Late-onset relapsing neurotoxicity after Brexucabtagene autoleucel associated with high chimeric antigen receptor T cells in cerebrospinal fluid.

BACKGROUND AIMS: Mounting evidence suggests that persistent cell expansion is the main driver for both efficacy and toxicity of chimeric antigen receptor (CAR) T-cell therapy. Hereby, we describe a case of delayed recurrent neurotoxicity associated with late CAR T-cells re-expansion. CASE DESCRIPTION: A 44-year-old man suffering from mantle cell lymphoma received brexu-cel. After infusion, he developed grade 2 cytokine release syndrome. On day +11, grade 3 neurotoxicity was reported and high-dose methylprednisolone was started with a complete resolution of neurological manifestations. On day +30, he experienced a late-onset CAR T-cell toxicity associated with CAR T-cell re-expansion. The patient was treated with tocilizumab and dexamethasone, with resolution of symptoms. On day +58, he was readmitted for new onset of neurotoxicity. Notably, a new CAR T-cell expansion was observed, with an unexpectedly elevated cerebrospinal fluid/blood ratio. The patient was promptly treated with dexamethasone and then escalated to high-dose methylprednisolone and anakinra, with resolution of his neurologic condition noted. CONCLUSIONS: CAR T-cell-related neurotoxicity usually has an early monophasic course. To our knowledge, this is the first case of late-onset, recurrent neurotoxicity. Moreover, an elevated level of cerebrospinal fluid CAR T cells was observed, which may suggest that the delayed neurotoxicity was primarily caused by the brain infiltration of CAR T cells rather than driven by cytokine-mediated neuroinflammation.

Total duration of spontaneous blastocyst collapse during the expansion stage is an independent predictor of euploidy and live birth rates.

RESEARCH QUESTION: Is the total duration of spontaneous blastocyst collapse to re-expansion before biopsy related to ploidy and live birth rates after single euploid blastocyst transfer? DESIGN: This was a retrospective cohort study of 600 preimplantation genetic testing cycles for aneuploidy (PGT-A) cycles, involving 2203 biopsied blastocysts, at a large reproductive medicine centre. Features of spontaneous blastocyst collapse from full to expanded stage, before biopsy, were observed using an embryoscope viewer for embryos cultured in a time-lapse incubator. In total, 568 cycles of frozen blastocyst transfers, either single euploid or mosaic, were performed. Correlations between collapse features and PGT-A outcomes were evaluated, as well as live birth rate, following euploid embryo transfer. RESULTS: Blastocysts with lower morphological quality or delayed development had significantly higher rates of collapse, multiple collapses, and a longer duration of collapse to re-expansion. After controlling for confounders, such as oocyte age, morphological quality of blastocyst, and day of biopsy, multivariate logistic regression revealed that the total duration of collapse to re-expansion was an independent predictor of lower euploidy rate; the multivariate OR was 0.85 (95% CI 0.77-0.95; P = 0.00). Furthermore, even with euploid embryo transfer, the probability of a live birth decreased as the total duration of collapse to re-expansion increased; the multivariate OR was 0.79 (95% CI 0.64-0.98; P = 0.033). CONCLUSION: The total duration of blastocyst collapse to re-expansion could be used as a predictor of lower euploidy and live birth rate. When developing blastocyst algorithms for pregnancy prediction, the duration of spontaneous blastocyst collapse should be included as a significant variable.

Using blastocyst re-expansion rate for deciding when to warm a new blastocyst for single vitrified-warmed blastocyst transfer.

RESEARCH QUESTION: Can predictive post-warm parameters that support the decision to transfer a warmed blastocyst or to warm another blastocyst be identified in women with multiple frozen-vitrified blastocysts? DESIGN: Retrospective single-centre observational cohort analysis. A total of 1092 single vitrified-warmed blastocyst transfers (SVBT) with known Gardner score, maternal age and live birth were used to develop live birth prediction models based on logistic regression, including post-warm re-expansion parameters. Time-lapse incubation was used for pre-vitrification and post-warm embryo culture. A dataset of 558 SVBT with the same inclusion criteria was used to validate the model, but with known clinical pregnancy outcome instead of live birth outcome. RESULTS: Three different logistic regression models were developed for predicting live birth based on post-warm blastocyst re-expansion. Different post-warm assessment times indicated that a 2-h post-warm culture period was optimal for live birth prediction (model 1). Adjusting for pre-vitrification Gardner score (model 2) and in combination with maternal age (model 3) further increased predictability (area under the curve [AUC] = 0.623, 0.633, 0.666, respectively). Model validation gave an AUC of 0.617, 0.609 and 0.624, respectively. The false negative rate and true negative rate for model 3 were 2.0 and 10.1 in the development dataset and 3.5 and 8.0 in the validation dataset. CONCLUSIONS: Clinical application of a simple model based on 2 h of post-warm re-expansion data, pre-vitrification Gardner score and maternal age can support a standardized approach for deciding if warming another blastocyst may increase the likelihood of live birth in SVBT.

Pulmonary edema ex vacuo after drainage of pyo-pneumothorax.

This case presents a rare occurrence of re-expansion pulmonary edema following a drainage of pyo-pneumothorax in a 33-year-old patient. The diagnosis was established through a thoracic radiography, and the treatment consisted of symptomatic management, showing positive progress. Later on, the patient was diagnosed with pleural tuberculosis via GeneXpert testing and subsequently initiated on anti-bacterial therapy.This case report aims to shed light on the infrequent pulmonary edema ex vacuo as a complication of pleural drainage. It explores its causes, risk factors, diagnostic approaches, and treatment options. this study highlights the necessity of effective prevention and management strategies.

Re-expansion pulmonary edema after minimally invasive cardiac surgery in children.

Re-expansion pulmonary edema is a serious complication that can occur after minimally invasive cardiac surgery through a right mini-thoracotomy. Herein, we describe two paediatric cases where re-expansion pulmonary edema was observed after simple atrial septal defect closure through a right mini-thoracotomy. This is the first case report of re-expansion pulmonary edema after a paediatric cardiac surgery.

Time from trophectoderm biopsy to vitrification affects the developmental competence of biopsied blastocysts.

Purpose: The present study aimed to examine the correlations of the time interval from trophectoderm (TE) biopsy to vitrification with the blastocyst survival rate and blastocyst outgrowth ability. Methods: A total of 1,202 mouse blastocysts were randomly divided into control (non-biopsy) and TE biopsy groups. The biopsied blastocysts were vitrified at various time points. The survival rate after warming, blastocyst adhesion rate, and outgrowth area was investigated. Several biopsied blastocysts were cultured in a time-lapse incubator, and the time required for re-expansion was measured. Results: Blastocyst survival rates after warming and blastocyst adhesion rates were comparable between the control and biopsy groups. The area of trophoblast outgrowth in the 1-h biopsy group was significantly smaller than that in the control, 0-h biopsy, and 4-h biopsy groups (p = 0.0304, p = 0.0058, and p = 0.0029, respectively). Re-expansion of blastocysts was observed at a high incidence 1-2 h after TE biopsy. Conclusions: The vitrification of biopsied blastocysts in the process of re-expansion impairs outgrowth competence; therefore, blastocyst vitrification should be performed immediately after TE biopsy and before initiation of re-expansion.

Large Intrathoracic Desmoid Tumor and Re-Expansion Pulmonary Edema: Case Report and Review of the Literature.

Re-expansion pulmonary edema is a potentially life-threatening situation following thoracic surgery of a compromised lung. We report the case of a 24-year-old female scheduled for a resection of a large intrathoracic desmoid tumor that presented with re-expansion pulmonary edema at the conclusion of her surgery and discuss the clinical presentation, mechanism and predictors of this entity and review similar cases reported in the literature.

Re-expansion pulmonary edema following a pneumothorax drainage in a patient with COVID-19.

BACKGROUND: Re-expansion pulmonary edema is an uncommon complication following drainage of a pneumothorax or pleural effusion. While pneumothorax is noted to complicate COVID-19 patients, no case of COVID-19 developing re-expansion pulmonary edema has been reported. CASE REPRESENTATION: A man in his early 40 s without a smoking history and underlying pulmonary diseases suddenly complained of left chest pain with dyspnea 1 day after being diagnosed with COVID-19. Chest X-ray revealed pneumothorax in the left lung field, and a chest tube was inserted into the intrathoracic space without negative pressure 9 h after the onset of chest pain, resulting in the disappearance of respiratory symptoms; however, 2 h thereafter, dyspnea recurred with lower oxygenation status. Chest X-ray revealed improvement of collapse but extensive infiltration in the expanded lung. Therefore, the patient was diagnosed with re-expansion pulmonary edema, and his dyspnea and oxygenation status gradually improved without any intervention, such as steroid administration. Abnormal lung images also gradually improved within several days. CONCLUSIONS: This case highlights the rare presentation of re-expansion pulmonary edema following pneumothorax drainage in a patient with COVID-19, which recovered without requiring treatment for viral pneumonia. Differentiating re-expansion pulmonary edema from viral pneumonia is crucial to prevent unnecessary medication for COVID-19 pneumonia and pneumothorax.

Embryo re-expansion does not affect clinical pregnancy rates in frozen embryo transfer cycles: a retrospective study.

PURPOSE: A retrospective study examining the effects of embryo re-expansion before transfer on pregnancy outcomes for frozen embryo transfers (FET). METHODS: A total of 486 FET cycles from November 2017 through December 2019 were studied. These cycles included patients using autologous, donor oocytes, and donor embryo with patients ranging from ages 23 to 48 years with infertility diagnoses. Programmed FET priming was performed with exogenous estrogen and progesterone. All blastocysts were cultured in trigas incubators for 20 min to 4 h and 42 min. Pictures of each blastocyst after thaw and before transfer were taken utilizing the Hamilton Thorne Zilos laser software (Beverly, MA). The longest portion of the embryo was measured in µm. Pregnancy was defined by a positive hCG, and ongoing clinical pregnancy was defined by the presence of fetal cardiac activity. Wilcoxon rank sum tests were used to access differences in change parameters. RESULTS: There is no significant difference in the amount of embryo expansion or contraction to achieve an ongoing pregnancy. The difference remained non-significant when stratified by embryo expansion or contraction. The amount of change over time and percent change from the first measurement were also not associated with achieving an ongoing pregnancy. This remained true after adjustment for patient age and whether or not a biopsy was performed. CONCLUSIONS: Embryos that do not re-expand after warming appear to have a similar chance of achieving a successful pregnancy as those that do re-expand.

Rarely fatal bilateral re-expansion pulmonary edema after inserting a chest tube for unilateral spontaneous pneumothorax: a case report.

We describe a case of a 32-year-old man who died due to bilateral re-expansion pulmonary edema (RPE) following the insertion a chest tube for unilateral spontaneous pneumothorax. Fifteen minutes after inserting the chest tube, the patient with right spontaneous pneumothorax was diagnosed with right re-expansion edema by chest radiograph. Although multiple treatments were administered, the patient died. However, the findings from autopsy showed bilateral RPE existed in the decedent but not unilateral RPE. Autopsy, microscopic examination, and clinical records concluded that the cause of death was acute cardiac and respiratory failure due to bilateral re-expansion pulmonary edema following unilateral spontaneous pneumothorax. Bilateral RPE due to a unilateral pneumothorax is quite rare in clinical and forensic practice. To the best of our knowledge, this is the first time that the pathological changes of RPE have been described by gross and microscopic examinations. This case is reported to provide histopathologic references for diagnosis of RPE and indicate that combining death investigation, pathological findings and clinical courses plays a vital role in diagnosis of RPE in forensic pathology.

Re-expansion Pulmonary Edema-A Rare Entity: A Thin Line between Pulmonary and Cardiac Decompensation.

Re-expansion pulmonary edema (RPE) is a rare complication that may occur after treatment of lung collapse caused by pneumothorax, atelectasis, or pleural effusion. The amount of fluid drained and the degree of pleural suction influence the development of RPE. We present a case of RPE in a critically ill patient of scrub typhus with rheumatic heart disease, after draining only 800 mL of pleural fluid, thereby proving that the complex cardiac and pulmonary interactions play an important role in the development of RPE. How to cite this article: Khanoria R, Chauhan R, Sarna R, Bloria S. Re-expansion Pulmonary Edema-A Rare Entity: A Thin Line between Pulmonary and Cardiac Decompensation. Indian J Crit Care Med 2021;25(3):343-345.

The Impact of Continuous Positive Airway Pressure upon Pleural Fluid Pressures during Thoracentesis.

BACKGROUND: Excessive drop of pleural pressure (Ppl) during therapeutic thoracentesis may be related to adverse events and/or to repeated procedures due to incomplete drainage. OBJECTIVE: This was a pilot study of the impact of the application of continuous positive airway pressure (CPAP) at +5 cm H2O upon the Ppl profile during thoracentesis. METHODS: This was a prospective, controlled study of 49 consecutive adults who underwent thoracentesis. Enrollment was via alternation on a one-to-one basis. Pleural manometry was used to compare serial Ppl in patients using CPAP at +5 cm H2O (CPAP group) with Ppl in patients without CPAP (control group). RESULTS: Mean volumes drained were comparable between CPAP and control groups (1,380 vs. 1,396 mL). Patients in the CPAP group had a significantly greater change in volume per centimeter water column pressure (p = 0.0231, 95% confidence interval 6.41-82.61). No patient in the CPAP group had a Ppl less than -20 cm H2O at termination of the procedure, while 8 (33%) control group patients developed a pressure lower than -20. No patient in either group developed re-expansion pulmonary edema. CONCLUSION: The application of CPAP at +5 cm H2O mitigates the decreases in Ppl caused by thoracentesis via an increase in pleural compliance. The clinical implications of this finding merit study.

Cryosurvival after exposure of IVF-derived Nellore embryos to different cryoprotectants and exposure times during vitrification.

We evaluated the effects of the vitrification solution (i.e., ethylene glycol (EG) + dimethyl sulfoxide (DMSO) with or without propylene glycol (PG)) and of exposure time on the re-expansion and hatching rates of vitrified Bos indicus embryos. In vitro produced embryos (n = 1050) were divided into seven groups: control group (non-vitrified embryos) and six vitrification groups with different cryoprotectant concentrations and exposure times. After vitrification, embryos were cultured for determination of re-expansion and hatching rates. Vitrification with 25% DMSO +25% EG (exposure for 1 min and 20 s) resulted in the highest re-expansion (65.2%) and hatching (68.2%) rates. The lowest re-expansion and hatching rates were observed in vitrification with 12.5% DMSO + 25% EG + 12.5% PG with both tested exposure times (i.e., 3 min + 1 min and 1 min + 20 s). A combination of DMSO + EG is efficient to preserve blastocysts, especially following a short exposure time.

Blastocoele re-expansion time in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome.

AIM: To assess the predictive value of blastocoele re-expansion time in clinical pregnancy outcome in vitrified-warmed cycles. METHODS: Data on 468 single vitrified-thawed blastocyst transfer cycles (in patients aged <38 years) carried out from January 2012 through December 2012, at the Reproductive Medicine Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, were analyzed. Vitrified-warmed blastocysts were divided into three groups according to blastocoele re-expansion time: group A, <1 h; group B, 1-2 h; and group C, >2 h, and the clinical pregnancy outcomes (i.e. live birth rate, miscarriage rate and occurrence of singleton pregnancies) compared between the groups. RESULTS: Significant differences were observed in the implantation/clinical pregnancy rate between groups A, B and C (70.10%, 51.76% and 28.74%, respectively, P < 0.01). There was a significant linear decline in this rate with increasing blastocyst re-expansion time. The rate of miscarriage also tended to increase with increasing blastocyst re-expansion time, but the difference was not statistically significant (P > 0.05). Of the pregnant patients, no significant difference was observed in the rates of monozygotic twins and ectopic pregnancy between the three groups. For the newborns, similar live birth, low-birthweight and premature delivery rates were observed between the groups. CONCLUSIONS: Timing of blastocoele re-expansion in vitrified-warmed cycles is a strong predictor of clinical pregnancy outcome. The faster the re-expansion of the blastocoele, the higher the developmental potential of the blastocysts.

Morphokinetics of vitrified and warmed blastocysts predicts implantation potential.

PURPOSE: It was studied whether morphokinetics of blastocoele re-expansion and hatching in vitrified-warmed blastocysts is predictive of implantation, clinical pregnancy, and live birth. METHODS: In 144 patients aiming for single warmed blastocyst transfer, blastocysts were cultured in a new time-lapse system (Miri® TL) immediately after warming. Video sequences with an image interval of 5 min were annotated and the corresponding morphokinetic variables were correlated with pregnancy outcome. In detail, tRE (start of re-expansion), tCRE (completion of re-expansion), tAH (hatching from the manipulated zona pellucida), and presence of collapses were recorded. RESULTS: In the pregnant group, tRE and tCRE were significantly lower (0.69 ± 0.45 h and 2.16 ± 0.94 h) as compared to the non-pregnant group (1.23 ± 1.08 h and 2.70 ± 1.20 h). Both variables and the duration of re-expansion (tCRE-tRE) allowed for distinction between "non-pregnant," "loss of pregnancy," and live birth/ongoing pregnancy. Presence and number of collapses showed no correlation with outcome. CONCLUSIONS: Time-lapse imaging of vitrified-warmed blastocysts offers additional selection criteria allowing for prediction of implantation potential. As a consequence, cumulative pregnancy rate could be increased and time-to-pregnancy reduced.

Use of the CryoPredict algorithm to predict live birth from cryopreserved embryos.

BACKGROUND: Currently, the viability of cryostored blastocysts that are subsequently re-warmed is determined via the percentage of cell survival. However, the large number of cells that forms the blastocyst can make this estimate difficult and unreliable. Studies have shown that fast re-expanding blastocysts have superior pregnancy rates. AIM: To determine whether the degree and speed of blastocoele re-expansion following cryopreservation and warming correlate with rates of live birth. MATERIALS AND METHODS: A retrospective cohort study of 757 frozen embryo transfer cycles over a 4-year period at Royal Prince Alfred Hospital, Sydney. Clinical and embryology notes were retrieved. Details regarding patient demographics, stimulation cycle from which embryos were derived, frozen embryo transfer cycles, embryology and pregnancy outcomes were recorded. RESULTS: Female (P = 0.01) and male age (P = 0.02) at the time of embryo creation were inversely associated with live birth. Fertilisation method (P = 0.03), embryo type at cryopreservation (P = 0.009), embryo grade at cryopreservation (P < 0.0001), percentage of cell survival post-thaw (P < 0.0001) and the degree of re-expansion (P = 0.003) were the IVF and embryology factors significantly associated with live birth. A predictive model (CryoPredict) was created in order to individualise the probability that the transfer of a given embryo would result in live birth. CONCLUSIONS: The degree and speed of blastocoele re-expansion postcryopreservation and subsequent warming can be used in conjunction with other parameters to predict live birth.

Thoracentesis outcomes: a 12-year experience.

BACKGROUND: Despite a lack of evidence in the literature, several assumptions exist about the safety of thoracentesis in clinical guidelines and practice patterns. We aimed to evaluate specific demographic and clinical factors that have been commonly associated with complications such as iatrogenic pneumothorax, re-expansion pulmonary oedema (REPE) and bleeding. METHODS: We performed a cohort study of inpatients who underwent thoracenteses at Cedars-Sinai Medical Center (CSMC) from August 2001 to October 2013. Data were collected prospectively including information on volume of fluid removed, procedure side, whether the patient was on positive pressure ventilation, number of needle passes and supine positioning. Iatrogenic pneumothorax, REPE and bleeding were tracked for 24 h after the procedure or until a clinical question was reconciled. Demographic and clinical characteristics were obtained through query of electronic medical records. RESULTS: CSMC performed 9320 inpatient thoracenteses on 4618 patients during the study period. There were 57 (0.61%) iatrogenic pneumothoraces, 10 (0.01%) incidents of REPE and 17 (0.18%) bleeding episodes. Iatrogenic pneumothorax was significantly associated with removal of >1500 mL fluid (p<0.0001), unilateral procedures (p=0.001) and more than one needle pass through the skin (p=0.001). For every 1 mL of fluid removed there was a 0.18% increased risk of REPE (95% CI 0.09% to 0.26%). There were no significant associations between bleeding and demographic or clinical variables including International Normalised Ratio, partial thromboplastin time and platelet counts. CONCLUSIONS: Our series of thoracenteses had a very low complication rate. Current clinical guidelines and practice patterns may not reflect evidence-based best practices.

Re-expansion Pulmonary Edema (REPE) Following Thoracentesis: Is Large-Volume Thoracentesis Associated with Increased Incidence of REPE?

PURPOSE: To determine the safety and efficacy associated with drainage volumes greater than 1,500 mL in a single, unilateral thoracentesis without pleural manometry measurements. MATERIALS AND METHODS: This retrospective, single-institution study included 872 patients (18 years and older) who underwent ultrasound-guided thoracentesis. Patient and procedures data were collected including demographics, number of and laterality of thoracenteses, volume and consistency of fluid removed, and whether clinical or radiologic evidence of re-expansion pulmonary edema (REPE) developed within 24 h of thoracentesis. Fisher's exact test was used to test the significance of the relationship between volume of fluid removed and evidence of REPE. RESULTS: A total of 1376 thoracenteses were performed among the patients included in the study. The mean volume of fluid removed among all procedures was 901.1 mL (SD = 641.7 mL), with 194 (14.1%) procedures involving the removal of ≥ 1,500 mL of fluid. In total, six (0.7%) patients developed signs of REPE following thoracentesis, five of which were a first-time thoracentesis. No statistically significant difference in incidence of REPE was observed between those with ≥ 1,500 mL of fluid removed compared to those with < 1,500 mL of fluid removed (p-value = 0.599). CONCLUSIONS: Large-volume thoracentesis may safely improve patients' symptoms while preventing the need for repeat procedures.

Risk factors for re-expansion pulmonary edema following chest tube drainage in patients with spontaneous pneumothorax: A systematic review and meta-analysis.

Re-expansion pulmonary edema (RPE) is a rare but potentially life-threatening complication that can occur after rapid lung expansion following the management of lung collapse. This meta-analysis aimed to investigate the risk factors for RPE following chest tube drainage in patients with spontaneous pneumothorax. We conducted a comprehensive systematic literature search in electronic databases of PubMed, ScienceDirect, Cochrane Library, and ProQuest to identify studies that explore the risk factors for RPE following chest tube drainage in spontaneous pneumothorax. Pooled odds ratios (OR) or weighted mean differences (WMD) were calculated to evaluate the risk factors. Statistical analysis was conducted using Review Manager 5.3 software. Five studies involving 1.093 spontaneous pneumothorax patients were included in this meta-analysis. The pooled analysis showed that the following risk factors were significantly associated with increased risk of RPE following chest tube drainage: the presence smoking history (OR=1.94, 95% CI: 1.22-3.10, P=0.005, I2=0%), longer duration of symptoms (WMD=3.76, 95% CI: 2.07-5.45, P<0.0001, I2=30%), and larger size of pneumothorax (WMD=16.76, 95% CI: 8.88-24.64, P<0.0001, I2=78%). Age, sex, and location of pneumothorax had no significant association. In patients with spontaneous pneumothorax, the presence of smoking history, longer duration of symptoms, and larger size of pneumothorax increase the risk of development of RPE following chest tube drainage.