FGF23 facilitates IL-1ß synthesis in rheumatoid arthritis through activating PI3K, Akt, and NF-κB pathways.

Rheumatoid arthritis (RA) is a well-known autoimmune disorder related with joint pain, joint swelling, cartilage and bone degradation as well as deformity. Fibroblast growth factor 23 (FGF23) is an endocrine factor of the FGF family primarily produced by osteocytes and osteoblasts, involves an essential effect in pathogenesis of RA. IL-1ß is a vital proinflammatory factor in the development of RA. However, the role of FGF23 on IL-1ß synthesis in RA has not been fully explored. Our analysis of database revealed higher levels of FGF23 and IL-1ß in RA samples compared with healthy controls. High-throughput screening demonstrated that IL-1ß is a potential candidate factor after FGF23 treatment in RA synovial fibroblasts (RASFs). FGF23 concentration dependently promotes IL-1ß synthesis in RASFs. FGF23 enhances IL-1ß expression by activating the PI3K, Akt, and NF-κB pathways. Our findings support the notion that FGF23 is a promising target in the remedy of RA.

Mitoquinone Inactivates Mitochondrial Chaperone TRAP1 by Blocking the Client Binding Site.

Heat shock protein 90 (Hsp90) family proteins are molecular chaperones that modulate the functions of various substrate proteins (clients) implicated in pro-tumorigenic pathways. In this study, the mitochondria-targeted antioxidant mitoquinone (MitoQ) was identified as a potent inhibitor of mitochondrial Hsp90, known as a tumor necrosis factor receptor-associated protein 1 (TRAP1). Structural analyses revealed an asymmetric bipartite interaction between MitoQ and the previously unrecognized drug binding sites located in the middle domain of TRAP1, believed to be a client binding region. MitoQ effectively competed with TRAP1 clients, and MitoQ treatment facilitated the identification of 103 TRAP1-interacting mitochondrial proteins in cancer cells. MitoQ and its redox-crippled SB-U014/SB-U015 exhibited more potent anticancer activity in vitro and in vivo than previously reported mitochondria-targeted TRAP1 inhibitors. The findings indicate that targeting the client binding site of Hsp90 family proteins offers a novel strategy for the development of potent anticancer drugs.

S1P promotes IL-6 expression in osteoblasts through the PI3K, MEK/ERK and NF-κB signaling pathways.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks joint tissue. Interleukin (IL)-6 is a key proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we examined the effects of S1P on IL-6 expression in osteoblasts. Our results and records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-6 in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P increased mRNA and protein expression of IL-6. PI3K, MEK, ERK and NF-κB inhibitors and their small interfering RNAs (siRNAs) reduced S1P-promoted IL-6 expression. S1P also facilitated PI3K, MEK/ERK and NF-κB signaling cascades. Our results indicate that S1P promotes the expression of IL-6 in osteoblasts via the PI3K, MEK/ERK and NF-κB signaling pathways.

S1P facilitates IL-1ß production in osteoblasts via the JAK and STAT3 signaling pathways.

Rheumatoid arthritis (RA) is a systemic autoimmune inflammatory disease, in which the immune system attacks synovial joint tissues. Interleukin (IL)-1ß is a critical proinflammatory cytokine in RA progression. Sphingosine-1-phosphate (S1P), a platelet-derived lysophospholipid mediator, reportedly regulates osteoimmunology. Here, we investigated how S1P mediates IL-1ß expression in osteoblasts. Our analysis of records from the Gene Expression Omnibus (GEO) database demonstrate higher levels of IL-1ß in patients with RA compared with those with osteoarthritis. Stimulation of osteoblasts with S1P concentration dependently increased mRNA and protein expression of IL-1ß. Elevations in IL-1ß mRNA expression induced by S1P were reduced by the small interfering RNA (siRNA) against the S1P1 receptor. S1P also augmented JAK and STAT3 molecular cascades. We also found that JAK and STAT3 inhibitors and their siRNAs antagonized S1P-promoted IL-1ß expression. Our results indicate that S1P promotes the expression of IL-1ß in osteoblasts via the S1P1 receptor and the JAK and STAT3 signaling pathways.

Myostatin induces tumor necrosis factor-α expression in rheumatoid arthritis synovial fibroblasts through the PI3K-Akt signaling pathway.

In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor-α (TNF-α), a well-known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose-dependently induced TNF-α expression through the phosphatidylinositol 3-kinase (PI3K)-Akt-AP-1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP-1-induced luciferase activity and activation of the c-Jun binding site on the TNF-α promoter. Our results indicated that myostatin increases TNF-α expression via the PI3K-Akt-AP-1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.

Melatonin attenuates TNF-α and IL-1ß expression in synovial fibroblasts and diminishes cartilage degradation: Implications for the treatment of rheumatoid arthritis.

The hormone melatonin has many properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. Melatonin has been demonstrated to be beneficial in several inflammatory autoimmune diseases, but its effects in rheumatoid arthritis (RA) remain controversial. We sought to determine how melatonin regulates inflammation in RA. We found that melatonin dose-dependently inhibits tumor necrosis factor-α (TNF-α) and interleukin (IL)-1ß expression through the PI3K/AKT, ERK, and NF-κB signaling pathways. We also identified that melatonin inhibits TNF-α and IL-1ß production by upregulating miR-3150a-3p expression. Synovial tissue specimens from RA patients and culture of human rheumatoid fibroblast-like synoviocytes confirmed that the MT1 receptor is needed for the anti-inflammatory activities of melatonin. Importantly, melatonin also significantly reduced paw swelling, cartilage degradation, and bone erosion in the collagen-induced arthritis mouse model. Our results indicate that melatonin ameliorates RA by inhibiting TNF-α and IL-1ß production through downregulation of the PI3K/AKT, ERK, NF-κB signaling pathways, as well as miR-3150a-3p overexpression. The role of melatonin as an adjuvant treatment in patients with RA deserves further clinical studies.

VEGF-C Gene Polymorphisms Increase Susceptibility to Rheumatoid Arthritis.

Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194. In analyses adjusted for potential covariates, we found that compared with subjects with the A/A genotype of SNP rs11947611, those with the A/G genotype were 40% more likely to develop RA (adjusted odds ratio [AOR] 0.61; 95% confidence interval [CI] 0.40 to 0.92; p = 0.02). In addition, subjects lacking the A/A genotype (A/G, G/G) of SNP rs2046463 were more than twice as likely as those with the A/A genotype to require methotrexate (AOR 2.23, 95% CI 1.25 to 3.98; p = 0.01), while those who lacked the G/G genotype (G/C, C/C) in the SNP rs3775194 had a significantly lower risk of requiring prednisolone as compared with those with the G/G genotype (AOR 0.39, 95% CI 0.19 to 0.79; p = 0.01). Our findings suggest that VEGF-C gene polymorphisms might serve as a diagnostic marker and therapeutic target for RA therapy. Pharmacotherapies that modulate the activity of the VEGF-C gene may be promising for RA treatment.

Clinical features, management, and outcome of iliopsoas abscess associated with cardiovascular disorders: a hospital-based observational case series study.

BACKGROUND: Iliopsoas abscess (IPA) is a rare clinical entity and is difficult to diagnose due to its insidious onset and nonspecific symptoms. The association between IPA and cardiovascular disorders (CVD) has been rarely reported. Computed tomographic (CT) scan can provide a definitive diagnosis of IPA and associated foci of adjacent structures. IPA is a life-threatening condition, especially when associated with CVD. MATERIALS AND METHODS: We conducted a hospital-based observational study of IPA associated with CVD. Data were collected from the electronic clinical database of Taichung Veterans General Hospital (1520-bed tertiary referral hospital in central Taiwan) between July 2007 and December 2017. The diagnosis of IPA associated with CVD was confirmed by classical findings on CT and transesophageal echocardiography with compatible clinical presentation and cultures from pus/tissue and blood. RESULTS: Fifteen patients of IPA associated with CVD were studied. They included 12 males (80%) and 3 females (20%), with a mean age 63.2 ± 16.9 years (31-85 years). CVD included stent-graft/endograft infection of abdominal aortic aneurysm (AAA) (40%), primary mycotic AAA (33.3%), and infective endocarditis (26.7%). Staphylococcus aureus is the most common microorganism in pus/tissue cultures (n = 3, 37.5%) and in blood cultures (n = 6, 40%). The average length of hospital stay was 33.1 ± 20.5 days (range, 3-81 days; median, 33 days). Hospital stay lasted 42.6 ± 19.2 days in the survival group and 19.0 ± 14.1 days (P = 0.018) in the non-survival group. Incidence of patients staying in the intensive care unit (ICU) with intubation > 3 days was 33% in the survival group and 100% (P = 0.028) in the non-survival group. Intra-hospital mortality rate was 40%. Poor prognostic factors in the non-survival group were hypoalbuminemia, hyponatremia, involved disc/vertebral body and/or epidural abscess, and ICU stay with intubation > 3 days. Cumulative survival rate was 25% under conservative treatments and 66.3% under aggressive treatments (P = 0.038). CONCLUSION: Due to high mortality rates, clinicians should keep a high suspicion index for IPA associated with CVD through clinical presentation, physical examination, and imaging study. Timely empiric antibiotics for common bacteria, drainage for IPA, endovascular repair, or vascular reconstruction by graft replacement or bypass with intensive care should be mandatory to shorten the hospital stay, reduce medical costs, and lower mortality rate.

Primary aortoduodenal fistula associated with abdominal aortic aneurysm with presentation of gastrointestinal bleeding: a case report.

BACKGROUND: Primary aortoduodenal fistula (ADF) is a rare cause of gastrointestinal (GI) bleeding and is difficult to diagnose as the clinical presentation is subtle. Clinicians should keep a high level of suspicion for an unknown etiology of GI bleeding, especially in older patients with or without abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA) can be used to detect primary ADF. Open surgery or endovascular aortic repair (EVAR) for ADF with bleeding will improve the survival rate. CASE PRESENTATION: We report a rare case of AAA complicating ADF with massive GI bleeding in a 73-year-old Taiwanese man. He presented with abdominal pain and tarry stool for 5 days and an initial upper GI endoscopy at a rural hospital showed gastric ulcer only, but hypotension with tachycardia and a drop in hemoglobin of 9 g/dl from 12 g/dl occurred the next day. He was referred to our hospital for EVAR and primary closure of fistula defect due to massive GI bleeding with shock from ADF caused by AAA. Diagnosis was made by CTA of aorta. CONCLUSIONS: A timely and accurate diagnosis of primary ADF may be challenging due to insidious episodes of GI bleeding, which are frequently under-diagnosed until the occurrence of massive hemorrhage. Clinical physicians should keep a high index of awareness for primary ADF, especially in elderly patients with unknown etiology of upper GI bleeding with or without a known AAA.

Stretching-Induced Conductance Variations as Fingerprints of Contact Configurations in Single-Molecule Junctions.

Molecule-electrode contact atomic structures are a critical factor that characterizes molecular devices, but their precise understanding and control still remain elusive. Based on combined first-principles calculations and single-molecule break junction experiments, we herein establish that the conductance of alkanedithiolate junctions can both increase and decrease with mechanical stretching, and the specific trend is determined by the S-Au linkage coordination number (CN) or the molecule-electrode contact atomic structure. Specifically, we find that the mechanical pulling results in the conductance increase for the junctions based on S-Au CN two and CN three contacts, while the conductance is minimally affected by stretching for junctions with the CN one contact and decreases upon the formation of Au monatomic chains. Detailed analysis unravels the mechanisms involving the competition between the stretching-induced upshift of the highest occupied molecular orbital-related states toward the Fermi level of electrodes and the deterioration of molecule-electrode electronic couplings in different contact CN cases. Moreover, we experimentally find a higher chance to observe the conductance enhancement mode under a faster elongation speed, which is explained by ab initio molecular dynamics simulations that reveal an important role of thermal fluctuations in aiding deformations of contacts into low-coordination configurations that include monatomic Au chains. Pointing out the insufficiency in previous notions of associating peak values in conductance histograms with specific contact atomic structures, this work resolves the controversy on the origins of ubiquitous multiple conductance peaks in S-Au-based single-molecule junctions.

Risk Factors and Scoring Systems to Predict the Mortality Risk of Afebrile Adult Patients with Monomicrobial Gram-Negative Bacteremia: A 10-Year Observational Study in the Emergency Department.

BACKGROUND: The mortality rate of afebrile bacteremia has been reported to be as high as 45%. This investigation focused on the risk factors and predictive performance of scoring systems for the clinical outcomes of afebrile patients with monomicrobial gram-negative bacteria (GNB) in the emergency department (ED). METHODS: We conducted a retrospective analysis of afebrile adult ED patients with monomicrobial GNB bacteremia from January 2012 to December 2021. We dissected the demographics, clinical pictures, and laboratory investigations. We applied five scoring systems and three revised systems to predict the clinical outcomes. RESULTS: There were 600 patients included (358 males and 242 females), with a mean age of 69.6 ± 15.4 years. The overall mortality rate was 50.17%, reaching 68.52% (74/108) in cirrhotic patients. Escherichia coli was the leading pathogen (42.83%). The non-survivors had higher scores of the original MEDS (p < 0.001), NEWS (p < 0.001), MEWS (p < 0.001), qSOFA (p < 0.001), and REMS (p = 0.030). In univariate logistic regression analyses, several risk factors had a higher odds ratio (OR) for mortality, including liver cirrhosis (OR 2.541, p < 0.001), malignancy (OR 2.259, p < 0.001), septic shock (OR 2.077, p = 0.002), and male gender (OR 0.535, p < 0.001). The MEDS demonstrated that the best predictive power with the maximum area under the curve (AUC) was measured at 0.773 at the cut-off point of 11. The AUCs of the original NEWS, MEWS, qSOFA, and REMS were 0.663, 0.584, 0.572, and 0.553, respectively. We revised the original MEDS, NEWS, and qSOFA by adding red cell distribution width, albumin, and lactate scores and found a better predictive power of the AUC of 0.797, 0.719, and 0.694 on the revised MEDS ≥11, revised qSOFA ≥ 3, and revised NEWS ≥ 6, respectively. CONCLUSIONS: The original MEDS, revised MEDS, revised qSOFA, and revised NEWS were valuable tools for predicting the mortality risk in afebrile patients with monomicrobial GNB bacteremia. We suggested that clinicians should explore patients with the risk factors mentioned above for possible severe infection, even in the absence of fever and initiate hemodynamic support and early adequate antibiotic therapy in patients with higher scores of the original MEDS (≥11), revised MEDS (≥11), revised NEWS (≥6), and revised qSOFA (≥3).

Good Performance of Revised Scoring Systems in Predicting Clinical Outcomes of Aeromonas Bacteremia in the Emergency Department: A Retrospective Observational Study.

BACKGROUND: Aeromonas species, Gram-negative, non-sporulating, facultative, and anaerobic bacilli, widely distributed in aquatic environments, derive various infections, including bacteremia. Most of these infections were opportunistic and found in patients with predisposing conditions. Among the infections, bacteremia remains with notable mortality, reported from 15% to 45%. However, predicting systems for assessing the mortality risk of this disease have yet to be investigated. We aimed to validate the performance of specific predictive scoring systems to assess the clinical outcomes of Aeromonas bacteremia and applied the revised systems to predict mortality risk. METHODS: A retrospective observational study reviewed patients with bacteremia caused by Aeromonas spp. based on at least one positive blood culture sample collected in the emergency department from January 2012 to December 2020. The outcome was in-hospital mortality. We used seven predictive scoring systems to predict the clinical outcome. According to the effectiveness in predicting mortality, we revised three of the seven predictive scoring systems by specific characteristics to refine their risk-predicting performances. RESULTS: We enrolled 165 patients with bacteremia caused by Aeromonas spp., including 121 males (73.3%) and 44 females (26.7%), with a mean age of 66.1 ± 14.9 years and an average length of hospital stay of 12.4 ± 10.9 days. The overall mortality rate was 32.7% (54/165). The non-survivors had significantly higher scores in MEDS (6.7 ± 4.2 vs. 12.2 ± 3.3, p < 0.001), NEWS (4.0 ± 2.8 vs. 5.3 ± 3.0, p = 0.008), and qSOFA (0.3 ± 0.6 vs. 0.6 ± 0.7, p = 0.007). Regarding mortality risk prediction, the MEDS demonstrated the best predictive power with AUC of ROC measured up to 0.834, followed by NEWS (0.626) and qSOFA (0.608). We revised the MEDS, NEWS, and qSOFA by hemoglobin and lactate. We found that the revised scores had better powerful performance, including 0.859, 0.767, and 0.691 of the AUC of ROC, if the revised MEDS ≥10, revised NEWS ≥8, and revised qSOFA ≥2, respectively. CONCLUSIONS: MEDS, NEWS, and qSOFA were good tools for predicting outcomes in patients with Aeromonas spp. bacteremia. The revised MEDS, NEWS, and qSOFA demonstrated more powerful predicting performance than the original scoring systems. We suggested that patients with higher scores in revised MEDS (≥10), revised NEWS (≥8), and revised qSOFA (≥2) received early goal-directed therapy and appropriate broad-spectrum antibiotic treatment as early as possible to reduce mortality.

The Short- and Long-Term Risk of Mortality in Intracranial Hemorrhage Patients with Tranexamic Acid Treatment in a Population-Based Cohort Study.

Background: The mortality rate associated with nontraumatic intracranial hemorrhage (NTICrH) remains consistently high under the current care modality. The effectiveness of tranexamic acid (TXA) as a treatment option is still a subject of debate. This study aims to assess the association between TXA administration and both short-term and long-term mortality rates in patients with NTICrH. Methods: We conducted a retrospective cohort study using data from the Taiwan National Health Insurance Research Database (NHIRD) spanning from January 2000 to December 2017. The study population consists of NTICrH patients admitted to the ICU, divided into two groups: patients who were treated with TXA and those who were not. Propensity score matching (PSM) was conducted to balance the baseline characteristics of the two groups. Cox proportional hazard analysis was conducted to estimate the hazard ratio (HR) for the all-cause mortality. Sensitivity analyses were performed using the inverse probability of treatment-weighted hazard ratio (IPTW-HR). To assess the timing of TXA use, we compared the risk of all-cause mortality within 180 days between patients receiving early TXA treatment and those receiving late TXA treatment. Results: There was no significant difference in 180-day all-cause mortality between the groups; the hazard ratio was 1.07 (95% CI: 0.96-1.20) in patients treated with TXA compared to those without TXA treatment. Within 7 days of admission, patients treated with TXA had a lower hazard ratio of 0.81 (95% CI: 0.74-0.90) for all-cause mortality. Conclusions: Lower mortality within the first 7 days was observed in patients with NTICrH who received TXA.

Better Performance of Modified Scoring Systems to Predict the Clinical Outcomes of Vibrio Bacteremia in the Emergency Department: An Observational Study.

BACKGROUND: Vibrio is a genus of Gram-negative bacteria found in various aquatic environments, including saltwater and freshwater. Vibrio bacteremia can lead to sepsis, a potentially life-threatening condition in which the immune system enters overdrive in response to the disease, causing widespread inflammation and damage to tissues and organs. V. vulnificus had the highest case fatality rate (39%) of all reported foodborne infections in the United States and a high mortality rate in Asia, including Taiwan. Numerous scoring systems have been created to estimate the mortality risk in the emergency department (ED). However, there are no specific scoring systems to predict the mortality risk of Vibrio bacteremia. Therefore, this study modified the existing scoring systems to better predict the mortality risk of Vibrio bacteremia. METHODS: Cases of Vibrio bacteremia were diagnosed based on the results from at least one blood culture in the ED. Patient data were extracted from the electronic clinical database, covering January 2012 to December 2021. The primary outcome was in-hospital mortality.This study used univariate and multivariate analyses to evaluate the mortality risk. RESULTS: This study enrolled 36 patients diagnosed with Vibrio bacteremia, including 23 males (63.9%) and 13 females (36.1%), with a mean age of 65.1 ± 15.7 years. The in-hospital mortality rate amounted to 25% (9/36), with 31.5% in V. vulnificus (6/19) and 17.6% in V. non-vulnificus (3/17). The non-survivors demonstrated higher MEDS (10.3 ± 2.4) than the survivors (6.2 ± 4.1) (p = 0.002). Concerning the qSOFA, the survivors scored 0.3 ± 0.5, and the non-survivors displayed a score of 0.6 ± 0.7 (p = 0.387). The AUC of the ROC for the MEDS and qSOFA was 0.833 and 0.599, respectively. This study modified the scoring systems with other predictive factors, including BUN and pH. The AUC of the ROC for the modified MEDS and qSOFA reached up to 0.852 and 0.802, respectively. CONCLUSION: The MEDS could serve as reliable indicators for forecasting the mortality rate of patients grappling with Vibrio bacteremia. This study modified the MEDS and qSOFA to strengthen the predictive performance of mortality risk for Vibrio bacteremia. We advocate the prompt initiation of targeted therapeutic interventions and judicious antibiotic treatments to curb fatality rates.

Utilizing the National Early Warning Score 2 (NEWS2) to confirm the impact of emergency department management in sepsis patients: a cohort study from taiwan 1998-2020.

BACKGROUND: Most sepsis patients could potentially experience advantageous outcomes from targeted medical intervention, such as fluid resuscitation, antibiotic administration, respiratory support, and nursing care, promptly upon arrival at the emergency department (ED). Several scoring systems have been devised to predict hospital outcomes in sepsis patients, including the Sequential Organ Failure Assessment (SOFA) score. In contrast to prior research, our study introduces the novel approach of utilizing the National Early Warning Score 2 (NEWS2) as a means of assessing treatment efficacy and disease progression during an ED stay for sepsis. OBJECTIVES: To evaluate the sepsis prognosis and effectiveness of treatment administered during ED admission in reducing overall hospital mortality rates resulting from sepsis, as measured by the NEWS2. METHODS: The present investigation was conducted at a medical center from 1997 to 2020. The NEWS2 was calculated for patients with sepsis who were admitted to the ED in a consecutive manner. The computation was based on the initial and final parameters that were obtained during their stay in the ED. The alteration in the NEWS2 from the initial to the final measurements was utilized to evaluate the benefit of ED management to the hospital outcome of sepsis. Univariate and multivariate Cox regression analyses were performed, encompassing all clinically significant variables, to evaluate the adjusted hazard ratio (HR) for total hospital mortality in sepsis patients with reduced severity, measured by NEWS2 score difference, with a 95% confidence interval (adjusted HR with 95% CI). The study employed Kaplan-Meier analysis with a Log-rank test to assess variations in overall hospital mortality rates between two groups: the "improvement (reduced NEWS2)" and "non-improvement (no change or increased NEWS2)" groups. RESULTS: The present investigation recruited a cohort of 11,011 individuals who experienced the first occurrence of sepsis as the primary diagnosis while hospitalized. The mean age of the improvement and non-improvement groups were 69.57 (± 16.19) and 68.82 (± 16.63) years, respectively. The mean SOFA score of the improvement and non-improvement groups were of no remarkable difference, 9.7 (± 3.39) and 9.8 (± 3.38) years, respectively. The total hospital mortality for sepsis was 42.92% (4,727/11,011). Following treatment by the prevailing guidelines at that time, a total of 5,598 out of 11,011 patients (50.88%) demonstrated improvement in the NEWS2, while the remaining 5,403 patients (49.12%) did not. The improvement group had a total hospital mortality rate of 38.51%, while the non-improvement group had a higher rate of 47.58%. The non-improvement group exhibited a lower prevalence of comorbidities such as congestive heart failure, cerebral vascular disease, and renal disease. The non-improvement group exhibited a lower Charlson comorbidity index score [4.73 (± 3.34)] compared to the improvement group [4.82 (± 3.38)] The group that underwent improvement exhibited a comparatively lower incidence of septic shock development in contrast to the non-improvement group (51.13% versus 54.34%, P < 0.001). The improvement group saw a total of 2,150 patients, which represents 38.41% of the overall sample size of 5,598, transition from the higher-risk to the medium-risk category. A total of 2,741 individuals, representing 48.96% of the sample size of 5,598 patients, exhibited a reduction in severity score only without risk category alteration. Out of the 5,403 patients (the non-improvement group) included in the study, 78.57% (4,245) demonstrated no alteration in the NEWS2. Conversely, 21.43% (1,158) of patients exhibited an escalation in severity score. The Cox regression analysis demonstrated that the implementation of interventions aimed at reducing the NEWS2 during a patient's stay in the ED had a significant positive impact on the outcome, as evidenced by the adjusted HRs of 0.889 (95% CI = 0.808, 0.978) and 0.891 (95% CI = 0.810, 0.981), respectively. The results obtained from the Kaplan-Meier analysis indicated that the survival rate of the improvement group was significantly higher than that of the non-improvement group (P < 0.001) in the hospitalization period. CONCLUSION: The present study demonstrated that 50.88% of sepsis patients obtained improvement in ED, ascertained by means of the NEWS2 scoring system. The practical dynamics of NEWS2 could be utilized to depict such intricacies clearly. The findings also literally supported the importance of ED management in the comprehensive course of sepsis treatment in reducing the total hospital mortality rate.

Impact of occupational noise exposure on the hearing level in hospital staffs: a longitudinal study.

The study aimed to evaluate the impact of occupational noise on hearing loss among healthcare workers using audiometry. A longitudinal study was conducted with a six-month follow-up period in a hospital with 21 participants, divided into high-noise-exposure (HNE) and low-noise-exposure (LNE) groups. Mean noise levels were higher in the HNE group (70.4 ± 4.5 dBA), and hearing loss was measured using pure-tone audiometry at baseline and follow-up. The HNE group had significantly higher mean threshold levels at frequencies of 0.25 kHz, 0.5 kHz, 4.0 kHz, and an average of 0.5, 1, 2, and 4 kHz (all p-values < 0.05) after the follow-up period. After adjusting for confounding factors, the HNE group had significantly higher hearing loss levels at 0.25 kHz, 0.5 kHz, and average frequencies of 0.5, 1, 2, and 4 kHz compared to the LNE group at the second measurement. Occupational noise levels above 65 dBA over six months were found to cause significant threshold changes at frequencies of 0.25 kHz, 0.5 kHz, and an average of 0.5-4.0 kHz. This study highlights the risk of noise-induced hearing loss among healthcare workers and emphasizes the importance of implementing effective hearing conservation programs in the workplace. Regular monitoring and assessment of noise levels and hearing ability, along with proper use of personal protective equipment, are crucial steps in mitigating the impact of occupational noise exposure on the hearing health of healthcare workers.

Features and treatment modality of iliopsoas abscess and its outcome: a 6-year hospital-based study.

BACKGROUND: Percutaneous drainage (PCD) and surgical intervention are two primary treatment options for iliopsoas abscess (IPA). However, there is currently no consensus on when to use PCD or surgical intervention, especially in patients with gas-forming IPA. This study compared the characteristics of patients with gas-forming and non-gas forming IPA and their mortality rates under different treatment modalities. An algorithm for selecting appropriate treatment for IPA patients is proposed based on our findings. METHODS: Eighty-eight IPA patients between July 2007 and February 2013 were enrolled in this retrospective study. Patients < 18 years of age or with an incomplete course of treatment were excluded. Demographic information, clinical characteristics, and outcomes of different treatment approaches were compared between gas-forming IPA and non-gas forming IPA patients. RESULTS: Among the 88 enrolled patients, 27 (31%) had gas-forming IPA and 61 (69%) had non-gas forming IPA. The overall intra-hospital mortality rate was 25%. The gas-forming IPA group had a higher intra-hospital mortality rate (12/27, 44.0%) than the non-gas forming IPA group (10/61, 16.4%) (P < 0.001). Only 2 of the 13 patients in the gas-forming IPA group initially accepting PCD had a good outcome (success rate = 15.4%). Three of the 11 IPA patients with failed initial PCD expired, and 8 of the 11 patients with failed initial PCD accepted salvage operation, of whom 5 survived. Seven of the 8 gas-forming IPA patients accepting primary surgical intervention survived (success rate = 87.5%). Only 1 of the 6 gas-forming IPA patients who accepted antibiotics alone, without PCD or surgical intervention, survived (success rate = 16.7%). In the non-gas forming IPA group, 23 of 61 patients initially accepted PCD, which was successful in 17 patients (73.9%). The success rate of PCD was much higher in the non-gas forming group than in the gas-forming group (P <0.01). CONCLUSIONS: Based on the high failure rate of PCD and the high success rate of surgical intervention in our samples, we recommend early surgical intervention with appropriate antibiotic treatment for the patients with gas-forming IPA. Either PCD or primary surgical intervention is a suitable treatment for patients with non-gas forming IPA.

Effect of temporal distance and goal type on predictions of future information security: Focus on moderation of self-efficacy and social responsibility.

We investigate how predictions of future information security vary according to temporal distance, goal type, and personal characteristics. A total of 368 participants rated the likelihood of achieving the two-goal types at present, and then one and ten years later. The future information security bias was found to be greater for a distant place than shortly, and it was found to be greater for private goal types than public goal types. Personal characteristics were classified into self-efficacy and social responsibility, and their effectiveness was verified. A self-efficacy test revealed that the information security bias for the two types of goals was higher when it was higher than the low self-efficacy group. In the case of social responsibility, the bias was found in the higher group than the lower group only in the public goal type, but not the private goal type. We conclude by presenting some implications for information security policy and suggestions for further research.