Kenneth Nugent

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator used as rescue therapy in acute respiratory distress syndrome (ARDS) for transient improvement in oxygenation. Although multiple studies demonstrate improvements in oxygenation parameters, iNO has not consistently shown a mortality benefit or reduced ventilation duration. Methods: A retrospective cohort study was conducted of mechanically ventilated adults with SARS-CoV-2 (COVID-19) admitted to a medical intensive care unit who received iNO. Demographic characteristics, comorbidities, illness severity scores, timing of iNO initiation, and clinical outcomes were analyzed, with comparisons made between survivors and non-survivors. Results: A total of 94 patients were included. The mean age was 52.0 years (Standard Deviation (SD) 14.1), 70.2% were male, and the mean body mass index was 36.5 kg/m² (SD 10.0). Hypertension (58.5%) and diabetes (36.2%) were the most common comorbidities. The mean Sequential Organ Failure Assessment (SOFA) score was 4.22 (SD 2.79), and the mean Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 11.69 (SD 6.98). Overall, in-hospital mortality was 85.1% (80/94). The median time from intubation to iNO initiation was 7.6 days (mean 7.7 days). Survivors received iNO significantly earlier than non-survivors (mean 4.14 vs. 8.3 days after intubation, p = 0.024) and had a longer hospital length of stay (mean 37 vs. 23 days, p < 0.01). Duration of iNO therapy did not differ between groups (p = 0.12). Conclusions: In this cohort of critically ill patients with COVID-19 and severe respiratory failure, overall mortality was extremely high. Earlier initiation of inhaled nitric oxide was associated with improved survival, whereas duration of therapy was not. These findings suggest that the timing of iNO administration may be associated with clinical outcomes and warrant further prospective investigation to confirm this association.

Background and Objective: Military personnel serving in Southwest Asia have had frequent exposure to fumes from burn pits. These pits provide a crude way to eliminate waste, including unused food, chemicals, plastic, etc. These exposures can have toxic effects on the respiratory system and other organ systems. This review will provide an overview of the toxic effects of burn pits on the respiratory system and the health of military personnel. Methods: The PubMed database was searched using the terms military medical, military burn pit AND dyspnea OR deployment OR respirator OR toxicity. All articles used in this review were published in English and after 1980. Key Content and Findings: Thousands of military personnel have been exposed to burn pits during their service in Afghanistan and Iraq. Some of these exposures have resulted in adverse health effects, including new or increased respiratory symptoms. Some service members underwent comprehensive evaluations that included lung biopsies. Fumes from burn pits can damage the epithelial surfaces. The most important factors in this damage include the type of exposure, the temperature of the burn pit, and the duration of exposure. Conclusions: Exposure to burn pit fumes can have toxic effects on the respiratory system and other organ systems, such as the kidney. This review outlines these concerns and provides resources the reader can use to develop more information or to design studies related to these ideas, or to help manage patients in their military clinics. The military needs to perform longitudinal studies to learn the natural history of these respiratory symptoms.

Background: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator used as rescue therapy in acute respiratory distress syndrome (ARDS) for transient improvement in oxygenation. Although multiple studies demonstrate improvements in oxygenation parameters, iNO has not consistently shown a mortality benefit or reduction in the duration of ventilation[1]. Methods: We conducted a retrospective cohort study of mechanically ventilated adults with COVID-19 admitted to a medical intensive care unit who received iNO. Demographic characteristics, comorbidities, illness severity scores, timing of iNO initiation, and clinical outcomes were analyzed, with comparisons made between survivors and non-survivors. Results: A total of 94 patients were included. The mean age was 52.0 years (SD 14.1), 70.2% were male, and mean body mass index was 36.5 kg/m² (SD 10.0). Hypertension (58.5%) and diabetes (36.2%) were the most common comorbidities. Mean SOFA score was 4.22 (SD 2.79), and mean APACHE II score was 11.69 (SD 6.98). Overall, in-hospital mortality was 85.1% (80/94). The median time from intubation to iNO initiation was 7.6 days. Survivors received iNO significantly earlier than non-survivors (mean 4.14 vs 8.3 days after intubation, p = 0.024) and had a longer hospital length of stay (mean 37 vs 23 days, p < 0.01). Duration of iNO therapy did not differ between groups (p = 0.12). Conclusion: In this cohort of critically ill patients with COVID-19 and severe respiratory failure, overall mortality was extremely high. Earlier initiation of inhaled nitric oxide was associated with improved survival, whereas duration of therapy was not. These findings suggest that the timing of iNO administration may be an important determinant of outcomes and warrant further prospective investigation.

Background: Chronic obstructive pulmonary disease (COPD) is increasing in prevalence in our aging population in the United States, contributing to morbidity and mortality. Chronic obstructive pulmonary disease and osteoporosis have significant overlapping pathogenic risk factors, including smoke exposure, a chronic inflammatory state, poor nutritional status, immobility, and chronic steroid exposure. This study determines the use of DEXA screening, the prevalence of fragility fractures, and prescription and the use of antiresorptive medications for treatment of osteoporosis and osteopenia in patients with COPD. Methods: A retrospective chart review of patients at our health sciences center, including both clinics and hospital, was performed based on ICD-10 codes for COPD, chronic steroid use, and chronic oxygen support in the Cerner database from 2019 to 2023. Exclusion criteria included preexisting or alternative primary lung disease and/or cancer or if further chart review excluded them for not having severe COPD (FEV1 <50%) or not requiring oxygen therapy. Results: One hundred seventy-one patients of the original 203 enrolled patients qualified for further analysis after thorough review of charts for confounding diagnosis, lack of oxygen therapy, or lack of formal COPD diagnosis. Forty-one (24%) were screened for osteopenia/osteoporosis using DEXA screening. Of those, 18 (43%) had osteopenia, and 18 (43%) had osteoporosis. Of the 171 eligible patients enrolled in the analysis, 59 (35%) had a fragility fracture. Patients on both inhaled and oral systemic steroids had the highest fracture rate (39%). Overall, 14% (24/171) of patients received treatment for osteopenia/osteoporosis using antiresorptive medications. Treatment rates varied among those receiving steroids versus those who did not. Of the screened group, only 8/18 (44%) patients with osteopenia and 7/18 (39%) patients with osteoporosis received treatment. Conclusion: This study demonstrates the patients with severe COPD, based on oxygen requirements and/or the use of corticosteroids, do not have adequate screening for osteopenia and/or osteoporosis. This screening could lead to antiresorptive drug treatment and reduce the morbidity and mortality associated with osteoporotic and osteopenia fractures.

Introduction: Hypertension is an important risk factor for myocardial infarction, stroke, peripheral arterial disease, and chronic kidney disease. The World Health Organization has determined that approximately 1.28 billion adults worldwide have high blood pressure. Its definition has changed over the years, and in 2017 the American College of Cardiology and the American Heart Association have defined blood pressures ≥ 130/80 mmHg as hypertension. Methods: The PubMed database was searched using the MeSH terms sodium, capillary resistance, hypertension, and microvascular rarefaction to identify articles relevant to skin sodium levels, peripheral circulations and vascular rare fraction, and hypertension. Results: Experimental animal and human studies indicate that there are fewer capillaries and arterioles in patients with primary hypertension, and decreased density, also known as rarefaction, increases peripheral resistance. Microvascular density can be estimated noninvasively by methods such as intravital video microscopy in cutaneous regions or in nailfolds. The mechanisms of the reduction in density have been studied and could be used as a parameter when evaluating therapeutic options for patients. The skin provides a reservoir for sodium and can help moderate fluctuations in blood pressure associated with changes in sodium intake. In addition, the skin can modulate fluid volumes in the body through transepidermal water loss. Conclusions: This review discusses microvascular rarefaction, changes in microvasculature structure including the skin capillaries with hypertension, the association between sodium and skin physiology relevant to hypertension, transepidermal water loss, and the vascular effects associated with some antihypertensive medications that help explain their benefit in the prevention of cardiovascular events.

Resumo Introdução: Introdução: Hipertensão é fator de risco importante para infarto do miocárdio, acidente vascular cerebral, doença arterial periférica e doença renal crônica. A OMS estimou que, globalmente, aproximadamente 1,28 bilhão de adultos apresentam hipertensão. Sua definição mudou ao longo dos anos e, em 2017, o American College of Cardiology e a American Heart Association definiram pressão arterial ≥ 130/80 mmHg como hipertensão. Métodos: Realizou-se pesquisa no banco de dados PubMed utilizando os descritores MeSH “sódio”, “resistência capilar”, “hipertensão”, “rarefação microvascular” para identificar artigos relevantes sobre níveis de sódio na pele, circulações periféricas e rarefação vascular, hipertensão. Resultados: Estudos experimentais em animais e humanos indicam que há menos capilares e arteríolas em pacientes com hipertensão primária, e a redução da densidade, também conhecida como rarefação, aumenta a resistência periférica. A densidade microvascular pode ser estimada de forma não invasiva por métodos como microscopia intravital por vídeo em regiões cutâneas ou pregas ungueais. Os mecanismos da redução da densidade foram estudados e podem ser usados como parâmetro na avaliação de opções terapêuticas. A pele fornece um reservatório de sódio e pode ajudar a moderar flutuações na pressão arterial associadas a mudanças na ingestão de sódio. Ademais, pode modular volumes de fluido no corpo pela perda de água transepidérmica. Conclusões: Esta revisão discute rarefação microvascular, alterações na estrutura da microvasculatura, incluindo capilares da pele com hipertensão, associação entre sódio e fisiologia da pele relacionada à hipertensão, perda de água transepidérmica e efeitos vasculares de alguns medicamentos anti-hipertensivos que contribuem para explicar seus benefícios na prevenção de eventos cardiovasculares.