Defining and Improving Outcomes Measurement for Virtual Care: Report from the VHA State-of-the-Art Conference on Virtual Care.

Virtual care, including synchronous and asynchronous telehealth, remote patient monitoring, and the collection and interpretation of patient-generated health data (PGHD), has the potential to transform healthcare delivery and increase access to care. The Veterans Health Administration (VHA) Office of Health Services Research and Development (HSR&D) convened a State-of-the-Art (SOTA) Conference on Virtual Care to identify future virtual care research priorities. Participants were divided into three workgroups focused on virtual care access, engagement, and outcomes. In this article, we report the findings of the Outcomes Workgroup. The group identified virtual care outcome areas with sufficient evidence, areas in need of additional research, and areas that are particularly well-suited to be studied within VHA. Following a rigorous process of literature review and consensus, the group focused on four questions: (1) What outcomes of virtual care should we be measuring and how should we measure them?; (2) how do we choose the "right" care modality for the "right" patient?; (3) what are potential consequences of virtual care on patient safety?; and (4) how can PGHD be used to benefit provider decision-making and patient self-management?. The current article outlines key conclusions that emerged following discussion of these questions, including recommendations for future research.

Chronic Disease Management through Clinical Video Telehealth on Health Care Utilization, and Mortality in the Veterans Health Administration: A Retrospective Cohort Study.

Background: Chronic health diseases such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) affect 6 in 10 Americans and contribute to 90% of the $4.1 trillion health care expenditures. The objective of this study was to measure the effect of clinical video telehealth (CVT) on health care utilization and mortality. A retrospective cohort study of Veterans ≥65 years with CHF, COPD, or DM was conducted. Measures: Veterans using CVT were matched 1:3 on demographic characteristics to Veterans who did not use CVT. Outcomes included 1-year incidence of ED visits, inpatient admissions, and mortality, reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Final analytical cohorts included 22,280 Veterans with CHF, 51,872 Veterans with COPD, and 170,605 Veterans with DM. CVT utilization was associated with increased ED visits for CHF (aOR: 1.24; 95% CI: 1.15-1.34), COPD (aOR: 1.20; 95% CI: 1.14-1.26), and DM (aOR: 1.07; 95% CI: 1.00-1.10). For CHF, there was no difference between CVT utilization and inpatient admissions (aOR: 0.98; 95% CI 0.91-1.05) or mortality (aOR: 1.03; 95% CI: 0.93-1.15). For COPD, CVT was associated with increased inpatient admissions (aOR: 1.08; 95% CI: 1.02-1.13) and mortality (aOR: 1.36; 95% CI: 1.25-1.48). For DM, CVT utilization was associated with lower risk of inpatient admissions (aOR: 0.83; 95% CI: 0.80-0.86) and mortality (aOR: 0.89; 95% CI: 0.84-0.95). Conclusions: CVT use as an alternative care site might serve as an early warning system, such that this mechanism may indicate when an in-person assessment is needed for potential exacerbation of conditions. Although inpatient and mortality varied, ED utilization was higher with CVT. Exploring pathways accessing clinical care through CVT, and how CVT is directly or indirectly associated with immediate and long-term clinical outcomes would be valuable.

Effect of Chronic Disease Home Telehealth Monitoring in the Veterans Health Administration on Healthcare Utilization and Mortality.

BACKGROUND: The high prevalence of chronic diseases, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM), accounts for a large burden of cost and poor health outcomes in US hospitals, and home telehealth (HT) monitoring has been proposed to improve outcomes. OBJECTIVE: To measure the association between HT initiation and 12-month inpatient hospitalizations, emergency department (ED) visits, and mortality in veterans with CHF, COPD, or DM. DESIGN: Comparative effectiveness matched cohort study. PATIENTS: Veterans aged 65 years and older treated for CHF, COPD, or DM. MAIN MEASURES: We matched veterans initiating HT with veterans with similar demographics who did not use HT (1:3). Our outcome measures included a 12-month risk of inpatient hospitalization, ED visits, and all-cause mortality. KEY RESULTS: A total of 139,790 veterans with CHF, 65,966 with COPD, and 192,633 with DM were included in this study. In the year after HT initiation, the risk of hospitalization was not different in those with CHF (adjusted odds ratio [aOR] 1.01, 95% confidence interval [95%CI] 0.98-1.05) or DM (aOR 1.00, 95%CI 0.97-1.03), but it was higher in those with COPD (aOR 1.15, 95%CI 1.09-1.21). The risk of ED visits was higher among HT users with CHF (aOR 1.09, 95%CI 1.05-1.13), COPD (1.24, 95%CI 1.18-1.31), and DM (aOR 1.03, 95%CI 1.00-1.06). All-cause 12-month mortality was lower in those initiating HT monitoring with CHF (aOR 0.70, 95%CI 0.67-0.73) and DM (aOR 0.79, 95%CI 0.75-0.83), but higher in COPD (aOR 1.08, 95%CI 1.00-1.16). CONCLUSIONS: The initiation of HT was associated with increased ED visits, no change in hospitalizations, and lower all-cause mortality in patients with CHF or DM, while those with COPD had both higher healthcare utilization and all-cause mortality.

Perceived Need and Potential Applications of a Telehospitalist Service in Rural Areas.

Background: Rural hospitals struggle to staff inpatient services and may not have the clinical expertise to achieve optimal outcomes. Telehospitalist services could address these problems by bringing hospital medicine expertise to rural communities. Introduction: Veterans Health Administration (VHA) rural hospitals need staffing alternatives to address gaps in inpatient coverage. This needs assessment identified perceived need for telehospitalist services as well as potential applications, benefits, and barriers from an administration perspective. Materials and Methods: We used a rapid qualitative assessment approach based on semistructured interviews with 15 physician administrators at 12 rural and low-complexity hospitals in VHA in 2018. Results: We identified a range of needs that could be addressed by telehospitalist services, including direct care delivery, support for local providers, and on-demand coverage to fill staffing gaps. Potential benefits included cost reductions, improved care quality, education, and addressing feelings of insular practice. Potential barriers included provider buy-in, cost, and technological limitations. Discussion: Our findings suggest that telehospitalist services could address inpatient coverage gaps, but with a range of views on how the service could be deployed. Telehospitalist services providing intermittent coverage could meet unmet clinical needs at appropriate economies of scale. Administrators were enthusiastic about applying innovative inpatient telemedicine initiatives, but perceived staff reluctance. The dynamic and multidisciplinary nature of inpatient care requires program acceptance at multiple levels, which may account for why it traditionally lags behind outpatient telemedicine. Conclusions: Rural hospital physician administrators perceived telehospitalist models as a viable option to address staffing needs and improve quality of care.

Leveraging Policy Solutions for Diabetes Disparities: Suggestions for Improving the National Clinical Care Commission Report's Recommendations for Hispanic/Latino Populations.

In the U.S., Hispanic/Latino populations face increased disparities in both the prevalence and management of type 2 diabetes mellitus (T2DM). This article critically examines the multifaceted nature of T2DM disparities among Hispanic/Latino populations in the U.S. and identifies key factors contributing to T2DM prevalence within these communities, including socioeconomic status, cultural influences, and healthcare access. Utilizing a modified expert consensus procedure, we evaluate the ways in which the National Clinical Care Commission (NCCC) recommendations apply to the Hispanic/Latino community as well as propose recommendations for improved efficacy. Through a comprehensive analysis of government-community health initiatives, food security, environmental exposures, and housing inequalities, we emphasize the need for targeted interventions and health policies to effectively address and dismantle these disparities. Overall, while the National Clinical Care Commission's recommendations provide a valuable framework for the implementation of policies pertaining to diabetes management and prevention in the general population, our analysis suggests that recommendations may be strengthened by considering the unique cultural, social, and economic needs of the Hispanic/Latino population moving forward.

Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study.

BACKGROUND: Alcohol withdrawal is a common reason for admission to acute care hospitals. Prescription of medications for alcohol-use disorder (AUD) and close outpatient follow-up are commonly recommended, but few studies report their effects on postdischarge outcomes. OBJECTIVES: The objective of this study is to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence. METHODS: This retrospective cohort study evaluated veterans admitted for alcohol withdrawal to medical services at 19 Veteran Health Administration hospitals between October 1, 2018 and September 30, 2019. Factors associated with all-cause 30-day readmission and 6-month abstinence were examined using logistic regression. RESULTS: Of the 594 patients included in this study, 296 (50.7%) were prescribed medications for AUD at discharge and 459 (78.5%) were discharged with follow-up appointments, including 251 (42.8%) with a substance-use clinic appointment, 191 (32.9%) with a substance-use program appointment, and 73 (12.5%) discharged to a residential program. All-cause 30-day readmission occurred for 150 patients (25.5%) and 103 (17.8%) remained abstinent at 6 months. Medications for AUD and outpatient discharge appointments were not associated with readmission or abstinence. Discharge to residential treatment program was associated with reduced 30-day readmission (adjusted odds ratio [AOR]: 0.39, 95% confidence interval [95% CI]: 0.18-0.82) and improved abstinence (AOR: 2.50, 95% CI: 1.33-4.73). CONCLUSIONS: Readmission and return to heavy drinking are common for patients discharged for alcohol withdrawal. Medications for AUD were not associated with improved outcomes. The only intervention at the time of discharge that improved outcomes was discharge to residential treatment program, which was associated with decreased readmission and improved abstinence.

Contemporary Management and Outcomes of Veterans Hospitalized With Alcohol Withdrawal: A Multicenter Retrospective Cohort Study.

OBJECTIVES: Few studies describe contemporary alcohol withdrawal management in hospitalized settings or review current practices considering the guidelines by the American Society of Addiction Medicine (ASAM). METHODS: We conducted a retrospective cohort study of patients hospitalized with alcohol withdrawal on medical or surgical wards in 19 Veteran Health Administration (VHA) hospitals between October 1, 2018, and September 30, 2019. Demographic and comorbidity data were obtained from the Veteran Health Administration Corporate Data Warehouse. Inpatient management and hospital outcomes were obtained by chart review. Factors associated with treatment duration and complicated withdrawal were examined. RESULTS: Of the 594 patients included in this study, 51% were managed with symptom-triggered therapy alone, 26% with fixed dose plus symptom-triggered therapy, 10% with front loading regimens plus symptom-triggered therapy, and 3% with fixed dose alone. The most common medication given was lorazepam (87%) followed by chlordiazepoxide (33%), diazepam (14%), and phenobarbital (6%). Symptom-triggered therapy alone (relative risk [RR], 0.68; 95% confidence interval [CI], 0.57-0.80) and front loading with symptom-triggered therapy (RR, 0.75; 95% CI, 0.62-0.92) were associated with reduced treatment duration. Lorazepam (RR, 1.20; 95% CI, 1.02-1.41) and phenobarbital (RR, 1.28; 95% CI, 1.06-1.54) were associated with increased treatment duration. Lorazepam (adjusted odds ratio, 4.30; 95% CI, 1.05-17.63) and phenobarbital (adjusted odds ratio, 6.51; 95% CI, 2.08-20.40) were also associated with complicated withdrawal. CONCLUSIONS: Overall, our results support guidelines by the ASAM to manage patients with long-acting benzodiazepines using symptom-triggered therapy. Health care systems that are using shorter acting benzodiazepines and fixed-dose regimens should consider updating alcohol withdrawal management pathways to follow ASAM recommendations.

Telemental health in emergency care settings: A qualitative analysis of considerations for sustainability and spread.

OBJECTIVES: Following rapid uptake of telehealth during the COVID-19 pandemic, we examined barriers and facilitators for sustainability and spread of telemental health video (TMH-V) as policies regarding precautions from the pandemic waned. METHODS: We conducted a qualitative study using semistructured interviews and observations guided by RE-AIM. We asked four groups, local clinicians, facility leadership, Veterans, and external partners, about barriers and facilitators impacting patient willingness to engage in TMH-V (reach), quality of care (effectiveness), barriers and facilitators impacting provider uptake (adoption), possible adaptations to TMH-V (implementation), and possibilities for long-term use of TMH-V (maintenance). Interviews were recorded, transcribed, and analyzed using framework analysis. We also observed TMH-V encounters in one emergency department (ED) and one urgent care (UC) to understand how clinicians and Veterans engaged with the technology. RESULTS: We conducted 35 interviews with ED/UC clinicians and staff (n = 10), clinical and facility leadership (n = 7), Veterans (n = 5), and external partners (n = 13), January-May 2022. We completed 10 observations. All interviewees were satisfied with the TMH-V program, and interviewees highlighted increased comfort discussing difficult topics for Veterans (reach). Clinicians identified that TMH-V allowed for cross-coverage across sites as well as increased safety and flexibility for clinicians (adoption). Opportunities for improvement include alleviating technological burdens for on-site staff, electronic health record (EHR) modifications to accurately capture workload and modality (telehealth vs. in-person), and standardizing protocols to streamline communication between on-site and remote clinical staff (implementation). Finally, interviewees encouraged its spread (maintenance) and thought there was great potential for service expansion. CONCLUSIONS: Interviewees expressed support for continuing TMH-V locally and spread to other sites. Ensuring adequate infrastructure (e.g., EHR integration and technology support) and workforce capacity are key for successful spread. Given the shortage of mental health (MH) clinicians in rural settings, TMH-V represents a promising intervention to increase the access to high-quality emergency MH care.

A systematic review of telehealth applications in hospital medicine.

BACKGROUND: Despite the proliferation of telehealth, uptake for acute inpatient services has been slower. Hospitalist shortages in rural and critical access hospitals as well as the COVID-19 pandemic have led to a renewed interest in telehealth to deliver acute inpatient services. Understanding current evidence is crucial for promoting uptake and developing evidence-based practices. OBJECTIVE: To conduct a systematic review of telehealth applications in acute inpatient general medicine and pediatric hospital wards and synthesize available evidence. DATA SOURCES: A search of five databases (PubMed, CINAHL, Embase, Scopus, and ProQuest Theses, and Dissertations) using a combination of search terms including telemedicine and hospital medicine/inpatient care keywords yielded 17,015 citations. STUDY SELECTION AND DATA EXTRACTION: Two independent coders determined eligibility based on inclusion and exclusion criteria. Data were extracted and organized into main categories based on findings: (1) feasibility and planning, (2) implementation and technology, and (3) telehealth application process and outcome measures. RESULTS: Of the 20 publications included, three were feasibility and planning studies describing the creation of the program, services provided, and potential cost implications. Five studies described implementation and technology used, including training, education, and evaluation methods. Finally, twelve discussed process and outcome measures, including patient and provider satisfaction and costs. CONCLUSION: Telehealth services for hospital medicine were found to be effective, well received, and initial cost estimates appear favorable. A variety of services were described across programs with considerable benefit appreciated by rural and smaller hospitals. Additional work is needed to evaluate clinical outcomes and overall program costs.

Implementing a Telehospitalist Program Between Veterans Health Administration Hospitals: Outcomes, Acceptance, and Barriers to Implementation.

BACKGROUND: Telehospitalist services are an innovative alternative approach to address staffing issues in rural and small hospitals. OBJECTIVE: To determine clinical outcomes and staff and patient satisfaction with a novel telehospitalist program among Veterans Health Administration (VHA) hospitals. DESIGN, SETTING, AND PARTICIPANTS: We conducted a mixed-methods evaluation of a quality improvement program with pre- and postimplementation measures. The hub site was a tertiary (high-complexity) VHA hospital, and the spoke site was a 10-bed inpatient medical unit at a rural (low-complexity) VHA hospital. All patients admitted during the study period were assigned to the spoke site. INTERVENTION: Real-time videoconferencing was used to connect a remote hospitalist physician with an on-site advanced practice provider and patients. Encounters were documented in the electronic health record. MAIN OUTCOMES: Process measures included workload, patient encounters, and daily census. Outcome measures included length of stay (LOS), readmission rate, mortality, and satisfaction of providers, staff, and patients. Surveys measured satisfaction. Qualitative analysis included unstructured and semi-structured interviews with spoke-site staff. RESULTS: Telehospitalist program implementation led to a significant reduction in LOS (3.0 [SD, 0.7] days vs 2.3 [SD, 0.3] days). The readmission rate was slightly higher in the telehospitalist group, with no change in mortality rate. Satisfaction among teleproviders was very high. Hub staff perceived the service as valuable, though satisfaction with the program was mixed. Technology and communication challenges were identified, but patient satisfaction remained mostly unchanged. CONCLUSION: Telehospitalist programs are a feasible and safe way to provide inpatient coverage and address rural hospital staffing needs. Ensuring adequate technological quality and addressing staff concerns in a timely manner can enhance program performance.

[Vasoconstriction is required for edema of contralateral lung after reperfusion injury of one lung]. / Edema pulmonar contralateral secundario al daño por isquemia-reperfusión de un pulmón. Papel de la vasoconstricción arterial pulmonar.

Ischemia-reperfusion (IR) lung injury is a significant cause of morbidity and mortality in certain clinical scenarios that include transplantation, thromboendarterectomy and reexpansion injury of the lung. Edema of the contralateral lung after IR injury of one lung has been reported and this study was aimed to clarify the pathophysiology of this phenomenon. One-lung ischemia/hypoxia followed by reperfusion with either blood or an acellular plasma substitute was achieved in an isolated rabbit lung model by hilum clamping. After reperfusion, we studied the isolated effects of vasoconstriction and inflammation on contralateral lung injury by using papaverine or hydrocortisone as vasodilator and anti-inflammatory, respectively. We observed that IR of one lung induces edema of the contralateral lung. Absence of leukocytes and platelets in the perfusate or use of hydrocortisone completely inhibits IR injury. Moreover, papaverine suppresses edema of the contralateral, but not that of the reperfused lung. We concluded that IR of one lung produces edema in the contralateral lung that requires vasoconstriction of the latter.

Perceptions of Telehospitalist Services to Address Staffing Needs in Rural and Low Complexity Hospitals in the Veterans Health Administration.

PURPOSE: Rural hospitals are disproportionally affected by physician shortages and struggle to staff inpatient services. Telemedicine presents an opportunity to address staffing problems and bring the advantages of hospital medicine to rural areas. METHODS: In this study we surveyed administrators from 34 rural and low complexity hospitals in the Veterans Health Administration (VHA) to evaluate staffing needs and perceptions of a potential telehospitalist service. FINDINGS: Of the 25 respondent facilities (74% response rate), 96% reported vacancies that resulted in staffing difficulties within the last 3 years and 84% relied on intermittent providers to staff their inpatient services in the last year. Almost two-thirds of respondents thought that a telehospitalist service could help address their staffing needs and 72% were interested in participating in a pilot program. CONCLUSIONS: The results of this study corroborate staffing challenges in rural hospitals within VHA and support the use of alternative staffing models like a telehospitalist service to address intermittent and long-term staffing needs.

Sleep disturbances in HIV-infected patients associated with depression and high risk of obstructive sleep apnea.

OBJECTIVE: To evaluate sleep disturbances in a diverse, contemporary HIV-positive patient cohort and to identify demographic, clinical, and immune correlates. METHODS: A convenience sample of 176 patients from a racially and ethnically diverse HIV-positive patient cohort in an urban population. This was a cross-sectional, epidemiologic study. We surveyed participants using multiple standardized instruments to assess depression, sleep quality, and risk for sleep apnea. We analyzed demographic, behavioral, and clinical correlates. RESULTS: A total of 56% of participants were female, 75% Black and 64% had heterosexual HIV risk. The median age was 49 years. Poor sleep quality (Pittsburgh Sleep Quality Index > 5) was reported by 73% of patients and 52% met insomnia diagnosis criteria. A single question about self-reported sleep problems predicted a Pittsburgh Sleep Quality Index > 5 with a sensitivity and specificity of 82% and 81%, respectively. Female sex was significantly associated with higher risk of poor sleep quality, depression, and insomnia, whereas higher risk of obstructive sleep apnea was significantly associated with older age, male sex, obesity (body mass index ⩾ 30 kg/m2), and metabolic comorbidities. High risk for obstructive sleep apnea, high rate of depression, and poor sleep hygiene represent treatment targets for sleep problems in HIV patients. CONCLUSION: Sleep disturbances were common in this patient cohort, although largely undiagnosed and untreated. Sleep problems are linked to worse disease progression and increased cardiovascular mortality. Screening for sleep problems with a single question had high sensitivity and specificity. In those patients with self-reported sleep problems, screening for obstructive sleep apnea, depression, and sleep hygiene habits should be part of routine HIV care.

[Effect of hypocapnia/alkalosis on the fluid filtration rate in isolated and perfused rabbit lungs]. / Efecto de la hipocapnia/alcalosis sobre la tasa de filtración de liquidos en pulmones aislados y perfundidos de conejos.

Hypocapnia/alkalosis is a consequence of several lung and metabolic pathologies. The aim of this study was to determine whether the increase of fluid filtration rate (FFR) that occurs during Hypocapnia/alkalosis circumstances is determined by hypocapnia, alkalosis or both. 7 groups were formed (N=36) using isolated rabbit lungs. Group 1: Control (PCO2 6%, pH: 7.35-7.45); Group 2 (n=6): Hypocapnia/Alkalosis (CO2 1%, pH: 7.9); Group 3 (n=6): Hypocapnia/Normo-pH (CO2 1% pH 7.35-7.45), Group 4 (n=6) Normocapnia/Alcalosis (CO2 6%, pH: 7.9). Fenoterol, papaverine and hydrocortisone were added to Groups 5, 6 and 7 (n=4) respectively, all under Normocapnia/Alkalosis. FFR and Pulmonary Arterial Pressure (Pap) were considerably higher in group 2 than in control (FFR: 1.92g/min +/- 0.6 vs 0.0 g/min +/- 0.006). A strong influence exerted by pH was observed when Group 3 and group 4 were compared (FFR: 0.02 g/min +/- 0.009 vs 2.3 g/min +/- 0.9) and (Pap: 13.5 cmH2O +/- 1.4 vs 90 cmH2O +/- 15). A reduced effect was observed in groups 5 and 6 (papaverine and hydrocorisone) and a totally abolished effect was observed in group 7 (fenoterol) (FFR: 0.001 +/- 0.0003 mL/min and Pap: 14 +/- 0.8 cmH2O). Pulmonary edema induced by Hypocapnia/alkalosis is a consequence of alkalosis and not of hypocapnia. This effect could be due to inflammatory damage in the lung parenchyma and alkalosis-mediated vasoconstriction.

A Novel non-sense Mutation in Keratin 10 Causes a Familial Case of Recessive Epidermolytic Ichthyosis.

Epidermolytic ichthyosis (EI) is a rare skin disorder characterized by generalized erythroderma and cutaneous blistering at birth, which is substituted by hyperkeratosis later in life. It is caused by autosomal dominant mutations in highly conserved regions of KRT1 and KRT10. To date, only 4 mutations with autosomal recessive inheritance of EI have been described in consanguineous families. All of them affect the 2B domain of KRT10. In the present study we describe four patients with EI (including one lethal case) born from unaffected parents in a consanguineous family of a native Venezuelan community. The objective of this study was to characterize the clinical, genetic and morphological aspects of the disease in this family, as well as understand its functional implications. Genomic DNA was sequenced for KRT10 and KRT1. Immunofluoresence for keratin expression was performed on cutaneous biopsies. After examination of cutaneous biopsies histology, our results showed hyperkeratosis and acantholysis with an expanded granular layer. Sequencing of KRT10 demonstrated a non-sense mutation (p.Tyr282Ter.) corresponding to the 1B domain of the protein in patients and a heterozygous pattern in other family members, resulting in complete absence of K10. The loss of K10 was compensated by upregulation of K14 and K17. In conclusion, this novel mutation in KRT10 is the first recessive genetic variation that is not located in the so called "hot spot" for recessive EI, suggesting that other areas of the gene are also susceptible for such mutations.

Glucose depletion in the airway surface liquid is essential for sterility of the airways.

Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources--including glucose--in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.

Beneficial effects of hydrocortisone and papaverine on a model of pulmonary embolism induced by autologous blood clots in isolated and perfused rabbit lungs.

BACKGROUND AND OBJECTIVE: Mechanical obstruction has been considered the prime determinant of haemodynamic changes after pulmonary embolism (PE); however, the function of vasoconstrictive and inflammatory mediators in the physiopathology of this disease is unclear. The aim of this investigation was to study the effect of an anti-inflammatory and a vasodilator in a setting of induced PE. METHODS: A prospective, laboratory study was undertaken using 30 New Zealand white rabbits. A model of isolated and perfused rabbit lungs was used; PE was induced using autologous blood clots. Six study groups were established (each n = 5): PE without any drug (PG); PE + papaverine (PpG); PE + hydrocortisone (HG); PE in West's Zone III (ZIIIG); PE using acellular perfusate (AG) and PE using acellular perfusate + papaverine (APpG). The pulmonary artery pressure (PAP) and fluid filtration rate (FFR) were continuously measured during the experiments. RESULTS: Increases in PAP and oedema formation were observed in the PG after embolization. The PpG and the APpG showed neither oedema nor significant PAP increases. The HG group developed less oedema and less increase in PAP compared with the PG. The ZIIIG developed oedema the fastest. The AG developed less oedema and increases in PAP compared with the PG. CONCLUSION: These findings suggest that vasoconstriction and inflammatory mediators play an important role in the physiopathology of PE, as neither PAP increases nor oedema were observed in the PpG and a reduction of oedema and PAP was seen in the HG group. The decrease in oedema and PAP in the acellular group strongly suggests a key role of circulating blood cells.

Edema pulmonar contralateral secundario al daño por isquemia-reperfusión de un pulmón: papel de la vasoconstricción arterial pulmonar / Vasoconstriction is required for edema of contralateral lung after reperfusion injury of one lung

El daño pulmonar por isquemia-reperfusión (IR) es una importante causa de morbilidad y mortalidad en ciertas condiciones clínicas que incluyen trasplantes, tromboendarterectomía y daño pulmonar por reexpansión. El edema pulmonar contralateral posterior al daño por IR de un pulmón ha sido reportado y esta investigación tiene como objetivo esclarecer la fisiopatología de dicho fenómeno. En un modelo de pulmones aislados y perfundidos de conejo, fue ocluido el hilio pulmonar de forma unilateral induciendo isquemia/hipoxia de dicho órgano, seguido de reperfusiones con sangre o con un substituto plasmático acelular. Los efectos aislados de vasoconstricción e inflamación en el daño pulmonar contralateral fueron estudiados posterior a la reperfusión, usando papaverina e hidrocortisona como agente vasodilatador y antiinflamatorio, respectivamente. En esta investigación se observó que la IR de un pulmón induce edema en el pulmón contralateral. La ausencia de leucocitos y plaquetas en la perfusión y el uso de hidrocortisona inhibió por completo el daño por IR. La papaverina suprimió el edema en el pulmón contralateral mas no en el reperfundido. Se concluye que la IR de un pulmón produce edema en el pulmón contralateral, para lo cual se requiere la presencia de vasoconstricción.

Ischemia-reperfusion (IR) lung injury is a significant cause of morbidity and mortality in certain clinical scenarios that include transplantation, thromboendarterectomy and reexpansion injury of the lung. Edema of the contralateral lung after IR injury of one lung has been reported and this study was aimed to clarify the pathophysiology of this phenomenon. One-lung ischemia/hypoxia followed by reperfusion with either blood or an acellular plasma substitute was achieved in an isolated rabbit lung model by hilum clamping. After reperfusion, we studied the isolated effects of vasoconstriction and inflammation on contralateral lung injury by using papaverine or hydrocortisone as vasodilator and anti-inflammatory, respectively. We observed that IR of one lung induces edema of the contralateral lung. Absence of leukocytes and platelets in the perfusate or use of hydrocortisone completely inhibits IR injury. Moreover, papaverine suppresses edema of the contralateral, but not that of the reperfused lung. We concluded that IR of one lung produces edema in the contralateral lung that requires vasoconstriction of the latter.