Advanced age and neurological recovery in elderly patients with out-of-hospital cardiac arrest treated with targeted temperature management: a nationwide population­based registry study 2016-2020.

The likelihood of neurological recovery after out-of-hospital cardiac arrest (OHCA) may be influenced by advanced age. This study aims to evaluate the impact of advanced age on neurological recovery in elderly OHCA survivors treated with targeted temperature management (TTM). This retrospective observational study, using a nationwide population-based OHCA registry, was conducted from January 2016 to December 2020. Non-traumatic elderly (≥ 65 years) comatose OHCA survivors treated with TTM were categorized according to age (65-69, 70-74, 75-79, and ≥ 80 years). Among 23,336 admitted OHCA patients, 3,398 were treated with TTM. Excluding 2,033 non-elderly patients, 1,365 were analyzed. Among the four groups, the rate of good neurological outcomes decreased by advanced age (24.2%, 16.1%, 11.4%, and 5.9%, respectively), which was also observed after subgroup analysis based on the initial shockable (40.6%, 31.5%, 28.6%, and 14.9%, respectively) and non-shockable rhythm (10.6%, 7.2%, 4.1%, and 3.4%, respectively). Multivariate analysis showed the adjusted odds ratio (aOR) for good neurological outcome decreased as age increased (65-69: reference, 70-74: aOR 0.70, 75-79: aOR 0.49, and ≥ 80 years: aOR 0.25). The optimal age cutoffs for good outcomes in elderly OHCA survivors with shockable and non-shockable rhythm were 77 and 72 years, respectively. The neurologic recovery rate in OHCA survivors treated with TTM gradually decreased with increasing age. However, even patients aged ≥ 80 years with shockable rhythm had a good neurologic outcome of 14.9% compared with patients aged 65-69 years with non-shockable rhythm (10.6%).

Association between Initial Fibrinogen Levels and the Need for Massive Transfusion in Emergency Department Patients with Primary Postpartum Hemorrhage: A Retrospective Study from a Single Center in Korea.

BACKGROUND: This study aimed to evaluate the association between initial fibrinogen levels and massive transfusion (MT) in emergency department (ED) patients with primary postpartum hemorrhage (PPH). METHODS: This retrospective study was conducted in the ED of a university-affiliated, tertiary referral center from January 2004 to August 2023. Patients were divided into two groups: the MT group, which included those who received a transfusion of 10 or more units of packed red blood cells within the first 24 h, and the Non-MT group. RESULTS: Out of the 364 patients included in the study, 97 (26.6%) required MT. Fibrinogen, shock index, and lactate were independently associated with MT (odds ratio [OR] 0.987; 95% confidence interval [CI] 0.983-0.991; p < 0.001, OR 7.277; 95% CI 1.856-28.535; p = 0.004, and OR 1.261; 95% CI 1.021-1.557; p = 0.031, respectively). The area under the receiver operating characteristic curve for fibrinogen, shock index, and lactate in predicting MT was 0.871 (95% CI 0.832-0.904; p < 0.001), 0.821 (95% CI 0.778-0.859; p < 0.001), and 0.784 (95% CI 0.738-0.825; p < 0.001), respectively. When the cutoff value of fibrinogen was 400 mg/dL, both the sensitivity and negative predictive values for predicting MT were 100.0%. When the cutoff value of fibrinogen was 100 mg/dL, the specificity and positive predictive values were 91.8% and 70.7%, respectively. CONCLUSION: The initial fibrinogen levels were independently associated with the need for MT in ED patients with primary PPH.

Prognostic Role of Initial Thromboelastography in Emergency Department Patients with Primary Postpartum Hemorrhage: Association with Massive Transfusion.

BACKGROUND: The early prediction of the need for massive transfusions (MTs) and the preparation of blood products are essential for managing patients with primary postpartum hemorrhage (PPH). Thromboelastography (TEG) enables a thorough evaluation of coagulation status and is useful for guiding the treatment of hemorrhagic events in various diseases. We investigated the role of TEG in predicting the need for MT in patients with primary PPH. METHODS: A retrospective observational study was conducted in the emergency department (ED) of a university-affiliated, tertiary referral center between November 2015 and August 2023. TEG was performed upon admission. We defined MT as the requirement for transfusion of more than 10 units of packed red blood cells within the first 24 h. The primary outcome was the need for MT. RESULTS: Among the 184 patients with initial TEG, 34 (18.5%) required MT. Except for lysis after 30 min, the MT and non-MT groups had significantly different TEG values. Based on multivariate analysis, an angle < 60 was an independent predictor of MT (odds ratio (OR) 7.769; 95% confidence interval (CI), 2.736-22.062), along with lactate (OR, 1.674; 95% CI, 1.218-2.300) and shock index > 0.9 (OR, 4.638; 95% CI, 1.784-12.056). Alpha angle < 60 degrees indicated the need for MT with 73.5% sensitivity, 72.0% specificity, and 92.3% negative predictive value. CONCLUSIONS: Point-of-care testing of TEG has the potential to be a useful tool in accurately predicting the necessity for MT in ED patients with primary PPH at an early stage.

Comparison of Modified Shock Index and Shock Index for Predicting Massive Transfusion in Women with Primary Postpartum Hemorrhage: A Retrospective Study.

BACKGROUND The modified shock index (MSI) is calculated as the ratio of heart rate (HR) to mean arterial pressure (MAP) and has been used to predict the need for massive transfusion (MT) in trauma patients. This retrospective study from a single center aimed to compare the MSI with the traditional shock index (SI) to predict the need for MT in 612 women diagnosed with primary postpartum hemorrhage (PPH) at the Emergency Department (ED) between January 2004 and August 2023. MATERIAL AND METHODS The patients were divided into the MT group and the non-MT group. The predictive power of MSI and SI was compared using the areas under the receiver operating characteristic curve (AUC). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value were calculated. RESULTS Out of 612 patients, 105 (17.2%) required MT. The MT group had higher median values than the non-MT group for MSI (1.58 vs 1.07, P<0.001) and SI (1.22 vs 0.80, P<0.001). The AUC for MSI, with a value of 0.811 (95% confidence interval [CI], 0.778-0.841), did not demonstrate a significant difference compared to the AUC for SI, which was 0.829 (95% CI, 0.797-0.858) (P=0.066). The optimal cutoff values for MSI and SI were 1.34 and 1.07, respectively. The specificity and PPV for MT were 77.1% and 40.2% for MSI, and 83.2% and 45.9% for SI. CONCLUSIONS Both MSI and SI were effective in predicting MT in patients with primary PPH. However, MSI did not demonstrate superior performance to SI.

Respiratory rate­oxygenation (ROX) index for predicting high-flow nasal cannula failure in patients with and without COVID-19.

BACKGROUND: The predictive value of the respiratory rate­oxygenation (ROX) index for a high-flow nasal cannula (HFNC) in patients with COVID-19 with acute hypoxemic respiratory failure (AHRF) may differ from patients without COVID-19 with AHRF, but these patients have not yet been compared. We compared the diagnostic accuracy of the ROX index for HFNC failure in patients with AHRF with and without COVID-19 during acute emergency department (ED) visits. METHODS: We performed a retrospective analysis of patients with AHRF treated with an HFNC in an ED between October 2020 and April 2022. The ROX index was calculated at 1, 2, 4, 6, 12, and 24 h after HFNC placement. The primary outcome was the failure of the HFNC, which was defined as the need for subsequent intubation or death within 72 h. A receiver operating characteristic (ROC) curve was used to evaluate discriminative power of the ROX index for HFNC failure. RESULTS: Among 448 patients with AHRF treated with an HFNC in an ED, 78 (17.4%) patients were confirmed to have COVID-19. There was no significant difference in the HFNC failure rates between the non-COVID-19 and COVID-19 groups (29.5% vs. 33.3%, p = 0.498). The median ROX index was higher in the non-COVID-19 group than in the COVID-19 group at all time points. The prognostic power of the ROX index for HFNC failure as evaluated by the area under the ROC curve was generally higher in the COVID-19 group (0.73-0.83) than the non-COVID-19 group (0.62-0.75). The timing of the highest prognostic value of the ROX index for HFNC failure was at 4 h for the non-COVID-19 group, whereas in the COVID-19 group, its performance remained consistent from 1 h to 6 h. The optimal cutoff values were 6.48 and 5.79 for the non-COVID-19 and COVID-19 groups, respectively. CONCLUSIONS: The ROX index had an acceptable discriminative power for predicting HFNC failure in patients with AHRF with and without COVID-19 in the ED. However, the higher ROX index thresholds than those in previous publications involving intensive care unit (ICU) patients suggest the need for careful monitoring and establishment of a new threshold for patients admitted outside the ICU.

Ion Shift Index at the Immediate Post-Cardiac Arrest Period as an Early Prognostic Marker in Out-of-Hospital Cardiac Arrest Survivors.

The ion shift index (ISI) is a suggested marker to reflect the magnitude of ischemic damage. This study aimed to investigate the prognostic value of the ISI for predicting poor neurological outcomes at 6 months in comatose out-of-hospital cardiac arrest (OHCA) survivors by comparing it with the OHCA and Cardiac Arrest Hospital Prognosis (CAHP) scores. This observational registry-based cohort study included adult comatose OHCA survivors admitted to a tertiary care hospital in Korea between 2015 and 2021. The ISI was calculated using the serum electrolyte levels obtained within one hour of resuscitation. The primary outcome was poor neurological function (Cerebral Performance Category score of 3−5) at 6 months. Of the 250 OHCA survivors, 164 (65.6%) had poor neurological outcomes. These patients had a higher median ISI than those with good neurological outcomes (4.95 vs. 3.26, p < 0.001). ISI (adjusted odds ratio, 2.107; 95% confidence interval, 1.350−3.288, p = 0.001) was associated with poor neurological outcomes. The prognostic performance of ISI (area under the curve [AUC], 0.859) was similar to that of the OHCA score (AUC, 0.858; p = 0.968) and the CAHP score (AUC, 0.894; p = 0.183). ISI would be a prognostic biomarker for comatose OHCA survivors that is available during the immediate post-cardiac arrest period.

Elevation of the D-dimer cut-off level might be applicable to rule out pulmonary embolism for active cancer patients in the emergency department.

Recent guidelines for diagnosing acute pulmonary embolism (PE) are based on clinical decision rules and D-dimer. D-dimer measurement is recommended only for patients who are 'PE-unlikely'. We aimed to assess the current guidelines for cancer patients and to determine an optimal D-dimer cut-off level. This retrospective observational study was conducted in the emergency department of Asan Medical Center (Seoul, Korea) between 02/2017 and 09/2017 for the development cohort and between 06/2018 and 02/2019 for the validation cohort. Among adult active cancer patients with suspected PE, we included those who were 'PE-unlikely' according to Wells' criteria and who underwent D-dimer testing and computed tomographic pulmonary angiography (CTPA). A total of 498 patients (227 in the development cohort and 271 in the validation cohort) were included, and PE was diagnosed in 8.8% and 18.5% of patients, respectively. The optimal D-dimer cut-off level was 2.0 µg/mL. This elevated cut-off level showed a much higher specificity of 21.3% (95% confidence interval [CI] 16.2-27.3%) and 21.7% (95% CI 16.8-7.6%) in the development and validation sets, respectively, compared with the specificity of 4.4% (95% CI 2.3-8.1%) and 4.1% (95% CI 2.2-7.6%) using the age-adjusted cut-off. The new D-dimer cut-off value identified unnecessary CTPA for 21.3% of patients (absolute difference, 16.9%, 35 of 207) in the development cohort and 21.7% (absolute difference, 17.6%, 39 of 221) of patients in the validation cohort compared to using the standard age-adjusted cut-off. The elevated D-dimer cut-off value combined with Wells' criteria might reduce unnecessary CTPA in active cancer patients with a 'PE-unlikely' classification. Further clinical trials are warranted to improve the PE diagnostic strategy in cancer patients.

Viscous Cervical Environment-on-a-Chip for Selecting High-Quality Sperm from Human Semen.

When ejaculated sperm travels through the vagina to the uterus, mucus secreted by the cervical canal generally filters out sperm having low motility and poor morphology. To investigate this selection principle in vivo, we developed a microfluidic sperm-sorting chip with a viscous medium (polyvinylpyrrolidone: PVP) to imitate the biophysical environment mimic system of the human cervical canal. The material property of the PVP solution was tuned to the range of viscosities of cervical mucus using micro-viscometry. The selection of high-quality human sperm was experimentally evaluated in vitro and theoretically analyzed by the convection-diffusion mechanism. The convection flow is shown to be dominant at low viscosity of the medium used in the sperm-sorting chip when seeded with raw semen; hence, the raw semen containing sperm and debris convectively flow together with suppressed relative dispersions. Also, it was observed that the sperm selected via the chip not only had high motilities but also normal morphologies and high DNA integrity. Therefore, the biomimetic sperm-sorting chip with PVP medium is expected to improve male fertility by enabling the selection of high-quality sperm as well as uncovering pathways and regulatory mechanisms involved in sperm transport through the female reproductive tract for egg fertilization.

External validation of the post-varicocele repair semen analysis nomogram to predict total motile sperm count: A multicenter study.

Total motile sperm count is an important parameter for predicting the probability of natural pregnancy. We have externally validated the Samplaski's post-varicocele repair semen analysis nomogram to confirm the predictive accuracy of total motile sperm count. A total of 300 patients who had undergone varicocelectomy between July 2016 and July 2019 from 4 treatment centres were included in this validation cohort study. The predictive performance of the externally validated nomogram was revealed by applying the Pearson correlation coefficient (R = 0.328; 95% confidence interval (CI) 0.220-0.435; p < .001). Compared to Samplaski's nomogram result (R = 0.581; 95% CI 0.186-0.729), our study also revealed a statistically significant rate. However, it had a relatively lower correlation coefficient rate. Notably, the predicted total motile sperm count was lower than the observed post-varicocelectomy total motile sperm count. The calibration plot revealed that the discrepancy between the predicted and observed total motile sperm count was plausible. However, it had low explanatory power in this nomogram model. This validation study demonstrates that the post-varicocele repair Samplaski's nomogram predicts a relatively lower total motile sperm count than the observed count.

Quisqualis indica extract ameliorates low urinary tract symptoms in testosterone propionate-induced benign prostatic hyperplasia rats.

Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively. LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.

Motility enhancement of human spermatozoa using electrical stimulation in the nano-Ampere range with enzymatic biofuel cells.

Sperm motility is a crucial factor for normal fertilisation that is partly supported by mitochondrial activity. Enzymatic biofuel cells (EBFCs) generate electric currents by an electron grade from anodic to cathodic electrodes in a culture media. We demonstrate that electrical stimulation by EBFC at the nano-Ampere range enhances sperm motility that can potentially allow the development of a new therapeutic tool for male infertility, including poor motility. EBFC was set up with three different electrical currents (112 nA/cm2 and 250 nA/cm2) at two different times (1 h, 2 h). Each sample was evaluated for its motility by computer-assisted sperm analyses and sperm viability testing. In the expanded study, we used the optimal electrical current of the EBFC system to treat asthenozoospermia and sperm with 0% motility. Results showed that optimal electrical stimulation schemes with EBFCs enhanced sperm motility by 30-40% compared with controls. Activated spermatozoa led to tyrosine phosphorylation in the tail area of the sperm following the electrical stimulation in the nano-Ampere range. However, the electrically stimulated group did not exhibit increased acrosomal reaction rates compared with the control group. In cases related to asthenozoospermia, 40% of motility was recovered following the electrical stimulation at the nano-Ampere range. However, motility is not recovered in sperm with 0% motility. In conclusion, we found that sperm motility was enhanced by exposure to electrical currents in the nano-Ampere range induced by optimal EBFCs. Electrical stimulation enhanced the motility of the sperm though tyrosine phosphorylation in spermatozoa. Therefore, our results show that electrical currents in the nano-Ampere range can be potentially applied to male infertility therapy as enhancers of sperm motility in assisted reproductive technology.

A study on the physical fitness of children with juvenile rheumatoid arthritis.

[Purpose] This study was conducted to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA). [Subjects and Methods] In total, 26 children with juvenile rheumatoid arthritis (JRA) and 25 healthy controls participated in this study. Using the physical fitness measurement instruments, the Inbody 720 and Quark b2, the elements of physical fitness that were assessed included muscular strength, muscular endurance, flexibility, lung capacity, and body composition. [Results] The results revealed significant differences in muscular strength, muscular endurance, lung capacity, body composition, functional ability, and health-related quality of life between the children with juvenile rheumatoid arthritis (JRA) and the control group. [Conclusion] These results suggested that children with juvenile rheumatoid arthritis (JRA) have inferior physical fitness when compared to healthy children. The present study was conducted to develop an accurate evaluation standard to assess the physical fitness of children with juvenile rheumatoid arthritis (JRA).

Systematic functional analysis of kinases in the fungal pathogen Cryptococcus neoformans.

Cryptococcus neoformans is the leading cause of death by fungal meningoencephalitis; however, treatment options remain limited. Here we report the construction of 264 signature-tagged gene-deletion strains for 129 putative kinases, and examine their phenotypic traits under 30 distinct in vitro growth conditions and in two different hosts (insect larvae and mice). Clustering analysis of in vitro phenotypic traits indicates that several of these kinases have roles in known signalling pathways, and identifies hitherto uncharacterized signalling cascades. Virulence assays in the insect and mouse models provide evidence of pathogenicity-related roles for 63 kinases involved in the following biological categories: growth and cell cycle, nutrient metabolism, stress response and adaptation, cell signalling, cell polarity and morphology, vacuole trafficking, transfer RNA (tRNA) modification and other functions. Our study provides insights into the pathobiological signalling circuitry of C. neoformans and identifies potential anticryptococcal or antifungal drug targets.

Use of cryopreserved cadaveric arterial allograft as a vascular conduit for peripheral arterial graft infection.

Major peripheral arterial graft infection is a potentially devastating complication of vascular surgery, associated with significant mortality and high amputation rates. Autologous saphenous veins are considered optimal arterial conduits for lower extremity revascularization in infected fields, but they are often unavailable or unsuitable in these patients. This study describes two patients with major peripheral graft infection, but without available autologous veins, who underwent graft excision and cryopreserved cadaveric arterial allograft reconstruction. Although long-term graft durability is unclear because of gradual deterioration and degeneration, these findings suggest that cadaveric allografts may be good options for patients with major peripheral graft infection.

Relation between functional ability and health-related quality of life of children with juvenile rheumatoid arthritis.

[Purpose] The aim of this study was to assess patients' health-related quality of life, compare it with a healthy age-matched population, and examine associations between functional ability and quality of life among juvenile rheumatoid arthritis (JRA) patients. [Subjects and Methods] The study participants were 26 JRA patients and 25 controls. The Childhood Health Assessment Questionnaire and the Pediatric Quality of Life Inventory 4.0 Generic Core Scales were used to evaluate functional ability and health-related quality of life, respectively. [Results] Functional ability scores averaged 0.37 in the JRA group and 0.08 in the control group. There were significant between-group differences in functional ability scores in the overall cohort and in the subgroup of participants aged 14-16 years. Health-related quality of life scores were significantly lower in the JRA group than in the control group (68.39 vs. 85.17). In the JRA group, functional ability was statistically positively correlated with health-related quality of life. [Conclusion] We conclude that the mental state of adolescents with JRA affects their particular functional abilities. Subjects in the 14-16 age group who had a longer disease duration and higher difficulty scores showed a lower health-related quality of life than children in the other age groups.

Systematic functional profiling of transcription factor networks in Cryptococcus neoformans.

Cryptococcus neoformans causes life-threatening meningoencephalitis in humans, but its overall biological and pathogenic regulatory circuits remain elusive, particularly due to the presence of an evolutionarily divergent set of transcription factors (TFs). Here, we report the construction of a high-quality library of 322 signature-tagged gene-deletion strains for 155 putative TF genes previously predicted using the DNA-binding domain TF database, and examine their in vitro and in vivo phenotypic traits under 32 distinct growth conditions. At least one phenotypic trait is exhibited by 145 out of 155 TF mutants (93%) and ∼85% of them (132/155) are functionally characterized for the first time in this study. The genotypic and phenotypic data for each TF are available in the C. neoformans TF phenome database (http://tf.cryptococcus.org). In conclusion, our phenome-based functional analysis of the C. neoformans TF mutant library provides key insights into transcriptional networks of basidiomycetous fungi and human fungal pathogens.

9-O-butyl-13-(4-isopropylbenzyl)berberine, KR-72, is a potent antifungal agent that inhibits the growth of Cryptococcus neoformans by regulating gene expression.

In this study we explored the mode of action of KR-72, a 9-O-butyl-13-(4-isopropylbenzyl)berberine derivative previously shown to exhibit potent antifungal activity against a variety of human fungal pathogens. The DNA microarray data revealed that KR-72 treatment significantly changed the transcription profiles of C. neoformans, affecting the expression of more than 2,000 genes. Genes involved in translation and transcription were mostly upregulated, whereas those involved in the cytoskeleton, intracellular trafficking, and lipid metabolism were downregulated. KR-72 also exhibited a strong synergistic effect with the antifungal agent FK506. KR-72 treatment regulated the expression of several essential genes, including ECM16, NOP14, HSP10 and MGE1, which are required for C. neoformans growth. The KR-72-mediated induction of MGE1 also likely reduced the viability of C. neoformans by impairing cell cycle or the DNA repair system. In conclusion, KR-72 showed antifungal activity by modulating diverse biological processes through a mode of action distinct from those of clinically available antifungal drugs such as polyene and azole drugs.

A Nudix Hydrolase Protein, Ysa1, Regulates Oxidative Stress Response and Antifungal Drug Susceptibility in Cryptococcus neoformans.

A nucleoside diphosphate-linked moiety X (Nudix) hydrolase-like gene, YSA1, has been identified as one of the gromwell plant extract-responsive genes in Cryptococcus neoformans. Ysa1 is known to control intracellular concentrations of ADP-ribose or O-acetyl-ADP-ribose, and has diverse biological functions, including the response to oxidative stress in the ascomycete yeast, Saccharomyces cerevisiae. In this study, we characterized the role of YSA1 in the stress response and adaptation of the basidiomycete yeast, C. neoformans. We constructed three independent deletion mutants for YSA1, and analyzed their mutant phenotypes. We found that ysa1 mutants did not show increased sensitivity to reactive oxygen species-producing oxidative damage agents, such as hydrogen peroxide and menadione, but exhibited increased sensitivity to diamide, which is a thiol-specific oxidant. Ysa1 was dispensable for the response to most environmental stresses, such as genotoxic, osmotic, and endoplasmic reticulum stress. In conclusion, modulation of YSA1 may regulate the cellular response and adaptation of C. neoformans to certain oxidative stresses and contribute to the evolution of antifungal drug resistance.