Partial Versus Complete Thymectomy in Non-Myasthenic Patients With Thymoma: A Systematic Review and Meta-Analysis of Clinical Outcomes.

OBJECTIVE: The optimal extent of surgical resection for non-myasthenic patients with thymoma is controversial. The objective of this meta-analysis was to compare complete to partial thymectomy in non-myasthenic patients for oncological and postoperative clinical outcomes. METHODS: We performed a PubMed and EMBASE search (from inception to January 2020) for English-language studies directly comparing partial thymectomy (thymomectomy) to complete thymectomy for thymoma resection. Clinical endpoints studied included overall and disease-free survival, Masaoka and World Health Organization staging, adjuvant therapy, postoperative complications, postoperative drainage, length of hospital stay, thymoma-related deaths, postresection development of myasthenia gravis, incomplete resection, and recurrence. Random effects meta-analyses across all clinical endpoints was done. RESULTS: There was no statistically significant difference between the two approaches with regard to recurrence (odds ratio [OR], 1.22; 95% confidence interval [CI], 0.78-1.92), completeness of resection (OR, 1.17; 95% CI, 0.66-2.10), adjuvant therapy (OR, 0.71; 95% CI, 0.40-1.26), or thymoma-related deaths (OR, 0.76; 95% CI, 0.12-4.66). There was a statistically significant decrease in postoperative complications (OR, 0.61; 95% CI, 0.39-0.97), drainage (mean difference [MD], -0.99; 95% CI, -1.98 to -0.01), and length of hospital length (MD, -1.88; 95% CI, -3.39 to -0.36) with partial thymectomy. CONCLUSIONS: The evidence appeared to suggest that partial thymectomy is oncologically equivalent to complete thymectomy for non-myasthenic patients with early-stage thymoma. There is an additional advantage of reduced postoperative complications and decreased length of hospital stay with partial thymectomy.

Postoperative Psychological Disorders Among Heart Transplant Recipients: A Meta-Analysis and Meta-Regression.

OBJECTIVE: This meta-analysis evaluates the pooled prevalence of depression, anxiety, adjustment disorder, and posttraumatic stress disorder (PTSD) among heart transplant recipients globally and determines underlying moderators. METHODS: The authors searched PubMed, Embase, PsychINFO, BIOSIS, Science Direct, and Cochrane CENTRAL databases from inception to March 1, 2019, and 1321 records and 42 full-text articles were selected and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We calculated the pooled prevalence proportion of depression, anxiety, adjustment disorder, and PTSD using random-effects models. Meta-regression was performed to identify important moderators that contribute to heterogeneity. RESULTS: Twenty studies met the inclusion criteria and comprised 2169 patients. The pooled prevalence of depression was 21.6% (95% confidence interval [CI] = 16.8%-27.3%), anxiety 11.1% (95% CI = 3.8%-28.5%), adjustment disorder 11.0% (95% CI = 3.1%-32.1%), and PTSD 13.5% (95% CI = 8%-21.8%). There was significant heterogeneity. Meta-regression was conducted to account for the heterogeneity of the prevalence proportion. Predisposing factors, for example, New York Heart Association classes II and III/IV, steroid treatment, and acute rejection of transplant (<3 months), were associated with high prevalence of depression. Protective factors, for example, age and higher ejection fraction after transplant of patients, were associated with low prevalence of depression. Female sex, single status, and number of months since transplant were associated with high prevalence of anxiety. Single status was associated with high prevalence of both adjustment disorder and transplant-related PTSD. CONCLUSIONS: The prevalence of psychiatric conditions, particularly depression, is high in heart transplant recipients. The identified protective and risk factors may guide psychological interventions in heart transplant recipients.

The antimalarial drug artesunate inhibits primary human cultured airway smooth muscle cell proliferation.

Airway smooth muscle (ASM) cell hyperplasia contributes to airway wall remodeling (AWR) in asthma. Glucocorticoids, which are used as first-line therapy for the treatment of inflammation in asthma, have limited impact on AWR, and protracted usage of high doses of glucocorticoids is associated with an increased risk of side effects. Moreover, patients with severe asthma often show reduced sensitivity to glucocorticoids. Artesunate, a semisynthetic artemisinin derivative used to treat malaria with minimal toxicity, attenuates allergic airway inflammation in mice, but its impact on AWR is not known. We examined the effects of artesunate on ASM proliferation in vitro and in vivo. Primary human ASM cells derived from nonasthmatic donors were treated with artesunate before mitogen stimulation. Artesunate reduced mitogen-stimulated increases in cell number and cyclin D1 protein abundance but had no significant effect on ERK1/2 phosphorylation. Artesunate, but not dexamethasone, inhibited phospho-Akt and phospho-p70(S6K) protein abundance. Artesunate, but not dexamethasone, inhibited mitogen-stimulated increases in cell number, cyclin D1, and phospho-Akt protein abundance on ASM cells derived from asthmatic donors. In a murine model of allergic asthma, artesunate reduced the area of α-smooth muscle actin-positive cells and decreased cyclin D1 protein abundance. Our study provides a basis for the future development of artesunate as a novel anti-AWR agent that targets ASM hyperplasia via the PI3K/Akt/p70(S6K) pathway and suggests that artesunate may be used as combination therapy with glucocorticoids.

Extracellular vesicle drug occupancy enables real-time monitoring of targeted cancer therapy.

Current technologies to measure drug-target interactions require complex processing and invasive tissue biopsies, limiting their clinical utility for cancer treatment monitoring. Here we develop an analytical platform that leverages circulating extracellular vesicles (EVs) for activity-based assessment of tumour-specific drug-target interactions in patient blood samples. The technology, termed extracellular vesicle monitoring of small-molecule chemical occupancy and protein expression (ExoSCOPE), utilizes bio-orthogonal probe amplification and spatial patterning of molecular reactions within matched plasmonic nanoring resonators to achieve in situ analysis of EV drug dynamics. It measures changes in drug occupancy and protein composition in molecular subpopulations of EVs. When used to monitor various targeted therapies, the ExoSCOPE revealed EV signatures that closely reflected cellular treatment efficacy. We further applied the technology for clinical cancer diagnostics and treatment monitoring. Using a small volume of blood, the ExoSCOPE accurately classified disease status and rapidly distinguished between targeted treatment outcomes, within 24 h after treatment initiation.

Integrin α7 expression is increased in asthmatic patients and its inhibition reduces Kras protein abundance in airway smooth muscle cells.

Airway smooth muscle (ASM) cells exhibit plastic phenotypic behavior marked by reversible modulation and maturation between contractile and proliferative phenotypic states. Integrins are a class of transmembrane proteins that have been implicated as novel therapeutic targets for asthma treatment. We previously showed that integrin α7 is a novel marker of the contractile ASM phenotype suggesting that targeting this protein may offer new avenues to counter the increase in ASM cell mass that underlies airways hyperresponsiveness (AHR) in asthma. We now determine whether inhibition of integrin α7 expression would revert ASM cells back to a proliferative phenotype to cause an increase in ASM cell mass. This would be detrimental to asthmatic patients who already exhibit increased ASM mass in their airways. Using immunohistochemical analysis of the Melbourne Epidemiological Study of Childhood Asthma (MESCA) cohort, we show for the first time that integrin α7 expression in patients with severe asthma is increased, supporting a clinically relevant role for this protein in asthma pathophysiology. Moreover, inhibition of the laminin-integrin α7 signaling axis results in a reduction in smooth muscle-alpha actin abundance and does not revert ASM cells back to a proliferative phenotype. We determined that integrin α7-induced Kras isoform of p21 Ras acts as a point of convergence between contractile and proliferative ASM phenotypic states. Our study provides further support for targeting integrin α7 for the development of novel anti-asthma therapies.

Are medical students' views of an ideal physician eroding? A study on perceived qualities of a "role model" doctor before and after housemanship and between two cohorts five years apart.

INTRODUCTION: This study aimed to examine the impact of housemanship and cohort effect on the perceptions of what constitutes a "role model physician" between 2 cohorts of medical students. MATERIALS & METHODS: Final year medical students of the Yong Loo Lin School of Medicine, National University of Singapore, from the classes of 2005 (pre- and post-housemanship) and class of 2009 (pre-housemanship) responded to an anonymous 25-statement questionnaire reflecting Fones et al's 25-item characterisation of a "role model" doctor. Qualitative data was also collected on student's perceived qualities of a role model doctor. RESULTS: For the 2005 cohort pre- and post-housemanship, only 3 of the 25 items had increased in importance post-housemanship. However, when comparing the 2005 and 2009 cohorts pre-housemanship, the latter cohort placed significantly greater importance on 12 of the 25 items. Willingness to teach was identified via qualitative analysis as a new important quality of a role model doctor for medical students. CONCLUSION: The importance placed on characteristics of "role model" physicians were relatively unchanged by housemanship within the same cohort but increased with time between 2 cohorts 5 years apart. This suggests that professional standards of an "ideal" doctor expected and aspired to by medical students may not be eroding as feared by the medical profession and society.

Total muscle-sparing uniportal video-assisted thoracoscopic surgery lobectomy.

BACKGROUND: Conventional video-assisted thoracoscopic lobectomy uses multiple incisions, including an access incision and several port incisions. This series aims to evaluate the technical feasibility and early results of uniportal video-assisted thoracoscopic surgery (UVATS) lobectomy using a small, total muscle-sparing incision. METHODS: We performed the first UVATS lobectomy in June 2009, and 38 major resections were attempted using this approach until September 2011. A single, small, muscle-sparing incision was made without rib spreading. True anatomic hilar dissection, individual vascular and bronchial ligation, and mediastinal lymph node dissection were performed under thoracoscopic visualization on a monitor. RESULTS: Thirty-two patients (84%) had malignant diseases, and 6 patients (16%) had benign diseases. Of the primary lung cancers, 85% were in stage I. Of the 38 attempted major resections, 32 UVATS lobectomies were successfully completed and 6 were converted to open thoracotomy. The early outcomes of successful UVATS lobectomy were analyzed (32 patients); 97% had no postoperative complications. There were no deaths. Mean pain score was 0.4 on postoperative day 1 and decreased to 0 by 1 week. Ninety-seven percent of patients received only oral analgesia postoperatively. Eight percent of patients experienced mild intercostal neuralgia not requiring treatment. No patients complained of shoulder dysfunction. The median duration of returning to full normal activities was 7 postoperative days. CONCLUSIONS: Total muscle-sparing UVATS lobectomy is technically feasible with low morbidity and mortality rates. Patients had minimal postoperative pain and narcotic use; and good functional outcomes with no shoulder dysfunction and early return to full normal activities.