Comparison of Long-Term Outcomes of Surgical Treatment of Human Papillomavirus-Dependent Neoplastic Lesions in Patients With Chronic Immunosuppression After Allogenic Organ Transplantation and Patients With Primary or Acquired Immunodeficiency-A One-Center Experience.

Immunodeficiency predisposes to severe manifestations of human papillomavirus (HPV) infection, including extensive, recalcitrant anogenital lesions and their progression towards carcinomas. This holds for primary and acquired immunodeficiencies, and post-transplant immunosuppressive therapy. About 50% to 90% of patients receiving chronic immunosuppression after allogenic transplantation develop HPV-associated lesions within 4 to 5 years, comprising 10% to 15% of patients presenting with (pre)cancerous HPV-dependent anogenital lesions. Immunodeficiency is one of the highest risk factors associated with severe clinical manifestations of HPV-associated cancers. The primary objective of this work is to compare the long-term therapeutic effectiveness of surgical intervention for HPV-dependent lesions in transplant recipients undergoing chronic immunosuppression and patients burdened with primary or acquired immunodeficiencies. Two groups of 30 patients (selected for most extensive presentations of HPV-dependent neoplastic anogenital lesions), who underwent surgical treatment of these lesions were followed up for 3 to 5 years. The first group comprised patients who qualified and underwent kidney or liver transplantation (10 for a rare disease indication) and are under chronic immunosuppressive regimens. The second group comprised patients burdened by primary or acquired immunodeficiency (15 each). The recurrence rate in the follow-up period was the primary compared parameter. The recurrence rate was higher in the second group, amounting to >15%. For the first group a <5% recurrence rate was observed for recipients without rare disease indications, compared to <15% for recipients with such indications. The importance of rapid surgical intervention and the need for postoperative monitoring for recurrence is highlighted. Chronic immunosuppression demonstrates high relative safety and efficacy in terms of HPV-dependent anogenital lesion recurrence.

Amantadine in unvaccinated patients with early, mild to moderate COVID-19: A randomized, placebo-controlled, double-blind trial.

BACKGROUND AND PURPOSE: Adamantanes were listed as an interesting option as an early intervention against COVID-19. We aimed to evaluate the effectiveness of amantadine in preventing the progression of COVID-19 and its neurological sequelae. METHODS: Unvaccinated patients with confirmed SARS-CoV-2 infection within 5 days were enrolled. Subjects were randomized (50:50) to amantadine (AMD; 100 mg twice daily) or placebo (PLB) for 14 days. The Ordinal Scale for Clinical Improvement of the World Health Organization (OSCI-WHO) was the primary measure. Secondary endpoints included assessment for fatigue; depression, disorders of smell and taste, and sleepiness on Days 1 and 15. RESULTS: We enrolled 99 patients (49 AMD and 50 PLB). Disease progression (OSCI-WHO = 4) was observed in 6% (AMD) and 8% (PLB) patients (p > 0.05) with further deterioration (OSCI-WHO〉4) in 0% (AMD) and 8% (PLB) patients (p > 0.05). Complete recovery on Day 15 was 60% higher in the AMD compared with the PLB group (p = 0.025). There was improvement in taste (AMD: p = 0.003; PLB: p = 0.0001) and smell (AMD: p = 0.005; PLB: p = 0.0004) but not in fatigue in both groups. Improvement was observed in the AMD (p = 0.010) but not in the PLB group (p = 0.058) when assessing depression as well as sleepiness (AMD: p = 0.0002; PLB: p = 0.341). There was one death in the PLB group (2.0%) and none in the AMD group (p > 0.05) until Day 210. Overall, the drug was well tolerated. CONCLUSION: The central effects of amantadine on the nervous system with reduction of sleepiness and depression might have had a supportive effect on faster recovery in early COVID-19 patients.

POLCOVID: a multicenter multiclass chest X-ray database (Poland, 2020-2021).

The outbreak of the SARS-CoV-2 pandemic has put healthcare systems worldwide to their limits, resulting in increased waiting time for diagnosis and required medical assistance. With chest radiographs (CXR) being one of the most common COVID-19 diagnosis methods, many artificial intelligence tools for image-based COVID-19 detection have been developed, often trained on a small number of images from COVID-19-positive patients. Thus, the need for high-quality and well-annotated CXR image databases increased. This paper introduces POLCOVID dataset, containing chest X-ray (CXR) images of patients with COVID-19 or other-type pneumonia, and healthy individuals gathered from 15 Polish hospitals. The original radiographs are accompanied by the preprocessed images limited to the lung area and the corresponding lung masks obtained with the segmentation model. Moreover, the manually created lung masks are provided for a part of POLCOVID dataset and the other four publicly available CXR image collections. POLCOVID dataset can help in pneumonia or COVID-19 diagnosis, while the set of matched images and lung masks may serve for the development of lung segmentation solutions.

Pathological changes or technical artefacts? The problem of the heterogenous databases in COVID-19 CXR image analysis.

BACKGROUND: When the COVID-19 pandemic commenced in 2020, scientists assisted medical specialists with diagnostic algorithm development. One scientific research area related to COVID-19 diagnosis was medical imaging and its potential to support molecular tests. Unfortunately, several systems reported high accuracy in development but did not fare well in clinical application. The reason was poor generalization, a long-standing issue in AI development. Researchers found many causes of this issue and decided to refer to them as confounders, meaning a set of artefacts and methodological errors associated with the method. We aim to contribute to this steed by highlighting an undiscussed confounder related to image resolution. METHODS: 20 216 chest X-ray images (CXR) from worldwide centres were analyzed. The CXRs were bijectively projected into the 2D domain by performing Uniform Manifold Approximation and Projection (UMAP) embedding on the radiomic features (rUMAP) or CNN-based neural features (nUMAP) from the pre-last layer of the pre-trained classification neural network. Additional 44 339 thorax CXRs were used for validation. The comprehensive analysis of the multimodality of the density distribution in rUMAP/nUMAP domains and its relation to the original image properties was used to identify the main confounders. RESULTS: nUMAP revealed a hidden bias of neural networks towards the image resolution, which the regular up-sampling procedure cannot compensate for. The issue appears regardless of the network architecture and is not observed in a high-resolution dataset. The impact of the resolution heterogeneity can be partially diminished by applying advanced deep-learning-based super-resolution networks. CONCLUSIONS: rUMAP and nUMAP are great tools for image homogeneity analysis and bias discovery, as demonstrated by applying them to COVID-19 image data. Nonetheless, nUMAP could be applied to any type of data for which a deep neural network could be constructed. Advanced image super-resolution solutions are needed to reduce the impact of the resolution diversity on the classification network decision.

Lymphogranuloma venereum: an emerging problem in Poland.

Lymphogranuloma venereum (LGV) is a sexually transmitted disease that increases in incidence, particularly in more developed countries worldwide. LGV is caused by Chlamydia trachomatis serovars/genovars L1-3, including their subvariants, and in Europe mostly affects men who have sex with men (MSM). It can be asymptomatic but has now emerged as a frequent cause of severe proctitis/proctocolitis, especially in MSM. LGV has often been misdiagnosed as C. trachomatis serovars/genovars D-K infection. It is essential with accurate diagnosis that ensures appropriate treatment and protects the patient from complications and sequelae as well as from the consequences of misdiagnosis, e.g. as inflammatory bowel disease or cancer. We present a systematic review of LGV and two new LGV cases diagnosed in Poland.

The use of amantadine in the prevention of progression and treatment of COVID-19 symptoms in patients infected with the SARS-CoV-2 virus (COV-PREVENT): Study rationale and design.

BACKGROUND: COVID-19, a disease caused by infection with the SARS-CoV-2 virus, is asymptomatic or mildly symptomatic in most cases. Some patients, usually burdened with risk factors develop acute respiratory failure and other organ dysfunction. In such cases, the mortality rate is very high despite the use of intensive therapy. Amantadine has complex activity including antiviral, antiinflammatory and dopaminergic effects. This clinical trial will assess the efficacy and safety of amantadine in the prevention of COVID-19 progression toward acute respiratory failure and neurological complications. METHODS AND RESULTS: The trial will enroll 200 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included as hospitalized or ambulatory subjects for early treatment of illness. The recruitment will take place in 8 centers covering different regions of Poland. For 14 days they will be given either 200 mg of amantadine a day or placebo. Our hypothesis is a considerable reduction in the number of patients with progression toward respiratory insufficiency or neurological complications thanks to the treatment of amantadine. CONCLUSIONS: Demonstrating the efficacy and safety of amantadine treatment in improving the clinical condition of patients diagnosed with COVID-19 is of great importance in combating the effects of the pandemic. It has potential to influence on the severity and course of neurological complications, which are very common and persist long after the infection as long-COVID syndrome. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identification no. NCT04854759; Eudra CT number: 2021-001144-98 (dated 27 February 2021).

Local, non-systemic, and minimally invasive therapies for calcinosis cutis: a systematic review.

Calcinosis cutis is a deposition of calcium in the skin and subcutaneous tissue, often accompanied by pain, reduced mobility, and chronic infections. Limited evidence is available about the feasibility and efficacy of therapies alternative to systemic treatment and surgical excision, both of which often lead to unsatisfactory results or complications. We conducted a systematic review to evaluate the efficacy and safety of topical and intralesional sodium thiosulfate, extracorporeal shock-wave lithotripsy (ESWL), and laser for calcinosis cutis. PubMed, Embase, and Web of Science were searched. Reports of calciphylaxis and treatment combined with systemic medications were excluded. A total of 40 studies including 136 patients were analysed. Partial or complete remission after monotherapy was observed in 64% to 81% of cases. Self-applied topical sodium thiosulfate required patient's adherence (mean treatment duration, 4.9 months; range 2-24). Laser therapy enabled complete remission of microcalcifications after a single procedure (57%; 12/21). ESWL and intralesional sodium thiosulfate injections decreased calcinosis-associated pain (median reduction in VAS score, 3; range 0-9 and 1; range 0-5, respectively). The most common adverse event was scarring and hyperkeratosis, observed after CO2 laser (56%; 10/18). Intralesional sodium thiosulfate injections caused transient pain in over 11% of patients. Recurrences within the follow-up were rare (2%; 3/136). This study provides an overview of minimally invasive and local therapies that in selected cases might transcend conventional treatment. The limitation of this study is the poor level of evidence, which emerges mainly from non-randomized studies at high risk of bias.

Abdominoplasty Skin-Based Dressing for Deep Wound Treatment-Evaluation of Different Methods of Preparation on Therapeutic Potential.

The management of hard-to-heal wounds is a significant clinical challenge. Acellular dermal matrices (ADMs) have been successfully introduced to enhance the healing process. Here, we aimed to develop protocol for the preparation of novel ADMs from abdominoplasty skin. We used three different decellularization protocols for skin processing, namely, 1M NaCl and sodium dodecyl sulfate (SDS, in ADM1); 2M NaCl and sodium dodecyl sulfate (SDS, in ADM1); and a combination of recombinant trypsin and Triton X-100 (in hADM 3). We assessed the effectiveness of decellularization and ADM's structure by using histochemical and immunochemical staining. In addition, we evaluated the therapeutic potential of novel ADMs in a murine model of wound healing. Furthermore, targeted transcriptomic profiling of genes associated with wound healing was performed. First, we found that all three proposed methods of decellularization effectively removed cellular components from abdominoplasty skin. We showed, however, significant differences in the presence of class I human leukocyte antigen (HLA class I ABC), Talin 1/2, and chondroitin sulfate proteoglycan (NG2). In addition, we found that protocols, when utilized differentially, influenced the preservation of types I, III, IV, and VII collagens. Finally, we showed that abdominoplasty skin-derived ADMs might serve as an effective and safe option for deep wound treatment. More importantly, our novel dressing (ADM1) improves the kinetics of wound closure and scar maturation in the proliferative and remodeling phases of wound healing. In conclusion, we developed a protocol for abdominoplasty skin decellularization suitable for the preparation of biological dressings. We showed that different decellularization methods affect the purity, structure, and therapeutic properties of ADMs.

Optimization of Novel Human Acellular Dermal Dressing Sterilization for Routine Use in Clinical Practice.

Gamma rays and electrons with kinetic energy up to 10 MeV are routinely used to sterilize biomaterials. To date, the effects of irradiation upon human acellular dermal matrices (hADMs) remain to be fully elucidated. The optimal irradiation dosage remains a critical parameter affecting the final product structure and, by extension, its therapeutic potential. ADM slides were prepared by various digestion methods. The influence of various doses of radiation sterilization using a high-energy electron beam on the structure of collagen, the formation of free radicals and immune responses to non-irradiated (native) and irradiated hADM was investigated. The study of the structure changes was carried out using the following methods: immunohistology, immunoblotting, and electron paramagnetic resonance (EPR) spectroscopy. It was shown that radiation sterilization did not change the architecture and three-dimensional structure of hADM; however, it significantly influenced the degradation of collagen fibers and induced the production of free radicals in a dose-dependent manner. More importantly, the observed effects did not disrupt the therapeutic potential of the new transplants. Therefore, radiation sterilization at a dose of 35kGy can ensure high sterility of the dressing while maintaining its therapeutic potential.

Review of the Latest Methods of Epidermolysis Bullosa and Other Chronic Wounds Treatment Including BIOOPA Dressing.

Epidermolysis bullosa (EB) is a hereditary genetic skin disorder, classified as a type of genodermatosis, which causes severe, chronic skin blisters associated with painful and potentially life-threatening complications. Currently, there is no effective therapy or cure for EB. However, over the past decade, there have been several important advances in treatment methods, which are now approaching clinical application, including gene therapy, protein replacement therapy, cell therapy (allogeneic fibroblasts, mesenchymal stromal cells), bone marrow stem cell transplant, culture/vaccination of revertant mosaic keratinocytes, gene editing/engineering, and the clinical application of inducible pluripotent stem cells. Tissue engineering scientists are developing materials that mimic the structure and natural healing process to promote skin reconstruction in the event of an incurable injury. Although a cure for EB remains elusive, recent data from animal models and preliminary human clinical trials have raised the expectations of patients, clinicians, and researchers, where modifying the disease and improving patients' quality of life are now considered attainable goals. In addition, the lessons learned from the treatment of EB may improve the treatment of other genetic diseases.

Chronic Diabetic Wounds and Their Treatment with Skin Substitutes.

With the global prevalence of type 2 diabetes mellitus steeply rising, instances of chronic, hard-healing, or non-healing diabetic wounds and ulcers are predicted to increase. The growing understanding of healing and regenerative mechanisms has elucidated critical regulators of this process, including key cellular and humoral components. Despite this, the management and successful treatment of diabetic wounds represents a significant therapeutic challenge. To this end, the development of novel therapies and biological dressings has gained increased interest. Here we review key differences between normal and chronic non-healing diabetic wounds, and elaborate on recent advances in wound healing treatments with a particular focus on biological dressings and their effect on key wound healing pathways.

Correlation of Cancer Development and Human Papilloma Virus Infection in Patients After Organ Transplantation.

Immunosuppressed patients are at higher risk of developing human papilloma virus (HPV) cancerous and precancerous lesions in the anogenital region Carcinogenesis after organ transplantation due to immunosuppressive therapy is the major cause of long-term negative transplantation results. This is a rationale for the improvement of transplantation programs with carcinogenesis risk stratification in patients referred for transplantation. There is a need for a study on HPV-related carcinogenesis also in terms of its risk factors in the population after organ transplantation. This study aimed to assess the morbidity of anogenital carcinoma in patients with HPV infection, including those after organ transplantation and evaluate risk factors for carcinoma occurrence in patients after organ transplantation and with HPV infection. Our analysis directly indicates the group of patients with a high risk of HPV-related oncological complications of immunosuppression in anogenital region.

New Approach to Treatment of High-Risk Allograft Recipients Under Chronic Immunosuppression With Tooth Loss. Evaluation of Safety and Longevity of Dental Implants: A Case Report.

Patients eligible for solid organ transplant often lose their teeth and show numerous caries as well as periodontal and mucous membrane pathologies. The conventional methods of restoring teeth, including bridges and removable dentures, may result in progress of periodontal disease or even the creation of local source of general infection. Dental implants are not recognized as a therapeutic method in solid organ transplant recipients receiving immunosuppression because of the possibility of implant osseointegration disorders and suspicion as to the possibility of dysfunction of the transplanted organ and the spread of systemic infection. The authors present a case of the patient after liver transplant receiving immunosuppression treatment, who benefits from dental implants because of tooth loss. Three dental implants introduced because of the conventional loading protocol were healed and have osseointegrated without complication. Dental crown supported on them have restored the dental arches of the patient with good esthetic and functional effect. The results of treatment were stable in the 2-year follow-up period. No local signs of infection or general health disturbance were found. The function of the transplanted liver was unaffected.

New Surgical Technique Using Xenograft as a Microinvasive Method to Avoid Extensive Bone Reconstruction in Patients With Compromised General Health: Promising Surgical Methodology and First Clinical Results.

The innovative microinvasive immediate implantation technique of dental implants insertion was described. The technique uses bovine xenograft material to restore the bone defect resulting from teeth pathologies and subsequent extraction. Ten patients had extractions of their premolar upper teeth and immediate implantations with xenograft socket augmentation. This unique procedure allowed primary stability of implant above 70 implant stability quotient in all cases. All of the implants healed without complications and were restored with screwed ceramic crowns. Two-year uneventful follow-ups confirmed alveolar xenograft condensation technique as a microinvasive and safe technique, especially for patients with compromised general health who may not undergo complicated restorative operations.

Preliminary Clinical Data and the Comparison of the Safety and Efficacy of Autogenous Bone Grafts Versus Xenograft Implantations in Vertical Bone Deficiencies Before Dental Implant Installation.

Two different techniques of vertical bone augmentation were compared to apply them to immunocompromised patients. One of them used autogenous bone graft; the other used xenograft. Thirty patients were involved in the study. Fifteen received autogenous ring shape grafts harvested from the mental region, and 15 received xenograft vertical tunnel augmentation. They have a total of 60 implants placed in the posterior region of the mandible (2 for each patient). Fixed full ceramic crowns were delivered. Two-year follow-up appointments after implant placement were made. Both autogenous bone grafts and xenografts showed similar long-term clinical regeneration outcome of vertical bone defects. Using autogenous bone rings simultaneously fixed by dental implants, the total treatment time and cost were shortened, but the traumatic reactions and complication rates were higher when compared to xenograft vertical tunnel augmentation. Due to the less traumatic character of the procedure, smaller complication rates and higher safety for the patients receiving chronic immunosuppression should avoid bone block augmentation and reap the benefits from vertical tunnel bone augmentation using xenograft materials.

Differences in the Incidence of Pathologic Lesions on the Oral Mucosa in Patients Undergoing Hemodialysis vs Renal Organ Transplant Recipients Subjected to Long-term Pharmacologic Immunosuppressive Therapy.

Disorders of homeostasis and an increased incidence of infection in patients undergoing hemodialysis causes frequent appearance of pathologic changes in the oral mucosa. The organ transplant and subsequent pharmacologic immunosuppression may result in systemic disorders manifesting by pathologic oral lesions. METHODS: The study was conducted on 18 patients undergoing hemodialysis and 18 patients after renal transplant. The study comprised case taking and physical examination, including detailed intraoral and extraoral examination. RESULTS: The intraoral examination revealed gingivitis in 61.1% of patients in both groups. In the renal transplant group compared with the hemodialysis group 55.6% vs 38.9% of patients had gingival recession, 55.6% vs 44.4% had periodontitis, 27.8% vs 22.2% had macroglossia, and 11.1% vs 5.6% had geographic tongue, respectively. In the patients on hemodialysis leukoplakia and pallor or pathologic pigmentation of oral mucosa were more frequently observed lesions. Other significant findings in the renal transplant group were lingual papillary atrophy, aphthae, and erythroplakia. Patients of both group reported xerostomia, halitosis, gum bleeding, dysgeusia in their history. DISCUSSION: Both groups of patients after renal transplant and patients undergoing hemodialysis presented pathologic lesions in the oral cavity. The study revealed the differences between type and frequency of these pathologic changes, which shows different effect of the above methods of treatment of end-stage renal failure on the oral cavity.

Viruses in transplantology.

The 3 leading causes of death in patients after solid organ transplantation (SOT) include cardiovascular diseases, malignancies, and infections. According to our current understanding, the latter play the key role in the pathogenesis of atherosclerosis. Similarly, infections (mainly viral) are implicated in the pathogenesis of at least 20% of known neoplasms. In other words, the implications of acute and chronic infectious diseases in modern medicine, not only transplantology, are significant and ever­increasing. Immunosuppressive treatment impairs the immune function, which renders the patient more susceptible to infections. Furthermore, treatment of infections in immunocompromised patients poses a challenge and SOT. The current publication provides a brief summary of the key information provided in 20 lectures on viral infections in patients after SOT delivered during the 9th Practical Transplantology Course in Warsaw, Poland on September 15-16, 2017.

Adverse events in patients with ankylosing spondylitis treated with TNF inhibitors: a cross-sectional study.

Background Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors safety have been performed in rheumatoid arthritis patients. Meanwhile, it seems that TNF inhibitors in ankylosing spondylitis may present a better safety profile than we thought. Objective The aim of our study was to retrospectively investigate the occurrence of adverse events in ankylosing spondylitis patients treated with TNF inhibitors. Setting A single referral center in Poland. Methods Detailed medical history of ankylosing spondylitis patients was obtained during the interview with the patient and by reviewing electronic medical records. Patients treated with TNF inhibitors and patients without TNF inhibitors treatment were compared. Main outcome measure The incidence of adverse events during the 3 months period before the interview. Results A total of 150 patients, 103 in the treatment group and 47 in the control group, were included in the study. There were no differences in the incidence of adverse events, serious adverse events, infections and opportunistic infections between both groups. However, in the treatment group, noninfectious adverse events were significantly less frequent than in control group (RR 0.39, 95% CI 0.23-0.66), with abdominal pain as the most common noninfectious adverse event (RR 0.20, 95% CI 0.07-0.63). The differences in incidence rates of specific infections were not significant, except acute infectious diarrhea which also was less frequent in patients treated with TNF inhibitors (RR 0.17, 95% CI 0.03-0.85). The female gender was significantly associated with any adverse event occurrence (OR 2.36, 95% CI 1.15-4.83). Conclusion TNF inhibitors show a good safety profile in ankylosing spondylitis patients.

Preclinical assessment of the potential of a 3D chitosan drug delivery system with sodium meloxicam for treating complications following tooth extraction.

Current medical healthcare has no sufficient innovative drug delivery formulations for treating patients with alveolar osteitis. This study presents a portion of research conducted to design, fabricate, and characterize systems for the treatment of alveolar osteitis. The results demonstrate that intra-alveolar formulations can be designed to function as drug carriers, facilitate wound dressing, and promote tissue regeneration. Our aim was to design cone-shaped implants made of microcrystalline chitosan filled with sodium meloxicam, i.e., a nonsteroidal anti-inflammatory agent. SEM analysis revealed the porous structure and monophasic characteristic of the formulation. Moreover, textural analysis demonstrated the effect of different factors (shape, hydration, addition of an active substance) on the hardness, springiness and cohesiveness of the studied systems. The active substance was released in a two-phase process. In vitro biocompatibility tests performed according to ISO 10993-5 confirmed the lack of cytotoxicity of the tested formulations. The designed formulations did not stimulate human THP1-XBlue™ monocytes to activate the transcription nuclear factor NF-κB, which ensures that the performed systems do not induce local inflammation. These initial results indicate that the innovative sodium meloxicam release system can improve safety and efficacy in clinical settings.

The Safety Profile of Tumor Necrosis Factor Inhibitors in Ankylosing Spondylitis: Are TNF Inhibitors Safer Than We Thought?

Tumor necrosis factor (TNF) inhibitors significantly improved the treatment options for patients with ankylosing spondylitis. Unfortunately, currently, there is no strategy for sustaining remission of the disease with TNF inhibitors; after discontinuation, a high percentage of patients experience flares in a short time. Therefore, up-to-date, long-term use of TNF inhibitors in patients with ankylosing spondylitis remains necessary. For this reason, the issue of the long-term safety of TNF inhibitors in patients with ankylosing spondylitis raises concerns. Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors' safety have been performed in patients with rheumatoid arthritis. Until recently, there were very few studies of TNF inhibitors' safety in ankylosing spondylitis. Meanwhile, TNF inhibitors appear to have different safety profiles in ankylosing spondylitis and rheumatoid arthritis. In this review, we describe available data on the occurrence of adverse events associated with TNF inhibitor treatment in ankylosing spondylitis, including serious adverse events, infections, serious infections, tuberculosis, opportunistic infections, hepatitis B reactivation, malignancies, laboratory test abnormalities, autoimmune diseases, paradoxical adverse events, and heart failure.