Marker Of Disease Severity Research Articles

Are enterococcal bloodstream infections an independent risk factor for a poorer 5-year survival or just a marker for severity of illness?-The Munich multicentric enterococci cohort.

The present study provides a substantial contribution to literature, showing that patients with enterococcal bloodstream infections (BSI) have a lower survival rate than those with Escherichia coli (E. coli) bloodstream infections after adjusting for 17 limiting prognostic factors and excluding patients with a limited life expectancy [metastatic tumor disease, Charlson Comorbidity Index (CCI) (greater than or equal to) 5]. This difference in the 5-year long-term survival was mainly driven by Enterococcus faecium (ECFM) bloodstream infections, with vancomycin resistance not being a significant contributing factor. Our findings imply that E. faecium bloodstream infections seem to be an independent risk factor for poor long-term outcomes. As such, future research should confirm this relationship and prioritize investigating its causality through prospective studies.

Triglyceride-glucose index as a predictor of obstructive sleep apnoea severity in the absence of traditional risk factors.

We evaluated the association between the triglyceride-glucose (TG) index, a marker of insulin resistance, and obstructive sleep apnoea (OSA) severity in patients without diabetes mellitus, obesity, and metabolic syndrome. This retrospective cohort study included 1,527 patients. We used univariate and multivariate analyses to identify the independent predictors associated with OSA. Most patients were males (81.5%) with a mean age of 43.9 ± 11.1 (15-90) years. Based on the apnoea-hypopnea index (AHI), 353 (23.1%) patients were included in the control group, whereas 32.4%, 23.5%, and 21% had mild, moderate, and severe OSA, respectively. The TG index values demonstrated significant associations with OSA patients compared with the control group (p = 0.001). In addition, the mean values of the oxygen desaturation index (ODI), AHI, minimum oxygen saturation, and total sleep time percentage with saturation below 90% demonstrated statistically significant differences among the TG index groups (p: 0.001; p:0.001; p:0.001; p:0.003). The optimal TG index cutoff value to predict OSA was 8.615 (AUC = 0.638, 95% CI = 0.606-0.671, p = 0.001). In multivariate logistic regression analysis, after adjusting for age, sex, and body mass index, the TG index was independently associated with OSA patients. The TG index is independently associated with increased risk for OSA. This indicates that this index, a marker for disease severity, can be used to identify severe OSA patients on waiting lists for PSG.

Hypoxia Inducible Factor-1α in SM22α Expressing Cells Modulates Alveolarization.

Worldwide, the incidence of both preterm births and chronic lung disease of infancy, or bronchopulmonary dysplasia (BPD), remains high. Infants with BPD have larger and fewer alveoli, pathology that can persist into adulthood. Though hypoxia inducible factor-1α (HIF-1α) plays a significant role in mediating pulmonary angiogenesis and alveolarization, the cell specific role of HIF-1α remains incompletely understood. To determine whether HIF-1α, in a mesenchymal cells (MC) subset, mediates postnatal alveolarization. We generated mice with cell-specific deletion of HIF-1α by crossing SM22α-promoter-driven Cre mice with HIF-1αflox/flox mice (SM22α- HIF-1α-/-), determined SM22α-expressing cell identity using single cell RNA-seq, and interrogated clinical samples from preterm infants. Measurement and Main Outcomes: Deletion of HIF-1α in SM22α expressing cells had no effect on lung structure at day (d) 3 of life. However, at 8d there were fewer and larger alveoli, a difference that persisted into adulthood. Microvascular density, elastin organization, and peripheral branching of the lung vasculature were decreased in SM22α-HIF-1α-/-, compared to control, mice. Single cell RNA-seq demonstrated that 3 MC subtypes (myofibroblasts, airway and vascular smooth muscle cells (VSMC)) express SM22α. Pulmonary VSMC from SM22α- HIF-1α-/- had decreased angiopoetin 2 expression and, in co-culture experiments, a diminished capacity to promote angiogenesis that was rescued by angiopoetin-2. Angiopoetin-2 expression in the tracheal aspirates of preterm infants was inversely correlated with overall time on mechanical ventilation, a marker of disease severity. SM22α-specific HIF-1α expression drives peripheral angiogenesis and alveolarization in the lung, perhaps by promoting angiopoetin-2 expression.

PB0097 Intracellular Nuclear Proteins Histone H3 and HMGB1 are Predictive Markers of Disease Severity and Prognosis of COVID-19 Patients

PB0097 Intracellular Nuclear Proteins Histone H3 and HMGB1 are Predictive Markers of Disease Severity and Prognosis of COVID-19 Patients

The relationship between serum soluble ACE 2 protein level and the clinical course of COVID-19 disease

Aims: The angiotensin converting enzyme 2 (ACE 2) molecule, which mediates the entry of the virus into the cell, plays a very important role in the pathogenesis of COVID-19 disease. However, its effect on prognosis has not been fully explained. In this study, it was aimed to investigate the relationship between soluble ACE 2 (sACE 2) levels in the blood and the course of the disease.
 Methods: sACE 2 levels at 0, 3 and 5 days were measured in patients with mild, moderate and severe COVID-19 pneumonia who were hospitalized between March 15, 2020 and August 30, 2020.
 Results: 69 patients, 35 (51.5%) female and 34 (49.3%) male, with a mean age of 64.3±2.1 were included in the study. 42.0% of the patients had mild, 30.4% moderate, 27.5% severe pneumonia. Clinical follow-up of 7 patients resulted in death. There was no statistically significant difference between sACE 2 levels and gender, severity of pneumonia, initial hospitalization, presence of intubation and mortality.
 Conclusion: sACE 2 levels were not associated with disease severity and inflammatory markers. Studies in larger patient populations are needed to explain the relationship between sACE 2 activity and SARS-CoV-2 infection and to develop new treatment strategies.

Pilonidal Sinus Disease is Associated with Severe Hidradenitis Suppurativa in a Spanish Cohort.

Hidradenitis suppurativa is a chronic inflammatory disorder of the hair follicle with a high level of morbidity. Pilonidal sinus disease is a comorbid disorder and may be the reason for first contact with the healthcare system of patients with hidradenitis suppurativa. The aim of this study was to evaluate the frequency of association of pilonidal sinus disease and hidradenitis suppurativa and to explore whether pilonidal sinus disease defines a different clinical profile for patients with hidradenitis suppurativa. A cross-sectional study in which data regarding past history of pilonidal sinus disease, clinical and sociodemographic information were recorded during the first visit to the Hidradenitis Suppurativa Clinic of 2 tertiary hospitals. A total of 839 patients were included in the study. Of these, 51.7% (434/839) were male and mean age was 37.3 ± 13.6 years. Pilonidal sinus disease was present in 32.6% (269/839) of the patients and was associated with an early debut of hidradenitis suppurativa, a higher Hurley stage, inflammatory phenotype and a greater number of fistulas and perianal involvement. Elapsed time between pilonidal sinus disease and diagnosis of hidradenitis suppurativa was associated with higher disease severity. Pilonidal sinus disease is a frequent comorbidity and risk marker for hidradenitis suppurativa disease severity. Pilonidal sinus disease could be a sentinel event to identify patients who would benefit from close treatment and follow-up.

Expression of IFN-Gamma is significantly reduced during severity of covid-19 infection in hospitalized patients.

Cytokines play an important role in SARS-CoV-2 infection progression and severity. A number of inflammatory cytokines have been directly associated with disease severity including IL-6 (interleukin-6), IL-10, TNF-α (tumor necrosis factor alpha), IFN-γ (interferon-gamma). Here, in this study, the aim was to better understand the interplay between host immune response mediated by cytokines and severity of SARS-CoV-2 infection by assessing cytokine expression. Therefore, we measured expression levels of a total of 12 genes (IFNA-1, IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-7, IL-10, IL-11, IL-13, IL-15, and IL-27) encoding inflammatory, anti-inflammatory and regulatory cytokines using QRT-PCR in hospitalized patients with severe infection compared to mildly infected. IFN-γ was identified as a potent marker of disease severity as indicated previously. Moreover, levels of IL-7 were also found to be partially reduced in patients compared to the healthy controls and linked negatively to disease severity. Identification of these cytokines may be helpful in not only understanding disease pathogenesis but also in better management of the patients after covid infection.

Retinal Thinning as a Marker of Disease Severity in Progressive Supranuclear Palsy.

Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2β-carbomethoxy-3β-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

Haptoglobin is an independent marker for disease severity and risk for metabolic complications in hidradenitis suppurativa: A prospective study.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease that is highly correlated with obesity. Haptoglobin serum levels have recently been recognized as an important biomarker linking obesity with chronic inflammation. To compare haptoglobin with previously proposed serum biomarkers for the determination of disease severity in HS patients. For this purpose, disease severity of HS patients was determined by a panel of clinical scores as well as several risk factors, such as weight and smoking habits. A prospective, diagnostic accuracy study was performed at the International Centre for Hidradenitis suppurativa/Acne inversa Bochum (ICH). The study included a total of 263 patients, including 131 who had a confirmed diagnosis of HS in Hurley I (n = 16), II (n = 56) and III (n = 59) HS, and 132 healthy controls. The main outcome was to identify serological inflammatory markers for HS disease severity [severe (III) vs. moderate/mild (II/I)] as assessed by Hurley classification. The serum levels of acute phase proteins haptoglobin and CRP, as well as the number of neutrophils in peripheral blood, number of monocytes, the systemic immune-inflammation index and the pan-immune-inflammatory value correlated with disease severity according to established clinical scores (mHSS, SAHS, Hurley, DLQI). HS patients had significantly higher haptologlobin levels compared to healthy controls. Logistic regression analysis revealed haptoglobin as the only independent marker predicting severe HS. In this prospective study, we discovered that the serum levels of the acute phase protein haptoglobin levels serve as an independent marker of disease severity in HS. While this presents the first study in the context of HS. Thus, the present data not only yield a highly promising serum marker to be further validated.

Assessment of α9β1 ıntegrın as a new dıagnostıc and therapeutıc target ın Behcet's dısease.

This study aimed to investigate the roles of α9β1 integrin and its ligands in Behçet's disease (BD) by examining serum levels and gene expressions. 15 healthy controls and 30 BD patients (14 active and 16 inactive) were included in the study. Serum levels of ITGA9, ITGB1, TNC, OPN, VCAM-1, VEGF, TSP1, TGM2, Emilin-1, and vWF, were measured by ELISA. Gene expressions of α9β1 (ITGA9 and ITGB1) and its ligands (TNC and SPP1) were evaluated by RT-PCR. Laboratory findings (CRP, ESR, HGB, WBC, RBC, neutrophil, lymphocyte, PLT, RDW, MPV, PCT, and HLA-B51) were obtained from the electronic database. Active BD patients had higher serum levels of α9β1 integrin and its ligands than inactive patients and healthy controls. No significant difference was observed between healthy controls and inactive patients. Gene expressions of ITGB1 and SPP1 were increased in both patient groups compared to healthy controls. ITGA9 and TNC gene expression levels were lower in the active group than in the inactive group. No noticeable differences were found in ITGB1 and SPP1 gene expressions between the patient groups. BD patients exhibited elevated CRP, ESR, WBC, neutrophil, PLT, and PCT levels, while HGB, RBC, and RDW values were lower than healthy controls. Active patients had higher CRP, ESR, WBC, neutrophil, and PLT levels. Significant positive correlations were found between CRP, ESR, WBC, neutrophil, PLT, PCT and serum levels of α9β1 integrin and its ligands. Increased release of α9β1 integrin and its ligands is associated with BD, suggesting their potential as markers for disease severity.

Herpes simplex virus reactivation among severe COVID-19 patients: to treat or not to treat?

Background: Herpes simplex virus type 1 (HSV-1) reactivation in the airways is a common finding among patients admitted to the intensive care unit and has been more recently been reported in critically ill COVID-19 patients. Evidence suggests that HSV-1 reactivation in critically ill patients may be associated with higher morbidity and mortality rates. However, there is conflicting data about whether treatment with acyclovir impacts outcomes. Objectives: The primary aim of this study is to assess whether acyclovir improves survival in critically ill COVID-19 patients with concomitant HSV-1 reactivation. Additionally, we explore the effect of acyclovir on cardiorespiratory instability, biochemical markers of inflammation and renal function. Incidence, potential risk factors and outcomes of HSV-1 reactivation in COVID-19 ICU patients are studied last. Methods: A retrospective single-center cohort study set in a Belgian tertiary-care university hospital. All COVID-19 patients admitted to the ICU between March 1st, 2020, and April 15th, 2021, and were tested for HSV-1 using real-time PCR in airway samples were included for analysis. The administration of acyclovir for patients with HSV-1 reactivation was not randomized. Mortality and various markers of morbidity (cardiorespiratory instability, biochemical markers of inflammation, and renal function) were compared between patients that had received acyclovir and those that had not. Secondary outcome measures were respiratory and inflammatory markers of disease severity. Results: 34.7% (42/121) of patients had HSV-1 reactivation, of which 67% (28/42) received acyclovir. ICU mortality was 36% (n = 10) in the acyclovir group versus 0% in the untreated group. Multivariate analysis resulted in OR 3.82 (95% CI 1.37 – 10.68) for ICU mortality in the treated group. Patients treated with acyclovir had a longer length of stay (41.8 vs. 26.8 days, p = .018), longer duration of invasive mechanical ventilation (33.4 vs. 21.8 days, p = .050), and lower PaO2/FiO2 ratio (59.9 vs. 73.4 mmHg, p = .008). Conclusions: The role of acyclovir in patients with HSV-1 reactivation in the ICU remains controversial. According to this study, respiratory HSV-1 reactivation for this specific patient group might be better left untreated. Treatment selection bias, however, could not be fully excluded.

Clinicopathological and circulating cell-free DNA profile in myositis associated with anti-mitochondrial antibody.

Anti-mitochondrial antibodies (AMAs) are associated with idiopathic inflammatory myopathies (IIMs). We aimed to summarize the clinicopathological characteristics, assess circulating cell-free mitochondrial DNA (ccf-mtDNA), and circulating cell-free nuclear DNA (ccf-nDNA) in AMA-associated IIMs. Medical records of 37 IIMs patients with AMAs were reviewed. Circulating cell-free mtDNA and ccf-nDNA levels in sera from IIMs patients with AMAs (n = 21), disease controls (n = 66) and healthy controls (HCs) (n = 23) were measured and compared. Twenty-eight immune-mediated necrotizing myopathy (IMNM) patients, 23 dermatomyositis (DM) patients, and 15 anti-synthetase syndrome (ASS) patients were enrolled as disease controls. Correlations between variables were analyzed. Limb weakness was observed in 75.7% and neck weakness in 56.8% of patients. Cardiac involvement occurred in 51.4% of patients. Muscle pathology revealed 81.1% of IMNM, 5.4% polymyositis, and 13.5% nonspecific myositis. Microinfarction was observed in 8.1% of patients. Serum ccf-mtDNA levels in AMA-associated IIMs were significantly higher than those in HCs (p < 0.001), but no significant differences between AMA-associated IIMs and IMNM, DM, or ASS. Serum ccf-nDNA levels in AMA-associated IIMs were significantly higher than those in HCs (p = 0.02), and significantly lower than those in DM (p = 0.02). Serum ccf-nDNA levels correlated negatively with MMT8 total scores (rs = -0.458, p = 0.037) and positively with mRS scores (rs = 0.486, p = 0.025). Serum ccf-nDNA levels were significantly higher in the non-remission group (p < 0.01). AMA-associated IIMs exhibit distinct clinicopathological features. Serum ccf-nDNA may serve as a potential marker for disease severity and prognosis in AMA-associated IIMs.

Serum Pentraxin 3 as Promising Biomarker for the Long-Lasting Inflammatory Response of COVID-19.

Currently, biological markers for COVID-19 disease severity still constitute the main goal of enhancing an efficient treatment to reduce critical consequences such as an abnormal systemic inflammatory response. In this regard, the latest research has shown that Pentraxin 3 (PTX3), a highly conserved innate immunity protein, may serve as a valuable biochemical marker. Based on this evidence, we conducted a case-control study to compare the PTX3 serum levels and several immune-inflammatory mediators of 80 healthcare workers who were subdivided into subjects who were previously infected with SARS-CoV-2 (n = 40) and individuals who were never infected (n = 40). Using a commercially available Enzyme-Linked Immunosorbent Assay (ELISA), PTX3 and various immune-inflammatory protein levels were assessed in serum samples, while also considering possible variables (e.g., gender-related differences). We have shown elevated levels of PTX3 and other inflammatory proteins in previously infected COVID-19-positive subjects (p < 0.001). Moreover, the obtained data also indicate a degree of severity influenced by gender, as shown by the subgroup analysis, in which PTX3 expression was more pronounced in previously COVID-19-positive males (p < 0.001) than in females (p < 0.05) compared to the respective controls. In addition, our data further validate, through a direct comparison of previously COVID-19-positive subjects, greater pro-inflammatory levels in males than in females. Overall, our results may support the validity of PTX3 as a systemic biomarker in prolonged systemic inflammatory responses in the context of COVID-19. Thus, PTX3 modulation could constitute an effective therapeutic strategy for improving the recovery from COVID-19 and its systemic long-term consequences.

Demographics and deprivation in obstetric brachial plexus palsy: a retrospective cohort study.

The present study analyses the relationships between deprivation and obstetric brachial plexus palsy (OBPP). A retrospective observational study was conducted of infants with OBPP seen between 2008 and 2020 (n = 321). The index of multiple deprivation (IMD) was used to assign an IMD rank to patients based on birth postcode and the relationship with OBPP was analysed, including deprivation, gestational diabetes, age at referral and at first assessment. Quintile-based analysis demonstrated over-representation of patients from more deprived neighbourhoods (n = 109, 39%) living in the top 20% most deprived neighbourhoods. A total of 48 (15%) mothers had diabetes and 98 (31%) infants underwent surgical brachial plexus exploration (a marker of disease severity). Neither diabetes, age at referral nor age at first assessment were associated with IMD score. This suggests that neighbourhood deprivation is associated with OBPP, though the mechanisms are unclear. Further studies in this area may enable targeted health intervention for more deprived maternal and infant groups.Level of evidence: III.

Left atrial remodeling in hypertrophic cardiomyopathy and Fabry disease: A CMR-based head-to-head comparison and outcome analysis

BackgroundHypertrophic cardiomyopathy (HCM) and Fabry disease cardiomyopathy (FD) are phenocopies, as they show left ventricular hypertrophy (LVH). The left atrium (LA) is emerging as a potential marker of disease severity in both cardiomyopathies. The present study compares HCM and FD cardiomyopathy with similar degree of LVH, exploring LA morpho-functional parameters and the correlates of clinical outcome. MethodsWe performed a comprehensive CMR-based comparison between 30 HCM and 30 FD patients matched on age, sex, BSA, LV mass and major cardiovascular risk factors affecting LA remodeling (arterial hypertension and diabetes). 30 healthy controls were also included. CMR feature tracking (CMR-FT) analysis, T1 mapping and conventional parameters were evaluated. Patients also underwent transthoracic echocardiography for LV diastolic function assessment. Clinical events at follow-up were collected (atrial and ventricular events, bradyarrhythmia, heart failure (HF) hospitalization and death). ResultsHCM patients showed greater LA remodeling compared to FD patients, namely higher LA end-systolic volume index (LAVi max), lower LA-ejection fraction (LA-EF) and worse reservoir (εs) and booster function (εa) (all p < 0.05). Accordingly, these parameters have demonstrated good potential for distinguishing between FD and HCM (AUC 0.68–0.73, all p < 0.05), with LAVi max being an independent predictor for HCM diagnosis (OR 1.07, 95%CI 1.011–1.132, p 0.02). Moreover, in HCM patients a significant association between εs and HF occurrence was observed at 2-year follow-up (OR 0.85, 95%CI 0.72–0.99, p 0.04). ConclusionsIn HCM, LA remodeling is greater than in FD cardiomyopathy with similar LVH, and reservoir strain is associated with HF at follow-up.

Diabetes exacerbates inflammatory bowel disease in mice with diet-induced obesity.

The increased prevalence of inflammatory bowel disease (IBD) among patients with obesity and type 2 diabetes suggests a causal link between these diseases, potentially involving the effect of hyperglycemia to disrupt intestinal barrier integrity. To investigate whether the deleterious impact of diabetes on the intestinal barrier is associated with increased IBD severity in a murine model of colitis in mice with and without diet-induced obesity. Mice were fed chow or a high-fat diet and subsequently received streptozotocin to induce diabetic-range hyperglycemia. Six weeks later, dextran sodium sulfate was given to induce colitis. In select experiments, a subset of diabetic mice was treated with the antidiabetic drug dapagliflozin prior to colitis onset. Endpoints included both clinical and histological measures of colitis activity as well as histochemical markers of colonic epithelial barrier integrity. In mice given a high-fat diet, but not chow-fed animals, diabetes was associated with significantly increased clinical colitis activity and histopathologic markers of disease severity. Diabetes was also associated with a decrease in key components that regulate colonic epithelial barrier integrity (colonic mucin layer content and epithelial tight junction proteins) in diet-induced obese mice. Each of these effects of diabetes in diet-induced obese mice was ameliorated by restoring normoglycemia. In obese mice, diabetes worsened clinical and pathologic outcomes of colitis via mechanisms that are reversible with treatment of hyperglycemia. Hyperglycemia-induced intestinal barrier dysfunction offers a plausible mechanism linking diabetes to increased colitis severity. These findings suggest that effective diabetes management may decrease the clinical severity of IBD.

Peripheral Eosinophilia as an Ominous Marker of Poor Quality of Life: A Cross-Sectional Study Evaluating the Correlation Between Absolute Eosinophilia and Dermatology Life Quality Index in Various Pruritic Dermatoses

Background: Eosinophils are multifunctional cells of innate immunity and play a pivotal role in allergic, antiparasitic, phagocytotic, and tissue repair functions. These cells are sentinel mediators of pruritus. The increase in the absolute eosinophil count (AEC) in pruritic dermatoses is considered an objective marker of disease severity. The dermatology life quality index (DLQI) is a questionnaire assessing subjective impairment in quality of life. Objectives: To assess the correlation between AEC and DLQI in pruritic dermatoses. Methods: This cross-sectional observational-correlational study was carried out over a period of 6 months in a tertiary care center on 100 patients diagnosed with various clinical forms of pruritic dermatoses after obtaining informed consent. The DLQI score was calculated using a pre-validated questionnaire followed by the determination of AEC in whole blood samples. Results: Most patients had inflammatory diseases (26%), followed by infections (16%) and urticaria (14%). Mild eosinophilia was observed in 28% of cases, moderate eosinophilia in 22%, and severe eosinophilia in 6% of the cases. In terms of the DLQI score, the impact of the disease on quality of life was profound in 37% of the patients and enormous among 12% of them. Quality of life was unaffected in 5% of the cases. Overall, there was a significant strong positive correlation between AEC and DLQI (r = 0.649, P &lt; 0.0001). Conclusions: A significant correlation was noticed between AEC and subjective DLQI as a marker of disease burden in various forms of pruritic dermatoses. Thus, AEC can be regarded as a perceived marker of disease prognostication, an objective equivalent to quality of life, and, most importantly, a potential target for therapeutic interventions.

Mpox in people with past infection or a complete vaccination course: a global case series

Since May, 2022, a large global outbreak of human mpox (formerly known as monkeypox) has predominantly affected men who have sex with men. The strain responsible, Clade IIb, has mutated substantially from precursors originating from the 2017-18 outbreak in Nigeria. Immunity to smallpox, another orthopoxvirus, via previous infection or vaccination provides lifelong immunity. However, since the 2022 mpox outbreak, recent clusters were described in individuals with presumed immunity through recent infection or vaccination. We aim to describe the epidemiological and clinical characteristics of mpox in individuals with past infection or vaccination to improve the understanding of this disease in the setting of previous immunity. In this global case series, international collaborators from nine countries provided data on individuals with PCR-confirmed mpox after documented previous infection or vaccination between May 11, 2022, and June 30, 2023. We excluded cases that could not confirm vaccination status or cases with partial immunisation or any doses received before the current multi-national mpox outbreak (cutoff date May 1, 2022). Data were collected via a case report spreadsheet that reported on dates of infection and vaccination, route of immunisation, demographic characteristics, clinical findings, HIV status, concomitant sexually transmitted infections, and markers of disease severity (mpox severity score system). We describe case epidemiology, clinical course, and mpox severity scores; all analyses were descriptive. We report mpox infections in 37 gay and bisexual men who have sex with men: seven individuals had mpox reinfections, 29 individuals had mpox infections that occurred after two appropriately spaced Modified Vaccinia Ankara-Bavarian Nordic vaccine courses, and one individual had an infection that met the criteria for both reinfection and infection after vaccination. The median age of individuals was 36 years (IQR 30-45; range 21-58). Those with natural immunity after initial infection had a shorter disease course with less mucosal disease upon reinfection than with their initial infection. Infections post-vaccination were characterised by few lesions, little mucosal disease, and minimal analgesia requirements; two people received oral tecovirimat. Overall, there were no deaths, no bacterial superinfections, and all individuals were managed in the ambulatory clinic with one hospital admission for a necrotising neck lesion. The epidemiology of people with mpox reinfection or infection post-vaccination was similar to other published cohorts during the 2022 outbreak-predominantly young, sexually active gay and bisexual men who have sex with men. Clinical features and outcomes of repeat infection and infection after vaccination appear to be less clinically severe than those described in 2022 case literature. Specifically, compared with the 2022 case series, these individuals in the present study had fewer confluent lesions, less mucosal involvement, reduced analgesia requirement, and fewer admissions. Natural immunity and vaccine-induced immunity are not fully protective against mpox infection. However, in this small series both disease duration and severity appear to be reduced. None.

Characteristics and Outcomes of Culture-Positive and Culture-Negative Pediatric Sepsis

To compare the outcomes of pediatric severe sepsis and septic shock among patients with culture-positive and culture-negative sepsis and to determine if there are differentiating markers of disease severity between these 2 populations during their initial presentation and emergency department (ED) stay. Retrospective cohort study of patients ≤21years of age who presented to the ED of a single children's hospital with severe sepsis or septic shock from June 1, 2017 to June 5,2019. There were 235 patients who met criteria for severe sepsis or septic shock. Of these, 139 (59.1%) had culture-negative sepsis and 96 (40.9%) had culture-positive sepsis. In the adjusted multivariable model, children with culture-negative sepsis had more intensive care unit (ICU)-free days than those with culture-positive sepsis (27.3 vs 24.1; adjusted median differences [aMD] -2.6 [-4.4, -0.8]). There were no differences in mortality or hospital-free days. On initial presentation, there were no differences in fever, hypothermia, tachycardia, tachypnea, or hypotension between the 2 groups. There were no differences in proportion of patients receiving the following interventions: intravenous (IV) antibiotics, IV fluids, vasoactive medications, CPR, intubation, or time from arrival to provision of these interventions. Culture-negative sepsis constitutes a substantial proportion of pediatric severe sepsis and septic shock. In this study, patients with culture-negative and culture-positive sepsis presented similarly on arrival to the ED and received similar treatments while there. Patients with culture-negative sepsis had more ICU-free days than those with culture-positive sepsis, although differences in hospital length of stay (LOS) and mortality were not observed.

Utility of baseline D-dimer and neutrophil-to-lymphocyte ratio (NLR) in predicting the severity among COVID-19 patients in an Indian cohort during the first wave of the pandemic

Introduction and Aim: COVID-19 outbreak was declared as pandemic by WHO Director-General on 11th March 2020 in his opening remarks at the media briefing. The global population infected by Corona virus appeared to be responding at different levels in the first wave which warranted WHO to categorise the disease as mild, moderate, and severe. Haematological, biochemical, and radiological parameters played a crucial role in critically triaging and following-up disease progression. Amongst various laboratory parameters, this work aimed to identify the most specific marker in predicting disease severity. Materials and Methods: Blood samples from study population of 510 laboratory confirmed COVID-19 cases admitted in our hospital were selected. The patients who were classified as having mild, moderate, and severe disease were analysed for biochemical and haematological inflammatory markers. Results were analysed by ANOVA and post-hoc tests. ROC curves were derived to determine the cut-off values between severe and non-severe groups. Correlation between D-dimer and NLR was done by Pearson’s correlation. Results: Patients with co-morbidities were likely to develop severe complications which could lead to poor outcome. From ROC curves, we determine that NLR, with highest area under curve, is the best marker of disease severity. A significant positive correlation was found between D-dimer and NLR (p=0.000) across groups. Baseline cut-off values for D-dimer and NLR based to differentiate between severe and non-severe cases were 0.5 and 4.875 respectively. Conclusion: We conclude that baseline NLR is a simple and most useful tool that would assist clinicians in designing treatment strategies for a COVID-19 infected patient.