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Successful repigmentation of hypopigmented scars with micropunch grafting with a skin-seeding technique
Hypopigmented scars are challenging to treat, and the focus for successful treatment is to cause pigment cells to produce more melanin. In this study, we evaluated the repigmentation effects of 0.4 mm motorized-micropunch grafting with skin-seeding for hypopigmented scars. Twenty-one patients with hypopigmented scars on the face and neck that had been resistant to conventional treatment and who had finally undergone micropunch grafting with a skin-seeding technique (SST) were retrospectively reviewed. Repigmentation outcomes were evaluated with global assessment by a physician using a 4-point repigmentation scale. Adverse events were noted. The subjects were followed for a 2-year follow-up period post grafting. All 21 subjects exhibited excellent to complete repigmentation of more than 75% of the hypopigmented scars. More than 90% repigmentation was observed in 17 patients. The mean duration for repigmentation that the subjects were satisfied with was 5.5 months. No adverse effects or recurrence instances were observed. Motorized micropunch grafting is an effective and promising alternative treatment for repigmentation of hypopigmented scars
Efficacy and safety of fexuprazan in patients with symptoms and signs of laryngopharyngeal reflux disease: a randomized clinical trial
Purpose: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. Methods: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. Results: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p =.036 and.045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. Conclusion: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. Trial registration: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100
Endovascular Stroke Thrombectomy for Patients with Large Ischemic Core: A Review
Importance: Recently, 6 randomized clinical trials - RESCUE-Japan-LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra-Acute Embolism - Japan Large Ischemic Core Trial), ANGEL-ASPECT (Trial of Endovascular Therapy for Acute Ischemic Stroke With Large Infarct), SELECT2 (Trial of Endovascular Thrombectomy for Large Ischemic Strokes), TESLA (Thrombectomy for Emergent Salvage of Large Anterior Circulation Ischemic Stroke), TENSION (Endovascular Thrombectomy for Acute Ischemic Stroke With Established Large Infarct), and LASTE (Large Stroke Therapy Evaluation) - have concluded their investigations on the efficacy and safety of endovascular thrombectomy (EVT) for the treatment of patients with ischemic stroke, anterior-circulation large vessel occlusions, and large areas of ischemic changes defined as an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 5 or less. Overall, the results appeared to be positive, with 5 of the 6 trials meeting their primary efficacy end point, and 1 trial that was a near miss. However, questions remain regarding how these trial results should be interpreted and incorporated into routine clinical practice. Observations: In this narrative review and analysis of published trials, important nuances of the available clinical data were identified, and important areas of lingering uncertainty were highlighted, including the efficacy and safety of EVT for patients with a low ASPECTS score in late treatment windows and those with large core volumes. Also emphasized was the possibly important role of advanced neuroimaging modalities such as perfusion and magnetic resonance imaging when making EVT treatment decisions for select patients with low ASPECTS scores. Conclusions and Relevance: Recent trial data provide strong evidence that EVT is safe and effective for patients with anterior, large vessel-occlusion stroke and low ASPECTS scores who present within 6 hours from stroke onset. However, patient outcomes often remain poor despite EVT treatment. The efficacy and safety of EVT for patients with low ASPECTS scores who present beyond 6 hours of stroke onset remain uncertain, and the current trial data seem too scarce to justify forgoing advanced stroke imaging during this extended time window. Furthermore, the efficacy and safety of EVT for patients with large core volumes (100 mL or greater) or M2 occlusions (ie, occlusions of the second segment of the middle cerebral artery) remain uncertain. Future research to better identify patients likely to meaningfully respond to EVT is needed to further optimize the stroke triage process and health care resource utilization
Incidence and Risk of Depressive Disorder in Patients with Retinitis Pigmentosa
Importance: There is a lack of large-scale clinical studies exploring mental health among patients with retinitis pigmentosa (RP). Additionally, few studies have evaluated the associations of visual impairment with mental health in young patients. Objective: To investigate the association between depressive disorder and RP. Design, Setting, and Participants: This was a retrospective, nationwide, population-based cohort study using data obtained from the Health Insurance Review and Assessment service in Korea between 2008 and 2022. A total of 10879 individuals who were newly diagnosed with RP between January 2011 and December 2021, as verified by both the RP registration code (National Registry of Rare and Intractable Disease in Korea code V209) and diagnostic code (International Statistical Classification of Diseases, 10th Revision code H35.51), were included. Data analysis was performed from October 2023 to January 2024. Exposure: Diagnosis of RP. Main Outcomes and Measures: Participants were categorized into 3 groups based on age at diagnosis (<20, 20-39, and ≥40 years). The incidence of depressive disorder in RP was determined after excluding those diagnosed with depressive disorder prior to RP diagnosis. Age- and sex-adjusted standardized incidence ratios (SIRs) of depressive disorder in patients with RP compared with the general population were calculated. Subgroup analyses by sex and age group were conducted. Results: A total of 10879 patients (638 aged <20 years, 2233 aged 20-39 years, and 8008 aged ≥40 years; 5710 [52.5%] female) newly diagnosed with RP between 2011 and 2021 were included. The 10-year cumulative incidence of depressive disorder was 17.67% (95% CI, 16.57%-18.84%) in patients with RP. Subgroup analysis showed higher incidence of depressive disorder in female patients (hazard ratio [HR], 1.46; 95% CI, 1.29-1.65; P <.001) and those aged 40 years or older (HR, 1.93; 95% CI, 1.63-2.29; P <.001). The overall SIR of depressive disorder in patients with RP was 1.19 (95% CI, 1.12-1.27; P <.001), indicating a higher risk of depressive disorder compared with that in the general population. Both male and female patients with RP showed increased incidence rates of depressive disorder (17.53 [95% CI, 15.91-19.27] and 25.57 [95% CI, 23.58-27.67] per 1000 person-years, respectively) and increased SIRs of depressive disorder (1.21 [95% CI, 1.10-1.33] and 1.18 [95% CI, 1.09-1.28], respectively) (all P <.001) compared with the general population. Subgroup analysis by age group showed that the SIR peaked in patients in their 20s (1.50; 95% CI, 1.17-1.90; P =.006) and aged 60 years or older (1.25; 95% CI, 1.14-1.37; P <.001). Conclusions and Relevance: Individuals diagnosed with RP had a higher risk of developing depressive disorder. These findings support consideration of providing emotional and social support to patients with RP
Optimal timing of chemoradiation after resection or biopsy of glioblastomas: a nationwide population-based study
Background: This study investigated the optimal timing of concurrent chemoradiotherapy (CCRT) following surgery for patients with newly diagnosed glioblastoma (GBM). The focus was on understanding whether the interval between surgery and CCRT impacts survival outcomes. Methods: Data from the Korean National Health Insurance Research Database (https://opendata.hira.or.kr/) were collected to retrospectively review 3,586 patients diagnosed with GBM in South Korea between 2008 and 2021. Patients were divided into early CCRT (≤ 21 days between surgery and CCRT) and late CCRT (> 21 days between surgery and CCRT) groups and further categorised based on the type of surgery (biopsy alone or surgical resection). The study estimated overall survival (OS) and conducted univariable and multivariable Cox regression analyses. Results: The median overall survival (OS) for the entire cohort was 19.98 months (95% Confidence Interval [CI]: 19.12–20.86 months). In univariable analysis, the late CCRT group demonstrated a longer median OS compared to the early CCRT group (20.47 vs. 17.94 months, P = 0.0002, log-rank test). However, this difference was not significant in multivariable analysis (Hazard Ratio [HR] = 0.98, 95% CI: 0.782–1.091, P = 0.6663). Subgroup analysis revealed that late CCRT was associated with prolonged OS in patients who underwent surgical resection (adjusted HR = 0.85, 95% CI: 0.752–0.955, P = 0.0065), whereas in the biopsy-alone group, late CCRT was associated with shorter OS (adjusted HR = 1.80, 95% CI: 1.378–2.346, P < 0.0001). Conclusions: Patients who initiated CCRT more than 21 days post-resection demonstrated improved overall survival (OS) compared to those who began CCRT earlier. In contrast, among patients who underwent biopsy alone, initiating CCRT within 21 days was associated with better outcomes. These findings suggest that the optimal timing for CCRT initiation in GBM may depend on the extent of residual tumour
Treatment patterns and healthcare resource utilization among patients with alopecia areata: A real-world chart review in South Korea
Alopecia areata (AA) is a clinically heterogeneous, immune-mediated, non-scarring hair loss disorder. This real-world chart review sought to characterize treatment patterns and healthcare resource use among patients with severe AA in South Korea. A web-based chart review of 40 dermatologists was conducted in which the medical charts of 151 adult patients diagnosed with severe AA between May 2019 and April 2021 were reviewed. Anonymized data on patient characteristics, treatment patterns, healthcare resource use, and clinical outcomes were extracted from the date of severe disease diagnosis until the date of data collection (September–November 2022). Sixty-six percent of patients were diagnosed with severe disease at initial presentation, while 34% were re-classed to severe during the disease course. Mean estimated patient age at the time of diagnosis of severe AA was 37.1 (range 22–68) years. Fifty-three percent of patients were male. Most patients (93.4%) received pharmacological treatment for their condition; 45.5% received ≥2 lines of treatment with a mean duration of 24 months. First-line treatment discontinuation due to lack of efficacy occurred in 46.0% of cases. Hair regrowth occurred in 71.0% of patients, 59.2% of whom experienced major regrowth (≥60%) during the follow-up period. Median (95% confidence interval) time to regrowth was 13.7 (11.0–20.6) months. Treatment visit rates per person-year ranged from two (phototherapy) to 10 (topical treatment), dermatologist visits occurred at a rate of 12.9 per person-year and 6.0% of patients were hospitalized due to alopecia areata. The majority of hospitalizations were related to treatment and occurred in patients who received pulse systemic corticosteroid therapy. The patient and economic burden of AA in South Korea is high and there remains a critical unmet need among patients with severe AA with respect to the effectiveness of commonly used treatment strategies
Association of HLA-B∗13:01 with DRESS and HLA-A∗31:01 with eosinophilia in SJS/TEN induced by carbamazepine
Global, regional, and national stillbirths at 20 weeks' gestation or longer in 204 countries and territories, 1990–2021: findings from the Global Burden of Disease Study 2021
Background: Stillbirth is a devastating and often avoidable adverse pregnancy outcome. Monitoring stillbirth levels and trends—in a comprehensive manner that leaves no one uncounted—is imperative for continuing progress in pregnancy loss reduction. This analysis, completed as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, methodically accounted for different stillbirth definitions with the aim of comprehensively estimating all stillbirths at 20 weeks or longer for 204 countries and territories from 1990 to 2021. Methods: We extracted data on stillbirths from 11 412 sources across 185 of 204 countries and territories, including 234 surveys, 231 published studies, 1633 vital statistics reports, and 10 585 unique location-year combinations from vital registration systems. Our final dataset comprised 11 different definitions, which were adjusted to match two gestational age thresholds: 20 weeks or longer (reference) and 28 weeks or longer (for comparisons). We modelled the ratio of stillbirth rate to neonatal mortality rate with spatiotemporal Gaussian process regression for each location and year, and then used final GBD 2021 assessments of fertility and all-cause neonatal mortality to calculate total stillbirths. Secondary analyses evaluated the number of stillbirths missed with the more restrictive gestational age definition, trends in stillbirths as a function of Socio-demographic Index, and progress in reducing stillbirths relative to neonatal deaths. Findings: In 2021, the global stillbirth rate was 23·0 (95% uncertainty interval [UI] 19·7–27·2) per 1000 births (stillbirths plus livebirths) at 20 weeks' gestation or longer, compared to 16·1 (13·9–19·0) per 1000 births at 28 weeks' gestation or longer. The global neonatal mortality rate in 2021 was 17·1 (14·8–19·9) per 1000 livebirths, corresponding to 2·19 million (1·90–2·55) neonatal deaths. The estimated number of stillbirths occurring at 20 weeks' gestation or longer decreased from 5·08 million (95% UI 4·07–6·35) in 1990 to 3·04 million (2·61–3·62) in 2021, corresponding to a 39·8% (31·8–48·0) reduction, which lagged behind a global improvement in neonatal deaths of 45·6% (36·3–53·1) for the same period (down from 4·03 million [3·86–4·22] neonatal deaths in 1990). Stillbirths in south Asia and sub-Saharan Africa comprised 77·4% (2·35 million of 3·04 million) of the global total, an increase from 60·3% (3·07 million of 5·08 million) in 1990. In 2021, 0·926 million (0·792–1·10) stillbirths, corresponding to 30·5% of the global total (3·04 million), occurred between 20 weeks' gestation and 28 weeks' gestation, with substantial variation at the country level. Interpretation: Despite the gradual global decline in stillbirths between 1990 and 2021, the overall number of stillbirths remains substantially high. Counting all stillbirths is paramount to progress, as nearly a third—close to 1 million in total—are left uncounted at the 28 weeks or longer threshold. Our findings draw attention to the differential progress in reducing stillbirths, with a high burden concentrated in countries with low development status. Scarce data availability and poor data quality constrain our capacity to precisely account for stillbirths in many locations. Addressing inequities in universal maternal health coverage, strengthening the quality of maternal health care, and improving the robustness of data systems are urgently needed to reduce the global burden of stillbirths. Funding: Bill & Melinda Gates Foundation
Role of Platelet-Activating Factor in the Pathogenesis of Chronic Spontaneous Urticaria
Chronic spontaneous urticaria (CSU) is a debilitating condition characterized by mast cell activation. Platelet-activating factor (PAF) is produced by various immune cells, including mast cells, basophils, lymphocytes, and eosinophils, which play crucial roles in CSU pathogenesis. It induces mast cell degranulation, increases vascular permeability, and promotes the chemotaxis of inflammatory cells. These effects result in the release of inflammatory mediators, the development of edema, and the persistence of inflammation, which are key features of CSU. Notably, elevated PAF levels have been linked to heightened disease activity and resistance to antihistamine treatment in CSU patients. Despite these findings, the precise role of PAF in CSU pathogenesis remains unclear. Rupatadine, an antihistamine, and heat shock protein 10, a natural anti-inflammatory peptide that selectively inhibits PAF-induced mast cell degranulation, have demonstrated anti-PAF activity. Furthermore, with the molecular structure of the PAF receptor now identified, several experimental PAF receptor antagonists have been synthesized. However, there remains a significant need for the development of therapeutic options targeting PAF in CSU management
Risk factors for Implant Failure in Thoracolumbar Fractures Treated with Posterior Long-Segment Instrumentation
Background: Posterior long-segment instrumentation (PLSI) enables the stable repair of thoracolumbar fractures (TLFx) and is thus widely used. However, patients with highly unstable fractures may experience implant failure and related complications (e.g., pain and kyphosis) despite PLSI. Few studies have considered the implant failure rate and risk factors associated with PLSI for TLFx. Methods: This study reviewed 162 consecutive patients with TLFx who underwent PLSI and completed > 1 year of follow-up between April 2011 and December 2019. Implant failure was defined as rod breakage, cap dislodgement, or screw breakage. Risk factors for implant failure were evaluated by multivariate regression analysis that included demographic, injury-related, and surgical factors. Results: There were 15 cases (9.3%) of implant failure at the final follow-up (mean, 28.0 ± 18.0 months). Current smoker at the time of injury, fracture level, load sharing score, and anterior compression ratio (ACR) significantly differed between the implant failure and control groups (all p < 0.05). Multivariate logistic regression identified current smoker at the time of injury (adjusted odds ratio [aOR], 5.924; 95% CI, 1.405–24.988), mid to low lumbar fracture (aOR, 15.977; 95% CI, 4.064–62.810), and ACR (aOR, 1.061; 95% CI, 1.009–1.115) as predictors of implant failure. Conclusions: This study demonstrated a high implant failure rate in patients with TLFx treated with PLSI. Smoking at the time of injury, mid to low lumbar fracture, and higher ACR were identified as significant risk factors for implant failure. These findings can help guide treatment decisions and improve patient outcomes in TLFx surgery