The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.

Respiratory viruses constitute a significant cause of illness and death worldwide. Respiratory virus-associated injuries include oxidative stress, ferroptosis, inflammation, pyroptosis, apoptosis, fibrosis, autoimmunity, and vascular injury. Several studies have demonstrated the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) in the pathophysiology of viral infection and associated complications. It has thus emerged as a pivotal player in cellular defense mechanisms against such damage. Here, we discuss the impact of Nrf2 activation on airway injuries induced by respiratory viruses, including viruses, coronaviruses, rhinoviruses, and respiratory syncytial viruses. The inhibition or deregulation of Nrf2 pathway activation induces airway tissue damage in the presence of viral respiratory infections. In contrast, Nrf2 pathway activation demonstrates protection against tissue and organ injuries. Clinical trials involving Nrf2 agonists are needed to define the effect of Nrf2 therapeutics on airway tissues and organs damaged by viral respiratory infections.

A Focus on the Pathophysiology of Adrenomedullin Expression: Endothelitis and Organ Damage in Severe Viral and Bacterial Infections.

Adrenomedullin (ADM) is a peptide hormone produced primarily in the adrenal glands, playing a crucial role in various physiological processes. As well as improving vascular integrity and decreasing vascular permeability, ADM acts as a vasodilator, positive inotrope, diuretic, natriuretic and bronchodilator, antagonizing angiotensin II by inhibiting aldosterone secretion. ADM also has antihypertrophic, anti-apoptotic, antifibrotic, antioxidant, angiogenic and immunoregulatory effects and antimicrobial properties. ADM expression is upregulated by hypoxia, inflammation-inducing cytokines, viral or bacterial substances, strength of shear stress, and leakage of blood vessels. These pathological conditions are established during systemic inflammation that can result from infections, surgery, trauma/accidents or burns. The ability to rapidly identify infections and the prognostic, predictive power makes it a valuable tool in severe viral and bacterial infections burdened by high incidence and mortality. This review sheds light on the pathophysiological processes that in severe viral or bacterial infections cause endothelitis up to the development of organ damage, the resulting increase in ADM levels dosed through its more stable peptide mid-regional proadrenomedullin (MR-proADM), the most significant studies that attest to its diagnostic and prognostic accuracy in highlighting the severity of viral or bacterial infections and appropriate therapeutic insights.

Blood-borne viruses and neurological manifestations: An overview.

Infections caused by blood-borne viruses, such as human immunodeficiency virus (HIV), human T-lymphotropic virus (HTLV), hepatitis C virus (HCV), and hepatitis B virus (HBV), are systemic diseases that can lead to a wide range of pathological manifestations. Besides causing severe immune and hepatic disorders, these viral pathogens can also induce neurological dysfunctions via both direct and indirect mechanisms. Neurological dysfunctions are one of the most common manifestations caused by these viruses that can also serve as indicators of their infection, impacting the clinical presentation of the disease. The main neurological manifestations of these blood-borne viral pathogens consist of several central and peripheral nervous system (CNS and PNS, respectively) dysfunctions. The most common neurological manifestations of HIV, HTLV, HCV, and HBV include HIV-associated peripheral neuropathy (PN), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and HCV-/HBV-associated PN, respectively. Nonetheless, patients infected with these viruses may experience other neurological disorders, either associated with these conditions or manifesting in isolation, which can often go unnoticed or undiagnosed by physicians. The present review aims to provide an overview of the latest evidence on the relationship between blood-borne viruses and neurological disorders to highlight neurological conditions that may be somewhat overlooked by mainstream literature and physicians.

Exploring viral infections' role in Kawasaki disease onset: A study during the COVID-19 pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, known viral diseases declined in all ages. By using the current situation as a natural experiment, this study aimed to evaluate whether the change in the incidence of Kawasaki disease (KD) during the COVID-19 pandemic varies with age and whether a specific infectious disease mediates the occurrence of KD. Monthly number of KD patients were extracted from the nationwide inpatient database. Segmented regression analysis was conducted on the interrupted time series data. Additionally, causal mediation analysis was performed to examine the role of viral infections in the changes in the number of KD patients. After the first emergency declaration for COVID-19 in Japan, there was an immediate decrease in the number of KD patients per 100 000 population aged between 6 months and 4 years (immediate change = -2.66; 95% confidence interval [CI]: -5.16 to -0.16) and aged 5-15 years (immediate change = -0.26; 95% CI: -0.49 to -0.04). However, no immediate change was observed in patients under 6 months of age. In the causal mediation analysis for each viral infection, it was found that the decrease in the number of patients with KD was mediated by changes in the number of patients with pharyngoconjunctival fever and infectious gastroenteritis. The current results suggest that viral infections may be one of the etiological agents for KD, while they may not be the main cause in early infancy. Specifically, we found that adenovirus infection and gastroenteritis was closely related to the onset of KD in some areas of Japan.

Viral infections and inborn errors of immunity.

PURPOSE OF REVIEW: The purpose of this focused review is to discuss unusual presentations of viral infections in the context of specific inborn errors of immunity. We will discuss hyper immunoglobulin E (IgE) syndromes, epidermodysplasia verruciformis, and X-linked agammaglobulinemia as examples of inborn errors of immunity associated with specific presentations of viral infection and disease. RECENT FINDINGS: Advances in both genetic and viral diagnostics have broadened our understanding of viral pathogenesis in the setting of immune dysfunction and the variable phenotype of inborn errors of immunity. Dedicator of cytokinesis 8 (DOCK8) deficiency is now recognized as an inborn error of immunity within the hyper IgE syndrome phenotype and is associated with unusually aggressive cutaneous disease caused by herpes simplex and other viruses. Studies of patients with epidermodysplasia verruciformis have proven that rarely detected human papillomavirus subtypes may cause malignancy in the absence of adequate host defenses. Finally, patients with X-linked agammaglobulinemia may remain at risk for severe and chronic viral infections, even as immune globulin supplementation reduces the risk of bacterial infection. SUMMARY: Susceptibility to viral infections in patients with inborn errors of immunity is conferred by specific, molecular defects. Recurrent, severe, or otherwise unusual presentations of viral disease should prompt investigation for an underlying genetic defect.

Association between viral infection and bronchopulmonary dysplasia in preterm infants: a systematic review and meta-analysis.

Bronchopulmonary dysplasia (BPD) is the most common serious complication of very preterm infants (VPI) or very low birth weight (VLBW) infants. Studies implicate viral infections in etiopathogenesis. The aim of this study was to summarize the relationship between viral infections and BPD through a systematic review and meta-analysis. We searched PubMed, Embase, the Web of Science Core Collection, and the Cochrane Database on December 19, 2023. We included observational studies that examined the association between viral infections and BPD in preterm infants. We extracted data on study methods, participant characteristics, exposure assessment, and outcome measures. We assessed study risk of bias using the Newcastle-Ottawa Scale (NOS). We included 17 and 15 studies in the qualitative review and meta-analysis, respectively. The meta-analysis showed a significant association between viral infection and BPD diagnosed at 36 weeks postmenstrual age (odds ratio (OR): 2.42, 95% confidence interval: 1.89-3.09, 13 studies, very low certainty of evidence). In a subgroup analysis of specific viruses, cytomegalovirus (CMV) proved to be significantly associated with BPD diagnosed at 36 weeks postmenstrual age (OR: 2.34, 95% confidence interval: 1.80-3.05, 11 studies). We did not find an association between viral infection and BPD diagnosed on the 28th day of life, probably due to the small sample size of the included prospective studies.  Conclusion: Viral infections, especially CMV, are associated with an increased risk of BPD in preterm infants. Methodologically reliable prospective studies with large samples are needed to validate our conclusions, and high-quality randomized controlled studies are needed to explore the effect of prevention or treatment of viral infections on the incidence of BPD. What is Known: • Studies have attempted to identify viral infections and bronchopulmonary dysplasia in preterm infants; however, results have been inconsistent. What is New: • Systematic demonstration that viral infections, particularly cytomegalovirus, are positively associated with bronchopulmonary dysplasia diagnosed in preterm infants at the 36th week of postmenstrual age. • The importance of screening for viral infections in preterm infants, especially cytomegalovirus. More high-quality studies should be produced in the future to investigate the causal relationship between viral infections and bronchopulmonary dysplasia.

Virus-induced diabetes mellitus: revisiting infection etiology in light of SARS-CoV-2.

Diabetes mellitus (DM) is comprised of two predominant subtypes: type 1 diabetes mellitus (T1DM), accounting for approximately 5 % of cases worldwide and resulting from autoimmune destruction of insulin-producing ß-cells, and type 2 (T2DM), accounting for approximately 95 % of cases globally and characterized by the inability of pancreatic ß-cells to meet the demand for insulin due to a relative ß-cell deficit in the setting of peripheral insulin resistance. Both types of DM involve derangement of glucose metabolism and are metabolic diseases generally considered to be initiated by a combination of genetic and environmental factors. Viruses have been reported to play a role as infectious etiological factors in the initiation of both types of DM in predisposed individuals. Among the reported viral infections causing DM in humans, the most studied include coxsackie B virus, cytomegalovirus and hepatitis C virus. The recent COVID-19 pandemic has highlighted the diabetogenic potential of SARS-CoV-2, rekindling interest in the field of virus-induced diabetes (VID). This review discusses the reported mechanisms of viral-induced DM, addressing emerging concepts in VID, as well as highlighting areas where knowledge is lacking, and further investigation is warranted.

Prevalence and impact of viral myocarditis in patients with severe fever with thrombocytopenia syndrome.

To explore the association and impact between viral myocarditis and mortality in patients with severe fever with thrombocytopenia syndrome. A dynamic analysis was conducted between fatal group and nonfatal group regarding the daily epidemiology data, clinical symptoms, and electrocardiogram (ECG), echocardiogram, and laboratory findings. Outcomes of patients with and without viral myocarditis were compared. The association between viral myocarditis and mortality was analyzed. Among 183 severe fever with thrombocytopenia syndrome patients, 32 were in the fatal group and 151 in the nonfatal group; there were 26 (81.25%) with viral myocarditis in the fatal group, 66 (43.70%) with viral myocarditis in the nonfatal group (p < 0.001), 79.35% of patients had abnormal ECG results. The abnormal rate of ECG in the fatal group was 100%, and in the nonfatal group was 74.83%. Univariate analysis found that the number of risk factors gradually increased on Day 7 of the disease course and reached the peak on Day 10. Combined with the dynamic analysis of the disease course, alanine aminotransferase, aspartate aminotransferase, creatine kinase, creatine kinase fraction, lactate dehydrogenase, hydroxybutyrate dehydrogenase, neutrophil count, serum creatinine, Na, Ca, carbon dioxide combining power, amylase, lipase, activated partial thromboplastin time and thrombin time had statistically significant impact on prognosis. The incidence of fever with thrombocytopenia syndrome combined with viral myocarditis is high, especially in the fatal group of patients. Viral myocarditis is closely related to prognosis and is an early risk factor. The time point for changes in myocarditis is Day 7 of the course of the disease.

Virus-Induced Epilepsy vs. Epilepsy Patients Acquiring Viral Infection: Unravelling the Complex Relationship for Precision Treatment.

The intricate relationship between viruses and epilepsy involves a bidirectional interaction. Certain viruses can induce epilepsy by infecting the brain, leading to inflammation, damage, or abnormal electrical activity. Conversely, epilepsy patients may be more susceptible to viral infections due to factors, such as compromised immune systems, anticonvulsant drugs, or surgical interventions. Neuroinflammation, a common factor in both scenarios, exhibits onset, duration, intensity, and consequence variations. It can modulate epileptogenesis, increase seizure susceptibility, and impact anticonvulsant drug pharmacokinetics, immune system function, and brain physiology. Viral infections significantly impact the clinical management of epilepsy patients, necessitating a multidisciplinary approach encompassing diagnosis, prevention, and treatment of both conditions. We delved into the dual dynamics of viruses inducing epilepsy and epilepsy patients acquiring viruses, examining the unique features of each case. For virus-induced epilepsy, we specify virus types, elucidate mechanisms of epilepsy induction, emphasize neuroinflammation's impact, and analyze its effects on anticonvulsant drug pharmacokinetics. Conversely, in epilepsy patients acquiring viruses, we detail the acquired virus, its interaction with existing epilepsy, neuroinflammation effects, and changes in anticonvulsant drug pharmacokinetics. Understanding this interplay advances precision therapies for epilepsy during viral infections, providing mechanistic insights, identifying biomarkers and therapeutic targets, and supporting optimized dosing regimens. However, further studies are crucial to validate tools, discover new biomarkers and therapeutic targets, and evaluate targeted therapy safety and efficacy in diverse epilepsy and viral infection scenarios.

Characterization of the brain virome in human immunodeficiency virus infection and substance use disorder.

Viruses can infect the brain in individuals with and without HIV-infection: however, the brain virome is poorly characterized. Metabolic alterations have been identified which predispose people to substance use disorder (SUD), but whether these could be triggered by viral infection of the brain is unknown. We used a target-enrichment, deep sequencing platform and bioinformatic pipeline named "ViroFind", for the unbiased characterization of DNA and RNA viruses in brain samples obtained from the National Neuro-AIDS Tissue Consortium. We analyzed fresh frozen post-mortem prefrontal cortex from 72 individuals without known viral infection of the brain, including 16 HIV+/SUD+, 20 HIV+/SUD-, 16 HIV-/SUD+, and 20 HIV-/SUD-. The average age was 52.3 y and 62.5% were males. We identified sequences from 26 viruses belonging to 11 viral taxa. These included viruses with and without known pathogenic potential or tropism to the nervous system, with sequence coverage ranging from 0.03 to 99.73% of the viral genomes. In SUD+ people, HIV-infection was associated with a higher total number of viruses, and HIV+/SUD+ compared to HIV-/SUD+ individuals had an increased frequency of Adenovirus (68.8 vs 0%; p<0.001) and Epstein-Barr virus (EBV) (43.8 vs 6.3%; p=0.037) as well as an increase in Torque Teno virus (TTV) burden. Conversely, in HIV+ people, SUD was associated with an increase in frequency of Hepatitis C virus, (25 in HIV+/SUD+ vs 0% in HIV+/SUD-; p=0.031). Finally, HIV+/SUD- compared to HIV-/SUD- individuals had an increased frequency of EBV (50 vs 0%; p<0.001) and an increase in TTV viral burden, but a decreased Adenovirus viral burden. These data demonstrate an unexpectedly high variety in the human brain virome, identifying targets for future research into the impact of these taxa on the central nervous system. ViroFind could become a valuable tool for monitoring viral dynamics in various compartments, monitoring outbreaks, and informing vaccine development.

Implication of viruses in the etiology of preeclampsia.

Preeclampsia is one of the most common disorders that poses threat to both mothers and neonates and a major contributor to perinatal morbidity and mortality worldwide. Viral infection during pregnancy is not typically considered to cause preeclampsia; however, syndromic nature of preeclampsia etiology and the immunomodulatory effects of viral infections suggest that microbes could trigger a subset of preeclampsia. Notably, SARS-CoV-2 infection is associated with an increased risk of preeclampsia. Herein, we review the potential role of viral infections in this great obstetrical syndrome. According to in vitro and in vivo experimental studies, viral infections can cause preeclampsia by introducing poor placentation, syncytiotrophoblast stress, and/or maternal systemic inflammation, which are all known to play a critical role in the development of preeclampsia. Moreover, clinical and experimental investigations have suggested a link between several viruses and the onset of preeclampsia via multiple pathways. However, the results of experimental and clinical research are not always consistent. Therefore, future studies should investigate the causal link between viral infections and preeclampsia to elucidate the mechanism behind this relationship and the etiology of preeclampsia itself.

Viral infections in pregnancy and impact on offspring neurodevelopment: mechanisms and lessons learned.

Pregnant individuals with viral illness may experience significant morbidity and have higher rates of pregnancy and neonatal complications. With the growing number of viral infections and new viral pandemics, it is important to examine the effects of infection during pregnancy on both the gestational parent and the offspring. Febrile illness and inflammation during pregnancy are correlated with risk for autism, attention deficit/hyperactivity disorder, and developmental delay in the offspring in human and animal models. Historical viral epidemics had limited follow-up of the offspring of affected pregnancies. Infants exposed to seasonal influenza and the 2009 H1N1 influenza virus experienced increased risks of congenital malformations and neuropsychiatric conditions. Zika virus exposure in utero can lead to a spectrum of abnormalities, ranging from severe microcephaly to neurodevelopmental delays which may appear later in childhood and in the absence of Zika-related birth defects. Vertical infection with severe acute respiratory syndrome coronavirus-2 has occurred rarely, but there appears to be a risk for developmental delays in the infants with antenatal exposure. Determining how illness from infection during pregnancy and specific viral pathogens can affect pregnancy and neurodevelopmental outcomes of offspring can better prepare the community to care for these children as they grow. IMPACT: Viral infections have impacted pregnant people and their offspring throughout history. Antenatal exposure to maternal fever and inflammation may increase risk of developmental and neurobehavioral disorders in infants and children. The recent SARS-CoV-2 pandemic stresses the importance of longitudinal studies to follow pregnancies and offspring neurodevelopment.

Respiratory tract viral infections associated sepsis in patients with underlying liver disease: Viral sepsis an entity to look forward!

BACKGROUND: Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients. METHODS: In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, Utah, USA). RESULTS: Of 1391 patients tested, a respiratory viral etiology was detected in 23%. The occurrence of sepsis was seen in 35%. Among these, isolated viral etiology with no other bacterial/fungal coinfection was found in 55% of patients. Rhinovirus/Enterovirus was found as the most common underlying viral etiology (23.4%). The sepsis prevalence was higher among patients with associated comorbidities (45%) and decompensated cirrhosis (84%). On multi-variable analysis, no factor was found independently associated with sepsis-related mortality. CONCLUSION: This study underlines the importance of isolated viral etiology in causation of sepsis among liver disease patients. Patients with comorbidities, older age and decompensated cirrhosis are at an increased risk of developing sepsis and are associated with poorer outcomes. Accurate and timely identification of the viral etiology in sepsis would prevent the misuse of antibiotics and improve overall patient care.

[Factors of the hemostasis system as biomarkers of severe course of acute viral infections]. / Faktory sistemy gemostaza kak biomarkery tyazhelogo techeniya ostrykh virusnykh infektsii.

The authors give literature review of hemostasis and immune system factors intraction as main biomarkers of a severe cause of viral infectious diseases. Pro-inflamatory cytokines as the main markers of inflammation, can serve both as biomarkers of the clinical severity of the infectious process and reflect the state of the hemostatic and fibrinolytic systems, since components of these systems are present in various structures of the central nervous system and affect the development of neurons and synaptic plasticity. An inverse correlation has been proven between the concentration of D-dimer and the oxygenation index, and the development of DIC is not associated with the presence of respiratory failure in patients with influenza type A, while the ferritin concentration directly reflects the severity of the disease. One of the markers of endothelial damage may be soluble thrombomodulin, which, however, is rarely used in routine clinical practice. Cytoflavin is a highly effective pathogenetic drug that affects various parts of the hemostasis system, has anti-ischemic, antioxidant, antihypoxic, immunocorrective effect, which is indicated for any generalized infectious disease since its debut.

Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation.

Introduction: Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI. Methods: We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT. Results: For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival. Conclusion: These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.

Squamous Cell Carcinoma of the Supraglottis Presenting as Hoarseness.

Hoarseness is a well-known condition in primary care offices, with over 1% of primary care visits secondary to this ailment.1 The most common causes are acute laryngitis (40%), functional dysphonia (30%), benign and malignant tumors (2.2 to 30%), neurogenic factors such as vocal cord paralysis (8%), physiological aging (2%), and psychogenic factors (2.2%). Most of these cases are secondary to viral infections and do not require antibiotics on most occasions. These viral infections subside after 1 to 2 weeks, and in the case of persistent hoarseness (above 4 weeks) the American Academy of Otolaryngology recommends direct visualization with a laryngoscopy before treatment with proton pump inhibitors, antibiotics, or steroids. Our patient presented with prolonged hoarseness (greater than eight weeks) but had a quick turn around time interval between primary care visit and laryngoscopy evaluation (less than 2 weeks). This led to her diagnosis and treatment with chemo and radiation therapy within three months of diagnosis with Squamous Cell Carcinoma of the Supraglottis. The Primary care physician serves as the number one point of visitation by sufferers of hoarseness. It is important that they are knowledgeable and up to date with recommendations and guidelines for managing this condition, as unwarranted delay can affect overall outcome on the part of the patient. This is especially important in patients such as ours with high risk factors including Nicotine dependence, alcohol use, asbestos exposure, and HPV infection.

La voix rauque est une condition bien connue dans les cabinets de soins primaires, avec plus de 1 % des visites en soins primaires dues à ce problème. Les causes les plus courantes sont la laryngite aiguë (40%), la dysphonie fonctionnelle (30 %), les tumeurs bénignes et malignes (2,2 à 30 %), les facteurs neurogènes tels que la paralysie des cordes vocales (8 %), le vieillissement physiologique (2 %) et les facteurs psychogènes (2,2 %). La plupart de ces cas sont dus à des infections virales et ne nécessitent pas d'antibiotiques dans la plupart des cas. Ces infections virales disparaissent après 1 à 2 semaines, et en cas de voix rauque persistante (plus de 4 semaines), l'American Academy of Otolaryngology recommande une visualisation directe avec une laryngoscopie avant le traitement par inhibiteurs de la pompe à protons, antibiotiques ou stéroïdes. Notre patiente présentait une voix rauque prolongée (plus de huit semaines), mais a bénéficié d'un délai rapide entre la visite en soins primaires et l'évaluation par laryngoscopie (moins de 2 semaines). Cela a conduit à son diagnostic et à son traitement par chimiothérapie et radiothérapie dans les trois mois suivant le diagnostic de carcinome épidermoïde du supraglotte. Le médecin de soins primaires est le premier point de visite pour les personnes souffrant de voix rauque. Il est important qu'ils soient informés et à jour des recommandations et des lignes directrices pour la prise en charge de cette condition, car un retard non justifié peut affecter le résultat global pour le patient. Ceci est particulièrement important chez les patients comme le nôtre présentant des facteurs de risque élevés, y compris la dépendance à la nicotine, la consommation d'alcool, l'exposition à l'amiante. MOTS-CLÉS: Laryngoscopie, Supraglotte, Larynx, Enrouement.

Late transplant-associated thrombotic microangiopathy verified in bone marrow biopsy specimens is associated with chronic GVHD and viral infections.

OBJECTIVES: To describe late transplant-associated thrombotic microangiopathy (TA-TMA) as chronic endothelial complication in bone marrow (BM) after allogeneic hematopoietic stem cell transplantation (HSCT). METHODS: BM specimens along with conventional diagnostic parameters were assessed in 14 single-institutional patients with late TA-TMA (more than 100 days after HCST), including 11 late with history of early TA-TMA, 10 with early TA-TMA (within 100 days), and 12 non TA-TMA patients. Three non-HSCT patients served as control. The time points of BM biopsy were +1086, +798, +396, and +363 days after HSCT, respectively. RESULTS: Late TA-TMA patients showed an increase of CD34+ and von Willebrand Factor (VWF)+ microvascular endothelial cells with atypical VWF+ conglomerates forming thickened VWF+ plaque sinus in the BM compared to patients without late TA-TMA and non-HSCT. Severe chronic (p = .002), steroid-refractory GVHD (p = .007) and reactivation of HHV6 (p = .002), EBV (p = .003), and adenovirus (p = .005) were pronounced in late TA-TMA. Overall and relapse-free survival were shorter in late TA-TMA than in patients without late TA-TMA (5-year OS and RFS: 78.6% vs. 90.2%, 71.4% vs. 86.4%, respectively). CONCLUSION: Chronic allo-immune microangiopathy in BM associated with chronic, steroid-refractory GVHD and/or viral infections are key findings of late, high-risk TA-TMA, which deserves clinical attention.

Oral manifestations associated with neutropenia in Syrian patients diagnosed with hematological malignancies and undergoing chemotherapy: A cross-sectional study.

Neutropenia can be caused by a variety of congenital and acquired factors, with Chemotherapy-induced myelosuppression being the most common cause. Neutropenia significantly affects oral health, leading to the manifestation of oral lesions such as ulcers, fungal and viral infections, and mucositis. This study aims to investigate oral lesions in patients with hematological malignancies who developed neutropenia after chemotherapy. This cross-sectional study included 50 patients with hematological malignancies. The participants were divided into 2 groups: the first group consisted of 25 patients with hematological malignancies who developed chemotherapy-induced neutropenia and the second group consisted of 25 patients with hematological malignancies who did not develop chemotherapy-induced neutropenia. Patients were assigned to one of the groups based on the absolute neutrophil count (ANC). Full oral clinical examination was performed to determine the presence of oral lesions. In the Chemotherapy-Induced Neutropenia group, the most common lesion was ulceration, observed in 12 patients (48%). Fungal infections were the second most common, present in 5 patients (20%), followed by viral infections in 4 patients (15%), and mucositis, which occurred in a single patient (4%). A statistically significant association was found between neutropenia and the presence of oral ulcers (P value = .015). In contrast, in the Chemotherapy group, oral changes were less frequent. Fungal infections were the most common, occurring in 4 patients (15%), followed by oral mucositis in 3 patients (12%). Ulceration and viral infections were the least common, each observed in 1 patient (4%). The frequency of various forms of oral ulcers increases with the severity of neutropenia. However, there was no significant increase in other oral lesions in patients with neutropenia.

Role of the VEGF in virus-associated cancers.

The role of numerous risk factors, including consumption of alcohol, smoking, having diet high in fat and sugar and many other items, on caner progression cannot be denied. Viral diseases are one these factors, and they can initiate some signalling pathways causing cancer. For example, they can be effective on providing oxygen and nutrients by inducing VEGF expression. In this review article, we summarised the mechanisms of angiogenesis and VEGF expression in cancerous tissues which are infected with oncoviruses (Epstein-Barr virus, Human papillomavirus infection, Human T-lymphotropic virus, Kaposi's sarcoma-associated herpesvirus, Hepatitis B and hepatitis C virus).