Background
It is not clear if all Americans have benefitted equally from the availability of chimeric antigen receptor T‐cell (CART) therapy. We aimed to evaluate if demographic differences existed ...among adult patients who received CART therapy and to assess predictors of CART treatment outcomes.
Methods
Records of patients ≥18 years who received CART therapy for non‐Hodgkin’s lymphoma, acute lymphoblastic leukemia, and multiple myeloma in 2018 were evaluated in the National Inpatient Sample. Acute complications and inhospital mortality were compared between two groups of CART recipients: Whites and non‐Whites. Logistic regression analysis was used to evaluate the association between sociodemographic factors and inhospital mortality.
Results
Of 1275 CART recipients that met inclusion criteria, there were 40.4% of females, 66.9% of Whites, Blacks (4.2%), Hispanics (13.3%), Asians or Pacific Islanders (4.2%), and Native Americans (1.3%). Up to 96.8% of CART procedures were performed in urban teaching hospitals, and 85.3% of CART recipients lived in metropolitan counties. Non‐Whites, compared to Whites, were younger at the time of CART therapy (p < 0.001). The inhospital mortality rate was higher in non‐Whites, though not statistically significant (5.4% vs. 4.4%, p = 0.764). There were no differences in length of hospital stay, hospital charges, or rates of acute toxicities between the two race groups. We found no association between race and treatment outcomes. Gender, neurotoxicity, and Charlson Comorbidity Index were significant predictors of inhospital mortality.
Conclusions
CART therapy recipients in the United States were more likely to be Whites and more likely to be residents of metropolitan areas. These observed demographic differences were not associated with treatment outcomes or inhospital mortalities.
The first CART product was approved for commercial use in 2017, but it is not clear if all Americans have benefitted equally from the availability of CART therapies. In this retrospective study, we evaluated the demographic characteristics of CART therapy recipients for the year 2018. We found that racial minorities (especially Blacks) and people who live outside metropolitan areas were less likely to receive CART therapies.
•Nearly one-third of hospitalized patients who had chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia and aggressive lymphomas in 2018 had a neuropsychiatric disorder.•Females ...and patients with acute lymphoblastic leukemia are at higher risk for neuropsychiatric disorders during hospitalization for chimeric antigen receptor T-cell treatment.•Chimeric antigen receptor T-cell recipients who are mechanically ventilated are likely underdiagnosed with neuropsychiatric disorders.
To evaluate risk factors for neuropsychiatric disorders (NPD) in recipients of CART therapy.
Patients ≥ 18 years with acute lymphoblastic leukemia (ALL), and aggressive B-cell lymphomas who received CART in 2018 were evaluated. Patients with and without NPD were compared.
NPD was diagnosed in 31.2% of patients. Compared to patients without NPD, patients with NPD were likely to be females (P = 0.035) and have ALL (P = 0.039). NPD was significantly associated with female gender (OR = 2.03) and diagnosis of ALL (OR = 2.76). No association between NPD and outcomes.
Female gender and ALL were risk factors for NPD.
Psoriasis is a chronic relapsing/remitting autoimmune disease affecting skin and fingernails. It is associated with many other autoimmune diseases such as rheumatoid arthritis, celiac disease, ...Crohn's disease, and thyroid diseases. Two important autoimmune thyroid diseases - Hashimoto's thyroiditis (hypothyroidism) and Grave's disease (hyperthyroidism) - affect the body's significant organs such as the brain, muscles, digestive function, and the skin. Although some studies have established the connection between psoriasis and thyroid diseases with autoimmunity, our article provides an in-depth analysis of the connection between these two diseases and other common etiological factors associated with them, along with autoimmunity. We reviewed articles from PubMed using regular keywords and Medical Subject Headings (MeSH) keywords and finalized 45 articles to find an association between these two diseases. These articles showed that this association is more prevalent in obese patients and late-onset psoriasis. Most of the articles showed a positive association, but few articles showed no connection between them. However, there is no concrete explanation to prove the association due to limited research; additional studies are necessary. It requires the attention of both clinicians and researchers to develop a universal drug that will work on both diseases, and also thyroid evaluation could be included in psoriatic patient care so that there is a possibility to decrease cost and efforts while treating these diseases.
Shwachman-Diamond syndrome (SDS) is an autosomal recessive inherited disease of the SBDS gene. It has multi-organ involvement but primarily affects the bone marrow and the pancreas. This disease is ...more commonly found in males than females, and its earliest manifestation in infancy is pancytopenia, most especially neutropenia. Our article attempts an in-depth analysis of the hepatic and cardiac association in this disease and the severity of this association. For the purpose of this study, we engaged in an in-depth research of critically appraised literature and published articles. We searched for such articles on PubMed and Google Scholar using regular and Medical Subject Headings (MeSH) keywords. We eventually selected 32 articles from the search results and carefully read through and analyzed them. These articles showed the usual age of diagnosis of SDS to be at infancy (before age one), with a predominantly median survival age of 35 years. All the published articles we reviewed showed some hepatic and cardiac associations with SDS, but the extent of the associations varied. Even though most hepatic involvements were found to be benign, some severe cases led to fibrosis and hepatic failure. Although there is no particular consensus as to the exact outcome of cardiac involvement, the few cases we reviewed showed that cardiac association could be a severe complication and could even be fatal. Most of the cases reported in the literature had been diagnosed at autopsy.
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Background: Chimeric antigen receptor T cell therapy (CART) has shown efficacy in acute lymphoblastic leukemia (ALL), diffuse large B cell lymphoma (DLBCL), and primary ...mediastinal B cell lymphoma (PMBCL). While neurological toxicities of CART are known, neuropsychiatric disorders (NPD) in patients undergoing CART has not been well described. Our study assessed the prevalence of NPD in hospitalized patients (pts) undergoing CART, and explored association of NPD with clinical variables. Methods: Using the National Inpatient Sample database, we conducted a retrospective study of pts with ALL, DLBCL and PMLCL aged ≥ 18 years who underwent CART in 2018. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes. NPD of interest included anxiety, depression, adjustment disorder, insomnia, psychosis, dementia, bipolar disorder. Delirium was not included in the inventory of NPD since delirium is a neurotoxicity of CART, and inclusion of delirium as NPD would confound results. Patient, disease, and CART complications were extracted from hospitalization records. Regression analyses were used to assess association of NPD with clinical variables. Results: 945 CART procedures met the inclusion criteria (56 % males and 60% Caucasians). Majority of CART (88%) were performed for DLBCL and PMBCL. NPD was diagnosed in 31 % of pts. Anxiety was the most common NPD, followed by insomnia and depression. ALL pts were more likely to have NPD compared to pts with lymphoma (52% versus 28%, p<0.05). More females had NPD compared to males (40% versus 25%, p<0.05). Univariable analysis showed association of NPD with female gender Odds ratio (OR)=2.03, 95% CI = 1.05-3.93 and ALL (OR=2.76, 95% CI = 1.03-7.43). In a multivariable model, NPD was associated with ALL (OR =3.57, 95% CI= 1.01-12.55), while the association of NPD with female gender was less certain (OR =1.41, 95% CI=0.73 - 2.74). There was no association between NPD and mortality, neurotoxicity, systemic inflammatory response syndrome or hemophagocytic lymphohistiocytosis. Conclusions: One in every 3 pts who underwent in-hospital CART for ALL or aggressive B cell lymphoma in 2018 had comorbid NPD. Females and ALL pts were at higher risk for NPD. As CART pts transition into longer follow up and survivorship, ours and similar results should inform the planning and allocation of psychosocial services.
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e19042
Background: For patients undergoing intensive chemotherapy, pulmonary fungal infections (PFI) represent a major cause of morbidity and mortality. Our study examined predictors ...and outcomes of PFI in hospitalized patients (pts) with hematological malignancies in the current era of antifungal prophylaxis for high-risk patients. Methods: Using the 2018 National Inpatient Sample (NIS) database, we conducted a retrospective study of hospitalized pts aged ≥ 18 years, with acute leukemias or aggressive lymphomas. Hospitalizations were selected using International Classification of Disease, Tenth Revision (ICD-10) codes for leukemias, lymphomas and PFI (candidiasis, aspergillosis, cryptococcus, and mucormycosis). Demographics, comorbidities, and outcomes were compared between pts with and without PFI using Chi-squared test. Multivariable logistic regression was performed to explore predictors associated with PFI. Results: Of 205,525 hospitalizations that met the inclusion criteria, PFI was diagnosed in 1635 (0.8%). Frequent infections were aspergillosis (80%) and candidiasis (11%). Pts with acute myeloid leukemia (AML) accounted for 64% of all PFI. The PFI group, compared to non-PFI, were more likely to be non-Caucasian (39% vs 32%, p<0.05), have higher Charlson comorbidity index (CI) 64% vs 55%, p<0.01, longer mean length of stay (23 vs 9 days, p<0.001), and more likely to have AML (64% vs 33%, p<0.001). Pts with PFI had higher odds of acute respiratory failure, severe sepsis, and in-hospital mortality. Mortality rates for PFI and non-PFI group were 17% and 6% respectively (p<0.001). Predictors associated with PFI were Hispanic or Native American race, Charlson CI ≥ 3, neutropenia, malnutrition, bone marrow transplant status and diagnosis of AML (Table). Conclusions: Our study identified clinical variables that predicted for PFI in patients with acute leukemias and aggressive lymphomas. Pts with these high-risk characteristics should get priority for close surveillance, mold-specific prophylaxis, and antifungal therapeutic drug monitoring. Selected predictors associated with pulmonary fungal infections. Adjusted Odds ratio (OR).Table: see text
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Background:
Pulmonary arterial hypertension (PAH) is a life-threatening disease that initiates in response to pulmonary artery endothelial cells (PAEC) damage followed by inadequate ...repair. The Receptor for Advanced Glycation Endproducts (RAGE) triggered upon the damage, plays a crucial role in vascular regeneration. However, its specific impact on PAH remains incompletely explored.
Hypothesis:
In this study, we investigated the sex-specific outcome of RAGE deletion on PAEC homeostasis.
Methods:
The effect of the global RAGE knockout (KO) on pulmonary hemodynamics, cardiac and endothelial function was studied disaggregated by sex in WT and RAGE KO rats. Endothelial integrity was evaluated via the expression of endothelial junction proteins, the activity of barrier disruptive signaling pathways, and in vivo pulmonary vascular permeability assay. To understand the significance of diminished RAGE signaling in male PAH, we measured membrane RAGE levels in untreated and Sugen/Hypoxia treated rats of both sexes and examined the publicly available single-cell transcriptomic profiles of human PAECs.
Results:
Male but not female RAGE KO rats developed a spontaneous PAH characterized by a significant increase in the right ventricle (RV) systolic pressure and RV hypertrophy. The PAH phenotype in males corresponded with a male-specific decrease in the expression of CD31 (WT vs. RAGE KO: 1.0 ± 0.07 vs. 0.1 ± 0.02, p <0001, N=6), activation of p38/RhoA signaling axis (p-p38 in WT vs. RAGE KO: 1.0 ± 0.2 vs. 3.2 ± 0.6, p=0.01, N=4), significant PAEC cytoskeletal rearrangement, and increased FITC-dextran extravasation, while female RAGE KOs remained unaffected. We also discovered that Sugen/Hypoxia treatment induced a substantial loss of membrane RAGE, specifically in males. Additionally, human PAEC transcriptomic data revealed that RAGE is expressed primarily in young females but not in males or older females.
Conclusions:
We conclude that the male sex associates with a reduced RAGE expression and signaling in PAEC, which is further diminished in PAH. The disruption in RAGE signaling, in turn, impairs the pulmonary endothelial barrier, instigates spontaneous PAH, and may contribute to the more severe phenotype observed in male PAH patients.
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Introduction:
Pulmonary hypertension (PH) is a fatal disease lacking effective treatment strategies to prevent its progression or reverse its effects. PH is characterized by vascular ...remodeling caused by excessive cell proliferation in the vascular layers. Often, pulmonary artery smooth muscle cells (PASMC) are implicated in the proliferative remodeling of the artery. We recently discovered that in PH, PASMC’s highly expressed a pericyte marker, CD13. Previous studies have shown CD13 pathology in cancer. We hypothesized that increased CD13 expression and activation could mediate a phenotype switch from pericytes to proliferative “PASMC like” cells.
Methods:
In this study, we used rats with a mutation in NFU1G206C, which spontaneously develop PH with severe vascular remodeling. We also used isolated PASMC from PH patients. We used whole lung single cell transcriptomics to uncover the phenotypes of various lung cells.
Results:
Pericytes of NFU1 rats showed a significant increase in CD13. Additionally, we found a 40-fold increase of CD13 in NFU1 PASMC. scRNA transcriptomics revealed a high similarity of PASMCs with pericytes in the NFU1 rats. Conversely, we also observed that pericytes of NFU1 rats highly expressed canonical SMC markers like SMMHC and CNN3. CellChat analysis revealed pericyte dysfunction with decreased interaction strength and interaction numbers with endothelial cells (ECs). Correspondingly, confocal imaging revealed a severe decrease in pericyte-EC association and a greater coverage area by pericytes in the NFU1 lungs. Treatment of NFU1 rats with a peptide blocking CD13 signaling (B-CD13) significantly attenuated right ventricular systolic pressure, Fulton index and vascular remodeling. Excitingly, treating isolated PASMC from PH patients and NFU1 rats with B-CD13 reverted the high proliferation rates back to control, indicating the pathological role of CD13 in cell proliferation. scRNA analysis of rat lungs treated with B-CD13 showed improvement in pericyte- EC interaction numbers and interaction strength, indicating that CD13 could play an important role in the migratory and proliferative switch of pericytes.
Conclusion:
Targeting CD13 signaling is a novel strategy to potentially reverse vascular remodeling in PH.
Chimeric antigen receptor T-cell (CAR-T) therapies have shown efficacy in treatment of relapsed/refractory multiple myeloma (MM). Neuropsychiatric disorders (NPD) in patients undergoing CAR-T have ...not been well described.
To evaluate prevalence of NPD in patients who underwent in-hospital CAR-T therapy for MM and explore association of NPD with in-hospital outcomes of CAR-T therapy.
Retrospective.
We evaluated NPD among patients undergoing in-hospital CAR-T therapy for MM in 2018 using data from the National Inpatient Sample (NIS). We applied discharge level weights to extrapolate findings to hospitalizations across the nation.
Hospitalizations for patients ≥ 18 years who received investigational CAR-T therapy for MM were selected from the NIS database using International Classification of Disease, Tenth Revision (ICD-10) procedure and diagnostic codes. Demographic and CAR-T treatment variables were collected. Regression models were fit to assess association of NPD with clinical variables, and odds ratios (OR) were reported.
The primary outcome was prevalence and distribution of NPD. The secondary outcome was association of NPD with CAR-T outcomes.
A total of 200 CAR-T procedures met inclusion criteria; 65% males, 71% Caucasians, and 15.8% African Americans, with a median age of 59 years. Most CAR-T procedures (95%) were performed in urban teaching hospitals. Prevalence of NPD was 27.5%. Anxiety was the most common NPD, then depression and insomnia. Patients with NPD, compared to those without, were more likely to have Charlson comorbidity index (CCI) > 3 (54.5% versus 20.7%, p= 0.01). There were no observed differences in the distribution of NPD with regard to race, age, gender, insurance, or prior receipt of bone marrow transplantation. Association was noted between NPD and CCI ≥ 3 (OR= 4.60, 95% CI= 1.29–16.40), between NPD and fever (OR= 0.16, 95% CI= 0.04–0.70). No significant association were found between NPD and neurotoxicity, in-hospital mortality, respiratory or renal failure, length of stay, or hospital charges.
One in every four patients who underwent CART therapy for MM in 2018 had NPD. Patients with multiple comorbidities were at higher risk, while patients with fever during CART therapy were likely underdiagnosed with NPD.
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