The Effects of Microbial Additive Supplementation on Growth Performance, Blood Metabolites, Fecal Microflora, and Carcass Characteristics of Growing-Finishing Pigs.

This study aimed to assess the effects of microbial additives that produce antimicrobial and digestive enzymes on the growth performance, blood metabolites, fecal microflora, and carcass characteristics of growing-finishing pigs. A total of 180 growing-finishing pigs (Landrace × Yorkshire × Duroc; mixed sex; 14 weeks of age; 58.0 ± 1.00 kg) were then assigned to one of three groups with three repetitions (20 pigs) per treatment for 60 days of adaptation and 7 days of collection. Dietary treatments included 0, 0.5, and 1.0% microbial additives in the basal diet. For growth performance, no significant differences in the initial and final weights were observed among the dietary microbial additive treatments, except for the average daily feed intake, average daily gain, and feed efficiency. In terms of blood metabolites and fecal microflora, immunoglobulin G (IgG), blood urea nitrogen, blood glucose, and fecal lactic acid bacteria count increased linearly, and fecal E. coli counts decreased linearly with increasing levels of microbial additives but not growth hormones and Salmonella. Carcass quality grade was improved by the microbial additive. In addition, carcass characteristics were not influenced by dietary microbial additives. In conclusion, dietary supplementation with 1.0% microbial additive improved average daily gain, feed efficiency, IgG content, and fecal microflora in growing-finishing pigs.

Comparison between a tubeless, on-body automated insulin delivery system and a tubeless, on-body sensor-augmented pump in type 1 diabetes: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP). METHODS: This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19-69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates. RESULTS: A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: -0.7 mmol/mol [95% CI -2.0, 0.8 mmol/mol] (-0.1% [95% CI -0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group. CONCLUSIONS/INTERPRETATION: The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP. TRIAL REGISTRATION: Clinical Research Information Service (CRIS) KCT0008398 FUNDING: The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).

Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to compare the effectiveness of stand-alone intermittently scanned continuous glucose monitoring (isCGM) with or without a structured education programme and blood glucose monitoring (BGM) in adults with type 2 diabetes on multiple daily insulin injections (MDI). METHODS: In this 24 week randomised open-label multicentre trial, adults with type 2 diabetes on intensive insulin therapy with HbA1c levels of 58-108 mmol/mol (7.5-12.0%) were randomly assigned in a 1:1:1 ratio to isCGM with a structured education programme on adjusting insulin dose and timing according to graphical patterns in CGM (intervention group), isCGM with conventional education (control group 1) or BGM with conventional education (control group 2). Block randomisation was conducted by an independent statistician. Due to the nature of the intervention, blinding of participants and investigators was not possible. The primary outcome was change in HbA1c from baseline at 24 weeks, assessed using ANCOVA with the baseline value as a covariate. RESULTS: A total of 159 individuals were randomised (n=53 for each group); 148 were included in the full analysis set, with 52 in the intervention group, 49 in control group 1 and 47 in control group 2. The mean (± SD) HbA1c level at baseline was 68.19±10.94 mmol/mol (8.39±1.00%). The least squares mean change (± SEM) from baseline HbA1c at 24 weeks was -10.96±1.35 mmol/mol (-1.00±0.12%) in the intervention group, -6.87±1.39 mmol/mol (-0.63±0.13%) in control group 1 (p=0.0367 vs intervention group) and -6.32±1.42 mmol/mol (-0.58±0.13%) in control group 2 (p=0.0193 vs intervention group). Adverse events occurred in 28.85% (15/52) of individuals in the intervention group, 26.42% (14/53) in control group 1 and 48.08% (25/52) in control group 2. CONCLUSIONS/INTERPRETATION: Stand-alone isCGM offers a greater reduction in HbA1c in adults with type 2 diabetes on MDI when education on the interpretation of graphical patterns in CGM is provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT04926623. FUNDING: This study was supported by Daewoong Pharmaceutical Co., Ltd.

Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression.

Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross-validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase-4 (DPP-4), the selected senescent chondrocyte-specific marker, had multiple senescence phenotypes, such as increased senescence-associated-galactosidase, p16, p21, and senescence-associated secretory phenotype expression, and showed OA chondrocyte phenotypes. To examine the effects of DPP-4 inhibition on DPP-4+ SnCs, sitagliptin, a DPP-4 inhibitor, was treated in vitro. As a result, DPP-4 inhibition selectively eliminates DPP-4+ SnCs without affecting DPP-4- chondrocytes. To assess in vivo therapeutic efficacy of targeting DPP-4+ SnCs, three known senolytics (ABT263, 17DMAG, and metformin) and sitagliptin were comparatively verified in a DMM-induced rat OA model. Sitagliptin treatment specifically and effectively eliminated DPP-4+ SnCs, compared to the other three senolytics. Furthermore, Intra-articular sitagliptin injection to the rat OA model increased collagen type II and proteoglycan expression and physical functions and decreased cartilage destruction, subchondral bone plate thickness and MMP13 expression, leading to the amelioration of OA phenotypes. Collectively, OARSI score was lowest in the sitagliptin treatment group. Taken together, we verified DPP-4 as a surface marker for SnCs and suggested that the selective targeting of DPP-4+ chondrocytes could be a promising strategy to prevent OA progression.

Exploring the Role of Gut Microbiota in Patients with Alopecia Areata.

Imbalances in gut microbiota reportedly contribute to the development of autoimmune diseases, but the association between the etiopathogenesis of alopecia areata (AA) and gut microbial dysbiosis remains unclear. This cross-sectional study was conducted to identify and compare the composition of the gut microbiome in patients affected by AA and those in a healthy control (HC) group, and to investigate possible bacterial biomarkers for the disease. Fecal samples were collected from 19 AA patients and 20 HCs to analyze the relationship with fecal bacteria. The three major genera constituting the gut microbiome of AA patients were Bacteroides, Blautia, and Faecalibacterium. The alpha diversity of the AA group was not statistically significant different from that of the HC group. However, bacterial community composition in the AA group was significantly different from that of HC group according to Jensen-Shannon dissimilarities. In patients with AA, we found an enriched presence of the genera Blautia and Eubacterium_g5 compared to the HC group (p < 0.05), whereas Bacteroides were less prevalent (p < 0.05). The gut microbiota of AA patients was distinct from those of the HC group. Our findings suggest a possible involvement of gut microbiota in in the as-yet-undefined pathogenesis of AA.

Estimating the burden of vitiligo: a systematic review and modelling study.

BACKGROUND: Vitiligo is a chronic autoimmune disease characterised by depigmented skin patches, which can pose substantial psychosocial challenges particularly in individuals with dark skin tones. Despite its impact on quality of life, there is an absence of standardised global epidemiological data. We sought to address this gap with the present study. METHODS: In this study we did a systematic review and modelling analysis to estimate the global, regional, and national prevalence and incidence of vitiligo. We did a comprehensive search of nine digital libraries (PubMed, Embase, Web of Science, Scientific Electronic Library Online, KCI Korean Journal Database, Russian Science Citation Index, Western Pacific Region Index Medicus, Informit, and Health Research and Development Information Network) from inception up to May 25, 2023. We included cross-sectional or cohort studies reporting the incidence rate or prevalence of vitiligo, or data from which incidence rate or prevalence could be calculated, in the general population of a country or area of a country. Summary estimate data were extracted. A main outcome was to estimate the worldwide, regional, and country-specific lifetime prevalence of vitiligo diagnosed by physicians or dermatologists among the general population and in adults and children (as per age groups defined in included studies). We used a Bayesian hierarchical linear mixed model to estimate prevalence, and calculated number of affected individuals using the UN population structure in 2022. In estimating lifetime prevalence, studies reporting point or period prevalence were excluded. Our other main outcome was to estimate incidence rates of vitiligo, but due to a small number of studies, the data on incidence were presented in a descriptive summary. This study was registered on PROSPERO, CRD42023390433. FINDINGS: Our search identified 22 192 records, of which 90 studies met our inclusion criteria. Of these studies, six focused on the incidence of vitiligo, 79 reported on the prevalence of vitiligo, and five provided data on both incidence and prevalence. 71 studies reported on lifetime prevalence. In the most recent years studied, incidence rates in the general population ranged from 24·7 cases (95% CI 24·3-25·2) per 100 000 person-years in South Korea in 2019, to 61·0 cases (60·6-61·4) in the USA in 2017. In individual studies, incidence rates showed an increasing trend over the periods studied. The global lifetime prevalence of vitiligo diagnosed by a physician or dermatologist was estimated at 0·36% (95% credible interval [CrI] 0·24-0·54) in the general population (28·5 million people [95% CrI 18·9-42·6]), 0·67% (0·43-1·07) in the adult population (37·1 million adults [23·9-58·9]), and 0·24% (0·16-0·37) in the child population (5·8 million children [3·8-8·9]). Vitiligo prevalence was higher in adults than in children across all regions. Central Europe and south Asia reported the highest prevalence (0·52% [0·28-1·07] and 0·52% [0·33-0·82], respectively, in the general population). INTERPRETATION: This study highlights the need for standardised epidemiological data collection globally to inform public health policies and improve vitiligo diagnosis and management. Emphasis on the impact on individuals with darker skin tones is crucial to reducing stigma and improving quality of life. Furthermore, our study highlights the need to conduct more research in regions and populations that have been historically under-represented, to effectively address the worldwide burden of vitiligo. FUNDING: None.

Ibuprofen-induced multiorgan malformation during embryogenesis in Xenopus laevis (FETAX).

Ibuprofen, one of the most commonly prescribed nonsteroidal anti-inflammatory drugs, has not been fully assessed for embryonic toxicity in vertebrates. Here, we systematically assessed the embryotoxicity of ibuprofen in Xenopus laevis at various concentrations during embryogenesis. Embryos were treated with different concentrations of ibuprofen, ranging from 8 to 64 mg/L, at 23 °C for 96 h, and examined daily and evaluated at 72 hpf. Lethal or teratogenic effects were documented. For histological analysis, paraffin embedded embryos were transversely sectioned at a thickness of 10-µm and stained with hematoxylin and eosin. Total RNA was isolated from embryos at stages 6, 12, 22 and 36, and real-time quantitative PCR was performed. Ibuprofen-treated embryos showed delayed or failed dorsal lip formation and its closure at the beginning of gastrulation. This resulted in herniation of the endodermal mass after gastrulation under high concentrations of ibuprofen-treated embryos. Underdeveloped intestines with stage and/or intestinal malrotation, distorted microcephaly, and hypoplastic heart, lungs, and pronephric tubules were observed in ibuprofen-treated embryos. Cephalic, cardiac, and truncal edema were also observed in them. The severity of the deformities was observed in a concentration-dependent manner. The teratogenic index was 2.28. These gross and histological disruptions correlated well with the altered expression of each organ marker gene. In conclusion, ibuprofen induced delayed and disrupted gastrulation in the early developmental stage and multiorgan malformation later in the organogenesis stage of Xenopus laevis embryos.

Spatio-temporal structuring and assembly of abundant and rare bacteria in the benthic compartment of a marginally eutrophic lagoon.

The investigations on ecological processes that structure abundant and rare sub-communities are limited from the benthic compartments of tropical brackish lagoons. We examined the spatial and temporal patterns in benthic bacterial communities of a brackish lagoon; Chilika. Abundant and rare bacteria showed differences in niche specialization but exhibited similar distance-decay patterns. Abundant bacteria were mostly habitat generalists due to their broader niche breadth, environmental response thresholds, and greater functional redundancy. In contrast, rare bacteria were mostly habitat specialists due to their narrow niche breadth, lower environmental response thresholds, and functional redundancy. The spatial patterns in abundant bacteria were largely shaped by stochastic processes (88.7 %, mostly dispersal limitation). In contrast, rare bacteria were mostly structured by deterministic processes (56.4 %, mostly heterogeneous selection). These findings provided a quantitative assessment of the different forces namely spatial, environmental, and biotic that together structured bacterial communities in the benthic compartment of a marginally eutrophic lagoon.

Development of finely tuned liposome nanoplatform for macrophage depletion.

BACKGROUND: Immunotherapy with clodronate-encapsulated liposomes, which induce macrophage depletion, has been studied extensively. However, previously reported liposomal formulation-based drugs (Clodrosome® and m-Clodrosome®) are limited by their inconsistent size and therapeutic efficacy. Thus, we aimed to achieve consistent therapeutic effects by effectively depleting macrophages with uniform-sized liposomes. RESULTS: We developed four types of click chemistry-based liposome nanoplatforms that were uniformly sized and encapsulated with clodronate, for effective macrophage depletion, followed by conjugation with Man-N3 and radiolabeling. Functionalization with Man-N3 improves the specific targeting of M2 macrophages, and radioisotope labeling enables in vivo imaging of the liposome nanoplatforms. The functionalized liposome nanoplatforms are stable under physiological conditions. The difference in the biodistribution of the four liposome nanoplatforms in vivo were recorded using positron emission tomography imaging. Among the four platforms, the clodronate-encapsulated mannosylated liposome effectively depleted M2 macrophages in the normal liver and tumor microenvironment ex vivo compared to that by Clodrosome® and m-Clodrosome®. CONCLUSION: The newly-developed liposome nanoplatform, with finely tuned size control, high in vivo stability, and excellent ex vivo M2 macrophage targeting and depletion effects, is a promising macrophage-depleting agent.

Association between total cholesterol levels and all-cause mortality among newly diagnosed patients with cancer.

We aimed to determine the association between cholesterol values and the risk of all-cause mortality in newly diagnosed patients with cancer in a large-scale longitudinal cohort. Newly diagnosed patients with cancer were reviewed retrospectively. Cox proportional hazards regression models determined the association between baseline levels of total cholesterol (TC), triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol and the risk of all-cause mortality. A restricted cubic spline curve was used to identify the association between total cholesterol (TC) and low-density lipoprotein (LDL) cholesterol with the risk of death on a continuous scale and to present the lowest values of lipid measurements associated with death. The median follow-up duration of the study was 5.77 years. Of the 59,217 patients with cancer, 12,624 patients were expired. The multivariable adjusted hazard ratio (aHR) for all-cause mortality in patients with cancer with 1st-5th (≤ 97 mg/dL) and 96th-100th (> 233 mg/dL) in TC levels was 1.54 (95% CI 1.43-1.66) and 1.28 (95% CI 1.16-1.41), respectively, compared to 61st-80th (172-196 mg/dL). The TC level associated with the lowest mortality risk in the multivariable model was 181 mg/dL. In comparison with LDL-C levels in the 61st-80th (115-136 mg/dL), the multivariable aHR for all-cause mortality in cancer patients with LDL-C levels in the 1st-5th (≤ 57 mg/dL) and 96th-100th (> 167 mg/dL) was 1.38 (95% CI 1.14-1.68) and 0.94 (95% CI 0.69-1.28), respectively. The 142 mg/dL of LDL cholesterol showed the lowest mortality risk. We demonstrated a U-shaped relationship between TC levels at baseline and risk of mortality in newly diagnosed patients with cancer. Low LDL levels corresponded to an increased risk of all-cause death.

Endoscopic Intervention for Anastomotic Leakage After Gastrectomy.

Anastomotic leaks and fistulas are significant complications of gastric surgery that potentially lead to increased postoperative morbidity and mortality. Surgical intervention is reserved for cases with severe symptoms or hemodynamic instability; however, surgery carries a higher risk of complications. With advancements in endoscopic treatment options, endoscopic approaches have emerged as the primary choice for managing these complications. Endoscopic clipping is a traditional method comprising 2 main categories: through-the-scope clips and over-the-scope clips. Through-the-scope clips are user friendly and adaptable to various clinical scenarios, whereas over-the-scope clips can close larger defects. Another promising approach is endoscopic stent insertion, which has shown a high success rate for leak closure, although vigilant monitoring is required to monitor stent migration. Infection control is essential in post-surgical leakage cases, and endoscopic internal drainage provides a relatively safe and noninvasive means to manage fluids, contributing to infection control and wound healing promotion. Endoscopic suturing offers full-thickness wound closure, but requires additional training and endoscopic versatility. As a promising tool, endoscopic vacuum therapy potentially surpasses stent therapy by draining inflammatory materials and closing defects. Furthermore, the use of tissue sealants, such as fibrin glue and cyanoacrylate, has been reported to be effective in selected situations. The choice of endoscopic device should be tailored to individual cases and specific patient conditions, with careful consideration of the nature of the defect. Further extensive studies involving larger patient populations are required to provide more robust evidence on the efficacy of endoscopic approach in managing post-gastric anastomotic leaks.

Extracranial Vascular Malformations Increase Cardiovascular Disease Risk: A Nationwide Population-Based Cohort Study.

BACKGROUND: Extracranial vascular malformations affect vessel inflammation, clotting, and ischemia. However, the relationship between extracranial vascular malformations and myocardial infarction (MI) or stroke has not been fully elucidated. Limited studies have investigated the association between extracranial vascular malformations and cardiovascular diseases. METHODS: A total of 48,701 patients with extracranial vascular malformations and a control cohort with 487,010 age- and sex-matched participants from the Korean National Health Insurance database were included. The incidence and risk of MI, ischemic stroke (IS), and hemorrhagic stroke (HS) between participants with extracranial vascular malformations and the control cohort was then compared. RESULTS: After adjusting for other cardiovascular disease risk factors, the adjusted hazard ratios (aHRs) for VMs, CMs, AVMs, and LMs in patients with acute MI were 1.25 [CI 1.04-1.50], 1.41 [CI 1.24-1.61], 1.68 [CI 1.18-2.37], and 1.40 [CI 1.31-1.48], respectively. For IS, the aHRs were 1.55 [CI 1.35-1.77], 1.92 [CI 1.74-2.11], 1.13 [CI 0.78-1.64], and 1.51 [CI 1.44-1.58], respectively. For HS, the aHRs were 1.51 [CI 1.12-2.05], 5.63 [CI 4.97-6.38], 2.93 [CI 1.82-4.72], and 1.34 [CI 1.20-1.50], respectively. CONCLUSIONS: Independent of cardiovascular risk factors, extracranial vascular malformations were associated with an increased risk of MI, IS, and HS. For patients with CMs and AVMs, intracerebral hemorrhage risk was particularly high, accounting for 563% and 293%, respectively. Therefore, even in patients with extracranial CMs or AVMs, performing diagnostic evaluations for cerebral AVMs and employing measures to prevent intracerebral hemorrhage are very crucial.

Real-World Continuous Glucose Monitoring Data from a Population with Type 1 Diabetes in South Korea: Nationwide Single-System Analysis.

Background: We used continuous glucose monitoring (CGM) data to investigate glycemic outcomes in a real-world population with type 1 diabetes (T1D) from South Korea, where the widespread use of CGM and the nationwide education program began almost simultaneously. Methods: Data from Dexcom G6 users with T1D in South Korea were collected between January 2019 and January 2023. Users were included if they provided at least 90 days of glucose data and used CGM at least 70% of the days in the investigational period. The relationship between CGM utilization and glycemic metrics, including the percentage of time in range (TIR), time below range (TBR), and time above range (TAR), was assessed. The study was approved by the Institutional Review Board of Samsung Medical Center (SMC 2023-05-030). Results: A total of 2288 users were included. Mean age was 41.5 years (57% female), with average uploads of 428 days. Mean TIR was 62.4% ± 18.5%, mean TBR <70 mg/dL was 2.6% ± 2.8%, mean TAR >180 mg/dL was 35.0% ± 19.3%, mean glucose was 168.1 ± 35.8 mg/dL, mean glucose management indicator was 7.2% ± 0.9%, and mean coefficient of variation was 36.7% ± 6.0%. Users with higher CGM utilization had higher TIR (67.8% vs. 52.7%), and lower TBR <70 mg/dL (2.3% vs. 4.7%) and TAR >180 mg/dL (30.0% vs. 42.6%) than those with low CGM utilization (P < 0.001 for all). Users whose data were shared with others had higher TIR than those who did not (63.3% vs. 60.8%, P = 0.001). Conclusions: In this South Korean population, higher CGM utilization was associated with a favorably higher mean TIR, which was close to the internationally recommended target. Using its remote data-sharing feature showed beneficial impact on TIR.

The discriminative role of PROX-1 immunohistochemistry between venous malformation and lymphatic malformation of the deep type with no visible diagnostic surface skin lesion.

BACKGROUND: Venous malformations (VMs) are distinguished from lymphatic malformations (LMs) when specific diagnostic skin lesions are present. In the deep type, this is difficult by clinico-radiologic evaluation alone. We aimed to investigate the usefulness of lymphatic vessel endothelial cell (LEC) markers for the differential diagnosis of the deep VMs and LMs. METHODS: A retrospective study was conducted based on the medical records of patients with VMs and LMs who underwent biopsy with both D2-40 and PROX-1 immunohistochemistry. We compared the initial clinico-radiological diagnosis with the final pathological diagnosis and identified which ones showed a difference. RESULTS: From 261 patients who had VMs and LMs, 111 remained after the exclusion of those who showed definite surface diagnostic features. After pathological diagnosis with the expressions of D2-40 and PROX-1, 38 of 111 (34.2%) patients' final diagnoses were changed. Among these 38 cases, diagnosis was not changed by D2-40 positivity alone, but changed by PROX-1 positivity alone (52.6%) or by both (47.4%). The diagnostic changes were more frequent in the deep category (43.7%) than in the superficial category. CONCLUSIONS: Identifying the expression of D2-40, and especially PROX-1, in the differential diagnosis of VMs and LMs may provide important treatment guidelines and understanding their natural course.

Rare deep vein thrombosis in pregnancy and puerperium 3 case series; upper extremities vein thrombosis, ovarian vein thrombosis, portal and superior mesenteric vein thrombosis.

Pregnancy induces a hypercoagulable state, elevating thrombosis risk by 5-6 times compared to non-pregnant conditions. Predominantly affecting the left lower extremity due to anatomical and hematological factors, deep vein thrombosis can escalate into pulmonary embolism, impacting mortality. The authors aim to report rare incidents of thrombosis beyond the norm, including upper extremity vein thrombosis, right ovarian vein thrombosis, and portal vein and superior mesenteric vein thrombosis, highlighting their significance. Obstetricians should be mindful that thrombosis can occur not only in the lower extremities but also in other areas. Especially when symptoms such as fever unresponsive to antibiotics, atypical pain, and an abnormally high C-reactive protein level are present. Considering the possibility of a rare thrombosis is crucial. Understanding these less common thrombotic events during pregnancy and the postpartum period can contribute to the improvement of timely diagnosis and management strategies.

Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study.

AIMS: Omega-3 fatty acids and fenofibrates have shown some beneficial cardiovascular effects; however, their efficacy has not been compared. This study aimed to compare the effectiveness of currently available omega-3 fatty acids and fenofibrate for reducing major adverse cardiovascular events (MACE). METHODS AND RESULTS: From a nationwide population-based cohort in South Korea (2008-2019), individuals with metabolic syndrome (≥30 years) who received statin with omega-3 fatty acids and those receiving statin with fenofibrate were matched by propensity score (n = 39 165 in both groups). The primary outcome was MACE, including ischaemic heart disease (IHD), ischaemic stroke (IS), and death from cardiovascular causes. The risk of MACE was lower [hazard ratio (HR), 0.79; 95% confidence interval (CI), 0.74-0.83] in the fenofibrate group than in the omega-3 fatty acid group. Fenofibrate was associated with a lower incidence of IHD (HR, 0.72; 95% CI, 0.67-0.77) and hospitalization for heart failure (HR, 0.90; 95% CI, 0.82-0.97), but not IS (HR, 0.90; 95% CI, 0.81-1.00) nor death from cardiovascular causes (HR, 1.07; 95% CI, 0.97-1.17). The beneficial effect of fenofibrate compared to omega-3 fatty acids was prominent in patients with preexisting atherosclerotic cardiovascular disease and those receiving lower doses of omega-3 fatty acids (≤2 g per day). CONCLUSION: In a real-world setting, fenofibrate use was associated with a lower risk of MACE compared with low-dose omega-3 fatty acids when added to statins in people with metabolic syndrome.

Initial Combination Therapy in Type 2 Diabetes.

Type 2 diabetes (T2D) is a progressive disease in which it is challenging to achieve long-term durable glycemic control. However, intensive glycemic control is crucial for preventing diabetes-related complications. Previous studies showed that monotherapy with a stepwise add-on approach was seldom effective for long-term durable glycemic control. Combination therapy, which refers to the use of two or more drugs to control hyperglycemia, has multiple benefits, including the ability to target a variety of pathophysiological processes underlying hyperglycemia. In clinical trials, initial combination therapy showed better glycemic control than monotherapy or a stepwise approach. Emerging evidence indicates that initial combination therapy is associated with preserved ß-cell function and fewer complications in T2D. However, cost-effectiveness and adverse events with combination therapy are issues that should be considered. Therefore, initial combination therapy is an important option for patients with T2D that clinicians should consider with a view toward balancing benefits and potential harms. In this review, we summarize the literature addressing initial combination therapy in T2D, and we suggest optimal strategies based on clinical situations and patient characteristics.

Increased risk of incident mental disorders in adults with new-onset type 1 diabetes diagnosed after the age of 19: A nationwide cohort study.

AIM: This population-based study aimed to investigate the risk of mental disorders in adults with new-onset type 1 diabetes mellitus compared to the general population without diabetes. METHODS: We selected 10,391 adults with new-onset type 1 diabetes and 51,995 adults in the general population without diabetes with a median follow-up of 7.94 years using the National Health Insurance Database in South Korea between January 2009 and December 2020. The adjusted hazard ratios (aHRs) were estimated for the occurrence of mental disorders. RESULTS: The incidence of mental disorders was more than twice as high in patients with new-onset type 1 diabetes (66 per 1000 person-years) than in those without diabetes (29 per 1000 person-years). The aHR [95 % confidence interval] comparing adults with new-onset type 1 diabetes with those without diabetes were 2.20 [2.12.2.29] for mental disorders, 3.16 [2.99.3.35], for depression, 2.55 [2.32.2.80] for mood disorders, 1.89 [1.80.1.97] for anxiety and stress related disorders, 2.50 [1.48.4.22] for eating disorders, 2.62 [1.45.4.73] for personality and behavior disorders and 4.39 [3.55.5.43] for alcohol and drug misuse disorders. When new-onset type 1 diabetes occurred at the age of 41 to 50, the aHR of developing mental illness was 2.43 [2.19.2.70], compared to those without diabetes. CONCLUSIONS: In this nationwide prospective study, new-onset type 1 diabetes in adulthood was significantly associated with a higher risk of mental disorders than in the general population without diabetes.

Relationships among self-esteem, ego-resilience, and caregiver burden among families of children with hematologic and oncologic disease: A cross-sectional study.

Background: Pediatric hematology and oncology disease is a physically and emotionally demanding health condition for families. High self-esteem and ego-resilience among caregivers, which have recently gained increased recognition, might help ease caregiver burdens. Few studies, however, have simultaneously investigated the relationships between self-esteem, ego-resilience, and caregiver burden among caregivers of children with hematologic and oncologic disease. Objective: The purpose of this study is to investigate the relationships between caregiver burden, self-esteem, and ego-resilience and examine whether ego-resilience plays a role in mediating the relationship between self-esteem and caregiver burden among family caregivers of children with hematologic and oncologic disease. Design: Descriptive correlational study. Setting: The outpatient clinic of the department of pediatric hematology and oncology at a flagship university hospital in a metropolitan city in South Korea. Participants: The sample comprised 109 primary family caregivers of children with hematologic and oncologic disease. Convenience sampling method was used. Methods: The participants completed the Ego-Resiliency Scale, Rosenberg Self-Esteem Scale, and Family Burden Questionnaire. One-way analysis of variance, independent t-tests, and correlation analyses were conducted using IBM SPSS 25.0. The mediating effect of ego-resilience was estimated using the PROCESS macro and bootstrap method in SPSS. Results: Caregiver burden showed significant negative associations with self-esteem and ego-resilience, with moderate effect sizes (r = -.391 and -0.361, respectively, p = .001). Ego-resilience mediated the relationship between self-esteem and caregiver burden (b = -0.019; 95 % bias-corrected bootstrap confidence interval -0.035 and -0.001). Conclusions: Self-esteem and ego-resilience may lessen caregiver burden among families of children with hematologic and oncologic disease, and self-esteem of caregivers tends to promote their ego-resilience. Therefore, self-esteem and ego-resilience should be improved among family caregivers to reduce their caregiver burden.

Optimal treatment duration of bismuth-containing quadruple therapy in Helicobacter pylori infection: A retrospective study.

The use of bismuth-containing quadruple therapy (BQT) in Helicobacter pylori eradication has been increasing. Although the recommended treatment length for BQT is 14 days, longer durations may be associated with higher rates of adverse events. The aim of this study was to evaluate the optimal duration of BQT by comparing eradication rates and adverse events among 7, 10, and 14-day regimens. A total of 328 patients treated with BQT at Seoul National University Hospital from January 2010 to May 2022 were retrospectively evaluated. The eradication rates of different treatment groups were compared using intention-to-treat (ITT) and per-protocol (PP) analyses. Baseline characteristics of the enrolled patients and adverse events were also analyzed. A total of 74, 177, and 77 patients were included in the 7-, 10-, and 14-day groups, respectively. Forty-one patients were lost during the follow-up. The eradication rates were 71.6%, 84.2%, and 80.5% (P = .106) by ITT, and 84.1%, 94.9%, and 92.5% (P = .028) by PP analysis in the 7-, 10-, and 14-day groups, respectively. The 10-day regimen showed significantly higher eradication rates than the 7-day regimen in both ITT (P = .024) and PP (P = .018) analyses. However, there were no significant differences in eradication rates between the 10- and 14-day groups in either ITT (P = .667) or PP (P = .537) analysis. Adverse event incidence was comparable among the groups (P = .835). Treatment with BQT for 10 days was as effective as 14 days without increasing the adverse events.