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Purpose: We investigated the relationship between body mass index (BMI), radiological body composition, and survival outcomes in patients with metastatic renal cell carcinoma (mRCC) underwent first-line immune checkpoint inhibitor (ICI)-based therapy. Methods: Analyzing data from 102 patients treated between November 2019 and March 2023, pre-treatment computed tomography (CT) scans assessed fat and muscle areas. BMI and body composition indices were examined, including skeletal muscle index, subcutaneous fat index (SFI), visceral fat index, and total fat index. Kaplan-Meier curves and Log rank tests compared progression-free survival (PFS) and overall survival (OS), while multivariable Cox proportional regression analysis was performed to identify the variables significantly associated with survival outcomes. Results: 54 patients (52.9%) experienced disease progression, and 26 (25.5%) died during a median follow-up of 17.4 months. High SFI was significantly associated with improved OS (p = 0.018) but not PFS (p = 0.090). Multivariable analysis confirmed the positive impact of high SFI on OS (adjusted HR: 0.37, p = 0.029) and suggested a trend towards improved PFS (adjusted HR: 0.61, p = 0.088). Notably, in the ipilimumab + nivolumab subgroup, high SFI significantly correlated with both PFS and OS (p = 0.047 and p = 0.012, respectively). Conclusion: High SFI predicts favorable OS in patients with mRCC receiving first-line ICI-based therapy, especially patients treated with ipilimumab + nivolumab displayed a significant association between high SFI and favorable PFS and OS.
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Vibrio parahaemolyticus is a major seafood-borne zoonotic pathogen that causes gastroenteritis in humans and acute hepatopancreatic necrosis disease (AHPND) in shrimp. In this study, we isolated and characterized Vibrio phage vB_VpM-pA2SJ1, which infects clinical and AHPND-associated strains of V. parahaemolyticus. The phage genome is a linear dsDNA 51,054 bp in length with a G + C content of 43.7%, and it contains 89 open reading frames. Genome comparisons revealed basal similarity to other Vibrio phages, particularly Vibrio phage vB_VpP_1, with 84.2% identity and 46% coverage. Phylogenetic analysis based on the whole genome, the terminase large subunit, and the major capsid protein revealed that phage vB_VpM-pA2SJ1 did not cluster with other known phage families, thus indicating its uniqueness.
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Bacteriófagos , Composición de Base , Genoma Viral , Sistemas de Lectura Abierta , Filogenia , Vibrio parahaemolyticus , Vibrio parahaemolyticus/virología , Vibrio parahaemolyticus/genética , Bacteriófagos/genética , Bacteriófagos/aislamiento & purificación , Bacteriófagos/clasificación , Animales , Penaeidae/virología , Penaeidae/microbiología , Vibriosis/microbiología , Vibriosis/virología , Vibriosis/veterinaria , Hepatopáncreas/virología , Hepatopáncreas/microbiología , Hepatopáncreas/patología , ADN Viral/genéticaRESUMEN
BACKGROUND: The prevalence of type 1 diabetes (T1D) is increasing worldwide, with a much higher proportion of adult patients. However, achieving stable glycemic control is difficult in these patients. OBJECTIVE: After periodic implementation of structured education for patients with T1D through the Home and Self-Care Program, a pilot home health care project promoted by the Korean government, we evaluated the program's effects on glycemic control. METHODS: This study was conducted from April 2020 to March 2023. We analyzed 119 participants with T1D aged >15 years. Nursing and nutrition education were provided separately up to 4 times per year, with physician consultation up to 6 times per year. A distinguishing feature of this study compared with previous ones was the provision of remote support using a general-purpose smartphone communication app offered up to 12 times annually on an as-needed basis to enhance the continuity of in-person education effects. Patients were followed up on at average intervals of 3 months for up to 24 months. The primary end point was the mean difference in glycated hemoglobin (HbA1c) at each follow-up visit from baseline. For continuous glucose monitoring (CGM) users, CGM metrics were also evaluated. RESULTS: The mean HbA1c level of study participants was 8.6% at baseline (mean duration of T1D 10.02, SD 16.10 y). The HbA1c level reduction in participants who received at least 1 structured educational session went from 1.63% (SD 2.03%; P<.001; adjustment model=1.69%, 95% CI 1.24%-2.13% at the first follow-up visit) to 1.23% (SD 1.31%; P=.01; adjustment model=1.28%, 95% CI 0.78%-1.79% at the eighth follow-up visit). In the adjustment model, the actual mean HbA1c values were maintained between a minimum of 7.33% (95% CI 7.20%-7.46% at the first follow-up visit) and a maximum of 7.62% (95% CI 7.41%-7.82% at the sixth follow-up visit). Among CGM users, after at least 1 session, the mean time in the target range was maintained between 61.59% (adjusted model, 95% CI 58.14%-65.03% at the second follow-up visit) and 54.7% (95% CI 50.92%-58.48% at the eighth follow-up visit), consistently staying above 54.7% (corresponding to an HbA1c level of <7.6%). The mean time below the target range (TBR) also gradually improved to the recommended range (≤4% for TBR of <70 mg/dL and ≤1% for TBR of <54 mg/dL). CONCLUSIONS: The Home and Self-Care Program protocol for glycemic control in patients with T1D is effective, producing significant improvement immediately and long-term maintenance effects, including on CGM indexes.
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Diabetes Mellitus Tipo 1 , Hemoglobina Glucada , Control Glucémico , Autocuidado , Humanos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/terapia , Femenino , Masculino , Adulto , Control Glucémico/métodos , Autocuidado/métodos , Hemoglobina Glucada/análisis , Persona de Mediana Edad , Estudios de Cohortes , Automonitorización de la Glucosa Sanguínea/métodos , Servicios de Atención de Salud a Domicilio , República de Corea , Glucemia , Proyectos Piloto , Adulto JovenRESUMEN
Sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors, antidiabetic drugs that reduce blood sugar levels by inhibiting glucose reabsorption in the renal proximal tubules, also ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of SGLT2 inhibition on hepatic steatosis and nonalcoholic steatohepatitis (NASH) using an in vitro model of NAFLD progression. HepG2 cells and a coculture of Hepa1c1c7 and Raw 264.7 cells were treated with 400 µM palmitic acid (PA), followed by treatment with or without 10 µM empagliflozin and dapagliflozin. In HepG2 cells, PA increased hepatic lipid accumulation, the expression of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß), exocytosis mediators (VAMP3 and SNAP23), and ER stress markers (GRP78, PERK, IRE1α, ATF6, ATF4, and CHOP), and the gene and protein expression of CD36. SGLT2 inhibitors reversed the effects of PA. SGLT2 inhibition via siRNA reduced proinflammatory-cytokine gene expression in thapsigargin-treated HepG2 cells. Transfection with CD36 siRNA reversed the elevated ATF4 and CHOP expression in PA-treated HepG2 cells. SGLT2 inhibition via an SGTL2 inhibitor and SGLT2 siRNA reduced CD36, Tnf-α, Il-6, Il-1ß, Vamp2, Snap23, Atf4, and Chop expression in the PA-treated Hepa1c1c7-Raw 264.7 cell coculture and suppressed Tnf-α release in the Hepa1c1c7-Raw 264.7 cell coculture treated with lipopolysaccharide and PA. These findings indicate that SGLT2 inhibitors inhibited NAFLD progression by reducing hepatic lipid accumulation and inflammation.
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Monzogranite is known for its high surface area and cation exchange capacity, which play a crucial role in ameliorating the challenges by enhancing nutrient adsorption and facilitating nutrient availability during the weaning period. Weaned crossbred piglets (Duroc × Yorkshire × Landrace), initially weighing 5.36 ± 0.26 kg, were allocated into four treatments with 6 replicates each (10 pigs per replicate). The treatments encompassed CON (basal diet), Z0.1 (0.1% monzogranite supplementation in basal diet), Z0.2 (0.2% monzogranite supplementation), and Z0.3 (0.3% monzogranite supplementation). In phase 1, a linear increase in total average daily gain (ADG) was observed across treatment groups, with a concomitant linear increase in ADG and gain-to-feed ratio (G/F). The overall results showed a linear increase in ADG and G/F. A linear decrease in aspartate aminotransferase and lactate dehydrogenase levels was observed across treatment groups. Conversely, no significant differences were noted in the levels of albumin, alkaline phosphatase, alanine aminotransferase, high-density lipoprotein, low-density lipoprotein, total cholesterol, blood urea nitrogen, triglycerides, and gamma-glutamyl transferase among the treatment groups. Faecal scoring indicated a linear reduction in scores at Day 7 among the treatment groups. However, no significant differences were observed at Days 14 and 28. The assessment of immunoglobulins demonstrated a significant increase in both immunoglobulin G and immunoglobulin A levels in the Z0.1 treatment group compared to the CON. In both phase 1 and phase 2, a linear decrease in cortisol levels was evident. In conclusion, a linear increase in total ADG and G/F during phase 1, sustained across both phases, suggests monzogranite potential to enhance growth performance. Moreover, stress mitigation was shown through a consistent linear decrease in cortisol levels across phases. These findings underscore monzogranite multifaceted impact, emphasizing its potential as a dietary supplement to enhance growth, liver health, and stress resilience in weanling pigs.
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BACKGROUND: Therapeutic advancements based on immuno-oncology combinations have revolutionized the management of patients with renal cell carcinoma. However, patients who have progressive disease as the best response, "primary refractory" (Pref), face dismal outcomes. OBJECTIVE: Our multicenter retrospective real-world study aims to assess the prevalence and clinicopathological characteristics of Pref patients. METHODS: This study collected data from 72 centers across 22 countries (1709 patients), involving patients aged ≥18 years with metastatic clear cell renal cell carcinoma. All patients were treated with first-line immune-oncology combinations. Data included patient demographics, histology, metastatic sites, and treatment responses. Radiological assessments followed Response Evaluation Criteria in Solid Tumors version 1.1. Statistical analyses employed Kaplan-Meier method, Cox proportional hazard models, logistic regression, and the receiver operating characteristic curve. RESULTS: In our study, the Pref rate was 19%. Nivolumab/ipilimumab showed the highest Pref rate (27%), while pembrolizumab/lenvatinib exhibited the lowest (10%). Primary refactory patients demonstrated significantly lower median overall survival (7.6 months) compared with non-Pref patients (55.7 months), p < 0.001. At the multivariate analysis, nephrectomy, sarcomatoid de-differentiation, intermediate/poor International Metastatic RCC Database Consortium risk, and bone and brain metastases emerged as significant predictors of overall survival for Pref patients with renal cell carcinoma. Logistic regression showed a significant relationship between liver metastases, intermediate/poor International Metastatic RCC Database Consortium risk, and no surgery and an increased risk of Pref. This study presents limitations, mainly because of its retrospective design. CONCLUSIONS: The ARON-1 study provides valuable insights into Pref patients, emphasizing the challenges of this precociously resistant subgroup. Identified predictors could guide risk stratification, aiding clinicians in tailored therapeutic approaches.
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We aimed to determine the in vitro and in vivo synergistic antiallergic effect of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC), and the antiallergic rhinitis (AR) properties of guaijaverin-rich Psidium guajava and EGCG-rich Camellia sinensis (ILS-F-2301). GEC showed synergistic inhibition of ß-hexosaminidase by 4.20% and interleukin (IL)-4, -5, and -13 by 4.08%, 0.67%, and 4.71%, respectively, while increasing interferon (IFN)-γ by 12.43%, compared with EGCG only. In addition, 50 µg/mL of ILS-F-2301 inhibited ß-hexosaminidase release, and inhibited IL-4, -5, and -13 by 61.54%, 58.79%, and 59.25%, respectively, while increasing IFN-γ (showing 133.14% activation). Moreover, 50 µg/mL of ILS-F-2301 suppressed p-STAT6 and GATA3, while p-STAT1 and T-bet increased, and 0.039 µg/mL of guaijaverin or 5.275 µg/mL of EGCG modulated T helper (Th)1- and Th2-related proteins. These data suggested that guaijaverin and EGCG in ILS-F-2301 was the main active compound involved in Th1/Th2 modulation. In the AR mouse model, the administration of ILS-F-2301 inhibited ovalbumin (OVA)-specific IgE, histamine in serum; it also inhibited IL-4 and -5 by 28.23% and 47.15%, respectively, while increasing IFN-γ (showing 37.11% activation), compared with OVA/Alu-treated mice. Taken together, our findings suggest that ILS-F-2301 is a functional food for alleviating anti-AR.
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Camellia sinensis , Catequina , Factor de Transcripción GATA3 , Ratones Endogámicos BALB C , Factor de Transcripción STAT1 , Factor de Transcripción STAT6 , Proteínas de Dominio T Box , Células TH1 , Células Th2 , Animales , Catequina/análogos & derivados , Catequina/farmacología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Ratones , Proteínas de Dominio T Box/metabolismo , Proteínas de Dominio T Box/genética , Células TH1/efectos de los fármacos , Células TH1/inmunología , Factor de Transcripción STAT6/metabolismo , Camellia sinensis/química , Antialérgicos/farmacología , Psidium/química , Femenino , Extractos Vegetales/farmacología , Citocinas/metabolismo , Humanos , Interferón gamma/metabolismo , Interferón gamma/inmunología , Inmunoglobulina E/inmunología , Interleucina-4/inmunología , Interleucina-4/metabolismo , Rinitis Alérgica/tratamiento farmacológico , Transducción de Señal/efectos de los fármacosRESUMEN
Drosophila TrpA1 (transient receptor potential ankyrin 1) transcripts are alternatively spliced at two distinct sites each with a choice of mutually exclusive exons. The first site determines exon1 encoding the amino terminus to produce either nucleophile-, electrophile- and noxious temperature-gated TRPA1(A) or electrophile- and innocuous warmth-gated TRPA1(B). The second site selects for exon10, resulting in TrpA1 variants with either exon10a or exon10b encoding a domain between the N-terminal ankyrin repeats and the transmembrane segments. Although unbiased assembly would generate TRPA1 with four different domain combinations, the functional impact of these alternative domains remains to be thoroughly examined. Here, we find that there is a relatively strong linkage in mRNA splicing between the two sites in case of TrpA1(B), but not TrpA1(A), transcripts. Our semi-quantitative assay, consisting of reverse transcription polymerase chain reaction (RT-PCR) and Sanger sequencing, revealed that exon10b is little coupled with TrpA1(B) transcripts, suggesting that only three isoforms, TRPA1(A)-exon10a [denoted as TRPA1(A)], TRPA1(A)-exon10b [TRPA1(A)10b] and TRPA1(B)-exon10a [TRPA1(B)], are present at detectable levels using our method. Interestingly, heterologously expressed TRPA1(A)10b showed elevated sensitivity to low concentrations of N-methyl maleimide (NMM), a cysteine-modifying electrophile, compared with other isoforms. Equivalent isoforms in malaria-transmitting Anopheles gambiae displayed a similar pattern of isoform-dependent NMM dose dependences, suggesting that the chemosensory regulation by selective domain assembly is conserved in insect TRPA1s. Thus, alternative RNA splicing of exon10 is coordinated in conjunction with the first exons, regulating chemical sensitivity of insect TRPA1s.
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STUDY DESIGN: Retrospective study. OBJECTIVE: To analyze the risk factors for bony proximal junctional failure (B-PJF) and ligamentous PJF (L-PJF) separately after adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: Despite numerous studies about the risk factors of PJF, it remains unclear whether same risk factors can be applied to both B-PJF and L-PJF. METHODS: Patients who underwent corrective surgery from low thoracic level (T9-T12) to pelvis with minimum follow-up duration of two years were included in this study. Patients with PJF were divided into two groups according to the involvement of bony structure: B-PJF and L-PJF. The control group was created using patients who did not develop PJF for ≥2 years postoperatively (no-PJF group). Risk factors were analyzed by comparing various clinical and radiographic parameters between no PJF versus B-PJF group and between no PJF versus L-PJF groups. RESULTS: The final study cohort comprised 240 patients. The mean age was 68.7 years, and there were 205 women (85.4%). On average, 8.1 levels were fused. PJF developed in 103 patients, with 70 (68.0%) in the B-PJF group and 33 (32.0%) in the L-PJF group. Stepwise logistic regression analyses revealed that older age (odds ratio [OR]=1.088), higher body mass index (BMI) (OR=1.161), osteoporosis (OR=3.293), greater postoperative lumbar distribution index (OR=1.032), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis (OR=3.964) were significant risk factors for B-PJF. Meanwhile, no use of transverse process (TP) hook was the single risk factor for L-PJF (OR=4.724). CONCLUSIONS: Understanding the difference in risk factors between B-PJF and L-PJF will facilitate the optimization of surgical outcome for patients with ASD. Appropriate correction of sagittal malalignment along with use of TP hook is advisable to mitigate both B-PJF and L-PJF development.
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STUDY DESIGN: Retrospective study. OBJECTIVES: To validate the sagittal age-adjusted score (SAAS) in predicting proximal junctional kyphosis/failure (PJK/F) and good clinical outcomes following adult spinal deformity (ASD) surgery. SUMMARY OF BACKGROUND DATA: SAAS is a relatively new assessment system that incorporates age-adjusted sagittal parameters of pelvic incidence (PI) - lumbar lordosis (LL), pelvic tilt (PT), and T1 pelvic angle (TPA) to predict the PJK/F. External validation is required to verify its clinical usefulness. METHODS: We included patients with ASD undergoing ≥5-level fusion including the sacrum or pelvis. SAAS was calculated based on the scores of the three components: PI-LL, PT, and TPA. PJK/F rates and clinical outcomes were compared among the correction categories (undercorrection, matched correction, and overcorrection) for the SAAS as well as for each of the three components. PJK/F rates were compared according to the correction groups of the sagittal components and total SAAS using the chi-square test. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive ability of overcorrection to develop PJK/F for the three sagittal parameters and SAAS. PROMs at final follow-up were compared among correction groups using ANOVA with Bonferroni post-hoc corrections. RESULTS: A total 411 patients were included in the study (mean age: 69.3 y, mean body mass index: 25.9 kg/m2, total levels fused: 7.7 levels, and follow-up duration: 43.3 mo). Postoperative SAAS categories were as follow: undercorrection (13.4%), matched correction (30.2%), and overcorrection (56.4%). The PJK/F rates were significantly higher in the overcorrection group relative to PI-LL component (P=0.001) as well as SAAS (P=0.038) compared to undercorrection or matched correction groups. The clinical outcomes were best in patients who achieved matched correction relative to PI-LL component as well as SAAS compared to the other correction groups. However, the differentiating power of clinical outcomes across the correction categories was greater in the PI-LL component than in the SAAS. CONCLUSION: This study validated the efficacy of SAAS system to differentiate PJK/F development and good clinical outcomes. However, its differentiating power seems to be largely attributable to the function of the PI-LL component, as the PI-LL correction status better predicted PJK/F risk and clinical outcomes than SAAS.
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Our aim in the current study was to determine the in vitro and in vivo synergistic antiinflammatory and antiallergic effect associated with the IL-12 production of guaijaverin and epigallocatechin gallate (EGCG) complex (GEC) and ILS-F-2301 (2:8 extract of Psidium guajava and Camellia sinensis). Compared to EGCG alone, GEC showed synergistic inhibition of nitric oxide (NO), inducible NO synthase, and cyclooxygenase-2 by 3.8, 5.1, and 4.1%, respectively. The downregulation of interleukin-12 (IL-12) by 2,4-dinitrophenyl-human serum albumin conjugate/DNP-immunoglobulin E or ovalbumin (OVA) was synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of downregulation of IL-12 in plasma increased by 100 mg/kg with ILS-F-2301 (28.7%) when compared to the OVA/Alu-treated group. Also, GEC synergistically increased by GEC by about 7.5% or 5.4% compared to EGCG alone. The level of down and cyclooxygenase C synergistically inhibited p-Akt, PI3K, mTOR, p-STAT6, and GATA3 by 4.9%, 4.1%, 19.2%, 23.8%, and 35.3%, respectively, while increasing the expressions of p-STAT1 and T-bet (showing 53.3% and 9.4% activation) when compared to EGCG alone. In an allergenic rhinitis mouse model, 100 mg/kg of ILS-F-2301 was shown to inhibit p-Akt, PI3K, mTOR, p-c-Jun N-terminal kinase (p-JNK), p-extracellular signal-regulated kinase (p-ERK), and p-p38 by 23.3%, 43.8%, 17.2%, 32.2%, 29.1%, and 41.8% when compared to the OVA/Alu-sensitized group. Taken together, our findings suggest that ILS-F-2301 may have potential as a functional food for alleviating antiallergic rhinitis.
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This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.
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Background: Treating wide-neck bifurcated cerebral aneurysms (WNBAs) using various techniques and new devices has shown favorable outcomes. However, endovascular coiling can be technically challenging when the aneurysm neck is incorporated into the parent vessel. Furthermore, although recent research has reported favorable outcomes of Neuroform Atlas stent (NAS)-assisted coiling, broad inclusion criteria have hampered precise evaluations of their effectiveness and safety for treating complex WNBAs. Therefore, this study evaluated whether the use of a single NAS is a safe and effective approach for treating complex WNBAs. Methods: We treated 76 complex WNBAs (unruptured, n = 49; ruptured, n = 27) using single NAS-assisted coil embolization and retrospectively analyzed the clinical and angiographic outcomes. Results: In a cohort of 68 patients (mean age, 58.3 ± 11.6 years; males n = 20, 29.4%; females, n = 48, 70.6%), 76 stents were successfully delivered to the target aneurysms, yielding a technical success rate of 98.6%. Complete occlusion was evident in 59 (77.6%) of 76 aneurysms, with neck remnants found in 16 (21.1%) and partial occlusion in 1 (1.3%). Treatment-related morbidities comprised one branch occlusion and one parenchymal hemorrhage. However, no new neurological symptoms of unruptured aneurysms were evident at discharge. The outcomes of 20 of the 27 ruptured aneurysms were favorable (Glasgow Outcome Scale scores of 4 or 5) at the final follow-up assessment (mean 12.2 [6-29] months), except for one initial subarachnoid hemorrhage. Post-treatment angiography revealed complete occlusion in 89.1%, neck remnants in 7.8%, and incomplete occlusion in 3.1% of the aneurysms. Approximately 88.2% of the patients were assessed at least once by follow-up diagnostic or magnetic resonance angiography (mean, 12.5 ± 4.3 [range, 6-29] months), with five (7.8%) minor and two (3.1%) major recurrences. Conclusion: A single NAS is safe and effective for treating WNBAs incorporated into parent vessels.
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The operation of microfluidic devices requires precise and constant fluid flow. Microfluidic systems in low-resource settings require a portable, inexpensive, and electricity-free pumping approach due to the rising demand for microfluidics in point-of-care testing (POCT). Open-source alternatives, employing 3D printing and motors, offer affordability. However, using motors require electrical power, which often relies on external sources, hindering the on-site use of open-source pumps. This study introduces a spring-driven, 3D-printed syringe pump, eliminating the need for an external power source. The syringe pump is operated by the flat spiral spring's torque. By manually winding up the mainspring, the syringe pump can be operated without electricity. Various flow rates can be achieved by utilizing different syringe sizes and choosing the right gear combinations. All the parts of the syringe pump can be fabricated by 3D printing, requiring no additional components that require electricity. It operates by winding a mainspring and is user-friendly, allowing flow rate adjustments by assembling gears that modulate syringe plunger pushing velocity. The fabrication cost is $25-30 and can be assembled easily by following the instructions. We expect that the proposed syringe pump will enable the utilization of microfluidic technologies in resource-limited settings, promoting the adoption of microfluidics. Detailed information and results are available in the original research paper (https://doi.org/10.1016/j.snb.2024.135289).
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BACKGROUND: Despite numerous studies identifying risk factors for proximal junctional failure (PJF), risk factors for recurrent PJF (R-PJF) are still not well established. Therefore, we aimed to identify the risk factors for R-PJF following adult spinal deformity (ASD) surgery. METHODS: Among 479 patients who underwent ≥5-level fusion surgery for ASD, the focus was on those who experienced R-PJF at any time or did not experience R-PJF during a follow-up duration of ≥1 year. PJF was defined as a proximal junctional angle (PJA) ≥28° plus a difference in PJA ≥22° or performance of revision surgery regardless of PJA degree. The patients were divided into 2 groups according to R-PJF development: no R-PJF and R-PJF groups. Risk factors were evaluated focusing on patient, surgical, and radiographic factors at the index surgery as well as at the revision surgery. RESULTS: Of the 60 patients in the final study cohort, 24 (40%) experienced R-PJF. Significant risk factors included greater postoperative sagittal vertical axis (OR = 1.044), overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis (PI-LL; OR = 7.794) at the index surgery, a greater total sum of the proximal junctional kyphosis severity scale (OR = 1.145), and no use of the upper instrumented vertebra cement (OR = 5.494) at the revision surgery. CONCLUSIONS: We revealed that the greater postoperative sagittal vertical axis and overcorrection relative to age-adjusted pelvic incidence-lumbar lordosis at the index surgery, a greater proximal junctional kyphosis severity scale score, and no use of upper instrumented vertebra cement at the revision surgery were significant risk factors for R-PJF. CLINICAL RELEVANCE: To reduce the risk of R-PJF after ASD surgery, avoiding under- and overcorrection during the initial surgery is recommended. Additionally, close assessment of the severity of PJF with timely intervention is crucial, and cement augmentation should be considered during revision surgery.
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BACKGROUND: Evaluation of hospital-specific antimicrobial use is necessary for successful national antimicrobial stewardship. This study aimed to identify antimicrobial use in long-term care hospitals (LCHs) in Korea. METHODS: We conducted a multicentre retrospective study to evaluate the prescription patterns and appropriateness of antimicrobials in 20 LCHs in Korea. The medical record data of hospitalised patients who were newly prescribed antimicrobials at each hospital were collected manually between 10 July and 31 October 2023 to evaluate the appropriateness of antimicrobial use. RESULTS: The prevalence of antimicrobial prescriptions was 8.9% (365/4,086) and 10.3% (402/3,892) on July 12, 2023 and October 18, 2023, respectively. A total of 885 antimicrobials were prescribed to 740 patients. Among the antimicrobials, third- or fourth-generation cephalosporins (31.9%) represented the most prescribed antimicrobial class. A large majority of antimicrobials (855/885, 96.6%) were prescribed for the treatment of infectious diseases; however, only 37.7% (322/855) of antimicrobials were appropriately prescribed for infections. The route of administration, dosage, and prescribed antimicrobial were appropriate in 99.6% (852/855), 56.1% (480/855), and 62.0% (530/855) of cases, respectively. In total, 35.2% (252/715) of patients were appropriately prescribed antimicrobials. The diagnosis of infectious diseases was appropriate for 52.9% (472/892) of the cases. Of the 5, 15, and 10 antimicrobials used for surgical site infection prophylaxis, medical prophylaxis, and other purposes, respectively, none were appropriately used. CONCLUSION: The proportion of antimicrobials used appropriately is low in Korean LCHs. These data highlight the importance of establishing antimicrobial stewardship in LCHs.
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BACKGROUND CONTEXT: While numerous studies have been conducted on proximal junctional failure (PJF), the clinical significance of acute and delayed PJF remains poorly understood. PURPOSE: The primary object of this study is to investigate the risk factors separately for acute and delayed PJF. Secondly, we aim to assess the incidence of each failure mode and their clinical consequences in relation to acute and delayed PJF. STUDY DESIGN/SETTING: Retrospective comparative study. PATIENT SAMPLE: Patients aged ≥60 years who underwent deformity correction with ≥5-level fusion to sacrum. OUTCOME MEASURES: Risk factor, failure modes, and patient-reported outcome measure (PROM). METHODS: Acute PJF is defined as PJF occurring within 6 months, while delayed PJF occurring after 6 months. Risk factors were analyzed by comparing various clinical and radiographic parameters among 3 groups: no, acute, and delayed PJF groups. The failure modes, including soft tissue failure, vertebral fracture, fixation failure, and myelopathy, were compared among these groups. The clinical subsequences after PJF development were evaluated by assessing the change in proximal junctional angle (PJA), revision rate, and patient-reported outcome measure (PROM). RESULTS: A study cohort of 363 patients was included in the analysis. Among them, 156 patients experienced PJF, with 87 patients (55.8%) in the acute PJF group and 69 patients (44.2%) in the delayed PJF group. Multivariate analyses showed that older age (Odds ratio [OR] = 1.057, 95% confidence interval [CI] = 1.002-1.118), osteoporosis (OR=2.149, 95% CI = 1.074-4.300), high American Society of Anesthesiology ASA score (OR=2.150, 95% CI = 1.089-4.245), and overcorrection relative to the age-adjusted pelvic incidence - lumbar lordosis target (OR=4.031, 95% CI = 1.962-8.280) were identified as risk factors for the development of acute PJF. On the other hand, a high body mass index (OR=1.150, 95% CI = 1.049-1.251) and an uppermost instrumented vertebra located at ≤T10 (OR=2.267, 95% CI = 1.205-4.268) were found to be associated with delayed occurrence of PJF. No radiographic parameters were found to be related to the development of delayed PJF. In terms of failure modes, vertebral fracture and fixation failure were more commonly observed in acute PJF, while soft tissue failure and myelopathy were more predominant in delayed PJF. The clinical course was more aggressive in the acute PJF group compared to the delayed PJF group, as evidenced by a greater increase in PJA, a higher revision rate, and worse PROM. CONCLUSIONS: This study demonstrated different risk factors between the acute and delayed PJF. It was found that overcorrection relative to the age-adjusted PI-LL target increased the risk of acute PJF, but had no impact on the development of delayed PJF. Therefore, a different surgical strategy needs to be established to mitigate both acute and delayed PJF.
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This study investigated the relationship between fundamental movement skills (FMSs) and health-related fitness (HRF) among first and second graders in South Korean elementary schools. It aimed to provide foundational data for developing physical education programs tailored to the motor development stages and fitness levels of younger elementary school students. This study utilized secondary data from the physical activity competence evaluation conducted by the Health Physical Activity Institute (HPAI). In October 2023, the HPAI evaluated the fundamental movement skills (jumping, running, hopping, static balance, dynamic balance, overhand throwing, and kicking) and health-related fitness (muscular strength, cardiorespiratory endurance, and flexibility) of 291 first and second-grade students. The collected data were analyzed through frequency and multiple regression analyses performed using SPSS software. The results revealed that higher scores in jumping and hopping are associated with greater muscular strength, cardiorespiratory endurance, and flexibility. Running had no significant effect on HRF elements. Higher scores in static balance (i.e., that used in single-leg stance) were associated with increased muscular strength, cardiorespiratory endurance, and flexibility, but dynamic balance (balance beam walking) did not have a significant effect. Higher scores in overhand throwing were associated with greater muscular strength and cardiorespiratory endurance, but kicking did not show a significant association. Overall, these findings emphasize the importance of prioritizing jumping and static balance in physical education for the well-rounded health development of first and second graders. Based on the results derived from this study, it is expected to serve as a theoretical basis for including "jumping" and "static balance" in the first and second grade curriculum of elementary schools, thereby providing essential guidance.
RESUMEN
BACKGROUND: Belzutifan, a hypoxia-inducible factor 2α inhibitor, showed clinical activity in clear-cell renal-cell carcinoma in early-phase studies. METHODS: In a phase 3, multicenter, open-label, active-controlled trial, we enrolled participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies and randomly assigned them, in a 1:1 ratio, to receive 120 mg of belzutifan or 10 mg of everolimus orally once daily until disease progression or unacceptable toxic effects occurred. The dual primary end points were progression-free survival and overall survival. The key secondary end point was the occurrence of an objective response (a confirmed complete or partial response). RESULTS: A total of 374 participants were assigned to belzutifan, and 372 to everolimus. At the first interim analysis (median follow-up, 18.4 months), the median progression-free survival was 5.6 months in both groups; at 18 months, 24.0% of the participants in the belzutifan group and 8.3% in the everolimus group were alive and free of progression (two-sided P = 0.002, which met the prespecified significance criterion). A confirmed objective response occurred in 21.9% of the participants (95% confidence interval [CI], 17.8 to 26.5) in the belzutifan group and in 3.5% (95% CI, 1.9 to 5.9) in the everolimus group (P<0.001, which met the prespecified significance criterion). At the second interim analysis (median follow-up, 25.7 months), the median overall survival was 21.4 months in the belzutifan group and 18.1 months in the everolimus group; at 18 months, 55.2% and 50.6% of the participants, respectively, were alive (hazard ratio for death, 0.88; 95% CI, 0.73 to 1.07; two-sided P = 0.20, which did not meet the prespecified significance criterion). Grade 3 or higher adverse events of any cause occurred in 61.8% of the participants in the belzutifan group (grade 5 in 3.5%) and in 62.5% in the everolimus group (grade 5 in 5.3%). Adverse events led to discontinuation of treatment in 5.9% and 14.7% of the participants, respectively. CONCLUSIONS: Belzutifan showed a significant benefit over everolimus with respect to progression-free survival and objective response in participants with advanced clear-cell renal-cell carcinoma who had previously received immune checkpoint and antiangiogenic therapies. Belzutifan was associated with no new safety signals. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; LITESPARK-005 ClinicalTrials.gov number, NCT04195750.).
Asunto(s)
Antineoplásicos , Carcinoma de Células Renales , Everolimus , Indenos , Neoplasias Renales , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antineoplásicos/uso terapéutico , Antineoplásicos/efectos adversos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/mortalidad , Everolimus/administración & dosificación , Everolimus/efectos adversos , Estimación de Kaplan-Meier , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/mortalidad , Supervivencia sin Progresión , Indenos/administración & dosificación , Indenos/efectos adversos , Administración Oral , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/antagonistas & inhibidores , Adulto Joven , Resultado del TratamientoRESUMEN
We propose FD3, a fundus image enhancement method based on direct diffusion bridges, which can cope with a wide range of complex degradations, including haze, blur, noise, and shadow. We first propose a synthetic forward model through a human feedback loop with board-certified ophthalmologists for maximal quality improvement of low-quality in-vivo images. Using the proposed forward model, we train a robust and flexible diffusion-based image enhancement network that is highly effective as a stand-alone method, unlike previous diffusion model-based approaches which act only as a refiner on top of pre-trained models. Through extensive experiments, we show that FD3 establishes superior quality not only on synthetic degradations but also on in vivo studies with low-quality fundus photos taken from patients with cataracts or small pupils. To promote further research in this area, we open-source all our code and data used for this research at https://github.com/heeheee888/FD3.