Hypoxia, HIF-1α, and COVID-19: from pathogenic factors to potential therapeutic targets.

The pandemic of coronavirus disease 2019 (COVID-19) and its pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have become the greatest current threat to global public health. The highly infectious SARS-CoV-2 virus primarily attacks pulmonary tissues and impairs gas exchange leading to acute respiratory distress syndrome (ARDS) and systemic hypoxia. The current pharmacotherapies for COVID-19 largely rely on supportive and anti-thrombi treatment and the repurposing of antimalarial and antiviral drugs such as hydroxychloroquine and remdesivir. For a better mechanistic understanding of COVID-19, our present review focuses on its primary pathophysiologic features: hypoxia and cytokine storm, which are a prelude to multiple organ failure and lethality. We discussed a possible link between the activation of hypoxia inducible factor 1α (HIF-1α) and cell entry of SARS-CoV-2, since HIF-1α is shown to suppress the angiotensin-converting enzyme 2 (ACE2) receptor and transmembrane protease serine 2 (TMPRSS2) and upregulate disintegrin and metalloproteinase domain-containing protein 17 (ADAM17). In addition, the protein targets of HIF-1α are involved with the activation of pro-inflammatory cytokine expression and the subsequent inflammatory process. Furthermore, we hypothesized a potential utility of so-called "hypoxic conditioning" to activate HIF-1α-induced cytoprotective signaling for reduction of illness severity and improvement of vital organ function in patients with COVID-19. Taken together, we would propose further investigations into the hypoxia-related molecular mechanisms, from which novel targeted therapies can be developed for the improved management of COVID-19.

Do patients receiving hemodialysis regret starting dialysis? A survey of affected patients
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AIMS: End-stage renal disease (ESRD) is associated with high morbidity and mortality. A prior study showed that many Canadian patients regretted their decision to start dialysis. We sought to determine if US patients also regretted dialysis. MATERIALS AND METHODS: We surveyed hemodialysis patients within 55 miles of Rochester, MN, with a 25-question survey about their perceptions of their health, preparedness for dialysis, advance care planning, and regrets about starting dialysis. Surveys were administered in person at the patients' usual dialysis session from July 1 through December 1, 2014; responses were captured electronically. RESULTS: Of the 198 eligible patients, 128 participated (70% men); 80% received dialysis for more than 1 year; 38% reported their health and 58% described their quality of life as "good" or "very good"; 51% had started dialysis in the hospital; and 68% agreed they were prepared for what to expect. Only 35% of patients reported being offered supportive care without dialysis. Most patients (82%) recalled a discussion about prognosis. Only 43% completed an advance directive, but 72% thought it was at least "very important" to plan for the end of life. Nine (7%) reported regretting the decision to start dialysis. CONCLUSIONS: Most of our patients were optimistic about their health and prognosis. Few regretted the decision to start dialysis.
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Predictors and outcomes following naloxone administration during Phase I anesthesia recovery.

PURPOSE: To identify characteristics associated with postoperative respiratory depression that required naloxone intervention during Phase I recovery following general anesthesia. A secondary aim is to compare postoperative outcomes between patients who received naloxone and those who did not. METHODS: Patients who received naloxone to reverse opioid-induced respiratory depression or sedation during Phase I postanesthesia recovery from January 1, 2010 to December 31, 2013 were identified and matched to 2 controls based on age, sex, and surgical procedure during the same year. A chart review was performed to identify factors associated with risk for intervention requiring naloxone as well as to note the occurrence of adverse postoperative outcomes. Analyses to assess characteristics potentially associated with naloxone use were performed using conditional logistic regression taking into account the 1:2 matched set case-control study design. RESULTS: Naloxone was administered to 413 patients, with an incidence of 2.5 per 1000 anesthetics [95 % confidence interval (CI) 0.7-6.5]. Presence of obstructive sleep apnea [odds ratio (OR) = 1.74, 95 % CI 1.22-2.48, P = 0.002], ASA Physical Status (PS) ≥III (OR 1.44, 95 % CI 1.08-1.92, P = 0.013), and greater opioid administration (OR 1.22, 95 % CI 1.12-1.33, per 10 intravenous morphine equivalents mg, P < 0.001) were associated with naloxone administration. Naloxone administration was associated with increased adverse events (OR 3.39, 95 % CI 2.22-5.23, P < 0.001). CONCLUSIONS: Obstructive sleep apnea, higher ASA-PS scores and greater doses of intraoperative opioids were associated with naloxone administration during Phase I recovery. Patients administered naloxone had increased adverse events after discharge from the recovery room and may benefit from a higher level of postoperative care.

The Perception of Female Smokers with Fibromyalgia on the Effects of Smoking on Fibromyalgia Symptoms.

OBJECTIVE: Smokers with fibromyalgia have greater pain intensity and function impairment compared to nonsmokers. Patients' perceptions of interactions between smoking and fibromyalgia symptoms have not been described. The primary aim of this study was to report the perceptions of female smokers with fibromyalgia on how smoking affects symptoms. METHODS: Forty-eight daily smokers with fibromyalgia enrolled in the Mayo Clinic Fibromyalgia Treatment Center completed the Fibromyalgia Impact Questionnaire, Fagerstrom Test for Nicotine Dependence, Patient Health Questionnaire-9, General Anxiety Disorder-7 and a Fibromyalgia Symptoms and Smoking Survey which queried how smoking directly affected fibromyalgia symptoms (eg, pain, tiredness/fatigue, stiffness, nervousness/anxiety, depression/blueness, irritability, concentration, and overall) or indirectly as a coping mechanism. RESULTS: The majority of subjects reported smoking had no direct effect on fibromyalgia physical symptoms (pain [60% reported no effect], fatigue [56%], stiffness [81%]) but direct improvement of emotional symptoms (anxiety [62% reported improvement], irritability [64%]). The majority of subjects used smoking to cope with pain (69%) via distraction (83%) and relaxation (77%), lessening emotional distress by reducing a sense of frustration (83%) or sadness (54%) because of pain, and as a justification for resting vis-à-vis "smoke breaks" (69%). Thirty-one smokers were mildly and 17 moderately/severely dependent on tobacco, and no difference in fibromyalgia impact score (P = 0.70), pain (P = 0.39), depression (P = 0.20), and anxiety (P = 0.64) scores were detected, but more moderately/severely dependent subjects reported smoking improved pain (50% vs. 17%, P = 0.04). DISCUSSION: Smokers with fibromyalgia reported smoking helped to cope with fibromyalgia pain but generally did not directly ameliorate fibromyalgia physical symptoms.

Emergency pages using a computer-based anesthesiology paging system in ambulatory surgical centers: a retrospective review.

BACKGROUND: The nature of pages associated with periprocedural emergency events in ambulatory centers has never being examined. Our institution has a proprietary anesthesiology paging system with hierarchical paging capabilities (emergency versus routine) and maintains a log of all events. Here, we describe emergency pages in our ambulatory surgery centers. METHODS: We identified all emergency page activations between June 1, 2008, and December 31, 2012, in our ambulatory surgical centers. Electronic medical records were reviewed for rates and characteristics of pages such as primary cause, interventions performed, and outcomes. RESULTS: During the study time frame, 120,618 procedures were performed and 93 emergency pages were recorded (7.7 per 10,000 cases, 95% confidence interval, 6.2-9.4), of which 51 originated in the procedure room and 42 outside the procedure room (16 before and 26 after the procedure). Among those, 14/93 were associated with serious events (1.2 per 10,000 cases). Among emergency pages for bradyarrhythmias (N = 35, 2.9 per 10,000 cases), 15 occurred during IV line placement in the preprocedural area, 11 during postprocedural recovery, and 9 during the procedure. Bradyarrhythmias accounted for 60.4% of pages outside the procedural room. In contrast, respiratory and airway events (N = 31, 2.6 per 10,000 cases) typically occurred in the procedural room (28 vs 9, P = 0.0006). Only 1 patient sustained permanent injury, myocardial infarction, and death 4 months later. Another patient died after 8 days from unrelated causes. CONCLUSION: The rates of emergency page activations, especially those that are critical events, in our surgical ambulatory center are rare. Many emergency pages originated outside the procedural room; therefore, providers within these areas should be trained to promptly recognize and treat these events.