Effects Of Immunosuppressive Therapy Research Articles

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Proceedings of the 28th European Paediatric Rheumatology Congress (PReS 2022)

Parvovirus B19 infection and anemia after kidney transplantation: a report of two cases

Post-transplantation anemia is common among renal transplant recipients (RTR). The most frequent causes are erythropoietin deficiency, acute allograft rejection, iron deficiency, hemolytic anemia, adverse effects of immunosuppressive therapy, and virus infection. Human parvovirus B19 (HPV B19) can cause persistent viremia and erythropoietin-resistant erythroid aplasia in immunosuppressed patients. This case report describes two male renal transplant recipients who infected HPV B19 after kidney transplantation with severe anemia. Rapid and severe anemia that did not respond to blood transfusion. Adjustment of immunosuppressive drugs and intravenous immunoglobulin treatment resolved severe anemia after two months. In conclusion, when anemia develops rapidly and severely in renal transplant recipients in the absence of rejection and hemolysis, parvovirus B19 infection should be considered.

A nationwide analysis of renal and patient outcomes for adults with lupus nephritis in Japan

The prognosis of lupus nephritis (LN) has improved following the introduction of effective immunosuppressive therapy and progress in supportive care. This study examined recent renal and patient prognosis for adults with LN in Japan. We conducted a nationwide retrospective cohort study of LN patients who received a renal biopsy between 2007 and 2012 that were registered in the Japan Renal Biopsy Registry. Of 623 registered adults with LN from 25 institutions and their affiliated or community hospitals, 489 were eligible for this study. The median age at renal biopsy was 39years, and 82.2% of patients were female. Renal biopsies were performed in 348 patients with new-onset LN, 106 with relapse LN, and 35 with refractory LN. The distribution of ISN/RPS 2003 Classes was as follows: I 1.6%; II 5.3%; III (± V) 27.0%; IV (± V) 47.0%; V 18.4%; VI 0.6%. During the median observation period of 63.8months, 36 patients (7.3%) reached a doubling of serum creatinine or end-stage kidney disease (ESKD), and 28 patients (5.7%) died. The 5year renal and patient survival rates were 93.9% and 94.7%, respectively. Multivariate analysis revealed body mass index (BMI) and estimated glomerular filtration rate (eGFR) were independent risk factors for a doubling of serum creatinine in ESKD. Age and eGFR were independent risk factors for death. Recent prognosis for adults with LN are relatively good in Japan. Risk factors for impaired renal function are BMI and eGFR at renal biopsy, while age and eGFR are risk factors for death.

The Effects of Immunosuppressive Therapy on Mortality in Patients Followed in Intensive Care Units with the Diagnosis of Critical Coronavirus Disease-2019 Pneumonia

The Effects of Immunosuppressive Therapy on Mortality in Patients Followed in Intensive Care Units with the Diagnosis of Critical Coronavirus Disease-2019 Pneumonia

Oral Alterations in Individuals in Pre and Post Heart Transplantation

Abstract: Heart failure in advanced stages and unsuccessful alternative treatments can lead the patient to heart transplantation. Patients in pre-heart transplantation who present periodontal alterations can progress to an infectious condition and compromise the success of the transplant. Transplanted patients have intraoral changes associated with immunosuppressive therapy, such as gingival hyperplasia and opportunistic infections that deserve attention, as they result in poor quality of life and worse prognosis. This study searched the literature for oral alterations frequently found in patients with heart failure in a transplant program and heart transplant recipients, highlighting the importance of the dentist in the multidisciplinary team and the long-term follow-up of the transplanted patient. In this review, cohort studies, cross-sectional studies, case-control studies and clinical cases included in the PubMed, Biblioteca Eletrônica Científica Online (SciELO) and Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs) databases of the last 11 years (from 2009 to 2020) and in English, Portuguese and Spanish. The search result made available 577 articles, which were screened and selected, so that they included all the information necessary for the statistical analysis. Among the most relevant data regarding the oral condition of pre-heart transplant patients, it was observed that 74.21% of individuals have systemic arterial hypertension as the main comorbidity and 42.69% use immunosuppressants. As for the oral diagnosis, there is a high need for periodontal treatment in 75.57% of the patients. In the profile of transplanted patients, there is a higher prevalence of diabetes mellitus (48.26%), and all patients follow drug therapy, with an association of more than one drug. Of these individuals, 90% need periodontal treatment and 17.34% had gingival hyperplasia. The data obtained allowed us to conclude that both heart transplant and transplant patients need special attention with regard to oral care, as they are susceptible to opportunistic infections and have periodontal care needs, which suggests that oral adequacy prior to transplantation is relevant, as is the control of the secondary effects of immunosuppressive therapy

Invasive pulmonary aspergilosis in a child with HIV infection

Invasive pulmonary aspergillosis (IPA) is a rare disease occurring mainly in immunocompromised patients. Currently, there is a steady increase in the number of patients with oncohematological diseases, autoimmune pathology, requiring new highly effective immunosuppressive therapy, however, HIV infection remains one of the main reasons for the development of immunosuppression. Despite the progress made in studying issues related to HIV infection, many problems, especially in relation to the course of this disease and secondary infections in children, remain unresolved. One of them is invasive mycosis, including PLA. The article presents a clinical observation of IPA in a 7-year-old patient with newly diagnosed HIV infection, demonstrates the difficulties of diagnosing and treating such conditions.

Effect of MMF Immunosuppression Based on CNI Reduction on CNI-Related Renal Damage after Lung Transplantation.

In this paper, numerous effects of immunosuppressive regimen of mycophenolate mofetil (MMF) on CNI-related renal damage after lung transplantation are evaluated thoroughly. For this purpose, 110 lung transplant recipients who were treated in our hospital from March 2016 to January 2018 were randomly selected. All patients took prednisone acetate tablets or rapamycin at the same time or not at the same time. MMF is 1 g every time, twice a day, and adjusted according to the re-examination. According to the different drugs taken by 110 patients, they were divided into cyclosporine A group and tacrolimus group. Among them, 92 patients in cyclosporine A group took cyclosporine A; 18 patients in tacrolimus group took tacrolimus. The clinical data of age and gender of the two groups were collected, To observe and compare the occurrence of CNI-related renal damage in lung transplant recipients and different immunosuppressants. The CNI dosage of tacrolimus group and cyclosporine A group was compared before and after MMF. The changes of serum creatinine level and serum creatinine clearance rate were measured before MMF administration and 30, 60, and 90 days after MMF administration, to observe the complications of CNI-related renal damage after lung transplantation. Experimental results showed that there were 16 cases (14.55%) of CNI-related renal damage in lung transplant recipients and different immunosuppressants, including 10 cases (11.36%) in males, 6 cases (27.27%) in females, 11 cases (12.09%) in tacrolimus group, and 5 cases (26.32%) in cyclosporine A group. There was no significant difference between the two groups (P > 0.05). Compared with MMF before and after administration, CNI dosage of cyclosporine A group and tacrolimus group decreased significantly (P < 0.01). Compared with MMF before administration, serum creatinine level decreased and serum creatinine clearance rate increased significantly (P < 0.05). In the follow-up, 16 patients with CNI-related renal damage were found to be immune rejection before the adjustment of immunosuppression program, no complications such as immune rejection, myelosuppression, and infection occurred within 15 months after the adjustment of immunosuppression program, blood glucose increased in 3 patients within 2 years after operation, blood lipid increased in 1 patient, urea increased in 1 patient, and uric acid increased in 1 patient. MMF immunosuppressive therapy based on CNI reduction is a safe and effective immunosuppressive therapy, which can significantly reduce immune rejection, improve renal function, and play an important role in improving CNI-related renal damage after lung transplantation.

Prevalence and clinical characteristics of hepatitis B surface antigen-negative/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA

BackgroundTo determine the prevalence of detectable serum hepatitis B virus (HBV) DNA in patients who are hepatitis B surface antigen (HBsAg)-negative and hepatitis B core antibody (HBcAb)-positive. The correlation between HBV DNA viral load and serological markers, as well as liver and coagulation function indicators were investigated. Furthermore, the effects of immunosuppressive therapy on DNA replication were assessed.MethodsA total of 2,013 HBsAg-negative/HBcAb-positive patients admitted to our hospital between January and December 2019 were enrolled in this study. Patient clinical characteristics including serological markers, HBV DNA viral load, liver function and coagulation function indicators, and immune function status were analyzed.ResultsIn the Hunan province in China, the prevalence of detectable HBV DNA was 5.4% in HBsAg-negative/HBcAb-positive patients. However, the prevalence of detectable HBV DNA in HBsAg-negative/HBcAb-positive patients may vary because of different HBV serological markers. In patients with detectable serum HBV DNA, the log10 HBV DNA value was positively correlated with alanine transaminase (ALT) and aspartate transaminase (AST) levels, and negatively correlated with antithrombin III (AT III) concentrations. Moreover, in patients receiving immunosuppressive therapy, ALT and AST levels were higher than those of patients who did not receive immunosuppressive therapy. The ALT and AST levels in hepatitis B e antibody (HBeAb)-positive patients were significantly higher than that observed in HBeAb-negative patients.ConclusionsFor HBsAg-negative/HBcAb-positive patients, clinicians should pay attention to the patient's immune function status. In situations where HBV DNA cannot be detected, changes in serum ALT, AST, and AT III concentrations can be used to speculate on viral replication status to reduce the risk of HBV infection and transmission.

Синдром змішаної кріоглобулінемії: особливості клінічного перебігу та лікування. Огляд літератури та опис клінічного випадку, асоційованого з COVID-19

Abstract. The aim of the study was to analyze the literature rewiew regarding modern methods of diagnosis and treatment of mixed cryoglobulinemia. Mixed cryoglobulinemia syndrome (MCS) is a unique systemic inflammatory syndrome, which includes small- and medium-sized vessel vasculitis caused by cryoglobulin-containing immune complexes. MCS is potentially caused by hepatitis C virus infection. It may also be associated with autoimmune or lymphoproliferative disorders or, rarely, may be idiopathic. The diagnosis of MCS should be suspected in any patient who presents with one or more of the following clinical features: palpable purpura, skin ulcers, arthralgias and/or arthritis, peripheral neuropathy, and/or microscopic hematuria or proteinuria with or without chronic kidney disease. The general approach of management of moderate to severe mixed cryoglobulinemia should include targeted treatment of the underlying disease causing the cryoglobulinemia along or with additional immunosuppressive therapy. In some cases, immunosuppressive therapy is started first, and then, after stabilization of disease, therapy for the underlying disease is added. The main indication for immunosuppressive therapy is a progressive systemic disease of the kidneys, nervous system, gastrointestinal tract, skin, or vasculitis with necrosis. The prognosis is variable and depends on the severity of the disease and the response of the underlying disease to therapy. In this publication, we also describe a rare clinical case of mixed cryoglobulinemia associated with COVID-19. Thus, the syndrome of cryoglobulinemia is quite difficult both in diagnosis, taking into account the heterogeneity of clinical and laboratory data, and in treatment which makes it necessary to select effective immunosuppressive therapy in specific clinical cases.

SARS-CoV-2-specific T-cell responses after COVID-19 recovery in patients with rheumatic diseases on immunosuppressive therapy

BackgroundIn patients with immune-mediated rheumatic diseases (RMD), the development of T-cell responses against SARS-CoV-2 may be impaired by either the immune disturbances associated with the disease, or by the effects of immunosuppressive therapies. We aimed at determining the magnitude of SARS-CoV-2-specific interferon (IFN)-γ-producing T-cell response after COVID-19 recovery in a cohort of patients with RMD on different immunosuppressive therapies. Patients and methods53 adult patients with inflammatory or autoimmune RMD and 61 sex and age-matched non-RMD patients with confirmed COVID-19 were included. Peripheral blood mononuclear cells were obtained and T-cell-IFN-γ antigen-specific responses against the S1 domain of the spike glycoprotein, the nucleoprotein (N) and the membrane (M) protein from SARS-CoV-2 were assessed by FluoroSpot assay. ResultsPatients with RMD and COVID-19 showed positive T-cells-IFN-γ responses to SARS-COV-2 antigens, in a similar proportion and magnitude as non-RMD patients at a median of 298 [151–316] and 165 [162–167] days after COVID-19 respectively. Among RMD patients 83%, 87% and 90%, and among non-RMD patients, 95%, 87% and 93% responded to S1, N and M protein respectively. Similar responses were observed in the different diagnostic and therapeutic groups, including conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), TNF-α inhibitors, IL-17 inhibitors, rituximab, JAK inhibitors or other immunosuppressants. ConclusionT-cell responses to the main SARS-CoV-2 antigens are present after COVID-19 recovery in most patients with RMD and are not impaired by immunosuppressive therapies.

A Nationwide Survey of Lower Risk Myelodysplastic Syndromes in Japan

A Nationwide Survey of Lower Risk Myelodysplastic Syndromes in Japan

Postpartum Surgical Complications in Women with Inflammatory Bowel Disease After Caesarian Section: A Danish Nationwide Cohort Study.

Our aim is to determine the 30-day postpartum surgical complications in women with inflammatory bowel disease [IBD] who undergo a caesarian section rather than a vaginal delivery. Using the Danish national registries, we established a study population of liveborn singleton births from January 1, 1997, through December 2015. We examined all mothers with IBD who had a caesarian section or a vaginal delivery. We examined 30-day maternal postpartum abdominal and perineal surgical outcomes and adjusted for multiple confounders. We examined acute versus elective caesarian sections and the effect of immunosuppressive therapies on outcomes. In women with IBD, 2.1% undergoing caesarian section [n = 3255] versus 0.3% undergoing vaginal delivery [n = 6425] had a surgical complication. Women with IBD who had a caesarian section were more likely to have small bowel and colon surgery (adjusted odds ratio [aOR] 5.00, 95% confidence interval [CI] 2.00-12.51). Similar results were found regardless of acute [aOR 4.51, 95% CI 1.48-13.76] or elective [aOR 6.52, 95% CI 2.45-17.33] caesarian section. The risk of surgery after caesarian section was increased regardless of immunosuppressive use [aOR with immunosuppressives 8.79, 95% CI 2.86-27.05; and aOR without immunosuppressives 4.49, 95% CI 1.74-11.58]. The risk of a surgical complication after caesarian section as compared with a vaginal delivery is increased in women with IBD, regardless of whether the caesarian is performed for acute or elective reasons and/or of immunosuppressive use before delivery. Due to this increased risk, physicians should perform a caesarian delivery as the exception rather than the rule.

The effect of immunosuppressive therapy in patients with fibrinoid necrosis lesions in a large cohort of patients with IgA nephropathy

Fibrinoid necrosis is considered one of the active pathological lesions in IgA nephropathy. Whether patients with IgA nephropathy with fibrinoid necrosis lesions benefit from immunosuppressive therapy in terms of long-term outcomes remains uncertain. This study aimed to evaluate the response to immunosuppressive therapy in patients with fibrinoid necrosis lesions in a large cohort of patients with IgA nephropathy. A total of 1325 patients with kidney biopsy-proven IgA nephropathy from 1994 to 2016 were recruited from the Peking University First Hospital IgA Nephropathy Database. The clinicopathological characteristics of patients with fibrinoid necrosis lesions and the effect of immunosuppressive therapy on patients with fibrinoid necrosis lesions alone or in those with fibrinoid necrosis together with crescents or endocapillary hypercellularity lesions were analyzed. In total, 107/1325 (8.1%) patients showed fibrinoid necrosis lesions, and 92/107 (86.0%) of thesepatients showed fibrinoid necrosis associated eitherwithcellular/fibrocellular crescents or endocapillary hypercellularity lesions. The presence of fibrinoid necrosis together with crescents or endocapillary hypercellularity was an independent risk factor for the kidney composite endpoint (HR, 2.11; 95% CI, 1.16-3.84; P = 0.02) in patients without immunosuppression, while for those receiving immunosuppressive therapy, kidney outcome was improved (HR, 0.80; 95% CI, 0.46-1.39; P = 0.42). However, the predictive value of fibrinoid necrosis lesions alone did not change significantly between patients with and without immunosuppressive therapy. The presence of fibrinoid necrosis with crescents or endocapillary hypercellularity lesions together, but not fibrinoid necrosis lesions alone, was a pathological indicator of patients who may benefit from immunosuppressive therapy.

Effectiveness of immunosuppressive therapy for lymphocytic myocarditis according: data from actual clinical practice

Aim. To compare the effectiveness of standard heart failure therapy with and without combined immunosuppressive therapy in patients with documented lymphocytic myocarditis (LM) based on data from actual clinical practice.Material and methods. This observational study included 70 patients with documented LM, 40% (n=28) of whom received immunosuppressive therapy. All patients underwent standard echocardiographic and laboratory investigations, endomyocardial biopsy with histological, immunohistochemical and molecular genetic analysis. Contrast-enhanced cardiac magnetic resonance imaging was performed in 74% of patients. All patients received standard therapy for heart failure at baseline.Results. The groups did not differ in demographic and echocardiographic characteristics. The appointment of immunosuppressive therapy was accompanied by an increase in ejection fraction by 12,2% compared to 6,4% (p=0,02). There were no significant differences in combined endpoints (survival and the need for heart transplantation) depending on therapy regimen (log-rank p=0,97).Conclusion. The prognosis of patients with chronic LM depends on the process activity, the severity of impaired hemodynamics and ventricular arrhythmias, as well as on the presence of persistent viral infection. Compliance with patient selection algorithm before prescribing immunosuppressive therapy is associated with the improvement in myocardial global contractility.

The effectiveness of immunosuppressive therapy in patients with aplastic anaemia secondary to chemoradiotherapy for cancers.

The outcome of immunosuppressive therapy (IST) and prognosis in patients with aplastic anaemia (AA) secondary to chemotherapy or radiotherapy for cancers remains unknown. A total of 43 of 2559 patients with AA referred to our hospital had previously received chemoradiotherapy forvarious types of solid tumours (n = 25) or haematological malignancies (n = 18). Their cancer status was complete remission (CR) in 27, non-CRin 13, and unknown in three. Small populations of glycosylphosphatidylinositol-anchored protein-deficient [GPI(-)] granulocytes were detected in 16 patients (37·2%). Of 18 patients who were treated with IST, 50% improved regardless of the presence of GPI(-) cells. The overall survival (OS) rate was significantly higher in patients with a history of solid tumours patients than in those of haematological malignancies (median OS, 87 vs. 11 months, P = 0·0003), and in patients treated with IST than in those of untreated patients (median OS, 115 vs. 20 months, P = 0·028). Cancer aggravation occurred in two of four patients who were treated with IST while in non-CR of their original cancers. Progression to myelodysplastic syndromes was observed in two patients not possessing GPI(-) cells. IST should thus be considered for patients with AA secondary to chemoradiotherapy for cancers, particularly when their original solid tumours are in CR.

Impact of a new coronavirus infection on the clinical course of immunoinflammatory rheumatic diseases

BACKGROUND: The COVID-19 pandemic poses a particular threat to patients suffering from immunoinflammatory rheumatic diseases. New coronavirus infection has been found to be accompanied by the development of a wide range of extrapulmonary clinical and laboratory manifestations, which are characteristic of a number of immunoinflammatory rheumatic diseases.&#x0D; AIM: To evaluate the features of the clinical course of immunoinflammatory rheumatic diseases in patients who underwent new coronavirus infection.&#x0D; MATERIALS AND METHODS: The clinical course of immunoinflammatory rheumatic diseases was analyzed in 324 patients who underwent new coronavirus infection from March 2020 to February 2021 and were treated at the Clinical Rheumatology Hospital No. 25, Saint Petersburg, for exacerbation of the underlying disease.&#x0D; RESULTS: Analysis showed that the risk factors for severe new coronavirus infection in patients with immunoinflammatory rheumatic diseases were: age over 60, comorbidities, use of prednisolone in a dose greater than 12,5 mg, and ESR values 40 mm/hour before the development of new coronavirus infection. There was no effect of immunosuppressive and biological therapy on the severity of the course of viral infection. There was no effect of immunosuppressive therapy and biological therapy on the severity of the course of viral infection in patients with immunoinflammatory rheumatic diseases. The development of the postinfectious syndrome was observed in 1/4 of patients, which was characterized by the formation of postinfectious arthritis in 3,6% of patients, transformation of undifferentiated arthritis into various rheumatic diseases in 49% of patients (more often into early rheumatoid arthritis), as well as exacerbation of the underlying disease in 83,4% of patients with an advanced stage of rheumatoid arthritis. In patients with mixed connective tissue disease, there was a significant increase in immunologic activity due to antinuclear factor (up to a maximum of 1:163 840). Clinical cases of the development of arthritis associated with viral infection and the debut of rheumatoid arthritis after an new coronavirus infection are presented.&#x0D; CONCLUSIONS: New coronavirus infection in the cohort of patients with immunoinflammatory rheumatic diseases observed in the Clinical Rheumatology Hospital No. 25, Saint Petersburg, proceeded in the variant of medium severity in half of patients, initiated the development of lung lesions in 68,6% of patients, arthritis associated with viral infection in 3,6% of patients, immunoinflammatory rheumatic diseases which transformed from undifferentiated arthritis in 49% of cases and exacerbation of the main disease in an overwhelming number of patients. Patients with immunoinflammatory rheumatic diseases have a high risk of adverse outcome of new coronavirus infection, especially in cases of unstable course of the disease or exacerbation of this group of diseases.

Effects of Immunosuppressive Therapy on Cell Mediated Immunity in Idiopathic Acquired Aplastic Anaemia

Aplastic Anaemia is a clonal haematological disorder characterised by bone marrow hypoplasia and pancytopenia, in the absence of any abnormal cells or increased reticulin. Idiopathic acquired aplastic anaemia accounts for more than 50% cases where immune mediated pathophysiology had been proposed. Altered counts and ratio of CD4+ and CD8+ T cells result in increased apoptosis of haematopoietic stem cells, resulting in bone marrow hypoplasia. Aplastic anaemia is a clonal disorder with clonal evolution to other haematological disorders i.e. hypoplastic myelodysplastic syndrome, Paroxysmal nocturnal haemoglobinuria (PNH) and acute leukemia. Previous studies had reported that >50% cases of aplastic anaemia are transformed into PNH during the course of disease.Haemopoietic stem cells transplant is the treatment of choice however, this option is either unavailable or un-affordable for majority of people in developing countries including Pakistan. Standard immunosuppressive therapy (IST) includes anti-Thymocyte Globulin (ATG), is also an expensive option and needs extensive monitoring therefore, not a very favourable option for most of the patients. Other immunosuppressive drugs particularly calcineurin inhibitors like Cyclosporine and Tacrolimus, had shown promising results. These drugs act by decreasing the raised counts of CD4+ and CD8+ T cells. Almost all the patients diagnosed with idiopathic acquired aplastic anaemia in Pakistan are treated on these drugs either alone or in combination with other drugs. No study has been conducted so far to evaluate the effects of different immunosuppressive drugs on T cells at different stages and length of treatment. This study was planned to evaluate the effectiveness of these drugs in restoring the immunological imbalance in idiopathic aplastic anaemia.The counts and ratios of CD4+ and CD8+ T cells were performed on blood samples of 60 patients, using FACSCount system (BD Biosciences). Our study population included patients of Pakistani and Afghan nationalities, both genders and of paediatric and adults age. PNH screening was done by Hams test however, none of the patient was positive. Patients on active treatment were categorized into different groups on the basis of drugs they were receiving i.e. Cyclosporine only, Cyclosporine with Oxymetholone and Tacrolimus groups. Patients who were newly diagnosed and treatment naive at the time of inclusion, were also included along with a group of patients who had completed their treatment and were in remission (either complete or partial).Findings of our study showed that the disease was more prevalent in males of paediatric and young adult age. CD4+ T cell counts and CD4/CD8 ratios were prominently decreased in paediatric group receiving IST however, no significant difference was noted in counts or ratios in adult patients. CD8+ T cell counts did not show any remarkable reduction with treatment in adult patients but slightly decreased counts were noted in paediatric group. All the patients in different treatment groups showed an overall reduction of CD4+, CD8+ T cell counts and ratios as compared to treatment naive cases. This difference was more pronounced in patients receiving Cyclosporine with Oxymetholone and Tacrolimus. Cyclosporine levels were done and found to be consistent with the dose and treatment status but the therapeutic levels of Tacrolimus were never achieved however, significant improvement was observed even in sub-therapeutic levels. Off-treatment cases had their CD4+, CD8+ T cell counts and ratios within the lower normal range of CD4+, CD8+ T cell counts and CD4/CD8 ratio, suggestive of an alteration in T cell biology with IST, maintaining these counts within normal range for an indefinite period.Length of treatment has a great impact on the outcome of disease as well as relapse prevention however not studied in detail in aplastic patients treated on immunosuppressive drugs. Results of our study suggests that treatment for more than 6 months followed by slow tapering is more effective in normalizing the counts and ratios of CD4+ and CD8+ T cells. Our study was the first of its kind to evaluate the effects of different immunosuppressive drugs on CD4+ and CD8+ T cell counts and CD4/CD8 ratio, in our population. Further studies are needed to understand the underlying mechanisms responsible for this immunological imbalance as well as response to different treatment options available. DisclosuresNo relevant conflicts of interest to declare.

Effective chemotherapy and targeted therapy supplemented with stereotactic radiotherapy of a patient with metastatic colon cancer following renal transplantation: a case report

BackgroundPrevious studies have shown that patients who underwent renal transplantation were at a greater risk of developing malignancies. Due to advances in effective surgical techniques and immunosuppressive therapies, organ recipients live longer. Yet, there is insufficient information about the recommended type of therapy for colorectal cancer patients following transplantation. We describe the oncological treatment of a patient with renal transplantation, who presented with metastatic colon cancer 5 years after transplantation.Case presentationA 66-year-old Caucasian male patient, with hypertension, type 2 diabetes mellitus, paroxysmal atrial fibrillation, and renal failure underwent successful kidney transplantation in 2013. In April 2018, the adenocarcinoma of the sigmoid colon was found, and surgical resection was performed. The histological diagnosis was low-grade adenocarcinoma. Fluorodeoxyglucose positron emission tomography/computerized tomography scan showed a 2.5-cm metastasis in the VIIth segment of the liver and a metastatic paraaortical lymph node on the left. The clinical diagnosis was, therefore, metastatic (stage IV) sigmoid colon cancer (AJCC TNM system). The ongoing medications of the patient included immunosuppressive drugs and medication for his cardiovascular comorbidities. In July 2018, palliative cetuximab plus folinic acid–fluorouracil–irinotecan chemotherapeutic treatment was initiated, then cetuximab was substituted for panitumumab because of adverse events. In August 2018, the follow-up positron emission tomography/computerized tomography scan revealed stable disease. Because of side effects, the patient was unwilling to continue with the panitumumab plus folinic acid–fluorouracil–irinotecan treatment regimen. Therefore, the patient received 10× 5 Gy stereotactic body irradiation for his liver metastasis and mono-panitumumab therapy. By January 2019, the positron emission tomography/computerized tomography scan showed regression of the liver metastasis but a progression in the paraaortic lymph node. Therefore, 5× 8 Gy stereotactic irradiation was given to the paraaortic lesion. Meanwhile, the patient received altogether 16 cycles of panitumumab until June 2019, when complete remission was attained. In July 2019, the patient suffered a hemorrhagic stroke, probably due to his cardiovascular comorbidities, and died subsequently.ConclusionsSince information is scarce regarding oncological treatment of patients following organ transplantation, data about their oncological treatment is essential. To our knowledge, this is the first case report to describe the successful chemotherapy and targeted therapy supplemented with stereotactic radiotherapy of a posttransplant patient with metastatic colorectal cancer.

Effect of immunosuppressive therapy in inflammatory cardiomyopathy: data from The Czech Inflammatory Cardiomyopathy Immunosuppressive Trial.

The indications for specific treatment in the cases of inflammatory cardiomyopathy are based on limited data from several small clinical trials. A comparison of the effect of two dose regimens of combined immunosuppressive therapy by adding them to conventional heart failure therapy and comparing them with conventional heart failure therapy alone in patients with inflammatory cardiomyopathy. We enrolled 20 patients; mean age 46.10±7.33 years, duration of symptoms <6 months, LVEF ≤40 %, NYHA class II-IV, with biopsy‑proven myocarditis. Patients were randomly separated into groups treated with immunosuppressive therapy in addition to conventional heart failure therapy or to a group treated with conventional heart failure therapy alone. Clinical and echocardiographic parameters were evaluated. The baseline values of LVEF in the group of immunosuppressive therapy (LVEF 22.3±4.7 %) were similar to those in the group treated with conventional heart failure therapy (LVEF 21.7±4.7 %; p=0.757). After twelve months there was no statistically significant difference in LVEF between the two studied groups (LVEF 33.7±9.5 % for the immunosuppressive therapy group and 41.3±13.0 % for the conventional therapy group; p=0.175). In our study population, we proved no positive effect of combined immunosuppressive therapy on the left ventricular function over 12 months. The main limitation of the study is the small number of enrolled patients (Tab. 4, Fig. 1, Ref. 35).

Effect of Immunosuppressive Therapy on Clinical Outcomes for Patients With Aortic Stenosis Following Transcatheter Aortic Valve Implantation.

Transcatheter aortic valve implantation (TAVI) is an established treatment for symptomatic patients with severe aortic stenosis (AS). Sometimes patients with severe AS taking immunosuppressants are encountered. The effect of immunosuppressive therapy on clinical outcomes in patients with AS following TAVI were investigated.Methods and Results:In total, 282 consecutive patients with severe AS who underwent transfemoral TAVI from January 2016 to December 2018 at St. Marianna University School of Medicine were reviewed. They were divided into 2 groups: the immunosuppressants group (IM group) in which patients continually used immunosuppressive drugs (n=22) and the non-immunosuppressants group (non-IM group) (n=260). The composite endpoints of a major adverse cardiovascular and cerebrovascular event (MACCE) defined as non-lethal myocardial infarction, unstable angina pectoris, heart failure requiring hospitalization, stroke, and cardiovascular death were evaluated. There were no differences in the incidence of vascular access complications (32% vs. 20%, P=0.143) and the rate of procedure success (100% vs. 93%, P=0.377) between the IM and non-IM groups. During the median follow-up period of 567 (16-1,312) days after the TAVI procedure, there were no significant differences between the IM and non-IM groups in the incidence of infectious complications (14% vs. 9%, P=0.442) or MACCE (18% vs. 20%, respectively; P=0.845). The use of IM after TAVI is not associated with increased vascular access complications or mid-term MACCE in patients with severe AS treated with TAVI.