Ethno-demographic disparities in humoral responses to the COVID-19 vaccine among healthcare workers.

The COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.

Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors.

PURPOSE OF REVIEW: To provide a detailed overview of cardiovascular adverse events associated with the use of tyrosine kinase inhibitors across different tumor types. RECENT FINDINGS: Despite an undeniable survival advantage of tyrosine kinase inhibitors (TKIs) in patients with hematologic or solid malignancies, the accompanying off-target cardiovascular adverse events can be life-threatening. In patients with B cell malignancies, the use of Bruton tyrosine kinase inhibitors has been associated with atrial and ventricular arrhythmias, as well as hypertension. Cardiovascular toxic profiles are heterogeneous among the several approved breakpoint cluster region (BCR)-ABL TKIS. Notably, imatinib might be cardioprotective. Vascular endothelial growth factor TKIs, constituting the central axis in the treatment of several solid tumors, including renal cell carcinoma and hepatocellular carcinoma, have strongly been associated with hypertension and arterial ischemic events. Epidermal growth factor TKIs as therapy for advanced non-small cell lung cancer (NSCLC) have been reported to be infrequently associated with heart failure and QT prolongation. While tyrosine kinase inhibitors have been demonstrated to increase overall survival across different types of cancers, special consideration should be given to cardiovascular toxicities. High-risk patients can be identified by undergoing a comprehensive workup at baseline.

New cancers after autotransplantations for multiple myeloma.

We describe baseline incidence and risk factors for new cancers in 4161 persons receiving autotransplants for multiple myeloma in the United States from 1990 to 2010. Observed incidence of invasive new cancers was compared with expected incidence relative to the US population. The cohort represented 13,387 person-years at-risk. In total, 163 new cancers were observed, for a crude incidence rate of 1.2 new cancers per 100 person-years and cumulative incidences of 2.6% (95% confidence interval [CI], 2.09 to 3.17), 4.2% (95% CI, 3.49 to 5.00), and 6.1% (95% CI, 5.08 to 7.24) at 3, 5, and 7 years, respectively. The incidence of new cancers in the autotransplantation cohort was similar to age-, race-, and gender-adjusted comparison subjects with an observed/expected (O/E) ratio of 1.00 (99% CI, .81 to 1.22). However, acute myeloid leukemia and melanoma were observed at higher than expected rates with O/E ratios of 5.19 (99% CI, 1.67 to 12.04; P = .0004), and 3.58 (99% CI, 1.82 to 6.29; P < .0001), respectively. Obesity, older age, and male gender were associated with increased risks of new cancers in multivariate analyses. This large data set provides a baseline for comparison and defines the histologic type specific risk for new cancers in patients with MM receiving postautotransplantation therapies, such as maintenance.

Concomitant EGFR Mutations and ALK Rearrangements in Lung Adenocarcinoma Treated With Osimertinib.

Lung cancer is the third most common cancer in addition to being the cancer responsible for the most annual deaths in the United States, comprising 15% of all diagnosed cancers, and 28% of all cancer deaths in 2020. Major advances in survival are because of gene sequencing and the advent of targeted biological therapy. The prevalence of epidermal growth factor receptor (EGFR) mutations coexisting with anaplastic lymphoma kinase (ALK) rearrangements is quite low. However, the clinical relevance and effective treatment of these cancers require further investigation. This case series describes two patients diagnosed with stage IV adenocarcinoma with coexisting EGFR and ALK rearrangements. In Case 1, a 73-year-old male presented with worsening ataxia and headaches. In Case 2, a 64-year-old female presented with worsening dyspnea. Molecular studies revealed ALK gene fusion and the L861Q EGFR mutation in Case 1 and L858R EGFR mutation and ALK gene fusion in Case 2. Both patients received a gamma knife and an EGFR-tyrosine kinase inhibitor (TKI), osimertinib. In one of the cases, following the discovery of new brain metastases, the dose of osimertinib was increased from 80 to 160 mg. The patient passed away nine months after beginning EGFR-TKI treatment, one month after increasing the dose. The second patient experienced a significant interval reduction in the size of enhancing metastasis in both the right frontal and left parietal lobe after four months of EGFR-TKI treatment. The cases of coexisting EGFR mutations and ALK rearrangements are quite rare, and treatment can be challenging. Here, EGFR-TKI had a mixed response among our patients.

Successful Treatment of Refractory Thrombotic Thrombocytopenic Purpura (TTP) With Caplacizumab: A Case Report.

We report a female patient who presented with generalized weakness, episodes of altered mental status and slurred speech, and a history of systemic lupus erythematosus. Initial investigations showed profound thrombocytopenia and schistocytosis on peripheral blood smear. PLASMIC score was promptly calculated, and plasma exchange with steroids was initiated based on the initial high PLASMIC score. Bone marrow examination showed hypocellular marrow without any other obvious abnormalities. The patient's platelet counts initially improved but had a quick decline, on which, rituximab and subsequently caplacizumab were introduced. The patient was discharged after stabilization with plasma exchange (PLEX) therapy as needed on an outpatient basis.

TNF-α inhibitors: are they carcinogenic?

Biologic therapy has increasingly been used in the treatment of chronic diseases. Tumor necrosis factor (TNF) is a cytokine implicated in the pathogenesis of rheumatoid arthritis and inflammatory bowel disease. Anti-TNF therapy is being used in the treatment of these conditions. Since the introduction of anti-TNF agents, there have been many case reports of development of malignancy after the initiation of anti-TNF therapy. With increasing case reports, there is growing concern that anti-TNF therapy, albeit useful in the treatment of these chronic conditions, might be associated with the development of malignancy in patients. In this review we examine the different anti-TNF agents and different studies to evaluate any possible association between use of any anti-TNF agent and development of malignancy.

TNF-alpha inhibitor etanercept and hematologic malignancies: report of a case and review of the literature.

We report here a 57-year-old man treated with etanercept for 6 months for psoriasis who developed myelodysplasia with acute myeloid leukemia. Leukemia cells had distinct karyotype associated with poor prognosis. The patient did not respond to cytosine arabinoside 100 mg/m(2) continuous infusion over 7 days with daunorubicin 45 mg/m(2) daily for 3 days. He also did not respond to salvage induction therapy with gemtuzumab (6 mg/m(2) on day 1 and 4 mg/m(2) on day 8) and intravenous continuous infusion cytosine arabinoside 200 mg/m(2). We review other cases of lymphoma and leukemia associated with tumor necrosis factor inhibitors and suggest mechanisms by which inhibition of the TNF-alpha family may predispose to cancer. We also suggest that all patients being considered for TNF-alpha treatment be screened for hematologic malignancies or premalignancies with blood counts and bone marrow aspirates/biopsies if indicated.