Improving Neuromuscular Monitoring Through Education-Based Interventions and Studying Its Association With Adverse Postoperative Outcomes: A Retrospective Observational Study.

BACKGROUND: We assessed the association between education-based interventions, the frequency of train-of-four (TOF) monitoring, and postoperative outcomes. METHODS: We studied adults undergoing noncardiac surgery from February 1, 2020 through October 31, 2021. Our education-based interventions consisted of 3 phases. An interrupted time-series analysis, adjusting for patient- and procedure-related characteristics and secular trends over time, was used to assess the associations between education-based interventions and the frequency of TOF monitoring, postoperative pulmonary complications (PPCs), 90-day mortality, and sugammadex dosage. For each outcome and intervention phase, we tested whether the intervention at that phase was associated with an immediate change in the outcome or its trend (weekly rate of change) over time. In a sensitivity analysis, the association between education-based interventions and postoperative outcomes was adjusted for TOF monitoring. RESULTS: Of 19,422 cases, 11,636 (59.9%) had documented TOF monitoring. Monitoring frequency increased from 44.2% in the first week of preintervention stage to 83.4% in the final week of the postintervention phase. During the preintervention phase, the odds of TOF monitoring trended upward by 0.5% per week (odds ratio [OR], 1.005; 95% confidence interval [CI], 1.002-1.007). Phase 1 saw an immediate 54% increase (OR, 1.54; 95% CI, 1.33-1.79) in the odds, and the trend OR increased by 3% (OR, 1.03; 95% CI, 1.01-1.05) to 1.035, or 3.5% per week (joint Wald test, P < .001). Phase 2 was associated with a further immediate 29% increase (OR, 1.29; 95% CI, 1.02-1.64) but no significant association with trend (OR, 0.96; 95% CI, 0.93-1.01) of TOF monitoring (joint test, P = .04). Phase 3 and postintervention phase were not significantly associated with the frequency of TOF monitoring (joint test, P = .16 and P = .61). The study phases were not significantly associated with PPCs or sugammadex administration. The trend OR for 90-day mortality was larger by 24% (OR, 1.24; 95% CI, 1.06-1.45; joint test, P = .03) in phase 2 versus phase 1, from a weekly decrease of 8% to a weekly increase of 14%. However, this trend reversed again at the transition from phase 3 to the postintervention phase (OR, 0.82; 95% CI, 0.68-0.99; joint test, P = .05), from a 14% weekly increase to a 6.2% weekly decrease in the odds of 90-day mortality. In sensitivity analyses, adjusting for TOF monitoring, we found similar associations between study initiatives and postoperative outcomes. TOF monitoring was associated with lower odds of PPCs (OR, 0.69; 95% CI, 0.55-0.86) and 90-day mortality (OR, 0.79; 95% CI, 0.63-0.98), but not sugammadex dosing (mean difference, -0.02; 95% CI, -0.04 to 0.01). CONCLUSIONS: Our education-based interventions were associated with both TOF utilization and 90-day mortality but were not associated with either the odds of PPCs or sugammadex dosing. TOF monitoring was associated with reduced odds of PPCs and 90-day mortality.

Examining the Relationship Between Wound Complications and the Use of Resorbable Plates in Cranial Vault Reconstruction.

BACKGROUND: Resorbable plates are commonly used in cranial vault reconstruction surgery. There are few published papers examining their safety profile. The authors examined the prevalence of wound complications associated with the use of resorbable plates (Inion CPS Fixation System) in pediatric patients undergoing cranial vault reconstruction. METHODS: A retrospective review of patients (n = 182) who underwent cranial vault reconstruction using resorbable plate fixation was undertaken. All procedures were performed by a single Craniofacial Surgeon at the National Pediatric Craniofacial Center from 2008 to 2016. Wound complications were identified from a prospectively maintained database and medical note review. Several key patient characteristics and surgical variables were also recorded and tested for associations with wound complications. RESULTS: A total of 58.8% (107 of 182) of patients were male with a median age at surgery of 16.2 months. Overall, 12.1% (22 of 182) experienced a postoperative wound complication requiring hospital admission. A total of 2.73% (5 of 182) of the patients that returned to theatre had remnants of plates removed. The authors had a mean time from primary operation to secondary reoperation of 103 days. In univariate statistical analysis, females were more likely to develop a wound complication. However, in stratified analyses excluding patients with an underlying genetic syndrome, increasing age, and lower weight but not gender were associated with wound complications. CONCLUSIONS: A 12.1% (22 of 182) wound complication rate with the use of the Inion CPS Fixation System was observed. Inion plates appear to have an equivalent safety profile to other fixation devices. Increasing age and lower weight were associated with an increased risk of wound complications in nonsyndromic patients.

Divergent changes of p53 in pulmonary arterial endothelial and smooth muscle cells involved in the development of pulmonary hypertension.

The tumor-suppressive role of p53, a transcription factor that regulates the expression of many genes, has been linked to cell cycle arrest, apoptosis, and senescence. The noncanonical function or the pathogenic role of p53 has more recently been implicated in pulmonary vascular disease. We previously reported that rapid nuclear accumulation of hypoxia-inducible factor (HIF)-1α in pulmonary arterial smooth muscle cells (PASMCs) upregulates transient receptor potential channels and enhances Ca2+ entry to increase cytosolic Ca2+ concentration ([Ca2+]cyt). Also, we observed differences in HIF-1α/2α expression in PASMCs and pulmonary arterial endothelial cells (PAECs). Here we report that p53 is increased in PAECs, but decreased in PASMCs, isolated from mice with hypoxia-induced pulmonary hypertension (PH) and rats with monocrotaline (MCT)-induced PH (MCT-PH). The increased p53 in PAECs from rats with MCT-PH is associated with an increased ratio of Bax/Bcl-2, while the decreased p53 in PASMCs is associated with an increased HIF-1α. Furthermore, p53 is downregulated in PASMCs isolated from patients with idiopathic pulmonary arterial hypertension compared with PASMCs from normal subjects. Overexpression of p53 in normal PASMCs inhibits store-operated Ca2+ entry (SOCE) induced by passive depletion of intracellularly stored Ca2+ in the sarcoplasmic reticulum, while downregulation of p53 enhances SOCE. These data indicate that differentially regulated expression of p53 and HIF-1α/2α in PASMCs and PAECs and the cross talk between p53 and HIF-1α/2α in PASMCs and PAECs may play an important role in the development of PH via, at least in part, induction of PAEC apoptosis and PASMC proliferation.

Supervised exercise therapy in the management of peripheral arterial disease - an assessment of compliance.

BACKGROUND: Supervised exercise therapy (SET) is an effective option in the management of peripheral arterial disease (PAD). Unfortunately, poor compliance remains prevalent. This study aimed to assess patient exercise compliance and to identify factors influencing symptomatic improvement and SET participation. PATIENTS AND METHODS: Data regarding attendance at SET for this cohort study were extracted from a prospectively maintained database of patients with claudication attending SET at Dublin City University. All patients had ankle brachial index confirmed PAD with associated intermittent claudication. Exercise performance and symptomatic data were gathered retrospectively using patient charts and interviews. RESULTS: Ninety-eight patients were referred for SET during the study period. The mean age was 69.2 (± 10.1) with 18 % being female. Median follow-up was 25.1 months (IQ range 17.0-31.6). Overall, the mean number of sessions attended per patient was 19.5. Exercise compliance was associated with a significant improvement in symptoms (p = 0.001). Other factors including anatomical level of claudication (P = 0.042) and educational level (p = 0.007) were found to affect the outcome of SET. Multivariate analysis revealed hypertension as a predictor of symptomatic outcome after SET (p = 0.045). Furthermore, ex-smokers (p = 0.021) and those previously diagnosed with hypercholesterolaemia (p = 0.020) or ischaemic heart disease (p = 0.029) had superior exercise compliance. Using linear regression, smoking history (p = 0.024) was identified as a predictor of compliance to SET. CONCLUSIONS: Establishing exercise compliance remains challenging in the PAD cohort. Pre-exercise patient education and personalised exercise prescriptions may result in improvements in function and compliance.

Preoperative Predictors of Free Flap Failure.

OBJECTIVE: Microvascular free tissue transfer is an important reconstructive option for defects of the head and neck. The present study aims to identify preoperative patient- and tumor-specific characteristics, laboratory values, and other risk factors associated with early free flap failure. STUDY DESIGN: Retrospective cohort study of 1070 patients. SETTING: Head and neck surgical oncology service at a tertiary care center from 2005 to 2019. METHODS: Demographics, comorbidities, preoperative laboratory values, treatment history, and cancer stage were collected for consecutive patients who underwent free flap reconstruction of the head and neck and experienced early free flap failure (<8 days from surgery). RESULTS: In 1070 patients, the prevalence of early free flap failure was 3.8% (n = 41). Female sex (odds ratio [OR], 2.58; 95% CI, 1.36-4.99), presence of peripheral vascular disease (OR, 2.78; 95% CI, 1.05-6.57), and elevated preoperative platelet count (OR, 2.67; 95% CI, 1.20-5.47) were independently associated with risk of early free flap failure. CONCLUSION: Female sex, peripheral vascular disease, and preoperative thrombocytosis are all strong predictors of early free flap failure. This suggests that hypercoagulability and poor vessel quality may predispose patients to flap loss. Patients with elevated platelets or peripheral vascular disease warrant careful reconstructive decision making and close monitoring in the perioperative period.

Are Plastic Surgery Trainees Accurate Assessors of Their Own Microsurgical Skill?

Background: Microsurgery is a technically demanding surgical discipline with a steep learning curve. Trainees have faced several difficulties due to less hands-on theater time and pandemic-related limits on access to technical training. To overcome this, trainees engaged in self-directed training, which requires an accurate self-assessment of skill. This study aimed to assess the ability of trainees to accurately self-assess their performance while performing a simulated microvascular anastomosis. Methods: Novice and specialist plastic surgery trainees performed a simulated microvascular anastomosis on a high-fidelity chicken femoral vessel model. Each participant objectively rated the quality of their anastomosis using the Anastomosis Lapse Index (ALI). Two expert microsurgeons subsequently blindly rated each anastomosis. To determine the accuracy of self-evaluation, self-scores and expert-scores were compared using a Wilcoxon signed-rank test. Results: Twenty-seven surgical trainees completed the simulation, with a mean time to completion (TTC) of 40.3 minutes (range 14.2-106.0 minutes). For the entire cohort, the median ALI self-score was 4 (range 3-10), while the median ALI expert-score was 5.5 (range 2.5-9.5). There was a significant difference between the ALI self-score and the expert-score (p<0.001). When grouped by experience level, there was no significant difference between self-score and expert-score within the specialist group, while there was a significant difference within the novice group (p=0.001). Conclusion: These findings suggest that specialist trainees are accurate assessors of their own microsurgical skills, but novice trainees tend to overestimate their technical skills. While novice trainees can engage in independent self-directed microsurgical training, they should seek expert feedback to ensure targeted training.

Otolaryngology Residency Program Rankings and Social Media Usage: A Longitudinal Analysis.

OBJECTIVE: Social media is a powerful networking tool among health care organizations. This study determines correlations between program reputation and social media activity and popularity, specifically among otolaryngology residency programs. METHODS: Accredited programs, excluding military and osteopathic, in the United States were included. Activity and popularity on Facebook, Twitter, and Instagram were assessed during the same 7-month period from 2016 to 2020. Doximity Residency reputation scores (dividing programs into quartiles) and US News & World Report (comparing programs affiliated with top hospitals versus those with unranked hospitals) were utilized to compare differences based on reputation. RESULTS: Of 104 programs, 91 (88%) had social media accounts. Instagram and Twitter were more commonly used than Facebook, with 78 (75%), 49 (47%), and 42 (40%) accounts, respectively. The cumulative use of all three platforms grew yearly, while Twitter (R2  = 0.9863) and Instagram (R2  = 0.9955) presence increased exponentially. Doximity's top quartile programs had more Facebook (P = .020), Twitter (P < .001), and Instagram (P = .102) accounts. First-quartile programs also adopted each platform months before fourth-quartile programs. Stratified by US News & World Report, ranked programs had more social media accounts, with 24 (53%) on Facebook (P = .028), 32 (71%) on Twitter (P < .001), and 37 (82%) on Instagram (P = .155). Programs with higher reputations were more active and exhibited increased likes and followers over time. CONCLUSION: Social media use among otolaryngology programs has grown exponentially, with Instagram and Twitter becoming the dominant platforms. Higher ranked programs are more active on social media, have more followers, and adopt social media earlier. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2455-2460, 2021.

Halofuginone, a promising drug for treatment of pulmonary hypertension.

BACKGROUND AND PURPOSE: Halofuginone is a febrifugine derivative originally isolated from Chinese traditional herb Chang Shan that exhibits anti-hypertrophic, anti-fibrotic and anti-proliferative effects. We sought to investigate whether halofuginone induced pulmonary vasodilation and attenuates chronic hypoxia-induced pulmonary hypertension (HPH). EXPERIMENTAL APPROACH: Patch-clamp experiments were conducted to examine the activity of voltage-dependent Ca2+ channels (VDCCs) in pulmonary artery smooth muscle cells (PASMCs). Digital fluorescence microscopy was used to measure intracellular Ca2+ concentration in PASMCs. Isolated perfused and ventilated mouse lungs were used to measure pulmonary artery pressure (PAP). Mice exposed to hypoxia (10% O2 ) for 4 weeks were used as model of HPH for in vivo experiments. KEY RESULTS: Halofuginone increased voltage-gated K+ (Kv ) currents in PASMCs and K+ currents through KCNA5 channels in HEK cells transfected with KCNA5 gene. HF (0.03-1 µM) inhibited receptor-operated Ca2+ entry in HEK cells transfected with calcium-sensing receptor gene and attenuated store-operated Ca2+ entry in PASMCs. Acute (3-5 min) intrapulmonary application of halofuginone significantly and reversibly inhibited alveolar hypoxia-induced pulmonary vasoconstriction dose-dependently (0.1-10 µM). Intraperitoneal administration of halofuginone (0.3 mg·kg-1 , for 2 weeks) partly reversed established PH in mice. CONCLUSION AND IMPLICATIONS: Halofuginone is a potent pulmonary vasodilator by activating Kv channels and blocking VDCC and receptor-operated and store-operated Ca2+ channels in PASMCs. The therapeutic effect of halofuginone on experimental PH is probably due to combination of its vasodilator effects, via inhibition of excitation-contraction coupling and anti-proliferative effects, via inhibition of the PI3K/Akt/mTOR signalling pathway.

Endothelial platelet-derived growth factor-mediated activation of smooth muscle platelet-derived growth factor receptors in pulmonary arterial hypertension.

Platelet-derived growth factor is one of the major growth factors found in human and mammalian serum and tissues. Abnormal activation of platelet-derived growth factor signaling pathway through platelet-derived growth factor receptors may contribute to the development and progression of pulmonary vascular remodeling and obliterative vascular lesions in patients with pulmonary arterial hypertension. In this study, we examined the expression of platelet-derived growth factor receptor isoforms in pulmonary arterial smooth muscle and pulmonary arterial endothelial cells and investigated whether platelet-derived growth factor secreted from pulmonary arterial smooth muscle cell or pulmonary arterial endothelial cell promotes pulmonary arterial smooth muscle cell proliferation. Our results showed that the protein expression of platelet-derived growth factor receptor α and platelet-derived growth factor receptor ß in pulmonary arterial smooth muscle cell was upregulated in patients with idiopathic pulmonary arterial hypertension compared to normal subjects. Platelet-derived growth factor activated platelet-derived growth factor receptor α and platelet-derived growth factor receptor ß in pulmonary arterial smooth muscle cell, as determined by phosphorylation of platelet-derived growth factor receptor α and platelet-derived growth factor receptor ß. The platelet-derived growth factor-mediated activation of platelet-derived growth factor receptor α/platelet-derived growth factor receptor ß was enhanced in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal cells. Expression level of platelet-derived growth factor-AA and platelet-derived growth factor-BB was greater in the conditioned media collected from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell than from normal pulmonary arterial endothelial cell. Furthermore, incubation of idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell with conditioned culture media from normal pulmonary arterial endothelial cell induced more platelet-derived growth factor receptor α activation than in normal pulmonary arterial smooth muscle cell. Accordingly, the conditioned media from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell resulted in more pulmonary arterial smooth muscle cell proliferation than the media from normal pulmonary arterial endothelial cell. These data indicate that (a) the expression and activity of platelet-derived growth factor receptor are increased in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell compared to normal pulmonary arterial smooth muscle cell, and (b) pulmonary arterial endothelial cell from idiopathic pulmonary arterial hypertension patients secretes higher level of platelet-derived growth factor than pulmonary arterial endothelial cell from normal subjects. The enhanced secretion (and production) of platelet-derived growth factor from idiopathic pulmonary arterial hypertension-pulmonary arterial endothelial cell and upregulated platelet-derived growth factor receptor expression (and function) in idiopathic pulmonary arterial hypertension-pulmonary arterial smooth muscle cell may contribute to enhancing platelet-derived growth factor/platelet-derived growth factor receptor-associated pulmonary vascular remodeling in pulmonary arterial hypertension.

Determining the Effect of External Stressors and Cognitive Distraction on Microsurgical Skills and Performance.

Introduction: Microsurgery is an essential element of Plastic Surgery practice. There is a paucity of studies assessing the impact of stress and cognitive distraction on technical microsurgical performance. The ability to complete cognitive and technical skills in parallel has not been assessed in a microsurgical setting. Aim: To test the hypothesis that cognitive distraction and external stressors negatively affect microsurgical performance in a high fidelity simulation setting. Materials/Methods: Fourteen surgeons across all levels of training undertook 2 microsurgical skills sessions, 1 month apart. Session one established baseline microsurgical skill. In session two, skills were assessed with the introduction of realistic operative room cognitive distractions (ORDIs). Outcome measures were efficiency and accuracy, measured by Time to Completion (TTC) and Anastomosis Lapse Index (ALI), respectively. Key Results: Fourteen participants (6 novices, 5 plastic surgery specialist trainees and 3 consultants) completed both microsurgical skills sessions. In total, 28-microvascular anastomosis were analyzed. Mean baseline TTC for the group was 20.36 min. With cognitive distraction and external stress mean TTC decreased to 17.87 min. Mean baseline ALI score for the group was 3.32 errors per anastomosis. The introduction of cognitive distraction and external stress increased the mean to 4.86 errors per anastomosis. Total errors per anastomosis increased from 91 errors at baseline to 137 errors with cognitive distraction and external stress. Under stress, participants were more efficient but had reduced anastomotic accuracy. Conclusion: Under stress, surgeons were more efficient, this translated into faster completion of a microsurgical anastomosis. Efficiency, however, came at the expense of accuracy.

STIM2 (Stromal Interaction Molecule 2)-Mediated Increase in Resting Cytosolic Free Ca2+ Concentration Stimulates PASMC Proliferation in Pulmonary Arterial Hypertension.

An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary artery smooth muscle cells (PASMCs) triggers pulmonary vasoconstriction and stimulates PASMC proliferation leading to vascular wall thickening. Here, we report that STIM2 (stromal interaction molecule 2), a Ca2+ sensor in the sarcoplasmic reticulum membrane, is required for raising the resting [Ca2+]cyt in PASMCs from patients with pulmonary arterial hypertension (PAH) and activating signaling cascades that stimulate PASMC proliferation and inhibit PASMC apoptosis. Downregulation of STIM2 in PAH-PASMCs reduces the resting [Ca2+]cyt, whereas overexpression of STIM2 in normal PASMCs increases the resting [Ca2+]cyt The increased resting [Ca2+]cyt in PAH-PASMCs is associated with enhanced phosphorylation (p) of CREB (cAMP response element-binding protein), STAT3 (signal transducer and activator of transcription 3), and AKT, increased NFAT (nuclear factor of activated T-cell) nuclear translocation, and elevated level of Ki67 (a marker of cell proliferation). Furthermore, the STIM2-associated increase in the resting [Ca2+]cyt also upregulates the antiapoptotic protein Bcl-2 in PAH-PASMCs. Downregulation of STIM2 in PAH-PASMCs with siRNA (1) decreases the level of pCREB, pSTAT3, and pAKT and inhibits NFAT nuclear translocation, thereby attenuating proliferation, and (2) decreases Bcl-2, which leads to an increase of apoptosis. In summary, these data indicate that upregulated STIM2 in PAH-PASMCs, by raising the resting [Ca2+]cyt, contributes to enhancing PASMC proliferation by activating the CREB, STAT3, AKT, and NFAT signaling pathways and stimulating PASMC proliferation. The STIM2-associated increase in the resting [Ca2+]cyt is also involved in upregulating Bcl-2 that makes PAH-PASMCs resistant to apoptosis, and thus plays an important role in sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in patients with PAH.