Severity Criteria Research Articles

Underreporting of adverse events to health authorities by healthcare professionals: a red flag-raising descriptive study.

An adverse event (AE) is any undesirable medical manifestation in an individual who has received pharmacological treatment. To be considered serious (SAE), it needs to meet minimally one of the severity criteria by Health Canada. The most recent data (2006) suggested that AEs were underreported (<6%) to health authorities. In Canada, since the implementation of Vanessa's Law (2019), hospitals are required to report SAEs, however this law remains relatively unknown.. The objectives of the study were: 1) to document the incidence of any adverse event (AE) and serious adverse event (SAE) over time in a "real" clinical context, 2) to quantify SAEs reported to Health Canada, and 3) to assess whether Vanessa's Law has led to an increase in mandatory reporting to Health Canada. We carried out a descriptive retrospective study at the Institut universitaire de cardiologie et de pneumologie de Québec-Université Laval, including 500 patients hospitalized between 2018/01/01 and 2021/12/31 and randomized into 4 cohorts (125 patients/year). Descriptive and comparative analyses were performed. The characteristics of the cohorts were: 43.6% women; median age: 69 years [min-max: 21-96 years], number of comorbidities: 4 [1-12]. During their hospitalization, patients consumed 18 different drug products [2-56] and the median of observed SAEs/patients was 0 [0-10] (total: 302). The overall percentage of SAEs reported to Health Canada was 0%, before and following the implementation of Vanessa's Law. According to 500 electronic medical records, SAEs were underreported to Health Canada, even after the implementation of Vanessa's law.

Grading portal vein stenosis following partial hepatectomy by high-frequency ultrasonography: an in vivo study of rats.

To evaluate the diagnostic value of ultrasound in grading portal vein stenosis (PVS) in a rat model of 70% partial hepatectomy (PH). A total of 96 Sprague-Dawley rats were randomly divided into a PH group and PVS groups with mild, moderate, and severe PVS following PH. Hemodynamic parameters were measured using high-frequency ultrasound (5-12 MHz high-frequency linear transducer), including pre-stenotic, stenotic, and post-stenotic portal vein diameters (PVDpre, PVDs, PVDpost); pre-stenotic and stenotic portal vein velocity (PVVpre, PVVs); hepatic artery peak systolic velocity (PSV); end-diastolic velocity; and resistive index. The portal vein diameter ratio (PVDR) and portal vein velocity ratio (PVVR) were calculated using the following formulas: PVDR=PVDpre/PVDs and PVVR=PVVs/PVVpre. The value of these parameters in grading PVS was assessed. Portal vein hemodynamics showed gradient changes as PVS aggravated. For identifying >50% PVS, PVDs and PVDR were the best parameters, with areas under the curve (AUC) of 0.85 and 0.86, respectively. For identifying >65% PVS, PVDs, PVDR, and PVVR were relatively better, with AUCs of 0.94, 0.85, and 0.88, respectively. The AUC of hepatic artery PSV for identifying >65% PVS was 0.733. High-frequency ultrasonography can be used to grade PVS in rats, with PVDs, PVDR, and PVVR being particularly useful. Hepatic artery PSV may help in predicting >65% PVS. These findings provide valuable information for PVS rat model research and offer an experimental basis for further studies on PVS evaluation in living-donor liver transplantation (LDLT). Ultrasonography serves as a first-line technology for diagnosing PVS following LDLT. However, the grading criteria for PVS severity remain unclear. Investigating the use of ultrasonic hemodynamics in the early diagnosis of PVS and grading stenosis severity is important for early postoperative intervention and improving recipient survival rates.

The relative importance of severity and rarity criteria in health resource allocation: an umbrella review.

The primary objectives of this umbrella review were to (a) quantify the relative importance, of "severity" and "rarity" criteria in health resource allocation; and (b) analyze the contextual factors influencing the relative importance. The secondary objective was to examine how "severity" and "rarity" criteria are defined. Searches were carried out in PubMed and Embase to identify eligible systematic reviews. Quality appraisal of systematic reviews was undertaken. From identified systematic reviews, primary studies were extracted and further screened for eligibility. The inclusion of severity and rarity criteria and their respective weights in primary studies were examined. Descriptive and regression analyses were performed. Twenty-nine systematic reviews were screened, of which nine met the inclusion criteria. Primary studies included in these systematic reviews were retrieved and screened, resulting in forty articles included in the final analysis. Disease severity was more frequently considered (n=29/40) than disease rarity (n=23/40) as an evaluation criterion. Out of all cases where both were included as evaluation criteria, disease severity was assigned higher weights 84 percent of the time (n=21/25). Our review found consistent evidence that disease severity is more relevant and preferred to rarity as a priority-setting criterion albeit constraints in statistical analysis imposed by limited sample size and data availability. Where funding for rare diseases is concerned, we advocate that decision-makers be explicit in clarifying the significance of disease severity and/or rarity as a value driver behind decisions. Our findings also reinforce the relevance of disease severity as a criterion in priority setting.

The effects of pregnancy on disease progression of retinitis pigmentosa

PurposeRetinitis pigmentosa (RP) is the most common diagnosis in the ophthalmic genetics’ clinic. Women with RP are often diagnosed during their reproductive years, posing significant challenges for family planning. The effects of pregnancy on RP progression is a frequently unanswered concern for these patients. DesignRetrospective cohort study. SubjectsWomen who attended Moorfields Eye Hospital (London, UK) and met the following inclusion criteria were included in this study: (i) had their most recent visit at 30 years old or more, (ii) were diagnosed with RP, (iii) had information in their medical records about having had children, and (iv) were found to have biallelic rare or likely disease-causing variants in USH2A. MethodsThe cohort was divided into parous and nulliparous, and multivariate Cox regressions adjusting for multiple confounding effects was performed. A further analysis also included number of children as a variable. Main outcome measuresRP severity criteria based on visual acuity (VA) and ellipsoid zone (EZ) width, and national registration of sight impairment. Results142 women were included in the study, 98 parous (69%) and 44 nulliparous (31%). In the parous group, 21% had cystoid macular oedema (CMO) requiring treatment and 46% had cataracts or were pseudophakic, versus 18% with CMO and 59% with cataracts in the nulliparous. Women had a median of 2 children. A significant association was only found in parous women having 3.04 (1.23-7.48) times increased risk of having VA worse than LogMAR 0.7 than nulliparous (p= 0.016), after adjusting for baseline age, phenotype, cataract status, and CMO. ConclusionsThis is the first large-scale objective study analysing the effects of pregnancy in genetically-confirmed women with RP. Women with USH2A-associated RP who had children appeared to have 3.04 times the risk of reaching VA below 6/24 than those who did not have children. It is possible that other factors besides retinal degeneration are affecting central vision and causing this increased risk. A significant association between faster or slower EZ loss and pregnancy was not present in our cohort. We believe these findings will be relevant to all women with RP considering starting a family; although further studies are needed.

The Basque Impact Weather Catalogue

Abstract. This paper introduces the Basque Country impact weather catalogue, a versatile tool designed, developed, and maintained by the Basque Meteorology Agency (Euskalmet), with the primary objective of systematically recording detailed information regarding adverse weather events that generate some degree of impact in the Basque Autonomous Community (BAC). The catalogue serves as a repository where information is gathered for the comprehensive characterisation and evaluation of extreme weather events, focusing on both environmental conditions and their associated impacts. For this purpose, three key aspects are included: context, hazard and risk and impact. In the context section, we include information about the date, duration, spatial extent, measurement statistics data, synoptic/mesoscale aspects, and other metadata. The hazard and risk section includes information about hazard and risk typology according to Euskalmet severe weather criteria and warnings procedure. Regarding the impact, a range of metrics and indicators are defined to characterise critical aspects, encompassing the severity of impact including economic damages, human fatalities, and disruptions to normal life. The creation of the Catalogue involves utilising various data sources and repositories, not only from Euskalmet but also, particularly in terms of impact, from emergency interventions, newspapers, local media websites, social media, and data from the Spanish Insurance Consortium. While the volume of available material from each event description may vary from case to case, a standardised information structure and minimum content are imperative for all registered events. This ensures that qualitative analyses based on extensive reports, and quantitative analyses based on recorded or estimated metrics and indicators, are possible for events included. This paper outlines into the design and structuring of the catalogue, and the fundamental steps undertaken during its implementation.

Acute myocarditis presentation and intra-hospital prognosis: results of the multicenter prospective MYOCARDITIRM study

Abstract Background Acute myocarditis (AM) usually presents as chest pain with rising troponin and normal coronary arteries. Despite frequent favorable evolution at the acute phase, it is associated with heart failure and ventricular rhythm disorders and is considered the leading cause of sudden cardiac death in young apparently healthy adults. There is no recommendation for AM, only expert consensus, given the lack of important databases for a strong level of confidence. Methods We performed a multicenter prospective observational study of patients admitted for AM acknowledged by cardiac MRI to describe baseline characteristics, management, in-hospital and long-term outcomes of AM patients in France. Secondary objectives were to investigate determinants of prognosis, modalities of treatment and follow-up, and to identify gaps between expert consensus and real-life management. Results We enrolled 805 consecutive patients hospitalized for AM in 49 participating centers between May 2016 and February 2019. Median age was 31 (IQR 23-41) with 19% of female. Chest pain was the most frequent symptom (93%) and 112 (14%) had severity criteria upon admission (LVEF&amp;lt;50% or severe ventricular arrythmia or high-grade AV block or cardiogenic shock). ST elevation was observed in 49% of patients. One 26-years old patient died during initial hospital stay. Overall, 62 patients (8%) experienced intra-hospital complication of their AM, defined as a combined endpoint of death, LVEF&amp;lt;40% (MRI), sustained ventricular or supraventricular arrythmia, acute renal failure, cardiogenic shock, need for ventricular assistance device, need for inotropic drugs, temporary cardiac pacing, pace-maker or cardiac defibrillator implantation. Patients with initial severity criteria were 10 times more likely to present intra-hospital complication (33% vs 3.6%, p&amp;lt;0.001). Conclusion This prospective cohort represents the largest database on AM worldwide. Here we report baseline characteristics and in hospital events. Most patients had typical presentation with favorable outcomes but as much as 8% of patients did exhibit intra-hospital complication. The prospective follow up will provide valuable data to better identify subset of patients with poor prognosis that may be of interest to develop new therapeutic strategies.Acute myocarditis on cardiac MRI

Evaluation of bleeding events in a cohort of patients with transthyretin cardiac amyloidosis

Abstract Introduction and purpose transthyretin amyloidosis is an infiltrative disease with several comorbidities, including bleeding. The aim of this study was to evaluate the incidence of bleeding in patients with transthyretin amyloidosis and the underlying risk factors that promote bleeding. Methods a retrospective observational study was conducted on a cohort of patients with transthyretin amyloidosis diagnosed between 2016 and 2023 according to the diagnostic criteria of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology. Bleeding risk was calculated according to HAS-BLED score and bleeding events at follow-up were analysed. Results 184 patients were diagnosed with a median age of 84 years [IQR 79-8], 154 (8%) males. 123 patients (67%) were on anticoagulant therapy. 91 patients (50%) had a bleeding event, with a total of 189 events recorded and a median time from transthyretin amyloidosis diagnosis to bleeding of 10 months [IQR 6-14]. The most frequent bleeding sites were gastrointestinal (32%) and cutaneous (22%). 35 patients (39%) had a haemorrhage which fulfilled severe bleeding criteria and 4 patients died of haemorrhagic causes. As a consequence of bleeding, 6 atrial appendage closure were indicated and anticoagulation therapy was modified in 15 individuals. The incidence rate of haemorrhage was 50 bleeds per 100 patient-years and 58 per 100 patient-years in patients on anticoagulant treatment. Anticoagulant therapy resulted in a 3,5-fold raise in bleeding (95% CI 2-7) and a punctuation ≥2 in HAS-BLED score increased haemorrhages 4,6 times (95% CI 2-9), with higher rates of bleeding the higher the score on the scale. Conclusions bleeding is a frequent complication in transthyretin amyloidosis, with a higher risk in those individuals with anticoagulant therapy or with a HAS-BLED score ≥2. Subsequently, it should be considered in the follow-up both haemorrhagic risk and anticoagulant treatment, with the aim of implementing strategies to reduce the bleeding risk.

Defining ethical criteria to guide the expanded use of Noninvasive Prenatal Screening (NIPS): Lessons about severity from preimplantation genetic testing.

We hypothesized that ethical criteria that guide the use of preimplantation genetic testing (PGT) could be used to inform policies about expanded use of non-invasive prenatal screening (NIPS). We used a systematic review of reasons approach to assess ethical criteria used to justify using (or not using) PGT for genetic conditions. Out of 1135 identified documents, we retained and analyzed 216 relevant documents. Results show a clear distinction in acceptability of PGT for medical vs. non-medical conditions. Criteria to decide on use of PGT for medical conditions are largely based on their severity, but there is no clear definition of "severity". Instead, characteristics of the condition that relate to severity are used as sub-criteria to assess severity. We found that characteristics that are used as sub-criteria for assessing severity include monogenic etiology, high penetrance, absence of treatment, early age of onset, shortened lifespan, and reduced quality of life. Consensus about the use of PGT is highest for conditions that meet most of these criteria. There is no consensus around the acceptability of using PGT to detect non-medical conditions. We propose that the same severity criteria could be used by policymakers to assess the acceptability of using other genetic tests in screening and practice, including for the use of NIPS for additional conditions as indications broaden.

Severity levels of anorexia nervosa and atypical anorexia nervosa in a Korean cohort.

Despite its potential for informing tailored treatments, the severity of eating disorders (EDs) lacks clear conceptualisation. The present retrospective cohort study examined the clinical validity and utility of severity specifiers for anorexia nervosa (AN) and atypical AN in a Korean population. Data from 696 Korean outpatients with AN or atypical AN were analysed. Severity criteria for AN from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Medical Emergencies in Eating Disorders (MEED) guidance were used. Severity criteria applied for atypical AN were the frequency of intermittent fasting (ED Diagnostic Scale item 17), Eating Disorder Examination Questionnaire global scores, and the degree of weight suppression. Prevalence of extreme cases of AN in our cohort was higher than in Western populations in previous studies. MEED guidance further subclassified extreme AN, revealing distinct psychopathological profiles across severity levels. The proposed severity classification for atypical AN based on the weight loss behaviour of intermittent fasting showed merit. These findings suggest a potential need for a more nuanced AN severity classification that better represents severe medical aspects and encompasses cultural and ethnic diversities. In atypical AN, there is a need to examine severity indices measuring pathological behaviours.

Complete Blood Count in Children With COVID-19: A Predictor of Disease Severity.

Blood count abnormalities are frequent in patients with severe COVID-19 disease and there is still a lack of information in pediatric complete blood count (CBC) results. Thus, this study aims to correlate the CBC in the emergency room of children with COVID-19 between 0 and 10 years old and the clinical severity of the disease. A retrospective cohort study was performed in children with COVID-19 who collected at the emergency room CBC, C-reactive protein (CRP), platelet to lymphocyte ratio (PLR), neutrophil to lymphocyte ratio (NLR), neutrophil to monocyte ratio (NMR), lymphocyte to neutrophil ratio (LNR), lymphocyte to monocyte ratio (LMR), monocyte to neutrophil ratio (MNR) and monocyte to lymphocyte ratio (MLR). In total, demographic data from 93 children with median age of 19 months (0.3-126), 60.2% males, were included. The main changes in the CBC were atypical lymphocytes (51.6%) and eosinopenia (49.5%). From 69 hospitalized children, 21 were considered severe. There was no association between age, gender, and CRP value with clinical severity. The presence of underlying disease was five times higher (odds ratio [OR] = 5.08) in patients who required hospitalization and a higher NLR value was 54% (OR = 1.54) more likely to occur. Eosinopenia was three times more frequent in inpatients with disease severity criteria (OR = 3.05). In conclusion, children younger than 10 years of age with COVID-19 have changes in the CBC collected in the emergency room, mainly atypical lymphocytes and eosinopenia. The presence of a comorbidity or a higher NLR increases the chance of hospitalization. In addition, eosinopenia was a predictor of severity in inpatient children due to COVID-19.

Psychiatric outcomes among COVID-19 egyptian patients at ain shams university quarantine hospitals: A cross-sectional study

BackgroundPsychological repercussions resulting from coronavirus disease 2019 (COVID-19) have been encountered, such as anxiety, depression, insomnia, and post-traumatic stress disorder (PTSD). The study aimed to assess the frequency and severity of PTSD, depression, and anxiety in a sample of Egyptian patients with COVID-19 infection and analyze potential risk factors. The current study is a descriptive cross-sectional, hospital-based study, conducted from August 2020 to June 2021. The sample was selected from patients diagnosed with COVID-19 infection at Ain Shams University hospitals (outpatient clinics and inpatient units). Patients underwent a COVID severity criteria scoring system, structured clinical interview for DSM-IV (SCID-I), PTSD checklist–Civilian Version (PCLC), Beck depression inventory, and Taylor’s manifest anxiety scale.ResultsPTSD was observed in 79.29% of the study sample, 61.43% had depression, and 18.57% had anxiety. The severity of COVID-19 infection was significantly associated with PTSD severity mean scores (P value = 0.027). Furthermore, a significant relationship was observed between the severity of depression and COVID-19 infection severity (P value = 0.028). The number of comorbid medical risk factors demonstrated significance to PTSD severity (P value = 0.014).ConclusionA significant portion of the study’s patients experienced psychiatric consequences following COVID-19 infection, with 79.29% developing PTSD, 61.43% suffering from depression, and 18.57% experiencing anxiety. Various factors, such as the presence of chronic medical illnesses and the number of co-morbid medical risk factors, were observed to contribute to these psychiatric outcomes. Therefore, comprehensive psychiatric assessment and management in COVID-19 patients especially with severe forms of the disease and hospitalized patients are mandatory.

An international survey to better understand the current incidence, severity, and management of VOD/SOS.

This international questionnaire survey aimed to explore the current incidence, diagnostic policies, management, and outcomes of veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) among healthcare providers involved in the management of these patients. A questionnaire was e-mailed to practitioners with an interest in allogeneic hematopoietic cell transplantation (allo-HCT). Of the respondents, 144 of 215 (67.0%) felt that early detection or diagnosis of VOD/SOS was difficult. Regarding diagnostic criteria, 142 (66.1%) already declared using the 2023 EBMT refined criteria. Most respondents (163/215, 75.8%) found these recent refined EBMT criteria useful for diagnosis, and 193 (89.8%) found the severity criteria easy to use. The major risk factors identified for VOD/SOS were a second allo-HCT (41.4%), pre-existing liver disease (54.9%), and prior use of antibody-drug conjugates (49.8%). Preferences for starting VOD/SOS treatment varied, with 61 (28.4%) preferring initiating therapy at a mild stage, and 122 (56.7%) preferring the moderate stage. In summary, this survey provided valuable insight into the challenges and opportunities of the identification and management of VOD/SOS. By improving current knowledge and increasing collaboration among healthcare professionals, early detection, management, and clinical outcomes for patients with this potentially serious complication can also be improved.

Unveiling Immunological and Hematological Markers in COVID-19: Insights from a Clinical Study.

The COVID-19 pandemic has affected the global health system and economies largely. Therefore, knowledge about the clinical and laboratory profiles of patients with COVID-19 would help in the management and prognosis of the disease. The immunological and hematological indices have emerged as critical determinants for the severity of the disease and the prognosis; however, association with COVID-19 is clouded. The present study is aimed to characterize the immunological and hematological profiles of patients with COVID-19 in correlation with the disease severity. The study included 1,019 polymerase chain reaction (PCR)-confirmed patients with COVID-19 who were classified into serious and nonserious groups, considering severity criteria. Clinical laboratory investigations included hematological, biochemical, and immunological parameters regarding leukocyte counts, hemoglobin levels, and inflammatory markers. Our analysis of immunological and hematological differences between serious and nonserious patients with COVID-19 indicates that serious cases reflected elevated levels of pro-inflammatory markers such as lactate dehydrogenase, C-reactive protein (CRP), D-dimer, and ferritin, representing immune system dysregulation and systemic inflammation. Furthermore, in serious cases, discrepancies had also been noticed for many hematological parameters than nonserious ones, which also contained leukocyte count and hemoglobin level. Additionally, the CRP, D-dimer, blood urea nitrogen, alanine transaminase, and albumin levels could be independent predictors of COVID-19 severity by multivariate logistic regression analysis. Cutoff values for these biomarkers were defined by receiver operating characteristic curve analysis defining optimal parameters for the risk stratification and prognostication. The current investigation provides a comprehensive understanding of immunological and hematological correlation with COVID-19 severity, refining clinical decision-making and therapeutic interventions to improve patient outcomes.

Peripheral Perfusion Index in Ugandan Children With Plasmodium falciparum Severe Malaria: Secondary Analysis of Outcomes in a 2014-2017 Cohort Study.

Continuous, noninvasive tools to monitor peripheral perfusion, such as perfusion index (PI), can detect hemodynamic abnormalities and assist in the management of critically ill children hospitalized with severe malaria. In this study of hospitalized children with severe malaria, we aimed to assess whether PI correlates with clinical markers of perfusion and to determine whether combining PI with these clinical measures improves identification of children with greater odds of mortality. Post hoc analysis of a prospective, multicenter, cohort study conducted between 2014 and 2017. Two referral hospitals in Central and Eastern Uganda. Six hundred children younger than 5 years old with severe malaria and 120 asymptomatic community children. None. PI was measured at 6-hour intervals for the first 24 hours of hospitalization. We compared PI to standard clinical perfusion measures such as capillary refill time, presence of cold peripheral limbs, or temperature gradient. Admission PI was highly correlated with clinical measures of perfusion. Admission PI was lower in children with severe malaria compared with asymptomatic community children; and, among the children with severe malaria, PI was lower in those with clinical features of poor perfusion or complications of severe malaria, such as shock and hyperlactatemia (all p < 0.02). Among children with severe malaria, lower admission PI was associated with greater odds of mortality after adjustment for age, sex, and severe malaria criteria (adjusted odds ratio, 2.4 for each log decrease in PI [95% CI, 1.0-5.9]; p = 0.045). Diagnostically, the presence of two consecutive low PI measures (< 1%) predicted mortality, with a sensitivity of 50% and a specificity of 76%. In severe malaria, PI correlates with clinical complications (including shock and elevated serum lactate) and may be useful as an objective, continuous explanatory variable associated with greater odds of later in-hospital mortality.

Protective role of hypoxia-induced factor-1α and HIF-1A gene polymorphism in the development of acute pancreatitis

Acute pancreatitis (AP) is an acute surgical disease of the abdominal cavity that becomes severe in 20-30% of patients and has a mortality rate reaching 25%. Hypoxia that occurs during AP may be associated with the activation of a regulatory protein, hypoxia-inducible factor-1á (HIF-1á), which plays an important role in the body’s response to hypoxia. The HIF-1 transcription factor induces the expression of genes involved in cell proliferation, angiogenesis, neurogenesis, erythropoiesis and cellular metabolism, and maintenance of intracellular pH. The purpose of the work is to study the relationship between HIF-1á blood levels and polymorphism of the HIF-1A gene with the criteria of hypoxia, tissue damage and severity of AP. We examined 93 patients with AP of varying severity on days 1 and 3 of the disease, age 48 (39-67) years. We identified 3 groups of patients: with mild AP – 32 people, moderate – 26 people, or severe – 35 people. The comparison group consisted of 25 healthy volunteers, average age 47 (39-56) years. The HIF-1á levels, the presence of HIF-1A gene polymorphism, interleukin-6, C-reactive protein, procalcitonin, ferritin, D-dimer, S100 protein, clinical blood test, and blood gas composition were assessed. In patients with AP, clinical and laboratory signs of acute inflammation, microcirculation disorders, hypoxia and organ dysfunction were observed. With mild severity of AP on days 1-3 of observation, the HIF-1á level exceeded its content in the comparison group. With moderate and severe AP, the production of HIF-1á as a factor of adaptation to hypoxia decreased. A relationship was found between the HIF-1á level and the severity of AP. In the same patients, the HIF-1A gene polymorphism (1772CT, rs11549465) was studied to identify carriage of the C/C, C/T and T/T genotypes. It was determined that among the patients, patients with С/С predominated, in whom the concentration of HIF-1á was lower than in the group with С/T. Mortality among patients with the C/C genotype and severe AP was 47%. In the group with the C/T genotype, all patients were discharged, including those with severe AP. A relationship was found between HIF-1á blood levels and the marker of tissue damage S100, mixed hypoxia – lactate, and acid-base state – pHt. The results allow us to consider HIF-1A genotypes as potential predictors of the severity of AP.

Changes in cytokine profile as a criterion for severity prediction of skin toxicity in cancer patients receiving epidermal growth factor receptor inhibitors

BACKGROUND: Globally, colorectal cancer is the third most diagnosed cancer with an increased incidence of 1.93 million cases in 2020 according to World Health Organization. Approximately one quarter of the initial manifestations of colorectal cancer are metastatic, and 40–50% of individuals with early-stage disease eventually develop metastatic colorectal cancer (mCRC). Targeted drugs, which include epidermal growth factor receptor inhibitors (EGFRi), are a frequent choice in the therapy of metastatic colorectal cancer. Clinical observations and in vivo studies have established a significant association between the administration of EGFRi drugs and skin inflammation, particularly acute in the first 3 months. However, the role of proinflammatory cytokines in the formation of severe skin lesions has not been definitively studied. Here we present clinical evidence of the involvement of a few cytokines in the formation of the pathologic cascade of reactions during EGFR blockade on keratinocyte membranes. AIM: Evaluation of changes in cytokine profile parameters based on the MILLIPLEX Analyte MAP panel to identify predictors of the severity of unwanted skin toxicity associated with epidermal growth factor receptor inhibition. MATERIALS AND METHODS: Blood serum samples from 81 patients aged 18–80 years who were taking EGFRi for oncologic disease and had adverse dermatologic reactions of severity 2 or more were analyzed. The data were analyzed using SPSS software and R 4.3.1 programming language and tidyverse, rstatix packages. Detected changes with p 0.05 were analyzed considering subgroup analysis on the basis of selected cutaneous toxicity severity degrees based on the criteria developed by the US National Cancer Institute NCI-CTC v. 4. RESULTS: Blocking of EGF receptor inhibits the expression and release of vascular endothelial growth factor (VEGF), which is the main inducer of vascular proliferation, the consequence of which is inflammation of vascular endothelium of skin capillaries. Significant increase of IFN-γ and decrease of IFN-α2 level was found in patients with manifestations of skin toxicity of 2 and more severity degree. Also, a significant criterion of severity of the skin process was an increase in the level of TNF-α. At such dissociation there is induction of STING protein (interferon gene stimulator) and increase of TNF-β production that, in its turn, leads to increase of concentration of proinflammatory cytokines G-CSF, GM-CSF, IFN-α2, IFN-γ, IL-15, IL-17A, IL-1β, IL-3, IL-6, IL-8, IP-10, TNF-α, TGF-α, IL-9. This contributes not only to the maintenance of tissue inflammation, but also to the formation of a vicious circle leading to an increase in the severity of class-mediated inflammatory response against the background of further EGFRi administration. CONCLUSION: Determination of predictors of severity of adverse dermatologic reactions is extremely important for predicting the development of severity and further personalized tactics for correction of adverse events.

Biomarkers of COVID-19 short-term worsening: a multiparameter analysis within the prospective multicenter COVIDeF cohort.

During a pandemic like COVID-19, hospital resources are constrained and accurate severity triage of the patients is required. The objective of this study is to estimate the predictive performances of candidate biomarkers for short-term worsening (STW) of COVID-19. Prospective, multicenter (20 hospitals in Paris) cohort study of consecutive COVID-19 patients with systematic biobanking at admission, during the first waves of COVID-19 in France in 2020 (COVIDeF cohort). Consecutive COVID-19 patients were screened for inclusion. They were excluded in presence of severity criteria defined by either an ICU admission, mechanical ventilation (including noninvasive ventilation), acute respiratory distress, or in-hospital death before sampling. Routine blood tests measured during usual care and centralized systematic measurement of creatine kinase, C-reactive protein (CRP), procalcitonin, soluble urokinase plasminogen activator receptor (suPAR), high-sensitive troponin T (TnT-hs), N terminal pro-B natriuretic peptide (NT-proBNP), calprotectin, platelet factor 4, mid-regional pro-adrenomedullin (MR-proADM), and proendothelin were performed. The primary outcome was STW, defined by a severity criteria within 7 days. A backward stepwise logistic regression model and a 'best subset' approach were used to identify independent association, and the area under the receiving operator characteristics (AUROC) was computed. Five hundred and eleven patients were analyzed, of whom 60 (11.7%) experienced STW. Median time to occurrence of a severity criteria was 3 days. At admission, lower values of eosinophils, lymphocytes, platelets, alanine aminotransferase, and higher values of neutrophils, creatinine, urea, CRP, TnT-hs, suPAR, NT-proBNP, calprotectin, procalcitonin, MR-proADM, and proendothelin were predictive of worsening. Stepwise logistic regression identified three biomarkers significantly associated with worsening: CRP [adjusted odds ratio (aOR): 1.10, 95% confidence interval (95% CI): 1.06-1.15 for a 10-unit increase, AUROC: 0.73 (0.66-0.79)], procalcitonin [aOR: 0.42, 95% CI: 0.22-0.81, AUROC: 0.69 (0.64-0.88)], and MR-proADM [aOR: 2.85, 95% CI: 1.74-4.69, AUROC: 0.75 (0.69-0.81)]. These biomarkers outperformed clinical variables except diabetes and cancer comorbidities. In this multicenter prospective study that assessed a large panel of biomarkers for COVID-19 patients, CRP, procalcitonin, and MR-proADM were independently associated with the risk of STW. ClinicalTrials.gov NCT04352348.

Neuropsychiatric manifestations of hospitalized patients with coronavirus disease 2019 during the second wave in Egypt

BackgroundStudies suggested that COVID-19 virus causes neurological and psychiatric manifestations with different mechanisms. However, prevalence of neurological and psychiatric manifestations among COVID-19 patients varies across studies from 18.1%: 82.3%. The objective of this study was to determine neuropsychiatric manifestations in a sample of Egyptian COVID-19 hospitalized patients during the second wave of the pandemic and to detect factors affecting neurological and psychiatric prevalence. This cross-sectional study was conducted at Ain Shams university isolation hospitals and included 110 hospitalized COVID-19 patients, over a 2-month period from June 2021 to August 2021. Patients underwent a careful history taking, full neurological examination including Mini-Mental State Examination, the Structured Clinical Interview for DSM-IV (SCID I), COVID-19 severity criteria. Any available imaging and laboratory tests were recorded.Results83 (75.5%) patients had neurological manifestations. The most common neurological manifestations were headache (50.9%), hypogeusia (24.5%), hyposmia, paresthesia (23.6% each) and coma (15.5%). After exclusion of 17 patients who could not be examined by Mini-Mental State Examination, psychiatric manifestations were seen in 56 patients (61.5%) out of the remaining 91 patients. The most prevalent psychiatric disorders were delirium (30.8%), depression (19%), and adjustment disorder (17.5%). Moreover, hypertension, COVID-19 severity, place of admission, and high levels of LDH and ALT affected neurological manifestations prevalence.ConclusionsCOVID-19 infection and its immune reaction along with its social and psychological effects have a great impact on mental and physical health. Hence, neuropsychiatric evaluation cannot be ignored in any case with COVID-19 infection.

Effets du programme d'aide au retour à domicile (PRADO-IC) sur le parcours de soins à un an d'une population de patients insuffisants cardiaques

IntroductionCongestive heart failure (HF) is associated with prolonged and recurrent hospitalizations; the prognosis remains poor a better follow up might be beneficial. PRADO-IC program is provided in order to improve the transition of care. Aim of the studyTo evaluate PRADO-IC program in term of healthcare consumption and prognosis in a cohort of patients hospitalized for decompensated HF, using the insight of the national data base SNDS (Système National de Données de Santé). MethodsFrom September 2016 to September 2018, all patients hospitalized for heart failure at Saint-Joseph Hospital were included in an observational study. The inclusion in the PRADO-IC program was at physician's discretion. Two groups were compared according to the inclusion in PRADO-IC (P group) or not (control group (C)). The primary endpoints were the comparison of one-year mortality and heart failure readmission rate between the two groups. The secondary end points were time to the first contact with a general practitioner (GP), a cardiologist, CHF drugs prescription, and others follow up data. ResultsSix hundred and fifteen patients were included, 254 in the P group and 361 in the C group. Patients in the P cohort presented more frequently severity criteria (age, weight, BNP level, arrhythmia, anemia, renal failure). Mortality at one year (n = 47; 18.5% P group vs. n = 65; 16.2% C group, p = 0.87) did not differ in both groups. There was no significant difference in one-year re-hospitalization rate for HF (n = 93, 36.6% in P group vs. n = 133, 26.8% in C group, p = 0.95). Time to the first contact with the GP was shorter in P group (8.00 vs. 18.50 days, p < 0.0001). Time to first hospitalization (69.0 vs. 37.0 days, p = 0.028) and the length of hospitalization (6.0 vs. 4.0 days, p = 0.045) were longer in P group. There was no difference for HF drugs prescription rate between the two groups. ConclusionOur study shows that the PRADO-IC program concerned more severe patients. Despite this, the one-year mortality and the HF readmission rates are similar between the two groups. The follow up is improved in P group.

Homoeopathic Management of Acute Cholangitis in a Case of Adenocarcinoma of Gall Bladder with Metastasis: A Case Report

AbstractAcute cholangitis is a bacterial infection superimposed on an obstruction of biliary tree from a gall stone, neoplasm or stricture. The biliary obstruction is most commonly caused by choledocholithiasis benign or malignant stricture of the bile duct or hepatic ducts, pancreatic cancer, ampullary adenoma or cancer, porta hepatis tumour or metastasis, biliary stent obstruction (due to microbial biofilm formation, biliary sludge deposition and duodenal reflux of food content), primary sclerosing cholangitis and amyloid deposition in the biliary system. Classically, patients present with high fever persisting for more than 24 hours, abdominal pain and jaundice (Charcot's triad). The right upper quadrant abdominal (RUQ) pain is generally mild. When the cholangitis becomes more severe, patients become hypotensive and confused (Reynold's pentad). Charcot's triad has low sensitivity (26.4%) and high specificity (95.9%). Although the presence of Charcot's triad is suggestive of acute cholangitis, it is not diagnostic. Charcot's triad is present in 26.4 to 72% of patients with acute cholangitis. TG07 diagnostic criteria for acute cholangitis also do not have enough sensitivity and specificity and its severity criteria are also not suitable for clinical use. Antibiotics, intravenous fluid, Vitamin K supplementation and biliary drainage are the options available in conventional mode of treatment for acute cholangitis. Presented here is one case report of acute cholangitis in a patient of adenocarcinoma of gall bladder with metastasis. The case was treated using classical method of homoeopathy with complete improvement in clinical and laboratory parameters of acute cholangitis.