Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of more than 3300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, hepatocyte growth factor, interleukin-8, and granulocyte colony-stimulating factor, which were the strongest predictors of critical illness. Evidence of neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, these data suggest a central role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular markers that distinguish patients at risk of future clinical decompensation.

There are many ways in which women experience sleep differently from men. Women contending with distinct sleep challenges respond differently to sleep disorders, as well as sleep deprivation and deficiency, and face particular health outcomes as a result of poor sleep. Idiosyncrasies, including changes that occur with the biological life cycles of menstruation, pregnancy, and menopause, make the understanding of sleep in women an important topic to study. Each phase of a woman's life, from childhood to menopause, increases the risk of sleep disturbance in unique ways that may require distinct management. Indeed, new research is unraveling novel aspects of sleep pathology in women and the fundamental role that sex hormones play in influencing sleep regulation and arousals and possibly outcomes of sleep conditions. Moreover, studies indicate that during times of hormonal change, women are at an increased risk for sleep disturbances such as poor sleep quality and sleep deprivation, as well as sleep disorders such as OSA, restless legs syndrome, and insomnia. This article reviews sleep changes in female subjects from neonatal life to menopause.

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Upper airway surgery is an important treatment option for patients with obstructive sleep apnea (OSA), particularly for those who have failed or cannot tolerate positive airway pressure therapy. Surgery aims to reduce anatomical upper airway obstruction in the nose, oropharynx, and hypopharynx. Procedures addressing nasal obstruction include septoplasty, turbinectomy, and radiofrequency ablation (RF) of the turbinates. Surgical procedures to reduce soft palate redundancy include uvulopalatopharyngoplasty, uvulopalatal flap, laser-assisted uvulopalatoplasty, and RF of the soft palate with adenotonsillectomy. More significant, however, particularly in cases of severe OSA, is hypopharyngeal or retrolingual obstruction related to an enlarged tongue, or more commonly due to maxillomandibular deficiency. Surgeries in these cases are aimed at reducing the bulk of the tongue base or providing more space for the tongue in the oropharynx so as to limit posterior collapse during sleep. These procedures include genioglossal advancement, hyoid suspension, distraction osteogenesis, tongue RF, lingualplasty, and maxillomandibular advancement. Successful surgery depends on proper patient selection, proper procedure selection, and experience of the surgeon. Most surgeries are done in combination and in a multistep manner, with maxillomandibular advancement typically being reserved for refractory or severe OSA, or for those with obvious and significant maxillomandibular deficiency. Although not without risks and not as predictable as positive airway pressure therapy, surgery remains an important therapeutic consideration in all patients with OSA. Current research aims to optimize the success of these procedures by identifying proper candidates for surgery, as well as to develop new invasive procedures for OSA treatment.

Despite over 30 million infected and 800,000 deaths, the pathophysiological factors that determine the wide spectrum of clinical outcomes in COVID-19 remain inadequately defined. Importantly, patients with underlying cardiovascular disease have been found to have worse clinical outcomes (1), and autopsy findings of endotheliopathy in COVID-19 have accumulated (2). Nonetheless, circulating markers of endothelial or vascular injury associated with disease severity and mortality have not been reliably established. To address this limitation and better understand COVID-19 pathogenesis, we report plasma profiling of factors related to the vascular system from patients admitted to our Hospital with confirmed COVID-19 diagnosis, which revealed significant increases in markers of angiogenesis and endotheliopathy in hospitalized patients.

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Study Objectives The bases for sex disparities in obstructive sleep apnea (OSA), is poorly understood. We quantified the influences of event definitions, sleep-state, and body position on apnea–hypopnea indices (AHIs) in men and women, and evaluated sex differences in pathophysiological endotypes. Methods Polysomnography (PSG) data were analyzed from 2057 participants from the multi-ethnic study of atherosclerosis. Alternative AHIs were compared using various desaturation and arousal criteria. Endotypes (loop gain, airway collapsibility, arousal threshold) were derived using breath-by-breath analysis of PSG signals. Regression models estimated the extent to which endotypes explained sex differences in AHI. Results The sample (mean 68.5 ± 9.2 years) included 54% women. OSA (AHI4P ≥15/h, defined by events with ≥4% desaturations) was found in 41.1% men and 21.8% women. Compared to AHI4P, male/female AHI ratios decreased by 5%–10% when using 3%-desaturation and/or arousal criteria; p < 0.05. REM-OSA (REM-AHI ≥15/h) was similar in men and women regardless of event desaturation criteria. REM-AHI4P ≥15/h was observed in 57% of men and women each. In NREM, AHI4P in men was 2.49 (CI95: 2.25, 2.76) of that in women. Women demonstrated lower loop gain, less airway collapsibility, and lower arousal threshold in NREM (ps < 0.0005). Endotypes explained 30% of the relative sex differences in NREM-AHI4P. Conclusions There are significant sex differences in NREM-AHI levels and in physiological endotypes. Physiological endotypes explained a significant portion of the relative sex differences in NREM-AHI. Definitions that use 4%-desaturation criteria under-estimate AHI in women. Combining NREM and REM events obscures OSA prevalence in REM in women.

Pathologic immune hyperactivation is emerging as a key feature of critical illness in COVID-19, but the mechanisms involved remain poorly understood. We carried out proteomic profiling of plasma from cross-sectional and longitudinal cohorts of hospitalized patients with COVID-19 and analyzed clinical data from our health system database of over 3,300 patients. Using a machine learning algorithm, we identified a prominent signature of neutrophil activation, including resistin, lipocalin-2, HGF, IL-8, and G-CSF, as the strongest predictors of critical illness. Neutrophil activation was present on the first day of hospitalization in patients who would only later require transfer to the intensive care unit, thus preceding the onset of critical illness and predicting increased mortality. In the health system database, early elevations in developing and mature neutrophil counts also predicted higher mortality rates. Altogether, we define an essential role for neutrophil activation in the pathogenesis of severe COVID-19 and identify molecular neutrophil markers that distinguish patients at risk of future clinical decompensation.