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Background: COVID-19 is a major global health challenge that has affected all age groups and gender, with over 5 million deaths reported worldwide to date. The objective of this study is to assess available information on COVID-19 in children and adolescents with respect to clinical characteristics, co-morbidities, and outcomes, and identify gaps in the literatures for appropriate actions. Methodology: Electronic databases including Web of Science, PubMed, Scopus, and Google Scholar were searched for observational studies such as case series, cross-sectional and cohort studies published from December 2019 to September 2021, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guide. Data extracted included (i) patient demography (age and gender), (ii) clinical characteristics including vaccination status and presence of co-morbidities, (iii) clinical management including the use of sequential organ failure assessment (SOFA) scores, oxygen requirement, use of mechanical ventilation, and (iv) disease outcomes including length of hospital and intensive care unit (ICU) admission, recovery, complications with sequelae, or death. Data were analyzed using descriptive statistics. Results: A total of 11 eligible studies were included with a total of 266 children and adolescents; 137 (51.5%) females and 129 (48.5%) males. The mean age of the children was 9.8 years (range of 0 - 19 years), and children ≥ 6 years were more affected (40.7%) than age groups 1 - 5 years (31.9%) and < 1 year (27.4%). The major co-morbidities were respiratory diseases including pre-existing asthma (3.4%), neurologic conditions (3.4%) and cardiac pathology (2.3%). Majority (74.8%, 199/266) of the patients were discharged without sequelae, 0.8% (2/266) were discharged with sequalae from one study, and mortality of 1.9% (5/266) was reported, also from one study. SOFA scores of patients at admission were not stated in any of the study, while only one study reported patient vaccination status. Conclusion: It is recommended that safe vaccines for children < 1 year of age should be developed in addition to other preventive measures currently in place. SOFA scores should be used to assess risk of COVID-19 severity and monitor prognosis of the disease, and vaccination status of children should be documented as this may impact the management and prognosis of the disease. Contexte: Le COVID-19 est un défi sanitaire mondial majeur qui a touché tous les groupes d'âge et tous les sexes, avec plus de 5 millions de décès signalés dans le monde à ce jour. L'objectif de cette étude est d'évaluer les informations disponibles sur le COVID-19 chez les enfants et les adolescents en ce qui concerne les caractéristiques cliniques, les comorbidités et les résultats, et d'identifier les lacunes dans la littérature pour des actions appropriées. Méthodologie: Des bases de données électroniques, notamment Web of Science, PubMed, Scopus et Google Scholar, ont été recherchées pour des études d'observation telles que des séries de cas, des études transversales et de cohorte publiées de décembre 2019 à septembre 2021, en utilisant les éléments de rapport préférés pour les revues systématiques et les méta -Guide des analyses (PRISMA). Les données extraites comprenaient (i) la démographie des patients (âge et sexe), (ii) les caractéristiques cliniques, y compris le statut vaccinal et la présence de comorbidités, (iii) la prise en charge clinique, y compris l'utilisation des scores d'évaluation séquentielle des défaillances d'organes (SOFA), les besoins en oxygène, l'utilisation de la ventilation mécanique et (iv) les résultats de la maladie, y compris la durée de l'admission à l'hôpital et en unité de soins intensifs (USI), la récupération, les complications avec séquelles ou le décès. Les données ont été analysées à l'aide de statistiques descriptives. Résultats: Un total de 11 études éligibles ont été incluses avec un total de 266 enfants et adolescents ; 137 (51,5%) femmes et 129 (48,5%) hommes. L'âge moyen des enfants était de 9,8 ans (intervalle de 0 à 19 ans), et les enfants ≥ 6 ans étaient plus touchés (40,7%) que les tranches d'âge 1-5 ans (31,9%) et < 1 an (27,4%). Les principales comorbidités étaient les maladies respiratoires, y compris l'asthme préexistant (3,4%), les troubles neurologiques (3,4 %) et la pathologie cardiaque (2,3%). La majorité (74,8%, 199/266) des patients sont sortis sans séquelles, 0,8% (2/266) sont sortis avec des séquelles d'une étude et une mortalité de 1,9% (5/266) a été rapportée, également d'une étude. Les scores SOFA des patients à l'admission n'ont été indiqués dans aucune des études, tandis qu'une seule étude a rapporté le statut vaccinal des patients. Conclusion: Il est recommandé que des vaccins sûrs pour les enfants de < 1 an soient développés en plus des autres mesures préventives actuellement en place. Les scores SOFA doivent être utilisés pour évaluer le risque de gravité du COVID-19 et surveiller le pronostic de la maladie, et le statut vaccinal des enfants doit être documenté car cela peut avoir un impact sur la gestion et le pronostic de la maladie.

Alphaherpesviruses, as large double-stranded DNA viruses, were long considered to be genetically stable and to exist in a homogeneous state. Recently, the proliferation of high-throughput sequencing (HTS) and bioinformatics analysis has expanded our understanding of herpesvirus genomes and the variations found therein. Recent data indicate that herpesviruses exist as diverse populations, both in culture and in vivo, in a manner reminiscent of RNA viruses. In this chapter, we discuss the past, present, and potential future of alphaherpesvirus genomics, including the technical challenges that face the field. We also review how recent data has enabled genome-wide comparisons of sequence diversity, recombination, allele frequency, and selective pressures, including those introduced by cell culture. While we focus on the human alphaherpesviruses, we draw key insights from related veterinary species and from the beta- and gamma- subfamilies of herpesviruses. Promising technologies and potential future directions for herpesvirus genomics are highlighted as well, including the potential to link viral genetic differences to phenotypic and disease outcomes.

BACKGROUND Enzyme replacement therapy significantly reduces morbidity and mortality in patients with Pompe disease. Development of hypersensitivity reactions to enzyme replacement therapy is common and can adversely affect disease outcomes when treatment is halted or delayed. OBJECTIVE Our institution reports a case of successful alglucosidase alfa enzyme replacement therapy desensitisation in a 9-year-old girl with infantile onset Pompe disease. METHODS A desensitisation protocol was tailored to our patient with the help of a multidisciplinary team including the allergist, geneticist, nurses and pharmacists. RESULTS For our patient, desensitisation was successful using a multi-step three-fold dose escalation protocol. CONCLUSION Desensitisation is possible in individuals with hypersensitivity reactions to enzyme replacement. Desensitisation protocols need to be tailored according to the patient's needs and responses to find a protocol that is safe, effective and simple.

Elevated red blood cell distribution width (RDW) is a powerful predictor of poor prognosis in a variety of diseases, but a single measurement of RDW cannot reflect the dynamic change of diseases. ΔRDW, as a risk stratification tool, can be used to record changes in RDW before and after treatment; also, it allows investigators to name the unit change of RDW in the studied population. So far, there have been few relevant studies on the predictive value of ΔRDW for different diseases; this article aims to review the studies and summaries of the current understandings on the correlation between ΔRDW and disease outcomes.

People in different age groups are susceptible to SARS-CoV-2 infection as a newly emerging virus. However, the clinical course, symptoms and disease outcome vary from case to case. Although COVID-19 is usually milder in children than adults, some studies reported nonspecific symptoms. Here, we report eight pediatric cases of COVID-19 admitted in the Taleghani Children Hospital in Gorgan city, north of Iran, with complicated symptoms. The current case series poses several challenges to the pediatricians regarding the pediatric cases of COVID-19. As most literature relating to adults are not always transferable to children, clinicians should be warned about such presentations among children with COVID-19.

The combination of hepatitis B immunoglobulin and potent nucleos(t)ide analogs after liver transplantation is considered as the standard of care for prophylaxis against hepatitis B virus recurrence. However, the recommended doses, route of administration, and duration of HBIG administration remain unclear. Moreover, hepatitis B immunoglobulin-free prophylaxis with potent nucleos(t)ide analogs has shown promising disease outcomes in preventing hepatitis B virus recurrence. The current recommendations, produced by the Turkish Association for the Study of the Liver, Acute Liver Failure and Liver Transplantation Special Interest Group, suggest a reduced need for hepatitis B immunoglobulin administration with effective long-term suppression of hepatitis B virus replication using potent nucleos(t) ide analogs after liver transplantation.

PURPOSE OF REVIEW: Both social and genetic factors are associated with health outcomes in systemic lupus erythematosus (SLE), thus playing a role in its health disparities. Despite the growing list of social and genetic factors associated with SLE outcomes, studies integrating sociocultural and individual determinants of health to understand health disparities in SLE are lacking. We review the contributions of different social and genetic factors to the disparities in SLE, and propose a socioecological model to integrate and examine the complex interactions between individual and social factors in SLE outcomes. RECENT FINDINGS: Multiple studies collecting comprehensive social data and biospecimens from diverse populations are underway, which will contribute to the elucidation of the interplay and underlying mechanisms by which positive and negative social determinants of health influence epigenomic variation, and how the resulting biological changes may contribute to the lupus health disparities. SUMMARY: There is growing awareness of the need to integrate genomic and health disparities research to understand how social exposures affect disease outcomes. Understanding the contributions of these factors to the SLE health disparity will inform the development of interventions to eliminate risk exposures and close the health disparity gap.

Objective To present a developmental framework of family conflict in youth with type 1 diabetes (T1D) that aims to guide future research. Methods Developmental and pediatric literature are reviewed to highlight family factors that may modify the degree to which diabetes-related family conflict is related to adolescent health outcomes. Results Developmental literature suggests that family conflict is not inherently bad; rather, conflict that arises under optimal conditions (moderate frequency, warm and accepting relationships) can be adaptive for adolescents. However, family conflict is consistently associated with poor disease outcomes in youth with T1D, with few researchers examining specific moderators of these associations. In this topical review, we highlight moderators of family conflict and developmental outcomes identified in adolescents without chronic illness (e.g., cultural factors, parent–child relationship quality, conflict characteristics) and how these moderators may operate for a pediatric chronic illness such as T1D. Conclusions Incorporating conceptualizations of family conflict from mainstream developmental research has important implications for future research and intervention adaptations on family conflict in pediatric populations.

The COVID 19 pandemic has infected more than 19.4 crore persons in the world and 3 crores in India. It has killed more than 41 lakhs in the world and 4 lakhs in India (as on 24/7/2021). SARS COV-2 RNA virus (of beta genera) is mainly transmitted by droplets and aerosols and infects others by inhalation through the nose and mouth. The spike protein of the virus gets attached to ACE 2 receptors in the nasal mucosa and oral cavity and in about 20% cases may reach the lungs. Cytokine storm and vascular thrombosis are the main pathogenic mechanisms, which cause serious illness. The endothelium is inamed and damaged either directly by the virus or by host immune mechanism. This endothelial dysfunction causes a pro-coagulant state. D dimer is a brin degradation product. Studies have shown that serious cases of COVID have signicantly raised D dimer levels. The values vary a little from laboratory to laboratory and the normal cut-off level of a given laboratory should be considered. This study was aimed to correlate the levels of D dimer with outcomes (survival or death). The clinical feature and laboratory parameters of 300 (150 survivors and 150 deaths) conrmed COVID 19 cases were studied, and chi square test was applied to the levels of D dimer with the outcomes. It is observed that levels of D dimer at admission that were above 350 nanograms per ml (0.35 micrograms per ml) were signicantly associated with poor outcomes

The 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.To validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.Four experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.Among the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.The ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.

The role of type 2 inflammation in the pathogenesis of certain human diseases is an area of active investigation. Certain asthma, atopic dermatitis, eosinophilic esophagitis, and chronic rhinosinusitis phenotypes are characterized by a Th2 predominant inflammatory pathway and are frequently associated with comorbid conditions in patients. The purpose of this article is to review the evidence behind concurrent Th2-mediated diseases and explore how the presence of these comorbid conditions affect patient and disease outcomes.

Despite the popularity and utility of most machine learning techniques, expert knowledge is required in guiding choices about the suitable technique and settings that are good for solving a specific problem. The lack of expert information renders the procedures vulnerable to poor parameter settings. Several of these machine learning techniques configurations are offered under default settings. However, since different classification problems required suitable machine learning techniques, selecting the appropriate technique and tuning its settings are vital works that will rightly improve predictions in terms of reliability and accuracy. This study aims to perform grid search parameters tuning on 5-selected machine learning techniques on hepatitis disease. Comparative performance is drawn side-by-side with the default settings. The experimental results of the five tuning techniques show that using the configurations suggested in our work yield predictions of a greatly sophisticated quality than choice under its default settings. The result proves that tuning parameters of Support Vector Machine via grid search yields the best accuracy outcomes of 90% and has a competitive performance relative towards criteria of precision, recall, accuracy and Area Under the Curve. Present combinations of parameter settings for each of the techniques by identifying ranges of values for each setting that give good Hepatitis disease outcomes

Social factors have been linked to disease severity and mortality in COVID-19. These social factors are ethnicity, social disadvantage, age, gender and occupation. Pre-existing medical conditions have also been identified as an increasing risk. This paper explores the relationship between these social and biological factors using a syndemic frame of reference. The paper argues that although the associations have been very well documented, the mechanisms linking the social factors and disease outcomes are not well understood. An approach that seeks to find commensurability between the social and the biological, is suggested.

Introduction: Inflammatory bowel diseases (IBDs) are lifelong conditions causing relapsing inflammation of the intestine. In the absence of a cure, clinical management of IBDs is extremely challeng...

Cellular senescence is a critical part of human anti-tumor defence; however, the accumulation of senescent cells with age underpins a wide range of pathologies. Senescent change in immune cells, or immunosenescence, has a wide range of physiological effects and is at least partially responsible for many diseases associated with aging. Immunosenescence underpins inflammaging, increased vulnerability to infectious disease with age, malignant change in the elderly, and auto-immunity. Understanding the effects and mechanisms of immunosenescence will improve disease outcomes and prevention in older adults, and generate new treatments for common illnesses. In this review we summarize the key changes occurring in immunosenescence across each facet of the immune system, and identify their clinical correlates.

Summary Myeloid-derived suppressor cells (MDSCs) are one of the most discussed biological entities in immunology. While the context and classification of this group of cells has evolved, MDSCs most commonly describe cells arising during chronic inflammation, especially late-stage cancers, and are defined by their T cell immunosuppressive functions. This MDSC concept has helped explain myeloid phenomena associated with disease outcome, but currently lacks clear definitions and a unifying framework across pathologies. Here, we propose such a framework to classify MDSCs as discrete cell states based on activation signals in myeloid populations leading to suppressive modes characterized by specific, measurable effects. Developing this level of knowledge of myeloid states across pathological conditions may ultimately transform how disparate diseases are grouped and treated.

Background: There are limited data on the unique cardiovascular disease (CVD), non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC; ≥1000), especially compared with rates observed in secondary prevention populations. Methods: Our study population consisted of 6814 ethnically diverse individuals 45 to 84 years of age who were free of known CVD from MESA (Multi-Ethnic Study of Atherosclerosis), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC ≥1000 were compared with both CAC 0 and CAC 400 to 999 for CVD, non-CVD, and mortality outcomes with the use of Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC and compared them with those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Results: Compared with CAC 400 to 999, those with CAC ≥1000 (n=257) had a greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm 2 ), similar CAC density, and more extensive extracoronary calcification. After full adjustment, CAC ≥1000 demonstrated a 4.71- (3.63–6.11), 7.57- (5.50–10.42), 4.86-(3.32–7.11), and 1.94-fold (1.57–2.41) increased risk for all CVD events, all coronary heart disease events, hard coronary heart disease events, and all-cause mortality, respectively, compared with CAC 0 and a 1.65- (1.25–2.16), 1.66- (1.22–2.25), 1.51- (1.03–2.23), and 1.34-fold (1.05–1.71) increased risk compared with CAC 400 to 999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC ≥1000 was associated with a 1.95- (1.57–2.41) and 1.43-fold (1.12–1.83) increased risk for a first non-CVD event compared with CAC 0 and CAC 400 to 999, respectively. CAC 1000 corresponded to an annualized 3-point major adverse cardiovascular event rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3) and higher than those of the lower-risk FOURIER subgroups. Conclusions: Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, with 3-point major adverse cardiovascular event rates similar to those of a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary and secondary prevention patients in guiding aggressive preventive pharmacotherapy.

Background Susac's syndrome, a rare autoimmune vasculo-occlusive disease, may pose a diagnostic challenge and result in a devastating ocular and systemic outcome. Our study identifies a new retinal finding and evaluates disease outcome. We aimed to assess clinical and imaging findings, systemic manifestations and disease outcome in patients with ocular Susac's syndrome under immunosuppressive/immunomodulation therapies. Methods Retrospective tertiary center study including patients with a diagnosis of Susac's syndrome with >12 months follow up. Medical record review including ocular, neurological and auditory clinical and imaging findings, and treatment modalities. Main outcome measures were clinical manifestations and disease outcome. Results Seven patients (14 eyes) with a mean age of 34.1 years were included. Mean follow-up was 31.9 months (12.4-72.4). All had bilateral ocular disease. Retinal microaneurysms, a new ocular finding, were demonstrated in 5 patients and persisted at the final visit. In 5 eyes, they further extended during follow-up. All were treated with immunosuppressive drugs and 5/7 additional immunomodulation therapy. At last examination, best corrected visual acuity was >20/40 in all eyes, 1/10 eyes had visual field deterioration, no eye had active ocular disease, all patients achieved neurological stability, and 1 patient had auditory deterioration. Conclusion Retinal microaneurysms, a new ocular finding in Susac's syndrome, were present in most of our patients, indicating ischemic retinal damage. Immunosuppressive and immunomodulation therapies seem to be highly effective in the control of disease activity.

The aim was to analyze spectrum of comorbid pathology and age structure of oxygen-dependent patients with severe coronavirus disease 2019 (COVID-19) depending on outcomes of the disease. Materials and methods. The study included 85 oxygen-dependent patients with severe COVID-19. The patients were divided into groups: I – 70 patients with recovery; II – 15 patients in whom the disease was fatal. Statistical data processing was performed in the program Statistica for Windows 13 (StatSoft Inc., No. JPZ804I382130ARCN10-J). Results. Among the patients with fatal outcomes of the disease, elderly and senile were dominated – 93.3 % (14 of 15) versus 67.1 % (47 of 70) among patients who recovered (P < 0.05). Analysis of comorbid pathology structure in oxygen-dependent patients with severe COVID-19 showed that patients who died more often had hypertension (93.3 % vs. 30.0 %, P < 0.001), postinfarction cardiosclerosis (26.7 % vs. 2.9 %, P < 0.001), rhythm disturbance as persistent atrial fibrillation (20.0 % vs. 1.4 %, P < 0.01) as compared to those who survived. The patients of group II were more commonly diagnosed with chronic kidney disease (20.0 % vs. 4.3 %, P < 0.05) as the comorbid pathology. The presence of ischemic stroke in COVID-19 infection influenced the disease outcome (20.0 % vs. 4.3 %, P < 0.05). Fatal outcomes in the patients with COVID-19 were associated with a combination of 3 or more comorbid conditions in 46.7 % versus 17.4 % among oxygen-dependent survivors with severe disease (P < 0.01). Conclusions. Elderly and senile oxygen-dependent patients are more likely to die from severe COVID-19 (P < 0.05). Comorbid hypertension, postinfarction cardiosclerosis, arrhythmia in the form of persistent atrial fibrillation, chronic kidney disease and ischemic stroke or the combination of 3 or more comorbid conditions listed are more common among patients with COVID-19 who died (P < 0.05) as compared to survivors.

Measuring quality of care (QoC) from a patient’s perspective is becoming increasingly important in inflammatory bowel disease. The objective of this study was to determine whether patients’ evaluations of QoC correlate with better inflammatory bowel disease outcomes. A survey including patients’ characteristics, a decalogue of QoC indicators, and self-reported disease outcomes was completed by Spanish patients with inflammatory bowel disease. A QoC index (QoCI) was constructed with the sum of the “yes” answers in the decalogue. We evaluated the correlation of QoCI with outcomes. A sub-analysis comparing patients with high QoCI vs those with low QoCI was performed (QoCI = 10 or ≤ 7). Seven hundred and eighty-eight questionnaires were analyzed. Mean age of participants was 43.4 years (63% women). Mean QoCI was 8.1 (± 2.4). The QoCI correlated significantly with activity of the disease, number of flares, emergency/unscheduled visits, and disease control. Patients scoring in the first QoCI quartile reported a decreased rate of moderate/severe disease (34.8% vs 55.3%, p < 0.001), fewer numbers of flares (p < 0.001), and fewer emergency/unscheduled visits (p < 0.001) compared with those in the lower QoCI quartile. The high QoC group also reported better disease control. Patient-evaluated QoC correlates with better outcomes. Evaluation of QoC by patients may be useful to detect inadequate care and improve inflammatory bowel disease outcomes.

A generalized goal of many high-throughput data studies is to identify functional mechanisms that underlie observed biological phenomena, whether they be disease outcomes or metabolic output. Increasingly, studies that rely on multiple sources of high-throughput data (genomic, transcriptomic, proteomic, metabolomic) are faced with a challenge of summarizing the data to generate testable hypotheses. However, this requires a time-consuming process to evaluate numerous statistical methods across numerous data sources. Here, we introduce the leapR package, a framework to rapidly assess biological pathway activity using diverse statistical tests and data sources, allowing facile integration of multisource data. The leapR package with a user manual and example workflow is available for download from GitHub (https://github.com/biodataganache/leapR).

One of the biggest challenges of utilizing artificial intelligence (AI) in medicine is that physicians are reluctant to trust and adopt something that they do not fully understand and regarded as a "black box." Machine Learning (ML) can assist in reading radiological, endoscopic and histological pictures, suggesting diagnosis and predict disease outcome, and even recommending therapy and surgical decisions. However, clinical adoption of these AI tools has been slow because of a lack of trust. Besides clinician's doubt, patients lacking confidence with AI-powered technologies also hamper development. While they may accept the reality that human errors can occur, little tolerance of machine error is anticipated. In order to implement AI medicine successfully, interpretability of ML algorithm needs to improve. Opening the black box in AI medicine needs to take a stepwise approach. Small steps of biological explanation and clinical experience in ML algorithm can help to build trust and acceptance. AI software developers will have to clearly demonstrate that when the ML technologies are integrated into the clinical decision-making process, they can actually help to improve clinical outcome. Enhancing interpretability of ML algorithm is a crucial step in adopting AI in medicine.

Melioidosis is an emerging infectious disease with an estimated global burden of 4.64 million disability-adjusted life years per year. A major determinant related to poor disease outcomes is delay to diagnosis due to the fact that identification of the causative agent Burkholderia pseudomallei may be challenging. Over the last 25 years, advances in molecular diagnostic techniques have resulted in the potential for rapid and accurate organism detection and identification direct from clinical samples. While these methods are not yet routine in clinical practice, laboratory diagnosis of infectious diseases is transitioning to culture-independent techniques. This review article aims to evaluate molecular methods for melioidosis diagnosis direct from clinical samples and discuss current and future utility and limitations.

Introduction: The successful development of anti-inflammatory disease-modifying treatments (DMT) significantly improved disease outcomes and longevity of persons with multiple sclerosis (pwMS). How...

Background: The initial years of child nurturing plays an important role in child development and lifelong learning. Parents’ knowledge is considered to be the frame of reference for parents’ interpretations of their child’s behaviour and provides the basis for having the appropriate expectation of the child’s developmental stage. When developmental delays are identified at the appropriate time, it increases the scope to initiate early intervention. Early intervention in children with developmental delay, can not only improve the overall disease outcome but also it provides support to family members. Aim: To assess the caregivers’ knowledge about child development and to study the association between caregivers’ knowledge and sociodemographic parameters. Materials and Methods: 110 Caregivers of children presenting to the child psychiatry OPD were screened for assessment criteria. A semi-structured intake proforma was administered to collect the sociodemographic details. Caregiver knowledge of child developmental inventory was applied on caregivers to garner the responses. Results: 84% of caregivers were mothers. On an average, caregivers were able to answer only 36% of the questions correctly. Maternal age (p=0.048) and maternal education (p=0.009) were identified to be significant predictors of higher CKCDI scores. Conclusion: Caregiver’s knowledge regarding the child development is low. Younger mothers mother and higher maternal education are associated with higher knowledge about the development of their children. Keywords: Child development, Caregiver’s knowledge.

The deoxyhexose sugar L-fucose is important for many biological processes within the human body and the associated microbiota. This carbohydrate is abundant in host gut mucosal surfaces, numerous microbial cell surface structures, and some dietary carbohydrates. Fucosylated oligosaccharides facilitate the establishment of a healthy microbiota and provide protection from infection. However, there are instances where pathogens can also exploit these fucosylated structures to cause infection. Furthermore, deficiencies in host fucosylation are associated with specific disease outcomes. This review focuses on our current understanding of the impact of fucosylation within the mucosal environment of the gastrointestinal tract with a specific emphasis on the mediatory effects in host-microbe interactions.

To analyze the sex-based differences in the prevalence of cardiovascular disease risk factors and outcomes in older patients with prediabetes using demographically matched national cohorts of hospitalized patients aged ≥65 years.We queried the 2007-2014 National Inpatient Database to identify older patients (65 years) admitted with prediabetes using ICD-9 Clinical Modification codes. The older patients were then subcategorized based on sex. Comparative analyses of their baseline characteristics, the prevalence of cardiovascular(CV) disease comorbidities, hospitalization outcomes, and mortality rates were performed on propensity-matched cohorts for demographics.A total of 1,197,978 older patients with prediabetes (599,223 males; mean age 75years and 598,755 females; mean age 76years) were identified. Higher admission rates were found commonly among older white males (84.1%) and females (81.7%). Prediabetic older males showed a higher frequency of cardiovascular comorbidities compared to females. Prediabetic older males had higher all-cause in-hospital mortality (4.2% vs. 3.6%, p0.001), acute myocardial infarction (7.0% vs. 4.7%, p0.001), arrhythmia (36.3% vs. 30.5%, p0.001), stroke (4.8% vs. 4.6%, p0.001), venous thromboembolism (3.3% vs. 3.0%, p0.001) and percutaneous coronary intervention (3.1% vs. 1.5%, p0.001) compared to females.Our analysis revealed that among older patients hospitalized with prediabetes, males suffered worse in-hospital CV outcomes and survival rates compared to females.

SARS-CoV-2 has been the causative pathogen of the pandemic of COVID-19, resulting in catastrophic health issues globally. It is important to develop human-like animal models for investigating the mechanisms that SARS-CoV-2 uses to infect humans and cause COVID-19. Several studies demonstrated that the non-human primate (NHP) is permissive for SARS-CoV-2 infection to cause typical clinical symptoms including fever, cough, breathing difficulty, and other diagnostic abnormalities such as immunopathogenesis and hyperplastic lesions in the lung. These NHP models have been used for investigating the potential infection route and host immune response to SARS-CoV-2, as well as testing vaccines and drugs. This review aims to summarize the benefits and caveats of NHP models currently available for SARS-CoV-2, and to discuss key topics including model optimization, extended application, and clinical translation.

The models for the prognosis of infectious complications and the outcome of acute pancreatitis are developed based on a mathematical analysis of the totality of clinical and laboratory data on the course of the disease, which have the form of a decision tree. It was revealed that laboratory indicators show statistically significant intergroup differences and allow to form a prognosis of the course of the disease. The threshold values of laboratory parameters calculated as a result of applying the classification and regression algorithm by constructing a decision tree are the nodal points for the distribution of patients according to the likelihood of further development of the disease. Thus, the presence of an international normalized ratio of more than 1,31 or an international normalized ratio of more than 1,31 and a hematocrit of less than 40% with a predictive probability of 80% is associated with the development of infectious complications in any period of the disease in the first 3 days of the development of the disease. If in the first 3 days of the disease the glucose level exceeds 11,55 mmol / L and the concentration of Ca2+ ions is less than 0,66 mmol/L, the probability of death is more than 70%. If the glucose level is more than 11,5 mmol/L and the level of Ca2+ ions is less than or equal to 0,66 mmol / L, or the glucose level is less than or equal to 11,5 mmol/L and the prothrombin index is less than or 83% and the hematocrit is less than or equal to 39,8% the probability of developing a fatal outcome at any period of the disease is 3 times higher compared to other patients. Prediction models of infectious complications and disease outcome have an accuracy of 78 and 87%, respectively. The use of these models allows stratification of patients upon admission to the hospital, highlighting the most disadvantaged patients in the prognostic plan. The models are quite simple and easy to use, do not require complex expensive studies. Thanks to the algorithm used in building models, they have the properties of self-learning, which in the future will increase their accuracy.

The outcome in a chronic critical illness (CCI) after cerebral catastrophes occurs in 5-10% of patients in intensive care units and is accompanied by severe homeostasis disorders with a likely outcome in multiple organ failure. In this aspect there is a need for a deep study of the pathogenesis of a CCI with the identification of the most significant outcome criteria Purpose of the study: To reveal the prognostic in formativeness of functional activity and serum albumin concentration in patients in a CCI with different disease outcomes. Materials and methods: A comparative retrospective study was carried out of the concentration and functional activity (detoxifine efficiency - DTE) of serum albumin in 19 deceased (Group1) and 38 survived patients (Group 2) after cerebral catastrophic injury resulting in CCI. Samples for the study were obtained at the admission of patients, in the middle of the treatment and before discharge of patients. Results: It was established that in Group 1 the average value of albumin concentration and DTE decreased significantly, while in Group 2 values increased from the moment of admission to the discharge of patients. A ROC-analysis demonstrated a sufficiently high diagnostic informativeness of albumin DTE and concentration criteria, that differed in patients of Group 1 and 2 throughout all phases of the study. Conclusions: The outcome to a CCI after cerebral catastrophes is accompanied by changes in the concentration of serum albumin and violations of its functional activity – DTE. In patients with a fatal outcome, in contrast to patients with a positive effect of treatment, there is a progressive decrease in the concentration of serum albumin, which is combined with a pronounced decrease in its functional activity

Premature infants with extremely low birth weight are at high risk of developing severe disabling forms of retinopathy of prematurity. Nonsurgical therapy methods of treatment of retinopathy in prematurity are ineffective. Taking into consideration the multifactoriality of retinopathy in prematurity, studies aimed at analyzing accessory risk factors aiding the progression of active retinopathy of prematurity and the development in their pharmacological therapy are relevant for practical healthcare. Effective prevention of retinopathy of prematurity and prevention of severe disabling stages in premature infants at risk require timely diagnosis of the form and severity of anemia. This is the neonatologist’s task. The ophthalmologist should inform the neonatologist about the possibility of developing retinopathy of prematurity in a baby’s eye and about the necessity for diagnostic and remedial measure to treat anemia. The purpose of this study was to assess the impact of early anemia of prematurity on the frequency and severity of retinopathy of prematurity in infants at risk and the effectiveness of its treatment with erythropoietin. The frequency of anemia in preterm risk group (total 1603 children) and its treatment with the degree of prematurity were analyzed. Anemia was manifested in 99–100 % of children with retinopathy of prematurity. The comparative frequency and severity of retinopathy of prematurity was observed in three groups of infants: with extremely low birth weight and gestational age up to 28 weeks of pregnancy (245 children) group I, with gestational age 29–31 weeks of pregnancy (471 children) group II, and more than 31 weeks (581 children) group III. It was found that without treatment in group I retinopathy of prematurity developed in 100 % of cases and ended with adverse outcomes (IV–V degree of retinopathy of prematurity) in 13.64 %, which is significantly higher ( p < 0.01) than after treatment (1.78 %). Similar index was found in groups II and III. Conclusion. We traced the importance of early premature anemia in the pathogenesis of retinopathy of prematurity. It helped us to conclude that the lower the gestational age of the child at the time of birth stronger linked with the dependence of anemia and retinopathy of prematurity. Both of them are associated with the imperfection of the protective mechanisms of preterm infants. Early prescription of erythropoietin significantly improves the clinical course of retinopathy of prematurity and its prognosis.

PURPOSE To report the chronic toxicity and disease outcomes attributable to intensity-modulated radiation therapy (IMRT) in patients with cervical cancer. METHODS AND MATERIALS Between January 2014 and December 2018, a retrospective review of medical records of patients with cervical cancer who received radiation therapy with IMRT was performed. Disease and treatment-related details were documented. Follow-up notes were reviewed, and severity of late toxicities was recorded. Overall survival (OS) and disease-free survival (DFS) at 3 years were estimated. RESULTS A total of 222 patients’ records were reviewed. Mean age was 50.7 years. Median follow-up duration was 33 months (range, 2-70 months). The most common toxicity was vaginal stricture (grade 2, n = 59, 26.6%; grade 3, n = 4, 1.80%), followed by proctitis (grade 2, n = 24; 10.8%; grade 3, n = 7; 3.20%). Seven patients (grade 2, n = 5, 2.3%; grade 3, n = 2; 0.90%) developed cystitis, and only 5 (grade 2; 2.3%) were found to have colitis. None of the patients had grade 4 or grade 5 toxicities. There was a significant difference in late complications in patients with nodal disease or those who underwent prior surgery ( P < .05). Three-year OS and DFS rates were 79.7% and 81.9%, respectively. Patients with tumor size > 5 cm and those with pelvic lymph node metastasis had poor survival rates ( P < .05). CONCLUSION IMRT is an effective and well-tolerated technique that should be considered in patients with lymph node disease and in postoperative patients. There is an inverse relationship between tumor size and nodal involvement with respect to OS and DFS.

Recent cardiovascular safety trials on sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists have demonstrated the significant cardiovascular and renal benefits of these medications. Diabetes organisations have revised their medication guidelines to include a focus on disease outcomes for cardiovascular disease, heart failure and renal disease. This article summarises latest evidence, guideline recommendations and current Australian Pharmaceutical Benefits Scheme requirements.

Aim To analyze results of changing the management tactics in patients with acute coronary syndrome (ACS) in clinical practice from 2004 through 2018 expressed as improvement in prognosis.Material and methods Results of two observational studies were analyzed: ORACLE I (2004–2007), which included 1193 patients with ACS (mean age, 61.1±11.69 years; men, 63.3 %) and ORACLE II (2014–2017), which included 1652 patients from 4 vascular centers (mean age, 64.61±12.67 years; men, 62.3 %).Results Patients included into the ORACLE II study in 2014 were significantly older and the proportion of patients with diabetes mellitus was greater than in the ORACLE I study (14.7 and 22.6 %, respectively). After matching the groups by major clinical characteristics, it was found that introducing the invasive management tactics for ACS patients was associated with a reduced rate of all-cause death (from 8.2 to 6.1 % for one year), a tendency towards decreased number of coronary death cases (from 5.6 to 4.0 %), and a decrease in risk of recurrent coronary complications (from 17.4 to 7.7 %).Conclusion Implementing the vascular program statistically significantly decreased the total death rate for at least one-year observation in comparable patient groups.

Background Multidisciplinary team (MDT) discussions are widely held to facilitate the diagnosis and treatment of breast cancer, but patient compliance with the MDT recommendations and the impact of compliance on disease outcome are uncertain. Methods We conducted a retrospective review of data from a prospective database of breast cancer patients treated at Shanghai Ruijin Hospital between April 2013 and August 2018. MDT discussions were held for all patients before they started adjuvant therapy. The patients were classified into compliant and non-compliant groups according to whether they received the MDT-recommended regimens. We also analyzed which clinicopathological factors were associated with compliance and prognosis. Results Of 4501 breast cancer patients, 3681 (81.8%) and 820 (18.2%) were included in the compliant and non-compliant groups, respectively. Age >70 years (P, Highlights • A large consecutive breast cancer cohort with MDT-based treatment recommendation. • Factors identified associated with non-compliance with MDT recommendations. • A significantly better survival in patients compliant with MDT recommendation.

This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center's management policy of the disease severity on its long-term progression and cumulative damage development as well as provision of quality-driven medical care (QmC).Disease activity was assessed by the Physician Global Assessment and SLEDAI-2K, flares by SELENA/SLEDAI, and damage by the pediatric SLICC/DI at diagnosis, 6 months post-diagnosis, and annually thereafter. At the same time, QmC was evaluated by relevant indices and quality of life was captured by the Greek version of the General Health Questionnaire only at the last visit.A total of 35 patients (25/35 females) aged at diagnosis 5.5-15.16 years (median 11.83) with a median lag time to diagnosis 1.8 months had a follow-up of 5 (35/35) and 10 years (13/35), respectively. The predominant baseline manifestations were consistent with those previously reported. Out of 35 patients, 24 (68.5%) were clinically inactive at year 5, and 5/13 (38%) at year 10. All patients received immunosuppressives and 7/35 biologics in addition. At the end of their follow-up, damage was found in 9/35 patients, but none of them had a neuropsychiatric disorder. Over the study, 28/35 patients were compliant with the QmC recommendations.An early diagnosis combined with a longitudinal quantitative assessment of the disease activity and severity contributes to the continuous evaluation of the disease state. They are the key determinants for the selection of an early, targeted, and personalized management; they restrict the cumulative damage development and contribute to an optimal outcome. Key Points • Juvenile SLE has a heavier introductory profile than in adults and an unpredictable trajectory. • The application of contemporary metric tools for assessing the disease state leads to an objective assessment and regimen selection. • An early diagnosis combined with longitudinal quantitative assessment is a key determinant for an optimal management and a minimal damage development.

Tumors are supported by cancer-associated fibroblasts (CAFs). CAFs are heterogeneous and carry out distinct cancer-associated functions. Understanding the full repertoire of CAFs and their dynamic changes as tumors evolve could improve the precision of cancer treatment. Here we comprehensively analyze CAFs using index and transcriptional single-cell sorting at several time points along breast tumor progression in mice, uncovering distinct subpopulations. Notably, the transcriptional programs of these subpopulations change over time and in metastases, transitioning from an immunoregulatory program to wound-healing and antigen-presentation programs, indicating that CAFs and their functions are dynamic. Two main CAF subpopulations are also found in human breast tumors, where their ratio is associated with disease outcome across subtypes and is particularly correlated with BRCA mutations in triple-negative breast cancer. These findings indicate that the repertoire of CAF changes over time in breast cancer progression, with direct clinical implications. Scherz-Shouval and colleagues characterize the dynamic changes in cancer-associated fibroblast subpopulations during breast cancer progression. They find that the ratio of S100A4+ and PDPN+ CAF subsets is associated with clinical outcome.

Artificial intelligence (AI) is coming to medicine in a big wave. From making diagnosis in various medical conditions, following the latest advancements in scientific literature, suggesting appropriate therapies, to predicting prognosis and outcome of diseases and conditions, AI is offering unprecedented possibilities to improve care for patients. Gastroenterology is a field that AI can make a significant impact. This is partly because the diagnosis of gastrointestinal conditions relies a lot on image-based investigations and procedures (endoscopy and radiology). AI-assisted image analysis can make accurate assessment and provide more information than conventional analysis. AI integration of genomic, epigenetic, and metagenomic data may offer new classifications of gastrointestinal cancers and suggest optimal personalized treatments. In managing relapsing and remitting diseases such as inflammatory bowel disease, irritable bowel syndrome, and peptic ulcer bleeding, convoluted neural network may formulate models to predict disease outcome, enhancing treatment efficacy. AI and surgical robots can also assist surgeons in conducting gastrointestinal operations. While the advancement and new opportunities are exciting, the responsibility and liability issues of AI-assisted diagnosis and management need much deliberations.

LL-37, also called cathelicidin, is an important part of the human immune system, which can resist various pathogens. A plethora of experiments have demonstrated that it has the multifunctional effects of immune regulation, in addition to antimicrobial activity. Recently, there have been increasing interest in its immune function. It was found that LL-37 can have two distinct functions in different tissues and different microenvironments. Thus, it is necessary to investigate LL-37 immune functions from the two sides of the same coin. On the one side, LL-37 promotes inflammation and immune response and exerts its anti-infective and antitumor effects; on the other side, it has the ability to inhibit inflammation and promote carcinogenesis. This review presents a brief summary of its expression, structure, and immunomodulatory effects as well as brief discussions on the role of this small peptide as a key factor in the development and treatment of various inflammation-related diseases and cancers.

Evidences support the fact that sickle cell disease (SCD) is associated with a chronic inflammatory state characterized by haemolysis. C-reactive protein level (CRP) and white blood cell (WBC) count considered as biomarkers for inflammation. Also, elevation of serum total lactate dehydrogenase (LDH) levels are found to be associated with haemolysis, this makes LDH a nonspecific marker which has to be interpreted in a context of other markers of disease. The present study aims to assess the role of CRP levels, WBC counts, RBC counts, haemoglobin (Hb) concentrations and LDH levels in sickle hemoglobin (HbS) patients. Blood samples of 10 HbS patients (six females and four males) attending M.Y. Hospital, Indore during the period of Aug to Oct 2019 were screened for CRP, LDH and Hb levels and RBC and WBC counts using latex enhanced immune-turbidimetric assay, LDH optimize DGKC kinetic and differential automated hematology analyzer respectively. Data (mean ± SEM) was analyzed using Graphpad Prism software using Tukey’s multiple comparison post-hoc test. The mean Hb levels (7.73 ± 0.81 g/dl) and RBC counts (3.21 ± 0.53 million/µl) were found to be significantly decreased (p˂ 0.001 and 0.01 respectively) and mean WBC counts (15214.28 ± 1893.40 per mm3), CRP levels (85.73 ± 23.23 mg/l) and LDH levels (1334.00 ± 418.49 U/l) were found to be significantly increased (p˂ 0.0001, 0.01 and 0.01 respectively) in HbS patients in comparison with their respective controls. The variations in serum LDH and CRP levels are accompanied by changes in hematological parameters in HbS patients. These parameters may be considered as indicator of the severity of the disease. Keywords: C-reactive protein, LDH, Sickle cell disease

Deubiquitinases are enzymes that remove ubiquitin moieties from the vast majority of cellular proteins, controlling their stability, interactions, and localization. The expression and activity of deubiquitinases are critical for physiology and can go awry in various diseases, including cancer. Based on recent findings in human blood cancers, we discuss the functions of selected deubiquitinases in acute leukemia and efforts to target these enzymes with the aim of blocking leukemia growth and improving disease outcomes. We focus on the emergence of the newest generation of preclinical inhibitors by discussing their modes of inhibition and their effects on leukemia biology.

In view of the relatively limited efficacy of immunotherapies targeting the PD-1–PD-L1 axis in triple-negative breast cancer (TNBC) and of published reports on tumor-promoting roles of TNFR2+ tumor-infiltrating lymphocytes (TNFR2+ TILs), we determined the incidence of TNFR2+ TILs in TNBC patient tumors, their association with disease outcome and relations with PD-1+ TILs. Using a cohort of treatment-naive TNBC patients with long follow-up (n = 70), we determined the presence of TNFR2+ TILs and PD-1+ TILs by immunohistochemistry. TILs (≥ 1% of cellular mass) and TNFR2+ TILs (≥ 1% of total TILs) were detected in 96% and 74% of tumors, respectively. The presence of TILs at > 5% of tumor cell mass (“Positive TILs”), as well as of positive TNFR2+ TILs (> 5%), was independently associated with good prognosis, and combination of both parameters demonstrated superior outcome relative to their lower levels. PD1+ TILs (> 5/hot spot) were detected in 63% of patients. High levels of PD-1+ TILs (> 20/hot spot) showed an unfavorable disease outcome, and in their presence, the favorable outcome of positive TNFR2+ TILs was ablated. Thus, TNFR2+ TILs are strongly connected to improved prognosis in TNBC; these findings suggest that TNFR2+ TILs have favorable effects in TNBC patients, unlike the tumor-promoting roles attributed to them in other cancer systems. Overall, our observations propose that the TNFR2+ TIL subset should not be targeted in the course of TNBC therapy; rather, its beneficial impacts may become into power when anti-PD-1 regimens—that may potentiate immune activities—are administered to TNBC patients.

Relevance. The strategy for the development of vaccine prevention in the Russian Federation among other areas involves improving the National schedule of preventive vaccinations and ensuring its flexibility, taking into account the current epidemic situation and the emergence of new vaccines. Goal: to Assess the socio-economic damage from five vaccine-controlled infections in different vaccine prevention scenarios. Materials and methods : a simulated retrospective model was constructed with a time horizon of 3 years (2016-2018), which assumes an assessment of changes in lost/ saved years of life including in monetary terms in the context of differentiated disease outcomes and vaccine costs under different scenarios of vaccination coverage and the vaccine prevention algorithm. Results: if the established algorithm is maintained and the age cohort of children under 2 years of age is covered by vaccination, the annual loss of years of life will remain at a high level. Extending the five-component vaccine coverage to 60% of children in the 3-to 18-month age group will reduce losses to 20,215 years, saving 10,263 years of life (33.7% more than the current algorithm), and even more if coverage is close to 100%: annual losses will decrease to 2,134 years, which can provide 28,344 saved years of life (93% more than the current algorithm). The study showed that the more widely the combined pentavalent vaccine is used, the lower the average cost of saving each additional year of life. Conclusions. Expanding the coverage of a combination vaccine provides the greatest additional benefits due to a faster increase in the number of saved years of life (benefits) compared to the increase in costs (cost of vaccines).

Objectives Triple negative breast cancer (TNBC) is a heterogenous disease and associated with unfavorable outcomes. The role of sonographic features and its association with disease outcome in TNBC is uncertain. Our study aimed to determine the prognosis predictive value of sonographic features in TNBC. Methods Women with TNBC patients treated between January 2009 and December 2015 were retrospectively included. Patients’ clinic-pathological, sonographic features, recurrence-free survival (RFS), and breast cancer-specific survival (BCSS) events were reviewed and analyzed. Kaplan–Meier analysis and multivariable Cox regression were used to determine the prognostic factors in TNBC. Results A total of 433 TNBC patients were included. With a median follow-up of 4.8 years, 58 (13.4%) RFS and 35(8.1%) BCSS events were detected. Besides lymphatic vascular invasion (LVI), nuclear grade III, tumor >2.0 cm, and positive axillary lymph node (ALN), multivariable analysis found that vertical orientation in ultrasound imaging was independently associated with worse RFS (Hazard Ratio (HR) = 3.238; 95% Confidential Interval (CI), 1.661–6.312; P = 0.001) and BCSS (HR = 7.028; 95% CI, 3.199–15.436; P, Highlights • In TNBC, vertical orientation in US was associated with inferior RFS. • Vertical orientation in US independently predicted worse BCSS in TNBC. • Vertical orientation in US was related with more ALN metastasis in TNBC patients.

The macro-metastasis/organ parenchyma interface (MMPI) was previously considered an inert anatomical border which sharply separates the affected organ parenchyma from the macro-metastatic tissue. Recently, infiltrative growth of macro-metastases from various primary tumors was described in the brain, liver and lung, with significant impact on survival. Strikingly, the MMPI patterns differed between entities, so that at least nine different patterns were described. The MMPI patterns could be further classified into three major groups: displacing, epithelial and diffuse infiltrating. Additionally, macro-metastases are a source of further tumor cell dissemination in the affected organ; and these intra-organ metastatic dissemination tracks starting from the MMPI also vary depending on the anatomical structures of the colonized organ and influence disease outcome. In spite of their relevance, MMPIs and organ-specific dissemination tracks are still largely overlooked by many clinicians, pathologists and/or researchers. In this review, we aim to address this important issue and enhance our current understanding of the different MMPI patterns and dissemination tracks in the brain, liver and lung.

The tumour microenvironment (TME) determines vital aspects of tumour development, such as tumour growth, metastases and response to therapy. Cancer-associated fibroblasts (CAFs) are abundant and extremely influential in this process and interact with cellular and matrix TME constituents such as endothelial and immune cells and collagens, fibronectin and elastin, respectively. However, CAFs are also the recipients of signals—both chemical and physical—that are generated by the TME, and their phenotype effectively evolves alongside the tumour mass during tumour progression. Amid a rising clinical interest in CAFs as a crucial force for disease progression, this review aims to contextualise the CAF phenotype using the chronological framework of the CAF life cycle within the evolving tumour stroma, ranging from quiescent fibroblasts to highly proliferative and secretory CAFs. The emergence, properties and clinical implications of CAF activation are discussed, as well as research strategies used to characterise CAFs and current clinical efforts to alter CAF function as a therapeutic strategy.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are two common autoimmune rheumatic diseases that vary in severity, clinical presentation, and disease course between individuals. Molecular and genetic studies of both diseases have identified candidate genes and molecular pathways that are linked to various disease outcomes and treatment responses. Currently, patients can be grouped into molecular subsets in each disease, and these molecular categories should enable precision medicine approaches to be applied in rheumatic diseases. In this article, we will review key lessons learned about disease heterogeneity and molecular characterization in rheumatology, which we hope will lead to personalized therapeutic strategies.

From 2014–2019, invasive pulmonary aspergillosis complicated 7.2% (0–23.1% in different influenza seasons) of cases of influenza-associated respiratory failure in Edmonton, Alberta. Disease outcomes ranged from survival without therapy to death despite antifungals. Clinician vigilance, longitudinal local surveillance, and refined criteria to identify patients requiring therapy are needed.