Ferroptosis is a novel form of regulated cell death which is dependent on iron and reactive oxygen species (ROS) and associated with the accumulation of lipid peroxides. It is obviously different from other cell death types in terms of morphology, biochemistry, genetics, etc. Also, it is related to the production of iron catalyzed lipid peroxides which is triggered by non-enzymatic or enzymatic reactions. Ferroptosis has been proved to be involved in hematological diseases, cardio-cerebrovascular diseases, liver and kidney diseases. This paper will review the definition, mechanism, inducers of ferroptosis, as well as the function of ferroptosis in respiratory system. We expect to present a new concept for respiratory research and suggest potential targets for clinical prevention and treatment of respiratory diseases.
Cell Death ; Ferroptosis ; Humans ; Iron ; Reactive Oxygen Species ; Respiration Disorders

Animals ; Cell Respiration ; Electron Transport Complex III ; metabolism ; Humans ; Iron-Sulfur Proteins ; chemistry ; metabolism ; Mitochondria ; metabolism ; Peptide Fragments ; chemistry ; metabolism ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Subunits ; chemistry

Cyclophosphamide-induced cardiotoxicity is an uncommon complication especially in patients who have never undergone mediastinal irradiation or cardiotoxic chemotherapy and do not have underlying cardiac diseases. Here, we describe the case of a 19-year-old female with chronic myeloid leukemia. She was previously treated with oral tyrosine kinase inhibitors and developed cardiomyopathy after receiving infusion of 60 mg/kg intravenous cyclophosphamide for two days with a conditioning regimen for allogenic hematopoietic stem cell transplantation. Severe thickening of the left ventricle and reduced ejection fraction without triggering agents were characteristic for cyclophosphamide-induced cardiomyopathy. Her NT-pro BNP and troponin T concentrations surged to >70,000 pg/mL (0=130 pg/mL) and 2,031 pg/mL (0-14 pg/mL), respectively, during the course of the therapy and multiple organ failure seemed imminent evidenced by unresponsive decline in blood pressure. However, with close monitoring and persistent conservative management which consisted of intravenous hydration, continuous hemodialysis, and mechanical ventilation, her condition recovered.
Blood Pressure ; Cardiomyopathies* ; Cardiotoxicity ; Cyclophosphamide* ; Drug Therapy ; Female ; Heart Diseases ; Heart Failure* ; Heart Ventricles ; Heart* ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Multiple Organ Failure ; Protein-Tyrosine Kinases ; Renal Dialysis ; Respiration, Artificial ; Troponin T ; Young Adult

Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.
Adenosine Triphosphate ; Adult ; Adult Stem Cells ; Aging ; Animals ; Bone Marrow ; Cell Respiration ; Cytoplasm ; Diet ; Dietary Supplements ; Hematologic Neoplasms ; Hematopoiesis ; Hematopoietic Stem Cells* ; Humans ; Immune System ; Incidence ; Membrane Potentials ; Mice ; Mitochondria ; Niacin ; Niacinamide ; Phenotype ; Sirtuins ; Stem Cells ; Tryptophan ; Vitamins

BACKGROUND: Pneumocystis is difficult to culture or detect in laboratory environments. Its ecology including the timing and method of transmission as well as environmental sources and communicability remain unclear. METHODS: We retrospectively evaluated the pattern and treatment outcome of Pneumocystis jirovecii pneumonia (PCP) in children with acute lymphoblastic leukemia (ALL) who received chemotherapy. RESULTS: A total of 56 patients with ALL were evaluated. While on chemotherapy, all patients received PCP prophylaxis. PCP were found in a total of 6 patients, including definite PCP in 2, probable PCP in 2, and possible PCP in 2 patients. There were no significant differences in sex, age group, National Cancer Institute risk group, or pneumocystis prophylaxis type between PCP and non-PCP groups. However, there was a significant statistical difference in the times of ALL diagnosis. Regarding recent chemotherapy at the time of PCP diagnosis, there were one induction, one consolidation, and four maintenance cases. All PCP patients were treated with high-dose sulfamethoxazole (100 mg/kg/day) and trimethoprim (20 mg/kg/day) intravenously. Five patients survived, while one patient with endotracheal mechanical ventilation therapy died due to respiratory failure in spite of aggressive treatment. CONCLUSION: Pediatric PCP became extremely rare due to routine prophylaxis in clinical practice of pediatric malignancy. Nevertheless, we analyzed patients with acute lymphoblastic leukemia who had received PCP prophylaxis for 14 years, and analyzed the clustered outbreaks of PCP. It is still important to emphasize the need for prophylaxis and to increase the level of attention and isolation under environmental and personal risk factors.
Child ; Compliance ; Diagnosis ; Disease Outbreaks ; Drug Therapy ; Ecology ; Humans ; Methods ; National Cancer Institute (U.S.) ; Pneumocystis jirovecii ; Pneumocystis* ; Pneumonia ; Pneumonia, Pneumocystis* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Respiration, Artificial ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Sulfamethoxazole ; Treatment Outcome ; Trimethoprim

INTRODUCTIONThis study aimed to investigate the risk factors associated with mortality in haematopoietic stem cell transplant (HSCT) patients admitted to our paediatric intensive care unit (PICU) over an 8-year period.

MATERIALS AND METHODSA retrospective chart review was conducted of all HSCT patients requiring PICU admission at our centre (a tertiary care university hospital in Singapore) from January 2002 to December 2010. Chief outcome measures were survival at the time of PICU discharge and survival at 6 months after initial PICU admission.

RESULTSNinety-eight patients underwent HSCT during this period; 18 patients (18%) required 24 PICU admissions post-HSCT. The overall survival to PICU discharge was 62.5%. Of those who survived discharge from the PICU, 33% died within 6 months of discharge. Non-survivors to PICU discharge had a higher incidence of sepsis (89% vs 33%,= 0.013) and organ failure as compared to survivors (cardiovascular failure 100% vs 20%,= 0.0003; respiratory failure 89% vs 20%,= 0.002; and renal failure 44% vs 7%,= 0.047). Mortality rates were higher in patients requiring mechanical ventilation (70% vs 14%,= 0.010) and inotropic support (70% vs 14%,= 0.010). Mortality in all patients with renal failure requiring haemodialysis (n = 4) was 100%. Presence of 3 or more organ failures was associated with 80% mortality (= 0.003).

CONCLUSIONSepsis, multiple organ failure and the need for mechanical ventilation, inotropes and especially haemodialysis were associated with increased risk of mortality in our cohort of HSCT patients.

Adolescent ; Cardiotonic Agents ; therapeutic use ; Child ; Child, Preschool ; Female ; Heart Failure ; drug therapy ; epidemiology ; mortality ; Hematopoietic Stem Cell Transplantation ; Hospital Mortality ; Humans ; Infant ; Intensive Care Units, Pediatric ; Male ; Multiple Organ Failure ; epidemiology ; mortality ; Prognosis ; Renal Dialysis ; statistics & numerical data ; Renal Insufficiency ; epidemiology ; mortality ; therapy ; Respiration, Artificial ; statistics & numerical data ; Respiratory Insufficiency ; epidemiology ; mortality ; therapy ; Retrospective Studies ; Risk Factors ; Sepsis ; epidemiology ; mortality ; Singapore ; epidemiology

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth.
Biocompatible Materials ; Durapatite ; Fungi ; Humans ; Mastication ; Periodontium ; Printing, Three-Dimensional* ; Regeneration* ; Respiration ; Stem Cell Research ; Tooth ; Transplants ; Wounds and Injuries

Craniomaxillofacial injuries produce complex wound environments involving various tissue types and treatment strategies. In a clinical setting, care is taken to properly irrigate and stabilize the injury, while grafts are molded in an attempt to maintain physiological functionality and cosmesis. This often requires multiple surgeries and grafts leading to added discomfort, pain and financial burden. Many of these injuries can lead to disfigurement and resultant loss of system function including mastication, respiration, and articulation, and these can lead to acute and long-term psychological impact on the patient. A main causality of these issues is the lack of an ability to spatially control pre-injury morphology while maintaining shape and function. With the advent of additive manufacturing (three-dimensional printing) and its use in conjunction with biomaterial regenerative strategies and stem cell research, there is an increased potential capacity to alleviate such limitations. This review focuses on the current capabilities of additive manufacturing platforms, completed research and potential for future uses in the treatment of craniomaxillofacial injuries, with an in-depth discussion of regeneration of the periodontal complex and teeth.
Biocompatible Materials ; Durapatite ; Fungi ; Humans ; Mastication ; Periodontium ; Printing, Three-Dimensional* ; Regeneration* ; Respiration ; Stem Cell Research ; Tooth ; Transplants ; Wounds and Injuries

PURPOSE: The aim of this study was to investigate the prognostic factors for Pneumocystis jirovecii pneumonia (PCP) and to evaluate the influence of PCP prophylaxis in pediatric patients. METHODS: From January 2002 to April 2015, patients aged <18 years with a diagnosis of confirmed PCP at our institute were reviewed retrospectively. Clinical characteristics and outcomes were compared according to the groups with or without PCP prophylaxis. Risk factors associated with PCP-related death were analyzed by logistic regression analysis. RESULTS: During study period, a total of 24 patients were diagnosed with PCP by immunofluorescence assay and/or PCR. The median age of the patients was 5 years (range, 3 months-18 years) and 23 (96%) had immunocompromised conditions including hematologic disorders with or without hematopoietic stem cell transplantation (n=15), solid organ transplantation (n=4), and primary immune deficiency (n=4). Most common presenting symptoms were tachypnea and cough (92%, each). At the time of diagnosis, 79% (19/24) and 25% (6/24) suffered from respiratory failure and multi-organ dysfunction syndrome (MODS), respectively. Mechanical ventilation was required in 8 (33%) patients and 5 (21%) patients died of PCP. Multivariate analysis showed that MODS at initial presentation was an indicator of poor prognosis (OR, 17.1 [95% CI 1.13-257.67]; P=0.04). Compared to the patients without PCP prophylaxis, the frequency of MODS at diagnosis, need for mechanical ventilation and length of hospital days were significantly less common in the children who received PCP prophylaxis. CONCLUSIONS: MODS at presentation was a significant predictor for poor outcome and PCP prophylaxis could alleviate the clinical courses of pediatric PCP. Prospective study will be mandatory to determine the risk factors for development and deterioration of PCP in children.
Child* ; Cough ; Diagnosis ; Fluorescent Antibody Technique ; Hematopoietic Stem Cell Transplantation ; Humans ; Logistic Models ; Multiple Organ Failure ; Multivariate Analysis ; Organ Transplantation ; Pneumocystis jirovecii* ; Pneumocystis* ; Pneumonia* ; Polymerase Chain Reaction ; Prognosis ; Prospective Studies ; Respiration, Artificial ; Respiratory Insufficiency ; Retrospective Studies ; Risk Factors ; Tachypnea ; Transplants

Bronchiolitis obliterans (BO), which is associated with graft-versus-host disease after allogenic hematopoietic stem cell transplantation, is a major obstacle to survival after bone marrow transplantation due to its gradual progress, eventually leading to respiratory failure. Pumpless extracorporeal interventional lung assist (iLA) is effective in treatment of reversible hypercapnic respiratory failure. In this paper, we present a 23-year-old female patient who underwent allogeneic peripheral blood stem cell transplantation (PBSCT) for acute lymphocytic leukemia. After 6 months, she complained of shortness of breath and was diagnosed with BO. Five months later, she developed an upper respiratory tract infection that worsened her BO and caused life-threatening hypercapnia. Since mechanical ventilation failed to eliminate CO2 effectively, iLA was applied as rescue therapy. Her hypercapnia and respiratory acidosis showed significant improvement within a few hours, and she was successfully weaned off iLA after 12 days. This is the first case report of iLA application for temporarily aggravated hypercapnia of PBSCT-associated BO followed by successful weaning. This rescue therapy should be considered in ventilator-refractory reversible hypercapnia in BO patients.
Acidosis, Respiratory ; Bone Marrow Transplantation ; Bronchiolitis Obliterans* ; Bronchiolitis* ; Dyspnea ; Female ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Hypercapnia ; Lung* ; Peripheral Blood Stem Cell Transplantation* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Respiration, Artificial ; Respiratory Insufficiency ; Respiratory Tract Infections ; Weaning ; Young Adult