Immunogenicity and Loss of Effectiveness of Biologic Therapy for Inflammatory Bowel Disease Patients Due to Anti-Drug Antibody Development.

Many patients with inflammatory bowel disease (IBD) experience a loss of effectiveness to biologic therapy (i.e., anti-TNF therapy, etc.). Therefore, in addition to the adverse effects of the treatment, these patients also face failure to achieve and maintain remission. Immunogenicity, the process of production of antibodies to biological agents, is fundamental to the evolution of loss of response to treatment in IBD patients. The presence of these antibodies in patients is linked to decreased serum drug levels and inhibited biological activity. However, immunogenicity rates exhibit significant variability across inflammatory disease states, immunoassay formats, and time periods. In this review, we aimed to elucidate the immunogenicity and immune mechanisms of antibody formation to biologics, the loss of therapy response, clinical results of biological treatment for IBD from systematic reviews and meta-analyses, as well as to summarize the most recent strategies for overcoming immunogenicity and approaches for managing treatment failure in IBD.

Navigating the Challenges of Gluten Enteropathy and Infertility: The Role of Celiac-Related Antibodies and Dietary Changes.

Celiac disease (CD) is an autoimmune condition that is initiated in genetically susceptible individuals by the exposure of the intestines to gluten, and the early start of symptoms is related to malabsorption. Atypical variants of the illness are often identified in adulthood and are frequently associated with manifestations outside of the intestines, including metabolic osteopathy, anemia, and dermatitis herpetiformis. But also, empirical data suggest a correlation between CD and reproductive abnormalities, including repeated abortions. Infertility and repeated miscarriages frequently manifest in women diagnosed with CD and may serve as the initial clinical indication of a subclinical form. Furthermore, the condition may manifest as amenorrhea, infertility, and the delivery of infants with a low birth weight. Regarding the mechanisms of CD in infertility, along with the anti-tTG action to hinder the invasiveness of trophoblast, these antibodies could damage endometrial angiogenesis, which has been shown in in vitro models with human endometrial cells and in vivo in murine models. Another important aspect is the role of nutrient deficiencies, such as zinc deficiency (connected to impaired hormone production, secondary amenorrhea, and pre-eclampsia) and folic acid, etc. Therefore, our objective was to conduct a comprehensive review of the existing literature pertaining to this specific topic and to elucidate the role of the autoantibodies in its pathogenesis.

Blood Coagulation and Thrombotic Disorders following SARS-CoV-2 Infection and COVID-19 Vaccination.

Although abundant data confirm the efficacy and safety profile of the developed vaccines against COVID-19, there are still some concerns regarding vaccination in high-risk populations. This is especially valid for patients susceptible to thrombotic or bleeding events and hesitant people due to the fear of thrombotic incidents following vaccination. This narrative review focuses on various inherited and acquired thrombotic and coagulation disorders and the possible pathophysiologic mechanisms interacting with the coagulation system during immunization in view of the currently available safety data regarding COVID-19 vaccines. Inherited blood coagulation disorders and inherited thrombotic disorders in the light of COVID-19, as well as blood coagulation and thrombotic disorders and bleeding complications following COVID-19 vaccines, along with the possible pathogenesis hypotheses, therapeutic interventions, and imaging for diagnosing are discussed in detail. Lastly, the lack of causality between the bleeding and thrombotic events and COVID-19 vaccines is debated, but still emphasizes the importance of vaccination against COVID-19, outweighing the minimal risk of potential rare adverse events associated with coagulation.

Endothelial Dysfunction and Pregnant COVID-19 Patients with Thrombophilia: A Narrative Review.

Pregnancy with SARS-CoV-2 infection can raise the risk of many complications, including severe COVID-19 and maternal-fetal adverse outcomes. Additionally, endothelial damage occurs as a result of direct SARS-CoV-2 infection, as well as immune system, cardiovascular, and thrombo-inflammatory reactions. In this narrative review, we focus on endothelial dysfunction (ED) in pregnancy, associated with obstetric complications, such as preeclampsia, fetal growth retardation, gestational diabetes, etc., and SARS-CoV-2 infection in pregnant women that can cause ED itself and overlap with other pregnancy complications. We also discuss some shared mechanisms of SARS-CoV-2 pathophysiology and ED.

High Concordance of CT Colonography and Colonoscopy Allows for the Distinguishing and Diagnosing of Intestinal Diseases.

(1) Although new imaging methods for examining the GIT with high diagnostic capabilities were introduced, the improvement and implementation of safe, efficient, and cost-effective approaches continue, and GIT diseases are still challenging to diagnose; (2) Methods: We aim to show the possibilities of computed tomography (CT) colonography for early diagnosis of colon diseases using a multidetector 32-channel CT scanner after appropriate preparation; (3) Results: After a colonoscopy was performed earlier, 140 patients were examined with CT colonography. Complete colonoscopy was performed in 80 patients (57.1%) out of 140 who underwent CT colonography. Incomplete colonoscopy was observed in 52 patients (37.2%); in 5 patients (3.6%), it was contraindicated, and in 3 patients (2.1%), it was not performed because of patients' refusal. We determined that in cases of complete FCS in 95% of patients, CT colonography established the same clinical diagnosis as FCS. In cases of incomplete, refused, or contraindicated FCS in 32.7% (17 patients), FCS failed to diagnose correctly. The main reasons for incomplete colonoscopy were: intraluminal obturation of tumor nature-17 patients (33%), extraluminal obturation (compression) from a tumor formation-4 patients (8%), stenotic changes of non-tumor nature-11 patients (21%), congenital diseases with changes in the length of the lumen of the intestinal loops-7 patients (13%), and subjective factors (pain, poor preparation, contraindications) in 13 patients (25%); (4) Conclusions: Our results confirmed that CT colonography is a method of choice in cases of negative FCS results accompanied by clinical data for the neoplastic process and in cases of incomplete and contraindicated FCS. Also, the insufflation system we developed optimizes the method by improving the quality of the obtained images and ensuring good patient tolerance.

The End or a New Era of Development of SARS-CoV-2 Virus: Genetic Variants Responsible for Severe COVID-19 and Clinical Efficacy of the Most Commonly Used Vaccines in Clinical Practice.

Although the chief of the World Health Organization (WHO) has declared the end of the coronavirus disease 2019 (COVID-19) as a global health emergency, the disease is still a global threat. To be able to manage such pandemics in the future, it is necessary to develop proper strategies and opportunities to protect human life. The data on the SARS-CoV-2 virus must be continuously analyzed, and the possibilities of mutation and the emergence of new, more infectious variants must be anticipated, as well as the options of using different preventive and therapeutic techniques. This is because the fast development of severe acute coronavirus 2 syndrome (SARS-CoV-2) variants of concern have posed a significant problem for COVID-19 pandemic control using the presently available vaccinations. This review summarizes data on the SARS-CoV-2 variants that are responsible for severe COVID-19 and the clinical efficacy of the most commonly used vaccines in clinical practice. The consequences after the disease (long COVID or post-COVID conditions) continue to be the subject of studies and research, and affect social and economic life worldwide.

Long-term effectiveness, outcomes and complications of bariatric surgery.

Dietary imbalance and overeating can lead to an increasingly widespread disease - obesity. Aesthetic considerations aside, obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases, including diabetes; hypertension; atherosclerosis; coronary artery disease and stroke; obstructive sleep apnea; depression; weight-related arthropathies and endometrial and breast cancer. A body weight 20% above ideal for age, gender and height is a severe health risk. Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet, increased physical activity, behavioral changes and drugs have failed. The two most common procedures currently used are sleeve gastrectomy and gastric bypass. This procedure has gained popularity recently and is generally considered safe and effective. Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved, more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures. This review aims to synthesize and summarize the growing evidence on the long-term effectiveness, outcomes and complications of bariatric surgery.

Islet transplantation-immunological challenges and current perspectives.

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes (T1D) by transplanting pancreatic beta cells. Overall, pancreatic islet transplantation has improved to a great extent, and cellular replacement will likely become the mainstay treatment. We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced. Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h. Approximately 54% of the patients gained insulin independence at the end of the first year, while only 20% remained insulin-free at the end of the second year. Eventually, most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation, which imposed the need to improve immunological factors before transplantation. We also discuss the immunosuppressive regimens, apoptotic donor lymphocytes, anti-TIM-1 antibodies, mixed chimerism-based tolerance induction, induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes, pretransplant infusions of donor apoptotic cells, B cell depletion, preconditioning of isolated islets, inducing local immunotolerance, cell encapsulation and immunoisolation, using of biomaterials, immunomodulatory cells, etc.

Synchronous manifestation of colorectal cancer and intraductal papillary mucinous neoplasms.

High rates of extrapancreatic malignancies, in particular colorectal cancer (CRC), have been detected in patients with intraductal papillary mucinous neoplasm (IPMN). So far, there is no distinct explanation in the literature for the development of secondary or synchronous malignancies in patients with IPMN. In the past few years, some data related to common genetic alterations in IPMN and other affiliated cancers have been published. This review elucidated the association between IPMN and CRC, shedding light on the most relevant genetic alterations that may explain the possible relationship between these entities. In keeping with our findings, we suggested that once the diagnosis of IPMN is made, special consideration of CRC should be undertaken. Presently, there are no specific guidelines regarding colorectal screening programs for patients with IPMN. We recommend that patients with IPMNs are at high-risk for CRC, and a more rigorous colorectal surveillance program should be implemented.

COVID-19 related liver injuries in pregnancy.

While severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) quickly spread across the globe, our understanding of its pathogenic mechanisms evolved. Importantly, coronavirus disease 2019 (COVID-19) is now considered a syndromic multisystem inflammatory disease involving not only the respiratory system but also the cardiovascular, excretory, nervous, musculoskeletal, and gastrointestinal systems. Moreover, a membrane-bound form of angiotensin-converting enzyme 2, the entry receptor for SARS-CoV-2, is expressed on the surface of cholangiocytes and hepatocytes, suggesting the potential of COVID-19 to involve the liver. With the widespread distribution of SARS-CoV-2 throughout the population, infection during pregnancy is no longer a rare occurrence; however, little is known about the course of hepatic injuries and related outcomes in pregnant SARS-CoV-2-positive women. Thus, the understudied topic of COVID-related liver disease during pregnancy poses a great challenge for the consulting gynecologist and hepatologist. In this review, we aim to describe and summarize potential liver injuries in pregnant women with COVID-19.

Gut Microbiome Composition and Its Metabolites Are a Key Regulating Factor for Malignant Transformation, Metastasis and Antitumor Immunity.

The genetic and metabolomic abundance of the microbiome exemplifies that the microbiome comprises a more extensive set of genes than the entire human genome, which justifies the numerous metabolic and immunological interactions between the gut microbiota, macroorganisms and immune processes. These interactions have local and systemic impacts that can influence the pathological process of carcinogenesis. The latter can be promoted, enhanced or inhibited by the interactions between the microbiota and the host. This review aimed to present evidence that interactions between the host and the gut microbiota might be a significant exogenic factor for cancer predisposition. It is beyond doubt that the cross-talk between microbiota and the host cells in terms of epigenetic modifications can regulate gene expression patterns and influence cell fate in both beneficial and adverse directions for the host's health. Furthermore, bacterial metabolites could shift pro- and anti-tumor processes in one direction or another. However, the exact mechanisms behind these interactions are elusive and require large-scale omics studies to better understand and possibly discover new therapeutic approaches for cancer.

Intravenous Immunoglobulins as Immunomodulators in Autoimmune Diseases and Reproductive Medicine.

Intravenous administration of immunoglobulins has been routinely used for more than 60 years in clinical practice, developed initially as replacement therapy in immunodeficiency disorders. Today, the use of intravenous immunoglobulins (IVIGs) is embedded in the modern algorithms for the management of a few diseases, while in most cases, their application is off-label and thus different from their registered therapeutic indications according to the summary of product characteristics. In this review, we present the state-of-the-art use of IVIGs in various autoimmune conditions and immune-mediated disorders associated with reproductive failure, as approved therapy, based on indications or off-label. IVIGs are often an alternative to other treatments, and the administration of IVIGs continues to expand as data accumulate. Additionally, new insights into the pathophysiology of immune-mediated disorders have been gained. Therefore, the need for immunomodulation has increased, where IVIG therapy represents an option for stimulating, inhibiting and regulating various immune processes.

COVID-19 Vaccines for Adults and Children with Autoimmune Gut or Liver Disease.

The SARS-CoV-2 pandemic raised many challenges for all patients with chronic conditions and those with autoimmune diseases, both adults and children. Special attention is paid to their immunological status, concomitant diseases, and the need for immunosuppressive therapy. All of these factors may impact their COVID-19 course and outcome. COVID-19 vaccination is accepted as one of the most successful strategies for pandemic control. However, individuals with immune-mediated chronic diseases, including autoimmune liver and gut diseases, have been excluded from the vaccine clinical trials. Therefore, we rely on real-world data from vaccination after vaccine approval for these patients to fill the evidence gap for the long-term safety and efficacy of COVID-19 vaccines in patients with autoimmune gut and liver diseases. Current recommendations from inflammatory bowel disease (IBD) societies suggest COVID-19 vaccination in children older than 5 years old, adults and even pregnant females with IBD. The same recommendations are applied to patients with autoimmune liver diseases. Nevertheless, autoimmune disease patients still experience high levels of COVID-19 vaccine hesitancy, and more studies have to be conducted to clarify this issue.

Mucosal COVID-19 vaccines: Risks, benefits and control of the pandemic.

Based on mucosal immunization to promote both mucosal and systemic immune responses, next-generation coronavirus disease 2019 (COVID-19) vaccines would be administered intranasally or orally. The goal of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is to provide adequate immune protection and avoid severe disease and death. Mucosal vaccine candidates for COVID-19 including vector vaccines, recombinant subunit vaccines and live attenuated vaccines are under development. Furthermore, subunit protein vac-cines and virus-vectored vaccines have made substantial progress in preclinical and clinical settings, resulting in SARS-CoV-2 intranasal vaccines based on the previously successfully used nasal vaccines. Additional to their ability to trigger stable, protective immune responses at the sites of pathogenic infection, the development of 'specific' mucosal vaccines targeting coronavirus antigens could be an excellent option for preventing future pandemics. However, their efficacy and safety should be confirmed.

COVID-19 in patients with gastrointestinal stromal tumors: Recommendations for management and vaccination.

The coronavirus disease 2019 (COVID-19) pandemic profoundly affected the management and treatment of patients with malignancies. Based on the progress reported in the literature, we reviewed the recommendations for treatment and vaccination in patients with gastrointestinal stromal tumor (GIST) during COVID-19. We focus on whether there is a risk and what could be the possible effects of vaccinating patients with GIST/cancer. Since the situation is quickly changing, and the health services have been severely disrupted, the diagnosis, treatment and recommendations for vaccination of these patients against COVID-19 are still not updated. The approval of vaccines in the pandemic gave hope that we would soon be able to return to a more normal life. However, the oncology community needs to adapt and provide the most effective treatment and care models for patients with rare cancer, such as GIST. Collecting data on the impact of vaccination in patients with GIST/cancer also will be beneficial in expanding knowledge about the future planning of treatment strategies and optimizing care in the event of a subsequent pandemic.

Factors affecting complications development and mortality after single lung transplant.

Lung transplantation (LT) is a life-saving therapeutic procedure that prolongs survival in patients with end-stage lung disease. Furthermore, as a therapeutic option for high-risk candidates, single LT (SLT) can be feasible because the immediate morbidity and mortality after transplantation are lower compared to sequential single (double) LT (SSLTx). Still, the long-term overall survival is, in general, better for SSLTx. Despite the great success over the years, the early post-SLT period remains a perilous time for these patients. Patients who undergo SLT are predisposed to evolving early or late postoperative complications. This review emphasizes factors leading to post-SLT complications in the early and late periods including primary graft dysfunction and chronic lung allograft dysfunction, native lung complications, anastomosis complications, infections, cardiovascular, gastrointestinal, renal, and metabolite complications, and their association with morbidity and mortality in these patients. Furthermore, we discuss the incidence of malignancy after SLT and their correlation with immunosuppression therapy.

Antibiotic-Related Changes in Microbiome: The Hidden Villain behind Colorectal Carcinoma Immunotherapy Failure.

The interplay between drugs and microbiota is critical for successful treatment. An accumulating amount of evidence has identified the significant impact of intestinal microbiota composition on cancer treatment response, particularly immunotherapy. The possible molecular pathways of the interaction between immune checkpoint inhibitors (ICIs) and the microbiome can be used to reverse immunotherapy tolerance in cancer by using various kinds of interventions on the intestinal bacteria. This paper aimed to review the data available on how the antibiotic-related changes in human microbiota during colorectal cancer (CRC) treatment can affect and determine ICI treatment outcomes. We also covered the data that support the potential intimate mechanisms of both local and systemic immune responses induced by changes in the intestinal microbiota. However, further better-powered studies are needed to thoroughly assess the clinical significance of antibiotic-induced alteration of the gut microbiota and its impact on CRC treatment by direct observations of patients receiving antibiotic treatment.

What could microRNA expression tell us more about colorectal serrated pathway carcinogenesis?

In the last two decades, the vision of a unique carcinogenesis model for colorectal carcinoma (CRC) has completely changed. In addition to the adenoma to carcinoma transition, colorectal carcinogenesis can also occur via the serrated pathway. Small non-coding RNA, known as microRNAs (miRNAs), were also shown to be involved in progression towards malignancy. Furthermore, increased expression of certain miRNAs in premalignant sessile serrated lesions (SSLs) was found, emphasizing their role in the serrated pathway progression towards colon cancer. Since miRNAs function as post-transcriptional gene regulators, they have enormous potential to be used as useful biomarkers for CRC and screening in patients with SSLs particularly. In this review, we have summarized the most relevant information about the specific role of miRNAs and their relevant signaling pathways among different serrated lesions and polyps as well as in serrated adenocarcinoma. Additional focus is put on the correlation between gut immunity and miRNA expression in the serrated pathway, which remains unstudied.

Surveilling Russell body Helicobacter pylori-negative gastritis: A case report and review of literature.

BACKGROUND: Russell body gastritis (RBG) is very rare type of chronic inflammation of gastric mucosa. The pathologic hallmark of the disease is Russell bodies (RB) which represent accumulation of eosinophilic cytoplasmic inclusions in endoplasmic reticulum of mature plasma cells (Mott cells). Most published cases are associated with Helicobacter pylori (H. pylori) infection because of correlation between plasma cell activation and antigenic stimulation. There are insufficient data about H. pylori-negative RBG and very little is known about the natural course of the disease. CASE SUMMARY: A 51-year-old male patient underwent endoscopic screening for mild iron deficiency anemia. Gastroscopy revealed diffuse hyperemia, edema and nodularity of the fundic and corpus mucosa. Due to non-specific endoscopic findings and iron-deficiency anemia our preliminary diagnosis was diffuse type of gastric carcinoma or gastric lymphoma. Biopsy specimens of gastric mucosa showed inflammatory infiltrate rich in Mott cells, consisting entirely of cytoplasmic RB. Absence of nuclear atypia and mitosis of the plasma cells, polyclonal pattern of the Mott cells and negative staining for cytokeratins favored diagnosis of RBG. The patient was treated with proton-pump inhibitor for 8 wk. Long-term clinical and endoscopic surveillance was scheduled. Albeit, there was no improvement in endoscopic features of the gastric mucosa in three consecutive gastroscopies, histopathological findings demonstrated that the chronic inflammatory infiltrate in the fundic mucosa is less pronounced, rich in plasma cells, with almost absent RB and Mott cells. CONCLUSION: The prognosis of this entity is uncertain, that is why these patients are subjects of continuous follow up.