In vivo and in vitro study on the regulatory mechanism of XiaoChaiHu decoction on PANoptosis in sepsis-induced cardiomyopathy.

ETHNOPHARMACOLOGICAL RELEVANCE: In accordance with the tenets of traditional Chinese medicine, sepsis is categorized into three distinct syndromes: heat syndrome, blood stasis syndrome, and deficiency syndrome. Xiaochaihu decoction (XCHD) has many functions, including the capacity to protect the liver, cholagogue, antipyretic, anti-inflammatory, and anti-pathogenic microorganisms. XCHD exerts the effect of clearing heat and reconciling Shaoyang. The XCHD contains many efficacious active ingredients, yet the mechanism of sepsis-induced cardiomyopathy (SIC) remains elusive. AIM OF THE STUDY: To investigate the molecular mechanisms underlying the protective effects of XCHD against SIC using an integrated approach combining network pharmacology and molecular biology techniques. MATERIALS AND METHODS: Network pharmacology methods identified the active ingredients, target proteins, and pathways affected by XCHD in the context of SIC. We conducted in vivo experiments using mice with lipopolysaccharide-induced SIC, evaluating cardiac function through echocardiography and histology. XCHD-containing serum was analyzed to determine its principal active components using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The effects of XCHD-containing serum on SIC were further tested in vitro in LPS-treated H9c2 cardiac cells. Protein expression levels were quantified via Western blotting and enzyme-linked immunosorbent assay (ELISA). Additionally, molecular docking was performed between the active components and ZBP1, a potential target protein. Overexpression of ZBP1 in H9c2 cells allowed for a deeper exploration of its role in modulating SIC-associated gene expression. RESULTS: UPLC-MS/MS identified 31 shared XCHD and XCHD-containing serum components. These included organic acids, terpenoids, and flavonoids, which have been identified as the active components of XCHD. Our findings revealed that XCHD alleviated LPS-induced myocardial injury, improved cardiac function, and preserved cardiomyocyte morphology in mice. In vitro studies, we demonstrated that XCHD-containing serum significantly suppressed the expression of inflammatory cytokines (IL-6, IL-1ß, and TNF-α) in LPS-induced H9c2 cells. Mechanistic investigations showed that XCHD downregulated genes associated with PANoptosis, a novel cell death pathway, suggesting its protective role in sepsis-damaged hearts. Conversely, overexpression of ZBP1 abolished the protective effects of XCHD and amplified PANoptosis-related gene expression. CONCLUSIONS: Our study provides the first evidence supporting the protective effects of XCHD against SIC, both in vitro and in vivo. The underlying mechanism involves the inhibition of ZBP1-initiated PANoptosis, offering new insights into treating SIC using XCHD.

Accuracy study of Angiotensin 1-7 composite index test to predict pulmonary fibrosis and guide treatment.

BACKGROUND: Pulmonary fibrosis can develop after acute respiratory distress syndrome (ARDS). The hypothesis is we are able to measure phenotypes that lie at the origin of ARDS severity and fibrosis development. The aim is an accuracy study of prognostic circulating biomarkers. METHODS: A longitudinal study followed COVID-related ARDS patients with medical imaging, pulmonary function tests and biomarker analysis, generating 444 laboratory data. Comparison to controls used non-parametrical statistics; p < 0·05 was considered significant. Cut-offs were obtained through receiver operating curve. Contingency tables revealed predictive values. Odds ratio was calculated through logistic regression. RESULTS: Angiotensin 1-7 beneath 138 pg/mL defined Angiotensin imbalance phenotype. Hyper-inflammatory phenotype showed a composite index test above 34, based on high Angiotensin 1-7, C-Reactive Protein, Ferritin and Transforming Growth Factor-ß. Analytical study showed conformity to predefined goals. Clinical performance gave a positive predictive value of 95 % (95 % confidence interval, 82 %-99 %), and a negative predictive value of 100 % (95 % confidence interval, 65 %-100 %). Those severe ARDS phenotypes represented 34 (Odds 95 % confidence interval, 3-355) times higher risk for pulmonary fibrosis development (p < 0·001). CONCLUSIONS: Angiotensin 1-7 composite index is an early and objective predictor of ARDS evolving to pulmonary fibrosis. It may guide therapeutic decisions in targeted phenotypes.

"Lupus Myelitis" Revisited: A Retrospective Single-Center Study of Myelitis Associated With Rheumatologic Disease.

BACKGROUND AND OBJECTIVES: Previous reports of patients with myelitis associated with rheumatologic disease may have had unrecognized aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated disease (MOGAD). We clinicoradiologically and serologically characterized patients with myelitis associated with rheumatologic disease evaluated in the era of availability of MOG-IgG and more sensitive AQP4-IgG cell-based assays. METHODS: A retrospective cohort (2018-2023) at Johns Hopkins Medicine with diagnoses of myelopathy and rheumatologic comorbidity was identified by electronic medical record (EMR) query. All patients with myelitis unrelated to typical multiple sclerosis (MS) were included and analyzed by chart review. RESULTS: Of 238 patients identified by EMR query, 197 were excluded (148 not meeting prespecified inclusion criteria, 49 had typical MS), resulting in 41 patients for review. The mean age at myelitis onset was 44 ± 15 years; 39 (95%) were female. Rheumatologic diagnoses included 17 (41.5%) with systemic lupus erythematosus (SLE), 10 (24.3%) Sjögren syndrome (SS), 6 (15%) undifferentiated connective tissue disease (UCTD), 5 (12%) combinations of SLE/SS/UCTD with antiphospholipid antibody syndrome, 1 (2.4%) rheumatoid arthritis, 1 (2.4%) psoriatic arthritis, and 1 (2.4%) Behçet disease. 20 patients (49%) were diagnosed with AQP4-IgG seropositive NMOSD, 3 (7%) with MOGAD, and 18 (44%) had "double-seronegative" myelitis. Of these 18, 3 were diagnosed with AQP4-IgG seronegative NMOSD, 1 neuro-Behçet disease, and 14 other (unclassifiable) myelitis. Excluding 1 patient with neuro-Behçet disease, 18 (90%) of 20 AQP4-IgG seropositive patients had longitudinally extensive cord lesions compared with 5 (29%; p < 0.001) of 17 "double-seronegative" patients and 2 (67%) of 3 with MOGAD. "Double-seronegative" patients more commonly had CSF-restricted oligoclonal bands. Functional outcomes did not differ by diagnosis, and most patients received acute immunotherapy at the time of initial myelitis diagnosis with at least partial recovery over a median follow-up of 38 (interquartile range: 9-74) months. DISCUSSION: Approximately half of our rheumatologic disease cohort with myelitis unrelated to MS had AQP4-IgG seropositive NMOSD while MOGAD accounted for a small but clinically relevant proportion of patients. Further research is needed to characterize myelitis etiology in patients who are seronegative for both AQP4-IgG and MOG-IgG.

Cognitive function and brain structure in COVID-19 survivors: The role of persistent symptoms.

Persistent COVID-19 symptoms post-acute state have been shown to have a significant negative impact on brain structure and function. In this study, we conducted magnetic resonance imaging (MRI) of the whole brain in 43 working-age adults (mean age: 44.79±10.80; range: 24-65 years) with a history of COVID-19 (731.17±312.41 days post-diagnosis), and also assessed their cognitive function (processing speed, attention, working memory, executive function, and recognition memory), mental health, and sleep quality. MRI data were processed using FSL to derive regional volumes for bilateral nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, and hippocampus, and total grey matter, white matter, and cerebral spinal fluid volume, and analysed in relation to persistent COVID-19 symptom load, mental health, and sleep quality. Higher persistent COVID-19 symptom load was significantly associated with smaller putamen volume, lower response accuracy on working memory, executive function, and recognition memory tasks, as well as a longer time to complete the executive function task, and poorer mental health and sleep quality. Smaller putamen fully mediated the relationship between persistent COVID-19 symptom load and lower executive function. Further research is required to confirm whether reduced putamen volume and its association with poor executive function persists in COVID-19 survivors in the long term.

12-week melatonin supplementation improved dynamic postural stability and walking performance in persons living with multiple sclerosis: A randomized controlled trial.

BACKGROUND: Persons with multiple sclerosis (PwMS) suffer from sleep disturbances, fatigue and pain, which can be due, at least in part, to decreased levels of endogenous melatonin. These alterations could exacerbate postural instability, gait disorders and fall risk. Acute effects of exogenous melatonin on physical disorders have been studied in PwMS but its long-term effects on these parameters have not been explored yet in this population. This study aimed to determine the impact of chronic melatonin intake on dynamic postural stability, walking performance and fall risk in PwMS. METHODS: This randomized placebo-controlled study included 27 PwMS who were assigned to either melatonin group (MG, n=15) or placebo group (PG, n=12) (3 mg/night for 12 weeks). Dynamic postural balance (force platform), walking performance (locometer) and fall risk (Four Square Step Test) were evaluated pre (T0)- and post (T1)-intervention. Sleep quality (Pittsburgh Sleep Quality Index (PSQI)), fatigue perception (Fatigue Severity Scale (FSS)), neuropathic pain (Neuropathic Pain Questionnaire 4 (DN4)) and quality of life (International Multiple Sclerosis (MS) Quality of Life Questionnaire) were also assessed at T0 and T1. RESULTS: The center of pressure mean velocity decreased in MG compared with PG in the frontal plane (22.98 %, p=0.028). Stride length and walking speed increased in MG comparatively with PG (18.09 %, p=0.036; 9.65 %, p=0.025, respectively). The PSQI (55.89 %, p<0.001), FSS (32.38 %, p=0.003) and DN4 (32.41 %, p=0.035) scores decreased in MG compared with PG. CONCLUSION: 12-week melatonin supplementation can be recommended for managing MS-related gait disorders and dynamic postural imbalance. This therapy may also be prescribed for PwMS due to its anti-fatigue and analgesic effects as well as its benefits on sleep quality. CLINICAL REGISTRATION: This study was prospectively recorded in the Pan African Clinical Trial Registry database (PACTR202007465309582) (https://pactr.samrc.ac.za/.).

Sex-dependent perturbations in risky choice behavior and prefrontal tyrosine hydroxylase levels induced by repetitive mild traumatic brain injury.

Head trauma often impairs cognitive processes mediated within the prefrontal cortex (PFC), leading to impaired decision making and risk-taking behavior. Mild traumatic brain injury (mTBI) accounts for approximately 80 % of reported head injury cases. Most neurological symptoms of a single mTBI are transient; however, growing evidence suggests that repeated mTBI (rmTBI) results in more severe impairments that worsen with each subsequent injury. Although mTBI-induced disruption of risk/reward decision making has been characterized, the potential for rmTBI to exacerbate these effects and the neural mechanisms involved are unknown. Catecholamine neurotransmitters, dopamine (DA) and norepinephrine (NE), modulate PFC-mediated functions. Imbalances in catecholamine function have been associated with TBI and may underlie aberrant decision making. We used a closed head-controlled cortical impact (CH-CCI) model in rats to evaluate the effects of rmTBI on performance of a probabilistic discounting task of risk/reward decision making behavior and expression levels of catecholamine regulatory proteins within the PFC. RmTBI produced transient increases in risky choice preference in both male and female rats, with these effects persisting longer in females. Additionally, rmTBI increased expression of the catecholamine synthetic enzyme, tyrosine hydroxylase (TH), within the orbitofrontal (OFC) region of the PFC in females only. These results suggest females are more susceptible to rmTBI-induced disruption of risk/reward decision making behavior and dysregulation of catecholamine synthesis within the OFC. Together, using the CH-CCI model of rodent rmTBI to evaluate the effects of multiple insults on risk-taking behavior and PFC catecholamine regulation begins to differentiate how mTBI occurrences affect neuropathological outcomes across different sexes.

Acute Vascular Complications of VA-ECMO in COVID-19 Patients. Does COVID-19 Affect the Outcome?

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) through the femoral artery and vein can lead to significant vascular complications. We retrospectively studied the acute vascular complications of Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) in COVID-19 patients compared to non-COVID patients during the period from January 2020 to July 2023. RESULTS: Seventy-eight patients underwent VA-ECMO for various indications from January 2020 to July 2023. The studied patients had a mean age of 59.6 ± 6.9 years for non-COVID patients (38 patients), and 62.2 ± 7.6 years for COVID patients (40 patients), with a P = 0.268. In non-COVID patients, The baseline characteristics were similar in both groups. The primary indications for ECMO were cardiac diseases, followed by respiratory failure (78.9% vs 10.5%). Conversely, in COVID patients, respiratory failure due to COVID-19 infection was the main indication (45% vs 40%). The overall incidence of general complications, including cerebrovascular stroke, acute kidney injury, intracardiac thrombi, and wound infection, was comparable in both groups (31.6% vs 45%). The overall incidence of vascular complications in both groups was 33.3%. Ipsilateral acute lower limb ischemia occurred in 5.3% vs 10% of non-COVID and COVID patients, respectively. Thrombosis of the distal perfusion catheter (DPC) occurred in 10.5% vs 15%, respectively. CONCLUSION: During the COVID-19 pandemic, an increasing number of patients required VA-ECMO due to associated respiratory failure. Patients undergoing VA-ECMO are at high risk of developing various vascular complications. COVID-19 significantly increases the risk of acute limb ischemia and distal perfusion catheter thrombosis in both upper and lower limbs. However, other VA-ECMO-related vascular complications are comparable between COVID-19 and non-COVID patients.

Like Father like Daughter: Surgical Redo Thoracoabdominal Aneurysm Repairs in a Family With Loeys-Dietz Syndrome.

Loeys Dietz Syndrome (LDS) is an autosomal dominant connective tissue disorder resulting from a mutation in the transforming growth factor beta receptor (TGFBR) family of genes. It is commonly associated with the development of aortic aneurysms and dissections. We report the successful open surgical management of thoracoabdominal aneurysms in a father and daughter with Loeys-Dietz Syndrome after failed endovascular repair. The daughter required stent graft explantation, while the stent graft remained in the father. These cases highlight the importance of early genetic testing of both patients and first-degree family members in those with a strong history of aortic disease, even when there is a lack of typical connective tissue disorder associated physical exam findings and open surgical index operations.

Progressive Acute Lower Extremity Ischemia Resulting From Cardiac Myxoma Embolization: A Case Report.

Cardiac myxomas are the most common primary benign tumors of the heart. The occlusion of peripheral arteries and complete obstruction of the abdominal aorta by a tumor embolus presents with distinct clinical manifestations. Herein, we present the case of a 38-year-old male with acute paresthesia, muscle weakness, erythematous, and violaceous changes in skin color localized to the dorsum of the left forefoot initially treated as cutaneous vasculitis. Further studies revealed the total occlusion of the terminal abdominal aorta by a saddle embolus from a cardiac myxoma. A multidisciplinary team consisting of cardiothoracic and vascular surgeons were involved in treating the patient, which resulted in full resolution of the case. This paper details the progression of acute bilateral limb ischemia to chronic limb threatening ischemia resulting from the total occlusion of the terminal abdominal aorta by a saddle embolus.

Open Surgical Repair in a Patient With Loeys-Dietz Syndrome and Extensive Vascular Compromise: A Case Report and Literature Review.

Loeys-Dietz syndrome (LDS) has been associated with multiple vascular abnormalities involving the entire arterial tree. However, limited reports regarding compromise in the aortoiliac and femoral bifurcation are available. Further, recommendations for optimal approach, thresholds for diameter at the time of surgery, and surveillance are also limited. We present a case of a 67-year-old male patient with LDS and aneurysmal aortoiliac and enlarging common femoral arteries aneurysms, who underwent open surgical repair. His past surgical history included multiple vascular interventions for lower extremity claudication and bilateral hip replacements. The right hip arthroplasty was previously removed due to infection. From the vascular standpoint, the patient underwent staged endovascular left hypogastric artery embolization and open aorto-bi-profunda bypass with a Rifampin-soaked Dacron graft. At 5-month follow-up, he remains asymptomatic with healed incisions and patent bypasses. This case highlights the challenges in managing peripheral aneurysms in LDS patients, emphasizing the need for tailored treatment strategies. While open repair is preferred, endovascular options may be considered in selected cases. Surveillance remains critical with annual cross-sectional imaging. Surgical planning is intricate due to comorbidities, anatomical complexities, and previous surgical infection. Surveillance of these patients must be strict as multiple vascular and non-vascular complications may arise. Therefore, collaborative decision-making is essential for optimal outcomes in this known high-risk population with connective tissue disorders.

Copeptin associates with major adverse cardiovascular events in patients on maintenance hemodialysis.

BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.

Conocimiento en estudiantes de enfermería sobre sepsis quirúrgico / Knowledge in nursing students about surgical sepsis

Objetivo: Determinar el nivel de conocimiento de los estudiantes de enfermería de la Universidad Técnica de Ambato sobre sepsis quirúrgica. Material y método: La presente investigación tiene un diseño de desarrollo observacional, de tipo descriptivo, cohorte transversal, con un enfoque cuantitativo, ya que el nivel de cono-cimiento se verá representado mediante tablas y gráficos para des-cribir la problemática del periodo octubre 2023 febrero 2024. Re-sultados: Se evidencia un alto porcentaje de respuestas incorrectas por cada ítem por parte de los estudiantes. La categoría Nivel de Conocimiento sobre Definición de Sepsis, fue respondida de ma-nera incorrecta con un porcentaje del 83,9%, la categoría Nivel de Conocimiento sobre Diagnóstico de Sepsis obtuvo 51,7% y, por úl-timo, la Nivel de Conocimiento sobre Tratamiento de Sepsis con el 29,2%. Conclusiones: El nivel de conocimiento de los estudiantes sobre Sepsis Quirúrgica es malo, debido a que existe una subesti-mación de la gravedad de la sepsis como afección potencialmente mortal, lo que puede traer un impacto negativo en los pacientes[AU]

Objective: Determine the level of knowledge of nursing students at the Technical University of Ambato about surgical sepsis. Mate-rials and methods: This research has an observational, descriptive, transversal development design, with a quantitative approach since the level of knowledge will be represented through tables and gra-phs to describe the problems of the period October 2023-February 2024. Results: A high percentage of incorrect answers for each item by the students is evident. The category Level of Knowledge about Definition of Sepsis was answered incorrectly with a percentage of 83.9%, the category Level of Knowledge about Diagnosis of Sepsis obtained 51.7% and, finally, the category Level of Knowledge about Treatment of Sepsis. Sepsis with 29.2%. Conclusions: The level of knowledge of students about Surgical Sepsis is poor because there is an underestimation of the severity of sepsis as a potentially fatal condition, which can have a negative impact on patients[AU]

Objetivo: Determinar o nível de conhecimento dos estudantes de enfermagem da Universidade Técnica de Ambato sobre sepse ci-rúrgica. Material e método: Esta pesquisa possui desenho de coor-te observacional, descritivo, transversal, com abordagem quantita-tiva, uma vez que o nível de conhecimento será representado por meio de tabelas e gráficos para descrever o problema no período de outubro de 2023 a fevereiro de 2024. Resultados: Uma parada. É evidente o percentual de respostas incorretas para cada item por parte dos alunos. A categoria Nível de Conhecimento sobre Defi-nição de Sepse foi respondida incorretamente com percentual de 83,9%, a categoria Nível de Conhecimento sobre Diagnóstico de Sepse obteve 51,7% e por fim, a categoria Nível de Conhecimen-to sobre Tratamento de Sepse com 29,2%. Conclusões: O nível de conhecimento dos estudantes sobre a Sepse Cirúrgica é baixo, pois há uma subestimação da gravidade da sepse como uma condição potencialmente fatal, que pode ter um impacto negativo nos pa-cientes[AU]

Baseline level of interleukin-6 is associated with the risk of acute coronary syndrome development in SARS-CoV-2 infection.

BACKGROUND: Acute coronary syndrome (ACS) is frequently reported in patients with coronavirus disease 2019 (COVID-19). Cytokine storm induced by interleukin-6 (IL-6) has been suggested to potentially cause myocardial injury in COVID-19. We investigated the association between baseline level of IL-6 and development of ACS in COVID-19 patients. METHODS: Demographic and clinical data of hospitalized COVID-19 patients from 2020 to 2022 were reviewed. Extracted data including patient characteristics, laboratory biomarkers, and systemic inflammation indexes in patients with or without ACS were reviewed and analyzed. Logistic regression models were applied to analyze predictors of ACS development and receiver-operating characteristic (ROC) curves were used to assess discriminatory power of IL-6 and other risk factors for predicting ACS development. RESULTS: Among 1,753 COVID-19 patients, 37 cases experienced ACS and 159 patients without main COVID-19 complications were randomly selected as controls. ACS patients were older (p = 0.001) and suffered from more comorbidities including diabetes (43% vs. 18%, p = 0.001), hypertension (40.5% vs. 24.5%, p = 0.050), ischemic heart disease (49% vs. 9%, p = 0.001), and hyperlipidemia (19% vs. 5%, p = 0.010). Also, decreased level of consciousness (31.6% vs. 2.5%, p = 0.001), ICU admission (65% vs. 2%, p = 0.001), and mortality events (70% vs. 0.6%, p = 0.001) were more prevalent in the ACS group. Baseline levels of IL-6 (p = 0.001), D-dimer (p = 0.026), troponin (p = 0.001), blood urea nitrogen (p = 0.002), and creatinine (p = 0.008) were higher in ACS patients but erythrocyte sedimentation rate (p = 0.013), hemoglobin (p = 0.033), and red blood cells (p = 0.028) were lower compared with controls. Also, age (OR: 1.06, p = 0.019), IL-6 (OR: 1.44, p = 0.047), and cardiovascular disease (CVD) (OR: 3.66, p = 0.043) were associated with ACS development. The area under the curve (AUC) of IL-6 and combined predictors respectively was 0.661 (p = 0.002) and 0.829 (p = 0.001). CONCLUSIONS: High IL-6 concentration at baseline is a strong predictor for ACS development in COVID-19 patients. Also, elderly and concurrent CVD are significantly associated with ACS development.

Cerebral venous sinus thrombosis associated with JAK2 V617F mutation-related pre-primary myelofibrosis: a case report and literature review.

BACKGROUND: Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening subtype of stroke. Prompt and appropriate anticoagulation is crucial for improving the prognosis of CVST and preventing its recurrence. Identifying the underlying cause of CVST is decisive for guiding anticoagulant selection and determining treatment duration. CASE PRESENTATION: A 50-year-old man presented with a 35-day history of headache, nausea, vomiting, and blurred vision. Digital subtraction angiography performed at another facility revealed CVST. A contrast-enhanced black-blood MRI at our center confirmed the diagnosis, which was supported by a high intracranial pressure of 330mmH2O. Laboratory tests showed elevated leukocytes and platelet counts, raising suspicion of an underlying myeloproliferative neoplasms (MPNs). A bone marrow biopsy demonstrated increased megakaryocytes and granulocytes, and genetic testing identified the presence of the Janus kinase 2 V617F (JAK2 V617F) mutation, leading to a diagnosis of pre-primary myelofibrosis (pre-PMF). During hospitalization, anticoagulation with nadroparin calcium and fibrinolytic therapy were initiated. Upon discharge, rivaroxaban and aspirin were prescribed to prevent CVST recurrence and arterial thrombosis. CONCLUSION: This case highlights the importance of recognizing dynamic changes in routine blood tests that may link CVST to underlying hematological disorders. The JAK2 mutation is not only associated with MPNs but also increases the risk of thrombosis, including CVST. Further investigation is warranted to better understand the mechanisms by which JAK2 mutations contribute to thrombosis and to explore the potential benefits of JAK2 inhibitors in reducing this risk.

Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center.

BACKGROUND: Candidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia. METHODS: This retrospective cohort study included patients treated at Peru's oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05. RESULTS: A total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87-23.24, p = 0.003). CONCLUSIONS: The association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death.

The relationship between the Barthel Index and stroke-associated pneumonia in elderly patients and factors of SAP.

BACKGROUND: Stroke-associated pneumonia (SAP) is a common complication in stroke patients, and the Barthel Index (BI) is a well-established metric for assessing activities of daily living (ADL). However, the association between BI and SAP in acute ischemic stroke (AIS) patients remains unclear. This study aims to investigate the relationship between BI at admission and SAP, and explore the factors in AIS elderly patients. METHOD: Retrospective data were collected from ischemic stroke patients hospitalized at the Second Affiliated Hospital of Nanchang University between January 2018 and July 2021, including their basic demographic and laboratory test results. Restricted cubic spline regression, multivariate logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were employed to investigate the relationship between BI and SAP. Additionally, the Shapley Additive exPlanations (SHAP) method was used to identify the factors influencing SAP. RESULTS: The study included 7,548 eligible stroke patients with a mean age of 75.1 ± 7.6 years, among which 41.14% were female. The SAP group demonstrated significantly lower BI compared to the non-SAP group (50.86 ± 35.60 vs. 75.27 ± 26.33, P < 0.001). Additionally, a conspicuous trend of decreasing SAP risk across the Q1-4 groups was observed (P < 0.001). The RCS analysis further confirmed a gradual reduction in SAP risk with increasing BI. Based on the clinical model, both the BI (NRI = 0.014, P = 0.005; IDI = 0.04, P < 0.001) and the NIHSS score (NRI = 0.09, P = 0.03; IDI = 0.025, P < 0.001) demonstrated additional predictive value for SAP. Multivariate logistic regression and SHAP analysis identified WBC, CONUT, TG, UA, and RBC levels, as well as the type of health insurance (urban employee basic medical insurance), as important independent predictors of SAP. CONCLUSION: BI at admission constitutes a risk factor for the onset of SAP in elderly patients with AIS, Compared to the NIHSS and mRS score, BI may be a more reliable and practical predictor of SAP.

Risk factors for postoperative hepatic dysfunction in overweight patients with acute type A aortic dissection.

BACKGROUND: Acute hepatic dysfunction (AHD) is a common postoperative complication in patients with acute type A aortic dissection. The aim of this study was to identify risk factors for acute hepatic dysfunction after surgery for acute type A aortic dissection. METHODS: We performed a retrospective study from March 1, 2019, to February 28, 2021. The primary endpoints of this study were morbidity due to AHD and risk factors for incidence. Univariate analysis and multivariate logistic regression analysis were used to analyse the related factors, and receiver operating characteristic (ROC) curves were plotted to evaluate their predictive value. RESULTS: Among 147 patients, 29 (19.73%) developed postoperative acute hepatic dysfunction, and 9 (6.12%) died. Univariate analysis revealed that the ALT (P = 0.042), Cr (P < 0.001), and BUN (P = 0.008) levels were significantly different between the two groups. Multivariate logistic regression analysis revealed that Cr (OR = 1.013, 95% CI = 1.003-1.023, P = 0.008) was an independent risk factor for postoperative hepatic dysfunction in overweight (BMI > 24) patients with ATAAD. The area under the ROC curve (AUC) for Cr was 0.745 > 0.7, indicating good predictive value. CONCLUSION: A high Cr concentration is an independent risk factor for postoperative AHD in overweight (BMI > 24) patients with ATAAD.

Nocturnal blood pressure dipping and left ventricular hypertrophy among hypertensive outpatients in a Ghanaian hospital.

Objectives: To investigate the association between the extent of nocturnal systolic blood pressure decline and left ventricular hypertrophy in patients with primary hypertension who were receiving antihypertensive drug therapy. Design: This was a cross-sectional hospital-based study from November 2020 to March 2021. Setting: The study was conducted at the Polyclinic of Korle Bu Teaching Hospital, Ghana. Participants: Outpatients ≥18 years old with primary hypertension who were receiving antihypertensive drug therapy. Interventions: Each participant underwent a 24-hour ambulatory blood pressure monitoring and a transthoracic echocardiogram. Main outcome measures: Left ventricular hypertrophy and the extent of mean systolic blood pressure decline during sleep. Results: 180 participants were recruited, comprising 110 (61.1%) females. The participants' mean (±SD) age was 57.6 ± 11.0 years. 80% had a non-dipping blood pressure pattern, and 43.9% had left ventricular hypertrophy. Uncontrolled office blood pressure was an independent predictor of left ventricular hypertrophy in these patients (AOR 2.010, 95% CI 1.048-3.855, p=0.036); however, a non-dipping nocturnal systolic blood pressure status was not (AOR 1.849, 95% CI 0.850-4.022, p=0.121). 61.1% had abnormal left ventricular geometry, with concentric hypertrophy being the predominant geometric pattern. Conclusion: Left ventricular hypertrophy and non-dipping nocturnal blood pressure were common in these hypertensive Ghanaian patients on antihypertensive therapy. Left ventricular hypertrophy was associated with uncontrolled office blood pressure but not the extent of nocturnal systolic blood pressure declines during a single 24-hour ambulatory blood pressure recording. Funding: None declared.

Management and associated outcomes of COVID-19 infection among Ghanaian autoimmune rheumatic disease patients.

Objective: This study assessed the prevalence of infection, management strategies and associated disease outcomes of COVID-19 among Autoimmune Rheumatic Disease (AIRD) patients in a teaching hospital in Ghana. Design: This was a retrospective cross-sectional study. Setting: Rheumatology Unit, Korle Bu Teaching Hospital. Participants: Autoimmune Rheumatic Disease patients. Results: Thirty-one (31) out of approximately 1700 AIRD patients in the unit tested positive for COVID-19, registering a COVID-19 prevalence of 1.82%. The majority, 25(80.6%), were females with a mean ± SD age of 41.7 ± 12.8 years. Systemic lupus erythematosus was the most affected autoimmune rheumatic condition, reporting fever as the commonest COVID-19-related symptom. Most participants, 22(71%), were managed by the "self-isolation"/home management" strategy. In comparison, 7(22.5%) were monitored at the hospital, with both strategies having resulted in complete recovery. The remaining 2(6.5%) patients who managed under "intensive care unit" strategy resulted in mortality. Conclusion: These findings highlight the relatively low frequency of COVID-19 infection among AIRD patients, the encouraging recovery, and the low severe disease rates observed within this cohort. Additionally, the outcome of self-isolation and home management strategies underscore the importance of personalised approaches to COVID-19 management in this population. Funding: None.

Association between serum insulin-like growth factor-1 and bone mineral density in patients with type 2 diabetes.

Background: Secondary osteoporosis is associated with type 2 diabetes mellitus (T2DM), and there is conflicting evidence regarding the relationship between insulin-like growth factor-1 (IGF-1) and bone mineral density (BMD) in different populations. The objective of this study was to investigate the relationship between serum IGF-1 levels and BMD in patients with T2DM. Method: A retrospective cross-sectional study was performed on a cohort of 363 patients with T2DM, comprising men aged over 50 and women who are postmenopausal. Those with no significant medical history or medication affecting BMD or IGF-1 were considered. Data analyzed included IGF-1 levels, markers of bone metabolism, and measurements of BMD. To account for age and gender variations, we calculated IGF-1 standard deviation scores (IGF-1 SDS) for further investigation. Results: A significant increase in BMD at lumbar spine (LS), femoral neck (FN), and total hip (TH) was observed as IGF-1 SDS tertiles rose. We revealed a nonlinear correlation between IGF-1 SDS and BMD at these sites, with a common inflection point identified at an IGF-1 SDS level of -1.68. Additionally, our multivariate piecewise linear regression analysis highlighted a positive association between IGF-1 SDS and BMD at LS, FN, and TH when IGF-1 SDS exceeded the inflection point (ß 0.02, 95% CI 0.01, 0.04 for LS; ß 0.02, 95% CI 0.01, 0.03 for FN; ß 0.02, 95% CI 0.01, 0.03 for TH). Conversely, below the inflection point, this association was not significant (ß -0.04, 95% CI -0.10, 0.01 for LS; ß -0.04, 95% CI -0.08, 0.01 for FN; ß -0.03, 95% CI -0.08, 0.01 for TH). Conclusion: These findings reveal a nonlinear relationship between IGF-1 SDS and BMD in T2DM patients. Higher serum IGF-1 levels were connected to increased bone density only after surpassing a certain threshold.