Chylothorax after chimeric antigen receptor T cell therapy for relapsed and refractory diffuse large B-cell lymphoma: A case report.

RATIONALE: Anti-CD19-targeted chimeric antigen receptor (CAR) T cell therapy is effective in treating relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This therapy is associated with several side effects that can be life-threatening such as cytokine release syndrome (CRS). However, chylothorax associated with CRS after CAR-T therapy has not been reported. PATIENT CONCERNS: A 23-year-old male diagnosed with DLBCL relapsing after autologous peripheral blood stem cell transplantation was treated with anti-CD19-targeted CAR-T cell therapy. After CAR-T cell transfusion, he developed grade 3 CRS includes fever, dyspnea, tachycardia and hypotension. The symptoms of CRS persisted and chest plain film revealed bilateral pleural effusion. DIAGNOSIS: Chylothorax was confirmed by the pleural effusion analysis that triglyceride level was 1061 mg/dL. Bacterial and fungal culture of pleural fluid reported no pathogen was detected. Cytological examination of pleural effusion revealed no malignant cells. INTERVENTIONS: The chylothorax resolved after treatment with intravenous administration of tocilizumab. OUTCOMES: On 30-day follow-up, the patient was in stable clinical condition with complete remission of DLBCL on whole-body positron emission tomography scan. LESSONS: We reported a rare case of CAR-T associated chylothorax in a patient with relapsed and refractory DLBCL. Grade 3 CRS with high interleukin-6 level was presented in our patient. The symptoms of CRS were improved with tocilizumab treatment and the chylothorax resolved later on. It is suggested that high interleukin-6 releases might induce chyle leakage resulting from activations of endothelium and coagulation. Our finding highlights the occurrence of chylothorax during the course of CAR-T cell therapy and the importance of proper monitoring and prompt management of this life-threatening side effect.

A Cardiac Force Index Applied to the G Tolerance Test and Surveillance among Male Military Aircrew.

Military aircrew are occupationally exposed to a high-G environment. A tolerance test and surveillance is necessary for military aircrew before flight training. A cardiac force index (CFI) has been developed to assess long-distance running by health technology. We added the parameter CFI to the G tolerance test and elucidated the relationship between the CFI and G tolerance. A noninvasive device, BioHarness 3.0, was used to measure heart rate (HR) and activity while resting and walking on the ground. The formula for calculating cardiac function was CFI = weight × activity/HR. Cardiac force ratio (CFR) was calculated by walking CFI (WCFI)/resting CFI (RCFI). G tolerance included relaxed G tolerance (RGT) and straining G tolerance (SGT) tested in the centrifuge. Among 92 male participants, the average of RCFI, WCFI, and CFR were 0.02 ± 0.04, 0.15 ± 0.04, and 10.77 ± 4.11, respectively. Each 100-unit increase in the WCFI increased the RGT by 0.14 G and the SGT by 0.17 G. There was an increased chance of RGT values higher than 5 G and SGT values higher than 8 G according to the WCFI increase. Results suggested that WCFI is positively correlated with G tolerance and has the potential for G tolerance surveillance and programs of G tolerance improvement among male military aircrew.

Contributions of Hypoxia-Awareness Training to the Familiarization of Personal Symptoms for Occupational Safety in the Flight Environment.

Hypoxia remains a flight-safety issue in terms of aviation medicine. Hypoxia-awareness training has been used to help aircrew members recognize personal hypoxia symptoms. There is still no study, as yet, to establish the association of within-subject data between inflight hypoxia events and the altitude chamber. The main purpose of our study was to use paired subjects' data on inflight hypoxia symptoms compared with those experienced during training. A questionnaire was developed to obtain information on military aircrew members in 2018. Among 341 subjects, 46 (13.49%) suffered from inflight hypoxia. The majority of the subjects detected ongoing inflight hypoxia on the basis of their previous experience with personal hypoxia symptoms or sensations in previous chamber flights. Of the top five hypoxia symptoms, the data revealed that hot flashes, poor concentration, and impaired cognitive function appeared both during the inflight events and during the hypoxia-awareness training. The occurrence rate of hypoxia symptoms was found to not be significantly different between the in-flight events and the past chamber flights through an analysis of within-subject data. Because the individual memory had faded away over time, fresher hypoxia awareness training is still mandatory and valuable to recall personal hypoxia experience for military aircrew members.

Combined effect of heart rate responses and the anti-G straining manoeuvre effectiveness on G tolerance in a human centrifuge.

Increased heart rate (HR) is a reaction to head-to-toe gravito-inertial (G) force. The anti-G straining manoeuvre (AGSM) is the crucial technique for withstanding a high-G load. Previous studies reported the main effects of HR only or AGSM only on G tolerance. We assessed the combined effect of HR and AGSM on the outcome of 9G profile exposure. A total of 530 attempts for the 9G profile were extracted to clarify the association of interest. Subjects with an AGSM effectiveness of less than 2.5G had a 2.14-fold higher likelihood of failing in the 9G profile. Trainees with HR increases of less than 20% in the first five seconds also had higher odds of 9G profile intolerance (adjusted OR 1.83, 95% CI 1.09-3.07). The adjusted OR of 9G profile disqualification was 2.93 (95% CI 1.19-7.20) for participants with smaller HR increases and lower AGSM effectiveness. The negative effect of a smaller HR increase on the outcome was likely to be affected by improved AGSM effectiveness (adjusted OR 1.26, 95% CI 0.65-2.42). We speculate that low AGSM effectiveness and a small HR increase were separately associated with failure of high-G challenge. Nonetheless, good AGSM performance seemed to reduce the negative effect of weak HR responses on the dependent variable.

Roles of Physiological Responses and Anthropometric Factors on the Gravitational Force Tolerance for Occupational Hypergravity Exposure.

Gravity in the head-to-toe direction, known as +Gz (G force), forces blood to pool in the lower body. Fighter pilots experience decreases in blood pressure when exposed to hypergravity in flight. Human centrifuge has been used to examine the G tolerance and anti-G straining maneuver (AGSM) techniques of military pilots. Some factors that may affect G tolerance have been reported but are still debated. The aim of this study was to investigate the physiological responses and anthropometric factors correlated with G tolerance. We retrospectively reviewed the training records of student pilots who underwent high G training. Variables were collected to examine their correlations with the outcome of 7.5G sustained for 15 s (7.5G profile). There were 873 trainees who underwent 7.5G profile training, 44 trainees (5.04%) could not sustain the test for 15 s. The group with a small heart rate (HR) increase (less than 10%) during the first 1-5 s of the 7.5G profile had a nearly ten-fold higher failing chance compared with the large HR increase group (adjusted odds ratio: 9.91; 95% confidence interval: 4.11-23.88). The chances of failure were inversely related to the HR increase percentage (p for trend <0.001). Factors, including body mass index, relaxed and straining G tolerance, and AGSM, were found to be negatively correlated with the outcome.

Differential modulation of IL-12 family cytokines in autoimmune islet graft failure in mice.

AIMS/HYPOTHESIS: The relative contribution of T helper (Th)1 and Th17 cells in graft rejection is inconclusive, on the basis of evidence provided by different T cell-related cytokine-deficient animal models and graft types. METHODS: We used novel antigen-presenting-cell-specific Il-12p35 (also known as Il12a)-knockout (KO), IL-23p19-knockdown (KD) and IL-27p28-KD strategies to investigate T cell differentiation in islet graft rejection. RESULTS: In vitro dendritic cell-T cell coculture experiments revealed that dendritic cells from Il-12p35-KO and IL-23p19-KD mice showed reduced ability to stimulate IFN-γ and IL-17 production in T cells, respectively. To further explore the T cell responses in islet graft rejection, we transplanted islets into streptozotocin-induced diabetic NOD/severe combined immunodeficiency (SCID) recipient mice with IL-12-, IL-23-, or IL-27-deficient backgrounds and then challenged them with NOD.BDC2.5 T cells. The survival of islet grafts was significantly prolonged in Il-12p35-KO and IL-23p19-KD recipients compared with the control recipients. T cell infiltrations and Th1 cell populations were also decreased in the grafts, correlating with prolonged graft survival. CONCLUSIONS/INTERPRETATION: Our results suggest that IL-12 and IL-23 promote and/or maintain Th1 cell-mediated islet graft rejection. Thus, blockade of IL-12 and IL-23 might act as therapeutic strategies for reducing rejection responses.

Two-dimensional orthogonal DCT expansion in trapezoid and triangular blocks and modified JPEG image compression.

In the conventional JPEG algorithm, an image is divided into eight by eight blocks and then the 2-D DCT is applied to encode each block. In this paper, we find that, in addition to rectangular blocks, the 2-D DCT is also orthogonal in the trapezoid and triangular blocks. Therefore, instead of eight by eight blocks, we can generalize the JPEG algorithm and divide an image into trapezoid and triangular blocks according to the shapes of objects and achieve higher compression ratio. Compared with the existing shape adaptive compression algorithms, as we do not try to match the shape of each object exactly, the number of bytes used for encoding the edges can be less and the error caused from the high frequency component at the boundary can be avoided. The simulations show that, when the bit rate is fixed, our proposed algorithm can achieve higher PSNR than the JPEG algorithm and other shape adaptive algorithms. Furthermore, in addition to the 2-D DCT, we can also use our proposed method to generate the 2-D complete and orthogonal sine basis, Hartley basis, Walsh basis, and discrete polynomial basis in a trapezoid or a triangular block.