ABSTRACT
Peritoneal dialysis is a common treatment for end-stage renal disease, but complications often force its discontinuation. Preventive treatments for peritoneal inflammation and fibrosis are currently lacking. Cyclo(His-Pro) (CHP), a naturally occurring cyclic dipeptide, has demonstrated protective effects in various fibrotic diseases, yet its potential role in peritoneal fibrosis (PF) remains uncertain. In a mouse model of induced PF, CHP was administered, and quantitative proteomic analysis using liquid chromatography-tandem mass spectrometry was employed to identify PF-related protein signaling pathways. The results were further validated using human primary cultured mesothelial cells. This analysis revealed the involvement of histone deacetylase 3 (HDAC3) in the PF signaling pathway. CHP administration effectively mitigated PF in both peritoneal tissue and human primary cultured mesothelial cells, concurrently regulating fibrosis-related markers and HDAC3 expression. Moreover, CHP enhanced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) while suppressing forkhead box protein M1 (FOXM1), known to inhibit Nrf2 transcription through its interaction with HDAC3. CHP also displayed an impact on spleen myeloid-derived suppressor cells, suggesting an immunomodulatory effect. Notably, CHP improved mitochondrial function in peritoneal tissue, resulting in increased mitochondrial membrane potential and adenosine triphosphate production. This study suggests that CHP can significantly prevent PF in peritoneal dialysis patients by modulating HDAC3 expression and associated signaling pathways, reducing fibrosis and inflammation markers, and improving mitochondrial function.
Subject(s)
Histone Deacetylases , Peritoneal Fibrosis , Animals , Histone Deacetylases/metabolism , Histone Deacetylases/genetics , Peritoneal Fibrosis/metabolism , Peritoneal Fibrosis/prevention & control , Peritoneal Fibrosis/pathology , Mice , Humans , Male , Mice, Inbred C57BL , Signal Transduction/drug effects , Peritoneal Dialysis/adverse effects , Peritoneum/pathology , Peritoneum/metabolismABSTRACT
This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.
Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Humans , Animals , Mice , Mice, Inbred C57BL , Ligands , Kidney , Epithelial Cells , Renal Artery , Hypoxia , Receptors, CCR6/genetics , Chemokine CCL20/geneticsABSTRACT
BACKGROUND: Mycobacterium avium complex (MAC), including Mycobacterium intracellulare is a member of slow-growing mycobacteria and contributes to a substantial proportion of nontuberculous mycobacterial lung disease in humans affecting immunocompromised and elderly populations. Adaptation of pathogens in hostile environments is crucial in establishing infection and persistence within the host. However, the sophisticated cellular and molecular mechanisms of stress response in M. intracellulare still need to be fully explored. We aimed to elucidate the transcriptional response of M. intracellulare under acidic and oxidative stress conditions. RESULTS: At the transcriptome level, 80 genes were shown [FC] ≥ 2.0 and p < 0.05 under oxidative stress with 10 mM hydrogen peroxide. Specifically, 77 genes were upregulated, while 3 genes were downregulated. In functional analysis, oxidative stress conditions activate DNA replication, nucleotide excision repair, mismatch repair, homologous recombination, and tuberculosis pathways. Additionally, our results demonstrate that DNA replication and repair system genes, such as dnaB, dinG, urvB, uvrD2, and recA, are indispensable for resistance to oxidative stress. On the contrary, 878 genes were shown [FC] ≥ 2.0 and p < 0.05 under acidic stress with pH 4.5. Among these genes, 339 were upregulated, while 539 were downregulated. Functional analysis highlighted nitrogen and sulfur metabolism pathways as the primary responses to acidic stress. Our findings provide evidence of the critical role played by nitrogen and sulfur metabolism genes in the response to acidic stress, including narGHIJ, nirBD, narU, narK3, cysND, cysC, cysH, ferredoxin 1 and 2, and formate dehydrogenase. CONCLUSION: Our results suggest the activation of several pathways potentially critical for the survival of M. intracellulare under a hostile microenvironment within the host. This study indicates the importance of stress responses in M. intracellulare infection and identifies promising therapeutic targets.
Subject(s)
Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection , Humans , Aged , Mycobacterium avium Complex/genetics , Transcriptome , Mycobacterium avium-intracellulare Infection/microbiology , Gene Expression Profiling , Oxidative Stress , Nitrogen , SulfurABSTRACT
BACKGROUND: Modified FOLFIRINOX (mFOLFIRINOX) is one of the standard first-line therapies in borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). However, there is no globally accepted second-line therapy following progression on mFOLFIRINOX. METHODS: Patients with BRPC and LAPC (n = 647) treated with first-line mFOLFIRINOX between January 2017 and December 2020 were included in this retrospective analysis. The details of the treatment outcomes and patterns of subsequent therapy after mFOLFIRINOX were reviewed. RESULTS: With a median follow-up duration of 44.2 months (95% confidence interval [CI], 42.3-47.6), 322 patients exhibited disease progression on mFOLFIRINOX-locoregional progression only in 177 patients (55.0%) and distant metastasis in 145 patients (45.0%). The locoregional progression group demonstrated significantly longer post-progression survival (PPS) than that of the distant metastasis group (10.1 vs. 7.3 months, p = 0.002). In the locoregional progression group, survival outcomes did not differ between second-line chemoradiation/radiotherapy and systemic chemotherapy (progression-free survival with second-line therapy [PFS-2], 3.2 vs. 4.3 months; p = 0.649; PPS, 10.7 vs. 10.2 months; p = 0.791). In patients who received second-line systemic chemotherapy following progression on mFOLFIRINOX (n = 211), gemcitabine plus nab-paclitaxel was associated with better disease control rates (69.2% vs. 42.3%, p = 0.005) and PFS-2 (3.8 vs. 1.7 months, p = 0.035) than gemcitabine monotherapy. CONCLUSIONS: The current study showed the real-world practice pattern of subsequent therapy and clinical outcomes following progression on first-line mFOLFIRINOX in BRPC and LAPC. Further investigation is necessary to establish the optimal therapy after failure of mFOLFIRINOX.
Subject(s)
Adenocarcinoma , Pancreatic Neoplasms , Humans , Pancreatic Neoplasms/pathology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Gemcitabine , Retrospective Studies , Adenocarcinoma/pathology , Fluorouracil/therapeutic use , Leucovorin/therapeutic use , Neoadjuvant Therapy , Disease Progression , Irinotecan , OxaliplatinABSTRACT
Placental site nodules (PSNs) are non-neoplastic remnants of chorionic-type intermediate trophoblastic cells from a previous gestation that form a well-defined single nodule or multiple nodules in the uterine and extrauterine sites. As the cases of PSNs transformed into gestational trophoblastic tumors were described in the literature, "atypical placental site nodules" (APSNs) have been considered as putative transitional lesions between PSNs and gestational trophoblastic tumors. Although histologic criteria and cutoff point of Ki-67 proliferation index for differentiating an APSN from a typical PSN have not been clearly defined, nodules larger than 5 mm with increased cellularity, a corded or nested appearance, marked nuclear atypia, increased mitotic activity, and an increased Ki-67 proliferation index (>5% or >8%) of intermediate trophoblastic cells seem to be accepted as diagnostic criteria for APSNs. However, some of the criteria, including lesion size and histologic features of the trophoblastic cells in the nodule are not only subjective but have features inherent of the intermediate trophoblastic cells of the fetal membrane and a typical PSN. We thought that it is not reasonable to consider them as diagnostic features of APSNs, if not associated with cellular proliferation. We present 2 cases of incidentally identified PSNs that were larger than 10 mm in size with a corded or nested arrangement of trophoblastic cells, which could have been categorized as APSNs according to the currently proposed criteria to discuss whether the currently proposed diagnostic criteria for APSNs are appropriate.
Subject(s)
Gestational Trophoblastic Disease , Pregnancy Complications , Trophoblastic Tumor, Placental Site , Uterine Neoplasms , Female , Pregnancy , Humans , Placenta/pathology , Ki-67 Antigen , Uterine Neoplasms/diagnosis , Uterine Neoplasms/pathology , Pregnancy Complications/pathology , Uterus/pathology , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/pathology , Trophoblastic Tumor, Placental Site/diagnosis , Trophoblastic Tumor, Placental Site/pathologyABSTRACT
The aim of this study was to investigate the pathologic prognostic factors such as tumor cell clusters (TCCs) in the fallopian tube lumen, myometrial invasion patterns, and positive peritoneal cytology (PPC) in women with Stage I endometrial endometrioid carcinoma (EEC). From 2009 to 2020, consecutive patients with Stage I EEC who underwent hysterectomy and bilateral salpingectomy were included. The primary outcome was the recurrence-free survival (RFS) rate, and the clinicopathological factors affecting RFS were analyzed. A total of 765 patients were enrolled. Seventeen patients (2.2%) had TCC in the fallopian tube lumen, and 58 patients showed a microcystic elongated and fragmented pattern (7.6%). PPC was found in 19 patients (2.5%). The median follow-up period was 61.0 months (range: 2.0-149.7). The majority (88.6%) of patients had Stage IA EEC. The 5-year RFS and overall survival rates were 97.5% and 98.5%, respectively. In multivariate analysis for RFS, the significant prognostic factors were lymphovascular invasion (hazard ratio = 4.604; 95% CI: 1.387-15.288; P = 0.013) and grade (grade 2; hazard ratio = 4.949; 95% CI: 1.035-23.654; P = 0.045, and grade 3; hazard ratio = 5.469; 95% CI: 1.435-20.848; P = 0.013). Other pathologic factors including TCC in the fallopian tube lumen, myometrial invasion patterns, PPC, and hormonal status had no prognostic significance. TCC in the fallopian tube lumen, myometrial invasion pattern, PPC, and estrogen and progesterone receptor positivity were not significant prognostic factors in Stage I EEC. In contrast, lymphovascular invasion and grade were significant prognostic factors.
ABSTRACT
BACKGROUND: Percutaneous mitral valvuloplasty (PMV) is a standard treatment for severe rheumatic mitral stenosis (RMS). However, the prognostic significance of the change in mitral valve area (∆MVA) during PMV is not fully understood.MethodsâandâResults: This study analyzed data from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, which included 3,140 patients with severe RMS. We focused on patients with severe RMS undergoing their first PMV. Changes in echocardiographic parameters, including MVA quantified before and after PMV, and composite outcomes, including mitral valve reintervention, heart failure admission, stroke, and all-cause death, were evaluated. An optimal result was defined as a postprocedural MVA ≥1.5 cm2without mitral regurgitation greater than Grade II. Of the 308 patients included in the study, those with optimal results and ∆MVA >0.5 cm² had a better prognosis (log-rank P<0.001). Patients who achieved optimal results but with ∆MVA ≤0.5 cm² had a greater risk of composite outcomes than those with optimal outcomes and ∆MVA >0.5 cm² (nested Cox regression analysis, hazard ratio 2.27; 95% confidence interval 1.09-4.73; P=0.028). CONCLUSIONS: Achieving an increase in ∆MVA of >0.5 cm2was found to be correlated with improved outcomes. This suggests that, in addition to achieving traditional optimal results, targeting an increase in ∆MVA of >0.5 cm2could be a beneficial objective in PMV treatment for RMS.
ABSTRACT
BACKGROUND: Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. METHODS: We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24â h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. RESULTS: During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). CONCLUSIONS: Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.
Subject(s)
Hospital Mortality , Immunosuppressive Agents , Intensive Care Units , Kidney Transplantation , Sepsis , Humans , Retrospective Studies , Kidney Transplantation/adverse effects , Male , Female , Middle Aged , Sepsis/mortality , Sepsis/drug therapy , Immunosuppressive Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Adult , Aged , Organ Dysfunction Scores , Transplant Recipients/statistics & numerical data , PrognosisABSTRACT
BACKGROUND: Mycobacterium avium complex (MAC) is a group of slow-growing mycobacteria that includes Mycobacterium avium and Mycobacterium intracellulare. MAC pulmonary disease (MAC-PD) poses a threat to immunocompromised individuals and those with structural pulmonary diseases worldwide. The standard treatment regimen for MAC-PD includes a macrolide in combination with rifampicin and ethambutol. However, the treatment failure and disease recurrence rates after successful treatment remain high. RESULTS: In the present study, we investigated the unique characteristics of small colony variants (SCVs) isolated from patients with MAC-PD. Furthermore, revertant (RVT) phenotype, emerged from the SCVs after prolonged incubation on 7H10 agar. We observed that SCVs exhibited slower growth rates than wild-type (WT) strains but had higher minimum inhibitory concentrations (MICs) against multiple antibiotics. However, some antibiotics showed low MICs for the WT, SCVs, and RVT phenotypes. Additionally, the genotypes were identical among SCVs, WT, and RVT. Based on the MIC data, we conducted time-kill kinetic experiments using various antibiotic combinations. The response to antibiotics varied among the phenotypes, with RVT being the most susceptible, WT showing intermediate susceptibility, and SCVs displaying the lowest susceptibility. CONCLUSIONS: In conclusion, the emergence of the SCVs phenotype represents a survival strategy adopted by MAC to adapt to hostile environments and persist during infection within the host. Additionally, combining the current drugs in the treatment regimen with additional drugs that promote the conversion of SCVs to RVT may offer a promising strategy to improve the clinical outcomes of patients with refractory MAC-PD.
Subject(s)
Lung Diseases , Mycobacterium avium-intracellulare Infection , Humans , Mycobacterium avium Complex/genetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Mycobacterium avium-intracellulare Infection/drug therapy , Mycobacterium avium-intracellulare Infection/microbiology , Lung Diseases/drug therapy , Lung Diseases/microbiology , Ethambutol/pharmacology , Ethambutol/therapeutic useABSTRACT
Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.
Subject(s)
Endocrine Disruptors , Estrous Cycle , Parabens , Rats, Sprague-Dawley , Toxicokinetics , Animals , Parabens/toxicity , Parabens/pharmacokinetics , Parabens/administration & dosage , Male , Female , Estrous Cycle/drug effects , Endocrine Disruptors/toxicity , Endocrine Disruptors/pharmacokinetics , Dose-Response Relationship, Drug , Rats , No-Observed-Adverse-Effect Level , Preservatives, Pharmaceutical/toxicity , Preservatives, Pharmaceutical/pharmacokinetics , Preservatives, Pharmaceutical/administration & dosage , Injections, SubcutaneousABSTRACT
BACKGROUND: Digital dementia is a term that describes a possible decline in cognitive abilities, especially memory, attributed to the excessive use of digital technology such as smartphones, computers, and tablets. This concept has gained popularity in public discourse and media lately. With the increasing use of social media platforms such as Twitter (subsequently rebranded as X), discussions about digital dementia have become more widespread, which offer a rich source of information to understand public perceptions, concerns, and sentiments regarding this phenomenon. OBJECTIVE: The aim of this research was to delve into a comprehensive content and sentiment analysis of Twitter discussions regarding digital dementia using the hashtag #digitaldementia. METHODS: Retrospectively, publicly available English-language tweets with hashtag combinations related to the topic of digital dementia were extracted from Twitter. The tweets were collected over a period of 15 years, from January 1, 2008, to December 31, 2022. Content analysis was used to identify major themes within the tweets, and sentiment analysis was conducted to understand the positive and negative emotions associated with these themes in order to gain a better understanding of the issues surrounding digital dementia. A one-way ANOVA was performed to gather detailed statistical insights regarding the selected tweets from influencers within each theme. RESULTS: This study was conducted on 26,290 tweets over 15 years by 5123 Twitter users, mostly female users in the United States. The influencers had followers ranging from 20,000 to 1,195,000 and an average of 214,878 subscribers. The study identified four themes regarding digital dementia after analyzing tweet content: (1) cognitive decline, (2) digital dependency, (3) technology overload, and (4) coping strategies. Categorized according to Glaser and Strauss's classifications, most tweets (14,492/26,290, 55.12%) fell under the categories of wretched (purely negative) or bad (mostly negative). However, only a small proportion of tweets (3122/26,290, 11.86%) were classified as great (purely positive) or swell sentiment (mostly positive). The ANOVA results showed significant differences in mean sentiment scores among the themes (F3,3581=29.03; P<.001). The mean sentiment score was -0.1072 (SD 0.4276). CONCLUSIONS: Various negative tweets have raised concerns about the link between excessive use of digital devices and cognitive decline, often known as digital dementia. Of particular concern is the rapid increase in digital device use. However, some positive tweets have suggested coping strategies. Engaging in digital detox activities, such as increasing physical exercise and participating in yoga and meditation, could potentially help prevent cognitive decline.
Subject(s)
Dementia , Social Media , Social Media/statistics & numerical data , Humans , Dementia/psychology , Retrospective Studies , EmotionsABSTRACT
BACKGROUND: The rapid economic development of South Korea provides a unique model to study changes in the clinical characteristics, treatment approaches, and clinical outcomes of patients with rheumatic mitral stenosis (MS) relative to socioeconomic growth. METHODS: From the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry, 2,337 patients diagnosed with moderate or severe rheumatic MS between January 2001 and December 2020 were analyzed. Patients were grouped into consecutive 5-year intervals based on their year of diagnosis. Clinical characteristics, echocardiographic data, and clinical outcomes were assessed. RESULTS: Over 20 years, the severity of mitral stenosis increased from 79.1% to 90.2%; similarly, the average age at diagnosis increased from 54.3 to 63.0 years (all P < 0.001). Comorbidities such as hypertension and atrial fibrillation increased (6.3% to 29.5% and 41.4% to 46.9%, respectively; all P for trend < 0.05). The rate of mitral intervention within five years after diagnosis increased from 31.2% to 47.4% (P for trend < 0.001). However, clinical outcomes of rheumatic mitral stenosis deteriorated over time in the composite outcomes (log-rank test, P < 0.001). Conversely, the incidence of stroke remained stable (60.6-73.7%; P < 0.001), which might be attributed to the increased use of anticoagulation therapy. CONCLUSION: This study observed an increase in patient age, comorbidities, and valve disease severity as the country transitioned from a developing to developed status. Despite a rise in mitral valve interventions, clinical outcomes deteriorated over 20 years, highlighting the need for modified treatment approaches to improve patient outcomes.
Subject(s)
Echocardiography , Mitral Valve Stenosis , Registries , Rheumatic Heart Disease , Humans , Mitral Valve Stenosis/diagnosis , Mitral Valve Stenosis/pathology , Male , Republic of Korea/epidemiology , Female , Middle Aged , Rheumatic Heart Disease/epidemiology , Rheumatic Heart Disease/diagnosis , Treatment Outcome , Adult , Atrial Fibrillation/diagnosis , Atrial Fibrillation/drug therapy , Aged , Severity of Illness Index , Comorbidity , Stroke/diagnosis , Stroke/etiology , Stroke/epidemiologyABSTRACT
BACKGROUND: Atrial fibrillation (AF) screening was incorporated into an abdominal aortic aneurysm screening (AAA) program for New Zealand (NZ) Maori. METHODS: AF screening was performed as an adjunct to AAA screening of Maori men aged 60-74 years and women aged 65-74 years registered with primary health care practices in Auckland, NZ. Pre-existing AF was determined through coded diagnoses or medications in the participant's primary care record. Subsequent audit of the record assessed accuracy of pre-screening coding, medication use and clinical follow-up. RESULTS: Among 1,933 people successfully screened, the prevalence of AF was 144 (7.4%), of which 46 (2.4% of the cohort) were patients without AF coded in the medical record. More than half of these were revealed to be known AF but that was not coded. Thus, the true prevalence of newly detected AF was 1.1% (n=21). An additional 48 (2.5%) of the cohort had been coded as AF but were not in AF at the time of screening. Among the 19 at-risk screen-detected people with AF, 10 started appropriate anticoagulation therapy within 6 months. Of the nine patients who did not commence anticoagulation therapy, five had a subsequent adverse clinical outcome in the follow-up period, including one with ischaemic stroke; two had contraindications to anticoagulants. Among those with previously diagnosed AF, the proportion receiving anticoagulation therapy rose from 57% pre-screening to 83% at 6 months post-screening (p<0.0001); among newly diagnosed AF the proportion rose from 0% to 53% (p<0.01). CONCLUSIONS: AF screening is a feasible low-cost adjunct to AAA screening with potential to reduce ethnic inequities in stroke incidence. However, effective measures are needed to ensure that high-risk newly diagnosed AF is managed according to best practice guidelines.
Subject(s)
Aortic Aneurysm, Abdominal , Atrial Fibrillation , Brain Ischemia , Stroke , Female , Humans , Male , Anticoagulants/therapeutic use , Aortic Aneurysm, Abdominal/diagnosis , Aortic Aneurysm, Abdominal/epidemiology , Aortic Aneurysm, Abdominal/chemically induced , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/drug therapy , Maori People , Mass Screening , New Zealand/epidemiology , Prevalence , Stroke/etiology , Middle Aged , AgedABSTRACT
The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising anti-inflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template.
Subject(s)
Enzyme Inhibitors , Epoxide Hydrolases , Urea , Epoxide Hydrolases/antagonists & inhibitors , Epoxide Hydrolases/metabolism , Animals , Mice , Humans , Urea/pharmacology , Urea/analogs & derivatives , Urea/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides , Structure-Activity Relationship , Solubility , Disease Models, Animal , Pain/drug therapyABSTRACT
BACKGROUND: Cervical necrotizing fasciitis (CNF) is a rare, aggressive form of deep neck space infection with significant morbidity and mortality rates. Serial surgical debridement acts as the cornerstone of CNF treatment; however, it often results in defects requiring complex reconstructions. CASE SUMMARY: We report two cases in which the keystone flap (KF) was used for CNF defect coverage: Case 1, an 85-year-old patient with CNF in the anterior neck, and Case 2, a 54-year-old patient with CNF in the posterior neck. Both patients received empirical intravenous antibiotic therapy and underwent serial debridement, enabling adequate wound preparation and stabilization. The final defect size measured 5.5 cm × 12 cm in Case 1 and 6 cm × 11 cm in Case 2. For defect coverage, we employed an 8 cm × 19 cm type II KF based on perforators from the superior thyroid artery in Case 1 and a 9 cm × 18 cm type II KF based on perforators from the transverse cervical artery in Case 2. Both flaps showed complete survival. No postoperative complications occurred in both cases, and favorable outcomes were observed at 7- and 6-month follow-ups in case 1 and 2, respectively. CONCLUSION: We effectively treated CNF-associated defects using the KF technique; KF is viable for covering CNF defects in carefully selected cases.
ABSTRACT
Background: The screening tools for sarcopenia are measuring calf circumference, SARC-F or SPPB. However, not all of these tools have high sensitivity, specificity, and low margins of error. This research investigates potential of 3D anthropometry of the lower extremities on screening of sarcopenia. Methods: From October 2022 to February 2023, we retrospectively analyzed results of 3D body scanner and bio-impedance analysis for patients aged 45 to 85 at risk of sarcopenia. The 3D scanner measured the surface and volume values of both thighs and calves. When skeletal muscle index (SMI) is less than 5.7, patients were classified to Low SMI group, indicative of sarcopenia. Results: A total six out of 62 patients were classified to Low SMI group, showing significantly lower values of right, left, mean calf volumes and mean calf surface than the other patients (right calf volume 2.62 L vs. 3.34 L, p = 0.033; left calf volume 2.62 L vs. 3.25 L, p = 0.044; mean calf volume 2.62 L vs. 3.29 L, p = 0.029; mean calf surface 0.12 m2 vs. 0.13 m2, p = 0.049). There was no statistical difference in thigh volume and surface. Through AUC-ROC analysis, mean calf volume was the most significant cut-off value (right calf volume 2.80 L, AUC = 0.768; left calf volume 2.75 L, AUC = 0.753; mean calf volume 3.06 L, AUC = 0.774; mean calf surface 0.12 m2, AUC = 0.747). Conclusion: The calf volume and surface values have significant relationship with low SMI, and the mean calf volume was the most significant cut-off screening value for Low SMI. The 3D scanner demonstrated its value as a new means for screening sarcopenia.
ABSTRACT
This study analyzed the relationship between urine concentrations of phthalate metabolites (UCOM) and personal care products (PCPs) used in adults and examined the change in UCOM according to the usage frequency of PCPs based on raw data from the 3rd Korean National Environmental Health Survey conducted between 2015 and 2017. The relationship between PCP use frequency and UCOM was analyzed using multiple regression analysis, adjusting for baseline factors. The regression model consisted of a Crude Model with log-transformed UCOM before and after adjustment for urine creatinine concentrations. Model 1 was additionally adjusted for age, sex, and obesity, while Model 2 was additionally adjusted for smoking, alcohol consumption, pregnancy history, average monthly income of the household, and PCP exposure within the past 2 days. PCP usage frequency was significantly associated with the UCOM without adjustment for urine creatinine and correlated with demographic characteristics, urine creatinine concentration, and PCP exposure within the past 2 days. This study on exposure to urinary phthalates will play a crucial role in Korean public health by aligning with the fundamentals of research priorities and providing representative data on phthalate exposure for conducting population-level studies.
Subject(s)
Cosmetics , Environmental Pollutants , Phthalic Acids , Female , Pregnancy , Humans , Environmental Exposure/analysis , Creatinine/analysis , Phthalic Acids/metabolism , Cosmetics/analysis , Environmental Pollutants/metabolismABSTRACT
Research on the treatment outcomes and mortality of patients with cancer and hip fractures remains limited. We aimed to assess the treatment outcomes and mortality in older patients with cancer and hip fractures. We retrospectively reviewed the data of 1264 patients aged ≥ 60 years treated for hip fractures between January 2005 and April 2022. The operation time, blood transfusion-related indicators, postoperative complications, reoperation rate, length of hospital stay, admission to the intensive care unit, mortality rate, and clinical scores were compared. We also performed survival analysis. Subsequently, 1:1 propensity-score matching was performed. In the unmatched cohort, we compared 273 patients with cancer and 991 controls. The cancer group exhibited a higher incidence of pneumonia (P = 0.025) and higher in-hospital and 1-year follow-up mortality rates (P = 0.044 and P < 0.001, respectively). In the matched cohort, the 1-year mortality rate remained higher in the cancer group (P < 0.001). The control group showed a higher survival rate in both unmatched and matched cohorts (P < 0.001 for both). The surgical outcomes for hip fractures were comparable between patients with and without cancer. We recommend surgical treatment for hip fractures in patients with cancer.
Subject(s)
Hip Fractures , Neoplasms , Humans , Aged , Propensity Score , Retrospective Studies , Hip Fractures/surgery , ReoperationABSTRACT
Objective: Although some previous studies have investigated health in police officers, investigations of related factors have been limited to work-related associations or those affecting certain police officers. To address this gap, this study investigated relationships between sociodemographic factors, work-related factors, health behaviors, health conditions, and self-rated bad health (SRBH) in Korean police officers. Methods: In 2021, we conducted a cross-sectional survey in cooperation with the Korean National Police Agency (KNPA). The respondents were 6,591 police officers aged 21-60 years, all of whom agreed to complete the survey online using the police agency's intranet. After collecting data, we conducted a multiple logistic regression analysis to examine factors that were associated with SRBH, with calculations for adjusted odds ratios (ORs) and 95 % confidence intervals (CIs). The study model included a range of individual socioeconomic characteristics, work-related variables, health behaviors, and health conditions. Results: Although the associated factors varied according to age group, several factors generally related to SRBH, including the lack of exercise, stress, having one or more chronic diseases, and work-related pain. By contrast, neither sex nor sleep duration were associated with SRBH of respondents. Monthly night work, smoking, and alcohol consumption were only associated with SRBH of certain age groups. Conclusions: Several variables clearly related to SRBH of police officers. In this context, health-related associations, especially stress and chronic diseases, tended to differ according to age, including those that should be considered to improve health. These findings have important implications for relevant healthcare programs and interventions.
ABSTRACT
BACKGROUND: The fibular free flap is considered one of the most valuable options for mandible reconstruction. A perforator flap has gained widespread acceptance in oral and maxillofacial reconstruction. Typically, the fibula flap is obtained primarily with the distal perforator due to its reliable blood supply, with less attention given to the proximal perforators during the harvesting process. Normally, the distal perforator of the fibula exhibits stability and shows limited anatomical variations. However, there have been reported cases in which the distal perforator is absent. At times, these vascular abnormalities remain undetectable through Doppler examination or preoperative angiography evaluation. Therefore, this case details the experience of encountering the rare event of vascular abnormality in oral cancer surgery. CASE PRESENTATION: This article reports the case of a patient who presented with a congenital absence of the distal perforator in the peroneal artery, attributed to a vascular abnormality. Additionally, we provide a review of the concept of utilizing the proximal perforator as an alternative approach in the flap harvesting process. CONCLUSIONS: While the distal perforator of the peroneal artery is typically utilized for fibula free flap procedures, surgeons must remain cognizant of the potential for its absence due to aberrant anatomy. Recognizing an alternative approach in such cases can be pivotal for precise surgical planning and favorable outcomes in oral and maxillofacial reconstruction.