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Somatic mosaic states in telomere biology disorders are characterized by somatic variants in the spliceosome and DNA damage response and repair pathways. A likely maladaptive response to short telomeres that may lead to increased hematological cancer.
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Telomerasa , Telómero , Humanos , Factor de Empalme U2AF/genética , Telómero/genética , Telómero/metabolismo , Biología , Telomerasa/genética , Telomerasa/metabolismoRESUMEN
OBJECTIVE: The objective of this retrospective review was to evaluate the perioperative and procedural management of patients with pulmonary alveolar proteinosis (PAP) who presented for whole-lung lavage (WLL). DESIGN: The records of all adult patients with PAP who underwent WLL between January 1, 1988 and August 20, 2017 were reviewed and pertinent demographic, preoperative, anesthetic, procedural, and postoperative data were recorded. SETTING: Large academic tertiary referral center. PARTICIPANTS: Forty patients with PAP underwent 79 WLL procedures. INTERVENTIONS: Patients with PAP undergoing WLL. MEASUREMENTS: Successful WLL, defined by visual clearing of lavage fluid, was completed in 91% of cases. Whole-lung lavage was terminated prematurely in 9% of cases (refractory hypoxia most common), while 8% of cases were found to have 30-day complications. There were no cases of intraoperative death, hemodynamic collapse, pneumothorax or hydrothorax, or need for emergent reintubation. Postoperative clinical follow-up at the authors' institution within 6 months of WLL showed 68% of patients reported improvement in symptoms and/or functional status. CONCLUSION: The authors here present a retrospective study describing the perioperative and procedural management of PAP patients undergoing WLL to help familiarize providers with the management of this population (Fig 1). The findings of this study outline a successful and consistent approach to WLL using a multidisciplinary team experienced in this procedure. Even in experienced hands, procedural complications and 30-day postoperative complications emphasize the risk in this complex patient population.
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Lavado Broncoalveolar/métodos , Evaluación del Resultado de la Atención al Paciente , Proteinosis Alveolar Pulmonar/diagnóstico por imagen , Proteinosis Alveolar Pulmonar/cirugía , Adulto , Lavado Broncoalveolar/instrumentación , Líquido del Lavado Bronquioalveolar , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
We carried out the first matched retrospective cohort study aimed at studying the safety and efficacy of extracorporeal photopheresis (ECP) for bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT). Medical records of 1325 consecutive adult patients who underwent HCT between 2005 and 2015 were reviewed. Seventy-four patients (median age, 51 years) with a diagnosis of BOS were included in the study. After propensity-score matching for BOS severity, 26 patients who underwent ≥3 months of ECP were matched to 26 non-ECP-treated patients, who were assigned an index date corresponding to the ECP start date for their matched pairs. The rate of decline in FEV1 percentage predicted (FEV1PP) decreased after ECP initiation (and after index date in the non-ECP group), with no significant difference between the 2 groups (P = .33). On a multivariable analysis that included baseline transplant and pulmonary function test variables, matched related donor HCT (HR, .1; 95% CI, .03 to .5; P = .002), ECP (HR, .1; 95% CI, .01 to .3; P = .001), and slower rate of decline in FEV1PP before the ECP/index date (HR, .7; 95% CI, .6 to .8; P = .001) were associated with a better overall survival. At last follow-up, non-ECP-treated patients were more likely to be on >5 mg daily dose of prednisone (54% versus 23%; P = .04) and had a greater decline in their Karnofsky performance score (mean difference, -9.5 versus -1.6; P = .06) compared with ECP-treated-patients. In conclusion, compared with other BOS-directed therapies, ECP was found to improve survival in HCT patients with BOS, without significantly impacting measured pulmonary functions. These findings need prospective validation in a larger patient cohort.
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Bronquiolitis Obliterante/terapia , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fotoféresis/métodos , Pruebas de Función Respiratoria/métodos , Acondicionamiento Pretrasplante/efectos adversos , Adulto , Anciano , Bronquiolitis Obliterante/patología , Femenino , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Análisis de Supervivencia , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/mortalidad , Adulto JovenRESUMEN
During deployment, a 52-year-old male developed acute behavioral changes. Though initially considered to have PTSD and related agitation and confusional state, his evaluation was consistent with acute encephalopathy. Magnetic resonance imaging of the brain showed T2 hyperintensities, and CSF analysis was positive for anti-N-methyl-D-aspartate receptor antibody. A nuclear protein in testis carcinoma midline carcinoma was discovered in the lung. Immunotherapy and surgical resection led to steady improvement prior to adjuvant chemotherapy. Autoimmune encephalitis due to anti-N-methyl-D-aspartate receptor antibodies is increasingly being recognized as causal of acute behavioral change.
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Encefalitis , Neoplasias Pulmonares , Imagen por Resonancia Magnética , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico , Encefalitis/diagnóstico , Encefalitis/complicaciones , Imagen por Resonancia Magnética/métodos , Trastornos Psicóticos/etiología , Trastornos Psicóticos/diagnóstico , Enfermedad de Hashimoto/complicaciones , Enfermedad de Hashimoto/diagnósticoRESUMEN
BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.
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Broncoscopía , Trasplante de Pulmón , Siliconas , Stents , Humanos , Trasplante de Pulmón/efectos adversos , Masculino , Femenino , Constricción Patológica/cirugía , Constricción Patológica/etiología , Persona de Mediana Edad , Broncoscopía/métodos , Adulto , Impresión Tridimensional , Anastomosis Quirúrgica/efectos adversos , Volumen Espiratorio Forzado , Complicaciones Posoperatorias/etiología , Tomografía Computarizada por Rayos X , Anciano , Receptores de TrasplantesAsunto(s)
Fibrosis Quística/microbiología , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Pulmón/fisiopatología , Infecciones por Mycobacterium/tratamiento farmacológico , Adulto , Niño , Fibrosis Quística/fisiopatología , Femenino , Humanos , Masculino , Infecciones por Mycobacterium/complicaciones , Mycobacterium abscessus , Pruebas de Función RespiratoriaRESUMEN
Elexacaftor/Tezacaftor/Ivacaftor (ETI) is a recently approved cystic fibrosis (CF) transmembrane conductance regulator modulator therapy that has shown promising clinical and laboratory improvements on multiple organ systems in people with CF (pwCF). While original clinical trials found little to no effect on depression and anxiety, many post-marketing reports have suggested that ETI may be associated with adverse mental health effects. Here we report on two pwCF with adverse mental health effects shortly after starting ETI. Although many factors such as the burden of living with a chronic disease or widespread effects of the Covid-19 pandemic may have contributed to these events, similar reports have led to mounting concern that ETI may be the cause of such events. Regular mental health screening before the initiation of ETI and monitoring for signs and symptoms of mental diseases afterward should be a routine part of care, given the gravity of possible outcomes.
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COVID-19 , Fibrosis Quística , Humanos , Adolescente , Fibrosis Quística/tratamiento farmacológico , Intento de Suicidio , Pandemias , COVID-19/epidemiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Aminofenoles/efectos adversos , Benzodioxoles/efectos adversos , MutaciónRESUMEN
Background: Mycoplasma hominis, Ureaplasma urealyticum, and Ureaplasma parvum may cause post-transplant infections in lung transplant recipients. We evaluated routine pretransplant screening for these Mollicutes. Methods: We retrospectively reviewed records of lung transplant recipients at our tri-site institution from 01/01/2015 to 11/15/2019. M. hominis and/or Ureaplasma polymerase chain reaction (PCR) was performed on pretransplant recipient urine specimens and donor bronchial swabs at the time of transplantation. Development of Mollicute infection and hyperammonemia syndrome (HS) was recorded. Results: A total of 268 patients underwent lung transplantation during the study period, of whom 105 were screened with at least 1 Mollicute PCR. Twelve (11%) screened positive; 10 donors, 1 recipient, and 1 both. Among positive donors, 3 were positive for M. hominis, 5 for U. urealyticum, and 4 for U. parvum. Preemptive therapy included doxycycline, levofloxacin, and/or azithromycin administered for 1-12 weeks. Despite therapy, 1 case of M. hominis mediastinitis and 1 case of HS associated with Ureaplasma infection occurred, both donor-derived. Of those screened before transplant, cases with positive screening were more likely (P < 0.05) to develop Mollicute infection despite treatment (2/12, 17%) than those who screened negative (1/93, 1%). Conclusions: Pretransplant recipient urine screening had a low yield and was not correlated with post-transplant Mollicute infection, likely because most M. hominis and U. parvum/urealyticum infections in lung transplant recipients are donor-derived. Routine donor bronchus swab PCR for M. hominis, U. urealyticum, and U. parvum followed by preemptive therapy did not obviously impact the overall incidence of Mollicute infection or HS in this cohort.
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BACKGROUND: Continuous positive airway pressure (CPAP) is a common mode of respiratory support used in neonatal intensive care units. In preterm infants, nasal CPAP (nCPAP) therapy is often delivered via soft, biocompatible nasal mask suitable for long-term direct skin contact and held firmly against the face. Limited sizes of nCPAP mask contribute to mal-fitting related complications and adverse outcomes in this fragile population. We hypothesized that custom-fit nCPAP masks will improve the fit with less skin pressure and strap tension improving efficacy and reducing complications associated with nCPAP therapy in neonates. METHODS: After IRB approval and informed consent, we evaluated several methods to develop 3D facial models to test custom 3D nCPAP masks. These methods included camera-based photogrammetry, laser scanning and structured light scanning using a Bellus3D Face Camera Pro and iPhone X running either Bellus3D FaceApp for iPhone, or Heges application. This data was used to provide accurate 3D neonatal facial models. Using CAD software nCPAP inserts were designed to be placed between proprietary nCPAP mask and the model infant's face. The resulted 3D designed nCPAP mask was form fitted to the model face. Subsequently, nCPAP masks were connected to a ventilator to provide CPAP and calibrated pressure sensors and co-linear tension sensors were placed to measures skin pressure and nCPAP mask strap tension. RESULTS: Photogrammetry and laser scanning were not suited to the neonatal face. However, structured light scanning techniques produced accurate 3D neonatal facial models. Individualized nCPAP mask inserts manufactured using 3D printed molds and silicon injection were effective at decreasing surface pressure and mask strap pressure in some cases by more than 50% compared to CPAP masks without inserts. CONCLUSIONS: We found that readily available structured light scanning devices such as the iPhone X are a low cost, safe, rapid, and accurate tool to develop accurate models of preterm infant facial topography. Structured light scanning developed 3D nCPAP inserts applied to commercially available CPAP masks significantly reduced skin pressure and strap tension at clinically relevant CPAP pressures when utilized on model neonatal faces. This workflow maybe useful at producing individualized nCPAP masks for neonates reducing complications due to misfit.
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Acute eosinophilic pneumonia (AEP) is an infrequently seen interstitial lung disease secondary to medications. We report a series of 3 case of severe AEP which developed as a result of sulfa medication. 2 patients had received treatment with sulfamethoxazole for acne and 1 was treated with sulfasalazine for colitis. Patients were on sulfa medication for 1-3 weeks prior to presentation. All patients presented with fever, acute onset bilateral pulmonary infiltrates as well as marked peripheral eosinophilia. Mean eosinophil count was 2.21 × 109/L. There was a lack of response to steroids. One patient required extracorporeal membrane oxygenation and prolonged mechanical ventilation via tracheostomy. 2 patients underwent successful lung transplantation (1 bilateral living-related lobar lung transplant and 1 orthotropic cardiopulmonary allotransplantation). In all cases lung biopsy and explants showed acute and organizing diffuse alveolar damage with increased interstitial and airspace eosinophils. To our knowledge, our series is the first to show the clinical features of sulfa induced AEP in an adolescent population.
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Interstitial lung diseases (ILDs) in patients with shortened telomeres have not been well characterized. We describe demographic, radiologic, histopathologic, and molecular features, and p16 expression in patients with telomeres ≤10th percentile (shortened telomeres) and compare them to patients with telomere length >10th percentile. Lung explants, wedge biopsies, and autopsy specimens of patients with telomere testing were reviewed independently by 3 pathologists using defined parameters. High-resolution computed tomography scans were reviewed by 3 radiologists. p16-positive fibroblast foci were quantified. A multidisciplinary diagnosis was recorded. Patients with shortened telomeres (N=26) were morphologically diagnosed as usual interstitial pneumonia (UIP) (N=11, 42.3%), chronic hypersensitivity pneumonitis (N=6, 23.1%), pleuroparenchymal fibroelastosis, fibrotic nonspecific interstitial pneumonia, desquamative interstitial pneumonia (N=1, 3.8%, each), and fibrotic interstitial lung disease (fILD), not otherwise specified (N=6, 23.1%). Patients with telomeres >10th percentile (N=18) showed morphologic features of UIP (N=9, 50%), chronic hypersensitivity pneumonitis (N=3, 16.7%), fibrotic nonspecific interstitial pneumonia (N=2, 11.1%), or fILD, not otherwise specified (N=4, 22.2%). Patients with shortened telomeres had more p16-positive foci (P=0.04). The number of p16-positive foci correlated with outcome (P=0.0067). Thirty-nine percent of patients with shortened telomeres harbored telomere-related gene variants. Among 17 patients with shortened telomeres and high-resolution computed tomography features consistent with or probable UIP, 8 (47.1%) patients showed morphologic features compatible with UIP; multidisciplinary diagnosis most commonly was idiopathic pulmonary fibrosis (N=7, 41.2%) and familial pulmonary fibrosis (N=5, 29%) in these patients. In conclusion, patients with shortened telomeres have a spectrum of fILDs. They often demonstrate atypical and discordant features on pathology and radiology leading to diagnostic challenges.
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Enfermedades Pulmonares Intersticiales , Pulmón , Técnicas de Diagnóstico Molecular , Acortamiento del Telómero , Telómero/patología , Tomografía Computarizada por Rayos X , Adulto , Anciano , Biomarcadores/análisis , Biopsia , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Diagnóstico Diferencial , Femenino , Fibroblastos/química , Fibroblastos/patología , Humanos , Inmunohistoquímica , Pulmón/química , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/genética , Enfermedades Pulmonares Intersticiales/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Telómero/genéticaRESUMEN
Major basic protein (MBP) released from activated eosinophils may influence airway hyperresponsiveness (AHR) by either direct effects on airway myocytes or by an indirect effect. In this study, human bronchi, freshly isolated human eosinophils, or MBP purified from human eosinophil granules were incubated for studying eosinophil infiltration and MBP localization. Eosinophils immediately adhered to intact human airway as well as to cultured human airway myocytes and epithelium. Following incubation 18-24 h, eosinophils migrated into the airway media, including the smooth muscle layer, but had no specific recruitment to airway neurons. Eosinophils released significant amounts of MBP within the airway media, including areas comprising the smooth muscle layer. Most deposits of MBP were focally discrete and restricted by immunologic detection to a maximum volume of approximately 300 microm(3) about the eosinophil. Native MBP applied exogenously was immediately deposited on the surface of the airway, but required at least 1 h to become detected within the media of the airway wall. Tissue MBP infiltration and deposition increased in a time- and concentration-dependent manner. Taken together, these findings suggest that eosinophil-derived cationic proteins may alter airway hyperresponsiveness (AHR) in vivo by an effect that is not limited to the bronchial epithelium.
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Bronquios/fisiología , Proteína Mayor Básica del Eosinófilo/fisiología , Eosinófilos/fisiología , Mediadores de Inflamación/fisiología , Asma/patología , Asma/fisiopatología , Hiperreactividad Bronquial/etiología , Hiperreactividad Bronquial/fisiopatología , Adhesión Celular , Degranulación de la Célula , Movimiento Celular , Células Epiteliales/fisiología , Humanos , Técnicas In Vitro , Miocitos del Músculo Liso/fisiología , Distribución Tisular , Ubiquitina Tiolesterasa/fisiologíaRESUMEN
Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of infection worldwide, including a wide array of both hospital- and community-acquired infections-most commonly bacteremia, upper and lower respiratory tract infection, skin and soft-tissue infection, osteomyelitis, and septic arthritis. This chapter describes the epidemiology of MRSA infection, its ability to confer antibiotic resistance and produce a wide array of virulence factors, and its pivotal role in human infection, especially cystic fibrosis. It also provides an introduction to the strategies for treatment of both chronic and acute MRSA infections.
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Infecciones Comunitarias Adquiridas , Fibrosis Quística , Staphylococcus aureus Resistente a Meticilina , Infecciones del Sistema Respiratorio , Infecciones de los Tejidos Blandos , Infecciones Estafilocócicas , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/metabolismo , Infecciones Comunitarias Adquiridas/terapia , Fibrosis Quística/epidemiología , Fibrosis Quística/metabolismo , Humanos , Staphylococcus aureus Resistente a Meticilina/metabolismo , Staphylococcus aureus Resistente a Meticilina/patogenicidad , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/metabolismo , Infecciones del Sistema Respiratorio/terapia , Infecciones de los Tejidos Blandos/epidemiología , Infecciones de los Tejidos Blandos/metabolismo , Infecciones de los Tejidos Blandos/terapia , Infecciones Estafilocócicas/epidemiología , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/terapia , Factores de Virulencia/metabolismoRESUMEN
CASE PRESENTATION: A 48-year-old woman sought a second opinion for dyspnea and chronic productive cough; she was a never smoker. Mild respiratory symptoms persisted since childhood and had progressively worsened over the previous decade. In addition, an unintentional 30-pound weight loss had occurred over several years. Six years previously, a diagnosis of hypersensitivity pneumonitis was made following right upper lobe wedge resection that revealed chronic bronchiolitis with interstitial pneumonia and non-necrotizing granulomatous inflammation. Subsequent use of prednisone elicited mild intermittent improvement. She had used feather pillows in the past without any other significant exposures. There were no reports of sinus or GI symptoms.
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Alveolitis Alérgica Extrínseca/diagnóstico , Aminofenoles/administración & dosificación , Broncoscopía/métodos , Cefazolina/administración & dosificación , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Fibrosis Quística , Quinolonas/administración & dosificación , Infecciones Estafilocócicas , Antibacterianos/administración & dosificación , Bronquiectasia/diagnóstico , Bronquiectasia/etiología , Agonistas de los Canales de Cloruro/administración & dosificación , Fibrosis Quística/diagnóstico , Fibrosis Quística/fisiopatología , Fibrosis Quística/terapia , Diagnóstico Diferencial , Femenino , Pruebas Genéticas , Humanos , Enfermedades de Inicio Tardío/diagnóstico , Enfermedades de Inicio Tardío/fisiopatología , Enfermedades de Inicio Tardío/terapia , Persona de Mediana Edad , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus/aislamiento & purificación , Tomografía Computarizada por Rayos X/métodos , Resultado del TratamientoAsunto(s)
Hiperamonemia/microbiología , Infecciones por Mycoplasma/complicaciones , Mycoplasma hominis/aislamiento & purificación , Complicaciones Posoperatorias/inmunología , Resultado Fatal , Femenino , Humanos , Hiperamonemia/inmunología , Huésped Inmunocomprometido , Trasplante de Pulmón , Persona de Mediana Edad , Infecciones por Mycoplasma/inmunologíaRESUMEN
OBJECTIVE: The benefit of continuous on-site presence by a staff academic critical care specialist in the intensive care unit of a teaching hospital is not known. We compared the quality of care and patient/family and provider satisfaction before and after changing the staffing model from on-demand to continuous 24-hr critical care specialist presence in the intensive care unit. DESIGN: Two-year prospective cohort study of patient outcomes, processes of care, and family and provider survey of satisfaction, organization, and culture in the intensive care unit. SETTING: Intensive care unit of a teaching hospital. PATIENTS: Consecutive critically ill patients, their families, and their caregivers. INTERVENTIONS: Introduction of night-shift coverage to provide continuous 24-hr on-site, as opposed to on-demand, critical care specialist presence. MEASUREMENTS AND MAIN RESULTS: Of 2,622 patients included in the study, 1,301 were admitted before and 1,321 after the staffing model change. Baseline characteristics and adjusted intensive care unit and hospital mortality were similar between the two groups. The nonadherence to evidence-based care processes improved from 24% to 16% per patient-day after the staffing change (p = .002). The rate of intensive care unit complications decreased from 11% to 7% per patient-day (p = .023). When adjusted for predicted hospital length of stay, admission source, and do-not-resuscitate status, hospital length of stay significantly decreased during the second period (adjusted mean difference -1.4, 95% confidence interval -0.3 to -2.5 days, p = .017). The new model was considered optimal for patient care by the majority of the providers (78% vs. 38% before the intervention, p < .001). Family satisfaction was excellent during both study periods (mean score 5.87 +/- 1.7 vs. 5.95 +/- 2.0, p = .777). CONCLUSIONS: The introduction of continuous (24-hr) on-site presence by a staff academic critical care specialist was associated with improved processes of care and staff satisfaction and decreased intensive care unit complication rate and hospital length of stay.
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Comportamiento del Consumidor , Cuidados Críticos , Hospitales de Enseñanza , Unidades de Cuidados Intensivos , Satisfacción en el Trabajo , Cuidados Nocturnos , Calidad de la Atención de Salud , Actitud del Personal de Salud , Estudios de Cohortes , Comportamiento del Consumidor/estadística & datos numéricos , Encuestas de Atención de la Salud , Humanos , Estudios Longitudinales , Minnesota , Cultura Organizacional , Evaluación de Procesos y Resultados en Atención de Salud , Admisión y Programación de Personal , Estudios Prospectivos , Calidad de la Atención de Salud/estadística & datos numéricos , Recursos HumanosRESUMEN
OBJECTIVE: To describe the successful use of surfactant for treatment of respiratory distress refractory to conventional mechanical ventilation in a 4-wk-old with pulmonary hemorrhage. DESIGN: Case report. SETTING: Tertiary care center pediatric intensive care unit. PATIENT: Four-week-old infant. MAIN RESULT: Clinical improvement of respiratory distress as evidenced by 50% reduction in oxygenation index and subsequent extubation. CONCLUSION: Pulmonary hemorrhage is a rare but potentially fatal condition in children. Previously described therapeutic approaches include high-frequency oscillation ventilation and extracorporeal membrane oxygenation. Infants with pulmonary hemorrhage and respiratory distress may benefit from a trial of surfactant before escalating care.
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Hemorragia/tratamiento farmacológico , Enfermedades Pulmonares/tratamiento farmacológico , Surfactantes Pulmonares/uso terapéutico , Hemorragia/fisiopatología , Humanos , Recién Nacido , Enfermedades Pulmonares/fisiopatología , Masculino , Alveolos Pulmonares/efectos de los fármacos , Surfactantes Pulmonares/farmacología , Respiración Artificial , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/fisiopatología , Resultado del TratamientoRESUMEN
Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.