Marker Of Disease Severity Research Articles

Health-related quality of life of toddlers during and after cancer treatment

BackgroundThere is a knowledge gap regarding health-related quality of life (HRQOL) in childhood cancer patients below 2 years of age. The aim of this study was therefore to compare HRQOL of young children during and after treatment for cancer, to healthy controls, and to investigate effects of biopsychosocial factors. ProcedureThe study is based on data from an online monitoring program. Parent-proxy reports of HRQOL in 205 children aged 12–24 months were compared to 108 healthy children. The parents filled out the TNO-AZL Preschool Quality of Life questionnaire for young children, which consists of 12 subscales, in addition to a parental distress thermometer. ResultsParticipants undergoing treatment had less favorable HRQOL than children after treatment for eight of the subscales. They also had less favorable HRQOL than healthy children for seven scales, while the only significant difference between children off treatment and healthy controls was for motor functioning. For ten subscales, there were significant relationships between biopsychosocial variables and HRQOL outcomes. Parental distress and treatment with immunotherapy were the variables most frequently associated with lower HRQOL. ConclusionsParental distress should be considered when monitoring young childhood cancer patients. Treatment with immunotherapy is likely to be a marker of disease severity and might represent other underlying factors affecting HRQOL. The association between immunotherapy and HRQOL therefore needs more research. While there was a significant difference depending on treatment status, it cannot be concluded that this represents an improvement in HRQOL after end of treatment.

A near normal distribution of IQ in Fragile X Syndrome

Fragile X Syndrome (FXS) is an X-linked disorder leading to the loss of expression of FMR1-protein product, FMRP. The absence or deficiency of FMRP is thought to result in the characteristic FXS phenotypes, including intellectual disability. Identifying the relationship between FMRP levels and IQ may be critical to better understand underlying mechanisms and advance treatment development and planning. A sample of 143 individuals with FXS (69% male), aged 8–50 years, completed IQ testing and blood draw via venipuncture to determine the relationship between Deviation IQ scores and FMRP levels as well as the distribution of Deviation IQ scores. In both males and females with FXS, higher FMRP levels were associated with higher Deviation IQ. However, this relationship was no longer significant when only examining full mutation, fully-methylated males. Yet, both the full and restricted male samples showed a downward shifted but otherwise normal distribution of Deviation IQ scores. Our findings support and extend previous studies establishing molecular markers of disease severity in FXS as well as provide novel evidence of a “FXS IQ standard curve”. This latter finding suggests inter-individual variation in Deviation IQ in FXS, especially among males, may be driven by similar factors known to impact cognitive outcomes in typically-developing individuals. Thus, future work aimed at understanding the mechanisms by which FMRP loss leads to intellectual disability should revisit the biological/genetic, socio-environmental, and epigenetic factors contributing to inter-individual variation in IQ in FXS.

TLR2 reprograms glucose metabolism in CD4+ T cells of rheumatoid arthritis patients to mediate cell hyperactivation and TNF-α secretion.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease in which activated CD4+ T cells participate in the disease process by inducing inflammation. We aimed to investigate the role of Toll-like receptor 2 (TLR2) on CD4+ T cells in RA patients, and to elucidate the underlying mechanisms by which TLR2 contributes to the pathogenesis of RA. Serum samples were collected from RA patients and healthy controls. Soluble TLR2 levels were quantified using an enzyme-linked immunosorbent assay (ELISA). Flow cytometry was employed to assess the TLR2 expression level, activation status, cytokine production, reactive oxygen species (ROS) levels, and glucose uptake capacity of CD4+ T cells. Quantitative polymerase chain reaction (qPCR) was used to measure the expression of enzymes associated with glucose and lipid metabolism. The concentration of lactic acid in the culture supernatant was determined using a dedicated detection kit. RA patients had higher levels of TLR2 in their serum, which positively correlated with C-reactive protein and rheumatoid factor. The expression level of TLR2 in CD4+ T cells of RA patients was increased, and TLR2+ cells showed higher activation levels than TLR2- cells. Activation of TLR2 in CD4+ T cells of RA patients promoted their activation, TNF-α secretion, and increased production of ROS. Furthermore, TLR2 activation led to changes in enzymes related to glucose metabolism, causing a shift in glucose metabolism towards the pentose phosphate pathway. Blocking oxidative phosphorylation and the pentose phosphate pathway had varying effects on CD4+ T cell function. TLR2 reprograms the glucose metabolism of CD4+ T cells in RA patients, contributing to the development of RA through ROS-mediated cell hyperactivation and TNF-α secretion. Key Points • TLR2 is upregulated in CD4+ T cells of RA patients and correlates with disease severity markers such as CRP and RF. • Activation of TLR2 in CD4+ T cells promotes cell activation, TNF-α secretion, and increased ROS production, contributing to the pathogenesis of RA. • TLR2 activates glucose metabolism in CD4+ T cells, shifting towards the pentose phosphate pathway, which may be a novel therapeutic target for RA treatment. • Blocking glucose metabolism and ROS production can reduce CD4 + T cell hyperactivation and TNF-α secretion, indicating potential therapeutic strategies for RA management.

Investigation into the Effects of Allergen Exposure and Topical Vinegar and Water Spray on Skin Barrier Parameters in Atopic Dogs.

Increased skin pH and transepidermal water loss (TEWL) are documented in atopic people and dogs but no study has investigated how these parameters change during an allergy flare. Our primary aim was to challenge atopic beagles to dust mites and measure pH and TEWL during a flare of atopic dermatitis and correlate these parameters to clinical signs. A secondary aim was to evaluate in a randomized placebo-controlled study whether the daily application of 50/50 vinegar spray improves clinical signs and affects skin parameters despite the allergen challenge. Fifteen atopic dogs were challenged epicutaneously twice weekly for 2 weeks with allergen application on the inguinal and medial thigh areas. The severity of dermatitis was scored daily (CADESI-03). TEWL and pH were measured daily on the inguinal and medial thigh areas. A repeated measures ANOVA showed the significant effect of time, with increased pH (p < 0.0001), TEWL (p < 0.0001), and CADESI (p < 0.0001) during allergen challenge. Significant positive correlations were found between CADESI and pH (r = 0.3556; p < 0.0001), CADESI and TEWL (r = 0.36; p < 0.0001), and pH and TEWL (r = 0.45; p < 0.0001). Daily application of 50/50 vinegar did not improve dermatitis, pH, and TEWL compared to the control treatment. It can be concluded that both pH and TEWL are markers of disease severity in canine atopic dermatitis.

Predictors of interferon-gamma release assay results and their association with COVID-19 infection outcomes.

An 'indeterminate' interferon-gamma release assay (IGRA) result used in the diagnosis of latent TB infection (LTBI) is most commonly due to an inadequate control (or 'mitogen') response, which may reflect underlying T-cell dysfunction. We performed a single-centre, retrospective study on COVID-19 patients admitted to a tertiary referral hospital who had IGRA testing conducted over a 5-month period. The primary outcomes included predictors of indeterminate IGRA results and associations with COVID-19 outcomes. A total of 181 patients were included for analysis. Approximately one-third of patients hospitalised with COVID-19 with IGRA testing performed (60/181) had an indeterminate result. The likelihood of an indeterminate IGRA was increased in patients with a history of solid organ transplant and a higher severity of COVID-19 at the time of testing. An indeterminate IGRA was associated with a higher risk of severe COVID-19 and a higher risk of admission to the ICU during admission to the hospital. No difference in mortality between the two subgroups was found. Our study demonstrated that COVID-19 patients on immunosuppression had a high likelihood of an indeterminate IGRA result, which was associated with markers of disease severity and immunosuppression. In this cohort, an indeterminate result was associated with worse COVID-19 outcomes.

Anti-integrin αvβ6 autoantibodies are increased in PSC patients with concomitant IBD and correlate with liver disease severity

Anti-integrin αvβ6 autoantibodies (anti-αvβ6) are found in more than 50% of individuals with ulcerative colitis (UC). We aimed to determine the prevalence of anti-αvβ6 in patients with primary sclerosing cholangitis (PSC) and their association with liver disease severity. Four cohorts of pre-liver transplant PSC patients were recruited. Patients with inflammatory bowel disease (IBD) and healthy controls (HC) served as comparators. Total IgG and anti-αvβ6 levels were measured using enzyme-linked immunosorbent assay (ELISA). Olink® inflammation panel was run on a subset of samples. Multivariable linear regression analysis was performed to assess the association between anti-αvβ6 and indices of liver disease severity. A total of 137 PSC patients (including 76 with PSC-UC, 33 with PSC-Crohn's disease (CD) and 28 with PSC alone) and 160 controls (including 91 with IBD and 69 HC) were enrolled. Anti-αvβ6 levels were significantly higher in PSC-UC and PSC-CD compared to PSC alone (p<0.0001 and 0.003) and HC (p<0.0001 and p<0.0001). However, anti-αvβ6 levels in PSC alone were not increased compared to HC. In patients with PSC-IBD, anti-αvβ6 levels correlated with markers of liver disease severity including alkaline phosphatase level (r=0.32, p=0.004), the revised Mayo PSC risk score (r=0.25, p=0.02) and liver stiffness measurement (r=0.43, p=0.008) after adjusting for age, gender, race/ethnicity and IBD subtype. Additionally, anti-αvβ6 levels were associated with markers of systemic inflammation and tissue remodeling. Anti-αvβ6 autoantibodies identify a subset of PSC patients with concomitant IBD.

Association of serum and synovial adipokines (chemerin and resistin) with inflammatory markers and ultrasonographic evaluation scores in patients with knee joint osteoarthritis- a pilot study.

Chemerin and resistin are adipokines studied as potential markers for early diagnosis and disease severity in patients with knee osteoarthritis (KOA) Therefore, we aimed to investigate the associations serum and synovial levels of chemerin and resistin with inflammatory parameters and ultrasonographic scores (US) in KOA individuals. Serum was collected from 28 patients with KOA and synovial fluid was obtained from 16 of them. Another 31 age and sex matched cases with no joint disease were included as healthy controls. Concentrations of chemerin, resistin, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) were determined with ELISA. Erythrocyte sedimentation rate (ESR), C-reactive protein, serum uric acid (UA) were measured in the patients group. Participants with KOA underwent US assessment using the Outcome Measures in Rheumatology (OMERACT) scores. Patients with KOA had statistically significant higher level of serum resistin than healthy controls [11.05 (3.78-24.13) ng/mL and 7.23 (3.83-12.19) respectively, p < 0.001]. A strong correlation was found between serum chemerin and ESR (r = 0.434, p = 0.021), uric acid (r = 0.573, p = 0.001) as well as the US (r=-0.872, p < 0.001). Serum resistin demonstrated significant association with TNF-alpha (r = 0.398, p = 0.044). In conclusion, both chemerin and resistin might contribute to inflammatory changes associated with KOA. Further studies are needed to elucidate their potential role in the pathogenesis of the disease.

Serum immunoglobulin A levels: Diagnostic utility in alcoholic liver disease and association with liver fibrosis in steatotic liver disease.

The relationship between immunoglobulin A (IgA) levels and chronic liver disease remains poorly understood. The present study evaluated the clinical significance of IgA in 478 new patients who visited the Outpatient Clinic of Nagasaki Harbor Medical Center (Nagasaki, Japan). Serum IgA levels in comparison to liver stiffness (LS), as measured using a FibroScan® device, were evaluated in 358 patients. Furthermore, in 270 patients, the associations between serum IgA levels and body composition were analyzed using computed tomography. The IgA levels of patients in the groups with Child-Pugh classification B and C (CPGBC), alcoholic liver disease (ALD), steatotic liver disease (SLD) or diabetes were higher than the IgA levels of patients in the groups with CPGA, non-ALD, non-SLD or no diabetes, respectively. Logistic regression analysis showed that CPGBC, ALD, high IgG (>1,700 mg/dl), high macrophage galactose-specific lectin-2 binding protein glycosylation isomer (M2BPGi) (>1 cut-off index) and diabetes were contributing factors for high serum IgA level (>410 mg/dl). The ratio of IgA level divided by IgG level was highest in patients with ALD, followed by those with metabolic dysfunction-associated SLD (MASLD) and non-SLD. In SLD, IgA level was associated more with LS than M2BPGi and fibrosis-4 (FIB-4) in multiple regression analysis. In the receiver operating characteristic analysis, IgA level, M2BPG, and FIB-4 had similar area under the curve values for discriminating high LS (>8 kPa) from low LS (≤8 kPa) in SLD. IgA levels were also associated with visceral fat, and this association was only found in women. In conclusion, elevated IgA is an indicator of liver fibrosis that also reflects the presence of diabetes and an increased visceral fat level. Therefore, IgA is considered a useful marker of liver disease severity in the current era of increased SLD.

Atypical Mumps; are We Heading Towards an Outbreak?

Mumps, caused by the mumps virus, is a contagious disease primarily affecting children and young adults. While typically presenting with salivary gland swelling and systemic symptoms, mumps can lead to various complications including SNHL, orchitis/ oophoritis, aseptic meningitis. Recent observations suggest atypical features in mumps cases, raising concerns of a potential outbreak in India. To discuss the etiopathogenesis and clinical presentation in cases of atypical mumps with increasing number of cases, a prospective multicentric study was conducted across five major centers - SMS Medical College Jaipur, RDBP Jaipuria Hospital, Jaipur, Shri Ashwini Saxena ENT Hospital Rewari, AIIMS Bhubaneswar and SP Medical College Bikaner, in India to evaluate patients with acute salivary gland swellings. Clinical and laboratory data were collected, including demographics, presenting symptoms, history of vaccination, imaging findings, and treatment outcomes. Patients were followed for four weeks post-treatment to monitor for delayed complications. Among 53 patients, a bimodal age distribution was observed, with peaks in early adolescents and middle-aged individuals. Vaccination status was recorded based on recall. Fever and salivary gland swelling were predominant symptoms, with a significant proportion experiencing submandibular gland involvement. Elevated serum amylase and CRP levels correlated with disease severity and prolonged symptomatic resolution. Notably, cases of sensorineural hearing loss (SNHL) and airway complications emerged as significant concerns. The study highlights a shift in mumps demographics, with higher age groups affected and increased incidence of complications like SNHL and airway compromise. International trends also suggest periodic outbreaks and evolving clinical manifestations post-COVID-19 pandemic. Factors contributing to mumps resurgence include lack of vaccination or vaccine efficacy, population immunity, and seasonal variations. India appears to be facing a potential mumps outbreak, characterized by atypical features and increased risk of complications like SNHL and airway compromise. Serum amylase and CRP serve as valuable markers for disease severity. Early recognition and management of complications are crucial, emphasizing the importance of mumps immunization to mitigate the impact of the disease. ENT specialists should remain vigilant for emerging complications, particularly SNHL, advocating for comprehensive immunization strategies.

Leakage sign based on contrast-enhanced CT is a predictive marker for hematoma expansion and poor prognosis in primary brainstem hemorrhage

BackgroundAlthough hematoma expansion is a poor prognostic factor in patients with intracerebral hemorrhage (ICH), its effect on primary brainstem hemorrhage (PBSH) remains unclear. Since we previously observed the “leakage sign” (LS) on computed tomography (CT) to be a significant predictor for hematoma expansion, we herein investigated the effect of LS in PBSH. MethodsBetween January 2013 and August 2023, 515 patients with ICH were admitted to our institute. Thirty-six patients with PBSHs met the inclusion criteria, who were then divided into LS-positive (LS+) and LS-negative (LS-) groups based on the presence of LS. We evaluated hematoma expansion and prognosis at discharge. ResultsPatients in the LS+ group had larger baseline hematoma volume and lower Glasgow Coma Scale scores on admission and significantly poor prognosis at discharge. Subgroup analysis revealed that LS was frequently observed within 100 min after the onset of symptoms in patients with a hematoma size of >10 mm3 on CT; additionally, patients in the LS+ group more frequently experienced hematoma expansion and had poor prognosis at discharge. ConclusionLS is a significant predictive marker for disease severity at admission, hematoma expansion, and poor prognosis at discharge

Cognitive impairments in autoimmune encephalitis: the role of autoimmune antibodies and oligoclonal bands.

The presence of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is a pivotal diagnostic marker for multiple sclerosis (MS). These bands play a crucial role in the diagnosis and understanding of a wide array of immune diseases. In this study, we explore the relationship between the cognitive profile of autoimmune encephalitis (AIE) and the presence of OCBs in CSF, with a particular emphasis on NMDA receptor antibodies. We studied a cohort of 21 patients across five tertiary centers, segregated into two distinct categories. One group comprised individuals who tested positive only for autoimmune encephalitis antibodies indicative of encephalitis, while the other group included patients whose CSF was positive for both autoimmune encephalitis antibodies and OCBs. Our investigation focused primarily on cognitive functions and behavioral alterations, supplemented by auxiliary diagnostic assessments such as CSF cell count, magnetic resonance imaging (MRI), and electroencephalogram (EEG) results, evaluated for the two patient groups. To validate our findings, we employed statistical analyses such as Fisher's exact test with Benjamini-Hochberg correction. Our study included 21 patients, comprising 14 who were presented with only autoimmune encephalitis antibodies, and 7 who were dual-positive. Among these patients, we focused on those with NMDA receptor antibodies. Of these, five were dual positive, and nine were positive only for NMDA receptor antibodies. The dual-positive NMDA group, with an average age of 27 ± 16.47 years, exhibited significantly higher CSF cell counts (p=0.0487) and more pronounced language and attention deficits (p= 0.0264). MRI and EEG results did not differ significantly between the groups. Our results point to OCBs as an additional marker of disease severity in AIE, especially in NMDA receptor-antibody positive patients, possibly indicating a broader inflammatory process, as reflected in elevated CSF lymphocytes. Regular testing for OCBs in cases of suspected AIE may aid in disease prognosis and identification of patients more prone to language and attention disorders, improving diagnosis and targeting treatment for these cognitive aspects.

Evaluation of Fasting Bile Acid Levels in Pregnant Women Diagnosed with Hyperemesis Gravidarum

Background: Hyperemesis gravidarum is a common cause of nausea and vomiting during the early gestational week. At the same time, it can also lead to an increase in liver enzyme values in patients due to or independently of underlying liver disease. This study aimed to evaluate fasting bile acid (FBA) levels, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total and direct bilirubin, and urine ketone levels in pregnant women diagnosed with hyperemesis gravidarum (HG). Additionally, the study sought to investigate the relationship between HG and FBA levels. The diagnosis of HG remains primarily clinical, and identifying markers for disease severity is crucial. Methods: This retrospective cohort study obtained blood samples from 50 women diagnosed with HG and 25 healthy pregnant women. Serum levels of AST, ALT, total bilirubin (TBS), direct bilirubin, urine ketones, and FBA were measured. Statistical analysis was performed using the SPSS software version 28.0. Results: FBA levels were significantly higher in pregnant women diagnosed with HG compared to the healthy control group. Additionally, FBA levels increased simultaneously with ketonuria in the patient group. Our findings suggest that FBA levels can serve as a biomarker for diagnosing HG and indicating early-stage liver damage. Unlike previous studies, our research focused on the relationship between FBA levels and HG, providing valuable insights for future studies. Conclusions: FBA levels show promise as an objective biomarker for diagnosing HG and indicating early-stage liver damage. Further research with larger cohorts is necessary to validate these findings.

Characteristics, Management, and Outcomes of Acute Life-Threatening Asthma in Adult Intensive Care.

There is limited evidence regarding the management of acute life-threatening asthma in intensive care units (ICUs), and few guidelines have details on this. We aimed to describe the characteristics, management, and outcomes of adults with life-threatening asthma requiring ICU admission. In this single-centre retrospective observational study, we included consecutive adults with acute asthma requiring ICU admission between 1 January 2016 and 31 December 2023. Our primary outcome was requirement for invasive mechanical ventilation (IMV). We included 100 patients (median age 42.5 years, 67% female). The median pH, PaCO2, and white cell count (WCC) on ICU admission were 7.37, 39 mmHg, and 13.6 × 109/L. There were 30 patients (30%) who required IMV, and the best predictors of IMV requirement were pH (AUC 0.772) and PaCO2 (AUC 0.809). In univariate analysis, IMV requirement was associated with both increasing WCC (OR 1.14) and proven bacterial infection (OR 8.50). A variety of respiratory support strategies were utilised, with 38 patients (38%) receiving only non-invasive respiratory support. Our data highlight key characteristics which may be risk factors for acute asthma requiring ICU admission and suggest that pH, PaCO2, and WCC are prognostic markers for disease severity. Our overall outcomes were good, with an IMV requirement of 30% and a 28-day mortality of 1%.

Updates on the Association Between Anemia and Heart Failure: A Systematic Review.

This systematic review aims to investigate the potential relationship between anemia and heart failure (HF) by summarizing existing literature on the topic. A comprehensive search was performed using four major databases, PubMed, Scopus, Web of Science, and ScienceDirect, to find the relevant literature. Ten studies, including a total of 2,828 participants, with 1,451 (51.3%) males, were included in this review.Iron deficiency anemia was the most prevalent type in the included studies; however, two studies included megaloblastic anemia. The prevalence of anemia in patients diagnosed with HF ranged from 33.3% to 69.8%, with a total prevalence of 1,643 (58.1%). Hypertension, diabetes mellitus, chronic kidney disease, and atrial fibrillation were the most commonly associated comorbidities in patients with HF. Anemia patients had a considerably higher risk of mortality than those without anemia. Anemia served as a marker of disease severity rather than an independent predictor of death in congestive individuals. Anemia was substantially correlated with elevated serum creatinine, left ventricular hypertrophy, and left atrial enlargement. According to the findings of this review, anemia has a significant impact on the prognosis of HF. In patients with HF, anemia may be a reliable indicator of both short- and long-term all-cause mortality as well as the rates of all-cause HF events. Future and ongoing research may provide vital information that may help guide clinical judgments in the future.

Left Atrial Appendage Thrombus as a Marker of Disease Severity in 500 Patients with Atrial Fibrillation on Oral Anticoagulation: A 13-Year Follow-Up Study.

Background/Objective: Whether left atrial appendage thrombus (LAAT) in patients with atrial fibrillation (AF) on chronic anticoagulation significantly increases cardiovascular risk is unknown. This study aimed to assess LAAT prevalence and its predictive role in cardiovascular events among consecutive anticoagulated patients with AF admitted for electrical cardioversion. Methods: This prospective study included 500 patients. The primary outcome was LAAT on transesophageal echocardiography. Patients were followed up for a median of 1927.5 (interquartile range 1004-2643) days to assess cardiovascular events. Results: LAAT was detected in 65 (13%) patients. No significant differences in stroke, transient ischemic attack, systemic thromboembolic events, or myocardial infarction prevalence were observed between patients with AF with and without LAAT. Hospitalization for heart failure (HF) was more frequent in patients with LAAT than in those without LAAT; however, the effect of LAAT on HF hospitalization was not statistically significant. Patients with LAAT had a significantly higher risk of cardiovascular death than those without LAAT. LAAT and greater left atrial (LA) diameter were associated with higher rates of cardiovascular death. The independent HF hospitalization predictors were greater LA diameter, lower left ventricular ejection fraction (LVEF), and estimated glomerular filtration rate (eGFR). Conclusions: Patients with AF who received anticoagulation therapy showed a high prevalence of LAAT. LAAT and greater LA diameter were associated with significantly higher rates of cardiovascular death. LAAT, greater LA diameter, lower LVEF, and lower eGFR were associated with poor prognosis in anticoagulated patients with AF and were predictors of disease severity.

Acute kidney injury as a prognostic marker in severe fever with thrombocytopenia syndrome

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne illness with a notable morality risk that is becoming increasingly prevalent in East Asia (14–36%). Increasing evidence indicates a more direct role of the SFTS virus in renal impairment. However, few studies have explored the risk factors for and clinical outcomes of AKI in patients with SFTS. Therefore, in this study, we aimed to investigate risk factors and outcomes associated with AKI in patients with SFTS. In this retrospective cohort study, we included the data of 53 patients who were diagnosed with SFTS virus infection at Kangwon National University Hospital between 2016 and 2020. We incorporated laboratory data and medical information including comorbidities, complications, and mortality. Baseline characteristics, clinical features, laboratory parameters, and mortality rates of the non-AKI and AKI groups were compared. Patient survival of non-AKI and AKI groups were compared using the Kaplan–Meier method. To identify the population with poor prognosis, Cox regression analysis was used to identify the independent risk factors for in-hospital mortality in patients with SFTS. Of the 53 individuals, 29 (54.7%) were male, with an average age of 66.5 years. Nine patients (15.1%) died of SFTS. Twenty-seven (50.9%) patients exhibited AKI; the average time interval from fever onset to AKI occurrence was 3.6 days. Notably, 24 (88.9%) patients developed AKI within the first week of fever onset. Patients in the AKI group exhibited a significantly higher prevalence of diabetes and were older than those in the non-AKI group. The mortality rate was notably higher (29.6%) in the AKI group than in the non-AKI group (3.8%). Within the AKI cohort, advanced stages (stages 2 and 3) showed a 50% mortality rate, which was significantly higher than the 17.6% mortality rate in patients with stage 1 AKI. Additionally, Kaplan–Meier curves revealed lower survival rates among patients with AKI than among those without AKI (P = 0.017). Cox regression analysis identified leukopenia and elevated serum creatinine levels as significant risk factors for mortality. AKI is a common complication associated with SFTS. Moreover, the mortality rate was significantly higher in the patients who developed AKI than in those who did not. Our findings underscore the pivotal role of AKI as a prognostic marker of disease severity in patients with SFTS.

Acute-phase proteins as indicators of disease severity and mortality in COVID-19 patients

The aim of the study was to conduct of relationship of acute-phase proteins (APPs) with the severity of COVID-19 defined by National Institutes of Health and according to the criteria of MEWS scale, with the presence of a cytokine storm, oxygen therapy and patient survival. We enrolled 96 patients with COVID-19 and 30 healthy people. The samples were taken on the day of admission and after 9 days on average. Not only commonly used APPs such as CRP, procalcitonin and ferritin and also rarely assayed proteins such as transferrin, haptoglobin, α1-acid glycoprotein and α1-antitrypsin, were tested in the study. The levels of APPs depends on the severity of COVID-19 disease, on the presence of cytokine storm and used oxygen therapy. The greatest APPs changes occurred in the most advanced form of the disease, with the presence of a cytokine storm and the most intense oxygen therapy. The results obtained from MEWS scale were not consistent with National Institutes of Health scores. Studies in the second samples showed the quenching of the acute phase reactions and the effectiveness of oxygen therapy. Only two of the examined APPs i.e. procalcitonin and transferrin, differed between surviving and non-surviving patients, and these two predispose to the role of prognostic factors in Covid-19. In conclusion, the concentration of not all acute-phase proteins depends on the severity of COVID-19 disease, presence of cytokine storm, the used of oxygen therapy and only some of them (procalcitonin and transferrin) are related to the survival outcomes. Of the newly tested acute-phase proteins, only transferrin shows significance as a marker of disease severity and mortality in COVID-19 disease.

Longitudinal Changes in Bone Mineral Density in Adults with Cystic Fibrosis.

Improved survival in people with cystic fibrosis (pwCF) presents new complexities of care, including CF-related bone disease, a common complication in older pwCF. The trajectory of bone loss with age in this population remains unclear. The objective of this study was to estimate the average rate of change in bone mineral density (BMD) in adults with CF. This retrospective study included adults with CF, aged 25-48years, followed between January 2000 and December 2021. Subjects with at least one dual-energy X-ray absorptiometry (DXA) scan were included. Scans obtained post-transplantation, after the initiation of bisphosphonates or cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy were excluded. The primary outcome was BMD (g/cm2) at the lumbar spine (LS) and femoral neck (FN). A linear mixed-effects model with both random intercept and random slope terms was used to estimate the average annual change in BMD. A total of 1502 DXA scans in 500 adults (average age 28.4y) were included. There was a statistically significant annual decline in BMD of -0.008 gm/cm2/year (95% CI -0.009, -0.007) at the FN and -0.006 gm/cm2/year (95% CI -0.007, -0.004) at the LS. Relative to BMD at age 25, there was a -18.8% decline at the FN by age 48years and a -11% decline at the LS. Pancreatic insufficient (PI) subjects had a faster rate of decline in BMD compared to pancreatic sufficient (PS) subjects. After adjusting for markers of disease severity, the annual rate of decline remained significant. Individuals with CF experience bone loss at an age when it is not anticipated, thereby entering early adulthood, where further bone loss is inevitable especially with the decrease in estrogen during menopause, with suboptimal BMD. As the CF population ages, it will become very important to consider interventions to maximize bone health.

Effect of Opaganib on Supplemental Oxygen and Mortality in Patients with Severe SARS-CoV-2 Based upon FIO2 Requirements.

Once a patient has been diagnosed with severe COVID-19 pneumonia, treatment options have limited effectiveness. Opaganib is an oral treatment under investigation being evaluated for treatment of hospitalized patients with severe COVID-19 pneumonia. A randomized, placebo-controlled, double-blind phase 2/3 trial was conducted in 57 sites worldwide from August 2020 to July 2021. Patients received either opaganib (n = 230; 500 mg twice daily) or matching placebo (n = 233) for 14 days. The primary outcome was the proportion of patients no longer requiring supplemental oxygen by day 14. Secondary outcomes included changes in the World Health Organization Ordinal Scale for Clinical Improvement, viral clearance, intubation, and mortality at 28 and 42 days. Pre-specified primary and secondary outcome analyses did not demonstrate statistically significant benefit (except nominally for time to viral clearance). Post-hoc analysis revealed the fraction of inspired oxygen (FIO2) at baseline was prognostic for opaganib treatment responsiveness and corresponded to disease severity markers. Patients with FIO2 levels at or below the median value (≤60%) had better outcomes after opaganib treatment (n = 117) compared to placebo (n = 134). The proportion of patients with ≤60% FIO2 at baseline that no longer required supplemental oxygen (≥24 h) by day 14 of opaganib treatment increased (76.9% vs. 63.4%; nominal p-value = 0.033). There was a 62.6% reduction in intubation/mechanical ventilation (6.84% vs. 17.91%; nominal p-value = 0.012) and a clinically meaningful 62% reduction in mortality (5.98% vs. 16.7%; nominal p-value = 0.019) by day 42. No new safety concerns were observed. While the primary analyses were not statistically significant, post-hoc analysis suggests opaganib benefit for patients with severe COVID-19 requiring supplemental oxygen with an FIO2 of ≤60%. Further studies are warranted to prospectively confirm opaganib benefit in this subpopulation.

Predictors of Mortality in Patients with Cardiac Device-Related Infective Endocarditis.

Infective endocarditis (IE) associated with implantable cardiac devices (ICD) is a serious disease with high mortality rates. The increased number of ICD implants has led to increased ICD infection rates. The aim of this study was to characterize clinical, laboratory profiles and the prognosis of cardiac-device-related endocarditis (CDIE), as well as to identify predictors of in-hospital death. A total of 274 patients with IE were included in a prospective cohort (2007-2019). From these, 82 patients (30%) had CDIE (46 pacemakers, 23 cardioverter defibrillators, and 13 cardiac resynchronization therapy devices). Predisposed conditions; clinical, laboratory and echocardiographic parameters; etiologic agents; and in-hospital outcomes were evaluated. The mean age was 55.8 ± 16.4 years, where 64.6% were male. Among the clinical manifestations at diagnosis, the most prevalent were heart failure (67.9%), fever (60.5%), anorexia/hyporexia (44.4%), and heart murmur (37.5%). The median serum C-reactive protein (CRP) level at diagnosis was 63 mg/L (interquartile range [IQR] 20-161). Etiological agents were identified through positive blood cultures in 55% of cases. The main etiologic agents were negative-coagulase staphylococci (19.5%) and Staphylococcus aureus (18.3%). Vegetation was identified in 74 patients (90.1%). In-hospital mortality was 28%. CRP concentrations at diagnosis were identified as markers of disease severity (odds ratio [OR] 1.006; 95%CI 1.001-1.011; p = 0.016), and the worsening of heart failure was associated with unfavorable outcomes (OR 3.105; 95%CI 1.397-6.902; p = 0.005). Unlike what is traditionally accepted, CDIE does not have a better prognosis.