of pembrolizumab to chemoradiotherapy provided a statistically significant and clinically meaningful improvement in progression-free survival in patients with locally advanced cervical cancer. We report the overall survival results from the second interim analysis of this study. METHODS: Eligible patients with newly diagnosed, high-risk (FIGO 2014 stage IB2-IIB with node-positive disease or stage III-IVA regardless of nodal status), locally advanced, histologically confirmed, squamous cell carcinoma, adenocarcinoma, or adenosquamous cervical cancer were randomly assigned 1:1 to receive five cycles of pembrolizumab (200 mg) or placebo every 3 weeks with concurrent chemoradiotherapy, followed by 15 cycles of pembrolizumab (400 mg) or placebo every 6 weeks. Pembrolizumab or placebo and cisplatin were administered intravenously. Patients were stratified at randomisation by planned external beam radiotherapy type (intensity-modulated radiotherapy [IMRT] or volumetric-modulated arc therapy [VMAT] vs non-IMRT or non-VMAT), cervical cancer stage at screening (FIGO 2014 stage IB2-IIB node positive vs III-IVA), and planned total radiotherapy (external beam radiotherapy plus brachytherapy) dose (<70 Gy vs ≥70 Gy [equivalent dose of 2 Gy]). Primary endpoints were progression-free survival per RECIST 1.1 by investigator or by histopathological confirmation of suspected disease progression and overall survival defined as the time from randomisation to death due to any cause. Safety was a secondary endpoint. FINDINGS: Between June 9, 2020, and Dec 15, 2022, 1060 patients at 176 sites in 30 countries across Asia, Australia, Europe, North America, and South America were randomly assigned to treatment, with 529 patients in the pembrolizumab-chemoradiotherapy group and 531 patients in the placebo-chemoradiotherapy group. At the protocol-specified second interim analysis (data cutoff Jan 8, 2024), median follow-up was 29·9 months (IQR 23·3-34·3). Median overall survival was not reached in either group; 36-month overall survival was 82·6% (95% CI 78·4-86·1) in the pembrolizumab-chemoradiotherapy group and 74·8% (70·1-78·8) in the placebo-chemoradiotherapy group. The hazard ratio for death was 0·67 (95% CI 0·50-0·90; p=0·0040), meeting the protocol-specified primary objective. 413 (78%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 371 (70%) of 530 in the placebo-chemoradiotherapy group had a grade 3 or higher adverse event, with anaemia, white blood cell count decreased, and neutrophil count decreased being the most common adverse events. Potentially immune-mediated adverse events occurred in 206 (39%) of 528 patients in the pembrolizumab-chemoradiotherapy group and 90 (17%) of 530 patients in the placebo-chemoradiotherapy group. This study is registered with ClinicalTrials.gov, NCT04221945. INTERPRETATION: Pembrolizumab plus chemoradiotherapy significantly improved overall survival in patients with locally advanced cervical cancer These data, together with results from the first interim analysis, support this immuno-chemoradiotherapy strategy as a new standard of care for this population. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co.

Changes in the tumor immune microenvironment during disease progression in clear cell ovarian cancer.

OBJECTIVE: The tumor immune microenvironment in ovarian clear cell carcinoma has not been clearly defined. We analyzed the immunological changes from treatment-naive to recurrence to correlate them with clinical outcomes. METHOD: We compared the changes in immune infiltration of advanced-stage ovarian clear cell carcinoma samples before treatment and at the time of recurrence via immunohistochemistry (Programmed Cell Death-ligand 1 (PD-L1), cluster of differentiation 8 (CD8+), forkhead box P3 (Foxp3+)), tumor-infiltrating lymphocytes (TIL), and next-generation sequencing (54 patients). We analyzed the association between platinum sensitivity status and tumor immune microenvironment. RESULTS: Immunohistochemistry revealed significantly increased PD-L1 (p=0.048) and CD8+T cells (p=0.022) expression levels after recurrence. No significant differences were observed in TIL density or Foxp3+T cells. There was no significant correlation between TIL, PD-L1, CD8+T cell, and Foxp3+T cell levels in treatment-naive tumors and survival outcomes. The most common genomic alterations were PIK3CA (41.7%) and ARID1A (41.7%) mutations. There were no differences in the immunological changes or survival outcomes according to PIK3CA and ARID1A mutations. Patients with recurrent platinum-sensitive disease showed higher TIL expression levels. There were no significant differences in PD-L1, CD8+T cells, or Foxp3+T cells between platinum-sensitive and platinum-resistant diseases. CONCLUSION: We characterized the tumor immune microenvironment in patients with advanced-stage ovarian clear cell carcinoma. PD-L1 and CD8+T cell expression significantly increased after recurrence. Whether this could be used to select patients for immunotherapy in the recurrence setting should be investigated.