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Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers. Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans. Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown. HTR SNPs were assessed in two cohorts. Results: Pharmacological inhibition or siRNA knockdown of the serotonin receptors HTR1A or HTR1B in endothelial cells abrogated the inhibitory effects of 5HTP on eosinophil transendothelial migration. In contrast, eosinophil transendothelial migration was not inhibited by siRNA knockdown of HTR1A or HTR1B in eosinophils. Surprisingly, these HTRs were intracellular in endothelial cells and an extracellular supplementation with serotonin did not inhibit eosinophil transendothelial migration. This is consistent with the inability of serotonin to cross membranes, the lack of selective serotonin reuptake receptors on endothelial cells, and the studies showing minimal impact of selective serotonin reuptake inhibitors on asthma. To extend our HTR studies to humans with asthma, we examined the CHIRAH and GALA cohorts for HTR SNPs that affect HTR function or are associated with behavior disorders. A polygenic index of SNPs in HTRs was associated with lower lung function in asthmatics. Conclusions: Serotonin receptors mediate 5HTP inhibition of transendothelial migration and HTR SNPs associate with lower lung function. These results may serve to aid in design of novel interventions for allergic inflammation.
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Situs inversus is a rare congenital disorder where the reversal of some of the major thoracic or abdominal organs is present. In this disorder, alterations in the fetus's organ lateralization lead to a complete reversal in the arrangement of the internal organs. Most of the time, they are found incidentally when having a procedure or imaging modality. Little has been written regarding the challenges encountered while providing critical care to these patients. Here we present the case of a 68-year-old male patient admitted to the intensive care unit (ICU) with hypoxemic respiratory failure secondary to pneumonia who underwent diagnostic bronchoscopy for organism identification and was confirmed to have situs inversus totalis. Situs inversus totalis represents a challenge at different levels of care to these patients, including in the ICU. Limitations in critical care can be seen upon imaging identification, and during routine procedures performed at the ICU. Confusion might appear while performing bedside point of care ultrasound, obtaining vascular access, performing electrocardiogram, and sample identification, among others. The case brings the relevance of being able to recognize this rare disorder, which can be diagnosed even in advanced age since it might present the clinician with challenges at the time of providing care to patients.
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OBJECTIVE: In complicated parapneumonic effusion or Empyema, approximately 25% of patients require surgical intervention which can be associated with a mortality risk of almost 20%. However, the use combination of rt-tPA and DNase in elderly patients with prohibitive surgical risk has improved outcomes. The main goal of our study is to highlight the utility of intrapleural thrombolysis in patients with prohibitive risk for surgery. METHODS: A retrospective record review study of patients (n=23) with complicated parapneumonic pleural effusion or empyema treated with tPA and DNase from January 1st of 2015 to March 18th, 2019 at VACHCS. Data collected to describe the outcome of intrapleural thrombolytics included demographic, pleural fluid analysis, surgical risk assessment, diagnosis and initiation treatment day, doses, chest imaging, drainage rate, chest tube size and average days in place, inflammatory markers, microbiology, antibiotics, and complications. RESULTS: Only 21.7% of patients were considered surgical candidates. Seventy-four percent had a 30-day post-surgical mortality risk of > 2.5% using the National Surgery Office (NSO) risk calculator. Post-operative inpatient stay was 99.7% and estimated post operative ICU stay average was >80%. Primary outcome (pleural drainage improvement) obtained in 73.9%. Most common serious complications included sepsis (52.2%) and nonserious was residual hydropneumothorax (47.8%). CONCLUSION: This study demonstrates that administration of intrapleural thrombolytics through a percutaneous pleural catheter achieved successful drainage safely and without the need for surgical interventions in a selected group of advanced age, elderly patients with pleural infections who were deemed to be high surgical risk.
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Empiema , Derrame Pleural , Idoso , Humanos , Estudos Retrospectivos , Derrame Pleural/etiologia , Derrame Pleural/terapia , Fibrinolíticos , DesoxirribonucleasesRESUMO
Here, we present the case of a 61-year-old veteran Hispanic male with recurrent aspiration pneumonitis, aerophagia, tympanic abdominal bloating, and a positive Ono's sign; symptoms present were secondary to diagnosed tracheoesophageal fistulas (TEFs). TEFs are abnormal connections between the esophagus and the trachea. In adult cases, several risk factors have been identified for acquired cases, which include infection, trauma, and cancer. Diagnosis of TEF can be challenging and, in most cases, requires high suspicion. Currently, there are no established guidelines for diagnosing and managing TEF. Clinical assessment and various imaging techniques are essential in the diagnostic process. This article will discuss the etiology, clinical presentation, diagnostic approaches, and management options for acquired TEFs.
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OBJECTIVE: Lung Cancer (LC) in Puerto Rico (PR) is the fifth most common malignancy (5.2%), the third most common among men (5.9%) and the fifth among women (4.6%), with a mortality of 11.3%. Despite current data demonstrating the importance and clinical value for lung cancer screening LDCT Screening among high risk patients remains low regardless of the potential to prevent thousands of lung cancer deaths per year. Due to significant disparities in health care in PR it is believed that LDCT use for lung cancer screening in PR is not been enforced in the private sector. METHODS: A self-administered anonymous survey was provided to a group of pulmonologists at the annual meeting of the PR Pneumology Society. The survey contained questions regarding characteristics of their practice and implementation of lung cancer screening. Provided information was tabulated in percentages. RESULTS: A total of 31 pulmonologists participated in the administration of the survey. Most participants had their medical practice in the metropolitan area (52%), which is the most populated area with best access to physicians and health care services. The sample from the north area comprised 19% of the subjects. All respondents were affiliated to health care institutions. As most of them served 1-3 health care centers (96%) with access to specialized equipment such as Chest CT. Most of the physicians (99%) had availability of chest CT scan within 1 hour from their practices and 97% were aware of the U.S. Preventive Services Task Force lung cancer screening recommendations. Their age range was 41 and over (55%). Despite the above there were discrepancies when asked about lung cancer screening implementation. Sixteen (16) percent did not perform lung cancer screening at all, and 77% that performed screening, reported limitations to it. CONCLUSION: This data suggests that although lung cancer screening has shown to reduce mortality and is recommended by the USPTF, it is not been conducted appropriately in PR. The main limitation identified was what the health insurance had to offer rather than lack of health insurance. Other factor to take in consideration is the lack of a comprehensive screening program for Lung Cancer anywhere in the island. In addition, costs associated with staff and implementation were noted as a significant barrier among the surveyed pulmonologists.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Porto Rico , Pneumologistas , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: HPV is the most common sexually transmitted disease in the United States, the principal cause for cervical cancer, and the principal cause for the recent increase in head and neck squamous cell cancers. Current interventions and research goals fail to sufficiently address the need to prevent HPV, and continued stigmatization of HPV as a female disease further discourages young patients from seeking the vaccine. AREAS COVERED: This paper will review the epidemiology of HPV, including the rise in male cases and cancers, the immunogenicity of the vaccine, results of efficacy and effectiveness trials, and the social and operational challenges to preventing HPV infection within the United States. Statistics were sourced from the CDC. Studies were found through PubMed searches related to HPV. Priority was given to articles published in the last ten years, and policy statements from major associations were considered. EXPERT OPINION: To improve vaccination rates, diversified physician engagement in vaccinating adolescents, better knowledge sharing about vaccine hesitancy, and specifically targeting males to bridge the gender gap are all necessary. Further, childhood HPV vaccinations and therapeutic vaccinations remain under-researched but potentially effective methods to diminish the incidence of HPV-associated cancers.
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Infecções por Papillomavirus , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Adolescente , Criança , Feminino , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , Faringe , Fatores Sexuais , Estados Unidos/epidemiologia , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/prevenção & controle , VacinaçãoRESUMO
HLH is a rare and deadly disease increasingly more present in adults, but following treatment protocol may yield favorable results.
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A 72-year-old male patient was found with enlarged nodes in the anterior and posterior mediastinum on screening imaging studies of the chest. The anterior node appeared as a single cystic lesion without significant metabolic activity on scintigraphy images. The posterior node was a single solid lesion in the lower left periesophageal space above the diaphragmatic crura with moderate metabolic uptake. Endoscopic ultrasound allowed a transesophageal endosonography-guided fine needle aspiration of the posterior node. The anterior lesion was sampled via percutaneous transthoracic approach. Biopsy revealed aggregates of mesenchymal cells with spindle nuclei; immunohistochemistry confirmed two primary leiomyomas of the mediastinum.
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Leiomioma/diagnóstico , Linfonodos/diagnóstico por imagem , Neoplasias do Mediastino/diagnóstico , Mediastino/diagnóstico por imagem , Neoplasias Pleurais/diagnóstico , Idoso , Broncoscopia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Humanos , Metástase Linfática , Masculino , Neoplasias do Mediastino/secundário , Pleura/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Acute foreign body aspiration can cause severe damage to the respiratory system, leading to laceration and even death due to asphyxia. However, a foreign body that has been aspirated could go unnoticed acutely and lead to persistent shortness of breath symptoms. Most of the patients will be able to recall the acute aspiration event, but others do not. On the latter, a more meticulous approach will lead to the diagnosis and subsequent effective management. We hereby present the case of a 52-year-old male with history of partly controlled severe asthma and chronic persistent cough with bloody sputum. Upon evaluation, he was found with a right-sided pneumonia and pertinent history remarkable for several episodes of bronchitis in the past 3 years. There circumstances and subsequent images led to the successful finding and removal of a chronic foreign body aspirated 3 years prior to evaluation. A procedure led to almost complete resolution of symptoms of cough and asthma.
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RATIONALE: Severe early-life respiratory illnesses, particularly those caused by respiratory syncytial virus (RSV) and human rhinovirus (HRV), are strongly associated with the development of asthma in children. Puerto Rican children in particular have a strikingly high asthma burden. However, prior studies of the potential associations between early-life respiratory illnesses and asthma in Puerto Rican and other minority populations have been limited. OBJECTIVES: We sought to determine whether early-life respiratory illness was associated with asthma in Puerto Rican, Mexican American, and African American children. METHODS: Using a logistic regression analysis, we examined the association between early-life respiratory illnesses (report of upper respiratory infection (URI), pneumonia, bronchitis, and bronchiolitis/RSV) within the first two years of life and physician-diagnosed asthma after the age of two in a large cohort of Puerto Rican, Mexican American, and African American children. MEASUREMENTS AND MAIN RESULTS: While early-life respiratory illnesses were associated with greater asthma odds in Puerto Ricans, Mexican Americans, and African Americans, these associations were stronger among Puerto Rican children. Specifically, in Puerto Ricans, the odds was 6.15 (95% CI: 4.21-9.05) if the child reported at least one of the following respiratory illness: URI, pneumonia, bronchitis or bronchiolitis. The odds were also higher in Puerto Ricans when considering these conditions separately. CONCLUSIONS: We observed population-specific associations between early-life respiratory illnesses and asthma, which were especially significant and stronger in Puerto Ricans. Taken together with the known high burden of RSV in Puerto Rico, our results may help explain the high burden of asthma in Puerto Ricans.
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Asma/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Americanos Mexicanos/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Adolescente , Asma/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Modelos Logísticos , Masculino , Infecções Respiratórias/complicações , Infecções Respiratórias/virologia , Estados Unidos/etnologia , Adulto JovemRESUMO
In areas where the zoonotic disease leptospirosis is endemic, reduced morbidity and mortality is strongly linked to quick initiation of renal replacement therapy.
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An 86-year-old man was found with altered mental status, fever and aphasia. His physical exam revealed nuchal rigidity but no other meningeal signs. Because the patient's mental status was declining, he was intubated and placed in mechanical ventilation. His head CT scan was unremarkable, without evidence of mass effect. A lumbar puncture yielded cerebrospinal fluid that was remarkable for the presence of gram-positive cocci in pairs. His blood cultures showed gram-negative bacilli. Given the presence of these organisms, a polymicrobial infection was suspected. An abdomino pelvic CT scan showed a multi-septated abscess within the right hepatic lobe. CT-guided percutaneous drainage was performed and a specimen for culture obtained, which grew Klebsiella pneumoniae. After receiving intravenous antibiotics and supportive care, the patient showed clinical improvement. In this patient, there was a central nervous system infection secondary to bacteremia in the setting of an intrabdominal infection. The inquiring clinician should take note that whenever a polymicrobial infection is evidenced, more than one site of infection should be considered in the differential diagnosis.
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Coinfecção/complicações , Meningites Bacterianas/complicações , Sepse/microbiologia , Idoso de 80 Anos ou mais , Coinfecção/diagnóstico , Coinfecção/tratamento farmacológico , Humanos , Masculino , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/tratamento farmacológico , Sepse/diagnóstico , Sepse/tratamento farmacológicoAssuntos
Broncopatias/etiologia , Broncopatias/terapia , Corpos Estranhos/complicações , Corpos Estranhos/cirurgia , Traqueostomia/métodos , Idoso , Antibacterianos , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/etiologia , Infecções Bacterianas/terapia , Brônquios/diagnóstico por imagem , Broncopatias/diagnóstico por imagem , Broncoscopia , Doença Crônica , Desbridamento , Corpos Estranhos/diagnóstico por imagem , Humanos , Masculino , Respiração Artificial , Instrumentos Cirúrgicos , Tomografia Computadorizada por Raios X , Traqueia/cirurgiaRESUMO
American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.
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Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Broncodilatadores/uso terapêutico , Grupos Raciais/estatística & dados numéricos , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Negro ou Afro-Americano/estatística & dados numéricos , Broncodilatadores/farmacologia , Criança , Feminino , Volume Expiratório Forçado , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Americanos Mexicanos/estatística & dados numéricos , Porto Rico/etnologia , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To document (using available data) the profile of the patients seen by the hospital's palliative service (PS) and who died in the medicine intensive care unit (ICU) of the Veterans Affairs Caribbean Healthcare System. METHODS: A record review of subjects who died in the ICU from January 1, 2012, to December 31, 2014. Demographic data, underlying comorbidities, the cause of death, the length of stay, evaluation made by the PS, and the withdrawal of life support (when such occurred) were recorded for each patient. RESULTS: A total of 200 patients met the criteria, mostly males. All the women and 50% of the men were over 79 years old. Seventy three percent of the patients were on mechanical ventilation when admitted, most having come from the emergency department. Fewer than 15% had advance directives. Forty-nine percent had been admitted to a hospital facility at least once during the year prior to their current admission. Most of the patients (60.5%) died within the first week, while 13% died within the first 24 hours. PS was requested for 56% of those who survived more than 24 hours, of which only 10% underwent the withdrawal-of-care protocol. CONCLUSION: A small percentage of the patients who died in the ICU had advance directives at the time of admission, this though all were of advanced age, had recently been discharged after a prior hospital stay, suffered from 1 or more chronic illnesses, or had a history of mental or physical disease. Our findings underscore the need for the early referral of patients of the type previously mentioned to a PS.
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Morte , Mortalidade Hospitalar , Unidades de Terapia Intensiva/estatística & dados numéricos , Cuidados Paliativos/estatística & dados numéricos , Diretivas Antecipadas , Idoso , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Suspensão de Tratamento/estatística & dados numéricosRESUMO
OBJECTIVE: Severe sepsis and Septic Shock may progress in the first hours after presentation and has been associated with an increased mortality. Prompt recognition and treatment of early septic shock (ESS) may improve survival. The purpose of our study was to describe the monitoring and management strategies of ESS, within Intensive Care Units (ICU) in Puerto Rico (PR). METHODS: In order to achieve our objective, a self-administered survey, previously validated by the Canadian Critical Care Trials Group, was administered to 25 physicians during a Critical Care Medicine (CCM) Meeting. Questions about usual monitoring and resuscitation end-points were administered. RESULTS: Most of the participants were affiliated to community hospitals (84%) and 92% were pulmonary or CCM specialists, with more than 15 years of working experience (80%). Monitoring devices and parameters mostly used by at least 85% of the respondents were: Oxygen Saturation, Foley catheters, Telemetry, Heart Rate, Blood Pressure, and Urinary Output. Intra-arterial lines and Central Venous Pressure were less used. Most use normal saline (96%), as the initial fluid of resuscitation. Only 24% would use inotropes to improve perfusion. CONCLUSION: Significant variability exists in the management of ESS among physicians in the ICU in PR. Compared to other studies, fewer physicians in PR use invasive monitoring techniques. These results highlight the need for quality education and training in CCM as well as continuing education in the field.
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Cuidados Críticos/métodos , Médicos/estatística & dados numéricos , Ressuscitação/métodos , Choque Séptico/terapia , Adulto , Cuidados Críticos/estatística & dados numéricos , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Porto Rico , Ressuscitação/estatística & dados numéricosRESUMO
BACKGROUND: Acculturation is an important predictor of asthma in Latino youth, specifically Mexican Americans. Less is known about acculturation and pulmonary function measures. OBJECTIVE: We sought to estimate the association of acculturation measures with asthma and pulmonary function in Latino youth and determine whether this association varies across Latino subgroups. METHODS: We included 1849 Latinos (302 Caribbean Spanish, 193 Central or South Americans, 1136 Mexican Americans, and 218 other Latino children) aged 8 to 21 years from 4 urban regions in the United States. Acculturation measures include nativity status, age of immigration, language of preference, and generation in the United States. We used multivariable logistic and linear regression models to quantify the association of acculturation factors with the presence of asthma (case-control study) and pulmonary function (case-only study), adjusting for demographic, socioenvironmental, and clinical variables. RESULTS: For all acculturation measures (nativity status, age of immigration, language of preference, and generation in the United States), greater levels of acculturation were associated with greater odds of asthma. Among cases, high (English preference) and medium (equal preference for Spanish and English) levels of language acculturation were associated with decreased bronchodilator response compared with low (Spanish preference) levels (P = .009 and .02, respectively). Similarly, high language acculturation was associated with increased FEV1 compared with low language acculturation (P = .02). There was insufficient evidence of heterogeneity for associations across Latino subgroups. CONCLUSIONS: Acculturation was associated with diagnosed asthma and pulmonary function in Latino children and is an important factor to consider in the management of Latino youth with asthma.
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Aculturação , Asma/etnologia , Asma/epidemiologia , Hispânico ou Latino , Adolescente , Adulto , Asma/fisiopatologia , Estudos de Casos e Controles , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND: Inhaled corticosteroids (ICS) are the most widely prescribed and effective medication to control asthma symptoms and exacerbations. However, many children still have asthma exacerbations despite treatment, particularly in admixed populations, such as Puerto Ricans and African Americans. A few genome-wide association studies (GWAS) have been performed in European and Asian populations, and they have demonstrated the importance of the genetic component in ICS response. OBJECTIVE: We aimed to identify genetic variants associated with asthma exacerbations in admixed children treated with ICS and to validate previous GWAS findings. METHODS: A meta-analysis of two GWAS of asthma exacerbations was performed in 1347 admixed children treated with ICS (Hispanics/Latinos and African Americans), analysing 8.7 million genetic variants. Those with P ≤ 5 × 10-6 were followed up for replication in 1697 asthmatic patients from six European studies. Associations of ICS response described in published GWAS were followed up for replication in the admixed populations. RESULTS: A total of 15 independent variants were suggestively associated with asthma exacerbations in admixed populations (P ≤ 5 × 10-6 ). One of them, located in the intergenic region of APOBEC3B and APOBEC3C, showed evidence of replication in Europeans (rs5995653, P = 7.52 × 10-3 ) and was also associated with change in lung function after treatment with ICS (P = 4.91 × 10-3 ). Additionally, the reported association of the L3MBTL4-ARHGAP28 genomic region was confirmed in admixed populations, although a different variant was identified. CONCLUSIONS AND CLINICAL RELEVANCE: This study revealed the novel association of APOBEC3B and APOBEC3C with asthma exacerbations in children treated with ICS and replicated previously identified genomic regions. This contributes to the current knowledge about the multiple genetic markers determining responsiveness to ICS which could lead in the future the clinical identification of those asthma patients who are not able to respond to such treatment.