sirolimus and Respiratory-Insufficiency

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; Brain Neoplasms; Breakfast; Breast Milk Expression; Breast Neoplasms; Bronchi; Bronchoalveolar Lavage Fluid; Buffaloes; Cadherins; Calcification, Physiologic; Calcium Compounds; Calcium, Dietary; Cannula; Caprolactam; Carbon; Carbon Dioxide; Carboplatin; Carcinogenesis; Carcinoma, Ductal; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Carcinoma, Pancreatic Ductal; Carcinoma, Renal Cell; Cardiovascular Diseases; Carps; Carrageenan; Case-Control Studies; Catalysis; Catalytic Domain; Cattle; CD8-Positive T-Lymphocytes; Cell Adhesion; Cell Cycle Proteins; Cell Death; Cell Differentiation; Cell Line; Cell Line, Tumor; Cell Movement; Cell Nucleus; Cell Phone Use; Cell Proliferation; Cell Survival; Cell Transformation, Neoplastic; Cell Transformation, Viral; Cells, Cultured; Cellulose; Chemical Phenomena; Chemoradiotherapy; Child; Child Development; Child, Preschool; China; Chitosan; Chlorocebus aethiops; Cholecalciferol; Chromatography, Liquid; Circadian Clocks; Circadian Rhythm; Circular Dichroism; Cisplatin; Citric Acid; Clinical Competence; Clinical Laboratory Techniques; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clostridioides difficile; Clostridium Infections; Coculture Techniques; Cohort Studies; Cold Temperature; Colitis; Collagen Type I; Collagen Type I, alpha 1 Chain; Collagen Type XI; Color; Connective Tissue Diseases; Copper; Coronary Angiography; Coronavirus 3C Proteases; Coronavirus Infections; Cost of Illness; Counselors; COVID-19; COVID-19 Testing; Creatine Kinase; Creatinine; Cross-Over Studies; Cross-Sectional Studies; Cryoelectron Microscopy; Cryosurgery; Crystallography, X-Ray; Cues; Cultural Competency; Cultural Diversity; Curriculum; Cyclic AMP Response Element-Binding Protein; Cyclin-Dependent Kinase Inhibitor p21; Cycloparaffins; Cysteine Endopeptidases; Cytokines; Cytoplasm; Cytoprotection; Databases, Factual; Denitrification; Deoxycytidine; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Experimental; 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Risk Factors; Ritonavir; Rivers; RNA Interference; RNA-Seq; RNA, Messenger; RNA, Ribosomal, 16S; RNA, Small Interfering; Rosuvastatin Calcium; Rural Population; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Salivary Ducts; Salivary Gland Neoplasms; San Francisco; SARS-CoV-2; Satiation; Satiety Response; Schools; Schools, Pharmacy; Seasons; Seawater; Selection, Genetic; Sequence Analysis, DNA; Serine-Threonine Kinase 3; Sewage; Sheep; Sheep, Domestic; Shock, Hemorrhagic; Signal Transduction; Silver; Silymarin; Single Photon Emission Computed Tomography Computed Tomography; Sirolimus; Sirtuin 1; Skin; Skin Neoplasms; Skin Physiological Phenomena; Sleep Initiation and Maintenance Disorders; Social Class; Social Participation; Social Support; Soil; Soil Microbiology; Solutions; Somatomedins; Soot; Specimen Handling; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis; Spinal Fractures; Spirometry; Staphylococcus aureus; STAT1 Transcription Factor; STAT3 Transcription Factor; Streptomyces coelicolor; Stress, Psychological; Stroke; Stroke Volume; Structure-Activity Relationship; Students, Medical; Students, Pharmacy; Substance Abuse Treatment Centers; Sulfur Dioxide; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Analysis; Survival Rate; Survivin; Sweden; Swine; Swine, Miniature; Sympathetic Nervous System; T-Lymphocytes, Regulatory; Talaromyces; Tandem Mass Spectrometry; tau Proteins; Telemedicine; Telomerase; Telomere; Telomere Homeostasis; Temperature; Terminally Ill; Th1 Cells; Thiamethoxam; Thiazoles; Thiophenes; Thioredoxin Reductase 1; Thrombosis; Thulium; Thyroid Cancer, Papillary; Thyroid Carcinoma, Anaplastic; Thyroid Neoplasms; Time Factors; Titanium; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; TOR Serine-Threonine Kinases; Transcription Factor AP-1; Transcription Factors; Transcription, Genetic; Transcriptional Activation; Transcriptome; Transforming Growth Factor beta1; Transistors, Electronic; Translational Research, Biomedical; Transplantation Tolerance; Transplantation, Homologous; Transportation; Treatment Outcome; Tretinoin; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary; Tubulin Modulators; Tumor Microenvironment; Tumor Necrosis Factor Inhibitors; Tumor Necrosis Factor-alpha; Twins; Ultrasonic Therapy; Ultrasonography; Ultraviolet Rays; United States; Up-Regulation; Uranium; Urethra; Urinary Bladder; Urodynamics; Uromodulin; Uveitis; Vasoconstrictor Agents; Ventricular Function, Left; Vero Cells; Vesicular Transport Proteins; Viral Nonstructural Proteins; Visual Acuity; Vital Capacity; Vitamin D; Vitamin D Deficiency; Vitamin K 2; Vitamins; Volatilization; Voriconazole; Waiting Lists; Waste Disposal, Fluid; Wastewater; Water Pollutants, Chemical; Whole Genome Sequencing; Wine; Wnt Signaling Pathway; Wound Healing; Wounds and Injuries; WW Domains; X-linked Nuclear Protein; X-Ray Diffraction; Xanthines; Xenograft Model Antitumor Assays; YAP-Signaling Proteins; Yogurt; Young Adult; Zebrafish; Zebrafish Proteins; Ziziphus

Sirolimus-associated pulmonary disease should be considered in the differential diagnosis of acute respiratory distress syndrome in transplant recipients receiving this drug. It represents a rare, potentially lethal, and yet reversible adverse effect. We report the case an infant who presented with acute respiratory distress 57 days after heart transplantation 3 days after starting sirolimus. The acute presentation and prompt resolution after discontinuation of this drug suggest a direct toxic effect to the lungs. To our knowledge, this is the first published pediatric description of this syndrome after heart transplantation.

Topics: Acute Disease; Chylothorax; Female; Heart Transplantation; Humans; Immunosuppressive Agents; Infant; Lung Diseases, Interstitial; Radiography, Thoracic; Respiratory Insufficiency; Sirolimus

Middle East Respiratory Syndrome (MERS) is a novel respiratory illness firstly reported in Saudi Arabia in 2012. It is caused by a new corona virus, called MERS corona virus (MERS-CoV). Most people who have MERS-CoV infection developed severe acute respiratory illness.. This work is done to determine the clinical characteristics and the outcome of intensive care unit (ICU) admitted patients with confirmed MERS-CoV infection.. This study included 32 laboratory confirmed MERS corona virus infected patients who were admitted into ICU. It included 20 (62.50%) males and 12 (37.50%) females. The mean age was 43.99 ± 13.03 years. Diagnosis was done by real-time reverse transcription polymerase chain reaction (rRT-PCR) test for corona virus on throat swab, sputum, tracheal aspirate, or bronchoalveolar lavage specimens. Clinical characteristics, co-morbidities and outcome were reported for all subjects.. Most MERS corona patients present with fever, cough, dyspnea, sore throat, runny nose and sputum. The presence of abdominal symptoms may indicate bad prognosis. Prolonged duration of symptoms before patients' hospitalization, prolonged duration of mechanical ventilation and hospital stay, bilateral radiological pulmonary infiltrates, and hypoxemic respiratory failure were found to be strong predictors of mortality in such patients. Also, old age, current smoking, smoking severity, presence of associated co-morbidities like obesity, diabetes mellitus, chronic heart diseases, COPD, malignancy, renal failure, renal transplantation and liver cirrhosis are associated with a poor outcome of ICU admitted MERS corona virus infected patients.. Plasma HO-1, ferritin, p21, and NQO1 were all elevated at baseline in CKD participants. Plasma HO-1 and urine NQO1 levels each inversely correlated with eGFR (. SnPP can be safely administered and, after its injection, the resulting changes in plasma HO-1, NQO1, ferritin, and p21 concentrations can provide information as to antioxidant gene responsiveness/reserves in subjects with and without kidney disease.. A Study with RBT-1, in Healthy Volunteers and Subjects with Stage 3-4 Chronic Kidney Disease, NCT0363002 and NCT03893799.. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).. 3 组患者手术时间、术中显性失血量及术后 1 周血红蛋白下降量比较差异均无统计学意义（. 对于肥胖和超重的膝关节单间室骨关节炎患者，采用 UKA 术后可获满意短中期疗效，远期疗效尚需进一步随访观察。.. Decreased muscle strength was identified at both time points in patients with hEDS/HSD. The evolution of most muscle strength parameters over time did not significantly differ between groups. Future studies should focus on the effectiveness of different types of muscle training strategies in hEDS/HSD patients.. These findings support previous adverse findings of e-cigarette exposure on neurodevelopment in a mouse model and provide substantial evidence of persistent adverse behavioral and neuroimmunological consequences to adult offspring following maternal e-cigarette exposure during pregnancy. https://doi.org/10.1289/EHP6067.. This RCT directly compares a neoadjuvant chemotherapy regimen with a standard CROSS regimen in terms of overall survival for patients with locally advanced ESCC. The results of this RCT will provide an answer for the controversy regarding the survival benefits between the two treatment strategies.. NCT04138212, date of registration: October 24, 2019.. Results of current investigation indicated that milk type and post fermentation cooling patterns had a pronounced effect on antioxidant characteristics, fatty acid profile, lipid oxidation and textural characteristics of yoghurt. Buffalo milk based yoghurt had more fat, protein, higher antioxidant capacity and vitamin content. Antioxidant and sensory characteristics of T. If milk is exposed to excessive amounts of light, Vitamins B. The two concentration of ZnO nanoparticles in the ambient air produced two different outcomes. The lower concentration resulted in significant increases in Zn content of the liver while the higher concentration significantly increased Zn in the lungs (p < 0.05). Additionally, at the lower concentration, Zn content was found to be lower in brain tissue (p < 0.05). Using TEM/EDX we detected ZnO nanoparticles inside the cells in the lungs, kidney and liver. Inhaling ZnO NP at the higher concentration increased the levels of mRNA of the following genes in the lungs: Mt2 (2.56 fold), Slc30a1 (1.52 fold) and Slc30a5 (2.34 fold). At the lower ZnO nanoparticle concentration, only Slc30a7 mRNA levels in the lungs were up (1.74 fold). Thus the two air concentrations of ZnO nanoparticles produced distinct effects on the expression of the Zn-homeostasis related genes.. Until adverse health effects of ZnO nanoparticles deposited in organs such as lungs are further investigated and/or ruled out, the exposure to ZnO nanoparticles in aerosols should be avoided or minimised.

Topics: A549 Cells; Acetylmuramyl-Alanyl-Isoglutamine; Acinetobacter baumannii; Acute Lung Injury; Adaptor Proteins, Signal Transducing; Adenine; Adenocarcinoma; Adipogenesis; Administration, Cutaneous; Administration, Ophthalmic; Adolescent; Adsorption; Adult; Aeromonas hydrophila; Aerosols; Aged; Aged, 80 and over; Aging; Agriculture; Air Pollutants; Air Pollution; Airway Remodeling; Alanine Transaminase; Albuminuria; Aldehyde Dehydrogenase 1 Family; Algorithms; AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; Alzheimer Disease; Amino Acid Sequence; Ammonia; Ammonium Compounds; Anaerobiosis; Anesthetics, Dissociative; Anesthetics, Inhalation; Animals; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Infective Agents; Anti-Inflammatory Agents; Antibiotics, Antineoplastic; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Monoclonal, Humanized; Antifungal Agents; Antigens, Bacterial; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Antioxidants; Antitubercular Agents; Antiviral Agents; Apolipoproteins E; Apoptosis; Arabidopsis; Arabidopsis Proteins; Arsenic; Arthritis, Rheumatoid; Asthma; Atherosclerosis; ATP-Dependent Proteases; Attitude of Health Personnel; Australia; Austria; Autophagy; Axitinib; Bacteria; Bacterial Outer Membrane Proteins; Bacterial Proteins; Bacterial Toxins; Bacterial Typing Techniques; Bariatric Surgery; Base Composition; Bayes Theorem; Benzoxazoles; Benzylamines; beta Catenin; Betacoronavirus; Betula; Binding Sites; Biological Availability; Biological Oxygen Demand Analysis; Biomarkers; Biomarkers, Tumor; Biopsy; Bioreactors; Biosensing Techniques; Birth Weight; Blindness; Blood Chemical Analysis; Blood Gas Analysis; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Blood-Brain Barrier; Blotting, Western; Body Mass Index; Body Weight; Bone and Bones; Bone Density; Bone Resorption; Borates; Brain; Brain Infarction; Brain Injuries, Traumatic; 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Severe H1N1 pneumonia with acute respiratory failure results in infiltration of lungs due to the presence of hyperactive immune cells. Rapamycin and corticosteroids inhibit this immune response by blocking the activation of T and B cells.. Open-label prospective randomized controlled trial.. A tertiary medical center, Chang Gung Memorial Hospital, located in Taiwan.. Between 2009 and 2011, of 4,012 H1N1-infected patients, 38 patients with severe H1N1 pneumonia and acute respiratory failure were enrolled.. Thirty-eight patients with confirmed H1N1 pneumonia and on mechanical ventilatory support were randomized to receive adjuvant treatment of corticosteroids with an mTOR inhibitor, either with sirolimus (Rapamune 2 mg/d) (sirolimus group, n = 19) for 14 days or without sirolimus (nonsirolimus group, n = 19). The clinical values measured included PaO2/FIO2, Sequential Organ Failure Assessment score, duration of ventilatory support, and mortality. The baseline demography was similar between the two groups. After treatment, the PaO2/FIO2 values on day 3 (167.5 [95% CI, 86.7-209.2 mm Hg], n = 19 vs 106.8 [95% CI, 73.0-140.7 mm Hg], n = 19; p = 0.025] and day 7 (241.6 [95% CI, 185.2-297.9 mm Hg], n = 19 vs 147.0 [95% CI, 100.7-193.7 mm Hg], n = 17; p = 0.008) in the sirolimus group were significantly better over the nonsirolimus group. Similarly, the Sequential Organ Failure Assessment score on day 3 (4.3 [95% CI, 3.1-5.5]; p = 0.029) and day 7 (5.9 [95% CI, 4.8-6.9], n = 19 and 6.2 [95% CI, 4.7-7.8], n = 17, respectively) significantly improved in the sirolimus group. The liberation from a mechanical ventilator at 3 months was also better in the sirolimus combined with corticosteroids treatment. Similarly, the duration of ventilator use was significantly shorter in the sirolimus group (median, 7 vs 15 d; p = 0.03 by log-rank test). In the sirolimus combined with corticosteroids treatment group, a rapid clearance of virus also occurred after 7 days of treatment.. In patients with severe H1N1 pneumonia, early adjuvant treatment with corticosteroids and an mTOR inhibitor was associated with improvement in outcomes, such as hypoxia, multiple organ dysfunction, virus clearance, and shortened liberation of ventilator and ventilator days.

Topics: Acute Disease; Chemotherapy, Adjuvant; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Pneumonia, Viral; Prednisolone; Prospective Studies; Respiratory Insufficiency; Severity of Illness Index; Sirolimus; Treatment Outcome

This is a rare case of sporadic lymphangioleiomyomatosis (S-LAM) manifesting as refractory chylothorax and chyloperitoneum. A middle-aged woman with unremarkable medical history presented with respiratory failure, abdominal distension and anasarca. She was found to have high-output chylous effusion that required chest tube drainage, as well as chylous ascites. Notably initial chest and abdominal CT did not reveal characteristic pulmonary cysts or the presence of angiomyolipomas suggestive of LAM. An extensive oncologic and infectious work-up was undertaken with negative findings. The chylous effusion was persistent and refractory to thoracic duct embolization, total parenteral nutrition with octreotide, and talc pleurodesis. Diagnosis of S-LAM was confirmed after repeat chest CT showed subtle pulmonary cystic changes, and serum vascular endothelial growth factor-D level was found to be elevated at 834 pg/mL. Patient was started on sirolimus therapy, but lost to follow-up after hospital discharge. Patient died approximately 1 year later.

Topics: Antibiotics, Antineoplastic; Chest Tubes; Chylothorax; Drainage; Edema; Fatal Outcome; Female; Humans; Lymphangioleiomyomatosis; Middle Aged; Parenteral Nutrition, Total; Respiratory Insufficiency; Sirolimus; Thoracic Duct

Sirolimus is an effective therapy for children with kaposiform hemangioendothelioma with or without the Kasabach-Merritt phenomenon. We report the case of a child with kaposiform hemangioendothelioma and the Kasabach-Merritt phenomenon who developed

Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antineoplastic Agents, Phytogenic; Drug Therapy, Combination; Hemangioendothelioma; Humans; Immunosuppressive Agents; Infant; Kasabach-Merritt Syndrome; Male; Pneumocystis carinii; Pneumonia, Pneumocystis; Prednisolone; Propranolol; Respiratory Insufficiency; Sarcoma, Kaposi; Sirolimus; Vincristine

A 25-year-old woman, a never smoker with a history of heart-lung transplantation for World Health Organization group 1 pulmonary arterial hypertension performed 20 months prior to presentation, was evaluated for shortness of breath. Following transplantation, she was initiated on standard therapy of prednisone, tacrolimus, and azathioprine, along with routine antimicrobial prophylaxis. Her posttransplant course was complicated by persistent acute cellular rejection, as determined from a transbronchial biopsy specimen, without evidence of rejection in an endomyocardial biopsy specimen. The immunosuppressive medications were supplemented with pulse-dosed steroids, and the patient was transitioned from azathioprine to mycophenolate mofetil. Sirolimus was added 9 months prior to presentation. Three months prior to presentation, she was admitted for increasing oxygen requirements, shortness of breath, and bilateral infiltrates on the CT scans of the chest.

Topics: Adult; Female; Heart-Lung Transplantation; Humans; Immunosuppressive Agents; Postoperative Complications; Pulmonary Alveolar Proteinosis; Respiratory Insufficiency; Sirolimus

Sirolimus (SR) is a lipophilic macrocytic lactone with immunosuppressive properties (mTOR inhibitor) commonly used in solid organ transplantation and recently introduced in the prophylaxis and treatment of graft-versus-host disease. Its numerous side effects include: hyperlipidemia, arthralgias, noncardiac peripheral edema, thrombotic microangiopathy and interstitial pneumonitis. SR-associated pneumonitis is a rare but potentially serious complication due to its increasing utilization in transplant patients.. We report the case of a patient undergoing hematopoietic stem cell transplantation with severe respiratory distress and SR therapy.. Microbiological tests were all negative and other complications related to transplantation were discarded. The chest computed tomography of high-resolution showed pneumonitis. The SR therapy was interrupted and treatment was started with steroids with resolution of symptoms.. SR associated pneumonitis is a potentially fatal side effect. In patients treated with SR and respiratory failure, we must suspect this complication because early recognition along with drug discontinuation and steroid treatment is essential to reverse this complication.

Topics: Adrenal Cortex Hormones; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Leukemia, Myeloid, Acute; Male; Middle Aged; Oxygen Inhalation Therapy; Pneumonia; Respiratory Insufficiency; Sirolimus; Tomography, X-Ray Computed

Parainfluenza infection is a cause of significant morbidity and mortality in allogeneic hematopoietic stem cell transplant (HSCT) patients. DAS181 is a novel antiviral agent with activity against influenza and parainfluenza. We report the first 2 cases, to our knowledge, of successful DAS181 use in ventilated HSCT patients with severe parainfluenza lung disease.

Topics: Aged; Antiviral Agents; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunocompromised Host; Immunosuppressive Agents; Male; Middle Aged; Paramyxoviridae Infections; Pneumonia, Viral; Prednisone; Recombinant Fusion Proteins; Respiration, Artificial; Respiratory Insufficiency; Sirolimus; Treatment Outcome

Topics: Female; Glucocorticoids; Humans; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Pneumonia, Viral; Prednisolone; Respiratory Insufficiency; Sirolimus

Topics: Female; Glucocorticoids; Humans; Immunosuppressive Agents; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Pneumonia, Viral; Prednisolone; Respiratory Insufficiency; Sirolimus

A 76-year-old female with advanced renal cell carcinoma had been treated with everolimus for 3 months. She visited our hospital because of a cough and fever lasting a few days. Chest X-rays showed bilateral infiltrative shadows, and a chest computed tomography scan showed homogeneous ground-glass opacities with mosaic patterns, especially in the apical region. The laboratory results revealed a decreased white blood cell count with lymphocytopenia and high levels of lactate dehydrogenase, C-reactive protein and KL-6. Pneumonitis was suspected and, therefore, everolimus therapy was interrupted. At that time, the pneumonitis was thought to be drug-induced interstitial lung disease. However, it was not possible to rule out pneumocystis pneumonia, because the patient was immunocompromised and the computed tomography findings suggested the possibility of pneumocystis pneumonia. The pneumonitis progressed rapidly and the patient developed respiratory failure, so we performed bronchoalveolar lavage to make a definitive diagnosis, and simultaneously started treatment with prednisolone and trimethoprim-sulfamethoxazole to cover both interstitial lung disease and pneumocystis pneumonia. A polymerase chain reaction assay of the bronchoalveolar lavage fluid was positive for Pneumocystis carinii DNA, and the serum level of β-d-glucan was significantly elevated. Thus, the patient was diagnosed with pneumocystis pneumonia, which was cured by the treatment. Interstitial lung disease is a major adverse drug reaction associated with everolimus, and interstitial lung disease is the first condition suspected when a patient presents with pneumonitis during everolimus therapy. Pneumocystis pneumonia associated with everolimus therapy is rare, but our experience suggests that pneumocystis pneumonia should be considered as a differential diagnosis when pneumonitis is encountered in patients receiving everolimus therapy.

Topics: Aged; Anti-Infective Agents; Antineoplastic Agents; Bronchoalveolar Lavage; Carcinoma, Renal Cell; Diagnosis, Differential; Drug Administration Schedule; Everolimus; Female; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Neoplasms; Lung Diseases, Interstitial; Pneumocystis carinii; Pneumonia, Pneumocystis; Polymerase Chain Reaction; Respiratory Insufficiency; Sirolimus; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Chyle; Female; Humans; Immunosuppressive Agents; Lymphangioleiomyomatosis; Middle Aged; Respiratory Insufficiency; Sirolimus

We herein report two cases of everolimus-associated interstitial pneumonia in patients with renal cell carcinoma. A 68-year-old Japanese man (case 1) was admitted to our hospital because of progressive dyspnea, left infiltration and consolidation on chest radiographs. He had started receiving everolimus (10 mg daily) three months before the admission for the treatment of recurrent renal cell carcinoma. Bronchoalveolar lavage fluid taken from his left B(4) showed a marked increase of lymphocytes (42.9%). An organizing pneumonia pattern of everolimus-associated interstitial pneumonia was strongly suspected radiologically, and treatment with high-dose corticosteroids, discontinuation of everolimus and oxygen support was started. The treatment was successful, and the patient recovered with only minor pulmonary fibrotic changes in the left lower lobe. A 57-year-old Japanese man (case 2) was referred to our department for the evaluation of interstitial pneumonia. He had started to receive everolimus (10 mg daily) four months previously. Chest CT demonstrated interstitial pneumonia predominantly in bilateral lower lobes, with small pulmonary metastatic nodules. His pulmonary complications were spontaneously resolved eight days after the discontinuation of everolimus. To the best of our knowledge, Case 1 is the first reported case of successfully treated organizing pneumonia pattern of interstitial pneumonia with acute respiratory failure induced by everolimus in Japan.

Topics: Adrenal Cortex Hormones; Aged; Carcinoma, Renal Cell; Everolimus; Humans; Immunosuppressive Agents; Kidney Neoplasms; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Radiography; Respiratory Insufficiency; Sirolimus

Ingestion of large quantities of paraquat leads to irreversible, often fatal pulmonary fibrosis. Case presentation. A 50-year-old man (body weight of 78.6 kg) ingested 500 mL Gramoxone containing 200 g/L of paraquat in a suicide attempt. The patient did not seek medical attention until 15 h after ingestion. Initial treatment consisted of the administration of intravenous methylprednisolone, 250 mg once daily. Seventy-two hours after ingestion the patient was transferred to our tertiary care center. Paraquat concentration was 0.2 mg/L in the serum and urinary concentration was 4.42 mg/L. Antioxidative therapy including the administration of acetylcysteine and an anti-inflammatory therapy employing methylprednisolone (1 g/day) was started. Extended daily dialysis was initiated. As the high plasma concentration of paraquat indicated a 100% predicted mortality, we expanded treatment strategies by using the antiproliferative agent rapamycin. A dose of 8 mg/day was started 72 h after the intoxication. Maximum rapamycin concentrations amounted to 12.9 microg/L. Despite these efforts, the patient died on day 18 after intoxication from respiratory failure caused by severe pulmonary fibrosis.. Despite theoretical considerations suggesting the use of rapamycin in paraquat poisoning, the substance failed to halt the progression of pulmonary fibrosis in this case.

Topics: Anti-Inflammatory Agents; Antioxidants; Dialysis; Fatal Outcome; Herbicides; Humans; Intracellular Signaling Peptides and Proteins; Male; Methylprednisolone; Middle Aged; Oxygen Inhalation Therapy; Paraquat; Protein Serine-Threonine Kinases; Pulmonary Fibrosis; Reactive Oxygen Species; Respiratory Insufficiency; Sirolimus; Suicide; TOR Serine-Threonine Kinases; Treatment Failure

It has been proposed that exogenous pulmonary surfactant can be used as a drug delivery system for immunosuppressive agents to the alveolar compartment of the lung while reducing the risk of systemic toxicity. Before using this combination, however, alterations in activity of both substances should be examined. Therefore, this study investigated whether the activity of a natural derived surfactant preparation is changed after it is mixed with cyclosporine A (CsA) or rapamycin (RPM).. A surfactant suspension was mixed with CsA or RPM and minimal surface tension of these mixtures was measured in vitro. Surfactant activity was evaluated in vivo by its capacity to restore gas exchange in an established model of surfactant deficiency in rats. CsA-surfactant, RPM-surfactant or surfactant alone was instilled intratracheally and blood gases were measured under standardized ventilatory conditions.. Minimal surface tension of surfactant-CsA was comparable with that of surfactant alone, whereas minimal surface tension of the surfactant-RPM mixture was increased. In vivo partial arterial oxygen pressure levels increased immediately to prelavage values after instillation of CsA-surfactant, RPM-surfactant and surfactant only and were comparable during the entire study period.. The activity of a naturally derived surfactant was affected when mixed with RPM but not when mixed with CsA at the used concentrations.

Topics: Acute Disease; Animals; Blood Gas Analysis; Cyclosporine; Disease Models, Animal; Drug Delivery Systems; Immunosuppressive Agents; Male; Oxygen; Partial Pressure; Pharmaceutical Preparations; Positive-Pressure Respiration; Pulmonary Gas Exchange; Pulmonary Surfactants; Rats; Rats, Sprague-Dawley; Respiratory Insufficiency; Sirolimus; Surface Tension