Pneumocystis jirovecii-associated immune reconstitution inflammatory syndrome-like phenomenon in a child with leukaemia: a case report and literature review.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) refers to the phenomenon of intense immune responses against pathogens in patients with AIDS undergoing antiretroviral therapy to reconstitute immune function, resulting in functional impairment of multiple organs. Non-AIDS immunosuppressed hosts may also develop similar manifestations to IRIS during immune recovery. CASE PRESENTATION: An 8-year-old girl presented with acute lymphoblastic leukaemia was admitted for scheduled chemotherapy treatment. During chemotherapy, she experienced pancytopenia and Pneumocystis jirovecii pneumonia, which was diagnosed based on the abnormal shadows observed on chest computed tomography, the elevation of serum ß-D-glucan, and the positive mNGS results of Pneumocystis jirovecii in both sputum and blood. After treatment with Granulocyte Colony-Stimulating Factor, sulfamethoxazole, and caspofungin, aggravation of lung lesions was discovered and severe interstitial lung disease developed in a short period along with a rapidly increasing leukocyte count. Intravenous methylprednisolone pulse therapy was given, but lung function did not improve, and she finally died after the withdrawal of medical care. CONCLUSIONS: For patients with acute lymphocytic leukaemia infected with Pneumocystis jirovecii, the rapid aggravation of pulmonary lesions in the process of blood recovery and immune reconstitution should raise vigilance against the possibility of IRIS-like reactions. The use of granulocyte stimulating factors may aggravate the inflammatory response in the lungs. The timing, dosage, and duration of treatment of glucocorticoids and the impact of high-dose methylprednisolone pulse therapy on the prognosis of patients should be explored in further research.

Bone marrow mesenchymal stem cells attenuate lung inflammation of hyperoxic newborn rats.

BPD is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of BMSCs in neonatal lung disease. BMSCs were isolated, identified, and transfected by lentiviral vector carrying GFP gene in vitro. Neonatal rats were injected intravenously with either BMSCs or PBS after they had been already exposed to high oxygen for seven days, and assessed on post-injection day 3, day 7, and day 14 for weight gaining, lung histology, radical alveolar counts, and lung cytokine level. BMSCs were positive for CD29, CD44, and CD90 whereas negative for CD34, CD45, CD11b and with differentiation potential into osteoblasts, adipocytes, and chondrocytes. BMSCs expressed GFP after transfected by lentivirus. After injection, BMSCs exert their therapeutic benefit of improving weight gaining, preventing alveolar growth arrest, and suppressing lung inflammation of neonatal rats. Intravenous delivery of BMSCs in newborn rats conferred protection from hyperoxia-induced lung injury, and one of the effects of BMSCs treatment is suppressing lung inflammation.

[Clinical Analysis of Pediatric Acute Leukemia Complicated with Septic Shock].

OBJECTIVE: To analyze the clinical characteristics of predictors in pediatric acute leukemia complicated with septic shock and explore the prognostic factors. METHODS: The clinical characteristics of 70 children with acute leukemia and complicated with septic shock hospitalized in Sun Yat-sen Memorial Hospital from March 2012 to March 2021 were retrospectively analyzed. The clinical characteristics of patients in survival group and death group were analyzed and compared. Multiple logistic regression was used to test for predictors of death. RESULTS: Among the 70 children, 41 were males and 29 were females, with a median age of 7.0 (1.0-15.0) years old. 81.4% were hospital acquired infections. The pathogens were mostly Gram-negative bacteria (50/66, 75.8%) and the clinical manifestations were cold shock. Mortality rate was 34.3% (24/70). The length of hospitalization, duration of fever and antibiotic exposure longevity before the onset of septic shock were significantly different between survival group and death group. At septic shock onset, compared with the survival group, patients in the death group were younger, had lower platelet counts and higher levels of C-reactive protein and procalcitonin, and were more likely to have acute heart failure and more mechanical ventilation (all p<0.05). The results of multivariable analysis showed that mortality was independently associated with pediatric sequential organ failure assessment score (pSOFA) (odds ratio: 1.616, 95% CI: 1.160-2.251, p=0.005) and acute heart failure (odds ratio: 18.308, 95% CI: 1.939-172.911, p=0.011). In addition, the ROC curve analysis showed that pSOFA score had AUC of 0.8551 (95% CI: 0.7607-0.9495, p<0.001) predicting PICU mortality and its best predictive value was >9.5 (sensitivity 75.0%, specificity 87.0%). CONCLUSION: Pediatric acute leukemia complicated with septic shock is characterized as rapid deterioration and high mortality. A pSOFA score greater than 9.5 and acute heart failure are associated with poor outcomes.

[Clinical Characteristic, Diagnosis and Treatment of Acute Lymphoblastic Leukemia Combined with Pneumocystis Carinii Pneumonia in Children].

OBJECTIVE: To investigate the clinical characteristics and treatment of pneumocystis carinii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL), in order to improve the early diagnosis and effective treatment. METHODS: Clinical data of five children with ALL developing PCP in the post-chemotherapy granulocyte deficiency phase were analyzed retrospectively. The clinical manifestations, laboratory tests, imaging findings, treatment methods and effect were summarized. RESULTS: The male-to-female ratio of the five children was 1∶4, and the median age was 5.5 (2.9-8) years old. All patients developed PCP during granulocyte deficiency phase after induction remission chemotherapy. The clinical manifestations were generally non-specific, including high fever, tachypnea, dyspnea, non-severe cough, and rare rales in two lungs (wet rales in two patients). Laboratory tests showed elevated C-reactive protein (CRP), serum procalcitonin (PCT), (1,3)-ß-D-glucan (BDG), lactate dehydrogenase (LDH) and inflammatory factors including IL-2R, IL-6 and IL-8. Chest CT showed diffuse bilateral infiltrates with patchy hyperdense shadows. Pneumocystis carinii(PC) was detected in bronchoalveolar lavage fluid (BALF) or induced sputum by high-throughput sequencing in all patients. When PCP was suspected, chemotherapy was discontinued immediately, treatment of trimethoprim-sulfame thoxazole (TMP-SMX) combined with caspofungin against PC was started, and adjunctive methylprednisolone was used. Meanwhile, granulocyte-stimulating factor and gammaglobulin were given as the supportive treatment. All patients were transferred to PICU receiving mechanical ventilation due to respiratory distress during treatment. Four children were cured and one died. CONCLUSION: PCP should be highly suspected in ALL children with high fever, dyspnea, increased LDH and BDG, and diffuse patchy hyperdense shadow or solid changes in lung CT. The pathogen detection of respiratory specimens should be improved as soon as possible. TMP/SMZ is the first-line drug against PCP, and the combination of Caspofungin and TMP/SMZ treatment for NH-PCP may have a better efficacy. Patients with moderate and severe NH-PCP may benefit from glucocorticoid.

NFATc1 is a Necessary Transcription Factor in Polarisation of T Helper Type 2 Lymphocytes Induced by Thymic Stromal Lymphopoietin.

Thymic stromal lymphopoietin (TSLP) activates lung dendritic cells (DCs) to promote a T helper type 2 lymphocyte (Th2) response in animal models. However, the mechanism behind this process remains unclear. In this study, we investigate the role of a nuclear factor for activated T-cells 1 (NFATc1) in the TSLP-induced polarisation towards a Th2 response. A cluster of differentiated (CD)14+ peripheral blood mononuclear cells (PBMCs) and naïve T cells were isolated from blood collected from healthy human volunteers, and TSLP was used to induce DC maturation. The effects of TSLP-DCs and treatments with FK506, an NFATc1 inhibitor, on naïve T cell differentiation were monitored by measuring the interleukin (IL)-4, IL-13, and interferon-γ (IFN-γ) expression levels. In addition, the mRNA levels of T-box expression in T cells (T-bet), GATA binding protein 3 (GATA-3), TSLP, and NFATc1 were measured for the same purpose. IL-4, IL-13, and mRNA levels of GATA-3 and NFATc1 significantly increased with TSLP-DC induction (P<0.01), indicating polarization towards the Th2 response. These changes were reversed by treatment with FK506 (P<0.01). Our findings suggest that NFATc1 plays a key role in the TSLP-induced differentiation of T cells to Th2, and NFATc1 is a potential therapeutic target for treating allergic diseases.

Mesenchymal stem cells protect against neonatal rat hyperoxic lung injury.

OBJECTIVES: Bronchopulmonary dysplasia (BPD) is a significant global health problem and currently lacks effective therapy. We established a neonatal rat model of BPD to investigate therapeutic potential of bone marrow-derived mesenchymal stem cells (BMSCs) in neonatal hyperoxic lung injury. METHODS: BMSCs were isolated, identified, and transfected by lentiviral vector carrying green fluorescent protein gene in vitro. Neonatal Sprague-Dawley rats were injected intravenously with either BMSCs or phosphate-buffered saline following 95% oxygen exposure, and assessed for the survival rate and alveolar injury during recovery. RESULTS: Treatment with BMSCs after oxygen exposure for 7 days improved survival of neonatal rat during recovery. BMSCs protected against neonatal rat hyperoxic lung injury during recovery as demonstrated by enhanced expression of AQP5 and SP-C, likely due to the suppression of alveolar cell apoptosis and lung inflammation responses to oxygen with up-regulation of the expression of BCL-2 gene and down-regulation of the expression of BAX gene and stimulation of vascular endothelial growth factor and so on. CONCLUSIONS: BMSCs protect against O2-mediated injury partially through stimulation of potent mediators that participate in tissue repair.