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Therapeutic monoclonal antibodies are an effective method of treating acute infectious diseases. However, knowing which of the produced antibodies in the vast number of human antibodies can cure the disease requires a long time and advanced technology. The previously introduced iBRAB method relies on studied antibodies to design a broad-spectrum antibody capable of neutralizing antigens of many different Influenza A viral strains. To evaluate the antigen-binding fragment as an applicable drug, the therapeutic antibody profiles providing guidelines collected from clinically staged therapeutic antibodies were used to access different measurements. Although the evaluated values were within an accepted range, the modification in the amino acid sequence is required for better properties. Thus, using the steered molecular dynamics (SMD) simulation to determine the binding capacity of amino acids in the functional region, the profile of interacted amino acids of Fab with the antigen was established for modified reference. As a result, the model was modified with amino acids elimination at positions 96–97 in the heavy chain and 26–27, 91, 96–97, and 102–103 in the light chain, which has better Therapeutic Antibody Profiler evaluations than the original designation. Thus again, SMD simulation is a promising computational approach for post-modification in rational drug design. [ABSTRACT FROM AUTHOR]

Management of undernourished children depends only on wasting yet it can coexist with underweight and/or stunting. Among children admitted to hospital with acute illness, we determined the proportion with wasting coexisting with underweight and/or stunting and their risk factors. A retrospective review of hospital records of children 6‒59 months old admitted at Garissa County referral hospital, Kenya, from January 2017 to December 2019 was conducted. Using World Health Organization 2006 growth standards, undernutrition were defined: wasting as Weight‐for‐height Z‐score < −2, stunting Height‐for‐age Z‐score < −2 and underweight Weight‐for‐age Z‐score < −2. We studied wasting coexisting with underweight and/or stunting. Among 624 children recruited, 347 (56%) were males and 511 (82%) <24 months old. Diarrhoea 210 (34%) and pallor/anaemia 310 (50%) were the most frequent admission diagnosis. HIV infection was present among 8 (1.3%) children. Wasting, underweight and stunting were present among 595 (95%), 518 (83%) and 176 (28%) children respectively. 161 (26%), 506 (81%) and 161 (26%) children had wasting coexisting with stunting, underweight and both stunting and underweight respectively. In the multivariable regression, diarrhoea was positively associated with wasting coexisting with stunting (adjusted risk ratio [aRR = 2.96] [95% CI = 2.06‒4.23]) and anaemia with wasting coexisting with underweight (aRR = 1.23) (95% CI = 1.03‒1.47). Overall, 343 (55%) children were discharged alive, 67 (11%) absconded from the wards, 164 (26%) were transferred to another hospital and 50 (8.0%) died before discharge. The risk of inpatient death was 10.3%, 7.9%, 8.4% and 6.8% among children not wasted, wasted only, wasted & underweight, and wasted and underweight and stunted respectively (Chi‐square p = 0.60). The study reports an unacceptably high levels of undernourishment, including coexisting forms of undernutrition among hospitalised children. This highlights a public health priority for current nutrition therapeutic care and need of continuity of care among those children discharged alive in the community‐based management of acute malnutrition programmes. [ABSTRACT FROM AUTHOR]

Acute upper gastrointestinal bleeding (UGIB) is a medical emergency with most common cause being peptic ulcer disease (PUD) or variceal bleeding. However, cancers that cause UGIB by invading the small intestine are uncommon, and the invasion of renal cell carcinoma (RCC) into the duodenum is an even rarer occurrence. A 55‐year‐old male presented with melena and right flank pain. Esophagogastroduodenoscopy (EGD) revealed an active bleeding source in the duodenum, later identified on contrast‐enhanced computed tomography (CECT) as a duodenorenal fistula (DRF) caused by direct extension of the RCC. The imaging confirmed the presence of a malignant renal mass infiltrating adjacent organs. This atypical presentation of RCC with DRF manifesting as UGIB underscores the importance of comprehensive evaluations in cases of gastrointestinal bleeding to identify rare underlying causes. [ABSTRACT FROM AUTHOR]

Background: Acute exacerbations of COPD (AECOPD) are common and significantly contribute to mortality in patients with COPD. Prognostic scores can assist clinicians in making tailored decisions to manage AECOPD. In the current study, we therefore aimed to evaluate the performance of the Noninvasive Ventilation Outcomes (NIVO) score, originally designed to assess in-ICU mortality, in predicting 1 year mortality and NIV failure in AECOPD. Methods: This retrospective study analyzed data from patients hospitalized for AECOPD requiring mechanical ventilation between January 1st, 2018, and December 31st, 2022. Mortality was assessed at the end of ICU stay and 1 year after admission, while NIV failure was defined as intubation or death without intubation. Results: Among 302 ICU admissions of COPD patients, 190 patients with AECOPD requiring mechanical ventilation were included. Of these, 44 (23%) died in the ICU, 62 out of 184 (34%) failed NIV, and 78 (41%) died within 1 year of admission. Patients who died in ICU or experienced NIV failure had more severe COPD and more impaired blood gas parameters at admission. The NIVO score demonstrated an AUC of 0.68 in predicting 1-year mortality and an AUC of 0.85 in predicting NIV failure. A NIVO score over 7 was associated with higher 1-year mortality and NIV failure (HR of 4.4 [1.8–10.9] and 41.6 [5.6–307.9], respectively). Conclusion: Beyond predicting in-ICU mortality, the NIVO-score is a reliable tool in predicting 1-year mortality and NIV failure in AECOPD. [ABSTRACT FROM AUTHOR]

Purpose: Patients with hypoalbuminemia, (serum albumin (SA) < 3.5 g/dL) are at greater risk for complications after surgery, including increased postoperative infection rates after total knee arthroplasty (TKA). This study aimed to analyze both preoperative and postoperative SA in patients who experienced acute periprosthetic infection within the first 4 weeks after surgery. Methods: We retrospectively analyzed data from 490 consecutive TKAs (314 patients). Five patients developed early acute infection requiring surgical treatment. SA data were collected preoperatively (SA0) and 1 week postoperatively (SA1W) to evaluate SA dynamics. Multiple patient and operative parameters that could influence SA were also analyzed. Results: No statistical differences were found in parameters expected to influence SA values between the surgically treated (STG) and non-treated groups (non-STG). None of the patients in STG had SA0 and SA1W below 3.5 g/dL. However, the amount and rate of SA reduction before and after surgery were significantly greater in STG than in non-STG. Conclusion: SA dynamics revealed a greater reduction in both the amount and rate in STG before and after surgery than in non-STG. No correlation was found between early acute periprosthetic infection after TKA and each SA0 and SA1W time point. Further evaluation of the SA value of 3.5 g/dL as a threshold for acute early acute infection is warranted. [ABSTRACT FROM AUTHOR]

Background Data on the true prevalence of respiratory syncytial virus (RSV) among medically attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over 3 seasons, which is informative in light of the recommendations for shared decision making for vaccination in older adults. Methods Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated multimorbidity-weighted index (MWI) were collected by in-person survey and electronic medical record review. Results Over 3 surveillance seasons (fall 2017 to spring 2020), 9.9% (n = 441) of 4442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months to 4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). Conclusions RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision making for vaccination. [ABSTRACT FROM AUTHOR]

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021–2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0–5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages. [ABSTRACT FROM AUTHOR]

Background Unlike influenza, information on the burden of human metapneumovirus (HMPV) as a cause of hospitalizations in adults with acute respiratory illness (ARI) is limited. Methods We compared the population-based incidence, seasonality, and clinical characteristics of these 2 viral infections among adults aged ≥20 years with ARI hospitalizations in Auckland, New Zealand, during 2012–2015 through the Southern Hemisphere Influenza Vaccine Effectiveness Research and Surveillance (SHIVERS) project. Results Of the 14 139 ARI hospitalizations, 276 of 6484 (4.3%) tested positive for HMPV and 1342 of 7027 (19.1%) tested positive for influenza. Crude rates of 9.8 (95% confidence interval [CI], 8.7–11.0) HMPV-associated and 47.6 (95% CI, 45.1–50.1) influenza-associated ARI hospitalizations were estimated for every 100 000 adult residents annually. The highest rates for both viruses were in those aged ≥80 years, of Māori or Pacific ethnicity, or living in low socioeconomic status (SES) areas. HMPV infections were more common than influenza in those with chronic medical conditions. Conclusions Although HMPV infections accounted for fewer hospitalizations than influenza in adults aged ≥20 years, HMPV-associated ARI hospitalization rates were higher than influenza in older adults, Māori and Pacific people, and those of low SES. This highlights a need for vaccine/antiviral development. [ABSTRACT FROM AUTHOR]

Advanced clinical practitioners (ACPs) are experienced health professionals educated to master's level. They are accountable for the assessment, diagnosis and treatment of individuals, and are responsible for making complex decisions. The case study presented in this article critically analyses the consultation involving a male patient in his sixties with a 2-day history of abdominal pain, who was referred by his GP to a surgical assessment unit. Analysis was carried out using the Calgary-Cambridge Model. The article discusses history-taking, abdominal examination and differential diagnoses, and presents the process of how the trainee ACP arrived at the diagnosis of appendicitis. [ABSTRACT FROM AUTHOR]

Ionized Mg (iMg) may offer a more reliable indicator of Mg status during acute illness than total Mg (tMg) concentrations. This study aimed to determine the prevalence of dysmagnesemia and their relationship using iMg and tMg. The clinical and biochemical characteristics as well as health outcomes and their association with iMg and tMg were also assessed. A prospective study including all eligible adult patients (≥18 years) who were hospitalized in the General Internal Medicine unit at Sultan Qaboos University Hospital (SQUH) for 3.5 months in 2023. The iMg and tMg concentrations were collected on all at the admission. In total 500 patients were included (females 49.2%) with a median age of 64.5 years (IQR: 48-77). The prevalence of hypomagnesemia and hypermagnesemia by iMg concentrations was 3.4% and 26.6%, respectively, while by tMg concentrations 13.2% and 11.0%, respectively. The agreement between both measurements was strong (r=0.665, p<0.01). An increased tMg concentration was independently associated with high dependency units' admission (adjusted odds ratio (aOR): 4.34, 95%CI: 1.24-15.06, p=0.02) and cardiac arrest (aOR: 14.64, 95%CI: 3.04-70.57, p<0.01), and 6-month all-cause mortality (aOR: 11.44, 95%CI: 2.46-53.17, p<0.01). During follow-up hypermagnesemia using tMg had a higher mortality compared to other groups (hazard ratio (HR): 1.82, 95%CI: 1.11-3.01, p=0.02) while no significant findings were demonstrated using iMg concentrations. iMg and tMg concentrations had a strong correlation that might be supporting the potential use of point-of-care devices. Multivariant regression analysis showed that hypermagnesemia by tMg was associated with adverse outcomes. However, the generalizability of the study findings should be taken with caution and the difference in the associations with outcomes highlight the importance of further research to examine the complex associations and impacts of dysmagnesemia in various clinical settings. [ABSTRACT FROM AUTHOR]

The 'shark-fin' ECG-sign is a rare electrocardiographic pattern seen in ACS, typically associated with poor prognosis. However, its manifestation in acute aortic syndromes remains largely unexplored. Here, we present a case of a patient diagnosed with Ascending Aortic Dissection, who presented to ED with acute chest pain and shark-fin ECG-pattern. [ABSTRACT FROM AUTHOR]

Background: Acute mesenteric ischemia (AMI) usually presents with abrupt and severe abdominal pain associated with nausea and vomiting. This case is notable due to the occurrence of AMI secondary to acute systolic heart failure caused by new onset complete heart block. Case Presentation: A 65-year-old male presented with sudden onset epigastric pain. ECG showed complete AV block and acute ischemia, and a subsequent CTA revealed complete occlusion of the mid superior mesenteric artery. His emergent left heart catheterization showed non-occlusive coronary artery disease. The patient underwent emergent laparotomy and SMA thrombectomy. Postoperative complications included worsening congestive heart failure and persistent bradycardia, requiring a permanent pacemaker. The patient was discharged to a skilled nursing facility in stable condition. Conclusions: This case highlights the diagnostic challenges of AMI in the setting of acute heart failure and new onset AV block mimicking acute cardiac events and emphasizes the importance of a multidisciplinary approach in managing such complex cases. [ABSTRACT FROM AUTHOR]

The authors present a case of an acute right middle cerebral artery infarct in a 65-year-old male with a history of diabetes, hypertension, and cardiovascular disease. The timeline of treatment and the evolution of the stroke is described. This case highlights the significant burden of right-sided cerebral artery stroke, even when intervention is swift. [ABSTRACT FROM AUTHOR]

ABSTRACT Filariae are parasitic nematodes of high veterinary and medical importance, responsible for some acute tropical diseases. They are transmitted through the bite of hematophagous vectors such as biting midges and blackflies. Filariae are among the most prevalent vector‐borne parasitoses in Neotropical primates in which severe infections can cause inflammatory reactions and tissue damage. Given the location inside the host (peritoneal cavity, bloodstream, and lymphatics), the detection of filariid nematodes is challenging and is mostly postmortem; hence the scarcity of studies on the prevalence of filariae in wild primate populations. Here, we report the prevalence of filariid infections in free‐ranging populations of Geoffroy's spider (Ateles geoffroyi) and black howler (Alouatta pigra) monkeys across southern Mexico, using a combination of noninvasive sampling and molecular diagnostic techniques. Fecal samples were screened for filariid DNA by qPCR protocols. A total of 88 samples were examined with an overall prevalence of 26%. Filariae were slightly more common in spider monkeys compared to howler monkeys. This study constitutes the first report of the prevalence of infection of filariid nematodes in populations of wild spider monkey across southern Mexico, and the first reporting of filariae in black howler monkeys, as part of a new era of primate parasitology and the diagnostics of parasite infections in light of the everyday more affordable molecular tools. [ABSTRACT FROM AUTHOR]

Introduction: When young children experience recurrent respiratory infections, caregivers face the challenge of preventing new episodes whilst maintaining close rapport with their children. Pediatric massage, such as pediatric Tuina, entails soft massage of the skin, administered by trained providers. This non-pharmaceutical measure is used to prevent new respiratory infections in China. The aim of this study is to deepen our understanding of caregivers' experiences and perceptions of providing pediatric Tuina treatment to their children with recurrent respiratory tract infections. Methods: A qualitative study, based on semi-structured interviews, was conducted in accordance with the Consolidated Criteria for Reporting Qualitative Research checklist. Sixteen mothers from Southern China, whose children had received pediatric Tuina for recurrent respiratory tract infections, participated online. Analysis was conducted according to the principles of reflexive thematic analysis, using the NVivo qualitative research software. Results: The overarching theme was "Fostering embodied care with children". Caregivers assessed pediatric Tuina by hearing others' experiences of pediatric Tuina, as well as observing the manipulations on their child's body and their bodily reactions during pediatric Tuina sessions. Caregivers also closely observed children's bodily changes after pediatric Tuina sessions. Embodied attachment between children and adults was nurtured through the pediatric Tuina. Compared to other treatments or medical consultations, children were more relaxed and more involved in embodied care, which involved direct skin touching and verbal communication from the pediatric Tuina provider. Children also took the initiative to bring pediatric Tuina into their family life, by asking caregivers to perform it on them and mimicking the manipulations on the caregivers' hand. Conclusions: Pediatric Tuina served as a means of interaction between children and adults, fostering an embodied care on both a physical and emotional level. Beyond its potentially preventive effect on recurrent respiratory tract infections, pediatric Tuina could be a support for parents of children with recurrent or chronic disease at home. [ABSTRACT FROM AUTHOR]

Background: Mucosal-associated invariant T (MAIT) cells play key roles in many inflammatory diseases. However, their effects on the long-term course of oral lichen planus (OLP) and recent-onset OLP remain unclear. In this study, we aimed to investigate the function of MAIT cells in the different processes of OLP and to explore the immunological background of this disease. Methods: The frequency, phenotype, cytokine secretion, and clinical relevance of MAIT cells were investigated. MAIT cells were collected from the peripheral blood of 14 adults with recent-onset OLP (7–120 days after disease onset) and 16 adults with long-term course OLP (>2 years after diagnosis) using flow cytometry and compared with 15 healthy blood donors. Statistical analyses were performed using the GraphPad Prism software. Results: MAIT cells from adults with recent-onset OLP exhibited an activated phenotype, as indicated by an increased frequency of CD69+ (p < 0.05) and CD38+MAIT cells (p < 0.01) and elevated production of the proinflammatory cytokine IL-17 A (p < 0.01), compared with healthy adult donors. In adults with long-term OLP, MAIT cells exhibited an activated and exhausted phenotype, characterized by high expression of CD69 (p < 0.01) and PD-1 (p < 0.001) and increased production of granzyme B released (p < 0.01). Compared with recent-onset OLP patients, long-term OLP patients showed a decreased production of CD8+, and CD4−CD8− cells, but an increase in PD-1+ production (p < 0.05). Conclusions: Circulating MAIT cells exhibited activation in OLP patients across varying disease durations. Given that PD-1 expression is elevated in adults with long-term OLP, it is reasonable to infer that circulating MAIT cells in long-term OLP may exhibit a more exhausted state than those in recent-onset OLP. [ABSTRACT FROM AUTHOR]

Background/Objectives: Anemia during acute inflammation is not well described in the literature. We aimed to study whether patients develop a transient hemoglobin decrease during an acute attack of recurrent pericarditis. Methods: We retrospectively analyzed patients with recurrent pericarditis. The primary endpoint was the difference in hemoglobin levels during an acute attack and in the following remission. As secondary endpoints, we correlated this variation with laboratory and clinical features; we also evaluated the available baseline hemoglobin values. Results: Sixty-two patients, including thirty females (48.4%), with a median age of 39 years, were observed during an acute attack and remission. The attack indexed was the first in 21 patients and the second or the third in 41, with pre-attack hemoglobin levels available for the latter group. Median hemoglobin levels (IQR) were 13.8 (12.8–15.1) g/dL at baseline, 12.0 (11.2–13.4) during attacks and 13.6 (13.1–14.0) during remission (p < 0.001). The median hemoglobin reduction between an acute attack and remission was 1.4 g/dL. Their mean corpuscular volume remained in the normal range. Hb reduction significantly correlated with C-reactive protein (CRP) elevation, neutrophilia and the neutrophil-to-lymphocyte ratio, but not serosal involvement. Only CRP elevation remained associated with the variation of Hb in a multivariate analysis (p = 0.007). Conclusions: This study is a proof of concept: hemoglobin levels may decline rapidly during acute inflammation in correlation with CRP elevation, with transient normocytic anemia, followed by a rapid rebound. In this regard, idiopathic pericarditis may represent a pathogenetic model of this type of anemia. [ABSTRACT FROM AUTHOR]

Acute diarrheal diseases are a leading cause of childhood mortality and morbidity worldwide. Psidium guajava has been globally used for its antidiarrheal potential. We conducted a systematic review of scientific articles published up to the year 2021, which included in vivo pre‐clinical tests and clinical trials involving patients with acute infectious diarrhea to verify the antidiarrheal, antibacterial and antispasmodic effects of galenic preparations or phytopharmaceuticals from P. guajava. PRISMA and Rayyan were used as tools for the selection of studies collected in four databases (Pubmed, Scopus, Web of Science and Science Direct). The keywords used to carry out the search were: 'Psidium guajava', 'guava', 'antidiarrhe*' and 'diarrhe*', joined by Boolean operators 'OR' or 'AND'. The characteristics of studies in animal models of acute diarrhea induction, as well as in vivo and in vitro motility and microbiological tests linked with its main pathophysiological mechanisms, were collected. Twenty‐three articles were included. Twenty (87%) of these reported heterogenic preclinical studies, predominating pharmacological studies of efficacy against conventional antidiarrheal agents, which utilized relevant outcomes and models of infectious diarrhea from the top pathogens in the clinic along with classical castor oil‐induced diarrhea associated with motility tests. Only three articles (13%) corresponded to clinical trials investigating the efficacy, dose and safety of these preparations. Most studies reported positive results and significant mechanistic evidence from antibacterial, anti‐motility, anti‐secretory and protective/anti‐inflammatory perspectives. However, further studies are needed to define the clinical significance and safety treatment with P. guajava extracts. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: To investigate the diagnostic and therapeutic value of direct visualization (single-use eyeMax subscope) endoscopic management of acute uncomplicated appendicitis. Methods: Thirty-six patients diagnosed with acute uncomplicated appendicitis, confirmed by computed tomography or ultrasonography, from Jan 2023 to Feb 2024 were enrolled in this study. We collected demographics, colonoscopy findings, subscope findings, clinical outcomes of endoscopic retrograde appendicitis therapy (ERAT), and adverse events associated with ERAT. Results: Appendiceal intubation was successful for all 36 patients. Thirty-five patients (97.2%) were definitely confirmed as having acute uncomplicated appendicitis. One patient with negative appendicitis was diagnosed as having cecal diverticulitis with fecalith incarceration. The mean procedure time was 13.1 ± 13.6 min. One patient presented with worsening abdominal pain, and a computed tomography scan suggested a perforated appendix. The mean length of hospitalizations was 1.78 ± 2 days. The mean follow-up was 158 days; during this period, two patients (5.6%) experienced recurrent abdominal pain after 23 and 88 days and subsequently underwent laparoscopic appendectomy. Conclusion: Direct visualization ERAT may be effective for diagnosing and treating acute uncomplicated appendicitis and seems to have a low complication rate. [ABSTRACT FROM AUTHOR]

Background Pain assessment and proper evaluation of pain are prerequisites for treatment of acute and chronic pain. Until now, most evaluations have used only resting pain intensity and a unidimensional scale, although multidimensional pain assessment and especially assessment of functional pain impact on activities are recommended. The Defense and Veterans Pain Rating Scale (DVPRS) permits this multidimensional assessment, but no validated French translation exists. Objectives To validate the French translation of the multidimensional DVPRS, called the Functional Pain Scale (FPS), in multiple settings of acute and chronic pain. Study design Prospective observational study. Setting Two large hospitals in the French-speaking region of Switzerland. Methods We recruited 232 patients from February 2022 to January 2023. Patients with acute or chronic pain in different settings received a paper questionnaire with both a numerical rating scale (NRS) and the FPS and a customized evaluation questionnaire. Correlation between the FPS and NRS, psychometric properties, and patient preferences were analyzed. Results Correlation between the FPS and NRS was high for the whole group of 232 patients, as well for all subgroups. The multi-item FPS scale showed excellent internal consistency. A large majority of patients, even those >75 years of age, preferred the FPS over the NRS and stated that the FPS was easy to use. Conclusions The study confirms that the French translation of the DVPRS (the FPS) is a valid measurement instrument for acute and chronic pain evaluation in a wide range of patient groups and is easy for patients to use. Trial registration ClinicalTrials.gov ID: NCT05307380. [ABSTRACT FROM AUTHOR]

This study investigated the alleviating effect of fermented ginsenosides obtained through yeast strain fermentation transformation on acute liver injury (ALI) induced by CCl4. Strains were screened for their ability to produce β-glucosidase, the transformation ability of the strain was verified by high-performance liquid chromatography, and the Saccharomyces cerevisiae strain F6 was obtained by 26S rRNA sequencing. After fermentation by F6 strain, it was found that the content of ginsenosides Re, Rb1, and Rb2 was significantly decreased (P < 0.05), and rare ginsenosides were detected, with the content of Rh4 and Rg5 reaching 2.65 mg·g−1 and 2.56 mg·g−1. We also explored the preventive effect of fermented ginsenoside extract (FGE) on ALI. Mice were evenly divided into 9 groups as follows: control group, ALI model group, positive drug bifendate group, and treatment group, which included 3 ginsenoside extract (GE) groups and 3 FGE groups (dosage of 150, 300, and 450 mg·kg−1 b.w.). The results showed that compared with the ALI model group, FGE significantly increased the levels of glutathione peroxidase, hydroperoxidase, and superoxide dismutase and also decreased the malondialdehyde level. The levels of alanine aminotransferase, aspartate aminotransferase, and total bilirubin markers were significantly reduced, and the levels of inflammatory cytokines TNF-α, IL-6, and IL-1β were significantly decreased. Bioinformatics analysis combined with Western blot validation explored the molecular mechanism of the effect of FGE. It was found that FGE could downregulate the expression of the p-AKT/AKT and the p-mTOR/mTOR ratios. These results suggested that FGE played an alleviative role in ALI by promoting autophagy to inhibit the AKT/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: Rotavirus was the leading cause of acute gastroenteritis among US children until vaccine introduction in 2006, after which, substantial declines in severe rotavirus disease occurred. We evaluated rotavirus vaccine effectiveness (VE) over 13 years (2009--2022). METHODS: We analyzed data from the New Vaccine Surveillance Network using a test-negative casecontrol design to estimate rotavirus VE against laboratory-confirmed rotavirus infections among children seeking care for acute gastroenteritis ($3 diarrhea or $1 vomiting episodes within 24 hours) in the emergency department (ED) or hospital. Case-patients and control-patients were children whose stool specimens tested rotavirus positive or negative, respectively, by enzyme immunoassay or polymerase chain reaction assays. VE was calculated as (1-adjusted odds ratio) x 100%. Adjusted odds ratios were calculated by multivariable unconditional logistic regression. RESULTS: Among 16 188 enrolled children age 8 to 59 months, 1720 (11%) tested positive for rotavirus. Case-patients were less often vaccinated against rotavirus than control-patients (62% versus 88%). VE for receiving $1 dose against rotavirus-associated ED visits or hospitalization was 78% (95%confidence interval [CI] 75%-80%). Stratifying by amodified Vesikari Severity Score, VE was 59% (95% CI 49%-67%), 80% (95% CI 77%-83%), and 94% (95% CI 90%-97%) against mild, moderately severe, and very severe disease, respectively. Rotavirus vaccines conferred protection against common circulating genotypes (G1P[8], G2P[4], G3P[8], G9P[8], and G12[P8]). VE was higher in children<3 years (73%to 88%); protection decreased as age increased. CONCLUSIONS: Rotavirus vaccines remain highly effective in preventing ED visits and hospitalizations in US children. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: In the 2023--2024 respiratory syncytial virus (RSV) season, Spain became one of the first countries to introduce universal RSV prophylaxis, during which all infants born at this time were eligible to receive nirsevimab. Locally, most Spanish regions also immunized infants younger than age 6 months at the start of the season (extended catch-up). The aim of this study was to assess how RSV prophylaxis affected the number of infants presenting to pediatric emergency departments with acute respiratory infections. METHODS: A retrospective study was conducted in 15 Spanish pediatric emergency departments from 9 different regions between the 2018 and 2024 epidemic seasons (November-January). We compared the seasons occurring in 2018-2023 and the 2023-2024 season regarding the number of episodes of lower respiratory tract infection and acute bronchiolitis, acute bronchiolitis- related hospital admissions, and PICU admissions. RESULTS: A comparison with the average rates for the previous epidemic seasons revealed a 57.7% decrease in episodes of lower respiratory tract infection in 2023-2024 (95% CI, 56.5-58.8; P < .001; range among hospitals, 4.8-82.8), a 59.2% decrease in episodes of acute bronchiolitis (95% CI, 57.9-60.4; P < .001; range, 6.9-84.1), a 63.1% reduction in acute bronchiolitis- related hospital admissions (95% CI, 60.9-65.2; P < .001; range, 31.4-86.8), and a 63.1% reduction in PICU admissions (95% CI, 58.1-67.9; P < .001; range, 18.2-81.8). Hospitals in regions applying extended catch-up showed better results. CONCLUSIONS: Nirsevimab can protect a broad infant population against RSV infection with high effectiveness. Approaches including extended catch-up are the most effective, although costeffectiveness must be considered. [ABSTRACT FROM AUTHOR]

Acute liver failure is rare in the neonatal and infant population; however, when encountered, it requires timely diagnosis, management, and identification of the underlying etiology to provide the best clinical outcomes. Here, we present a case of new-onset liver failure in a 4-month-old infant. She had previously been diagnosed with neonatal mucocutaneous herpes simplex virus disease, but had been healthy in the interval, and was referred to our hospital for evaluation of possible need for liver transplantation because of a rapidly progressing pace of disease. In this diagnostic dilemma article, we review the case history and presentation and consider the differential diagnosis from the points of view of the primary and consultative teams. We then follow the clinical evolution of disease, identify a final diagnosis, and explore the short- and long-term management and health implications of the diagnosis. This case should be of interest to primary care providers, intensivists who care for neonates or infants, and specialists who encounter liver failure in their clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: Coronary artery bypass grafting (CABG) surgery in patients with acute coronary syndrome (ACS) remains a high-risk procedure and is associated with adverse outcomes. The risk factors of acute stroke in the above-mentioned patients stay unclear and some appropriate data is lacking in the literature. Thus, we aimed to investigate the predictors of acute stroke in patients undergoing CABG surgery in ACS. Methods: The retrospective single-centre cohort analysis was conducted. All patients (n = 1344) who suffered from acute coronary syndrome and underwent CABG procedure at the University hospital Cologne from June 2011 until October 2019 were included in our study. In order to find the risk factors of acute stroke after bypass surgery, patients were divided into two groups (non-stroke group (n = 1297) and stroke group (n = 47)). In order to even above-mentioned groups propensity score matching (PSM) analysis was performed (non-stroke group (n = 46) and stroke group (n = 46). Results: Duration of cardiopulmonary bypass (p =.015) and cross clamp time (p =.006) were significantly longer in patients who suffered stroke. Perioperative myocardial infarction was significantly higher (p =.030) in the stroke group. Likewise, the duration of intensive care unit stay (p <.001) and in-hospital stay (p <.001) were significantly longer in patients with stroke. However, the mortality rate did not differ significantly (p =.131) between above-mentioned groups. Univariate and multivariate analysis showed cardiogenic shock (p =.003), peripheral vascular disease (PVD, p =.025) and previous stroke (p =.045) as relevant independent predictors for acute stroke after CABG procedure in patients with ACS. Conclusion: Based on our findings, acute stroke after bypass surgery in patients with ACS is associated with increased mortality and adverse outcomes. Cardiogenic shock, peripheral vascular disease and previous stroke were independent predictors of stroke after CABG procedure. Therefore, preoperative evaluation of potential risk factors may be crucial to improve postoperative results. [ABSTRACT FROM AUTHOR]

Introduction: Reducing cardiopulmonary bypass (CPB) induced inflammatory injury is a potentially important strategy for children undergoing multiple operations for single ventricle palliation. We sought to characterize the soluble receptor for advanced glycation end products (sRAGE), a protein involved in acute lung injury and inflammation, in pediatric patients with congenital heart disease and hypothesized that patients undergoing single ventricle palliation would have higher levels of sRAGE following bypass than those with biventricular physiologies. Methods: This was a prospective, observational study of children undergoing CPB. Plasma samples were obtained before and after bypass. sRAGE levels were measured and compared between those with biventricular and single ventricle heart disease using descriptive statistics and multivariate analysis for risk factors for lung injury. Results: sRAGE levels were measured in 40 patients: 19 with biventricular and 21 with single ventricle heart disease. Children undergoing single ventricle palliation had a higher factor and percent increase in sRAGE levels when compared to patients with biventricular circulations (4.6 vs. 2.4, p = 0.002) and (364% vs. 181%, p = 0.014). The factor increase in sRAGE inversely correlated with the patient's preoperative oxygen saturation (Pearson correlation (r) = −0.43, p = 0.005) and was positively associated with red blood cell transfusion (coefficient = 0.011; 95% CI: 0.004, 0.017; p = 0.001). Conclusions: Children with single ventricle physiology have greater increase in sRAGE following CPB as compared to children undergoing biventricular repair. Larger studies delineating the role of sRAGE in children undergoing single ventricle palliation may be beneficial in understanding how to prevent complications in this high-risk population. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study is to determine the experience of primary health care nurses regarding the application of nurse‐led management in patients with acute minor illnesses. Background: Nursing leadership of care for acute minor illnesses is a new challenge faced by nurses in Spain. Design: Qualitative, hermeneutical, interpretive phenomenological approach is used. The Consolidated criteria for reporting qualitative research guidelines were applied. Methods: Twenty primary care nurses participated; three focus group discussions and nine semi‐structured interviews were conducted between November 2019 and October 2020. All the focus group discussions and interviews were recorded, transcribed verbatim and analysed using content analysis. Results: Seven main themes emerged from the focus group discussions and interviews: concept, perception of the other actors, practice, history and social context, competencies, training, and legality. Conclusion: The study shows the diversity and complexity of nurses' experience when applying nurse‐led management in acute minor illnesses. This work has helped to show the gaps perceived by nurses, including the lack of training in the treatment of conditions historically attended by physicians, the lack of definition of the legal framework and the limitations on nurse prescribing. It also highlighted the power of the nursing profession in terms of autonomy, competencies and role expansion. Summary statement: What is already known about this topic? Nurse‐led management of acute minor illnesses is being applied in multiple countries.Nurse‐led management in patients with acute minor illnesses is known to have benefits for both the patient and the system.Nurses' perceptions of applying nurse‐led management in patients with acute minor illnesses are not known but such knowledge would allow the detection of drivers and barriers for this model of care.What this paper adds? The concept of nurse‐led management in patients with acute minor illnesses needs to be clarified to avoid confusion with triage.The topic was perceived as not properly covered in university studies and attended by a lack of ongoing training.Nurses express self‐doubt in their prescribing because they have been able to do so autonomously for only a short time.The implications of this paper: Nurses consider themselves competent to apply nurse‐led management of acute minor illnesses but need more training and knowledge of the legal framework.University curricula need reform and adaptation to the training needs of these new roles. In addition, continuing education will be required.National regulation is needed to enable this practice without dependence on other professionals. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Our study aimed to assess the efficacy and durability of holmium laser enucleation of the prostate (HoLEP) in managing acute urinary retention (AUR), neurogenic chronic urinary retention (NCUR), and non-neurogenic chronic urinary retention (NNCUR). We also sought to compare outcomes in patients with preoperative urinary retention (UR) to those without. METHODS: We conducted a retrospective analysis using prospectively gathered data from men who underwent HoLEP at our institution between October 2017 and July 2022. Patient demographics and outcome measures were recorded, including indications for the procedure, median urinary volume drained, or median postvoid residual urine volume (PVR) before catheterization or HoLEP. Chronic urinary retention (CUR) was defined as PVR >300 mL in males able to void; and initial catheter drainage >1000 mL in males unable to void, in the absence of pain. NCUR and NNCUR were differentiated based on the presence of any significant illness or injury with a neurologic impact on the bladder. All patients had postoperative followup visits at one, three, six, and 12 months. Our evaluation included the International Prostate Symptom Score (IPSS), quality of life (QoL) assessment, maximum urinary flow rate (Qmax), PVR, and catheter-free status. RESULTS: Three hundred sixty-eight males who underwent HoLEP were included in our study. The UR group consisted of 189 patients (70 AUR, 42 NCUR, and 77 NNCUR), and the lower urinary tract symptoms (LUTS) group was comprised of 179 individuals. There were no statistically significant differences between the NCUR and NNCUR subgroups regarding demographics and outcomes. At 12 months postoperative, the AUR group had a higher catheter-free rate than the CUR group (p=0.04), and other outcome variables were comparable between the two cohorts. The UR group had a significantly lower QoL score at one month (p=0.01) and a significantly lower IPSS score at one and 12 months (p=0.034 and p=0.018, respectively) than the LUTS cohort. During all followup visits, the UR group had a significantly higher PVR than the LUTS cohort. The successful first trial of void (TOV) rate for the UR and LUTS groups was 81% and 83.2%, respectively. At 12 months postoperative, the catheter-free rate for the UR and LUTS cohorts was 96.3% and 99.4%, respectively. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To validate a mathematical model using porous media theory for alveolar CO2 determination in ventilated patients. DESIGN: Mathematical modeling study with prospective clinical validation to simulate CO2 exchange from bloodstream to airway entrance. SETTING: ICU. PATIENTS: Thirteen critically ill patients without chronic or acute lung disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model outcomes compared with patient data showed correlations for end-tidal CO2 (EtCO2), area under the CO2 curve, and PaCO2 of 0.918, 0.954, and 0.995. Determination coefficients (R 2) were 0.843, 0.910, and 0.990, indicating precision and predictive power. CONCLUSIONS: The mathematical model shows potential in pulmonary critical care. Although promising, practical application demands further validation, clinician training, and patient-specific adjustments. The path to clinical use will be iterative, involving validation and education. [ABSTRACT FROM AUTHOR]

Objective: Herpes simplex virus encephalitis (HSVE) is associated with significant morbidity and mortality. Here, we present the occurrence of HSVE in a 36-year-old immunocompetent patient following craniotomy for a traumatic acute subdural hematoma (ASDH). Methods: Imaging after four days of progressive headache following a fall with head-strike demonstrated a 1 cm thick left holohemispheric ASDH with significant cerebral compression, edema, and 8 mm of left-to-right midline shift, and an emergent craniotomy and ASDH evacuation were performed, with additional treatment needed for reaccumulation. Postoperatively, the patient developed a worsening leukocytosis, became febrile, and was hypotensive requiring vasopressor support. Results: Despite empiric antibiotics, the patient remained persistently febrile with significant leukocytosis. Repeat head CT showed a new left insular hypodensity and a subsequent viral encephalitis panel was positive for HSV-1. The patient was then started on intravenous acyclovir, with progressive neurological exam improvement. Of note, the patient was noted to have a positive serum HSV-1 IgG antibody titer, indicative of prior infection. Conclusions: Given the known systemic immunosuppression in brain injury and the high prevalence of HSV seropositivity, clinicians should consider the possibility of HSVE from HSV reactivation in TBI patients with persistent fever, leukocytosis, and/or neurological deficits without an obvious etiology. [ABSTRACT FROM AUTHOR]

Purpose: The current diagnostic methods for leptospirosis diagnosis are technically complex and expensive, with limited applicability to specialized laboratories. Furthermore, they lack diagnostic accuracy in the acute stage of the disease, which coincides with a period when antibiotics are highly effective. New simple and accurate tests are mandatory to decentralize and improve diagnosis. Here, we introduced a new lateral flow immunoassay (Lepto-LF) for human leptospirosis. Methods: We conducted a double-blinded assay using 104 serum samples from patients with confirmed or discarded diagnosis for leptospirosis. The diagnostic performance of Lepto-LF was estimated across different ranges of days from onset of symptoms (dpo), considering the diagnostic algorithm as reference standard. Additionally, it was compared with the screening methods enzyme-linked immunosorbent assay (IgM-ELISA) and the slide agglutination test using temperature-resistant antigen (SATR). Results: Lepto-LF exhibited perfect diagnostic performance with a Youden´s index J = 1 from 6 dpo in the acute phase. IgM-ELISA gave slightly lower accuracy with J = 0.91 and 95.5% of both sensitivity and specificity; while SATR showed a markedly inferior yield (J = 0.41, sensitivity = 95.5%, specificity = 45.5%). The performances remained consistent in the convalescence phase of the disease (> 10 dpo). Conclusion: Lepto-LF was found to be a reliable test for simple, rapid and early diagnosis of leptospirosis, resulting a promising tool for decentralizing leptospirosis diagnosis and enabling timely treatment of patients. In addition, Lepto-LF may be employed as confirmatory test, especially in remote areas and vulnerable contexts where the standard MAT is not available. [ABSTRACT FROM AUTHOR]

• This study analyzes Yasmin-related adverse events (AEs) using FAERS database data from 2004 to 2023. • Hepatobiliary, vascular, and psychiatric disorders were the top reported AEs for Yasmin users. • Novel adverse reactions like fear of disease and acute cor pulmonale identified with high signal strength. • Results emphasize the need for cautious prescribing and patient awareness of potential AEs with Yasmin. This study aimed to elucidate the scope and nature of adverse events (AEs) associated with Yasmin. Among the 17,035,572 AE reports collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database between January 2004 and September 2023, 25,949 reports involved Yasmin. The demographic details, clinical outcomes, and sources of reports were extracted, and four algorithms were used to evaluate adverse drug reactions. The majority of the AE reports involved females aged 18–45 years. Hospitalization was the most frequently reported serious outcome (46.84 %), with death occurring in 292 patients (1.82 %). The highest number of reports originated from the United States. Adverse reactions spanned across 24 system organ categories (SOCs), and hepatobiliary, vascular, and psychiatric disorders were the most frequently reported AEs. A total of 229 Preferred Terms (PTs) were identified for adverse reactions, with high signal strength observed for conditions such as post-cholecystectomy syndrome. In addition, fear of disease, which has not been previously identified as an AE related to Yasmin, was also identified as a high signal strength side effect. The findings of the present study underscore the importance of monitoring and identifying potential AEs in patients receiving Yasmin, including those not currently listed in the medication instructions. [ABSTRACT FROM AUTHOR]

Paediatric acute liver failure (PALF) is often characterised by its rapidity of onset and potential for significant morbidity and even mortality. Patients often develop multiorgan dysfunction/failure, including severe acute kidney injury (AKI). Whilst the management of PALF focuses on complications of hepatic dysfunction, the associated kidney impairment can significantly affect patient outcomes. Severe AKI requiring continuous kidney replacement therapy (CKRT) is a common complication of both PALF and liver transplantation. In both scenarios, the need for CKRT is a poor prognostic indicator. In adults, AKI has been shown to complicate ALF in 25–50% of cases. In PALF, the incidence of AKI is often higher compared to other critically ill paediatric ICU populations, with reports of up to 40% in some observational studies. Furthermore, those presenting with AKI regularly have a more severe grade of PALF at presentation. Observational studies in the paediatric population corroborate this, though data are not as robust—mainly reflecting single-centre cohorts. Perioperative benefits of CKRT include helping to clear water-soluble toxins such as ammonia, balancing electrolytes, preventing fluid overload, and managing raised intracranial pressure. As liver transplantation often takes 6–10 h, it is proposed that these benefits could be extended to the intraoperative period, avoiding any hiatus. Intraoperative CKRT (IoCKRT) has been shown to be practicable, safe and may help sicker recipients tolerate the operation with outcomes analogous with less ill patients not requiring IoCKRT. Here, we provide a comprehensive guide describing the rationale, practicalities, and current evidence base surrounding IoCKRT during transplantation in the paediatric population. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction is a significant health issue, particularly in Jordan where ischemic heart disease is the leading cause of death. Effective management of acute myocardial infarction is essential to mitigate its consequences. Although health literacy is crucial for the successful management of acute myocardial infarction, research about the strengths and needs of health literacy among acute myocardial infarction patients is still limited. This study was conducted to identify the health literacy strengths and needs of Jordanian acute myocardial infarction patients using cluster analysis. A cross-sectional design was used to conduct this study in a sample of acute myocardial infarction patients in Jordan (N = 114). A demographics questionnaire and the Health Literacy Questionnaire were used to collect the data. Data analysis was performed using hierarchical cluster analysis using Ward's method. Seven distinct clusters of acute myocardial infarction patients were identified, each characterized by unique health literacy profiles and sociodemographic characteristics. Cluster 7 had the highest health literacy scores across all nine Health Literacy Questionnaire scales. Sociodemographic factors such as age, education level, and gender influenced health literacy levels, with female, younger, more educated patients exhibiting higher health literacy. Through identifying the specific strengths and needs, this research provides a foundation for developing targeted health literacy interventions for acute myocardial infarction patients. Improving health literacy among acute myocardial infarction patients can enhance their ability to manage their health and potentially reduce the complications associated with acute myocardial infarction. [ABSTRACT FROM AUTHOR]

The article discusses research which evaluated the effect of helmet continuous positive airway pressure (CPAP) on tidal volume assessed by bioelectrical impedance. The study analyzed the variation in respiratory parameters including tidal volumes, breathing frequency and minute ventilation before helmet application and after helmet CPAP application. Results of arterial blood gas analysis, respiratory and hemodynamics parameters are presented.

This article reports a study designed to evaluate the effectiveness of regular oral care protocol developed specifically for adults in intensive care to prevent mucositis. Data were collected using oral mucositis assessment scale, oral cavity assessment tool, and the National Cancer Institute Common Toxicity Criteria. The results indicated that oral mucositis can be reduced through the practice of administering oral care in accordance with oral health care guidelines. Oral care implemented in line with an evidence-based oral care guide and frequent observation of patients is the most important step in preventing oral mucositis. [ABSTRACT FROM AUTHOR]

Background: Triage is pivotal in intensive care for patient safety and resource allocation. The admission algorithm has been shown to correlate with the appropriateness of ICU admission and offer decision aid when facing challenges in times of scarce critical care resources. This study aimed to explore the development of a reference tool to support triage decisions for admission to the ICU. Methods: In this retrospective observational study, the Intensive Care Triage Score (ICTS) was generated as a reference to correlate with the triage decision made by clinical judgment. ICU admission would be advised for ICTS below 6. The primary outcome was ICU admission. The secondary outcomes included ICU, hospital, 90- day, and 1-year mortality. The receiver operating characteristic curve was used to assess the performance of ICTS. Results: A total of 1664 patients were included in the analysis. There were 1204 patients (72.4%) admitted to the ICU; 680 of 738 (92%) with ICTS below 6 were admitted to the ICU. The hospital mortality of the whole cohort was 25.1%; there was a positive correlation between ICTS and hospital mortality. The area under the receiver operating characteristic curve (AUC) of ICTS in predicting hospital mortality for all patients was 0.754 (95% CI 0.728-0.780). The correlation between ICTS and hospital mortality was observed in patients admitted and not admitted to the ICU. Conclusion: Developing a scoring system as a reference tool would be useful for ICU triage. [ABSTRACT FROM AUTHOR]

Background We assessed the influence of prior nonvitamin K antagonist (NOAC) use on stroke outcomes after endovascular treatment (EVT) in patients at a high risk of stroke based on their pre-stroke CHA2DS2-VASc score, and compared them with those who did not use any antithrombotic (NAU) or antiplatelet (APT) agents. Methods Data were collected from a multicenter database comprising consecutive acute ischemic stroke patients who underwent EVT during a span of 103 months. We evaluated pre-stroke CHA2DS2-VASc scores in enrolled patients and measured instances of successful reperfusion and symptomatic hemorrhagic transformation (SHT) following EVT as the main outcome measures. Results Among 12 807 patients with acute ischemic stroke, 3765 (29.4%) had a history of atrial fibrillation. Of these, 418 patients with CHA2DS2-VASc scores ≥2 received EVT alone. The prior NOAC group showed higher successful reperfusion rates compared with the prior NAU and APT groups (p=0.04). Multivariate analysis revealed that prior NOAC use increased the likelihood of successful reperfusion after EVT (OR [95% CI] 2.54 [1.34 to 4.83], p=0.004) and improved stroke outcomes, while the prior APT group did not. Furthermore, the prior NOAC use group was not associated with SHT after EVT. Propensity score matching confirmed these findings. Conclusion Prior use of NOAC is associated with improved outcomes in high-risk stroke patients (pre-stroke CHA2DS2-VASc score ≥2) undergoing EVT. [ABSTRACT FROM AUTHOR]

Background Acute basilar artery occlusion is a disabling and life-threatening condition. The purpose of this study was to evaluate the impact of occluded vessel location on the prognostic outcomes of patients who underwent endovascular treatment for acute basilar artery occlusion. Methods Patient data for this study were obtained from the ATTENTION registry. Baseline data of the patients were described and compared across different occlusion locations. Univariable and multivariable regression analyses were performed to assess the effect of occluded vessel location on associated prognostic outcomes. Results A total of 1672 patients were included in the analysis, with 583 having distal occlusion, 540 having middle occlusion, and 549 having proximal occlusion. Unlike distal occlusion, both proximal and middle occlusions were significantly and negatively associated with favorable clinical outcomes (for modified Rankin Scale score 0-3: adjusted odds ratio (aOR) 0.634, 95% confidence interval (95% CI) 0.493 to 0.816, P<0.001 in middle occlusion, and aOR 0.620, 95% CI 0.479 to 0.802, P<0.001 in proximal occlusion). Mortality was higher in patients with proximal and middle occlusions (aOR 1.461, 95% CI 1.123 to 1.902, P=0.005 in middle occlusion, and aOR 1.648, 95% CI 1.265 to 2.147, P<0.001 in proximal occlusion). The occluded vessel location was not associated with symptomatic intracranial hemorrhage. Conclusions Proximal and middle basilar artery occlusions were predominantly associated with poor clinical outcomes and increased risk of death following endovascular treatment. [ABSTRACT FROM AUTHOR]

Aspergillus flavus and its mycotoxin aflatoxin (AF) are widely present in the environment and cause various acute and chronic diseases in humans and animals. UV irradiation has been a versatile method for disinfecting A. flavus and detoxifying AFs. Combined effects of UV and other agents were scarcely tested yet. Here, we investigated the combinatorial effects of UVC and peroxymonosulfate (PMS) on the disinfection of A. flavus and accumulation of AFB1 under aqueous conditions. UVC efficiently disinfected A. flavus in a dose-dependent manner. PMS (~4 mM) exhibited no disinfection but enhanced the inactivation activity of UVC. Notably, PMS or UVC (72 J/cm²) increased the accumulation of AFB1 in the mycelia. Higher (144 J/cm²) doses of UVC suppressed AFB1 accumulation. At the genetic level, PMS and UVC upregulated the expression of the AF biosynthetic genes aflS and aflR. In contrast, UVC degraded AFB1 in vitro, which was enhanced by PMS treatment. The in-vivo and in-vitro studies indicated that AFB1 accumulation may be compromised by the dual effects of UVC and PMS on the upregulation of AF biosynthesis and degradation activities. In conclusion, PMS and UVC are efficient disinfecting agents against A. flavus but also stimulate AF biosynthesis under moderate treatment conditions. [ABSTRACT FROM AUTHOR]

Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen that causes severe acute fever disease in humans and requires a biosafety level 4 laboratory for handling. Hazara virus (HAZV), belonging to the same virus genus as CCHFV, does not exhibit pathogenesis in humans. To investigate host RNA-binding proteins (RBPs) that regulate CCHFV replication, we generated a series of mutant RAW264.7 cells by CRISPR/Cas9 system and these cells were infected with HAZV. The viral titers in the supernatant of these cells was investigated, and HuR (ELAVL1) was identified. HuR KO RAW264.7 cells reduced HAZV replication. HuR is an RBP that enhances mRNA stability by binding to adenyl-uridine (AU)-rich regions in their 3′ non-coding region (NCR). HuR regulates innate immune response by binding to host mRNAs of signaling molecules. The expression of cytokine genes such as Ifnb, Il6, and Tnf was reduced in HuR KO cells after HAZV infection. Although HuR supports the innate immune response during HAZV infection, we found that innate immune activation by HAZV infection did not affect its replication. We then investigated whether HuR regulates HAZV genome RNA stability. HAZV RNA genome was precipitated with an anti-HuR antibody, and HAZV genome RNA stability was lowered in HuR KO cells. We found that HuR associated with HAZV RNA and stabilized it to enhance HAZV replication. Furthermore, HuR-deficiency reduced CCHFV minigenome replication. CCHFV is a negative-strand RNA virus and positive-strand RNA is produced during replication. HuR was associated with positive-strand RNA rather than negative-strand RNA, and AU-rich region in 3'-NCR of S segment was responsible for immunoprecipitation with anti-HuR antibody and minigenome replication. Additionally, HuR inhibitor treatment reduced CCHFV minigenome replication. Our results indicate that HuR aids replication of the CCHFV minigenome by associating with the AU-rich region in the 3′-NCR. Author summary: Crimean-Congo Hemorrhagic Fever virus (CCHFV) is a tick-borne pathogen that causes severe acute fever disease in humans and requires a biosafety level 4 laboratory for handling. Hazara virus (HAZV), the same genus of CCHFV, has been used as a model virus to reveal the molecular mechanism of CCHFV infection. To investigate host factors for CCHFV replication, we generated a series of mutant RAW264.7 cells and conducted screening for host genes that regulate the replication of HAZV, identifying HuR (ELAVL1). HuR is an RNA-binding protein (RBP) that enhances mRNA stability by binding to its 3′ non-coding region (NCR). We found that HuR is associated with the CCHFV RNA stability by binding to its 3'-NCR, and the minigenome assay showed that CCHFV replication is supported by HuR. HuR inhibitor treatment also reduced CCHFV minigenome replication. These findings present a possible starting point for the future development of antiviral drug targeting host RBPs. Combination treatment with RdRp and RBP inhibitors may be a potential therapeutic strategy in the future. [ABSTRACT FROM AUTHOR]

At‐home storage of medications could pose a threat to public health and the environment if not handled appropriately. Excessive storage also creates health care and economic burdens. This study investigated storage practices, waste, and their determinants in China. Data were collected by pharmacy staff of urban‐dwelling households via online questionnaires. Descriptions at the household and medicine levels were conducted in Stata 16. Individual and family characteristics were associated with the presence of household medicine storage (84.6%, n = 5290), but storage location was poor. Expiration was the primary reason for discarding medicines. Respondents were inclined to buy medicines in pharmacies without prescription for storage purposes at out‐of‐pocket expenses, and 60.7% of medicines were purchased at out‐of‐pocket expenses, despite medical insurance coverage. Regarding wastage, 11.2% of medicines had expired and 38.2% were no longer needed. Purchasing for storage purposes was related to less waste due to expiration, while purchasing for treating acute diseases rather than chronic diseases was related to more waste, due to less for use. Accounting for 12.2% of all medications, antibiotics were associated with expiration and no further need for use. Source‐control measures targeting health facilities, pharmacies, and residents are needed under the combined efforts of all relevant departments. [ABSTRACT FROM AUTHOR]

Automation of surveillance of infectious diseases—where algorithms are applied to routine care data to replace manual decisions—likely reduces workload and improves quality of surveillance. However, various barriers limit large-scale implementation of automated surveillance (AS). Current implementation strategies for AS in surveillance networks include central implementation (i.e. collecting all data centrally, and central algorithm application for case ascertainment) or local implementation (i.e. local algorithm application and sharing surveillance results with the network coordinating center). In this perspective, we explore whether current challenges can be solved by federated AS. In federated AS, scripts for analyses are developed centrally and applied locally. We focus on the potential of federated AS in the context of healthcare associated infections (AS-HAI) and of severe acute respiratory illness (AS-SARI). AS-HAI and AS-SARI have common and specific requirements, but both would benefit from decreased local surveillance burden, alignment of AS and increased central and local oversight, and improved access to data while preserving privacy. Federated AS combines some benefits of a centrally implemented system, such as standardization and alignment of an easily scalable methodology, with some of the benefits of a locally implemented system including (near) real-time access to data and flexibility in algorithms, meeting different information needs and improving sustainability, and allowance of a broader range of clinically relevant case-definitions. From a global perspective, it can promote the development of automated surveillance where it is not currently possible and foster international collaboration.The necessary transformation of source data likely will place a significant burden on healthcare facilities. However, this may be outweighed by the potential benefits: improved comparability of surveillance results, flexibility and reuse of data for multiple purposes. Governance and stakeholder agreement to address accuracy, accountability, transparency, digital literacy, and data protection, warrants clear attention to create acceptance of the methodology. In conclusion, federated automated surveillance seems a potential solution for current barriers of large-scale implementation of AS-HAI and AS-SARI. Prerequisites for successful implementation include validation of results and evaluation requirements of network participants to govern understanding and acceptance of the methodology. [ABSTRACT FROM AUTHOR]

Background: The transfusion strategy in the acute phase of myocardial infarction (AMI) remains a debated topic with non-standardized guidelines. This study aimed to evaluate the impact of liberal versus restrictive transfusion strategies on mortality during AMI. Methods: A systematic search was conducted across MEDLINE, EMBASE, and the COCHRANE library databases, focusing on randomized controlled trials (RCTs). The primary endpoint was the latest measured mortality within 90 days following myocardial infarction (MI). Secondary endpoints included recurrence of MI, cardiovascular mortality, stroke occurrence, unplanned revascularization, and a composite endpoint of death or recurrent MI. Mixed and random-effects models were employed to estimate relative risks. Sensitivity analyses were conducted using two approaches: one incorporating only studies assessed as low risk of bias according to the Rob2 tool, and another employing a Bayesian analysis. Results: Four RCTs including a total of 4324 participants were analyzed. Neither the fixed-effect nor random-effects models demonstrated a significant reduction in mortality, with risk ratios (RR) of 1.16 (95% CI 0.95–1.40) for the fixed-effect model and 1.13 (95% CI 0.67–1.91) for the random-effects model (GRADE: low certainty of evidence). Sensitivity analyses, including the exclusion of two high-risk-of-bias studies and a Bayesian analysis, were consistent with the primary analysis. For the composite outcome death or MI both fixed-effect and random-effects models showed a statistically significant RR of 1.18 (95% CI 1.01–1.37) with negligible heterogeneity (I2 = 0%, p = 0.46), indicating results unfavorable to restrictive transfusion (GRADE: very low certainty of evidence). However, this result was primarily driven by a single study. For cardiac mortality, the fixed-effects model indicated a significant RR of 1.42 (95% CI 1.07–1.88), whereas the random-effects model showed non-significant RR of 1.05 (95% CI 0.36–3.80). Analyses of other secondary endpoints did not show statistically significant results. Conclusions: Our analysis did not demonstrate a significant benefit in early mortality with a liberal transfusion strategy compared to a restrictive strategy for AMI, low certainty of evidence. Liberal transfusion may reduce the risk of the composite outcome death or MI, with very low certainty of evidence. These findings should be interpreted with caution in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Symptoms of emotional and physical stress near death may be related to previous experiences of trauma. Objective: To investigate current evidence regarding the following: (1) Is previous trauma identified in people who are dying, and if so, how? (2) How is previous trauma associated with the experience of death/dying in people with or without cognitive impairment? and (3) What palliative care interventions are available to people with previous trauma at the end of life? Design: This integrative review was conducted per Whittemore and Knafl's guidelines, which involves a stepped approach, specifically (1) problem identification, (2) literature search, (3) data evaluation, (4) data analysis and (5) presentation. Methods: This integrative review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Electronic databases were searched in August 2021 and updated in August 2023. The articles were quality appraised, and narrative data were analysed using Grounded Theory (GT). Results: Of 1310 studies screened, 11 met the inclusion criteria (four qualitative and seven quantitative) conducted in Australia, Canada, Japan and the United States; and American studies accounted for 7/11 studies. Eight were focused on war veterans. Descriptive studies accounted for the majority, with only two publications testing interventions. Re-living trauma near death has additional features to a diagnosis of post-traumatic stress disorder alone, such as physical symptoms of uncontrolled, unexplained acute pain and this distress was reported in the last weeks of life. Conclusion: This study proposes that re-living trauma near death is a recognisable phenomenon with physical and psychological impacts that can be ameliorated with improved clinical knowledge and appropriate management as a new GT. Further research is needed to enable past trauma identification at the end of life, and trauma-informed safe interventions at the end of life are an urgent need. [ABSTRACT FROM AUTHOR]

Dengue, an acute febrile disease transmitted by Aedes mosquitoes, is caused by the dengue virus (DENV), presenting a formidable challenge to global public health. By examining clues from ancient Chinese books and conducting a comprehensive review, this study elucidates the characteristics of potential dengue epidemics in China prior to 1978. This evidence indicates that China may not have experience dengue epidemics before 1840. During 1840–1949, however, it experienced a noticeable dengue occurrence and prevalence in the 1870s, 1920s, and 1940s. Then from 1949 to 1978, only sporadic reports were accounted. The disparity in the frequency of dengue occurrences across three time periods suggests that the persistent characteristic of dengue epidemics in China primarily arises from imported cases resulting from international exchanges, subsequently leading to local outbreaks influenced by global epidemic trend. This research offers a novel perspective on retrospectively examining the historical trajectory of dengue epidemics and provides valuable insights into exploration of DENV epidemic patterns. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) poses a significant and escalating medical challenge, where precise diagnosis and timely intervention hold utmost importance in halting its deterioration. Nevertheless, persistent obstacles arise from the lack of agents proficient in both real‐time diagnosis and efficient mitigation of ALI. Here, a biocatalytic and second near‐infrared (NIR‐II) fluorescence‐illuminating nanoplatform is designed to simultaneously facilitate real‐time monitoring and robust inflammation alleviation in ALI. The study first develops a new aggregation‐induced emission luminogen with trifluoromethyl substitutions, which simultaneously increase NIR‐II emission wavelength and fluorescence brightness. The molecular probe is further integrated into biocatalytic hollow ceria nanostructures, and cloaked with pre‐activated macrophage membranes for targeted inflammation intervention. Upon inhalation administration in ALI mice, the theranostic nanoagents leverage the bright NIR‐II emission and active inflammation‐tropic properties for in vivo sensitive NIR‐II imaging of ALI, which also facilitates real‐time tracking of the nanoagents' distribution and dynamic fate within pneumonia milieu. Concurrently, the catalytic prowess of the nanoplatforms efficaciously scavenges excess reactive oxygen species, dampens proinflammatory cytokines, and promotes macrophage repolarization, substantially alleviating acute lung damage. The multifaceted nanoplatform integrates NIR‐II bioimaging with nanocatalysis‐mediated immunoregulation, offering a versatile and promising approach for addressing the intricate challenges posed by acute inflammation diseases. [ABSTRACT FROM AUTHOR]

Background: Efficacy of inhaled therapy such as Nitric Oxide (iNO) during mechanical ventilation may depend on airway patency. We hypothesized that airway closure and lung collapse, countered by positive end-expiratory pressure (PEEP), influence iNO efficacy. This could support the role of an adequate PEEP titration for inhalation therapy. The main aim of this study was to assess the effect of iNO with PEEP set above or below the airway opening pressure (AOP) generated by airway closure, on hemodynamics and gas exchange in swine models of acute respiratory distress syndrome. Fourteen pigs randomly underwent either bilateral or asymmetrical two-hit model of lung injury. Airway closure and lung collapse were measured with electrical impedance tomography as well as ventilation/perfusion ratio (V/Q). After AOP detection, the effect of iNO (10ppm) was studied with PEEP set randomly above or below regional AOP. Respiratory mechanics, hemodynamics, and gas-exchange were recorded. Results: All pigs presented airway closure (AOP > 0.5cmH2O) after injury. In bilateral injury, iNO was associated with an improved mean pulmonary pressure from 49 ± 8 to 42 ± 7mmHg; (p = 0.003), and ventilation/perfusion matching, caused by a reduction in pixels with low V/Q and shunt from 16%[IQR:13–19] to 9%[IQR:4–12] (p = 0.03) only at PEEP set above AOP. iNO had no effect on hemodynamics or gas exchange for PEEP below AOP (low V/Q 25%[IQR:16–30] to 23%[IQR:14–27]; p = 0.68). In asymmetrical injury, iNO improved pulmonary hemodynamics and ventilation/perfusion matching independently from the PEEP set. iNO was associated with improved oxygenation in all cases. Conclusions: In an animal model of bilateral lung injury, PEEP level relative to AOP markedly influences iNO efficacy on pulmonary hemodynamics and ventilation/perfusion match, independently of oxygenation. [ABSTRACT FROM AUTHOR]