Molecular and Clinical Characteristics of Different Toxicity Rates in Anti-CD19 Chimeric Antigen Receptor T Cells: Real-World Experience.

Commercially available anti-CD19 chimeric antigen receptor T cells (CARΤ cells) have offered long-term survival to a constantly expanding patient population. Given that novel toxicities including cytokine release syndrome (CRS) and neurotoxicity (ICANS) have been observed, we aimed to document the safety and toxicity of this treatment in a real-world study. We enrolled 31 adult patients referred to our center for CAR T therapy. Tisagenlecleucel was infused in 12 patients, axicabtagene ciloleucel in 14, and brexucabtagene autoleucel in 5. Cytokine release syndrome was noted in 26 patients while neurotoxicity was observed in 7. Tocilizumab was administered for CRS in 18 patients, along with short-term, low-dose steroid administration in one patient who developed grade III CRS and, subsequently, grade I ICANS. High-dose steroids, along with anakinra and siltuximab, were administered in only two MCL patients. With a median follow-up time of 13.4 months, nine patients were then in CR. The progression-free (PFS) and overall survival (OS) rates were 41.2% and 88.1% at one year, respectively. MCL diagnosis, which coincides with the administration of brexucabtagene autoleucel, was the only factor to be independently associated with poor OS (p < 0.001); meanwhile, increased LDH independently predicted PFS (p = 0.027).In addition, CRP at day 14 was associated with a poor OS (p = 0.001). Therefore, our real-world experience confirmed that commercial CAR T therapy can be administered with minimal toxicity.

Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit.

The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1±4 vs. 15.3±8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters.

Le but de cette étude était d'examiner si un algorithme basé sur des mesures de la procalcitonine (PCT) peut permettre la réduction de la durée de l'antibiothérapie, sans être dangereuse, chez les patients brûlés infectés. Tous les patients brûlés nécessitant une antibiothérapie en raison d'une infection bactérienne très probable ou confirmée étaient éligibles. Les patients ont été divisés en deux groupes: groupe à l'étude (durée de traitement guidé par PCT), et groupe de contrôle (durée selon les préconisations actuelles). Les variables suivantes ont été analysées et comparées: durée de traitement, mortalité, le pourcentage de patients avec une surinfection ou une rechute, score SOFA maximum entre J1 et J28, durées de séjour en soins intensifs et à l'hôpital. Un total de 46 patients, hospitalisés en soins intensifs et recevant une antibiothérapie ont été inclus dans cette étude, dont 24 dans le groupe PCT. Ces patients ont reçu une exposition aux antibiotiques inférieure (10,1 ± 4 vs 15,3 ± 8 jours, p = 0,034), sans effets négatifs sur le taux de mortalité et la durée du séjour à l'hôpital. Les résultats montrent que cette méthode peut contribuer à la réduction de l'utilisation des antibiotiques chez les brûlés en soins intensifs, sans compromettre leur avenir.

Evaluation of arterial waveform derived variables for an assessment of volume resuscitation in mechanically ventilated burn patients.

OBJECTIVE: The purpose of this study was to assess the usefulness of stroke volume variations to monitor the early fluid resuscitation in mechanically ventilated burn ICU patients. METHODS AND RESULTS: Data of 29 burn patients (APACHE II - 9.8±3.6, SAPS II - 29±5, TBSA - 39.5±14) were prospectively included in this observational study. Hemodynamic parameters were determined using arterial pressure wave analysis for up to 36h after burn. Statistically significant changes in cardiac index (CI), systemic vascular resistance index (SVRI), stroke volume variation (SVV) were recorded during the observation period. There were significant correlations between CI and SVV (r=-0.454, p=0.03), SVV and SVRI (r=0.482, p=0.02) at 16 h postburn; CI and SVV (r=-0.513, p=0.012), SVV and SVRI (r=0.480, p=0.02) at 24 h postburn, CI and SVV at 36 h postburn (r=-0.478, p=0.021). Significant changes in CI (1.9±1 vs. 3.4±0.9), p=0.02 and in SVV (24.9±3 vs. 14.6±2, p=0.01) were observed in patients with low cardiac output state after administration of 10 ml/kg of Ringer lactate. CONCLUSION: Our results suggest that measurement of stroke volume variations by arterial pulse contour analysis is valuable in monitoring volume administration and in predicting volume responsiveness during the early postburn period.

PCT as a diagnostic and prognostic tool in burn patients. Whether time course has a role in monitoring sepsis treatment.

OBJECTIVE: To evaluate the diagnostic and prognostic performance of inflammatory markers for septic and non septic (localized) bacterial infections in patients with severe burn. METHODS AND RESULTS: Data of 145 patients were prospectively included in this study. Serum procalcitonin and other inflammatory markers were measured within 24 h after burn and daily thereafter. Maximum procalcitonin (p=0.004) was independent predictors of outcome in logistic regression analysis. PCT thresholds of 1.5 ng/ml, 0.52 ng/ml and 0.56 ng/ml had adequate sensitivity and specificity to diagnose sepsis, respiratory tract and wound infections respectively. A threshold value of 7.8 ng/ml in PCT concentration on day 3 was associated with the effectiveness of the sepsis treatment with an AUC of 0.86 (95% CI 0.69-1.03, p=0.002). C-reactive protein levels and WBCs showed no significant change over the first 3 days in the patients with successfully treated sepsis (p=0.93). CONCLUSION: The maximum procalcitonin level has prognostic value in burn patients. PCT can be used as a diagnostic tool in patients with infectious complications with or without bacteremia during ICU stay. Daily consecutive PCT measurements may be a valuable tool in monitoring the effectiveness of antibiotic therapy in burn ICU patients.

Early endograft collapse following endovascular treatment of a traumatic thoracic aortic disruption: a case report.

The authors present the case of a 39-year-old man who underwent endovascular repair of a thoracic aortic disruption. Implantation of a Gore TAG stent-graft achieved total exclusion of the traumatic lesion with no contrast extravasation. However, on the third postoperative day, the patient developed complete anuria necessitating continuous venovenous hemofiltration. On the IV postoperative day there were no palpable femoral pulses and the pressure gradient between the lower and upper limbs was -80 mmHg. Given the development of severe intestinal and peripheral hypoperfusion status a possible endograft collapse was suspected. Urgent computed tomography (CT) angiography demonstrated central subtotal collapse of the device and proper distal sealing. A second TAG stent-graft was deployed successfully within the collapsed device with no contrast extravasation and good apposition of the stent-graft to the aortic wall. At 6 months, there is no sign of graft collapse or endoleak. Endovascular reintervention succeeded re-expansion of the collapsed endoprosthesis and resolution of the initial symptoms.

Resting energy expenditure in brain death.

OBJECTIVE: To evaluate resting energy expenditure (REE) in brain dead patients and to investigate the hypothesis that the reduction in REE results from a decrease in cerebral blood flow. DESIGN: Prospective, open labeled, control study. SETTING: General intensive care unit of a tertiary referral teaching hospital. PATIENTS: 30 critically ill patients with isolated head injury divided in two groups: group 1 patients (n = 10) with a Glasgow Coma Scale (GCS) score of 4 to 8 and group 2 patients (n = 20), in whom the final outcome was brain death (GCS = 3). Group 2 patients were divided into two subgroups: Group 2 a (n = 11) were admitted as brain dead (GCS = 3) and group 2 b (n = 9) were admitted with a GCS > 3 and progressed to brain death. INTERVENTIONS: Clinical and instrumental, using transcranial Doppler sonography (TCD), diagnosis of brain death. Cerebral blood flow studies of the middle cerebral artery bilaterally by bidimensional TCD and measurement of REE using indirect calorimetry. MEASUREMENTS AND RESULTS: Measurements of REE and TCD studies were performed simultaneously on admission and after hemodynamic and neurologic stabilization. In cases with progressive neurologic deterioration, serial measurements were performed REE values were expressed as percentage of basal metabolic rate (%BMR), which were estimated according to each patient's gender, age, height, and weight. Group 1 patients, had normal TCD patterns throughout their hospitalization and their REE value was 21 +/- 11 % higher than BMR. Group 2 patients demonstrated TCD patterns compatible with brain death and their REE value was 24.5 +/- 11 % lower than BMR (p < 0.01). Group 2 a patients, who were admitted as brain dead and remained brain dead, had REE values 30 +/- 11 % lower than BMR (p < 0.01). Group 2 b patients, who were not brain dead on admission but progressed to brain death, in serial measurements revealed a significant relationship between REE and TCD findings (R = -0.77, p < 0.0001). In this subgroup of patients, with multiple regression analysis a significant relationship was found only between REE and the TCD pattern, but not with body temperature. CONCLUSIONS: In brain dead patients, REE decreases to values lower than BMR. This can be attributed to the cessation of cerebral blood flow and consequently cerebral metabolism and not to hypothermia.