Science, Medicine, and the Anesthesiologist

Among U.S. surgeons, burnout prevalence varies between 39% and 48% and may be associated with adverse personal and professional consequences. This study hypothesized that external professional coaching positively influences burnout rate, at the same time also improving quality of life and resilience. The randomized controlled trial enrolled 80 surgeons allocated to either immediate professional coaching (n = 40) or a delayed protocol at month 7 (n = 40; control group) with coaching for 6 months (3.5 h in total). Evaluations were performed at baseline and after 6 and 12 months, respectively, using the Maslach Burnout Inventory test, the single-item linear analog scale for the assessment of the quality of life and the Connor-Davidson Resilience Scale. At 6 months, burnout rate decreased by 3% in the immediate coaching group and increased by 3% in the control arm (delta, –5.0%; 95% CI, –9 to –1%; P = 0.007). Resilience scores slightly improved in the intervention group. No intergroup difference was found in the quality-of-life scoring. At 12 months, burnout rate dropped by 18% in the delayed coaching group, while an increase of 3% in the immediate coaching group was reported (delta, –21%; 95% CI, –28 to –14%; P < 0.0010. No statistical difference was found for resilience and quality-of-life score.

Take home message: In this randomized controlled trial, external professional coaching had a positive effect on burnout rate, but only for the duration of the coaching. This approach might be an important instrument in an organization to reduce personal burdens as well as professional consequences of burnout.

Long-term associations between impaired pulmonary function and radiologic abnormalities in survivors of coronavirus infection are unknown. This single-center study from Wuhan, China, reports a 2-yr longitudinal assessment of lung computed tomography (CT) abnormalities and associated lung function in a cohort of 144 patients without prior pulmonary disease, hospitalized with severe acute respiratory coronavirus–2α, and discharged alive between January and March 2020. Subjects underwent CT scanning on admission and at 6 months, 12 months, and 2 yr after discharge, along with assessments with respiratory questionnaires and pulmonary function testing. Interstitial lung abnormalities on CT imaging were defined based on presence of bronchiectasis, honeycombing, or architectural distortions (fibrotic) versus only ground-glass opacities or reticulations (nonfibrotic). The incidence of nonfibrotic interstitial abnormalities decreased from 31% at 6 months to 16% at 2 yr, while fibrotic abnormalities remained 23% throughout. After 2 yr, more subjects with interstitial abnormalities had respiratory symptoms (34%) and a diffusing capacity for carbon monoxide ≤ 75% predicted (43%) than those without (15% and 20%; respectively; P = 0.007 and 0.004).

Take home message: This single-center longitudinal cohort analysis demonstrates that persistent pulmonary radiologic abnormalities are common after severe acute respiratory syndrome coronavirus infection and are associated with residual impaired lung function.

Heparin is a mainstay parenteral anticoagulant therapy for perioperative use. It has a rapid onset, has a short half-life, and is readily reversible, which facilitates managing patients for cardiovascular surgery or intravascular procedural interventions. Heparin and similar molecules line our arterial vasculature in the structure defined as the glycocalyx. Heparins also interact with antithrombin to further regulate thrombin generation, keep it from becoming systemic after injury, and exert both anticoagulant and nonanticoagulant effects. In the current pandemic, heparin was the primary anticoagulant used to prevent thromboembolic complications after SARS2-coronavirus infections. The extensive clinical use of unfractionated heparin and low-molecular-weight heparin also revisited the important role of thrombin generation to both humoral and cellular inflammatory responses. The interaction between thrombosis and inflammation is widely referred to as thromboinflammation and/or immunothrombosis, important pathways that are activated to further limit pathogen-mediated injury to the host. The critical application of heparins in the prevention of thromboembolic complications also provides anti-inflammatory effects. This review examines recent developments and clinical studies for novel uses of heparin and an overview of heparin-based drug development.

Take home message: Heparin is an important anticoagulant with anti-inflammatory effects in the treatment of SARS2-coronavirus and inflammatory conditions. Current studies with clinical and biologic implications are revisited in this extensive review article about heparin and its therapeutic applications.

Pulmonary arterial hypertension is characterized by proliferative remodeling and narrowing of small pulmonary arteries, leading to right heart failure and death. Current therapies are still associated with high mortality. This multicenter, double-blind phase 3 trial randomized adults with pulmonary arterial hypertension World Health Organization functional class II or III 1:1 to receive subcutaneous sotatercept (a fusion protein that traps selected transforming growth factor-β superfamily members, thereby inhibiting arterial growth) or placebo. The primary endpoint was the change in the 6-min walk distance from baseline to week 24. Nine secondary endpoints were defined, such as time to clinical worsening or death. In the sotatercept group (n = 163, 79% female), 6-min walk distance was 35 m (95% CI, 33.0 to 35.5) and 1 m in the placebo group (n = 160, 127 female sex, 79%) (95% CI, –0.3 to 3.5). The Hodges–Lehmann location-shift estimate of the between-group difference with 95% CI was 41 m (95% CI, 27.5 to 54.1; P < 0.001). For the time to first occurrence of death or nonfatal clinical worsening event, the hazard ratio after a median of 33 weeks in the sotatercept group compared with the placebo was 0.16 (95% CI, 0.08 to 0.35; P < 0.001).

Take home message: A multicenter, double-blind phase 3 trial of sotatercept compared to placebo in adults with pulmonary artery hypertension demonstrated a significant improvement distance covered during the 6-min walk test along with other secondary outcomes with a minor adverse event profile.

The use of corticosteroid supplementation to catechol and vasopressin-based therapies for vasoactive support in patients with septic shock is increasing. However, the comparative effectiveness of the two most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs. hydrocortisone alone) is not well studied. This retrospective cohort study (2016 to 2020) employed the Premier Healthcare Database to evaluate associations of steroid therapies with outcome in adult patients with septic shock receiving norepinephrine infusion receiving hydrocortisone treatment. The exposure of interest was the addition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated versus use of hydrocortisone alone. The primary outcome was a composite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation. The cohort considered 88,275 patients, 2,280 treated with hydrocortisone-fludrocortisone (median [interquartile range] age, 64 yr [54 to 73 yr]) vs. 85,995 (age, 67 yr [57 to 76 yr]) treated with hydrocortisone alone. The primary composite outcome was significantly improved in patients treated with hydrocortisone-fludrocortisone versus hydrocortisone alone (adjusted absolute risk difference, −4%; 95% CI, −4% to −3%; P < 0.001).

Take home message: In this comparative effectiveness cohort study of adult patients with septic shock receiving hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.

Transcarotid artery stenting is a rapidly growing novel alternative to transfemoral approaches based on more favorable long-term outcomes but has been investigated only in high-risk patients. This retrospective propensity-matched cohort study compared stroke, death, and myocardial infarction (MI) after transcarotid artery stenting versus open endarterectomy in patients with standard surgical risk. Patients lacking Medicare-defined high-risk medical or surgical characteristics and having transcarotid artery stenting (n = 2962) or endarterectomy (n = 35,063) in the multicenter Vascular Quality Initiative Carotid Artery Stent and Carotid Endarterectomy registries from August 2016 to August 2019 were followed until August 2020. The primary outcomes were a composite endpoint of 30-day stroke, death, or MI or 1-yr ipsilateral stroke. There was no statistically significant difference in the primary composite outcomes between the cohorts (transcarotid 3.0% vs. endarterectomy 2.6%; absolute difference, 0.40% [95% CI, −0.43 to 1.24%]; relative risk, 1.14 [95% CI, 0.87 to 1.50]; P = 0.34). The transcarotid approach was associated with a higher risk of 1-yr stroke (1.6% vs. 1.1%; absolute difference, 0.52% [95% CI, 0.03 to 1.08]; relative risk, 1.49 [95% CI, 1.05 to 2.11%]; P = 0.02) but no difference in 1-yr all-cause mortality (2.6% vs. 2.5%; absolute difference, −0.13% [95% CI, −0.18 to 0.33%]; relative risk, 1.04 [95% CI, 0.78 to 1.39]; P = 0.67).

Take home message: This retrospective propensity-matched cohort study of standard risk patients showed similar rates of 30-day stroke, death, and myocardial infarction and 1-yr ipsilateral stroke in those having either transcarotid artery stenting or open endarterectomy. The role of this approach in routine practice requires additional study.

Previous unblinded studies suggest that unilateral ultrasound ablation of part of the globus pallidus might reduce motor symptoms in Parkinson’s disease; thus, a blinded trial to establish potential efficacy was performed. Ninety-four patients with Parkinson’s disease were randomized in a 3:1 ratio to ultrasound ablation or sham procedure performed off medication. The primary outcome was a 3-point improvement in either the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (off medication) or the Unified Dyskinesia Rating Scale (on medication) at 3 months. An additional open-label assessment was performed at 12 months. Sixty-nine percent of patients in the active treatment arm had a favorable response at 3 months, compared to 32% in the sham treatment arm (treatment effect = 37%; 95% CI, 15 to 60%; P = 0.003). Of the 39 patients assessed at 12 months, 77% had a sustained response. Pallidotomy-related adverse events (dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness) occurred in approximately 15% of the treatment group.

Take home message: Unilateral pallidal ultrasound ablation resulted in a modest improvement in motor function or reduced dyskinesia compared to a sham procedure but was associated with mild to moderate adverse events.

Statins are widely prescribed drugs, but a common (up to 30%) adverse effect is myopathy. The mechanisms of statin-associated myopathy have not been fully resolved and its treatment consists in most cases solely of discontinuation of statin therapy. Using homozygosity mapping and exosome sequencing, the investigators show that a distinct form of human limb girdle muscular disease, a rare progressive autosomal orphan disease, is caused by a homozygous loss-of-function mutation in HMG-CoA reductase (HMGCR), the rate-limiting enzyme of the mevalonate pathway for cholesterol synthesis. Mevalonolactone (a downstream metabolite of the mevalonate pathway) was biochemically synthetized and orally applied (16 mg/kg three times per week) to safely and successfully treat patients with hereditary HMGCR myopathy. Muscle strength as assessed by dynamometry and manual muscle testing rapidly increased, and respiratory muscles as assessed by spirometry also showed remarkable improvements (peak expiratory flow +265%, from 6 to 22% of predicted value). Subsequent studies in mice with statin-induced myopathy also showed improvement upon oral mevalonolactone treatment, as assessed by the “wire hanging test” used to assess muscle performance in small rodents. These findings indicate that mevalonolactone is effective in mitigating HMGCR myopathy and protects from statin myotoxicity as both are caused by insufficient HMGCR activity.

Take home message: Mevalonolactone therapy appears highly promising in the treatment of a rare orphan muscle disease but also of the common statin-induced myopathy.

The impact of preoperative medical consultation on postoperative clinical outcomes is controversial. This retrospective cohort study of residents aged 40 yr or older who underwent a first intermediate- to high-risk noncardiac operation (2005 to 2018) in Ontario, Canada, used administrative databases linking demographics, physician characteristics and services, and receipt of inpatient and outpatient care to investigate associations comparing those who did and did not undergo preoperative medical consultation within 4 months of surgery (using propensity score matching). The primary outcome was 30-day all-cause postoperative mortality. Secondary outcomes included 1-yr mortality, inpatient myocardial infarction and stroke, in-hospital mechanical ventilation, length of stay, and 30-day health system costs. Of the 530,473 individuals analyzed (mean ± SD age, 67 ± 11 yr), 35% had preoperative medical consultation and 68% of the cohort were propensity score matched. The primary outcome was significantly higher in the consultation group (0.9% vs. 0.7% (odds ratio, 1.19; 95% CI, 1.11 to 1.29). Of the secondary outcomes, all physiologic outcomes except rates of inpatient myocardial infarction were also higher in the consultation group. Resource utilization outcomes were also higher, both inpatient and preoperative (use of preoperative echocardiography, cardiac stress testing, and new prescriptions for β-blockers).

Take home message: This large-scale, administrative data based, retrospective cohort study suggests paradoxically that preoperative medical consultation was associated with an increase, rather than a decrease in adverse postoperative outcomes, resource utilization and increased use of perioperative β-blockers.