Exploring CAR-T Cell Therapy Side Effects: Mechanisms and Management Strategies.

Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of malignancies, especially hematological tumors, but toxicities have tempered its success. The main impediments to the development of CAR-T cell therapies are the following: cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), tumor lysis syndrome (TLS), and on-target/off-tumor toxicity (OTOT). This review summarizes these side effects' underlying mechanisms and manifestations over time. It provides potential prevention and treatment according to the consensus grading, stressing the significance of establishing strategies that anticipate, reduce, and navigate the beginning of these side effects. It is essential to fully comprehend the mechanisms underlying these toxicities to create efficient treatment and preventive approaches.

CT predictors of outcomes in patients with connective tissue disease and progressive lung fibrosis.

PURPOSE: Progressive fibrosing interstitial lung disease (PF-ILD) is a phenotype defined by rapid clinical progression towards respiratory failure. While idiopathic pulmonary fibrosis is the archetype of PF-ILD, connective tissue disease associated interstitial lung disease (CTD-ILD) can also manifest as PF-ILD. Few studies have described the value of serial computed tomography (CT) in predicting clinical progression of ILD. We explore which single and serial clinical and radiographic variables, in particular serial CT variables and a novel variable, the right lower lobe anterior bronchial angle (RLL-ABA), best predict mortality, oxygen requirement, hospital admissions, and lung transplant in CTD-ILD. METHODS: This is a single-center retrospective study of 84 patients with a history of CTD-ILD. Cox survival analysis was used to predict two endpoints, all-cause mortality and composite negative outcomes (CNO): new oxygen requirement, respiratory admission, lung transplant, and death. RESULTS: On serial CT, change in pulmonary artery (PA) size and RLL-ABA were predictive of mortality and CNO, and change in fibrosis was predictive of mortality alone. On single CT, the extent of fibrosis, PA size, and PA to aorta ratio were predictive of mortality and CNO. Among clinical variables, oxygen requirement, forced vital capacity (FVC), change in FVC, and worsening shortness of breath were predictive of mortality and CNO, and diffusing capacity for carbon monoxide was predictive of mortality alone. CONCLUSIONS: In addition to clinical and single CT variables, serial CT measurements such as change in extent of fibrosis, PA size, PA to aorta ratio, and RLL-ABA were predictive of mortality and CNO.

A nomogram for predicting late radiation-induced xerostomia among locoregionally advanced nasopharyngeal carcinoma in intensity modulated radiation therapy era.

BACKGROUND: Dry mouth sensation cannot be improved completely even though parotids are spared correctly. Our purpose is to develop a nomogram to predict the moderate-to-severe late radiation xerostomia for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) in intensity modulated radiation therapy (IMRT) / volumetric modulated arc radiotherapy (VMAT) era. METHODS: A dataset of 311 patients was retrospectively collected between January 2010 and February 2013. The binary logistic regression was to estimate each factor's prognostic value for development of moderate-to-severe patient-reported xerostomia at least 2 years (Xer2y) after completion of radiotherapy. Therefore, we can develop a nomogram according to binary logistic regression coefficients. This novel model was validated by bootstrapping analyses. RESULTS: Contralateral Parotid mean dose (coMD<24.4Gy), VMAT (yes), and platinum-based concurrent chemoradiotherapy (no) were significantly related to patient-reported xerostomia at least 2 years (Xer2y) (all p < 0.001), and were included in the nomogram. Receiver operating characteristic (ROC) analysis revealed AUC (area under the ROC curve) with the value of 0.811 (0.710-0.912) of the nomogram, which was significantly higher than coMD 0.698 (0.560-0.840) from QUANTEC2010 (p<0.001). Calibration plots illustrated that the predicted Xer2y was close to the actual observation, and decision curve analyses (DCA) indicated valid positive net benefits. CONCLUSION: We developed a feasible nomogram to predict patient-rated Xer2y based on comprehensive individual data in patients with LA-NPC in the real world. The proposed model is able to facilitate the development of treatment plan and quality of life improvement.

Nomograms for predicting survival outcomes in intensity-modulated radiotherapy era of nasopharyngeal carcinoma: A study based on Epstein-Barr virus DNA biological responses.

BACKGROUND: Treatment of nasopharyngeal carcinoma (NPC) is evolving toward Intensity-modulated radiotherapy (IMRT) era, which requires patient-specific reestimation of survival outcomes in modern health care. METHODS: A total of 488 detectable pre-treatment Epstein-Barr virus (EBV) DNA patients (stage II-IVa) treated with induction chemotherapy (IC) and IMRT were examined (training set, n = 325; validation set, n = 163). RESULTS: Concurrent chemotherapy (CC) was still an independent prognosticator for overall survival (OS) and progression-free survival (PFS). Both nomograms included age, T classification, N classification, post-IC EBV DNA, and CC. Predictions correlated well with observed 3-/5-year OS and PFS. The concordance index was 0.776 (95% confidence interval (CI) 0.69-0.86) for OS and 0.742 (95% CI 0.65-0.83) for PFS in the validation cohort. The nomograms can successfully classify patients into low- and high-risk groups. CONCLUSION: The validated nomograms provided useful prediction of OS and PFS for detectable pre-treatment EBV DNA patients with NPC in IMRT era.

Characterization and clinical course of 1000 patients with COVID-19 in New York: retrospective case series.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) in a large New York City (NYC) medical center and describe their clinical course across the emergency department (ED), inpatient wards, and intensive care units (ICUs). Design: Retrospective manual medical record review. Setting: NewYork-Presbyterian/Columbia University Irving Medical Center (NYP/CUIMC), a quaternary care academic medical center in NYC. Participants: The first 1000 consecutive patients with laboratory-confirmed COVID-19. Methods: We identified the first 1000 consecutive patients with a positive RT-SARS-CoV-2 PCR test who first presented to the ED or were hospitalized at NYP/CUIMC between March 1 and April 5, 2020. Patient data was manually abstracted from the electronic medical record. Main outcome measures: We describe patient characteristics including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. Results: Among the first 1000 patients, 150 were ED patients, 614 were admitted without requiring ICU-level care, and 236 were admitted or transferred to the ICU. The most common presenting symptoms were cough (73.2%), fever (72.8%), and dyspnea (63.1%). Hospitalized patients, and ICU patients in particular, most commonly had baseline comorbidities including of hypertension, diabetes, and obesity. ICU patients were older, predominantly male (66.9%), and long lengths of stay (median 23 days; IQR 12 to 32 days); 78.0% developed AKI and 35.2% required dialysis. Notably, for patients who required mechanical ventilation, only 4.4% were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at 3-4 and 9 days. As of April 30, 90 patients remained hospitalized and 211 had died in the hospital. Conclusions: Hospitalized patients with COVID-19 illness at this medical center faced significant morbidity and mortality, with high rates of AKI, dialysis, and a bimodal distribution in time to intubation from symptom onset.

Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series.

OBJECTIVE: To characterize patients with coronavirus disease 2019 (covid-19) in a large New York City medical center and describe their clinical course across the emergency department, hospital wards, and intensive care units. DESIGN: Retrospective manual medical record review. SETTING: NewYork-Presbyterian/Columbia University Irving Medical Center, a quaternary care academic medical center in New York City. PARTICIPANTS: The first 1000 consecutive patients with a positive result on the reverse transcriptase polymerase chain reaction assay for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who presented to the emergency department or were admitted to hospital between 1 March and 5 April 2020. Patient data were manually abstracted from electronic medical records. MAIN OUTCOME MEASURES: Characterization of patients, including demographics, presenting symptoms, comorbidities on presentation, hospital course, time to intubation, complications, mortality, and disposition. RESULTS: Of the first 1000 patients, 150 presented to the emergency department, 614 were admitted to hospital (not intensive care units), and 236 were admitted or transferred to intensive care units. The most common presenting symptoms were cough (732/1000), fever (728/1000), and dyspnea (631/1000). Patients in hospital, particularly those treated in intensive care units, often had baseline comorbidities including hypertension, diabetes, and obesity. Patients admitted to intensive care units were older, predominantly male (158/236, 66.9%), and had long lengths of stay (median 23 days, interquartile range 12-32 days); 78.0% (184/236) developed acute kidney injury and 35.2% (83/236) needed dialysis. Only 4.4% (6/136) of patients who required mechanical ventilation were first intubated more than 14 days after symptom onset. Time to intubation from symptom onset had a bimodal distribution, with modes at three to four days, and at nine days. As of 30 April, 90 patients remained in hospital and 211 had died in hospital. CONCLUSIONS: Patients admitted to hospital with covid-19 at this medical center faced major morbidity and mortality, with high rates of acute kidney injury and inpatient dialysis, prolonged intubations, and a bimodal distribution of time to intubation from symptom onset.

A multidimensional nomogram combining overall stage, dose volume histogram parameters and radiomics to predict progression-free survival in patients with locoregionally advanced nasopharyngeal carcinoma.

OBJECTIVES: To develop a multidimensional nomogram for predicting the progression-free survival (PFS) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) (stage III-IVa). MATERIALS AND METHODS: A total of 224 patients with locoregionally advanced NPC (training cohort, n = 149; validation cohort, n = 75) were retrospectively included. We extracted 260 radiomic features from the primary tumor and lymph nodes on the axial contrast-enhanced T1 weighted and T2 weighted MRI. Radiomic signatures of the gross tumor volume (RSnx) and lymph node (RSnd), Dose Volume Histogram (DVH) signature reflecting planning score (PS), and clinical characteristics were included as potential predictors of PFS. The least absolute shrinkage and selection operator (LASSO) regression were applied for feature selection and data dimension reduction. A nomogram was developed by incorporating the selected predictors. The C-index and calibration curve were used to assess discrimination and calibration power of the nomogram, respectively. RESULTS: RSnd, PS, and tumor-node-metastasis (TNM) stage were the independent predictors for PFS (all p < 0.05). The nomogram integrating the three factors achieved a C-index of 0.811 (95% CI: 0.74-0.882) in the validation cohort for predicting PFS, which outperformed than that of the TNM stage alone (C-index, 0.613, 95% CI: 0.532-0.694). Subgroup analysis showed Epstein-Barr virus (EBV) DNA status improved the predictive accuracy of the nomogram (C-index, 0.86, 95% CI: 0.787-0.933). CONCLUSIONS: The multidimensional nomogram incorporating RSnd, PS, and TNM stage showed high performance for predicting PFS in patients with locoregionally advanced NPC.