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Introduction: Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10–15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part 1, presented in this manuscript) and the long-term phase (Part 2, presented in a separate manuscript) of IMD. Methods: This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers. Results: A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants' experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers' reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase. Conclusions: IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part 1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. 7CedpUhoy_P6EE5C2Mz6-e Video abstract (MP4 1,24,432 kb) Plain Language Summary: Invasive meningococcal disease (IMD) is an uncommon but serious infection. Even with treatment, IMD is deadly for up to 10–15% of people who get sick, and survivors may experience short-term and long-term health problems. While IMD can be prevented through vaccination, many people are not vaccinated. We asked 11 survivors and 3 of their caregivers in the USA about their experiences with IMD during the time of their infection and initial recovery (the "short term"). We were particularly interested in the symptoms that survivors experienced, their diagnosis and treatment experiences, and the impact on survivors' and caregivers' quality of life. Most survivors described leading healthy lives before getting sick. Severe skin rash, fever, and unconsciousness were common symptoms when survivors got the infection. Most participants were admitted to the hospital when symptoms started (many through the emergency room). However, not everyone was diagnosed quickly or accurately, and many experienced delays in receiving care. Treatments could be drastic, such as immediate surgery to remove arms or legs. Survivors and caregivers described feeling scared and traumatized, and many experienced challenges with day-to-day activities. Healthcare-related expenses and the inability to attend school or work led to financial challenges for some. The burden of IMD infection and initial recovery is significant. There is a need for increased public disease awareness, targeted education for healthcare providers, and improved access to prevention measures such as vaccination. The long-term effects of IMD infection were also explored in this study, and are presented in another paper [1]. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the prevalence of cognitive impairment among patients with major depressive disorder (MDD) hospitalized during the acute phase and to analyze the in-depth association between this cognitive impairment and clinical correlation factors. Methods: In this cross-sectional study, we recruited 126 patients aged between 18 and 65 years who were diagnosed with MDD. All these patients were inpatients from the Department of Psychiatry at the Second People's Hospital of Hunan Province. We employed a series of assessment tools, including the Pittsburgh Sleep Quality Index (PSQI), the 16-item Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Pre-sleep Arousal Scale (PSAS), the Morningness-Eveningness Questionnaire (MEQ), the Hamilton Anxiety Rating Scale (HAMA), and the 17-item Hamilton Depression Rating Scale (HAMD-17). The patients were divided into a cognitive impairment group and a non-cognitive impairment group based on their scores on the Montreal Cognitive Assessment Scale (MoCA). Through Spearman's correlation analysis, we explored the correlation between the total MoCA score and the score of each factor. Additionally, we utilized binary logistic regression analysis to investigate the relationship between cognitive impairment and clinically relevant factors in MDD patients hospitalized during the acute phase and plotted ROC curves to evaluate their clinical efficacy. Results: In this study, we found that the prevalence of cognitive impairment among MDD patients hospitalized during the acute phase was as high as 63.49%. Through statistical analysis, we observed significant differences between the cognitive impairment group and the non-cognitive impairment group in terms of age, place of residence, education level, and HAMD-17 scores. In the Spearman correlation analysis, we noted the following trends: visuospatial and executive abilities were negatively correlated with the HAMD-17 score (P < 0.05); naming ability was positively correlated with the PSAS score but negatively correlated with the MEQ score (P < 0.05); memory was also negatively correlated with the MEQ score (P < 0.05); attention was negatively correlated with the HAMA score; and abstract cognitive ability was negatively correlated with the MEQ score (P < 0.05). Through binary logistic regression analysis, we further revealed the relationship between cognitive impairment and factors such as living in a rural area (OR = 2.7, 95% CI = 1.083-6.731, P < 0.05), increased age (OR = 1.049, 95% CI = 1.013-1.087, P < 0.01), and the HAMD-17 score (OR = 1.10295, 95% CI = 1.031-11.79, P < 0.01). Additionally, ROC curve analysis demonstrated a significant correlation between the HAMD-17 score and the prediction of cognitive function in MDD patients hospitalized during the acute phase (P < 0.001). Specifically, the AUC for the HAMD-17 score was 0.73, with an optimal cut-off value of 19.5, sensitivity of 70.0%, and specificity of 63.0%. Furthermore, the AUC for age was 0.71, with an optimal cut-off value of 33.5, sensitivity of 59.0%, and specificity of 80.0%. Conclusions: This study indicates that MDD patients hospitalized during the acute phase have a higher prevalence of cognitive impairment. This phenomenon reflects a significant correlation between clinical factors such as age, sleep-related characteristics, and the severity of depression with cognitive impairment. Therefore, regular assessment of cognitive function in MDD patients and early intervention may be crucial for the treatment and prognosis of the disease. [ABSTRACT FROM AUTHOR]

Diffusion tensor imaging (DTI) has emerged as a promising neuroimaging tool for detecting blast-induced mild traumatic brain injury (bmTBI). However, lack of refined acute-phase monitoring and reliable imaging biomarkers hindered its clinical application in early diagnosis of bmTBI, leading to potential long-term disability of patients. In this study, we used DTI in a rat model of bmTBI generated by exposing to single lateral blast waves (151.16 and 349.75 kPa, lasting 47.48 ms) released in a confined bioshock tube, to investigate whole-brain DTI changes at 1, 3, and 7 days after injury. Combined assessment of immunohistochemical analysis, transmission electron microscopy, and behavioral readouts allowed for linking DTI changes to synchronous cellular damages and identifying stable imaging biomarkers. The corpus callosum (CC) and brainstem were identified as predominantly affected regions, in which reduced fractional anisotropy (FA) was detected as early as the first day after injury, with a maximum decline occurring at 3 days post-injury before returning to near normal levels by 7 days. Axial diffusivity (AD) values within the CC and brainstem also significantly reduced at 3 days post-injury. In contrast, the radial diffusivity (RD) in the CC showed acute elevation, peaking at 3 days after injury before normalizing by the 7-day time point. Damages to nerve fibers, including demyelination and axonal degeneration, progressed in lines with changes in DTI parameters, supporting a real-time macroscopic reflection of microscopic neuronal fiber injury by DTI. The most sensitive biomarker was identified as a decrease in FA, AD, and an increase in RD within the CC on the third day after injury, supporting the diagnostic utility of DTI in cases of bmTBI in the acute phase. [ABSTRACT FROM AUTHOR]

Haoran Deng, Shiping Zhu, Fei Yu, Xue Song, Xinlai Jin, Xuchun Ding Department of Respiratory and Critical Care Medicine, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Xuchun Ding, Email archon_01@163.comObjective: To explore the predictive value of cellular inflammatory factors and T cell subsets for disease recurrence and prognosis in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD).Methods: Serum samples were collected from the two groups to detect and compare the levels of inflammatory cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)], T cell subsets (CD4+, CD8+), and clinical related indicators. Pearson correlation analysis was used to analyze the correlation between inflammatory cytokines, T cell subsets, and clinical indicators. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of serum inflammatory factors and T cell subsets for acute exacerbations of COPD.Results: The observation group had higher levels of IL-1β, IL-6, TNF-α, and CD8+, and lower CD4+ levels (P< 0.05). The ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) was lower, while procalcitonin (PCT) and white blood cell count (WBC) were higher (P< 0.05). Correlation analysis showed positive correlations between IL-1β, IL-6, TNF-α, and CD8+, and negative correlations with CD4+ and FEV1/FVC (P< 0.05). After 6 months, 15 out of 73 patients had acute recurrences, with higher IL-1β, IL-6, TNF-α, and CD8+ levels (P< 0.05). Binary logistic regression identified IL-1β, IL-6, TNF-α, and CD8+ as significant predictors of exacerbations, while CD4+ was protective. ROC analysis showed that combined biomarkers had the highest predictive efficiency (AUC = 0.907).Conclusion: This study is the first to integrate multiple serum inflammatory factors and T cell subsets into a comprehensive predictive model for acute recurrence of COPD within six months (AUC = 0.907), offering a more accurate prediction than traditional methods. The findings underscore the value of these biomarkers in clinical follow-up and highlight their independent predictive power, providing new insights into the interaction between immune markers and clinical indicators in COPD exacerbations.Keywords: Cellular inflammatory factors, T cell subsets, COPD, acute phase, disease recurrence, predictive value, prognosis

Abstract Introduction Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10–15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part 1, presented in this manuscript) and the long-term phase (Part 2, presented in a separate manuscript) of IMD. Methods This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers. Results A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants’ experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers’ reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase. Conclusions IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part 1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. Video abstract (MP4 1,24,432 kb)

Purpose: The aim of this work was to analyze and contrast the effectiveness and safety of intralesional HA in the acute stage of PD with that of verapamil injection. Methods: In this prospective, randomized clinical trial, 42 PD-affected, sexually active men between the ages of >18 and 70 participated. Two groups of patients were recruited; group A obtained weekly intralesional treatment with HA for 12 weeks, whereas group B obtained weekly intralesional therapy with verapamil for 12 weeks. Physical examinations and Duplex Doppler ultrasound were performed on all patients. Results: The penile curvature was significantly decreased at 12 weeks after therapy in contrast to baseline in group A (34.1 ± 6.77° vs. 24.7 ± 9.72°, p = 0.005), and was significantly decreased at 12 weeks after therapy compared to baseline in group B (36.2 ± 7.43° vs. 30.8 ± 8.63 °, p = 0.047). The decrease in penile curvature at 12 weeks after therapy was noticeably better in group A in contrast to group B (24.7 ± 9.72° vs. 30.8 ± 8.63°, p = 0.038). Conclusion: HA is emerging as a valid choice for the treatment of PD in terms of resolution of the acute phase of the disease, and it is plausible to posit that the use of HA may contribute to the stabilization of the disease and decrease the need for the subsequent choice of a possible surgical strategy, with the ability to reduce penile pain and have a stronger impact on penile curvature and patient satisfaction. [ABSTRACT FROM AUTHOR]

Purpose: To continuously and dynamically monitor the sleep status of patients in the acute phase of cerebral infarction, and to investigate the characteristics of acute cerebral infarction(ACI)associated with sleep-disordered breathing (SDB), variations in sleep structure, and changes in sleep circadian rhythms. Methods: Patients with ACI within 48 h of onset who were admitted to the Department of Neurology at Kailuan General Hospital from November 2020 to December 2022 were selected. Detailed baseline information such as age, gender, smoking history, drinking history, were recorded for the selected participants. From the beginning of their hospitalization, the selected participants were monitored for their sleep status continuously for 5 days using the Intelligent Mattress-based Sleep Monitoring Platform System(IMSMPS). Based on the heart rate data obtained from the monitoring, the interdaily stability (IS) and intradaily variability (IV) of the sleep circadian rhythm were calculated. Results: 1,367 patients with ACI were selected. Monitoring results over 5 days indicated 147 cases (10.75%) without SDB, and 1,220 cases (89.25%) with SDB. Among the group with SDB, there were 248 cases (18.14%) with continuous mild SDB, 395 cases (28.90%) with moderate SDB, 295 cases (21.58%) with severe SDB, and 282 cases (20.63%) that fluctuated between different severity levels. Within this fluctuating group, 152 cases (53.90%) fluctuated between two severity levels, 120 cases (42.55%) between three levels, and 10 cases (3.55%) among all four levels. There were statistically significant differences (P < 0.05) in the sleep latency, sleep efficiency, non-rapid eye movement stages 1–2, rapid eye movement, proportion of non-rapid eye movement, proportion of rapid eye movement, wake after sleep onset, time out of bed, number of awakenings, respiratory variability index, and heart rate variability index among patients with ACI monitored from day 1 to 5. However, other monitored sleep structure parameters did not show statistically significant differences (P > 0.05). The coefficient of variation for all sleep monitoring parameters ranged between 14.54 and 36.57%. The IV in the SDB group was higher than in the group without SDB (P < 0.05), and the IS was lower than in the group without SDB (P < 0.05). Conclusion: Patients in the acute phase of cerebral infarction have a high probability of accompanying SDB. The sleep structure of these patients shows significant variability based on the onset time of the stroke, and some patients experience fluctuations among different severity levels of SDB. ACI accompanied by SDB can further reduce the IS of a patient's sleep circadian rhythm and increase its IV. [ABSTRACT FROM AUTHOR]

The emergence and spread of highly pathogenic avian influenza virus A subtype H5N1 (HP H5N1-IAV), particularly clade H5N1 2.3.4.4b, pose a severe global health threat, affecting various species, including mammals. Historically, cattle have been considered less susceptible to IAV, but recent outbreaks of H5N1-IAV 2.3.4.4b in dairy farms suggest a shift in host tropism, underscoring the urgency of expanded surveillance and the need for adaptable diagnostic tools in outbreak management. This study investigated the presence of anti-nucleoprotein (NP) antibodies in serum and milk and viral RNA in milk on dairy farms affected by outbreaks in Texas, Kansas, and Michigan using a multi-species IAV ELISA and RT-qPCR. The analysis of ELISA results from a Michigan dairy farm outbreak demonstrated a positive correlation between paired serum and milk sample results, confirming the reliability of both specimen types. Our findings also revealed high diagnostic performance during the convalescent phase (up to 96%), further improving sensitivity through serial sampling. Additionally, the evaluation of diagnostic specificity using serum and milk samples from IAV-free farms showed an excellent performance (99.6%). This study underscores the efficacy of the IAV NP-blocking ELISA for detecting and monitoring H5N1-IAV 2.3.4.4b circulation in dairy farms, whose recent emergence raises significant animal welfare and zoonotic concerns, necessitating expanded surveillance efforts. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers. [ABSTRACT FROM AUTHOR]

Background: Management options for Peyronie's disease (PD) are determined by the phase of the condition. Experts counsel against surgical intervention during the active phase of PD. Patients with chronic phase of PD are offered either collagenase injections or surgical intervention. Accurately characterising a patient's phase of PD is crucial in determining the appropriate treatment option. Objective: To investigate neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) as possible predictors for the determination of acute or chronic phase of PD. Methods: This study retrospectively queried all patients who presented for initial diagnosis of PD from 2016 to 2020 and had complete blood count (CBC) laboratory values before initial therapy. PD phase was defined per the American Urological Association guidelines. The active phase of PD was defined as a changing penile curvature and/or growing palpable plaque. The chronic phase of PD was defined as a stabilised penile curvature. All statistical analyses were two-tailed, using a significance level of 0.05. Results: One hundred nine patients met inclusion: 27 (25%) active phase and 82 (75%) chronic phase patients. Demographic and erectile characteristics were not statistically different between the two groups. NLR and PLR values between active and chronic phase patients were comparable (p > 0.05). A linear regression evaluated correlations between the duration of PD and either NLR or PLR. Neither NLR nor PLR was correlated with PD duration on Spearman, Pearson, or Kandall tests. In addition, NLR and PLR were not noted to be predictors of PD phase on multiple logistic regression. Finally, a receiver operator characteristic curve was generated. NLR and PLR yielded an area under curve of 58% and 57.8%, respectively. Conclusions: Two recent studies suggested NLR and PLR could be used to predict the phases of PD. However, after evaluating a cohort of 109 men from our institution, our data do not support the use of peripheral blood PLR or NLR to determine the phase of PD. [ABSTRACT FROM AUTHOR]

ObjectiveThis study aimed to investigate the prevalence of cognitive impairment among patients with major depressive disorder (MDD) hospitalized during the acute phase and to analyze the in-depth association between this cognitive impairment and clinical correlation factors.MethodsIn this cross-sectional study, we recruited 126 patients aged between 18 and 65 years who were diagnosed with MDD. All these patients were inpatients from the Department of Psychiatry at the Second People’s Hospital of Hunan Province. We employed a series of assessment tools, including the Pittsburgh Sleep Quality Index (PSQI), the 16-item Dysfunctional Beliefs and Attitudes about Sleep Scale (DBAS-16), the Pre-sleep Arousal Scale (PSAS), the Morningness-Eveningness Questionnaire (MEQ), the Hamilton Anxiety Rating Scale (HAMA), and the 17-item Hamilton Depression Rating Scale (HAMD-17). The patients were divided into a cognitive impairment group and a non-cognitive impairment group based on their scores on the Montreal Cognitive Assessment Scale (MoCA). Through Spearman’s correlation analysis, we explored the correlation between the total MoCA score and the score of each factor. Additionally, we utilized binary logistic regression analysis to investigate the relationship between cognitive impairment and clinically relevant factors in MDD patients hospitalized during the acute phase and plotted ROC curves to evaluate their clinical efficacy.ResultsIn this study, we found that the prevalence of cognitive impairment among MDD patients hospitalized during the acute phase was as high as 63.49%. Through statistical analysis, we observed significant differences between the cognitive impairment group and the non-cognitive impairment group in terms of age, place of residence, education level, and HAMD-17 scores. In the Spearman correlation analysis, we noted the following trends: visuospatial and executive abilities were negatively correlated with the HAMD-17 score (P < 0.05); naming ability was positively correlated with the PSAS score but negatively correlated with the MEQ score (P < 0.05); memory was also negatively correlated with the MEQ score (P < 0.05); attention was negatively correlated with the HAMA score; and abstract cognitive ability was negatively correlated with the MEQ score (P < 0.05). Through binary logistic regression analysis, we further revealed the relationship between cognitive impairment and factors such as living in a rural area (OR = 2.7, 95% CI = 1.083-6.731, P < 0.05), increased age (OR = 1.049, 95% CI = 1.013-1.087, P < 0.01), and the HAMD-17 score (OR = 1.10295, 95% CI = 1.031-11.79, P < 0.01). Additionally, ROC curve analysis demonstrated a significant correlation between the HAMD-17 score and the prediction of cognitive function in MDD patients hospitalized during the acute phase (P < 0.001). Specifically, the AUC for the HAMD-17 score was 0.73, with an optimal cut-off value of 19.5, sensitivity of 70.0%, and specificity of 63.0%. Furthermore, the AUC for age was 0.71, with an optimal cut-off value of 33.5, sensitivity of 59.0%, and specificity of 80.0%.ConclusionsThis study indicates that MDD patients hospitalized during the acute phase have a higher prevalence of cognitive impairment. This phenomenon reflects a significant correlation between clinical factors such as age, sleep-related characteristics, and the severity of depression with cognitive impairment. Therefore, regular assessment of cognitive function in MDD patients and early intervention may be crucial for the treatment and prognosis of the disease.

Abstract The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1–3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1–3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) is a plasma protein that is evolutionarily conserved, found in both vertebrates and many invertebrates. It is a member of the pentraxin superfamily, characterized by its pentameric structure and calcium-dependent binding to ligands like phosphocholine (PC). In humans and various other species, the plasma concentration of this protein is markedly elevated during inflammatory conditions, establishing it as a prototypical acute phase protein that plays a role in innate immune responses. This feature can also be used clinically to evaluate the severity of inflammation in the organism. Human CRP (huCRP) can exhibit contrasting biological functions due to conformational transitions, while CRP in various species retains conserved protective functions in vivo. The focus of this review will be on the structural traits of CRP, the regulation of its expression, activate complement, and its function in related diseases in vivo. [ABSTRACT FROM AUTHOR]

AbstractPurposeMethodsResultsConclusion\nIMPLICATIONS FOR REHABILITATIONTo synthesize evidence on the effect of early post-stroke spasticity interventions.Systematic literature search (PubMed, Embase, and Web of Science) encompassing studies on spasticity reducing interventions within 3 months post stroke on outcome defined within the International Classification of Functioning (ICF).In total, 27 studies were identified with n = 1.658 cases. Botulinum toxin (2–12 weeks; 10 studies, n = 794) showed consistent and significant reduced spasticity by Modified Ashworth Scale (MAS) or electromyography (EMG). Electrical muscle stimulation (1–8 weeks; 6 studies, n = 335) showed lower MAS/Composite Spasticity Scale scores in 4 studies. Transcranial stimulation (3 studies; n = 131), oral spasmolytics (1 study; n = 38), shockwave (1 study; n = 40), orthotics (3 studies; n = 197 and robot-assisted therapy (3 studies; n = 123) showed inconclusive results. Effects on ICF activity domain could not be established due to limited data and large outcome measures heterogeneity. One out of two studies showed significant benefit for early compared to late BoNT intervention (< 90 vs> 90 days).This study provides evidence for early applied (<3 months) BoNT to effectively reduce spasticity and probable effectiveness of electrical stimulation. Establishing effects of interventions in the acute/hospitalization phase (<7 days) needs further work, specifically on the ICF activity domain. Standardization of outcome measures is required.Spasticity, which may develop in the first weeks after stroke, is now mostly treated in the chronic phase.This study shows that early applied Botulinum Toxin (within three months after stroke) effectively reduces spasticity and suggests that electrical stimulation may reduce spasticity.Early application of treatment with Botulinum Toxin should be considered when spasticity occurs within three months post-stroke.Spasticity, which may develop in the first weeks after stroke, is now mostly treated in the chronic phase.This study shows that early applied Botulinum Toxin (within three months after stroke) effectively reduces spasticity and suggests that electrical stimulation may reduce spasticity.Early application of treatment with Botulinum Toxin should be considered when spasticity occurs within three months post-stroke. [ABSTRACT FROM AUTHOR]

Purpose: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. Methods: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. Results: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. Conclusions: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required. [ABSTRACT FROM AUTHOR]

Aims Patients with heart failure (HF) frequently experience decreased physical function, including walking speed. Slower walking speed is associated with poorer prognosis. However, most of these reports focused on patients with stable HF, and the relationship between walking speed in acute phase and clinical outcomes is unclear. Therefore, we aimed to investigate the associations between walking speed early after admission and clinical events in patients with acute decompensated HF (ADHF). Methods and results We reviewed consecutive 1391 patients admitted due to ADHF. We measured walking speed the first time to walk on the ward more than 10 m after admission, and the speed within 4 days after admission was included in this study. The primary outcome was combined events (all-cause death and/or re-admission due to HF). The follow-up period was up to 1 year from the discharge. The study population had a median age of 74 years [interquartile range (IQR): 65–80 years], and 35.9% of patients were females. The median walking speed was 0.70 m/s (IQR: 0.54–0.88 m/s). Combined events occurred in 429 (30.8%) patients. Faster walking speed was independently associated with lower rate of combined events (adjusted hazard ratio per 0.1 m/s increasing: 0.951, 95% confidence interval: 0.912–0.992). Conclusion Faster walking speed within 4 days after admission was associated with favourable clinical outcomes in patients with ADHF. The results suggest that measuring walking speed in acute phase is useful for earlier risk stratification. [ABSTRACT FROM AUTHOR]

Abstract Background Severe burns may alter the stability of the intestinal flora and affect the patient’s recovery process. Understanding the characteristics of the gut microbiota in the acute phase of burns and their association with phenotype can help to accurately assess the progression of the disease and identify potential microbiota markers. Methods We established mouse models of partial thickness deep III degree burns and collected faecal samples for 16 S rRNA amplification and high throughput sequencing at two time points in the acute phase for independent bioinformatic analysis. Results We analysed the sequencing results using alpha diversity, beta diversity and machine learning methods. At both time points, 4 and 6 h after burning, the Firmicutes phylum content decreased and the content of the Bacteroidetes phylum content increased, showing a significant decrease in the Firmicutes/Bacteroidetes ratio compared to the control group. Nine bacterial genera changed significantly during the acute phase and occupied the top six positions in the Random Forest significance ranking. Clustering results also clearly showed that there was a clear boundary between the communities of burned and control mice. Functional analyses showed that during the acute phase of burn, gut bacteria increased lipoic acid metabolism, seleno-compound metabolism, TCA cycling, and carbon fixation, while decreasing galactose metabolism and triglyceride metabolism. Based on the abundance characteristics of the six significantly different bacterial genera, both the XGboost and Random Forest models were able to discriminate between the burn and control groups with 100% accuracy, while both the Random Forest and Support Vector Machine models were able to classify samples from the 4-hour and 6-hour burn groups with 86.7% accuracy. Conclusions Our study shows an increase in gut microbiota diversity in the acute phase of deep burn injury, rather than a decrease as is commonly believed. Severe burns result in a severe imbalance of the gut flora, with a decrease in probiotics and an increase in microorganisms that trigger inflammation and cognitive deficits, and multiple pathways of metabolism and substance synthesis are affected. Simple machine learning model testing suggests several bacterial genera as potential biomarkers of severe burn phenotypes.

BackgroundPeyronie's disease (PD) can be subdivided into acute and chronic phases. Intralesional collagenase Clostridium histolyticum has been shown to improve curvature in the chronic phase. Initial clinical trials excluded patients in the acute phase from treatment. Recent studies show comparable results among men in the acute phase. The definition of acute phase varies among existing studies, but it is generally understood to last 12-18 months and is accompanied by penile pain and progression of deformity. We sought to evaluate the safety and efficacy of intralesional collagenase injection therapy during the acute phase of PD using multiple definitions of the acute phase.MethodsAll men receiving intralesional collagenase for PD from October 2015 through December 2020 at a single academic institution were retrospectively assessed for patient demographics and comorbidities, pre- and post-treatment curvature, and adverse events. Two definitions of acute phase were used: (I) acute phase duration ≤6 months, chronic phase duration >6 months; and (II) acute phase duration ≤12 months with penile pain, chronic phase duration >12 or no penile pain.ResultsOf 330 patients identified, 229 underwent intralesional collagenase treatment with pre- and post-treatment erect penile goniometry. 65 (28%) met criteria for definition 1 of acute phase, 37 (16%) met criteria for definition 2, and 76 (33%) met criteria for either. Percent change in penile curvature was not significantly different between acute and chronic phases using definition 1 (16.0% vs. 16.6%, P=0.89), definition 2 (19.9% vs. 15.7%, P=0.43), or either (16.5% vs. 16.3%, P=0.96). The rates of development of bruising, swelling, hematoma, or corporal rupture were not significantly different between the acute and chronic phases under either definition (all P>0.05).ConclusionsThis single-center, retrospective cohort analysis suggests that intralesional collagenase is both safe and effective for the treatment of men with acute phase PD. Limitations exist inherent to retrospective review, since many men did not return for post-treatment goniometry, possibly skewing our cohort toward incomplete responders. Prospective, randomized studies will be required to confirm these findings.

Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6–8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving. Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin). Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg−1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.mL−1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively. Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei. [ABSTRACT FROM AUTHOR]

Introduction: In the acute phase after a spinal cord injury or disease (SCI/D), various therapeutic assessments and interventions are applied with the goal of restoring structures, preventing complications and preparing the patient as best as possible for further activity and finally participation. The goal was to identify and evaluate the available evidence on assessments and interventions for body functions and structures to prepare adults with acute spinal cord SCI/D for activity and participation during the first 14 days. Methods: A scoping review was conducted. The search was performed on June 19, 2023 using the databases PubMed, PEDro, Cochrane library and Embase. These were screened for studies including patients with acute SCI/D and physiotherapeutic or occupational therapy assessments and interventions. Only studies in English or German published between 2012 and 2023 were included. Results: Twelve publications met the inclusion criteria, namely three systematic reviews, two randomized controlled trials, two observational studies and five clinical practice guidelines. Assessments as the Spinal Cord Independence Measure, as well as exercises such as daily passive mobilization of body structures against contractures were used in the entire population, while others were only applied in subgroups of SCI/D such as the Graded Redefined Assessment of Strength, Sensation and Prehension or functional electrical stimulation with and without additional movements. The methodological quality of the studies found varied greatly from good to very poor. Discussion: Heterogeneity in research design and study population as well as lack of high-quality studies do not cover the standard of clinical management in the acute phase and further comprehensive research is needed. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that functional abnormalities in the KNa1.2 channel are linked to epileptic encephalopathies. However, the role of KNa1.2 channel in traumatic brain injury (TBI) remains limited. We collected brain tissue from the TBI mice and patients with post-traumatic epilepsy (PTE) to determine changes in KNa1.2 channel following TBI. We also investigated whether the MAPK pathway, which was activated by the released cytokines after injury, regulated KNa1.2 channel in in vitro. Finally, to elucidate the physiological significance of KNa1.2 channel in neuronal excitability, we utilized the null mutant-Kcnt2−/− mice and compared their behavior patterns, seizure susceptibility, and neuronal firing properties to wild type (WT) mice. TBI was induced in both Kcnt2−/− and WT mice to investigate any differences between the two groups under pathological condition. Our findings revealed that the expression of KNa1.2 channel was notably increased only during the acute phase following TBI, while no significant elevation was observed during the late phase. Furthermore, we identified the released cytokines and activated MAPK pathway in the neurons after TBI and confirmed that KNa1.2 channel was enhanced by the MAPK pathway via stimulation of TNF-α. Subsequently, compared to WT mice, neurons from Kcnt2−/− mice showed increased neuronal excitability and Kcnt2−/− mice displayed motor deficits and enhanced seizure susceptibility, which suggested that KNa1.2 channel may be neuroprotective. Therefore, this study suggests that enhanced KNa1.2 channel, facilitated by the inflammatory response, may exert a protective role in an acute phase of the TBI model. [ABSTRACT FROM AUTHOR]

Objective: To find sexual dysfunction in acute-phase bipolar depression patients and subsequently characterize the gender-wise differences in sexual functioning. Materials and Methods: A cross-sectional, descriptive, observational, purposeful, and hospital-based study was done with 45 patients (age range: 18–59 years) with moderate to severe acute phase bipolar depression (HAM-D scores >18). The domain-wise (Pleasure, Desire/Frequency Desire/Interest, Arousal/Excitement, and Orgasm/Completion) sexual functioning was assessed by the Change in Sexual Functioning Questionnaire (CSFQ-14) (≤41 for females, ≤47 for males as a cut-off for dysfunction). This study is registered in the CTRI (Clinical Trials Registry India, Number: CTRI-2021-07-035182). Results: The prevalence of sexual dysfunction was 91% of bipolar disorder patients with more male participants (53.3%) compared to females (46.7%). The mean HAM-D score for the study sample was 27.93 ± 8.035. The female gender had more dysfunctional scores in desire/frequency (t = 2.229, P = 0.031), desire/interest (t = 2.448, P = 0.019), orgasm/completion (t = 2.974, P = 0.005), and overall total CSFQ (t = 2.946, P = 0.005). The odds of sexual dysfunction were significant given a one-unit increase in suicidal ideation in the index episode (adjusted OR = 1.222, 95% CI: 1.004-1.488, P = .049). Conclusion: Acute-phase bipolar patients have very high sexual dysfunction rates. Females have both global and specific sexual response cycle deficits in comparison to acute phase bipolar depressed males. Future trials shall amuse neurobiology grounded, more individualistic sexual rehabilitation-based interventional paradigms, and longitudinal research models in acute phase bipolar depression.

Multiple sclerosis (MS) is a chronic autoimmune disease with an unknown etiology. The purpose of this research was to assess miR-223, miR-146a, and miR-193a in acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) mice to consider the possible role of these genes in the pathogenesis of MS. EAE induction was given by myelin oligodendrocyte glycoprotein peptide on female C57BL/6 mice. Clinical scores and other criteria were followed daily until day 21 for the acute group and day 77 for the chronic group. At the end of the course, inflammation and demyelination of the central nervous system (CNS) were assessed by histological analysis. MicroRNA expression levels were assessed by real-time PCR. EAE development attenuated in the chronic group, and histological analysis showed less infiltration and demyelination in the chronic group compared to the acute group. The upper expression of miR-223 is demonstrated in the acute phase of EAE. Moreover, the expression levels of miR-146a and miR-193a decreased in the chronic phase of EAE. MiR-223 showed a highly coordinated elevation in the acute phase both in vivo and in vitro. MiR-146a shares a pathway with miR-223 through effecting IL-6 expression. Further studies are needed to reveal their impact on EAE and possible applications as drug targets and biomarkers.

The emergence and spread of highly pathogenic avian influenza virus A subtype H5N1 (HP H5N1-IAV), particularly clade H5N1 2.3.4.4b, pose a severe global health threat, affecting various species, including mammals. Historically, cattle have been considered less susceptible to IAV, but recent outbreaks of H5N1-IAV 2.3.4.4b in dairy farms suggest a shift in host tropism, underscoring the urgency of expanded surveillance and the need for adaptable diagnostic tools in outbreak management. This study investigated the presence of anti-nucleoprotein (NP) antibodies in serum and milk and viral RNA in milk on dairy farms affected by outbreaks in Texas, Kansas, and Michigan using a multi-species IAV ELISA and RT-qPCR. The analysis of ELISA results from a Michigan dairy farm outbreak demonstrated a positive correlation between paired serum and milk sample results, confirming the reliability of both specimen types. Our findings also revealed high diagnostic performance during the convalescent phase (up to 96%), further improving sensitivity through serial sampling. Additionally, the evaluation of diagnostic specificity using serum and milk samples from IAV-free farms showed an excellent performance (99.6%). This study underscores the efficacy of the IAV NP-blocking ELISA for detecting and monitoring H5N1-IAV 2.3.4.4b circulation in dairy farms, whose recent emergence raises significant animal welfare and zoonotic concerns, necessitating expanded surveillance efforts.

BackgroundThe treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values， quality of life is thus of relatively high evaluative value. In China， there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder.ObjectiveTo explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase， so as to provide references for optimizing the outcome of treatment for such patients.MethodsA prospective follow-up cohort study from August 24， 2020 to November 29， 2021 was conducted， including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes， recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into monotherapy group （n=969） and combination therapy group （n=361） according to the acute phase treatment protocol. At baseline， the end of the first half month as well as the 1st， 2nd， 3rd， 6th， 9th and 12th months of treatment， patients were assessed with Inventory of Depressive Symptomatology Self-report （IDS-SR30）， Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form （Q-LES-Q-SF）， Concise Health Risk Tracking Scale （CHRT） and Siehan Disability Scale （SDS）. Frequency， Intensity， and Burden of Side Effects Rating （FIBSER） was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk， adverse reactions and impaired social functioning among patients.ResultsAt the end of three months of treatment， the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group， and the difference was statistically significant （Z=2.008， P

Abstract Background Serum amyloid A (SAA) is a major acute phase protein in horses which could be a useful tool for assessing clinical response to treatment of bacterial pneumonia in adult horses. Objectives To monitor SAA concentration in response to treatment and identify associations among SAA concentration, WBC and neutrophil counts, and fibrinogen in bacterial pneumonia in adult horses. Animals Eighteen adult horses with bacterial pneumonia. Methods Prospective clinical study. Horses hospitalized with bacterial pneumonia were enrolled and SAA concentration and vital signs were assessed daily. SAA concentration was measured by a handheld meter. CBC and plasma fibrinogen were assessed on days 0, 1, and 2, then every 3 days until discharge. Data were not normally distributed and therefore were log transformed. Log‐transformed data were analyzed and comparisons were performed on LSMeans by the 2‐sided Student's t‐test at the 5% level of significance. Results Geometric mean SAA concentration on day 0 was 537 μg/mL (SE 383 μg/mL). Geometric mean SAA concentration decreased significantly over time (P = .0001), peaking at day 2 (geomean 1038 μg/mL, SE 261.7 μg/mL) and decreasing until discharge. Plasma concentration of fibrinogen (P = .06), neutrophil count (P = .48), and WBC count (P = .07) did not change significantly over time. Conclusions and Clinical Importance SAA concentration decreased significantly over the course of treatment and correlated with clinical improvement of pneumonia whereas fibrinogen, neutrophil, and WBC counts did not.

Introduction: Diving decompression theory hypothesizes inflammatory processes as a source of micronuclei which could increase related risks. Therefore, we tested 10 healthy, male divers. They performed 6–8 dives with a maximum of two dives per day at depths ranging from 21 to 122 msw with CCR mixed gas diving.Methods: Post-dive VGE were counted by echocardiography. Saliva and urine samples were taken before and after each dive to evaluate inflammation: ROS production, lipid peroxidation (8-iso-PGF2), DNA damage (8-OH-dG), cytokines (TNF-α, IL-6, and neopterin).Results: VGE exhibits a progressive reduction followed by an increase (p < 0.0001) which parallels inflammation responses. Indeed, ROS, 8-iso-PGF2, IL-6 and neopterin increases from 0.19 ± 0.02 to 1.13 ± 0.09 μmol.min−1 (p < 0.001); 199.8 ± 55.9 to 632.7 ± 73.3 ng.mg−1 creatinine (p < 0.0001); 2.35 ± 0.54 to 19.5 ± 2.96 pg.mL−1 (p < 0.001); and 93.7 ± 11.2 to 299 ± 25.9 μmol·mol−1 creatinine (p = 0.005), respectively. The variation after each dive was held constant around 158.3% ± 6.9% (p = 0.021); 151.4% ± 5.7% (p < 0.0001); 176.3% ± 11.9% (p < 0.0001); and 160.1% ± 5.6% (p < 0.001), respectively.Discussion: When oxy-inflammation reaches a certain level, it exceeds hormetic coping mechanisms allowing second-generation micronuclei substantiated by an increase of VGE after an initial continuous decrease consistent with a depletion of “first generation” pre-existing micronuclei.

IntroductionIn the acute phase after a spinal cord injury or disease (SCI/D), various therapeutic assessments and interventions are applied with the goal of restoring structures, preventing complications and preparing the patient as best as possible for further activity and finally participation. The goal was to identify and evaluate the available evidence on assessments and interventions for body functions and structures to prepare adults with acute spinal cord SCI/D for activity and participation during the first 14 days.MethodsA scoping review was conducted. The search was performed on June 19, 2023 using the databases PubMed, PEDro, Cochrane library and Embase. These were screened for studies including patients with acute SCI/D and physiotherapeutic or occupational therapy assessments and interventions. Only studies in English or German published between 2012 and 2023 were included.ResultsTwelve publications met the inclusion criteria, namely three systematic reviews, two randomized controlled trials, two observational studies and five clinical practice guidelines. Assessments as the Spinal Cord Independence Measure, as well as exercises such as daily passive mobilization of body structures against contractures were used in the entire population, while others were only applied in subgroups of SCI/D such as the Graded Redefined Assessment of Strength, Sensation and Prehension or functional electrical stimulation with and without additional movements. The methodological quality of the studies found varied greatly from good to very poor.DiscussionHeterogeneity in research design and study population as well as lack of high-quality studies do not cover the standard of clinical management in the acute phase and further comprehensive research is needed.

Peyronie's Disease (PD) causes penile curvature and pain in acute phase. In two preclinical studies, tamoxifen and vardenafil (T&T) together showed to be effective in the acute phase. The aim of this study was to describe the clinical results of the off-label treatment of PD patients with T&T in combination with vacuum erection device (VED) in St Antonius hospital, urology outpatient clinic. Baseline descriptive Statistics, Fisher Exact and Chi-Square Test were used. 48 Men were included, mean age 53.0 years (SD 9.5), baseline curvature 46.7° (SD 18.8), median duration four months, 70.8% (n = 48) painful erections. Dorsal curvature is found in 27 (56.3%) men, mean stretched penile length 13.4 cm. Mean use of T&T was 13 weeks (1–52 weeks). Curvature improvement in 27.7% men, pain reduction in 48.5% men, sexual intercourse/coitus improvement in 34.2% men, erection improvement in 14.6% men. Adverse reactions of T&T in 39.6% (n = 19). This was the first study investigating the use of T&T in acute phase PD patients. 27.7% of patients reported improvement in curvature with T&T. [ABSTRACT FROM AUTHOR]

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Objective: To find sexual dysfunction in acute-phase bipolar depression patients and subsequently characterize the gender-wise differences in sexual functioning. Materials and Methods: A cross-sectional, descriptive, observational, purposeful, and hospital-based study was done with 45 patients (age range: 18–59 years) with moderate to severe acute phase bipolar depression (HAM-D scores >18). The domain-wise (Pleasure, Desire/Frequency Desire/Interest, Arousal/Excitement, and Orgasm/Completion) sexual functioning was assessed by the Change in Sexual Functioning Questionnaire (CSFQ-14) (≤41 for females, ≤47 for males as a cut-off for dysfunction). This study is registered in the CTRI (Clinical Trials Registry India, Number: CTRI-2021-07-035182). Results: The prevalence of sexual dysfunction was 91% of bipolar disorder patients with more male participants (53.3%) compared to females (46.7%). The mean HAM-D score for the study sample was 27.93 ± 8.035. The female gender had more dysfunctional scores in desire/frequency (t = 2.229, P = 0.031), desire/interest (t = 2.448, P = 0.019), orgasm/completion (t = 2.974, P = 0.005), and overall total CSFQ (t = 2.946, P = 0.005). The odds of sexual dysfunction were significant given a one-unit increase in suicidal ideation in the index episode (adjusted OR = 1.222, 95% CI: 1.004-1.488, P =.049). Conclusion: Acute-phase bipolar patients have very high sexual dysfunction rates. Females have both global and specific sexual response cycle deficits in comparison to acute phase bipolar depressed males. Future trials shall amuse neurobiology grounded, more individualistic sexual rehabilitation-based interventional paradigms, and longitudinal research models in acute phase bipolar depression. [ABSTRACT FROM AUTHOR]

Hao Zhang, Fan Chen Department of Traditional Chinese Medicine, People’s Hospital of Dongxihu District, Wuhan, Hubei, 430040, People’s Republic of ChinaCorrespondence: Fan Chen, Department of Traditional Chinese Medicine, People’s Hospital of Dongxihu District, No. 48, Jinbei First Road, Jinghe Street, Wuhan, Hubei, 430040, People’s Republic of China, Tel +86 15972944985, Email chenfancf79@126.comObjective: To explore the efficacy of electroacupuncture (EA) with sparse-dense wave form on the improvement of facial nerve edema, facial spasm, and repair of nerve injury in patients with acute facial paralysis.Methods: This study enrolled 100 patients who were treated for acute facial paralysis in People’s Hospital of Dongxihu District from December 2019 to December 2020. They were randomly divided into the control group (continuous wave) and the sparse-dense wave group (sparse-dense wave), following by being intervened by EA with different wave forms. Then the facial disability index (FDI) score, serum levels of immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the two groups were evaluated.Results: The total effectiveness rate (98.00% and 86.00%, respectively; P < 0.05) and the recovery rate of facial spasm (76.00% and 56.00%, respectively; P< 0.05) in the sparse-dense wave group was both significantly higher than that of the control group. After treatment, the scores of physical functions of patients in both groups increased (P < 0.05), the scores of social/well-being dysfunctions decreased (P < 0.05). Besides, the levels of serum IgA, IgG, and IgM in both groups decreased (P < 0.05), and the serum levels in the sparse-dense wave group were significantly lower than the control group (P < 0.05).Conclusion: EA intervention with sparse-dense wave form is effective for patients with acute facial paralysis, in that it effectively reduced the occurrence of facial spasm and promoted the improvement of edema and repair of nerve injury.Keywords: acute phase, electroacupuncture, EA, facial spasm, nerve edema, nerve injury repair, peripheral facial paralysis, sparse-dense wave

Though it is well documented that antidepressants are associated with an increased risk of falls in older adults at the drug class level, the comparative risk between individual antidepressants for fall injury in older adults with depression is unknown. Currently, clinicians are making decisions at the drug class level without consideration of the potential that there could be safer choices within classes. We compared the risk of fall injury among initiators of bupropion, duloxetine, fluoxetine, paroxetine, and venlafaxine to those of (es)citalopram and, separately, sertraline. We performed a retrospective cohort study using the MarketScan® Medicare Supplemental claims from 2007 to 2019. Individuals had incident depression (washout in previous continually enrolled year) with a first antidepressant claim up to three months after depression diagnosis. Individuals were followed for the first three months of antidepressant use until the first occurrence of fall injury, change/discontinuation of antidepressant, discontinued insurance coverage, or end of study. Propensity score inverse probability of treatment-weighted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals for each antidepressant comparison and fall injury. We identified 114,505 individuals (mean age 76.6 years, 68% female, 97% without prior fall). A higher risk of fall injury was associated with initiating bupropion (HR 1.20 to 1.61), duloxetine (HR 1.27 to 1.36), paroxetine (HR 1.14 to 1.22), and venlafaxine (HR 1.22 to 1.34) when compared to (es)citalopram or sertraline. New use of duloxetine, bupropion, paroxetine, and venlafaxine was associated with a higher risk of fall injury compared to (es)citalopram and sertraline.

Abstract Backgrounds To characterize the acute phase clinical manifestations and visual outcomes of the patients with Vogt-Koyanagi Harada (VKH) disease in southern China. Methods In total, 186 patients with acute-onset VKH disease were recruited. The demographic data, clinical signs, ophthalmic examinations, and visual outcomes were analyzed. Results Among the 186 VKH patients, 3 were diagnosed as complete VKH, 125 as incomplete VKH, and 58 as probable VKH. All patients visited the hospital within 3 months of onset and complained of decreased vision. For the extraocular manifestations, 121 patients (65%) referred neurological symptoms. Anterior chamber activity was negative in most eyes within an onset of 7 days, which increased slightly with onset beyond 1 week. Exudative retinal detachment (366 eyes, 98%) and optic disc hyperaemia (314 eyes, 84%) were commonly observed at presentation. A typical ancillary examination helped with the diagnosis of VKH. Systemic corticosteroid therapy was prescribed. The logMAR best-corrected visual acuity improved significantly from 0.74 ± 0.54 at baseline to 0.12 ± 0.24 at the 1-year follow-up visit. The recurrence rate was 18% in the follow-up visits. Erythrocyte sedimentation rate and C-reactive protein were significantly correlated to VKH recurrences. Conclusion Posterior uveitis, followed by mild anterior uveitis, is the typical initial manifestation in the acute phase of Chinese VKH patients. Visual outcome improvement is promising in most patients receiving systemic corticosteroid therapy in the acute phase. Detection of the clinical features at the initial onset of VKH could facilitate early treatment and better vision improvement.

Worldwide, there has been an increasing prevalence of kidney disorders for several years. Kidney disorders are characterized by abnormal kidney biomarkers like uric acid, urea, cystatin C, creatinine, kidney injury molecule-1, C-related protein, etc., in the human body. A person suffering from kidney disorders is prone to several other serious health consequences, such as cardiac diseases and renal failure, which can lead to death. However, early diagnosis of kidney disorders requires effective disease management to prevent disease progression. Existing diagnostic techniques used for monitoring kidney biomarker concentration include chromatographic assays, spectroscopic assays, immunoassays, magnetic resonance imaging (MRI), computed tomography (CT), etc. They also necessitate equipped laboratory infrastructure, specific instruments, highly trained personnel working on these instruments, and monitoring kidney patients. Hence, these are expensive and time-consuming. Since the past few decades, a number of biosensors, like electrochemical, optical, immunosensors, potentiometric, colorimetric, etc., have been used to overcome the drawbacks of conventional and modern techniques. These biosensing systems have many benefits, such as being cost-effective, quick, simple, highly sensitive, specific, requiring a minimum sample amount, reliable, and easy to miniaturize. This review article discusses the uses of effectual biosensors for kidney biomarker detection with their potential advantages and disadvantages. Future research needs to be implicated in developing highly advanced biosensors that must be sensitive, economical, and simple so that they can be used for on-site early detection of kidney biomarkers to assess kidney function.

BackgroundMolecular mechanisms underlying perioperative acute phase reactions in cardiac surgery are largely unknown. We aimed to characterise perioperative alterations of the acute phase plasma proteome in a cohort of adult patients undergoing on-pump cardiac surgery using high-throughput mass spectrometry and to identify candidate proteins potentially relevant to postoperative clinical outcome through a novel, multi-step approach.MethodsThis study is an analysis of the Bern Perioperative Biobank, a prospective cohort of adults who underwent cardiac surgery with the use of cardiopulmonary bypass (CPB) at Bern University Hospital between January and December 2019. Blood samples were taken before induction of anaesthesia and on postoperative day one. Proteomic analyses were performed by mass spectrometry. Through a multi-step, exploratory approach, hit-proteins were first identified according to their perioperative prevalence and dynamics. The set of hit-proteins were associated with predefined clinical outcome measures (all-cause one-year mortality, length of hospital stay, postoperative myocardial infarction and stroke until hospital discharge).Results192 patients [75.5% male, median age 67.0 (IQR 60.0–73.0)] undergoing cardiac surgery with the use of CPB were included in this analysis. In total, we identified and quantified 402 proteins across all samples, whereof 30/402 (7%) proteins were identified as hit-proteins. Three hit-proteins—LDHB, VCAM1 and IGFBP2—demonstrated the strongest associations with clinical outcomes. After adjustment both for age, sex, BMI and for multiple comparisons, the scaled preoperative levels of IGFBP2 were associated with 1-year all-cause mortality (OR 10.63; 95% CI: 2.93–64.00; p = 0.046). Additionally, scaled preoperative levels of LDHB (OR 5.58; 95% CI: 2.58–8.57; p = 0.009) and VCAM1 (OR 2.32; 95% CI: 0.88–3.77; p = 0.05) were found to be associated with length of hospital stay.ConclusionsWe identified a subset of promising candidate plasma proteins relevant to outcome after on-pump cardiac surgery. IGFBP2 showed a strong association with clinical outcome measures and a significant association of preoperative levels with 1-year all-cause mortality. Other proteins strongly associated with outcome were LDHB and VCAM1, reflecting the dynamics in the acute phase response, inflammation and myocardial injury. We recommend further investigation of these proteins as potential outcome markers after cardiac surgery. Clinical Trial RegistrationClinicalTrials.gov; NCT04767685, data are available via ProteomeXchange with identifier PXD046496.

Background The treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values, quality of life is thus of relatively high evaluative value. In China, there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder. Objective To explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase, so as to provide references for optimizing the outcome of treatment for such patients. Methods A prospective follow-up cohort study from August 24, 2020 to November 29, 2021 was conducted, including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes, recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders, fifth edition(DSM-5 ). Patients were divided into monotherapy group(n=969) and combination therapy group(n=361) according to the acute phase treatment protocol. At baseline, the end of the first half month as well as the 1st, 2nd, 3rd, 6th, 9th and 12th months of treatment, patients were assessed with Inventory of Depressive Symptomatology Self-report(IDS-SR30), Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form(Q-LES-Q-SF), Concise Health Risk Tracking Scale(CHRT) and Siehan Disability Scale(SDS). Frequency, Intensity, and Burden of Side Effects Rating(FIBSER) was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk, adverse reactions and impaired social functioning among patients. Results At the end of three months of treatment, the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group, and the difference was statistically significant(Z=2. 008, P<0. 05). The time effects of both treatment protocols possessed statistical significance(F=111. 393, P<0. 01). At the end of three months of treatment, the Q-LES-Q-SF score was negatively correlated with CHRT and SDS scores, respectively, in both monotherapy group and combination treatment group(r=-0. 660, -0. 712, -0. 634, -0. 718, P<0. 01). Conclusion Both monotherapy and combination therapy can facilitate the improvement of the life quality of patients with acute depressive disorder, but monotherapy may achieve better than the combination therapy in this aspect. [Funded by The National Key Research and Development Program of China "Research on the Prevention and Control of Major Chronic Non-communicable Diseases"(number, 2017YFC1311101)]. [ABSTRACT FROM AUTHOR]

Background: Serum amyloid A (SAA) is a major acute phase protein in horses which could be a useful tool for assessing clinical response to treatment of bacterial pneumonia in adult horses. Objectives: To monitor SAA concentration in response to treatment and identify associations among SAA concentration, WBC and neutrophil counts, and fibrinogen in bacterial pneumonia in adult horses. Animals: Eighteen adult horses with bacterial pneumonia. Methods: Prospective clinical study. Horses hospitalized with bacterial pneumonia were enrolled and SAA concentration and vital signs were assessed daily. SAA concentration was measured by a handheld meter. CBC and plasma fibrinogen were assessed on days 0, 1, and 2, then every 3 days until discharge. Data were not normally distributed and therefore were log transformed. Log‐transformed data were analyzed and comparisons were performed on LSMeans by the 2‐sided Student's t‐test at the 5% level of significance. Results: Geometric mean SAA concentration on day 0 was 537 μg/mL (SE 383 μg/mL). Geometric mean SAA concentration decreased significantly over time (P =.0001), peaking at day 2 (geomean 1038 μg/mL, SE 261.7 μg/mL) and decreasing until discharge. Plasma concentration of fibrinogen (P =.06), neutrophil count (P =.48), and WBC count (P =.07) did not change significantly over time. Conclusions and Clinical Importance: SAA concentration decreased significantly over the course of treatment and correlated with clinical improvement of pneumonia whereas fibrinogen, neutrophil, and WBC counts did not. [ABSTRACT FROM AUTHOR]

Though it is well documented that antidepressants are associated with an increased risk of falls in older adults at the drug class level, the comparative risk between individual antidepressants for fall injury in older adults with depression is unknown. Currently, clinicians are making decisions at the drug class level without consideration of the potential that there could be safer choices within classes. We compared the risk of fall injury among initiators of bupropion, duloxetine, fluoxetine, paroxetine, and venlafaxine to those of (es)citalopram and, separately, sertraline. We performed a retrospective cohort study using the MarketScan® Medicare Supplemental claims from 2007 to 2019. Individuals had incident depression (washout in previous continually enrolled year) with a first antidepressant claim up to three months after depression diagnosis. Individuals were followed for the first three months of antidepressant use until the first occurrence of fall injury, change/discontinuation of antidepressant, discontinued insurance coverage, or end of study. Propensity score inverse probability of treatment-weighted Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals for each antidepressant comparison and fall injury. We identified 114,505 individuals (mean age 76.6 years, 68% female, 97% without prior fall). A higher risk of fall injury was associated with initiating bupropion (HR 1.20 to 1.61), duloxetine (HR 1.27 to 1.36), paroxetine (HR 1.14 to 1.22), and venlafaxine (HR 1.22 to 1.34) when compared to (es)citalopram or sertraline. New use of duloxetine, bupropion, paroxetine, and venlafaxine was associated with a higher risk of fall injury compared to (es)citalopram and sertraline. [ABSTRACT FROM AUTHOR]

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Abstract Background Peripheral facial paralysis (PFP) results in functional disorder and social dysfunction, when it is under a severe condition at onset, long-term poor outcomes do occur. Different acupuncture methods have been reported to be potentially effective for shortening the disease course and reducing the occurrence of sequelae when they are applied at an early stage. Neuro edema is a common pathological feature in the acute phase, and many clinical studies have suggested its effect of reducing facial nerve edema. It is of value to estimate the effectiveness and safety of acupuncture treatment at the onset, and to assess the most suitable acupuncture method for the acute period. Methods and analysis All the RCTs and quasi-RCTs on acupuncture therapy for patients who is during acute stage of PFP will be included. The recovery rate of facial function, the time it takes to restore facial function and the odds of sequelae occurring will be the key parts we focus on. Psychological well-being and quality of life will also be evaluated. Literature searching will be conducted until December 31th, 2022 from eight databases systematically. Two reviewers will screen the literature and extract the data independently. RevMan software will be used for data analysis, and the version 2 of the Cochrane risk-of-bias tool (RoB 2) will be used to assess the certainty of evidence. Forest plots and summary findings will be generated. If data permits, a meta-analysis will be conducted. Ethics and dissemination Since this study will not involve clinical treatment of patients, ethics approval is not required. The result of this study will be submitted to a peer-reviewed journal for publication and as a proposal for clinical practice and further study on acupuncture treatment at the early stage of PFP. Discussion This review will summarize the evidence on the different type of acupuncture therapy for acute Bell’s palsy and Ramsay-Hunt syndrome. We anticipate that it would be safe and effective when applied to the acute phase of PFP, and some specific suitable acupuncture methods would be found resulting from this review. Systematic review registration International Prospective Register for Systematic Reviews (PROSPERO) number CRD42020205127

Background: An early and effective immune response has a role in disease presentation and clearance of pathogen. Chemokine and cytokine responses in the immunopathogenesis of scrub typhus (ST) are the least explored aspect. This study aimed to analyze interleukin (IL)-2, IL-6, tumor necrosis factor-alpha (TNF-α), IL-10, transforming growth factor (TGF)-β, and human macrophage inflammatory protein-1 (HMIP-1) β cytokine levels in ST-positive patients during the acute phase of illness. Materials and Methods: A total of 112 ST-positive patients were included in the study with 30 healthy controls (HC). Diagnosis was confirmed by immunoglobulin M enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence assay. The serum levels of cytokines were measured using the ELISA. Statistical analysis was performed with the IBM SPSS Statistics 20 and MedCalc 16.1 Software. Results: The mean level of IL-6, IL-10, TNF-α, and HMIP1-β (72 pg/ml, 86.7 pg/ml, 187.05 pg/ml, and 12.23 pg/ml vs. 7.30 pg. ml, 8.73 pg/ml, 56.62 pg/ml, and 6.94 pg/ml, respectively) was significantly raised among the ST patients compared to the control group (P < 0.001) However, the mean and median levels of IL-2 and TGF-β were not differed significantly between ST patients and HC (P = 0.0207 and 0.0386, respectively). The severity of the disease involved respiratory complications. Around 90.1% (101/112) of patients showed high levels of IL-6, whereas IL-10, TNF-α, and HMIP-1 β levels were raised in 97 (86.6%), 63 (56.2%), and 69 (61.6%) cases, respectively. There was a higher TNF-α level in severe cases with a few values up to 298.77 pg/ml. Conclusion: Proinflammatory cytokines and IL-10 were found to be increased in ST patients during the acute phase of infection. A proper balance of these cytokines is required for a better outcome. These findings suggest that the status of TNF-α levels in the acute phase may predict the severity of ST disease.

Abstract Background To evaluate the effectiveness of enhanced check to the duration of the central venous catheters associated bloodstream infections (CABSIs), and the impact on infection rates. Methods A before-after, real-world study in six adult intensive care units was conducted. All adult patients who had only one central venous catheter were included during two consecutive periods. The intervention period, added cross-check that all patients with central venous catheter (CVC) need to be performed, and included nurses' checks for insertion practices and doctors' checks for maintenance practices. Propensity scores matching were used to account for potential confounding, and restricted cubic spline was served as visualizing the CABSI risk. Results A total of 2906 patients with 26,157 CVC-days were analyzed. After intervention, the density incidence of CABSI decreased from 10.24 to 6.33/1,000 CVC-days (P