Calcitonin Gene-Related Peptide Inhibition and Development of Acne and Rosacea.

This cohort study investigates whether calcitonin gene-related peptide inhibition is associated with reduced rates of developing acne or rosacea in patients who experience migraines.

Cooperative & competitive binding of anti-myosin tail antibodies revealed by super-resolution microscopy.

The MF30 monoclonal antibody, which binds to the myosin subfragment-2 (S2), was found to increase the extent of myofibril shortening. Yet, previous observations found no effect of this antibody on actin sliding over myosin during in vitro motility assays with purified proteins in which myosin binding protein C (MyBPC) was absent. MF30 is hypothesized to enhance the availability of myosin heads (subfragment-1 or S1) to bind actin by destabilizing the myosin S2 coiled-coil and sterically blocking S2 from binding S1. The mechanism of action likely includes MF30's substantial size, thereby inhibiting S1 heads and MyBPC from binding S2. Hypothetically, MF30 should enhance the ON state of myosin, thereby increasing muscle contraction. Our findings indicate that MF30 binds preferentially to the unfolded heavy chains of S2, displaying positive cooperativity. However, the dose-response curve of MF30's enhancement of myofibril shortening did not suggest complex interactions with S2. Single, double, and triple-stained myofibrils with increasing amounts of antibodies against myosin rods indicate a possible competition with MyBPC. Additional assays revealed decreased fluorescence intensity at the C-zone (central zone in the sarcomere, where MyBPC is located), where MyBPC may inhibit MF30 binding. Another monoclonal antibody named MF20, which binds to the light meromyosin (LMM) without affecting myofibril contraction, showed less reduction in fluorescence intensity at the C-zone in expansion microscopy than MF30. Expansion microscopy images of myofibrils labeled with MF20 revealed labeling of the A-band (anisotropic band) and a slight reduction in the labeling at the C-zone. The staining pattern obtained from the expansion microscopy image was consistent with images from photolocalization microscopy which required the synthesis of unique photoactivatable quantum dots, and Zeiss Airyscan imaging as well as alternative expansion microscopy digestion methods. Consistent with the hypothesis that MF30 competes with MyBPC binding to S2, cardiac tissue from MyBPC knockout mice was stained more intensely, especially in the C-zone, by MF30 compared to the wild type.

Erector spinae plane block: the ultimate 'plan A' block?

The erector spinae plane block (ESPB) is one of seven 'Plan A' blocks proposed by Regional Anaesthesia UK, covering the key areas of commonly encountered surgeries and acute pain. Unlike the other six blocks, the ESPB can be performed at all levels of the spine and provides analgesia to most regions of the body, leading to the argument that the ESPB is the ultimate Plan A block. Current studies show a high level of evidence supporting use in thoracoabdominal surgery but a lack of benefit in upper and lower limb surgery compared with local infiltration and other Plan A blocks. Thus, there is insufficient evidence to support the claim that the erector spinae plane block is the ultimate Plan A block.

Outcomes of Prolonged ICU Stay for Patients Undergoing Cardiac Surgery in Australia and New Zealand.

OBJECTIVE: To determine the effect of intensive care unit (ICU) length of stay (LOS) on hospital mortality and non-home discharge for patients undergoing cardiac surgery over a 16-year period in Australia and New Zealand. DESIGN: A retrospective, multicenter cohort study covering the period January 1, 2004 to December 31, 2019. SETTING: One hundred one hospitals in Australia and New Zealand that submitted data to the Australia New Zealand Intensive Care Society Adult Patient Database. PARTICIPANTS: Adult patients (aged >18) who underwent coronary artery bypass grafting, valve surgery, or combined valve + coronary artery surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors analyzed 252,948 cardiac surgical patients from 101 hospitals, with a median age of 68.3 years (IQR 60-75.5), of whom 74.2% (187,632 of 252,948) were male patients. A U-shaped relationship was observed between ICU LOS and hospital mortality, with significantly elevated mortality at short (<20 hours) and long (>5 days) ICU LOS, which persisted after adjustment for illness severity and across clinically important subgroups (odds ratio for mortality with ICU LOS >5 days = 3.21, 95% CI 2.88-3.58, p < 0.001). CONCLUSIONS: Prolonged duration of ICU LOS after cardiac surgery is associated with increased hospital mortality in a U-shaped relationship. An ICU LOS >5 days should be considered a meaningful definition for prolonged ICU stay after cardiac surgery.

Early Albumin Exposure After Cardiac Surgery.

OBJECTIVES: To determine whether the early use of albumin after cardiac surgery in the first 24 hours in the intensive care unit (ICU) is associated with reduced mortality. DESIGN: A single-center nonrandomized retrospective cohort study using the Medical Information Mart in Intensive Care IV database. SETTING: A single cardiothoracic ICU in the United States during a period between 2008 to 2019. PARTICIPANTS: Patients undergoing valvular and/or cardiac bypass graft surgeries. INTERVENTIONS: Albumin administered during the first 24 hours of the ICU admission. MEASUREMENTS AND MAIN RESULTS: A total of 8,136 patients were included in this study, of whom 4,444 (54.6%) received albumin at any stage during the first 24 hours of ICU admission, and 69 (1.6%) of those patients died. The patient population exposed to albumin had higher comorbidities and illness severity compared to the no-albumin group. Patients exposed to albumin during the first 24 hours of ICU admission had a statistically significant reduction in mortality (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.97, p < 0.05) after adjustment for age, the Oxford Acute Severity of Illness Score, and the Charlson comorbidity index. A sensitivity analysis of patients who received albumin at any stage during ICU admission showed increased mortality (OR, 1.93; 95% CI, 1.26-3.07, p < 0.01). Patients exposed to albumin had a significant increase in adjusted ICU length of stay (LOS) (geometric mean ratio 1.09; 95% CI, 1.05-1.10, p = < 0.001) and hospital LOS (geometric mean ratio 1.08; 95% CI, 1.05-1.10, p < 0.001). CONCLUSIONS: Exposure to albumin in the first 24 hours after cardiac surgery is associated with a reduction in adjusted hospital mortality and an increase in both hospital and ICU lengths of stay.

Cricoid pressure during intubation: A systematic review and meta-analysis of randomised controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to determine whether cricoid pressure protects against aspiration and whether this technique adversely affects intubating conditions in adult patients. METHODS: A systematic review of five databases was performed for randomised controlled trials comparing cricoid pressure to no cricoid or sham cricoid during intubation. The primary outcome was incidence of aspiration and the secondary outcomes included first attempt intubation success, time to intubation, Cormack and Lehane Grade 3 or 4 and difficult intubation. RESULTS: The search identified twelve high quality RCTs with 4,862 patients for inclusion. Among four studies reporting the primary outcome, there was no difference (RR=1.18; 95%CI=0.71 to 1.96; I2=0%; p=0.51). Only 3 studies were in patients at high risk of aspiration. There was significantly worse first attempt success (RR= 0.94; 95%CI= 0.89 to 0.99; I2=66%; p=0.02), time to intubation (WMD= 6.77seconds; 95%CI=4.40 to 9.14seconds; I2=97%) and laryngoscopy views (RR=1.69; 95%CI=1.41 to 2.02;I2=1%; p<0.00001) with cricoid pressure. CONCLUSIONS: Cricoid pressure failed to show any increase in protection from aspiration and may increase difficulty of intubation. Further studies in high-risk patients, such as intensive care patients, are required.