Clinical T2N0M0 Esophageal Cancer-Is Treatment Pathway Associated With Overall Survival?

INTRODUCTION: Esophageal cancer therapy is commonly multimodal. The CROSS trial demonstrated a survival benefit of neoadjuvant chemoradiation versus surgery alone in T1N1 or T2-3N0-1 patients. Theoretically, chemoradiation should be most beneficial to patients with advanced disease. Treating the intermediary stage, T2N0M0, is challenging as national guidelines offer multiple options. This study aims to compare survival outcomes and associated factors in clinical T2N0M0 esophageal cancer via treatment modality and compare clinical to pathological stage. The authors conclude that neoadjuvant therapy use has increased; however, there is no associated survival benefit, which may be due to over- or under-staging. METHODS: A retrospective study was performed using the National Cancer Database (2006-2016). Patients who underwent neoadjuvant chemoradiation followed by surgery (NCRT + ESOPH) were compared to patients who underwent esophagectomy first (ESOPH). Multivariable logistic regression was used to determine factors associated with treatment pathway. Overall survival was compared using Kaplan-Meier estimates and log-rank tests at 1-, 3-, and 5-y post-treatment. Additionally, a multiple logistic regression analysis was conducted to identify factors associated with adjuvant therapy in ESOPH patients. RESULTS: There were 1662 patients (NCRT + ESOPH: 904 [54.4%], ESOPH: 758 [45.6%]). There was no difference in 5-y survival between NCRT + ESOPH and ESOPH patients. Despite this, NCRT + ESOPH treatment rates rose from 33% to 74% between 2006 and 2016. Patients who received NCRT + ESOPH were younger and more commonly had no Charlson-Deyo comorbidities. Notably, 41% of patients were over-staged (T1 or lower), and 32.8% were under-staged (N ≥ 1). CONCLUSIONS: T2N0M0 remains difficult to characterize, and pathological staging corresponds poorly to clinical staging. Neoadjuvant therapy use has increased; however, the lack of a significant survival benefit to correlate with such may be secondary to over- or under-staging.

Post-Bariatric Plastic Surgery: Abdominoplasty, the State of the Art in Body Contouring.

Due to the increased prevalence of obesity in the last decades, bariatric surgery has been on the rise in recent years. Bariatric surgery is a compelling option for weight loss in obese patients with severe obesity-related comorbidities or for whom lifestyle modifications have proven ineffective. Redundant skin following significant weight loss is a common occurrence affecting up to 96% of patients who undergo bariatric surgery, negatively impacting physical and psychosocial health and detracting from activities of daily living. Statistics of the American Society of Plastic Surgeons show that 46,577 body contouring procedures were performed after massive weight loss in the USA in a 2020 report. Abdominoplasty, a well-established cosmetic surgery procedure for improving body contour, is performed by removing excess skin and fat from the abdominal wall and thereby restoring musculofascial integrity and skin elasticity, resulting in a more ideal body shape and increasing quality of life. Although abdominoplasty is a safe procedure, it has been associated with a higher complication rate compared with other body-contouring procedures. Technologic advances over the past decade have been developed as non-invasive alternatives or adjunctive tools to surgery to enhance cosmetic results and minimize complications. New energy-based technologies may supplant invasive surgery for mild to moderate skin laxity and/or diminish the extent of surgery and resulting scars. Plastic surgeons play a significant role in improving the quality of life of patients who suffer from obesity and underwent bariatric surgery. We are deeply convinced, however, that the advancement of knowledge and research in this field will determine the introduction of new technologies and custom-made techniques. This advancement will reduce the complication rate with a rapid reintegration of the patient into the world of work and resumption of daily activities.

The Toxin-Antitoxin MazEF Drives Staphylococcus aureus Biofilm Formation, Antibiotic Tolerance, and Chronic Infection.

Staphylococcus aureus is the major organism responsible for surgical implant infections. Antimicrobial treatment of these infections often fails, leading to expensive surgical intervention and increased risk of mortality to the patient. The challenge in treating these infections is associated with the high tolerance of S. aureus biofilm to antibiotics. MazEF, a toxin-antitoxin system, is thought to be an important regulator of this phenotype, but its physiological function in S. aureus is controversial. Here, we examined the role of MazEF in developing chronic infections by comparing growth and antibiotic tolerance phenotypes in three S. aureus strains to their corresponding strains with disruption of mazF expression. Strains lacking mazF production showed increased biofilm growth and decreased biofilm antibiotic tolerance. Deletion of icaADBC in the mazF::Tn background suppressed the growth phenotype observed with mazF-disrupted strains, suggesting the phenotype was ica dependent. We confirmed these phenotypes in our murine animal model. Loss of mazF resulted in increased bacterial burden and decreased survival rate of mice compared to its wild-type strain demonstrating that loss of the mazF gene caused an increase in S. aureus virulence. Although lack of mazF gene expression increased S. aureus virulence, it was more susceptible to antibiotics in vivo Combined, the ability of mazF to inhibit biofilm formation and promote biofilm antibiotic tolerance plays a critical role in transitioning from an acute to chronic infection that is difficult to eradicate with antibiotics alone.IMPORTANCE Surgical infections are one of the most common types of infections encountered in a hospital. Staphylococcus aureus is the most common pathogen associated with this infection. These infections are resilient and difficult to eradicate, as the bacteria form biofilm, a community of bacteria held together by an extracellular matrix. Compared to bacteria that are planktonic, bacteria in a biofilm are more resistant to antibiotics. The mechanism behind how bacteria develop this resistance and establish a chronic infection is unknown. We demonstrate that mazEF, a toxin-antitoxin gene, inhibits biofilm formation and promotes biofilm antibiotic tolerance which allows S. aureus to transition from an acute to chronic infection that cannot be eradicated with antibiotics but is less virulent. This gene not only makes the bacteria more tolerant to antibiotics but makes the bacteria more tolerant to the host.

Modified recombinant proteins can be exported via the Sec pathway in Escherichia coli.

The correct folding of a protein is a pre-requirement for its proper posttranslational modification. The Escherichia coli Sec pathway, in which preproteins, in an unfolded, translocation-competent state, are rapidly secreted across the cytoplasmic membrane, is commonly assumed to be unfavorable for their modification in the cytosol. Whether posttranslationally modified recombinant preproteins can be efficiently transported via the Sec pathway, however, remains unclear. ACP and BCCP domain (BCCP87) are carrier proteins that can be converted into active phosphopantetheinylated ACP (holo-ACP) and biotinylated-BCCP (holo-BCCP) by AcpS and BirA, respectively. In the present study, we show that, when ACP or BCCP87 is fused to the C-terminus of secretory protein YebF or MBP, the resulting fusion protein preYebF-ACP, preYebF-BCCP87, preMBP-ACP or preMBP-BCCP87 can be modified and then secreted. Our data demonstrate that posttranslational modification of preYebF-ACP, preYebF-BCCP87 preMBP-ACP and preMBP-BCCP87 can take place in the cytosol prior to translocation, and the Sec machinery accommodates these previously modified fusion proteins. High levels of active holo-ACP and holo-BCCP87 are achieved when AcpS or BirA is co-expressed, especially when sodium azide is used to retard their translocation across the inner membrane. Our results also provide an alternative to achieve a high level of modified recombinant proteins expressed extracellularly.