Impaired binding affinity of YTHDC1 with METTL3/METTL14 results in R-loop accumulation in myelodysplastic neoplasms with DDX41 mutation.

DEAD box helicase 41 (DDX41) mutations are the most prevalent predisposition to familial myelodysplastic syndrome (MDS). However, the precise roles of these variants in the pathogenesis of MDS have yet to be elucidated. Here, we discovered a novel mechanism by which DDX41 contributes to R-loop-induced DNA damage responses (DDR) in cooperation with the m6A-METTL complex (MAC) and YTHDC1 using DDX41 knockout (KO) and DDX41 knock-in (KI, R525H, Y259C) cell lines as well as primary samples from MDS patients. Compared to wild type (WT), DDX41 KO and KI led to increased levels of m6A RNA methylated R-loop. Interestingly, we found that DDX41 regulates m6A/R-loop levels by interacting with MAC components. Further, DDX41 promoted the recruitment of YTHDC1 to R-loops by promoting the binding between METTL3 and YTHDC1, which was dysregulated in DDX41-deficient cells, contributing to genomic instability. Collectively, we demonstrated that DDX41 plays a key role in the physiological control of R-loops in cooperation with MAC and YTHDC1. These findings provide novel insights into how defects in DDX41 influence MDS pathogenesis and suggest potential therapeutic targets for the treatment of MDS.

Reduced toxicity (FluBu3) versus myeloablative (BuCy) conditioning in acute myeloid leukemia patients who received first allogeneic hematopoietic stem cell transplantation in measurable residual disease-negative CR1.

In the present study, reduced toxicity (FluBu3) and myeloablative (BuCy) conditioning were compared in patients with AML who received first allogeneic HSCT in MRD-negative CR1. The study included 124 adult patients who underwent HSCT from an HLA-matched (8/8) sibling, unrelated, or 1-locus mismatched (7/8) unrelated donor (MMUD). The median age was 45 years and intermediate cytogenetics comprised majority (71.8%). The 2-year OS, RFS, CIR and NRM for BuCy (n = 78, 62.9%) and FluBu3 (n = 46, 37.1%) groups were 78.3% and 84.5% (p = 0.358), 78.0% and 76.3% (p = 0.806), 7.7% and 21.5% (p = 0.074) and 14.3% and 2.2% (p = 0.032), respectively. At the time of data cut-off, relapse and NRM were the main causes of HSCT failure in each of the FluBu3 and BuCy arms. Among patients, 75% of relapsed FluBu3 patients had high-risk features of either poor cytogenetics or FLT3-ITD mutation compared with 16.7% of BuCy patients. The majority of NRM in the BuCy group was due to GVHD (73%), half of whom received MMUD transplantation. To conclude, the FluBu3 reduced toxicity conditioning showed comparable post-transplant OS and RFS to BuCy and was associated with significantly reduced NRM that was offset by a trend towards higher risk of relapse even in MRD-negative CR1 population.

Quantitative Analysis of Hair Luster in a Novel Ultraviolet-Irradiated Mouse Model.

Hair luster is a key attribute of healthy hair and a crucial aspect of cosmetic appeal, reflecting the overall health and vitality of hair. Despite its significance, the advancement of therapeutic strategies for hair luster enhancement have been limited due to the absence of an effective experimental model. This study aimed to establish a novel animal model to assess hair gloss, employing ultraviolet (UV) irradiation on C57BL/6 mice. Specifically, UVB irradiation was meticulously applied to the shaved skin of these mice, simulating conditions that typically lead to hair luster loss in humans. The regrowth and characteristics of the hair were evaluated using a dual approach: an Investigator's Global Assessment (IGA) scale for subjective assessment and an image-based pixel-count method for objective quantification. These methods provided a comprehensive understanding of the changes in hair quality post-irradiation. To explore the potential reversibility of hair luster changes, oral minoxidil was administered, a treatment known for its effects on hair growth and texture. Further, to gain insights into the underlying biological mechanisms, bulk RNA transcriptomic analysis of skin tissue was conducted. This analysis revealed significant alterations in the expression of keratin-associated protein (KRTAP) genes, suggesting modifications in hair keratin crosslinking due to UV exposure. These changes are crucial in understanding the molecular dynamics affecting hair luster. The development of this new mouse model is a significant advancement in hair care research. It not only facilitates the evaluation of hair luster in a controlled setting but also opens avenues for the research and development of innovative therapeutic strategies. This model holds promise for the formulation of more effective hair care products and treatments, potentially revolutionizing the approach towards managing and enhancing hair luster.

Home Oxygen After Hospitalization for COVID-19: Results From the Multi-Center OXFORD Study.

BACKGROUND: In the first months of the pandemic, prior to the introduction of proven-effective treatments, 15-37% of patients hospitalized with COVID-19 were discharged on home oxygen. After proven-effective treatments for acute COVID-19 were established by evidence-based guidelines, little remains known about home oxygen requirements following hospitalization for COVID-19. METHODS: This was a retrospective, multi-center cohort study of subjects hospitalized for COVID-19 between October 2020-September 2021 at 3 academic health centers. Information was abstracted from electronic health records at the index hospitalization and for 60 d after discharge. The World Health Organization COVID-19 Clinical Progression Scale score was used to identify patients with severe COVID-19. RESULTS: Of 517 subjects (mean age 58 y, 47% female, 42% Black, 36% Hispanic, 22% with severe COVID-19), 81% were treated with systemic corticosteroids, 61% with remdesivir, and 2.5% with tocilizumab. About one quarter of subjects were discharged on home oxygen (26% [95% CI 22-29]). Older age (adjusted odds ratio [aOR] 1.02 per 5 y [95% CI 1.02-1.02]), higher body mass index (aOR 1.02 per kg/m2 [1.00-1.04]), diabetes (yes vs no, aOR 1.73 [1.46-2.02]), severe COVID-19 (vs moderate, aOR 3.19 [2.19-4.64]), and treatment with systemic corticosteroids (yes vs no, aOR 30.63 [4.51-208.17]) were associated with an increased odds of discharge on home oxygen. Comorbid hypertension (yes vs no, aOR 0.71 [0.66-0.77) was associated with a decreased odds of home oxygen. Within 60 d of hospital discharge, 50% had documentation of pulse oximetry; in this group, home oxygen was discontinued in 46%. CONCLUSIONS: About one in 41 subjects were prescribed home oxygen after hospitalization for COVID-19, even after guidelines established proven-effective treatments for acute illness. Evidence-based strategies to reduce the requirement for home oxygen in patients hospitalized for COVID-19 are needed.

Short term effect of intravenous treprostinil in term and preterm infants with pulmonary hypertension.

BACKGROUND: Pulmonary hypertension (PH) is a life-threatening condition in newborns. We aimed to assess the clinical and echocardiographic responses of term and preterm infants to treprostinil. METHODS: This retrospective study included newborns diagnosed with PH and treated with treprostinil as additional therapy after inhaled nitric oxide administration in the neonatal intensive care unit of a tertiary center. Term and preterm infants were compared in terms of echocardiographic findings and clinical findings 4 weeks after treprostinil treatment. RESULTS: During the study period, 11 term and 18 preterm infants were diagnosed with PH and received treprostinil. There were no differences in the echocardiographic findings of interventricular septal deviation, direction of shunt, and ratio of estimated pulmonary artery pressure over systolic blood pressure. Congenital diaphragmatic hernia was the most common condition occurring upon PH diagnosis among term infants, while severe bronchopulmonary dysplasia was the most common in preterm infants. Improvements in echocardiographic findings were more pronounced in term infants than in preterm infants (100% vs. 55.6%, P = 0.012). The inhaled nitric oxide dose was gradually tapered for term infants and was lower than that for preterm infants at 1, 2, and 3 weeks after treprostinil. CONCLUSION: Intravenous treprostinil could be an adjuvant therapy option for term and preterm infants with PH, especially for those who cannot receive oral medication. The efficacy and safety of treprostinil in this population with PH should be investigated further.

Cardiovascular disease prevention in women - the current state in 2023.

PURPOSE OF REVIEW: Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality for women globally. The purpose of this review is to provide an updated overview of CVD prevention in women, focusing on what is currently understood about female-specific or female-predominant CVD risk factors and the importance of tailored strategies for risk assessment and medical interventions. RECENT FINDINGS: Recent studies have demonstrated the need to account for risk factors specific to women in current risk assessment models for CVD, including early menarche, polycystic ovary syndrome, adverse pregnancy outcomes, early menopause, and chronic inflammatory conditions. Incorporation of these findings has led to advancements in sex-specific guidelines, diagnostic tools, and treatment approaches that have led to improvement in the precision of CVD prevention strategies. At-risk women benefit similarly to lipid-lowering and other preventive therapies as men but are less likely to be treated. SUMMARY: CVD prevention in women has made substantial progress over the past decade, marked by increasing awareness among clinicians, improved understanding of sex-specific risk-enhancing factors, and incorporation of sex-specific guidelines for management. However, there remain knowledge gaps that warrant ongoing efforts to optimize CVD prevention strategies in women, which will ultimately lead to improved cardiovascular health outcomes.

Dynamic changes in physical function during intensive chemotherapy affect transplant outcomes in older adults with AML.

Introduction: Intensive chemotherapy (IC) can affect all geriatric assessment (GA) domains in older adults with acute myeloid leukemia (AML), but data on the effects of these changes on transplant outcomes are lacking. Methods: Therefore, we prospectively assessed the prognostic role of GA domains at diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 51 patients with AML aged ≥60 years who achieved complete remission after IC. We performed both baseline and pre-allo-HSCT GA; moreover, physical function, including a short physical performance battery (SPPB), cognitive function, psychological function, nutritional status, and social support were examined. Results: All GA domains showed dynamic changes between the two time points. The directions of change were statistically significant for social support, self-reported physical and psychological functions, and distress, but not for nutritional status, cognitive function, or physical function. Among all GA domains at each time point, only poor physical function and its submaneuvers at diagnosis but not at allo-HSCT were significantly associated with inferior survival. In particular, since the direction of change varied between patients, we found that patients whose physical function improved before allo-HSCT were more likely to survive longer than those with persistently impaired SPPB (55.6% vs. 28.6%, p=0.268). Finally, persistent impairment in SPPB (28.6% vs. 65.9%, p=0.006), tandem stand (0% vs. 63.3%, p=0.012), sit-and-stand (41.2% vs. 70.6%, p=0.009), and gait speed (38.5% vs. 68.4%, p=0.027) further strongly predicted inferior survival. Discussion: This study showed that IC courses can induce dynamic changes in different directions in the GA domains of each patient and that changes in objectively measured physical function can predict transplant outcomes.

The salvage role of allogeneic hematopoietic stem-cell transplantation in relapsed/refractory diffuse large B cell lymphoma.

To clarify the role of allogeneic hematopoietic stem-cell transplantation (allo-HSCT) in the chimeric antigen receptor T-cell therapy era, we analyzed the clinical characteristics and outcomes of 52 patients treated with allo-HSCT with relapsed/refractory diffuse large B cell lymphoma. Most enrolled patients had previously undergone intensive treatments, the median number of chemotherapy lines was 4, and the median time from diagnosis to allo-HSCT was 27.1 months. Patients were divided into remission-achieved (n = 30) and active-disease (n = 22) groups before allo-HSCT. Over a median follow-up period of 38.3 months, overall survival (OS) and event-free survival (EFS) rates were 38.4% and 30.6%, respectively. The cumulative incidence of relapse (CIR) and the non-relapsed mortality (NRM) were 36.7% and 32.7%, respectively. OS, EFS, and graft-versus-host disease-free, relapse-free survival (GRFS) outcomes were significantly superior in the remission-achieved group with lower CIR. In a multivariate analysis, a shorter interval from diagnosis to allo-HSCT reflected relatively rapid disease progression and showed significantly poor OS and EFS with higher CIR. Patients with active disease had significantly lower EFS, GRFS, and higher CIR. Previous autologous stem-cell transplantation was associated with better GRFS. Allo-HSCT is an established modality with a prominent group of cured patients and still has a role in the CAR T-cell era, particularly given its acceptable clinical outcomes in young patients with chemo-susceptible disease.

Th17 cells target the metabolic miR-142-5p-succinate dehydrogenase subunit C/D (SDHC/SDHD) axis, promoting invasiveness and progression of cervical cancers.

During cervical carcinogenesis, T-helper (Th)-17 cells accumulate in the peripheral blood and tumor tissues of cancer patients. We previously demonstrated that Th17 cells are associated with therapy resistance as well as cervical cancer metastases and relapse; however, the underlying Th17-driven mechanisms are not fully understood. Here, using microarrays, we found that Th17 cells induced an epithelial-to-mesenchymal transition (EMT) phenotype of cervical cancer cells and promoted migration and invasion of 2D cultures and 3D spheroids via induction of microRNA miR-142-5p. As the responsible mechanism, we identified the subunits C and D of the succinate dehydrogenase (SDH) complex as new targets of miR-142-5p and provided evidence that Th17-miR-142-5p-dependent reduced expression of SDHC and SDHD mediated enhanced migration and invasion of cancer cells using small interfering RNAs (siRNAs) for SDHC and SDHD, and miR-142-5p inhibitors. Consistently, patients exhibited high levels of succinate in their serum associated with lymph node metastases and diminished expression of SDHD in patient biopsies correlated with increased numbers of Th17 cells. Correspondingly, a combination of weak or negative SDHD expression and a ratio of Th17/CD4+ T cells > 43.90% in situ was associated with reduced recurrence-free survival. In summary, we unraveled a previously unknown molecular mechanism by which Th17 cells promote cervical cancer progression and suggest evaluation of Th17 cells as a potential target for immunotherapy in cervical cancer.

Cytomegalovirus Infection after Allogeneic Hematopoietic Cell Transplantation under 100-Day Letermovir Prophylaxis: A Real-World 1-Year Follow-Up Study.

The prevention and management of cytomegalovirus (CMV) reactivation is important to improve the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The aim of this study was to analyze real-world data regarding the incidence and characteristics of CMV infections until 1 year after allo-HCT under 100-day letermovir prophylaxis. A single-center retrospective study was conducted between November 2020 and October 2021. During the study period, 358 patients underwent allo-HCT, 306 of whom received letermovir prophylaxis. Cumulative incidence of clinically significant CMV infection (CS-CMVi) was 11.4%, 31.7%, and 36.9% at 14 weeks, 24 weeks, and 1 year post-HCT, respectively. Through multivariate analysis, the risk of CS-CMVi increased with graft-versus-host disease (GVHD) ≥ grade 2 (adjusted odds ratio 3.640 [2.036-6.510]; p < 0.001). One-year non-relapse mortality was significantly higher in letermovir breakthrough CS-CMVi patients than those with subclinical CMV reactivation who continued receiving letermovir (p = 0.002). There were 18 (15.9%) refractory CMV infection cases in this study population. In summary, letermovir prophylaxis is effective at preventing CS-CMVi until day 100, which increased after the cessation of letermovir. GVHD is still a significant risk factor in the era of letermovir prophylaxis. Further research is needed to establish individualized management strategies, especially in patients with significant GVHD or letermovir breakthrough CS-CMVi.

Efficacy of inhaled tiotropium add-on to budesonide/formoterol in patients with bronchiolitis obliterans developing after hematopoietic stem cell transplantation.

BACKGROUND: Bronchiolitis obliterans syndrome (BOS) is the lung manifestation of chronic graft-versus-host disease after hematopoietic stem cell transplantation (HSCT). We assessed whether inhaled tiotropium add-on to the combination regimen including budesonide/formoterol improve pulmonary function and the chronic obstructive pulmonary disease assessment test (CAT) scores in patients with BOS. METHODS: Post-HSCT patients diagnosed as BOS in Seoul St. Mary's Hospital were reviewed retrospectively. Patients defined as BOS and treated with budesonide/formoterol/tiotropium combination therapy after budesonide/formoterol therapy from January 2011 to June 2019 were enrolled. RESULTS: Total of 86 patients were evaluated. After tiotropium add-on, the absolute FEV1 increased significantly from 1.47 ± 0.49 to 1.53 ± 0.57 L (p = 0.023) and the % predicted FEV1 from 45.0 ± 12.8 to 46.8 ± 14.5% (p = 0.031). The % predicted DLCO increased significantly after tiotropium add-on (from 61.6 ± 16.7 to 64.3 ± 16.3%, p = 0.028). Among 56 patients with complete CAT scores, no significant change was present in total CAT scores. In all, 30 of the 72 patients (41.7%) evidenced FEV1 increases > 100 mL, and 20 of 56 patients (35.7%) had CAT score decreases of ≥ 2 points. When the FEV1 and CAT scores were combined, the overall response rate to tiotropium add-on was 56.2% (41/73). The response group evidenced a significantly greater FVC increase, and a significant decrease in the RV/TLC ratio compared to the no-response group. CONCLUSIONS: Inhaled tiotropium add-on to combination budesonide/formoterol significantly improved lung function, but not respiratory symptoms, in patients with post-HSCT BOS.

Efficacy of ex vivo purging with CD34+ selection to maximize the effects of autologous stem cell transplantation in peripheral T-cell lymphoma patients.

BACKGROUND AIMS: Peripheral T-cell lymphomas (PTCLs) are rare and aggressive tumors with uncertain optimal treatment. This study investigated the clinical outcomes of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) after CD34+ selective purging in PTCL patients. METHODS: Retrospective analysis included 67 PTCL patients who achieved remission and underwent HDT/ASCT. CD34+ selective purging was performed using CliniMACS® (Miltenyi Biotec, Bergisch Gladbach, Germany). Survival outcomes, engraftment, lymphocyte subsets and viral infections were evaluated. RESULTS: CD34+ selective purged autografts were associated with significantly improved overall survival (OS) and disease-free survival (DFS) compared with unpurged autografts (5-year OS, 73.3% versus 37.8%, 5-year DFS, 73.8% versus 33.4%). The cumulative incidence of relapse was also lower in the purged group (31.5% versus 73.3%). Subgroup analysis revealed significant survival benefits in the high-risk group receiving purged autografts. Lymphocyte subset analysis showed increased natural killer (NK) cell counts in the purged group after ASCT. Higher post-ASCT lymphocyte-to-monocyte ratio (LMR) was associated with improved OS and DFS. CONCLUSIONS: CD34+ selective purging in PTCL patients undergoing HDT/ASCT improved survival outcomes and reduced relapse risk. The procedure increased NK cell counts and post-ASCT LMR. CD34+ selective purging may minimize autograft tumor cell contamination and enhance efficacy in T-cell lymphomas.

Telehealth interventions to support self-care of stroke survivors: An integrative review.

Background: Self-care is essential for stroke survivors to recover from neurological disorders caused by stroke and to prevent recurrences. Self-care behaviors are activities that individuals undertake to prevent recurrence and complications, and have a positive effect on the quality of life of patients. Telehealth is an emerging technology through which self-care intervention can be provided from a distance. Review-based research is needed to determine the value and development of telehealth-based self-care interventions for stroke survivors. Objective: Based on the middle range theory of self-care of chronic illness, to provide an effective guide when developing telehealth self-care interventions for stroke survivors by comprehensively understanding telehealth interventions to support self-care of stroke survivors. Methods: An integrative review, this study was performed in accordance with Whittemore and Knafl's stages of an integrative review (problem identification, literature search, data evaluation, data analysis, and presentation of the results). The key search terms included combinations of concepts related to stroke survivors and self-care, and telehealth. The research year of searched publications was not limited, and five electronic databases (PubMed, Ovid-MEDLINE, Ovid-EMBASE, CINAHL and Cochrane Library) were searched. Results: Four attributes were identified that represented telehealth's functions that appeared to be associated with a self-care intervention for stroke survivors. These included introducing the concept of interaction, monitoring, education, and store and forward. These self-care interventions were found to influence the behaviors of stroke survivors' self-care maintenance (physical activity and treatment adherence), self-care monitoring (blood pressure, healthy behaviors, health diet, psychological well-being, glucose control, and depression), and self-care management (sense of control, healthcare resource utilization, social integration, and support). Conclusions: The results of this study can provide a guide for developing effective telehealth self-care intervention by identifying the attributes of telehealth self-care intervention for stroke survivors.

Extramedullary plasmacytoma of the orbit with intracranial invasion: A case report.

RATIONALE: Plasmacytoma is a disease caused by the proliferation of monoclonal immunoglobulin-producing plasma cells and divided into multiple myeloma, solitary bone plasmacytoma, and extramedullary plasmacytoma. We report a case of orbital extramedullary plasmacytoma invading the dura mater in a patient with exophthalmos and diplopia. PATIENT CONCERNS: A 35-year-old female patient with exophthalmos in the right eye and diplopia visited the clinic. DIAGNOSES: The thyroid function tests showed nonspecific results. Orbital computed tomography and magnetic resonance imaging revealed a homogeneously enhancing orbital mass infiltrating the right maxillary sinus and adjacent brain tissue in the middle cranial fossa through the superior orbital fissure. INTERVENTIONS: To diagnose and alleviate the symptoms, an excisional biopsy was performed, which revealed a plasmacytoma. OUTCOMES: One month after the surgery, the protruding symptoms and eye movement restriction in the right eye improved, and the visual acuity in the right eye was restored. LESSONS: In this case report, we present a case of an extramedullary plasmacytoma that originated in the inferior wall of the orbit and invaded the cranial cavity. To our knowledge, no previous reports have described a solitary plasmacytoma that originated in the orbit, causing exophthalmos and invading the cranial cavity at the same time.

Performance Validation of Three Scoring Systems for the Prediction of Thrombotic Microangiopathy Due to Severe ADAMTS13 Deficiency and the Response to Therapeutic Plasma Exchange: First Study in Korea.

Background: The BENTLEY score (B-S), French thrombotic microangiopathy (TMA) Reference Center score (FTMA-S), and PLASMIC score (PLASMIC-S) have been developed for TMA diagnostic prediction. We retrospectively validated their predictive performances in patients with severe (<10%) disintegrin and metalloprotease with thrombospondin type 1 motif, member 13 (ADAMTS13) deficiency in terms of the risk of TMA and response to therapeutic plasma exchange (TPE). Methods: The predictive performances of the three scoring systems were compared in 145 patients with suspected TMA who underwent ADAMTS13 activity tests between January 2014 and September 2022. The response to TPE and mortality in TMA-positive patients were compared after risk stratification, using the Mann-Whitney U and Fisher's exact tests. Results: The PLASMIC-S, FTMA-S, and B-S showed area under the curve values of 0.820, 0.636, and 0.513, respectively, for predicting TMA positivity in high-risk patients. The PLASMIC-S showed higher sensitivity (81.8%), negative predictive value (91.2%), positive predictive value (PPV; 66.7%), and accuracy (82.1%) than the FTMA-S (72.7%, 82.1%, 41.0%, and 60.0%, respectively) and B-S (4.6%, 70.2%, 50.0%, and 69.7%, respectively). The PLASMIC-S also showed higher specificity than the FTMA-S (82.2% vs. 54.5%). The modified PLASMIC-S, including lactate dehydrogenase/upper limit of normal ratios, increased the specificity, PPV, and accuracy to 97.0%, 92.3%, and 92.4%, respectively. In TMA-positive patients, high risk assessed by the PLASMIC-S predicted higher platelet recovery rates and less TPE sessions required for recovery than for those assessed at low-to-intermediate risk. Conclusions: PLASMIC-S is the preferred scoring system for detecting patients with TMA positivity and for prognosis before confirmation of ADAMTS13 activity.

Predicting the need for intubation within 3 h in the neonatal intensive care unit using a multimodal deep neural network.

Respiratory distress is a common chief complaint in neonates admitted to the neonatal intensive care unit. Despite the increasing use of non-invasive ventilation in neonates with respiratory difficulty, some of them require advanced airway support. Delayed intubation is associated with increased morbidity, particularly in urgent unplanned cases. Early and accurate prediction of the need for intubation may provide more time for preparation and increase safety margins by avoiding the late intubation at high-risk infants. This study aimed to predict the need for intubation within 3 h in neonates initially managed with non-invasive ventilation for respiratory distress during the first 48 h of life using a multimodal deep neural network. We developed a multimodal deep neural network model to simultaneously analyze four time-series data collected at 1-h intervals and 19 variables including demographic, physiological and laboratory parameters. Evaluating the dataset of 128 neonates with respiratory distress who underwent non-invasive ventilation, our model achieved an area under the curve of 0.917, sensitivity of 85.2%, and specificity of 89.2%. These findings demonstrate promising results for the multimodal model in predicting neonatal intubation within 3 h.

Microbiologic Epidemiology of Early-onset Sepsis in Neonates Born at ≥35 0/7 Weeks' Gestation in Korea During 2009-2018.

BACKGROUND: Sepsis within the first 3 days of life remains a leading cause of neonatal mortality and morbidity. However, few studies have addressed the epidemiology of sepsis in late preterm and term neonates, particularly in Asia. We aimed to estimate the epidemiology of early-onset sepsis (EOS) in neonates born at ≥35 0/7 weeks' gestation in Korea. METHODS: A retrospective study was conducted in neonates with proven EOS born at ≥35 0/7 weeks' gestation from 2009 to 2018 at seven university hospitals. EOS was defined as identifying bacteria from a blood culture within 72 hours after birth. RESULTS: A total of 51 neonates (0.36/1,000 live births) with EOS were identified. The median duration from birth to the first positive blood culture collection was 17 hours (range, 0.2-63.9). Among the 51 neonates, 32 (63%) patients were born by vaginal delivery. The median Apgar score was 8 (range, 2-9) at 1 minute and 9 (range, 4-10) at 5 minutes. The most common pathogen was group B Streptococcus (n = 21; 41.2%), followed by coagulase-negative staphylococci (n = 7; 13.7%) and Staphylococcus aureus (n = 5, 9.8%). Forty-six (90.2%) neonates were treated with antibiotics on the first day of symptom onset, and 34 (73.9%) neonates received susceptible antibiotics. The overall 14-day case-fatality rate was 11.8%. CONCLUSION: This is the first multicenter study on the epidemiology of proven EOS in neonates born at ≥35 0/7 weeks' gestation and found that group B Streptococcus was the most common pathogen in Korea.

Association between urinary albumin creatinine ratio and cardiovascular disease.

INTRODUCTION: The association between microalbuminuria and cardiovascular disease (CVD) is accumulating in various patient populations. However, when stratified by sex, the relationship between microalbuminuria and CVD remains unclear. METHOD: We obtained data from the 2011-2014 and 2019-2020 Korea National Health and Nutrition Examination Survey (KNHANES). Microalbuminuria was measured based on spot urine albumin-creatinine ratio (UACR). The Framingham risk score (FRS) model was implemented to evaluate the CVD risk. Linear and logistic regression models were used to identify the associations of microalbuminuria status with cardiometabolic predictors and CVD status determined by the FRS score. RESULTS: Among 19,340 representative Korean participants, the (UACR) in Korean women and men with history of CVD was higher than in those without history of CVD. Among patients without history of CVD, multivariate regression analysis showed that a high UACR was related to older age, lower high-density lipoprotein cholesterol level, higher total cholesterol level, higher systolic blood pressure, higher prevalence of current smoking, higher prevalence of diabetes, and higher anti-hypertensive medication use in both women and men. The UACR showed a positive linear correlation with the Framingham risk score in both women and men. CONCLUSION: The presence of microalbuminuria was significantly associated with the cardiometabolic risk factors and the increased risk of CVD evaluated by FRS model in both women and men in a nationally representative sample of Korea.

Analysis of 2-year spherical equivalent progression in emmetropic children with non-cycloplegic refraction: a retrospective chart review.

BACKGROUND: We aimed to investigate children with an emmetropic non-cycloplegic refraction (NCR) to compare the difference in progression of NC spherical equivalent (SE) over 2 years between the children with emmetropic and hyperopic cycloplegic refraction (CR) values. METHODS: Through a retrospective medical record review, 59 children aged under 10 years were evaluated. Refractive error was calculated as the average of the SE values of both eyes. According to the CR results, children with emmetropia (-0.50 to 1.00 diopter [D]) were assigned to group 1 (n = 29), and those with hyperopia (≥ 1.00 D) were assigned to group 2 (n = 30). The prevalence of myopia and SE progression were compared over 2 years. Correlations between final SE progression and baseline age and refractive error were analyzed and multiple regression analysis was conducted. Receiver operating characteristic curves that achieved the best cutoff points to distinguish between the groups were calculated. RESULTS: Group 1 showed significantly myopic SE changes compared to baseline at the 1-year follow-up, and group 1 was significantly myopic compared with group 2 at the 2-year follow-up. Myopia prevalence was 51.7% in group 1 and 6.7% in group 2 after 1 year, and 61.1% and 16.7% after 2 years, respectively. In the correlation analysis, baseline age, baseline CR, and difference between CR and NCR showed significant correlations with the 2-year SE progression (r = -0.359, p = 0.005; r = 0.450, p < 0.001; r = -0.562, p < 0.001, respectively). However, NCR refractive error showed no significant correlation (r = -0.097, p = 0.468). In multiple regression analysis, baseline age (ß= -0.082), and CR-NCR difference (ß= -0.214) showed a significant effect on SE progression for 2 years. When an NCR value of 0.20 D was set as the cut-off value to distinguish between the groups, a sensitivity of 70% and specificity of 92% were obtained. CONCLUSION: Even if NCR showed emmetropia, children with baseline CR values of emmetropia showed greater SE progression compared with those with hyperopia. Cycloplegia is essential to confirm the correct refractive status in children. It may be useful for predicting prognosis of SE progression.

Efficacy and safety of mucous fistula refeeding in preterm infants: an exploratory randomized controlled trial.

BACKGROUND: This study aimed to evaluate whether mucous fistula refeeding (MFR) is safe and beneficial for the growth and intestinal adaptation of preterm infants with enterostomies. METHODS: This exploratory randomized controlled trial enrolled infants born before 35 weeks' gestation with enterostomy. If the stomal output was ≥ 40 mL/kg/day, infants were assigned to the high-output MFR group and received MFR. If the stoma output was < 40 mL/kg/day, infants were randomized to the normal-output MFR group or the control group. Growth, serum citrulline levels, and bowel diameter in loopograms were compared. The safety of MFR was evaluated. RESULTS: Twenty infants were included. The growth rate increased considerably, and the colon diameter was significantly larger after MFR. However, the citrulline levels did not significantly differ between the normal-output MFR and the control group. One case of bowel perforation occurred during the manual reduction for stoma prolapse. Although the association with MFR was unclear, two cases of culture-proven sepsis during MFR were noted. CONCLUSIONS: MFR benefits the growth and intestinal adaptation of preterm infants with enterostomy and can be safely implemented with a standardized protocol. However, infectious complications need to be investigated further. TRIAL REGISTRATION: clinicaltrials.gov NCT02812095, retrospectively registered on June 6, 2016.