Caplacizumab for immune thrombotic thrombocytopenic purpura: real-world multicenter data.

Given the limited real-world data of caplacizumab, our multicenter real-world study was designed to assess the safety and efficacy of caplacizumab in immune thrombotic thrombocytopenic pupura (iTTP), compared to historic controls. We have studied 70 patients: 23 in the caplacizumab and 47 in the historic control group. Plasma exchange was applied in all episodes except for two patients that denied plasma exchange. Rituximab as first-line treatment was more common in the caplacizumab group compared to historic control. Caplacizumab (10 mg daily) was given at a median on day 7 (1-43) from initial diagnosis for 32 (6-47) dosages. In the caplacizumab group, a median of 12 (8-23) patients required plasma exchange sessions versus 14 (6-32) in the control group. Caplacizumab administration did not produce any grade 3 complications or major hemorrhagic events. After a median of 19.0 (2.6-320) months since the iTTP diagnosis, 5 deaths occurred (4 in the control group and 1 in the caplacizumab group, p = 0.310). Caplacizumab patients achieved early platelet normalization and ADAMTS13 activity normalization at the end of treatment. Relapse was observed only in 2/23 (9%) caplacizumab patients, compared to 29/47 (62%) historic controls (p < 0.001). Overall, caplacizumab is safe and effective in treating iTTP, including cases refractory to plasma exchange, re-administration, and cases without previous plasma exchange treatment. No major hemorrhagic events were observed. Cessation of dosing guided by ADAMTS13 has ensured a low relapse rate.

Antiphospholipid syndrome in cardiovascular disease and cancer.

Antiphospholipid syndrome is an autoimmune disorder which is characterized by the presence of heterogeneous antiphospholipid antibodies. There is an evidence on antiphospholipid (aPL) antibodies related to thromboembolic events in cancer patients. In fact, the thrombotic complications in patients with malignancy occur at a rather high frequency, compared to other risk factors. In parallel with standard therapies available, there is need of case-by-case monitoring of each patient and the introduction of new therapies and need for more clinical trials which will address many questions for the optimal management of patients. This paper presents a basic review of the literature on the aPL antibodies associated with cardiovascular disease and cancer, as well as its complications, which are reported so far in the bibliography.

Effectiveness of Oral Nirmatrelvir/Ritonavir vs. Intravenous Three-Day Remdesivir in Preventing Progression to Severe COVID-19: A Single-Center, Prospective, Comparative, Real-Life Study.

BACKGROUND: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. METHODS: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. RESULTS: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07-0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01-0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. CONCLUSION: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

Factors predicting poor outcomes of patients treated with tocilizumab for COVID­19­associated pneumonia: A retrospective study.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic is a significant global issue that has major implications for the healthcare system. The mortality rates associated with SARS-CoV-2 infection vary according to the geographical region and are associated with age, comorbidities and vaccination status. Organ damage is caused by the cytokine release syndrome, which plays a crucial role in the course of coronavirus disease 2019 (COVID-19) infection. Innate and adaptive immune system stimulation in patients with COVID-19 results in inappropriate cytokine release. The anti-IL-6 receptor antagonist, tocilizumab, is used in the treatment of connective tissue diseases. The present single-center retrospective study on patients with COVID-19 admitted to hospital between September, 2020 and April, 2022 aimed to identify predictors of mortality and other unfavorable outcomes in patients treated with tocilizumab for COVID-19-associated pneumonia. Demographics, vaccination status against SARS-CoV-2, the Charlson comorbidity index (CCI), laboratory data and chest X-ray scores were recorded upon admission. In total, 174 subjects (121 males; mean age, 62.43±13.47 years) fulfilling the inclusion criteria were included. Among the 174 participants, 58 (33.3%) were intubated. The mortality rate was 35.1%. The non-survivors were older, mostly females, and had a higher CCI score. At the evaluation upon admission, the survivors presented with higher levels of alanine transferase and gamma glutamyl-transferase and with a greater number of platelets (PLTs), while patients that were intubated were also older, mostly females, and had a higher CCI score (P<0.05). Age was identified as the only independent factor predicting mortality in the Cox proportional hazards multivariate regression analysis. By performing a sub-analysis regarding sex, it was revealed that the value of PLTs was an independent factor predicting intubation and 90-day mortality in male patients, and the lymphocyte count was the only factor associated with intubation in female patients. On the whole, the data of the present study may be used to identify patient subpopulations responding to treatment with tocilizumab in prospective clinical trials.

COVID-19 induced hypoparathyroidism: A case report.

Low levels of serum calcium, elevated levels of serum phosphorus and absent or abnormally low levels of serum parathyroid hormone characterize hypoparathyroidism, a rare endocrine deficiency illness. Hypoparathyroidism is caused by injury to the parathyroid gland as a result of surgery or autoimmune disease. In addition, hypoparathyroidism may develop due to genetic causes or infiltrative diseases. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by multi-organ involvement, including the dysfunction of endocrine glands. Previous studies have demonstrated that SARS-CoV-2 infection induces endocrine tissue damage via various mechanisms, including direct cell damage from viral entry to the glands by binding to the angiotensin converting enzyme 2 receptors and replication, vasculitis, arterial and venous thrombosis, hypoxic cell damage, immune response and the cytokine storm. The effects of the new coronavirus, coronavirus disease 2019 (COVID-19) on the parathyroid glands have received limited attention. Hypoparathyroidism has been observed in a small number of individuals as a result of SARS-CoV-2 infection. The present study describes the case of a patient with primary hypoparathyroidism induced by COVID-19. Clinicians should also keep in mind that, despite the fact that SARS-CoV-2 has no known tropism for the parathyroid glands, it can result in primary hypoparathyroidism and decompensation of old primary hypoparathyroidism.

COVID-19-associated pneumonia in Swyer-James-MacLeod syndrome: A case report.

Coronavirus disease 2019 (COVID-19) exerts differential effects on various individuals. The majority of infected individuals experience mild-to-moderate disease and usually recover, without requiring hospitalization. It has been reported that those who have underlying chronic diseases are more susceptible to infection and may thus develop significantly more serious illness. As a result, COVID-19 may aggravate pre-existing respiratory illnesses, such as interstitial lung disease, chronic obstructive pulmonary disease and asthma. Swyer-James-MacLeod syndrome is an uncommon clinical condition marked by post-infectious infantile bronchiolitis obliterans. Traditionally, the diagnosis is made in infancy following an investigation for reoccurring respiratory infections, although in rare cases, the diagnosis is made in adulthood. The present study describes the case of a 45-year-old patient with Swyer-James-MacLeod syndrome hospitalized due to COVID-19, which is the first one to be reported. To the best of our knowledge, there are currently no data available on the effects of COVID-19 in these individuals, stheir optimal therapy, or the impact of COVID-19 vaccination on their clinical course. Thus, it is hoped that the present study sheds some light into this condition.

Exacerbation of bronchiectasis by Pseudomonas putida complicating COVID-19 disease: A case report.

Novel coronavirus infection presents with greater severity in individuals with comorbid chronic lung diseases. Bronchiectasis is an illness characterized by permanent enlargement of the airways, presenting with chronic cough and sputum production and vulnerability to lung infections. Bronchiectasis is not a common comorbid disease in patients with COVID-19 disease and bronchiectasis exacerbation rates were decreased during the pandemic. However, COVID-19 disease is associated with worse outcomes in patients with bronchiectasis and patients with bronchiectasis are more susceptible to SARS-CoV-2 infection development. Pseudomonas putida is an opportunistic pathogen, causing infections mostly in immunocompromised hosts and is not a frequent bacterial colonizer in patients with bronchiectasis. This present study reports a rare case of exacerbation of bronchiectasis by Pseudomonas putida complicating COVID-19 disease in an immunocompetent 70-year-old woman. Clinicians should be aware that SARS-CoV-2 infection is probably a precipitating factor of bronchiectasis exacerbation while bronchiectasis is a risk factor for greater severity of SARS-CoV-2 infection.

Asymptomatic SARS-CoV-2 infection in an unvaccinated 97-year-old woman: A case report.

Coronavirus disease (COVID-19) is an infection caused by the newly detected coronavirus, SARS-CoV-2. The majority of individuals will exhibit mild to moderate illness. Older individuals, and those suffering from co-existing diseases have a greater probability of experiencing a serious illness. Moreover, elderly patients have higher mortality rates than younger patients, especially those who are unvaccinated. Asymptomatic infection is mostly observed in individuals who are younger, as younger patients are more likely to exhibit a stronger immune response to the infection; aging is characterized by the decline immune function. In this article, a rare case of an unvaccinated 97-year-old woman is described who was admitted to Laiko General Hospital due to altered levels of consciousness, hypotension and a hematoma of the thoracic region, and tested positive for SARS-CoV-2 nucleic acid in a nasopharyngeal specimen and positive for IgG antibodies against the SARS-CoV-2 spike protein without a history of consistent manifestations, indicating a past asymptomatic infection.

Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review.

BACKGROUND: Failure after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell B non-Hodgkin lymphoma, especially when it happens early, is an emerging clinical problem. There are no specific recommendations and therefore treatment of these patients remains empiricaI. Immune checkpoint inhibitors are becoming a therapeutic option for these patients. CASE REPORT: We present a case of a primary mediastinal large B-cell lymphoma who experienced relapse 3.5 months after axicabtagene-ciloleucel therapy and received pembrolizumab. After four cycles of pembrolizumab, complete metabolic response was confirmed. Treatment was discontinued after the sixth cycle due to immune checkpoint inhibitor-related pneumonitis. The disease remains in remission 8 months after the last pembrolizumab dose. We propose mechanisms of action and optimal duration of pembrolizumab treatment in this setting. Finally, we review the existing literature on the sequential administration of CD19-directed CAR T-cell therapy and immune checkpoint inhibitors. CONCLUSION: Immune checkpoint inhibitors are a promising treatment option for patients after failure of CD19-directed CAR-T cell therapy.

Complete eradication of chronic lymphocytic leukemia with unusual skin involvement of high mitotic index after time-limited venetoclax/obinutuzumab treatment.

The novel time-limited combinations with the bcl-2 inhibitor venetoclax can induce deep responses even in CLL cases with unusual and biologically aggressive presentations, like the skin masses of our patient.

Richter's transformation as leptomeningeal infiltration in a chronic lymphocytic leukemia patient receiving venetoclax. Could blood-brain barrier be a disease "sanctuary" during venetoclax treatment?

Our unique case of Richter's Transformation presenting as leptomeningial infiltration in a CLL patient receiving venetoclax raises questions on whether the drug penetrates the blood-brain barrier and at what extend, especially in reduced doses given for drug-drug interactions.

Efficacy-safety of Facilitated Subcutaneous Immunoglobulin in Immunodeficiency Due to Hematological Malignancies. A Single-Center Retrospective Analysis.

BACKGROUND/AIM: Hematological malignancies are frequently complicated by secondary immunodeficiency (SID). Immunoglobulin replacement with intravenous gamma globulins (IVIg) reduces infection incidence, antibiotics' need and hospitalization days in these patients. Facilitated subcutaneous immunoglobulin replacement (fSCIg) has been studied in primary immunodeficiency patients and is equally efficacious with several advantages (self-administration, same bioavailability, long infusion intervals, fewer adverse drug reactions). fSCIg has been less extensively studied in SID. We present our retrospective single-center data of fSCIg administration to hematological patients with SID, focusing on efficacy and safety issues. PATIENTS AND METHODS: Overall, 33 hematological patients with hypogammaglobulinemia were treated with fSCIg according to ESMO 2015 guidelines, between mid-October 2015 and mid-January 2018 in our Department. RESULTS: The infection rate was very low (18.1%). Shorter infusion intervals further reduced it. ADRs were rare (9%) and mild (grade 1). fSCIg managed to reduce the everyday nursery/hospital burden of our tertiary hospital. CONCLUSION: fSCIg compares favorably to IVIg replacement in SID patients.

Autoimmune hemolytic anemia and autoimmune thrombocytopenia at diagnosis and during follow-up of Hodgkin lymphoma.

Autoimmune hemolytic anemia and thrombocytopenia (AIHA/AITP) frequently complicate the course of non-Hodgkin lymphomas, especially low-grade, but they are very rarely observed in Hodgkin lymphoma (HL). Consequently the frequency and the profile of patients with HL-associated AIHA/AITP have not been well defined. Among 1029 patients with HL diagnosed between 1990 and 2010, two cases of AIHA (0.19%) and three of AITP (0.29%) were identified at the presentation of disease. These patients were significantly older, and more frequently had features of advanced disease and non-nodular sclerosing histology, compared to the majority of patients, who did not have autoimmune cytopenias at diagnosis. ABVD combination chemotherapy (doxorubicin, bleomycin, vinblastine, dacarbazine) provided effective control of HL and the autoimmune condition as well. During approximately 6600 person-years of follow-up for the remaining 1024 patients, seven (0.7%) patients developed autoimmune cytopenias (three AITP, three AIHA, one autoimmune pancytopenia) for a 10- and 15-year actuarial incidence of 0.95% and 1.40%, respectively. Their features did not differ compared to the general population of adult HL. In this large series of consecutive, unselected patients, those who presented with autoimmune cytopenias had a particular demographic and disease-related profile. In contrast, patients developing autoimmune cytopenias during follow-up did not appear to differ significantly from those who did not.