Current Approaches to Wound Repair in Burns: How far Have we Come From Cover to Close? A Narrative Review.

Burn injuries are a significant global health concern, with more than 11 million people requiring medical intervention each year and approximately 180,000 deaths annually. Despite progress in health and social care, burn injuries continue to result in socioeconomic burdens for victims and their families. The management of severe burn injuries involves preventing and treating burn shock and promoting skin repair through a two-step procedure of covering and closing the wound. Currently, split-thickness/full-thickness skin autografts are the gold standard for permanent skin substitution. However, deep burns treated with split-thickness skin autografts may contract, leading to functional and appearance issues. Conversely, defects treated with full-thickness skin autografts often result in more satisfactory function and appearance. The development of tissue-engineered dermal templates has further expanded the scope of wound repair, providing scar reductive and regenerative properties that have extended their use to reconstructive surgical interventions. Although their interactions with the wound microenvironment are not fully understood, these templates have shown potential in local infection control. This narrative review discusses the current state of wound repair in burn injuries, focusing on the progress made from wound cover to wound closure and local infection control. Advancements in technology and therapies hold promise for improving the outcomes for burn injury patients. Understanding the underlying mechanisms of wound repair and tissue regeneration may provide new insights for developing more effective treatments in the future.

The Impact of Switching to a Second Antifibrotic in Patients With Idiopathic Pulmonary Fibrosis: A Retrospective Multicentre Study From the EMPIRE Registry

Introduction Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). Methods The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF – “lack of efficacy” (LE) and “intolerance” (INT). Results While 263 (43%) of 612 patients received no second AF (“non-switched”), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: −98ml/y in switched and −172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). Conclusion The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy (AU)

The Impact of Switching to a Second Antifibrotic in Patients With Idiopathic Pulmonary Fibrosis: A Retrospective Multicentre Study From the EMPIRE Registry.

INTRODUCTION: Most patients with idiopathic pulmonary fibrosis (IPF) treated with antifibrotics (AF) have progressive disease despite treatment. A switch of AF may improve survival, but evidence from randomised controlled trials is missing. We aimed to evaluate the efficacy of an AF switch on survival and FVC decline in patients from the European MultiPartner IPF registry (EMPIRE). METHODS: The study included 612 patients who discontinued the first antifibrotic therapy. Patients were grouped and analysed from two perspectives: (1) whether they had received a second antifibrotic treatment after the discontinuation of the first therapy, and (2) a reason for discontinuation of the first AF - "lack of efficacy" (LE) and "intolerance" (INT). RESULTS: While 263 (43%) of 612 patients received no second AF ("non-switched"), 349 (57%) patients switched. Overall survival was higher in patients who received a second AF (median 50 vs. 29 months; adjusted HR 0.64, P=0.023). Similarly, the annual FVC decline was significantly reduced in switched patients: -98ml/y in switched and -172ml/y in non-switched patients (P=0.023), respectively. The switched patients had similar risk for mortality in both LE and INT groups (adjusted HR 0.95, P=0.85). The high impact of switching on survival was demonstrated in LE patients (adjusted HR 0.27, P<0.001). CONCLUSION: The patients without a second AF had significantly shorter overall survival. Our analysis suggests the importance of switching patients with an ineffective first AF therapy to a second AF therapy.

News in respiratory medicine.

Pneumology and phthisiology (respiratory medicine) has undergone dynamic development in the last two decades. The main focus of pulmonology in the past was care for patients with tuberculosis and pneumonia. Since then, respiratory medicine evolved and the current focus is on chronic pulmonary diseases, including chronic obstructive pulmonary disease, bronchial asthma, interstitial lung diseases, but also on acute lung conditions (e.g., pneumonia, pleural diseases, respiratory failure), pneumooncology or highly specialized care for rare lung diseases (e.g., cystic fibrosis, rare interstitial diseases). Bronchology, interventional pneumology and pulmonary function testing are also important components of respiratory medicine. The importance of respiratory medicine was apparent during the COVID-19 pandemic. In this article, we provide a brief overview of the most important news to the field of respiratory medicine in the year 2022, addressing the thematic areas of bronchology, cystic fibrosis, chronic obstructive pulmonary disease, asthma, interstitial lung diseases, pleural diseases, pneumooncology, tuberculosis and non-tuberculous mycobacteria.

Germline variant of CTC1 gene in a patient with pulmonary fibrosis and myelodysplastic syndrome.

Introduction: Telomeropathies are associated with a wide range of diseases and less common combinations of various pulmonary and extrapulmonary disorders. Case presentation: In proband with high-risk myelodysplastic syndrome and interstitial pulmonary fibrosis, whole exome sequencing revealed a germline heterozygous variant of CTC1 gene (c.1360delG). This "frameshift" variant results in a premature stop codon and is classified as likely pathogenic/pathogenic. So far, this gene variant has been described in a heterozygous state in adult patients with hematological diseases such as idiopathic aplastic anemia or paroxysmal nocturnal hemoglobinuria, but also in interstitial pulmonary fibrosis. Described CTC1 gene variant affects telomere length and leads to telomeropathies. Conclusions: In our case report, we describe a rare case of coincidence of pulmonary fibrosis and hematological malignancy caused by a germline gene mutation in CTC1. Lung diseases and hematologic malignancies associated with short telomeres do not respond well to standard treatment.

Evaluation of genetic risk, its clinical manifestation and disease management based on 18 susceptibility gene markers among West-Slavonic patients with sarcoidosis.

Sarcoidosis is a heterogenous, multisystemic inflammatory disease that primarily affects lungs. In this study, we multiplex genotyped 18 single-nucleotide polymorphisms (SNPs) to replicate the findings from previous genome-wide association studies (GWAS) and candidate gene studies, and extended analyses to different clinical manifestations (Löfgren's syndrome and chest X-ray [CXR] stages) including treatment response among West-Slavonic subjects (564 sarcoidosis patients and 301 healthy controls). We confirm the replication (with Bonferroni's correction) of ANXA11 rs1049550 as protective variant for sarcoidosis (odds ratio [OR] = 0.71, p = 1.33 × 10-3), non-LS (OR = 0.66, p = 2.71 × 10-4) and CXR stages 2-4 (OR = 0.62, p = 7.48 × 10-5) compared to controls in West-Slavonic population. We also validate the association of risk variants C6orf10 rs3129927 (OR = 2.61, p = 2.60 × 10-8), TNFA rs1800629 (OR = 1.56, p = 6.65 × 10-4), ATF6B rs3130288 (OR = 2.75, p = 1.06 × 10-9) and HLA-DQA1 rs2187668 (OR = 1.74, p = 8.83 × 10-4) with sarcoidosis compared to controls. For sub-phenotypes compared to controls, risk variants C6orf10 rs3129927 (OR = 5.35, p = 1.07 × 10-12), TNFA rs1800629 (OR = 2.66, p = 5.94 × 10-7), ATF6B rs3130288 (OR = 5.24, p = 5.21 × 10-13), LRRC16A rs9295661 (OR = 2.97, p = 4.29 × 10-4), HLA-DQA1 rs2187668 (OR = 3.14, p = 1.09 × 10-6) and HLA-DRA rs3135394 (OR = 5.23, p = 8.25 × 10-13) were associated with LS while C6orf10 rs3129927 (OR = 1.96, p = 4.27 × 10-4) and ATF6B rs3130288 (OR = 2.15, p = 3.36 × 10-5) were associated with non-LS. For CXR stages compared to controls, C6orf10 rs3129927 (OR = 3.67, p = 3.63 × 10-11), TNFA rs1800629 (OR = 1.84, p = 1.32 × 10-4), ATF6B rs3129927 (OR = 3.63, p = 1.82 × 10-11), HLA-DQA1 rs2187668 (OR = 2.13, p = 9.59 × 10-5) and HLA-DRA rs3135394 (OR = 3.42, p = 3.45 × 10-10) were risk variants for early CXR stages 0-1 while C6orf10 rs3129927 (OR = 1.99, p = 5.51 × 10-4), ATF6B rs3129927 (OR = 2.23, p = 3.52 × 10-5) and HLA-DRA rs3135394 (OR = 1.85, p = 2.00 × 10-3) were risk variants for advanced CXR stages 2-4. The present findings nominate gene variants as plausible prognostic markers for clinical phenotypes, treatment response and disease resolution/progression and may form the basis for establishing genotype-phenotype relationships in patients with sarcoidosis among West-Slavonic population.

The effect of nintedanib on lung functions and survival in idiopathic pulmonary fibrosis: real-life analysis of the Czech EMPIRE registry.

INTRODUCTION: The antifibrotic drug nintedanib is used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the effect of nintedanib on antifibrotic treatment outcome in real-world cohorts of Czech EMPIRE registry. PATIENTS/METHODS: Data of 611 Czech IPF subjects, 430 (70%) treated with nintedanib (NIN group), 181 (30%) with no-antifibrotic treatment (NAF group) were analysed. The influence of nintedanib on overall survival (OS), pulmonary function parameters as forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO), as well as GAP score (gender, age, physiology) and and CPI (composite physiological index) were investigated. RESULTS: During 2 year follow-up we observed that nintedanib treated patients had longer OS, compared to those treated with no-antifibrotic drugs (p < 0.00001). Nintedanib reduces risk of mortality over no-antifibrotic treatment by 55% (p < 0.001). We have observed no significant difference in the rate of FVC and DLCO decline between the NIN and NAF group. Changes within 24 months from baseline in CPI were not significant between the groups (NAF and NIN). CONCLUSION: Our real-practice study showed the benefit of nintedanib treatment on survival. There were no significant differences between NIN and NAF groups in changes from baseline in FVC %, DLCO % predicted and CPI.

Antifibrotic therapy and its indications for interstitial pulmonary fibrosis.

Idiopathic pulmonary fibrosis and chronic fibrotic interstitial lung disease with progressive phenotype are characterized by fibrotic lung parenchyma. Current antifibrotic treatment does not affect pre-existing lung parenchyma fibrosis, but prevents fibrosis progression and reduces mortality by reducing fibrotization. This work summarizes fibrotic lung processes and their treatment options.

Langerhans cell histiocytosis (LCH). Overview of symptoms of LCH, which may lead the patients to any of these medical specialists.

Langerhans cell histiocytosis (LCH) is a rare condition with incidence in adults 1-2/1 million, wherein Langerhans cells proliferate abnormally, adversely impacting organs including most frequently bones, skin, lungs, pituitary gland, lymph nodes, gums and other organs. The LCH course varies widely among patients from a self-limiting condition, to one that progresses. But LCH only very rarely culminates in death. To aim of this text is to review all possible symptoms and manifestations of this disease.

IgG4-related disease. Clinical manifestation differential diagnosis and recent International Diagnostic Criteria for IgG4-related disease.

Immunoglobulin G4- related disease (IgG4-RD) is a rare systemic fibro-inflammatory disorder. Autoimmune pancreatitis is the most frequent manifestation of IgG4-RD. However, IgG4-RD can affect any organ such as salivary glands, orbits, retroperitoneum, prostate and many others. Recent research enabled a clear clinical and histopathological description of IgG4-RD and in 2019 four Clinical phenotypes of IgG4-related disease were described. Diagnosis is based on morphological examination with typical findings of lymphoplasmocellular inflammation, storiform fibrosis and obliterative phlebitis in IgG4-RD biopsies and the tissue invading plasma cells largely produce IgG4. Elevated serum IgG4 levels are found in many but not all patients. New diagnostic criteria for IgG4-RD have been published recently in 2019 and 2021. This review summarizes current knowledge on pathophysiology, clinical manifestations, diagnosis and differential diagnosis of IgG4-RD from the point of view 2022 and in next article brings overview of the IgG4-RD therapy.

Therapy of immunoglonuline IgG4 related disease (IgG4-RD).

Immunoglobulin IgG4 related disease (IgG4-RD) is a heterogeneous disorder with multi-organ involvement recognised as a separate entity at the beginning of this century only. Evolving therapy is reviewed in this paper. Glucocorticoids are first choice drug but long administration of glucocorticoids is connected with many adverse effects. In case of combination glucocorticoids and immunosuppressive agents lower doses of glucocorticoids are needed, the response rate is higher and therapy is better tolerated. Rituximab is drug, that is possible use as monotherapy or in combination with glucocorticoids and immunosuppressive drugs. Only one study compared two immunosuporessive drugs, mycophenolate mofetil and cyclophosphamide. The response rated was similar but remissions were longer after glucocorticoids with cyclophosphamide then glucocorticoids with mycofenolat mofetil. No other comparative study of combination of various imunossupressive drugs with glucocorticoids was published. Rituximab has high number (90 %) of response rate in monotherapy, but can be used in combination with glucocorticoids and immunosuppressives. Rituximab is now preferred and recommended for maintenance therapy administered in 6-month interval. In case of advanced disease, we prefer therefore combination of rituximab, cyclofosphamide and dexamethasone for initial therapy followed by maintenance with rituximab in 6 months interval. There are two new drugs under investigation abatacept and dupilimab with promising results. Although we have very intensive therapies for good results of therapy early diagnosis before irreversible fibrotic changes in IgG4-RD involved organs is still needed.

Allergic bronchopulmonary candidiasis: A review of the literature and a case report.

BACKGROUND: Allergic bronchopulmonary candidiasis (ABPC) is an uncommon clinical syndrome associated with immune hypersensitivity to Candida species. CASE PRESENTATION: The case presentation describes a 58-year-old man with acute respiratory failure and bilateral lung infiltrates. Due to high inflammatory markers and a chest X-ray indicating lung infiltration, he was initially treated for pneumonia with combined antibiotics. Despite comprehensive treatment at the ICU, the patient's clinical status deteriorated rapidly, and further investigations provided a rare diagnosis of ABPC. After several days of combined corticosteroid and antifungal therapy, we observed rapid clinical improvement and subsequent resolution of the pulmonary infiltrates. CONCLUSION: This case report presented a rare case of ABPC mimicking bilateral pneumonia and acute respiratory failure. Our case highlighted the importance of prompt corticosteroid and antifungal treatment initiation as it resulted in rapid clinical improvement and a near complete reversal of the bilateral lung infiltrates.

The possible role of hypoxia in the affected tissue of relapsed clubfoot.

Our aim was to study the expression of hypoxia-related proteins as a possible regulatory pathway in the contracted side tissue of relapsed clubfoot. We compared the expression of hypoxia-related proteins in the tissue of the contracted (medial) side of relapsed clubfoot, and in the tissue of the non-contracted (lateral) side of relapsed clubfoot. Tissue samples from ten patients were analyzed by immunohistochemistry and image analysis, Real-time PCR and Mass Spectrometry to evaluate the differences in protein composition and gene expression. We found a significant increase in the levels of smooth muscle actin, transforming growth factor-beta, hypoxia-inducible factor 1 alpha, lysyl oxidase, lysyl oxidase-like 2, tenascin C, matrix metalloproteinase-2, matrix metalloproteinase-9, fibronectin, collagen types III and VI, hemoglobin subunit alpha and hemoglobin subunit beta, and an overexpression of ACTA2, FN1, TGFB1, HIF1A and MMP2 genes in the contracted medial side tissue of clubfoot. In the affected tissue, we have identified an increase in the level of hypoxia-related proteins, together with an overexpression of corresponding genes. Our results suggest that the hypoxia-associated pathway is potentially a factor contributing to the etiology of clubfoot relapses, as it stimulates both angioproliferation and fibroproliferation, which are considered to be key factors in the progression and development of relapses.

Coating Ti6Al4V implants with nanocrystalline diamond functionalized with BMP-7 promotes extracellular matrix mineralization in vitro and faster osseointegration in vivo.

The present study investigates the effect of an oxidized nanocrystalline diamond (O-NCD) coating functionalized with bone morphogenetic protein 7 (BMP-7) on human osteoblast maturation and extracellular matrix mineralization in vitro and on new bone formation in vivo. The chemical structure and the morphology of the NCD coating and the adhesion, thickness and morphology of the superimposed BMP-7 layer have also been assessed. The material analysis proved synthesis of a conformal diamond coating with a fine nanostructured morphology on the Ti6Al4V samples. The homogeneous nanostructured layer of BMP-7 on the NCD coating created by a physisorption method was confirmed by AFM. The osteogenic maturation of hFOB 1.19 cells in vitro was only slightly enhanced by the O-NCD coating alone without any increase in the mineralization of the matrix. Functionalization of the coating with BMP-7 resulted in more pronounced cell osteogenic maturation and increased extracellular matrix mineralization. Similar results were obtained in vivo from micro-CT and histological analyses of rabbit distal femurs with screws implanted for 4 or 12 weeks. While the O-NCD-coated implants alone promoted greater thickness of newly-formed bone in direct contact with the implant surface than the bare material, a further increase was induced by BMP-7. It can be therefore concluded that O-NCD coating functionalized with BMP-7 is a promising surface modification of metallic bone implants in order to improve their osseointegration.

A novel temperature-controlled open source microcontroller based sampler for collection of exhaled breath condensate in point-of-care diagnostics.

Exhaled breath condensate (EBC) is an attractive, non-invasive sample for clinical diagnostics. During EBC collection, its composition is influenced by the collection temperature, a factor that is often not thoroughly monitored and controlled. In this study, we assembled a novel, simple, portable, and inexpensive device for EBC collection, able to maintain a stable temperature at any value between -7 °C and +12 °C. The temperature was controlled using a microcontroller and a thermoelectric cooler that was employed to cool the aluminum block holding the glass tube or the polypropylene syringe. The performance of the novel sampler was compared with the passively cooled RTube™ and a simple EBC sampler, in which the temperature was steadily increasing during sampling. The developed sampler was able to maintain a stable temperature within ±1 °C. To investigate the influence of different sampling temperatures (i.e., +12, -7, -80 °C) on the analyte content in EBC, inorganic ions and organic acids were analyzed by capillary electrophoresis with a capacitively coupled contactless conductivity detector. It was shown that the concentration of metabolites decreased significantly with decreasing temperature. The portability and the ability to keep a stable temperature during EBC sampling makes the developed sampler suitable for point-of-care diagnostics.

Increased Collagen Crosslinking in Stiff Clubfoot Tissue: Implications for the Improvement of Therapeutic Strategies.

Congenital clubfoot is a complex musculoskeletal deformity, in which a stiff, contracted tissue forms in the medial part of the foot. Fibrotic changes are associated with increased collagen deposition and lysyl oxidase (LOX)-mediated crosslinking, which impair collagen degradation and increase the tissue stiffness. First, we studied collagen deposition, as well as the expression of collagen and the amount of pyridinoline and deoxypyridinoline crosslinks in the tissue of relapsed clubfoot by immunohistochemistry, real-time PCR, and enzyme-linked immunosorbent assay (ELISA). We then isolated fibroblast-like cells from the contracted tissue to study the potential inhibition of these processes in vitro. We assessed the effects of a LOX inhibitor, ß-aminopropionitrile (BAPN), on the cells by a hydroxyproline assay, ELISA, and Second Harmonic Generation imaging. We also evaluated the cell-mediated contraction of extracellular matrix in 3D cell-populated collagen gels. For the first time, we have confirmed significantly increased crosslinking and excessive collagen type I deposition in the clubfoot-contracted tissue. We successfully reduced these processes in vitro in a dose-dependent manner with 10-40 µg/mL of BAPN, and we observed an increasing trend in the inhibition of the cell-mediated contraction of collagen gels. The in vitro inhibitory effects indicate that BAPN has good potential for the treatment of relapsed and resistant clubfeet.

DSP rs2076295 variants influence nintedanib and pirfenidone outcomes in idiopathic pulmonary fibrosis: a pilot study.

BACKGROUND: The antifibrotic drugs nintedanib and pirfenidone are used for the treatment of idiopathic pulmonary fibrosis (IPF). We analysed the association of common profibrotic polymorphisms in MUC5B (mucin 5B, rs35705950) and DSP (desmoplakin, rs2076295) on antifibrotic treatment outcomes in IPF. METHODS: MUC5B rs35705950 and DSP rs2076295 were assessed in IPF patients (n = 210, 139 men/71 women) from the Czech EMPIRE registry and age- or sex-matched healthy individuals (n = 205, 125 men/80 women). Genetic data were collated with overall survival (OS), acute exacerbation episodes, worsening lung function and antifibrotic treatment. RESULTS: We confirmed overexpression of the MUC5B rs35705950*T allele (55.2% versus 20.9%, p < 0.001) and the DSP rs2076295*G allele (80.4% versus 68.3%, p < 0.001) in IPF compared with controls. On antifibrotic drugs, lower mortability was observed in IPF patients with DSP G* allele (p = 0.016) and MUC5B T* allele (p = 0.079). Carriers of the DSP rs2076295*G allele benefitted from nintedanib treatment compared with TT genotype by a longer OS [hazard ratio (HR) = 7.99; 95% confidence interval (CI) = 1.56-40.90; p = 0.013] and a slower decline in lung function (HR = 8.51; 95% CI = 1.68-43.14; p = 0.010). Patients with a TT genotype (rs2076295) benefitted from treatment with pirfenidone by prolonged OS (p = 0.040; HR = 0.35; 95% CI = 0.13-0.95) compared with nintedanib treatment. Both associations were confirmed by cross-validation analysis. After stratifying by MUC5B rs35705950*T allele carriage, no difference in treatment outcome was observed for nintedanib or pirfenidone (p = 0.784). In the multivariate model, smoking, age, forced vital capacity (FVC) and DLCO (diffuse lung capacity) at the IPF diagnosis were associated with survival. CONCLUSION: Our real-world study showed that IPF patients with MUC5B T* allele or DSP G* allele profit from antifibrotic treatment by lower mortability. Moreover, carriers of the DSP rs2076295*G allele benefit from treatment with nintedanib, and TT genotype from treatment with pirfenidone. MUC5B rs35705950 did not impact the outcome of treatment with either nintedanib or pirfenidone. Our single-registry pilot study should be confirmed with an independent patient cohort.

Left ventricular myocardial deformation assessment in asymptomatic patients with recently diagnosed sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease affecting different organs including the heart. Myocardial strain analysis could potentially detect the early stages of cardiac dysfunction in sarcoidosis patients. The present study aims to assess the use of cardiac magnetic resonance (CMR) strain analysis using feature tracking (FT) in the detection of early cardiac involvement in asymptomatic patients with sarcoidosis. METHODS: One hundred and thirteen CMR studies of patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis without pre-existing known cardiovascular disease were included in the study and analysed using FT and compared to 22 age and gender-matched controls. Global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS) of the left ventricle (LV) were measured. RESULTS: The sarcoidosis patients did not significantly differ from the controls in basic demographic data and had normal global and regional systolic LV function-LV ejection fraction (EF) 66 ± 7% vs 65 ± 5% in the controls (p = NS). No statistically significant differences were found in all strain parameters between patients and controls: GLS (- 13.9 ± 3.1 vs. - 14.2 ± 2.5), GCS (- 23.4 ± 4.0 vs. - 22.2 ± 2.9) and GRS (53.4 ± 13.5 vs. 51.2 ± 13.6%) (p = NS). CONCLUSION: Patients with sarcoidosis of the respiratory tract and/or extrapulmonary sarcoidosis had normal myocardial deformation measured by CMR-FT derived global strain.

COVID-19's natural course among ambulatory monitored outpatients.

Research objective was to detail COVID-19's natural trajectory in relation to the Czech population's viral load. Our prospective detailed daily questionnaire-based telemonitoring study evaluated COVID-19's impact among 105 outpatients. In accordance with government quarantine requirements, outpatients were divided into a cohort with two negative tests at the end of the disease (40 patients) and a cohort with a new algorithm (65 patients) following a 14-day quarantine. Median follow-up differed significantly between the 2 groups (23 days vs. 16 days). Only 6% of patients were asymptomatic during the entire telemonitoring period. Another 13% of patients were diagnosed asymptomatic, as suspected contacts, yet later developed symptoms, while the remaining 81% were diagnosed as symptomatic on average 6 days following symptom onset. Telemonitoring enabled precise symptom status chronicling. The most frequently reported complaints were fevers, respiratory issues, and anosmia. Six patients were eventually hospitalized for complications detected early after routine telemonitoring. During the extended follow-up (median 181 days), anosmia persisted in 26% of patients. 79% of patients in the new quarantine algorithm cohort reported no symptoms on day 11 compared to just 56% of patients in the two negative test cohort upon first testing negative (median-19 days). The highest viral load occurred within 0-2 days of initial symptom onset. Both the PCR viral load and two consecutive PCR negative sample realizations indicated high interindividual variability with a surprisingly fluctuating pattern among 43% of patients. No definitive COVID-19 symptoms or set of symptoms excepting anosmia (59%) and/or ageusia (47%) were identified. No preexisting medical conditions specifically foreshadowed disease trajectory in a given patient. Without a PCR negativity requirement for quarantine cessation, patients could exhibit fewer symptoms. Our study therefore highlights the urgent need for routine ambulatory patient telemedicine monitoring, early complication detection, intensive mass education connecting disease demeanor with subsequent swift diagnostics, and, notably, the need to reevaluate and modify quarantine regulations for better control of SARS-CoV-2 proliferation.

Amiodarone induced pulmonary toxicity.

Amiodarone is one of the more frequently used drugs in the treatment of supraventricular and ventricular arrhythmias. Many adverse effects, more or less serious, are associated with its administration. Amiodaron-induced pulmonary toxicity (AIPT) is quite rare but represents one of the most severe adverse effects with high mortality. We present an 80 years old patient, who used amidorane due to paroxysmal atrial fibrillation for several years. Within 3 months, he was repeatedly hospitalized for a bilateral pneumonia. Eventually, AIPT was diagnosed. Early diagnosis, proper therapy of AIPT and changed antiarrhythmic therapy has significantly improved the clinical status of our patient. In this case we demonstrate typical clinical presentations of AIPT as well as the most common diagnostic procedures and recommended treatment methods. Finally, some other commonly used therapeutical options for supraventricular arrhythmias are mentioned. Future options are outlined.