Extrapulmonary Manifestations Research Articles

Cardiovascular Complications in Respiratory Viral Infections with a Focus on COVID-19

Patients with respiratory viral infections have altered immune responses, which may predispose them to cardiovascular complications. In the face of the pandemic of a new kind of severe acute respiratory syndrome (SARS), coronavirus disease 2019 (COVID-19), there is a resurgence of interest in the early diagnosis, prevention, and treatment of patients who are at risk. COVID-19 often manifests as viral pneumonia, although extrapulmonary manifestations are also common. Acute cardiac damage associated with elevated highsensitivity troponin levels crucially contributes to mortality in severe COVID-19. The present review clinically compares cardiovascular complications between COVID-19 and other respiratory infections caused by singlestranded RNA viruses, namely influenza, SARS, and Middle East respiratory syndrome (MERS). Estimating the death rate from RVIs has been a subject of intense research, but the mortality from cardiovascular complications in these infections is less understood and calls for further research.

Tuberculosis in infertility and in vitro fertilization-embryo transfer.

Tuberculosis (TB) is a prominent infectious disease globally that imposes a substantial health burden. Genital TB (GTB), an extrapulmonary manifestation, leads to complications such as tubal adhesions, blockage, and diminished ovarian function, culminating in infertility, and is recognized as a prevalent cause of infertility in nations with high-burden TB. In regions with low TB rates, infertility and active TB during pregnancy have been reported to be most common among female immigrants from countries with high-burden TB. In the context of TB, pregnant women often exhibit exacerbated symptoms after in vitro fertilization-embryo transfer (IVF-ET), heightening the risk of dissemination. Miliary pulmonary TB and tuberculous meningitis pose a serious threat to maternal and fetal health. This article integrates recent epidemiological data and clinical research findings, delineating the impact of TB on infertility and assisted reproduction and particularly focusing on the diagnosis and treatment of GTB, underscored by the imperative of TB screening before IVF-ET. Our objective is to increase awareness among respiratory and reproductive health professionals, promoting multidisciplinary management to enhance clinical vigilance. This approach seeks to provide patients with judicious reproductive plans and scientifically rigorous pregnancy management, thereby mitigating adverse pregnancy outcomes related to TB activity.

The correlation between the level of cellular classification in bronchoalveolar lavage fluid of children with severe Mycoplasma pneumoniae and clinical characteristics.

The BALF of children with SMPP is predominantly neutrophilic. A lower percentage of lymphocytes is related to a higher incidence of pleural effusion, extrapulmonary manifestations and progression to RMPP, as well as a longer length of hospitalisation. • Mycoplasma pneumonia in children is relatively common in clinical practice. Bronchoalveolar lavage (BAL) is a routine clinical procedure. However, there are relatively few studies focusing on the cytomorphological analysis of cells in BAL fluid.

Elexacaftor-tezacaftor-ivacaftor use after solid organ transplant.

In 2019, the United States Food and Drug Administration approved a breakthrough therapeutic for cystic fibrosis, elexacaftor-tezacaftor-ivacaftor (ETI), because of its profound effect on lung function in large phase III clinical trials. ETI acts directly on the dysfunctional protein that causes the systemic manifestations of cystic fibrosis and also leads to improvement in nonpulmonary symptoms of cystic fibrosis. Transplant recipients were excluded from the pivotal clinical trials of ETI but may stand to benefit from correction of the underlying protein defect. Drug interactions between the three drugs in ETI and immunosuppression medications are one of the primary concerns about using ETI after transplant. No rigorous studies exist to assess the safety of ETI in transplant recipients. Multiple recent publications describe the use of ETI after solid organ transplantation, including lung and nonlung transplants, and the real-world evidence for drug interactions between ETI and immunosuppression medications. In nonlung transplant recipients, the pulmonary benefits of ETI have been confirmed, but adverse events occur and may have implications for their transplanted organ (e.g. liver biopsy in the setting of elevated transaminases). Lung transplant recipients may have higher rates of ETI discontinuation than nontransplant recipients given a lack of direct pulmonary benefit and frequency of side effects. Drug interactions have not been difficult to manage, with most studies reporting variable rates of mild to moderate increased tacrolimus levels after initiation of ETI. Limited data exist to support the use of ETI after solid organ transplantation and further research is warranted. Given the unknown risks and benefits, case by case consideration of ETI use is indicated when extra-pulmonary manifestations are present in lung transplant recipients with cystic fibrosis. Given the proven benefit in cystic fibrosis lung disease, benefits likely outweigh the risks of ETI for nonlung solid organ transplant recipients.

Sarcoidosis versus Granulomatous and Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency: A Comparative Review.

Sarcoidosis and Granulomatous and Lymphocytic Interstitial Lung Diseases (GLILD) are two rare entities primarily characterised by the development of Interstitial Lung Disease (ILD) in the context of systemic immune dysregulation. These two conditions partially share the immunological background and pathologic findings, with granuloma as the main common feature. In this narrative review, we performed a careful comparison between sarcoidosis and GLILD, with an overview of their main similarities and differences, starting from a clinical perspective and ending with a deeper look at the immunopathogenesis and possible target therapies. Sarcoidosis occurs in immunocompetent individuals, whereas GLILD occurs in patients affected by common variable immunodeficiency (CVID). Moreover, peculiar extrapulmonary manifestations and radiological and histological features may help distinguish the two diseases. Despite that, common pathogenetic pathways have been suggested and both these disorders can cause progressive impairment of lung function and variable systemic granulomatous and non-granulomatous complications, leading to significant morbidity, reduced quality of life, and survival. Due to the rarity of these conditions and the extreme clinical variability, there are still many open questions concerning their pathogenesis, natural history, and optimal management. However, if studied in parallel, these two entities might benefit from each other, leading to a better understanding of their pathogenesis and to more tailored treatment approaches.

COVID-19 and Digestive Diseases: A Comprehensive Review on Pathophysiology and Clinical Management

Abstract: A serious pandemic has been presented by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a coronavirus that causes the severe acute respiratory infection known as Coronavirus disease 2019 (COVID-19). It has become a major health hazard that affects people all around the world. Although the respiratory symptoms are the main manifestations of COVID-19, several extrapulmonary manifestations have been observed, including cardiovascular, renal, and gastrointestinal symptoms. The digestive system may be an additional or non-traditional pathway for COVID-19 to spread and manifest as Angiotensin-Converting Enzyme 2 (ACE2), the entry point of SARS-CoV-2 into the cells is present in the gastrointestinal tract and liver. Gastrointestinal symptoms, such as vomiting, anorexia, nausea, and diarrhea, are infrequent in COVID-19 patients; however, some of these symptoms may manifest independently of other respiratory symptoms. Also, SARS-CoV-2 virus can cause liver and pancreatic damage. Studying the pathogenic mechanisms of COVID-19 in the digestive system could aid in improving patient diagnosis and treatment. The review aims to provide an overview of the mechanisms, symptoms, and management of SARS-CoV- 2's effects on the digestive system. Hence, medical professionals would be aware of the digestive symptoms associated with COVID-19 and would promptly alter treatment regimens for patients exhibiting abnormal hepatic and gastrointestinal manifestations.

Is Type and Grade of Emphysema Important for Bone Mineral Density and Aortic Calcifications?

Background: Chronic obstructive pulmonary disease has extrapulmonary manifestations, such as cardiovascular diseases and osteoporosis. The purpose of this research was to determine the relationship between the type and extent of emphysema with thoracic aorta calcification (TAC) and bone mineral density (BMD) at Th4, Th8, and L1 vertebrae. Methods: Emphysema was described by computed tomography parameters (both Fleischner classification and low attenuation value percentage, LAV%) and the clinical FEV1/FVC ratio (Tiffeneau-Pinelli index, TI, TI < 0.7; TI > 0.7). Results: Of 200 included patients (median age 64, 33% women), signs of clinical obstruction (TI) were observed in 104 patients, which had significantly lower BMD and more heavy TAC. BMD correlated negatively with LAV%, Rho = -0.16 to -0.23, while a positive correlation of aortic calcification with LAV% was observed, Rho = 0.30 to 0.33. Multiple linear regression showed that age and TI < 0.7 were independent predictors of BMD, β = -0.20 to -0.40, and β = -0.21 to -0.25; age and hypercholesterolemia were independent predictors of TCA, β = 0.61 and β = 0.19. Conclusions: Clinical TI and morphological LAV% parameters correlated with BMD and TAC, in contrast to Fleischer-graded emphysema, which showed no correlation. However, only TI was an independent predictor of BMD, while the morphologically described type and extent of emphysema could not independently predict any extrapulmonary manifestation.

Unusual Extra Pulmonary Clinical Manifestation as Initial Presenting Feature of COVID-19 and its Management: A Systematic Review of Case Reports

Unusual Extra Pulmonary Clinical Manifestation as Initial Presenting Feature of COVID-19 and its Management: A Systematic Review of Case Reports

Comprehensive Insights Into the Multi-faceted Manifestations of COVID-19: A Narrative Review.

The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and the ensuing COVID-19 pandemic had far-reaching and multifaceted effects on global health. This paper provides a comprehensive overview of the physical, extrapulmonary, and psychological manifestations associated with COVID-19. It highlights the wide-ranging impact of the virus on various organ systems, including the respiratory, cardiovascular, renal, gastrointestinal, ocular, dermatologic, and nervous systems. Additionally, it explores the complex connections between COVID-19 infection and neuropsychiatric symptoms, shedding light on the potential underlying mechanisms.The paper also delves into the phenomenon of "long COVID," a condition characterized by persistent symptoms extending well beyond the disease's acute phase. It discusses the diverse and often debilitating symptoms that individuals with long COVID may experience, encompassing physical, cognitive, and psychological aspects. The complexity and variability of long COVID underscore the challenges it poses to healthcare professionals and the importance of ongoing research to understand its underlying mechanisms.Furthermore, the paper touches on the current state of knowledge regarding the aetiology of long COVID and the various approaches to symptom management and treatment. While a definitive cure remains elusive, efforts are underway to alleviate the burden of long COVID through pharmacological interventions, physical therapy, cognitive-behavioral therapy, and support networks. This paper comprehensively explores COVID-19's far-reaching effects, emphasizing the need for a holistic and interdisciplinary approach to understanding and managing the diverse manifestations of this global health challenge. Ongoing research and collaborative efforts are essential in addressing the complex and evolving nature of COVID-19 and its aftermath.

Clinical Impact of Telomere Length Testing for Interstitial Lung Disease

BackgroundShortened telomere length (TL) is a genomic risk factor for fibrotic interstitial lung disease (ILD), but its role in clinical management is unknown. Research QuestionWhat is the clinical impact of TL testing on the management of ILD? Study Design and MethodsPatients were evaluated in the Columbia University ILD clinic and underwent CLIA-certified TL testing by flow cytometry and fluorescence in-situ hybridization (FlowFISH) as part of clinical management. Short TL was defined as below the 10th age-adjusted percentile for either granulocytes or lymphocytes by FlowFISH. Patients were offered genetic counseling and testing if they had short TL or a family history of ILD. FlowFISH TL was compared against research qPCR TL measurement. ResultsA total of 108 patients underwent TL testing, including those with clinical features of short telomere syndrome such as familial pulmonary fibrosis (50%) or extrapulmonary manifestations in the patient (25%) or a relative (41%). The overall prevalence of short TL was 46% and was similar across clinical ILD diagnoses. The number of short telomere clinical features was independently associated with detecting short TL (OR 2.00, 95% CI [1.27, 3.32]). TL testing led to clinical management changes for 35 (32%) patients, most commonly resulting in reduction or avoidance of immunosuppression. Of the patients who underwent genetic testing (n=34), a positive or candidate diagnostic finding in telomere-related genes was identified in 10 (29%) patients. Inclusion of TL testing below the 1st percentile helped reclassify 8 of 9 variants of uncertain significance (VUS) into actionable findings. The qPCR test correlated with FlowFISH, but age-adjusted percentile cutoffs may not be equivalent between the two assays. InterpretationIncorporating TL testing in ILD impacted clinical management and led to the discovery of new actionable genetic variants.

Extrapulmonary manifestations of &lt;i&gt;Mycoplasma pneumoniae&lt;/i&gt; infection in children

Mycoplasma pneumoniae (M. pn.), which is a well-known pathogen to cause atypical pneumonia, in 25% of cases can lead to a wide range of extra-pulmonary symptoms, reflecting damage to almost any organ or organ system (skin and mucous membranes, nervous, cardiovascular, gastrointestinal, urinary system etc.). Aspecific syndrome Mycoplasma pneumoniae-induced rash and mucositis (MIRM) has been identified recently. Among the CNS manifestations associated with M. pn., acute postinfectious cerebellar ataxia is worth mentioning. In this article we present clinical cases of a 14-year-old boy and a 6-year-old girl with extrapulmonary manifestations of M. pn. infection. This article considers etiological, pathogenetic and clinical features of mycoplasma infection in children with an emphasis on extra-respiratory manifestations.

Ultrasound criteria for assessing the correction of metabolic-associated fatty liver disease and liver blood flow disorders using arginine in patients with coronary artery disease in combination with COVID-19

Background. Coronavirus disease 2019 (COVID-19) remains one of the most urgent global health problems today. In the conditions of its spread around the world, the global scientific community is trying to study not only respiratory, but also extrapulmonary manifestations of this infection. It is known that with COVID-19, the endothelium, the hemostasis system, and the liver are affected with the occurrence of such a complication as metabolic dysfunction-associated steatotic liver disease (MASLD). The most vulnerable group of patients in terms of coronavirus disease and its complications (including MASLD) are those with coronary heart disease (CAD), therefore the search for effective drugs and optimal ultrasound criteria to evaluate liver steatosis in the dynamics of treatment is the main task of modern medicine. Goal: to determine the ultrasound criteria for assessing the correction of MASLD and liver blood flow disorders using arginine in patients with CAD associated with COVID-19. Materials and methods. A prospective study was conducted in 52 patients with CAD combined with PCR-positive COVID-19. The study was carried out upon admission to the hospital and 6 months after discharge. Group I (n = 27) consisted of CAD + COVID-19 patients who, in addition to standard therapy for MASLD, received arginine for 6 months after discharge from the hospital; group II (comparison group, n = 25) included participants who received standard therapy wi­thout arginine. Results. Splanchnic artery duplex scanning at baseline showed that 21 (78.0 %) patients in group I and 19 (76.0 %) in group II had a decrease in peak systolic velocity (PSV) in the proper hepatic artery (PHA), an increase in portal vein blood flow at the beginning of treatment, as well as increased liver size in 20 (74.0 %) patients in group I and 17 (68.0 %) in group II. An increase in the attenuation coefficient was detected in all patients of groups I and II. There were no differences between the groups at the time of inclusion in the study in terms of splanchnic blood flow and atte­nuation coefficient. After 6 months of arginine treatment, an improvement in the portal vein blood flow and a decrease in blood flow velocity in the PHA, a decrease in the diameter of the portal vein, a decrease in the size of the right and left liver lobes were found in group I, with no improvement in group II. A repeated study revealed a decrease in the attenuation coefficient in group I and no changes in group II. At the beginning of the study, a direct correlation was found between fibrinogen and the attenuation coefficient in group I (r = 0.54; p &lt; 0.05), as well as in group II (r = 0.51; p &lt; 0.05). After 6 months, C-reactive protein decreased in both groups. Conclusions. In patients with CAD combined with COVID-19 in the presence of MASLD, a decrease in the portal vein blood flow and an increase in PSV in the PHA were found. When arginine was used for 6 months in combination with standard therapy, according to the European Society of Cardiology protocols, there was a significant decrease in the attenuation coefficient, PSV in the PHA, and an increase in the portal vein blood flow. This indicates the possibility of using the attenuation coefficient as the main marker, and PSV in the PHA and the portal vein blood flow as additional criteria for ultrasound assessment of MASLD correction with arginine in patients with CAD combined with COVID-19.

Tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment: a case report

BackgroundOcular tuberculosis is a relatively rare extrapulmonary manifestation of tuberculosis. This vision-threatening disease is extremely challenging to diagnose, particularly because it can mimic other diseases. We report a case of tuberculous ciliary body granuloma initially diagnosed as bullous retinal detachment.Case reportA 52-year-old female presented with bullous retinal detachment in her left eye, and ultrasound biomicroscopy (UBM) verified the presence of a lesion with ciliary body granulomatous inflammation. The T-SPOT was positive, and the purified protein derivative (PPD) test was strongly positive (diameter of 20 mm). Following the administration of oral anti-tuberculosis regimen combined with prednisone, the retina gradually became reattached, the ciliary body granuloma became significantly reduced in size, and the visual acuity of the patient noticeably improved.ConclusionsTuberculous ciliary body granulomas can cause bullous exudative retinal detachment and can be diagnosed with UBM. Early and full-course anti-tuberculosis treatment (ATT) combined with corticosteroid therapy can improve the patient prognosis.

Extrapulmonary forms of tuberculosis. Clinical case report of a child with tuberculous osteoarthritis

Introduction: Tuberculous osteoarthritis, caused by Mycobacterium tuberculosis, is a very rare extrapulmonary manifestation of tuberculosis, especially in children. Aim: This article presents a clinical case of a 21-month-old male patient with tuberculous osteoarthritis affecting the ankle joint. The rarity of this pathology underscores the critical importance of swift diagnosis and a multidisciplinary approach involving specialists from diverse medical fields. Results: Early initiation of specific antituberculous treatment, coupled with timely surgical intervention, ameliorated the patient’s immediate suffering. Furthermore, this combined therapeutic strategy holds promise for a favorable long-term prognosis regarding joint function. Conclusion: Tuberculosis in children exhibits markedly diminished incidence, and its extrapulmonary variants are exceedingly rare. However, clinicians should maintain a high index of suspicion, particularly when confronted with recalcitrant diseases that defy conventional therapeutic approaches. A comprehensive understanding of tuberculous osteoarthritis, despite its rarity, is pivotal for effective management.

Exploring the Role of Genetics in Sarcoidosis and Its Impact on the Development of Cardiac Sarcoidosis

Sarcoidosis is a multifaceted and multisystemic inflammatory disorder, the etiology of which remains unknown. However, it has been suggested that an intricate interplay between genetic, environmental, and inflammatory factors may contribute to the development and progression of sarcoidosis. Although 30–50% of patients demonstrate extra-pulmonary manifestations, cardiac involvement is rare, affecting only 2–5% of cases. Diagnosis is often challenging, relying on the careful application of clinical judgment, histopathological evidence, and imaging biomarkers. In this literature review, we aim to provide a comprehensive overview of the current understanding of the genetic basis of sarcoidosis, the contribution to the pathogenesis of the disorder, and discuss the potential link between certain genetic variants and the development of cardiac sarcoidosis.

An elderly male with septic arthritis and bacteremia

Rhodococcus hoagii is a gram positive actinomycete found in horses and cattle. Humans can be infected by ingestion or inhalation through contaminated food or soil. The organism usually infects immunosuppressed hosts with pneumonia being the common presentation. We present a case of an 89 years old, apparently immunocompetent host presenting with fever, encephalopathy and arthritis who grew Rhodococcus hoagii in blood and synovial fluid, The patient responded well to a combination of vancomycin, azithromycin and imipenem-cilastatin. Our case demonstrates that extra-pulmonary manifestations such as septic arthritis and bacteremia can be seen in immune competent hosts.

Rhabdomyolysis – A Rare Presentation of COVID-19

Abstract COVID-19 pandemic presented a great global health-care challenge. The spectrum of illness comprises pulmonary and extrapulmonary manifestations including hepatic, renal, and neurological complications. Our patient is a young male who presented with fever, severe myalgia, and respiratory distress. After a thorough clinical examination and laboratory investigations, the diagnosis of COVID-19 pneumonia and associated rhabdomyolysis was made. He developed acute renal failure for which intravenous hydration was given. He also required renal replacement therapy. He was successfully treated and discharged with complete remission of symptoms. We did a literature search for similar cases and have discussed the potential mechanisms implied for these complications.

Sequential Infection with Influenza A Virus Followed by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Leads to More Severe Disease and Encephalitis in a Mouse Model of COVID-19.

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection ('twinfection') is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.

Acute Tuberculous Appendicitis, a Rare Entity

Tuberculous appendicitis is a rare disease, with an overall incidence of between 1.5-3.0% among tuberculosis patients. It was first described by Corbin et al in 1873 and since then has been rarely recorded in publications and case reports. In the USA, extrapulmonary disease is seen in around 20-30% of tuberculosis patients, with the most common extrapulmonary manifestations being bone (30%), urinary tract (24%) and lymph node (13%) involvement. A high index of suspicion is required to make the diagnosis of appendicular tuberculosis, although it can cause damage to the appendix without other signs of localized disease. We report a case of a woman diagnosed with primary tuberculous appendicitis in a patient with human immunodeficiency virus (HIV), with evidence of extra-intestinal disease.

Long-term therapy with CFTR modulators consistently improves glucose metabolism in adolescents and adults with cystic fibrosis

BackgroundImpaired glycemic control and the subsequent development of Cystic fibrosis Related Diabetes (CFRD) are prevalent complications, affecting up to 50 % of adults with cystic fibrosis (CF). CFTR modulator (CFTRm) therapies improve pulmonary functions, reduce exacerbation rates, increase survival in people with CF (pwCF) and appear to have a positive effect on extrapulmonary manifestations, such as nutritional state, improvements in upper respiratory symptoms, and quality of life. Initial findings indicate that CFTRm may have a positive impact on short-term glycemic control; however, long-term effects remain uncertain at present. MethodsIn this retrospective study, data were collected and analyzed on 15 pwCF, ages 13–37 years, started on CFTRm therapy. Oral Glucose Tolerance Test (OGTT) results were compared pre- and post-CFTRm therapy. ResultsThe 120-min OGTT value decreased from 159.7 mg/dL to 130.4 mg/dL post-CFTRm (p = 0.047). The average time elapsed between the two OGTTs was 49.87 months (ranging 9–157 months, median 38 months). Glycemic status improved in six pwCF (two CFRD to normal (NGT)/indeterminate (INDET) glucose tolerance; two impaired glucose tolerance (IGT) to INDET; two INDET to NGT) and worsened in one (IGT to CFRD). Six pwCF and NGT remained stable with no changes in glycemic status throughout the follow-up period. ConclusionsCFTRm therapy may decelerate the glycemic control deterioration in pwCF over an extended period. These findings indicate the need for periodic OGTTs following the initiation of CFTRm therapy to appropriately adjust insulin requirements and prevent hypoglycemia. Further larger cohorts are required to authenticate and substantiate these findings.