Impact of posaconazole prophylaxis and antifungal treatment on BAL GM performance in hematology malignancy patients with febrile neutropenia: a real life experience.

BACKGROUND: Diagnostic accuracy of galactomannan measurements is highly variable depending on the study population, diagnostic procedures, and treatment procedures. We aimed to evaluate the effect of posaconazole prophylaxis and empiric antifungal treatment upon diagnostic accuracy of GM measurements in bronchoalveolar lavage (BAL), bronchial lavage (BL), and serum in hematological malignancy population. METHODS: Patients hospitalized in a single tertiary care center with hematologic malignancies undergoing fiberoptic bronchoscopy (FOB) with a preliminary diagnosis of IPA were retrospectively included. RESULTS: In all the study population (n = 327), AUC for BAL, BL, and serum GM were as follows: 0.731 [0.666-0.790], 0.869 [0.816-0.912], and 0.610 [0.540-0.676] with BL samples having the best diagnostic value. GM measurements in patients under posaconazole prophylaxis (n = 114) showed similar diagnostic performance. While specificity was similar between patients with and without posaconazole prophylaxis, sensitivity of GM measurements was lower in patients with prophylaxis. Analyses with patient classified according to antifungal treatment at the time of FOB procedure (n = 166) showed a decreased diagnostic accuracy in serum GM and BAL GM measurements related with the duration of treatment. However, BAL, BL, and serum GM measurements presented similar sensitivity and specificity in higher cut-off values in longer durations of antifungal treatment. CONCLUSION: Our study shows that posaconazole prophylaxis and active short-term (3 days) antifungal treatment do not significantly affect overall diagnostic performance of GM measurements in bronchoalveolar lavage and bronchial lavage samples. However, using different cut-off values for patients receiving active treatment might be suggested to increase sensitivity.

Comparison of BAP65, DECAF, PEARL, and MEWS Scores in Predicting Respiratory Support Need in Hospitalized Exacerbation of Chronic Obstructive Lung Disease Patients.

OBJECTIVE: Prognostic models aid clinical practice with decision-making on treatment and hospitalization in exacerbation of chronic obstructive lung disease (ECOPD). Although there are many studies with prognostic models, diagnostic accuracy is variable within and between models. SUBJECTS AND METHODS: We compared the prognostic performance of the BAP65 score, DECAF score, PEARL score, and modified early warning score (MEWS) in hospitalized patients with ECOPD, to estimate ventilatory support need. RESULTS: This cross-sectional study consisted of 139 patients. Patients in need of noninvasive or invasive mechanical ventilation support are grouped as ventilatory support groups (n = 54). Comparison between receiver operating characteristic curves revealed that the DECAF score is significantly superior to the PEARL score (p = 0.04) in discriminating patients in need of ventilatory support. DECAF score with a cutoff value of 1 presented the highest sensitivity and BAP65 score with a cutoff value of 2 presented the highest specificity in predicting ventilatory support need. Multivariable analysis revealed that gender played a significant role in COPD exacerbation outcome, and arterial pCO2 and RDW measurements were also predictors of ventilatory support need. Within severity indexes, only the DECAF score was independently associated with the outcome. One-point increase in DECAF score created a 1.43 times higher risk of ventilatory support need. All severity indexes showed a correlation with age, comorbidity index, and dyspnea. BAP65 and DECAF scores also showed a correlation with length of stay. CONCLUSION: Objective and practical classifications are needed by clinicians to assess prognosis and initiate treatment accordingly. DECAF score is a strong candidate among severity indexes.

Brain death in children: is computed tomography angiography reliable as an ancillary test?

BACKGROUND: The diagnosis of brain death is primarily clinical. Sometimes ancillary tests are needed. OBJECTIVE: This study compared sensitivity and interobserver agreement of the 10-, 7- and 4-point CT angiography scoring systems for the diagnosis of brain death in children. MATERIALS AND METHODS: CT angiography examinations of 50 pediatric patients with a clinical diagnosis of brain death were evaluated according to 10-, 7- and 4-point scoring systems. Images were evaluated by two radiologists who considered the vessel opacification first in the arterial phase (A0-V50) and then in the venous phase (A0-V50). We evaluated interobserver agreement for the assessment of vessel opacification and diagnosis of brain death. We compared the differences among brain death diagnoses between children with craniotomy-craniectomy defects, open fontanelles and preserved bone integrity. We subdivided children into two groups according to age: ≤ 2 years and > 2 years. We calculated sensitivities according to age groups. RESULTS: Using the clinical exam as the reference standard, we found sensitivities for 10-, 7- and 4-point scoring systems to be 70%, 88% and 92% in the A0-V50 method and 40%, 82% and 82% in the A50-V50 method, respectively. Percentage agreement between readers was 78% for the 7-point scale using the A0-V50 method and more than 90% for other scoring systems for both the A0-V50 method and the A50-V50 method. The sensitivity was much lower in children with open anterior fontanelles compared to the groups with preserved bone integrity and with a craniotomy-craniectomy defect. CONCLUSION: Just as in adult age groups, in children the 4-point scale appears to be more sensitive than the 10- and 7-point scales for CT angiography-based assessment of brain death. Because the scoring systems have similar sensitivities, they could be used as ancillary tests in pediatric cases.

Pilot study for immunoglobulin E as a prognostic biomarker in coronavirus disease 2019.

BACKGROUND: Laboratory biomarkers to estimate the severity of coronavirus disease 2019 (COVID-19) are crucial during the pandemic since resource allocation must be carefully planned. AIMS: To evaluate the effects of basal serum total immunoglobulin E (IgE) levels and changes in inflammatory parameters on the clinical progression of patients hospitalised with COVID-19. METHODS: Patients hospitalised with confirmed COVID-19 were included in the study. Laboratory data and total IgE levels were measured on admission. Lymphocyte, eosinophil, ferritin, d-dimer and C-reactive protein parameters were recorded at baseline and on the 3rd and 14th days of hospitalisation. RESULTS: The study enrolled 202 patients, of which 102 (50.5%) were males. The average age was 50.17 ± 19.68 years. Of the COVID-19 patients, 41 (20.3%) showed clinical progression. Serum total IgE concentrations were markedly higher (172.90 (0-2124) vs 38.70 (0-912); P < 0.001) and serum eosinophil levels were significantly lower (0.015 (0-1.200) vs 0.040 (0-1.360); P = 0.002) in clinically worsened COVID-19 patients when compared with stable patients. The optimal cut-off for predicting clinical worsening was 105.2 ng/L, with 61% sensitivity, 82% specificity, 46.3% positive predictive value and 89.2% negative predictive value (area under the curve = 0.729). Multivariable analysis to define risk factors for disease progression identified higher total IgE and C-reactive protein levels as independent predictors. CONCLUSIONS: Our single-centre pilot study determined that total IgE levels may be a negative prognostic factor for clinical progression in patients hospitalised due to COVID-19 infection. Future studies are required to determine the impact of individuals' underlying immune predispositions on outcomes of COVID-19 infections.

The outcomes of using high oxygen concentration in pediatric patients.

Oxygen reserve index, available as part of Masimo Rainbow SET pulse oximetry, is a noninvasive and continuous variable intended to provide insight into a patient's oxygen status in the moderate hyperoxic range (PaO2 > 100 and ≤ 200 mm Hg), defined as a patient's oxygen "reserve". When used in conjunction with pulse oximetry, ORi extends the knowledge on a patient's oxygen status providing clinically important information helping to prevent hyperoxemia and hypoxemia. There are limited data on patients undergoing craniosynostosis surgery. Our primary goal was to evaluate the effects of different concentrations of inspiratory oxygen (FiO2) on patient oxygenation status by monitoring ORi. Thirty patients scheduled for craniosynostosis were included in this observational cohort study. Patients were randomized into two equal groups: Group 1 received a fraction of inspired oxygen of 0.8 and group 2 received a FiO2 of 0.6 during induction of anaesthesia. In addition to standard haemodynamic variables with ORi were recorded at baseline 1 min, 5 min, 60 min, and 120 min after intubation. Postoperative complications, length of stay in the intensive care unit and hospital were recorded. In total, 14 patients were evaluated in each group. Gender, age, BMI, ASA scores were similar between groups (p > 0.05). In Group 1, ORi values were significantly higher when compared to group 2 at baseline (0.86 ± 0.21 vs 0.45 ± 0.32, p = 0.001), one minute (0.61 ± 0.24 vs 0.27 ± 0.21, p = 0.001), and 5 min (0.34 ± 0.31 vs 0.10 ± 0.13, p = 0.033). High inspired oxygen concentration during induction of anesthesia in pediatric patients is associated with higher levels of ORi. Therefore, ORi may provide the means to safely reduce the inspired oxygen fraction during inhalational induction in paediatric patients.

AVAPS-NIV treatment in hypercapnic respiratory failure with insufficient response to fixed-level PS-NIV.

Introduction: Noninvasive ventilation (NIV) for acute hypercapnic respiratory failure (AHRF) is an established treatment modality. Current evidence does not conclude any superiority between fixed pressure support (PS) and average volume-assured pressure support (AVAPS) modes. However, given the ability of rapid PaCO2 decline in AVAPS mode, we hypothesized that COPD patients with AHRF who did not show the desired reduction in PaCO2 with fixed-level PS-NIV might benefit from the AVAPS mode. Materials and Methods: Patients admitted to the non-ICU pulmonary ward with acute exacerbation of COPD (AECOPD) and AHRF were included consecutively in this observational study. Patients with hypercapnic respiratory failure due to obesity-hypoventilation, neurological diseases, or chest wall deformities were excluded. All patients started NIV treatment with fixed pressure support (PS) and patients who did not reach clinical and laboratory stability under PS-NIV treatment were switched to the average volume-assured pressure support (AVAPS) mode of NIV. Result: Thirty-five COPD patients with hypercapnic respiratory failure were included. Under PS-NIV treatment, 14 (40%) patients showed a 17.9 (-0.0-29.2) percent change in terms of PaCO2, meaning no improvement or worsening. Therefore, these patients were treated with AVAPS mode. Arterial PaCO2 and pH levels significantly improved after AVAPS-NIV administration. AVAPS-NIV treatment created a significantly better PaCO2 change rate than using PS-NIV [-11.4 (-22.0 - -0.5) vs 8.2 (-5.3-19.5), p= 0.02]. Independent predictors of AVAPS mode requirement were higher Charlson Comorbidity Index [OR= 1.74 (95% CI= 1.02-2.97)] and higher PaCO2 upon admission [OR= 1.18 (95% CI= 1.03-1.35)]. Thirteen (92.8%) patients reaching significant clinical stability with AVAPS-NIV were able to return to fixed-level PS-NIV and maintain acceptable PaCO2 levels. Conclusions: Our study demonstrated that patients can benefit from AVAPSNIV despite insufficient response to fixed-level PS-NIV.

Influenza Virus Associated Pediatric Acute Respiratory Distress Syndrome: Clinical Characteristics and Outcomes.

BACKGROUND AND OBJECTIVE: The aim of this multicenter retrospective study was to determine the clinical characteristics, treatment approaches and the course of pediatric acute respiratory distress syndrome (PARDS) which developed associated with the influenza virus in the 2019-20 season. METHODS: Patients included 1 month to 18 years who were diagnosed with PARDS associated with the influenza virus in the 2019-20 season. RESULTS: Sixty-seven patients were included in the study. The mean age of the patients was 64.16 ± 6.53 months, with 60% of the group <5 years. Influenza A was determined in 54 (80.5%) patients and Influenza B in 13 (19.5%). The majority of patients (73.1%) had a comorbidity. Fifty-eight (86.6%) patients were applied with invasive mechanical ventilation, Pediatric Acute Lung Injury Consensus Conference classification was mild in 5 (8.6%), moderate in 22 (37.9%) and severe in 31 (52.5%) patients. Ventilation was applied in the prone position to 40.3% of the patients, and in nonconventional modes to 24.1%. A total of 22 (33%) patients died, of which 4 had been previously healthy. Of the surviving 45 patients, 38 were discharged without support and 7 patients with a new morbidity. CONCLUSION: Both Influenza A and Influenza B cause severe PARDS with similar characteristics and at high rates. Influenza-related PARDS cause 33% mortality and 15.5% morbidity among the study group. Healthy children, especially those aged younger than 5 years, are also at risk.

Interleukin-21: a potential biomarker for diagnosis and predicting prognosis in COVID-19 patients

Background/aim: COVID-19 patients have a wide spectrum of disease severity. Several biomarkers were evaluated as predictors for progression towards severe disease. IL-21 is a member of common γ-chain cytokine family and creates some specific effects during programming and maintenance of antiviral immunity. We aimed to assess IL-21 as a biomarker for diagnosis and outcome prediction in patients hospitalized with COVID-19. Materials and methods: Patients with a preliminary diagnosis of COVID-19 and pneumonia other than COVID-19 admitted to a tertiary care hospital were included consecutively in this comparative study. Results: The study population consisted of 51 patients with COVID-19 and 11 patients with non-COVID-19 pneumonia. Serum IL-21 concentration was markedly higher, and serum CRP concentration was significantly lower in COVID-19 patients compared to non-COVID-19 pneumonia patients. Within COVID-19 patients, 10 patients showed radiological and clinical progression. Patients with clinical worsening had lower lymphocyte count and haemoglobin. In addition to that, deteriorating patients had higher urea, LDH levels, and elevated concentration of both IL-6 and IL-21. The cut-off value of 106 ng/L for IL-21 has 80.0% sensitivity, %60.9 specificity for discriminating patients with clinical worsening. Multivariable analysis performed to define risk factors for disease progression identified IL-6 and IL-21 as independent predictors. Odds ratio for serum IL-6 concentrations ≥ 3.2 pg/mL was 8.07 (95% CI: 1.37-47.50, p = 0.04) and odds ratio for serum IL-21 concentrations ≥ 106 ng/L was 6.24 (95% CI: 1.04 ­ 37.3, p = 0.02). Conclusion: We identified specific differences in serum IL-21 between COVID-19 and non-COVID-19 pneumonia patients. Serum IL-21 measurement has promising predictive value for disease progression in COVID-19 patients. High serum IL-6 and IL-21 levels obtained upon admission are independent risk factors for clinical worsening.

A Rare Cause of Hypophosphatemia: Raine Syndrome Changing Clinical Features with Age.

Raine Syndrome (RS) is caused by biallelic loss-of-function mutations in FAM20C gene and characterized by hypophosphatemia, typical facial and skeletal features. Subperiosteal bone formation and generalized osteosclerosis are the most common radiological findings. Here we present a new case with RS. A 9-month-old male patient on a home-type ventilator was referred for hypophosphatemia. He was born with a weight of 3800 g to non-consanguineous parents. Prenatal ultrasound had demonstrated nasal bone agenesis. A large anterior fontanel, frontal bossing, exophthalmos, hypoplastic nose, high arched palate, low set ears, triangular mouth, and corneal opacification were detected on physical examination. Serial skeletal X-rays revealed diffuse osteosclerosis at birth which was gradually decreased by the age of 5 months with subperiosteal undermineralized bone formation and medullary space of long bone could be distinguishable with bone-within-a-bone appearance. At 9 months of age, hand X-ray revealed cupping of the ulna with loose radial bone margin with minimal fraying and osteopenia. Cranial computed tomography scan showed bilateral periventricular calcification and hydrocephalus in progress. The clinical, laboratory, and radiological examinations were consistent with RS. Molecular analyses revealed a compound heterozygous mutation in FAM20C gene (a known pathogenic mutation, c.1645C > T, p.Arg549Trp; and a novel c.863 + 5 G > C variant). The patient died due to respiratory failure at 17 months of age. This case allowed us to demonstrate natural progression of skeletal features in RS. Furthermore, we have described a novel FAM20C variant causing RS. Previous literature on RS is also reviewed.

Daily Practice of Mechanical Ventilation and Weaning in Turkish PICUs: A Multicenter Prospective Survey.

OBJECTIVES: To investigate conventional mechanical ventilation weaning characteristics of patients requiring conventional mechanical ventilation support for greater than 48 hours within the PICU. DESIGN: The prospective observational multicenter cohort study was conducted at 15 hospitals. Data were being collected from November 2013 to June 2014, with two designated researchers from each center responsible for follow-up and data entry. SETTING: Fifteen tertiary PICUs in Turkey. PATIENTS: Patients between 1 month and 18 years old requiring conventional mechanical ventilation for greater than 48 hours were included. A single-center was not permitted to surpass 20% of the total sample size. Patients with no plans for conventional mechanical ventilation weaning were excluded. INTERVENTIONS: Conventional mechanical ventilation MEASUREMENTS AND MAIN RESULTS:: Pertinent variables included PICU and patient demographics, including clinical data, chronic diseases, comorbid conditions, and reasons for intubation. Conventional mechanical ventilation mode and weaning data were characterized by daily ventilator parameters and blood gases. Patients were monitored until hospital discharge. Of the 410 recruited patients, 320 were included for analyses. A diagnosis of sepsis requiring intubation and high initial peak inspiratory pressures correlated with a longer weaning period (mean, 3.65 vs 1.05-2.17 d; p < 0.001). Conversely, age, admission Pediatric Risk of Mortality III scores, days of conventional mechanical ventilation before weaning, ventilator mode, and chronic disease were not related to weaning duration. CONCLUSIONS: Pediatric patients requiring conventional mechanical ventilation with a diagnosis of sepsis and high initial peak inspiratory pressures may require longer conventional mechanical ventilation weaning prior to extubation. Causative factors and optimal weaning for this cohort needs further consideration.

Diagnostic performance of EBUS-TBNA and its interrelation with PET-CT in patients with extra-thoracic malignancies.

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established diagnostic tool for lung cancer, sarcoidosis, and suspected metastatic extra-thoracic malignancy (ETM). Patients with primary ETM often have hypermetabolic mediastinal/hilar lymph node enlargement in the PET-scan done for initial staging or post treatment followup. We aimed to determine the diagnostic performance of EBUS-TBNA and the relationship between PET-SUV values and diagnosis of malignancy metastasis in patients with ETM. MATERIALS AND METHODS: Results of EBUS-TBNA in ETM patients with suspected MLN metastasis were retrospectively analysed (May 2016 to July 2019). Non-malign results were confirmed for surgery or clinical/radiological followup. Lymph nodes with a high FDG-uptake (SUV > 2.5, MLN) were reported as suspicious for metastasis. RESULT: Of the 588 EBUS procedures, 109 were included in the analysis. Patient' mean age was 62.5 ± 10.1 years; there were 35 men and 74 women. Primary malignancies were breast cancer in 33, gastrointestinal in 23, female genital tract in 17, head and neck in 14, genitourinary cancer in 13, malignant melanoma in 6, sarcoma in 2 and kaposi sarcoma in 1. According to EBUS-TBNA smear and cell block histopathologic evaluations, 16 patients' results (14.7%) were malignant compatible with metastasis of ETM. Among the 93 patients with non-malignant diagnosis, EBUS-TBNA revealed a granulomatous lympadenitis compatible with sarcoid reaction in 7 and tuberculosis in 2. A total of 9 patients underwent surgical procedures after EBUSTBNA, with a definitive histological diagnosis of granulomatous lymphadenitis in 2, malignancy in 5 and, reactive lymph node in 2. Overall sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of EBUS-TBNA were 76.19% (95% CI 52.83-91.78), 100% (95% CI 95.89-100.00), 100%, 94.62% (95% CI 89.12-97.12) and 95.4%, respectively. CONCLUSIONS: EBUS-TBNA sampling has high diagnostic performance. Histopathological confirmation requirement for MLN should be kept in mind in patients with ETM, even they have negative EBUS results.

Is serum iron responsive protein-2 level associated with pulmonary functions and frequent exacerbator phenotype in COPD?

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) exacerbations contribute to the overall severity in individual patients because they are associated with airway inflammation, pulmonary function loss, decreased quality of life and increased mortality. Although, identifying frequent exacerbator patients is important due to severe outcomes associated with frequent exacerbator phenotype in COPD patients there is no single biomarker which can differentiate this phenotype. Iron responding protein-2 (IRP2) is the protein product of IREB2 gene, which is a COPD susceptibility gene that regulates cellular iron homeostasis and has a key role in hypoxic conditions. Previous research indicates that IREB2 expression in lung tissue is associated with spirometric measurements and emphysema in COPD. In this study, our aim was to investigate whether serum IRP2 levels were associated with frequent exacerbator phenotype, to evaluate whether IRP2 levels in serum are associated with pulmonary functions and selected systemic inflammation biomarkers. MATERIALS AND METHODS: Designed as a single tertiary care center based, crosssectional study, included high risk (GOLD C, D) COPD patients who admitted to outpatient clinic consecutively between December 2015 and July 2016. RESULT: The study included 80 COPD patients. Serum IRP2 levels were negatively correlated with FEV1 ml (r= -0.25, p= 0.02) and body weight (r= -0.35, p= 0.002) but not with markers of systemic inflammation. COPD patients with at least one exacerbation history in the last year tended to have higher IRP2 levels than patients without any exacerbation [12.3 (IQR 25-75: 10.4- 17.1) vs 10.5 (IQR 25-75: 8.8-18.5), p= 0.06]. CONCLUSIONS: Serum IRP2 level is significantly correlated with FEV1 mL but not with FEV1 % predicted and cannot be used to differentiate frequent exacer bator patients. Although IREB2 gene expressions in lung tissue and bronchoalveolar lavage results have significant associations with emphysema and FEV1/FVC, FEV1 %predicted in COPD patients, our results suggests serum IRP2 level is not as promising.

The diagnostic value of soluble urokinase plasminogen activator receptor (suPAR) compared to C-reactive protein (CRP) and procalcitonin (PCT) in children with systemic inflammatory response syndrome (SIRS).

BACKGROUND: The aim of the present study was to determine the diagnostic and prognostic values of suPAR and to compare them to CRP and PCT in pediatric patients with systemic inflammatory response syndrome (SIRS). MATERIAL-METHODS: A prospective case-control study was performed.The study was performed in a tertiary university hospital which has a 649-bed capacity. Patients included 27 children with SIRS and 27 control subjects without any infection or immunosuppressive condition. Blood samples were obtained on the day of admission and on the 4-7th days of the hospital stay. RESULTS: The median (min-max) serum levels of suPAR obtained on the first day of the admission were 10.06 (2.7-57.46) and 2.22 (1.08-5.13) ng/Ml for the SIRS group and control group, respectively. The median serum levels of suPAR in the SIRS group was significantly higher than that in the control group (p < 0.05). The serum suPAR levels was significantly higher in nonsurvivors than in survivors in SIRS group (p < 0.05). In the SIRS group, the area under the receiver operating characteristics curve (AUCROC) for suPAR revealed an optimum cut-off value, sensitivity, specificity, NPV and PPV of 0.978, 3.8 ng/mL, 96%, 96%, 96%, and 96%, respectively. CONCLUSIONS: We conclude that suPAR does have diagnostic value in children with SIRS. Additionally, persistent high serum suPAR level predicts mortality in SIRS in children.

Lung cancer diagnosed with Mycobacterium tuberculosis or nontuberculosis mycobacteria concomitantly.

INTRODUCTION: The concomitant occurrence of disease of Mycobacterium tuberculosis or nontuberculosis mycobacteria (NTM) and lung cancer has been reported in previous studies. We aimed to determine characteristics of the patients with lung cancer diagnosed with M. tuberculosis or NTM concomitantly. MATERIALS AND METHODS: From 2010 to 2015, the patients diagnosed with lung cancer and M. tuberculosis or NTM concomitantly were enrolled in the study. Patient data were collected retrospectively. RESULT: Concomitant M. tuberculosis or NTM and lung cancer were diagnosed in 17 cases (1.2% of total lung cancer cases, 0.9% of total tuberculosis cases). M. tuberculosis was isolated from 11 (64.8%) patients and NTM disease was from 6 (35.2%) patients. Squamous cell carcinoma was the most common histological type. Tumoral stage was often advanced as stage III- IV (76.5%). Bronchial lavage smear positivity foracid-fast bacilli was found only in 4 (23.5%) patients. Tuberculosis treatment therapy was started only in 4 (23.5%) patients who had bronchial lavage smear positivity for acid-fast bacilli. So tuberculosis treatment was delayed for other 13 (76.5%) patients with bronchial lavage smear negative for acid-fast bacilli. Seven out of 17 (41.1%) patients died. CONCLUSIONS: Physicians should consider concomitant M. tuberculosis or NTM when managing lung cancer. Tuberculosis patients may be mis diagnosed as lung cancer or vice versa.

Think Again: First Do No Harm: A Case of Munchausen Syndrome by Proxy.

Apparent life-threatening events caused by Munchausen syndrome by proxy (MSP) are rare but difficult to resolve medically. Failure to properly diagnose MSP can lead to further abuse by the caregiver and increase the risk of complications due to long hospital stays and invasive tests. In this paper, we describe our experiences with a baby who ended up being diagnosed with MSP, including our initial failure to find a pathology, delay of MSP diagnosis, our growing suspicion of MSP despite technical setbacks, our actions after we confirmed MSP as the cause of his hospitalizations. We also describe the difficulties of diagnosing MSP compared to more traditional problems and explain a series of precautions and guidelines to help detect it in a timely manner.

Clinical heterogeneity of immunodysregulation, polyendocrinopathy, enteropathy, X-linked: pulmonary involvement as a non-classical disease manifestation.

PURPOSE: IPEX (Immunodysregulation, Polyendocrinopathy, Enteropathy, X-linked) is a rare X-linked recessive life-threatening disorder characterized by autoimmunity and early death. Pulmonary complication related with IPEX has not been elucidated exactly. Here, we report 4 IPEX patients, 3 of which died from severe pulmonary disease. METHODS: Clinical data and laboratory findings including autoantibodies, immunoglobulin levels as well as number of T, B and NK cells were evaluated. FOXP3 expression and T reg activity were analyzed. The FOXP3 gene was sequenced and RNA analysis was performed. RESULTS: Patient I (PI) presented with nephrotic syndrome at 3 years of age and then developed autoimmune hepatitis without eczema, enteropathy or high IgE and died at 9 years of age due to acute respiratory distress syndrome (ARDS). Two cousins of PI had the same hypomorphic splice site mutation leading to a deletion of 27 amino acids, but normal FOXP3 protein expression and normal suppressive capacity of T reg in a proliferation inhibition assay. However, they exhibited typical symptoms such as eczema, diabetes and enteropathy with eosinophilia at early age (PII, PIII) and were transplanted in infancy. One of them had severe respiratory distress right after birth (PIII). Patient IV from another family presented with chronic diarrhea without autoimmune manifestations and died due to ARDS. CONCLUSION: Lung disease related to IPEX syndrome has not been reported before and this entity could be a critical factor in disease outcome.

The nature of chronic rejection after lung transplantation: a murine orthotopic lung transplant study.

Introduction: Chronic rejection is a major complication post-transplantation. Within lung transplantation, chronic rejection was considered as airway centred. Chronic Lung Allograft Dysfunction (CLAD), defined to cover all late chronic complications, makes it more difficult to understand chronic rejection from an immunological perspective. This study investigated the true nature, timing and location of chronic rejection as a whole, within mouse lung transplantation. Methods: 40 mice underwent an orthotopic left lung transplantation, were sacrificed at day 70 and evaluated by histology and in vivo µCT. For timing and location of rejection, extra grafts were sacrificed at day 7, 35, 56 and investigated by ex vivo µCT or single cell RNA (scRNA) profiling. Results: Chronic rejection originated as innate inflammation around small arteries evolving toward adaptive organization with subsequent end-arterial fibrosis and obliterans. Subsequently, venous and pleural infiltration appeared, followed by airway related bronchiolar folding and rarely bronchiolitis obliterans was observed. Ex vivo µCT and scRNA profiling validated the time, location and sequence of events with endothelial destruction and activation as primary onset. Conclusion: Against the current belief, chronic rejection in lung transplantation may start as an arterial response, followed by responses in venules, pleura, and, only in the late stage, bronchioles, as may be seen in some but not all patients with CLAD.

Use of pumpless extracorporeal lung assist as rescue therapy in adolescent with cystic fibrosis.

There is abundant evidence that artificial ventilation can aggravate pre-existing lung disease, which may contribute to morbidity and mortality. This is especially true for patients with air leakages. This case report describes the use of a pumpless extracorporeal lung assist as a rescue therapy to provide time to heal during the mechanical ventilation of a 16-year-old with cystic fibrosis who could not be managed via conventional means.