Zaostrzenie choroby Leśniowskiego-Crohna w III trymestrze ciąży ― kiedy podać infliksymab? Opis przypadku i przegląd piśmiennictwa

Pacjentka z chorobą Leśniowskiego-Crohna (33 lata), w 27. tygodniu ciąży została przyjęta do Kliniki Chorób Wewnętrznych i Gastroenterologii z Pododdziałem Leczenia NChZJ w Warszawie z powodu ciężkiego zaostrzenia oraz z objawami znacznego niedożywienia. Mimo stosowanej wcześniej steroidoterapii systemowej, antybiotykoterapii oraz żywienia parenteralnego nie uzyskano poprawy klinicznej. Oprócz krwistej biegunki, do 8 stolców na dobę, występowały stany podgorączkowe, silne bóle jamy brzusznej oraz wysokie parametry zapalne. Ciężka hipoalbuminemia przyczyniła się do powstania masywnych obrzęków obwodowych oraz wodobrzusza. Po pomyślnym przeprowadzeniu kwalifikacji, chorej podano 300 mg infliksymabu dożylnie zgodnie z aktualnie obowiązującymi wytycznymi, leczenia indukcyjnego nie kontynuowano. Efekt kliniczny zaobserwowano 3 dni po podaniu jednorazowej dawki leku. Osiągnięto w krótkim czasie remisję kliniczną, ponadto znacznie ustąpiły obrzęki obwodowe. Zastosowane leczenie pozwoliło na bezpieczne przedłużenie okresu trwania ciąży o ponad 2 miesiące. Poród odbył się w 36. tygodniu, dziecko urodziło się prawidłowo rozwinięte: o masie 2100 g, w punktacji APGAR: 10. Wytyczne europejskie zalecają kontynuację leków anty-TNFα w ciąży u wszystkich chorych do początku III trymestru, natomiast opublikowane rok później wytyczne amerykańskie przesuwają granicę bezpiecznego podania ostatniej dawki leku do 30.–32. tygodnia ciąży w przypadku infliksymabu i 34.–36. tygodnia ― adalimumabu. Należy odroczyć podanie szczepionek żywych u noworodków o minimum 6 miesięcy. Podanie leków biologicznych nie wiąże się z ryzykiem wystąpienia powikłań okołoporodowych ani wzrostem częstości infekcji w pierwszych latach życia

Delayed diagnosis of human immunodeficiency virus infection in a patient with non-specific neurological symptoms and pancytopenia: a case report

INTRODUCTION: Both non-specific presentation and asymptomatic course of human immunodeficiency virus infection lead to undiagnosed long-term persistence of the virus in a patient's organism. CASE PRESENTATION: Here, we present a case of a 31-year-old Caucasian man with non-specific neurological symptoms and pancytopenia, who was referred to an internal medicine ward for further diagnosis. Upon admission to our hospital, he denied any past risky behaviors and refused to have his blood collected for human immunodeficiency virus testing. Later, he eventually provided consent to conduct the human immunodeficiency virus test which turned out to have a positive result. The overall clinical pattern indicated an advanced-stage of acquired immunodeficiency syndrome, which contrasted with the history he had provided. CONCLUSIONS: This case report indicates the need to consider human immunodeficiency virus/acquired immunodeficiency syndrome diagnosis in patients with non-specific neurological and hematological disorders. Our report also demonstrates difficulties that can be experienced by the physician while trying to obtain both a clear history and consent to perform human immunodeficiency virus testing

Czy oznaczanie stężeń peptydów natriuretycznych BNP i NT-proBNP przynosi korzyści w postępowaniu z pacjentem z nagłą dusznością?

W badaniach z ostatnich lat wykazano, że ocena peptydów natriuretycznych przeprowadzona u pacjentów z dusznością pozwala znacznie zwiększyć dokładność, z jaką może być wykluczone lub potwierdzone rozpoznanie niewydolności serca. Tym niemniej do dziś nie udało się jednoznacznie ustalić, czy wprowadzenie do rutynowej diagnostyki oznaczeń peptydów natriuretycznych u tych pacjentów mogłoby przynieść wymierne korzyści farmakoekonomiczne. Część badaczy sugeruje wręcz, że oznaczanie BNP i NT-proBNP w tej grupie pacjentów ma jedynie znaczenie poznawcze i nie przekłada się na zmianę postępowania diagnostyczno-terapeutycznego. Celem niniejszej pracy jest przedstawienie wyników badań — zarówno tych, w których skupiono się na ocenie roli peptydów natriuretycznych w dokonaniu właściwego rozpoznania, jak i tych, w których analizowano potencjalne farmakoekonomiczne korzyści wykonania takiego oznaczenia. Choroby Serca i Naczyń 2011, 8 (4), 215–22

Rola monocytów w patogenezie przewlekłej białaczki limfocytowej

Chronic lymphocytic leukemia (CLL) is one of the most common leukemias in adults. CLL is characterized by numerous immune disorders leading to the development of infections which have become the major cause of death in this group of patients. According to recent reports, many of immune alterations observed in the course of CLL could be attributed to dysfunctions of monocytes/macrophages and other cells of myeloid linage. In this article, we summarized the data on the role of monocytes and monocyte-derived cells in the pathogenesis of CLL

The short-term and long-term effects of intranasal mesenchymal stem cell administration to noninflamed mice lung

Mesenchymal stem cells (mesenchymal stromal cells; MSC)-based therapies remain a promising approach to treat degenerative and inflammatory diseases. Their beneficial effects were confirmed in numerous experimental models and clinical trials. However, safety issues concerning MSCs’ stability and their long-term effects limit their implementation in clinical practice, including treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease, and COVID-19. Here, we aimed to investigate the safety of intranasal application of human adipose tissue-derived MSCs in a preclinical experimental mice model and elucidate their effects on the lungs. We assessed short-term (two days) and long-term (nine days) effects of MSCs administration on lung morphology, immune responses, epithelial barrier function, and transcriptomic profiles. We observed an increased frequency of IFNγ- producing T cells and a decrease in occludin and claudin 3 as a long-term effect of MSCs administration. We also found changes in the lung transcriptomic profiles, reflecting redox imbalance and hypoxia signaling pathway. Additionally, we found dysregulation in genes clustered in pattern recognition receptors, macrophage activation, oxidative stress, and phagocytosis. Our results suggest that i.n. MSCs administration to noninflamed healthy lungs induces, in the late stages, low-grade inflammatory responses aiming at the clearance of MSCs graft

Surgical Treatment of Wounds Using Stem Cells in Epidermolysis Bullosa (EB)

Epidermolysis bullosa (EB) is a group of hereditary skin diseases, or genodermatoses, characterized by the formation of severe, chronic blisters with painful and life-threatening complications. Despite the previous and ongoing progress in the field, there are still no effective causative treatments for EB. The treatment is limited to relieving symptoms, which—depending on disease severity—may involve skin (blisters, poorly healing wounds caused by the slightest mechanical stimuli, contractures, scarring, pseudosyndactyly) and internal organ abnormalities (esophageal, pyloric, or duodenal atresia; renal failure; and hematopoietic abnormalities). The last decade saw a series of important discoveries that paved the way for new treatment methods, including gene therapy, bone marrow transplantation, cell therapy (allogenic fibroblasts, mesenchymal stem cells [MSCs], and clinical use of induced pluripotent stem cells. Tissue engineering experts are attempting to develop skin-like structures that can facilitate the process of healing to promote skin reconstruction in injuries that are currently incurable. However, this is incredibly challenging, due to the complex structure and the many functions of the skin. Below, we characterize EB and present its potential treatment methods. Despite the cure for EB being still out of reach, recent data from animal models and initial clinical trials in humans have raised patients’, clinicians’, and researchers’ expectations. Consequently, modifying the course of the disease and improving the quality of life have become possible. Moreover, the conclusions drawn based on EB treatment may considerably improve the treatment of other genetic diseases

Long-term effects of COVID-19 on the endocrine system – a pilot case-control study

BackgroundCoronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection.MethodsWe compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol.ResultsWe found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors.ConclusionOur study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels

Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19.

Rhinoviruses and allergens, such as house dust mite are major agents responsible for asthma exacerbations. The influence of pre-existing airway inflammation on the infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely unknown. We analyse mechanisms of response to viral infection in experimental in vivo rhinovirus infection in healthy controls and patients with asthma, and in in vitro experiments with house dust mite, rhinovirus and SARS-CoV-2 in human primary airway epithelium. Here, we show that rhinovirus infection in patients with asthma leads to an excessive RIG-I inflammasome activation, which diminishes its accessibility for type I/III interferon responses, leading to their early functional impairment, delayed resolution, prolonged viral clearance and unresolved inflammation in vitro and in vivo. Pre-exposure to house dust mite augments this phenomenon by inflammasome priming and auxiliary inhibition of early type I/III interferon responses. Prior infection with rhinovirus followed by SARS-CoV-2 infection augments RIG-I inflammasome activation and epithelial inflammation. Timely inhibition of the epithelial RIG-I inflammasome may lead to more efficient viral clearance and lower the burden of rhinovirus and SARS-CoV-2 infections