Anti Thymocyte Globulin-Based Treatment for Acquired Bone Marrow Failure in Adults

Idiopathic acquired aplastic anemia can be successfully treated with Anti Thymocyte Globulin (ATG)-based immune suppressive therapy and is therefore considered a T cell-mediated auto immune disease. Based on this finding, several other forms of idiopathic acquired bone marrow failure are treated with ATG as well. For this review, we extensively searched the present literature for evidence that ATG can lead to enduring remissions in different forms of acquired multi- or single-lineage bone marrow failure. We conclude that ATG-based therapy can lead to an enduring hematopoietic response and increased overall survival (OS) in patients with acquired aplastic aplasia. In patients with hypocellular myelodysplastic syndrome, ATG can lead to a hematological improvement without changing the OS. ATG seems less effective in acquired single-lineage failure diseases like Pure Red Cell Aplasia, Amegakaryocytic Thrombocytopenia and Pure White Cell Aplasia, suggesting a different pathogenesis in these bone marrow failure states compared to aplastic anemia. T cell depletion is hypothesized to play an important role in the beneficial effect of ATG but, as ATG is a mixture of polyclonal antibodies binding to different antigens, other anti-inflammatory or immunomodulatory effects could play a role as well.

Aplastic anemia secondary to dual cancer immunotherapies a physician nightmare: case report and literature review

Background Treatment with immune checkpoint inhibitors has revolutionized cancer treatment over the past several years. Despite their clinical benefits, a wide range of immune-mediated toxicities can be observed including hematological toxicities. Although, the majority can easily be managed, immune-mediated adverse events rarely can be severe and difficult to approach. Herein, we are reporting a case of very severe aplastic anemia secondary to ipilimumab (I) and nivolumab (N) treatment that failed various treatment including intensive immune suppressive therapy. Case presentation We described a case of a 45-year old white male, heavy smoker presented to the clinic complaining of left flank pain. He was found to have a metastatic renal cell carcinoma for which he was treated with dual immunotherapy and later complicated by severe immune related adverse events. The patient later died after failing intensive immune suppressive therapy. Conclusion Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with variant malignancies. Yet, lethal adverse events can occur in rare cases. It is our duty, as physicians, to remain alert and cautious.

COVID-19 ASSOCIATED MUCORMYCOSIS (CAM) AND IT’S MANAGEMENT

AIM - The onset of COVID-19 pandemic second wave, there have been multiple reports across the country of high incidence of MUCORMYCOSIS among the recovered patients of COVID-19, especially those who are diabetics or those who have received steroids therapy extensively. In this paper, we review about COVID-19 ASSOCIATED MUCORMYCOSIS (CAM) and its management. DISCUSSION - COVID 19 infection may be associated with a wide range of bacterial as well as fungal infections, post- covid. These infections are result of complex interplay of factors such as pre-existing disease such as Diabetes, previous respiratory pathology, use of immune -suppressive therapy. Additionally, the wide spread use of steroids/broad spectrum antibiotics as part of the regimen against COVID-19, may exacerbate the opportunistic fungal infections. COVID-19 ASSOCIATED MUCORMYCOSIS (CAM) has been associated with high morbidity and mortality, resulting in exorbitant treatment cost and also leads to shortage of anti-fungal drugs. RESULT - Successful management of this fatal infection requires early identication of the disease and aggressive and prompt medical and surgical interventions. Therapeutic agents should be used cautiously and closely monitored to achieve desired results.

The Course of COVID-19 in a Patient with Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria Clone: A Case Report and Literature Review

<b><i>Introduction:</i></b> Aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) are bone marrow failure syndromes. A 20–40% of patients with AA have a PNH clone at diagnosis. To date, there are little data about the course of COVID-19 in patients with AA and PNH. <b><i>Case Presentation:</i></b> A 36-year-old gentleman, who was previously diagnosed as a case of AA with PNH clones off immune-suppressive therapy, presented with fever and cough and was diagnosed with mild pneumonia due to COVID-19 with positive nasopharyngeal swab polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2. His clinical course was benign except transient thrombocytopenia. He was asymptomatic after day 4, and viral PCR was negative on day 21. <b><i>Discussion:</i></b> Though studies have shown that COVID-19 is associated with lymphopenia, our patient had a normal to high lymphocyte count. The neutrophil to lymphocyte ratio (NLR) was &#x3c;1 during COVID-19, which correlates with the mild course of the disease. To know whether elevated lymphocyte count, low NLR, and benign course of COVID-19 is a standard feature for all patients with underlying AA, we need more case reports and series. The significance of this case report is that it describes the course of COVID-19 in a patient with AA and PNH clones and, up to our knowledge, is the first report showcasing the association between these rare combinations of diseases.

Evidence-based treatment of ANCA-associated vasculitis with kidney involvement

ANCA-associated vasculitides (AAV) is a group of rare systemic autoimmune disorders characterized by inflammation of the small blood vessels in different organs. Kidney involvement is one the most common and severe features of AAV. The combination of immunosuppressive medications, predominantly cyclophosphamide and rituximab, with corticosteroids (CS) remains the standard of care for remission induction. The results of the PEXIVAS trial showed that redu-ced dose CS regimen was noninferior to the standard regimen. The results of two randomized trials suggested that mycophenolate mofetil can be used for remission induction in patients with non-life-threatening AAV. The role of plasma exchange in the treatment of AAV remains unclear, since it did not improve overall or renal survival in the PEXIVAS trial. The most well studied medications for maintenance therapy include azathioprine and rituximab. The results of randomized trials (MAINRITSAN, RITAZAREM) showed the superiority of rituximab over azathioprine in terms of relapse-free survival. The optimal duration of maintenance therapy is undefined and probably should be no less than 18 months. However, some patients might benefit from extended maintenance therapy of up to 48 months. Adverse effects of immune suppressive therapy, e.g. infectious diseases, malignancies, osteoporosis and venous thromboembolic events, are common and often require active prophylaxis.

Campylobacteriosis following immunosuppression for immune checkpoint inhibitor-related toxicity

Five patients receiving checkpoint inhibitor immunotherapy (CPI) under our care across two cancer centers over a 12-month period have subsequently developed campylobacterosis. All had received immune-suppressive treatment for CPI-related colitis in the weeks or months preceding the detection of Campylobacter infection, with negative stool cultures at presentation of CPI-related colitis. The immune-suppression required to treat CPI-related toxicity may lead to an increased risk of enteric infection within the gut. While the underlying immune and biologic mechanisms are not well understood, perturbation of the gut microbiota is an increasingly recognized factor capable of influencing CPI-mediated immune reconstitution and response to therapy. Clinicians should be aware that worsening of colitic symptoms in patients with a history of treatment for CPI-related colitis may be due to enteric infection, and not simply a relapse/deterioration of a previously treated CPI-related colitis. Judicious infectious disease evaluation is necessary for patients receiving CPIs as symptoms can mimic immune-related adverse events (irAEs). Furthermore, the benefits of immune-suppressive therapy for the treatment of presumptive irAEs must be weighed against the possible increased risk for either enteric infection or opportunistic infection. Prospective studies are required to investigate microbiome perturbations, resulting from immune-suppression, and guide future treatment of this patient cohort.

Studying some lymphocyte subpopulations in search for predictors of renal graft dysfunction

Introduction. One of the main problems in transplantology is the detection of simple, reliable and non-invasive markers that could predict adverse immune reactions and adjust immune suppressive therapy in allograft recipients in a timely manner. Objective. To determine the immunological criteria for the prediction of a graft dysfunction. Material and methods. We have examined 197 recipients who underwent kidney transplantation. All of them were immunologically examined with the identification of more than 40 subpopulations of leukocytes. Allograft function was assessed on day 7 with the division of patients into two groups: with either primary or graft dysfunction. Simple and multiple logistic regressions were used to predict a graft dysfunction. Preliminary statistical analysis was performed using nonparametric statistics. Results and discussion. A scoring system to predict the graft function has been worked out. At CD19+IgD+CD27-<72.7%, score 1 is assigned, and 0 score is given at > 72.7%. At CD3+CD8+CD69+>9.7% score 1 is assigned, and 0 score is given at CD3+CD8+CD69+<9.7%. Total score is calculated by summing up the scores. The total score = 0 predicts a primary graft function; total score >1 predicts a graft dysfunction. This scoring system has the sensitivity of 91.9%, еру specificity of 100%, еру accuracy of 94.9%, positive predictive value of 1 and negative predictive value of 0.877. Conclusions. 1. Percentage of CD19+IgD+CD27- and CD3+CD8+CD69+ subpopulations can be used to predict a graft dysfunction. 2. At values of CD19+IgD+CD27- not exceeding 72.7% and CD3+CD8+CD69+ more than 9.7%, the development of a graft dysfunction can be anticipated.

Case Report: Approach to Tinea incognito

Tinea incognito is a disease that gets the look of atipic form of mycotic infection, imitating many different dermatomes formed by misdiagnosing and giving improper topical, systemic steroids or immune suppressive therapy. Tinea incognito or steroid modified tinea is a dermatophytic infection in which topical or systemic steroids, administered as a result of dermatological misdiagnosis or pre existing pathologies, have modified the clinical appearance of the fungal infection, transforming the typical ring worm and mimicking other skin diseases [1,2]. In this case we demonstrate a patient who started topical corticosteroids application with misdiagnosis and after that insisting topical corticosteroids use on her treatment from doctors she see

The Human Respiratory Microbiome: Implications and Impact

Once considered a sterile site below the larynx, the tracheobronchial tree and parenchyma of the lungs are now known to harbor a rich diversity of microbial species including bacteria, viruses, fungi, and archaea. Many of these organisms, particularly the viruses which comprise the human respiratory virome, have not been identified, so their true role is unknown. It seems logical to conclude that a “healthy” respiratory microbiome exists which may be modified in disease states and perhaps by therapies such as antibiotics, antifungals, and antiviral treatments. It is likely that there is a critical relationship or equilibrium between components of the microbiome until such time as perturbations occur which lead to a state of dysbiosis or an “unhealthy” microbiome. The act of lung transplantation provides an extreme change to an individual's respiratory microbiome as, in effect, the donor respiratory microbiome is transplanted into the recipient. The mandatory ex-vivo period of the donor lungs appears to be associated with blooms of resident viral species in particular. Subsequently, allograft injury, rejection, and immune suppressive therapy all combine to create periods of dysbiosis which when combined with transient infections such as community acquired respiratory viruses may facilitate the development of chronic allograft dysfunction in predisposed individuals. As our understanding of the respiratory microbiome is rapidly expanding, based on the use of new-generation sequencing tools in particular, it is to be hoped that insights gained into the subtle relationship between the microbiome and the lung allograft will facilitate improved outcomes by directing novel therapeutic endeavors.