Is Robotic Surgery the Future for Resectable Esophageal Cancer?: A Systematic Literature Review of Oncological and Clinical Outcomes.

BACKGROUND: Radical esophagectomy for resectable esophageal cancer is a major surgical intervention, associated with considerable postoperative morbidity. The introduction of robotic surgical platforms in esophagectomy may enhance advantages of minimally invasive surgery enabled by laparoscopy and thoracoscopy, including reduced postoperative pain and pulmonary complications. This systematic review aims to assess the clinical and oncological benefits of robot-assisted esophagectomy. METHODS: A systematic literature search of the MEDLINE (PubMed), Embase and Cochrane databases was performed for studies published up to 1 August 2023. This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocols and was registered in the PROSPERO database (CRD42022370983). Clinical and oncological outcomes data were extracted following full-text review of eligible studies. RESULTS: A total of 113 studies (n = 14,701 patients, n = 2455 female) were included. The majority of the studies were retrospective in nature (n = 89, 79%), and cohort studies were the most common type of study design (n = 88, 79%). The median number of patients per study was 54. Sixty-three studies reported using a robotic surgical platform for both the abdominal and thoracic phases of the procedure. The weighted mean incidence of postoperative pneumonia was 11%, anastomotic leak 10%, total length of hospitalisation 15.2 days, and a resection margin clear of the tumour was achieved in 95% of cases. CONCLUSIONS: There are numerous reported advantages of robot-assisted surgery for resectable esophageal cancer. A correlation between procedural volume and improvements in outcomes with robotic esophagectomy has also been identified. Multicentre comparative clinical studies are essential to identify the true objective benefit on outcomes compared with conventional surgical approaches before robotic surgery is accepted as standard of practice.

Circumferential resection margin rates in esophageal cancer resection- oncological equivalency and comparable clinical outcomes between open versus minimally invasive techniques: A retrospective cohort study.

BACKGROUND: Radical surgery for esophageal cancer requires macroscopic and microscopic clearance of all malignant tissue. A critical element of the procedure is achieving a negative circumferential margin (CRM) to minimize local recurrence. The utility of minimally invasive surgery poses challenges in replicating techniques developed in open surgery, particularly for hiatal dissection in esophago-gastrectomy. In this study, the technical approach and clinical and oncological outcomes for open and laparoscopic esophago-gastrectomy are described with particular reference to CRM involvement. MATERIALS AND METHODS: This cohort study included all patients undergoing either open or laparoscopic esophago-gastrectomy between January 2004 to June 2022 in a single tertiary center. A standard surgical technique for hiatal dissection of the esophago-gastric junction developed in open surgery was adapted for a laparoscopic approach. Clinical parameters, length of stay (LOS), post-operative complications and mortality data were collected and analyzed by a Mann-Whitney U or Fisher's exact method. RESULTS: Overall 447 patients underwent an esophago-gastrectomy in the study with 219 open and 228 laparoscopic procedures. The CRM involvement was 18.8% in open surgery and 13.6% in laparoscopic surgery. The 90-day-mortality for open surgery was 4.1% compared with 2.2% for laparoscopic procedures. Median Intensive care unit (ITU), inpatient LOS and 30-day readmission rates were shorter for laparoscopic compared with open esophago-gastrectomy (ITU: 5 versus 8 days, P=0.0004; LOS: 14 versus 20 days, P=0.022; 30-day re-admission 7.46% versus 10.50%). Post-operative complication rates were comparable across both cohorts. The rates of starting adjuvant chemotherapy were 51.8% after open and 74.4% in laparoscopic esophago-gastrectomy. CONCLUSION: This study presents a standardized surgical approach to hiatal dissection for esophageal cancer. We present equivalence between open and laparoscopic esophago-gastrectomy in clinical, oncological and survival outcomes with similar rates of CRM involvement. We also observe a significantly shorter hospital length of stay with the minimally invasive approach.

Left atrial Thrombus formation after discontinuation of anticoagulation in patient with severe bioprosthetic mitral stenosis.

BACKGROUND: Mitral valve stenosis can be a highly symptomatic condition with significant complications if left untreated. In such cases, mitral valve replacement with a bioprosthetic or mechanical valve may be a viable solution to prevent progressive disease. Current guidelines do not recommend continued anticoagulation beyond 6 months for patients who have undergone bioprosthetic valve replacement without a separate indication for anticoagulation. With this case discussion we aim to 1) Review the current indications for anticoagulation for bioprosthetic mitral valves in patients without atrial fibrillation and 2) Discuss the constellation of comorbidities that may affect the decision to begin anticoagulation therapy. CASE PRESENTATION: We present a case describing a 55-year-old male with end-stage renal disease, coronary artery disease with coronary artery bypass graft surgery, and bioprosthetic mitral valve replacement 2 years prior with rapid degeneration of the replaced valve and on warfarin without a clear indication for anticoagulation. The patient was admitted for symptomatic, severe mitral stenosis and consideration of transcatheter mitral valve-in-valve replacement. During hospital admission, warfarin was discontinued and replaced with prophylactic anticoagulation. However, 8 days after warfarin cessation an intraoperative transesophageal echocardiography revealed a newly developed large left atrial thrombus leading to cancellation of the planned operation. CONCLUSIONS: This patient developed a left atrial thrombus after discontinuing warfarin in the setting of rapidly deteriorating bioprosthetic valve stenosis and vascular comorbidities. The decision to discontinue warfarin was made in concordance with current guidelines, which do not indicate systemic anticoagulation post 3-6 months after bioprosthetic valve replacement without separate indication for anticoagulation. This case identifies the need to investigate rebound hypercoagulability and further risk stratify comorbidities which may independently increase the risk of clot formation in the setting of severe mitral valve stenosis.

Trends in Time in Range-Related Publications and Clinical Trials: A Bibliometric Review.

Objective: The goal of this article was to describe trends in publications (including conference abstracts) and clinical trials that report on glycemic time in range (TIR). Data sources: Reviewed databases included but were not limited to MEDLINE and Embase. Clinical trial registries were also sourced. Study selection: All studies reporting TIR published between 2010 and 2021 were included. Clinical trials reporting TIR that started in or after 2010 were also included. Non-English publications, abstracts, and clinical trials were excluded. Book chapters, nonhuman studies, and studies not reporting TIR were excluded. Data extraction: Manuscript/abstract category, publication year, study region, interventional versus observational role of continuous glucose monitoring (CGM), and clinical trial start and completion dates were captured. Glycemic outcomes reported in publications or trials, including TIR as a primary outcome, A1C, time below range (TBR), and time above range (TAR), were also captured. Results: A total of 373 clinical trials, 531 publications, and 620 abstracts were included in the review. The number of trials, publications, and abstracts reporting TIR significantly increased, particularly between 2018 and 2021, during which time the number of clinical trials, publications, and conference abstracts reporting TIR increased by 6-fold, 12-fold, and 4.5-fold, respectively. About 35-44% of studies reported TIR as a primary outcome. Approximately 54% of clinical trials, 47% of publications, and 47% of conference abstracts reported the role of CGM to be observational. TBR was reported more often than TAR. Conclusion: The marked increase in the number of trials, publications, and abstracts reporting TIR highlights the increasing significance and acceptance of TIR as an outcome measure in diabetes management.

The Role of Mucin Expression in the Diagnosis of Oesophago-Gastric Cancer: A Systematic Literature Review.

Survival in oesophago-gastric cancer (OGC) is poor due to early diagnostic challenges. Non-invasive risk stratification may identify susceptible patients with pre-malignant or benign disease. Following diagnostic confirmation with endoscopic biopsy, early OGC may be treated sooner. Mucins are transmembrane glycoproteins implicated in OGC with potential use as biomarkers of malignant transformation. This systematic review defines the role of mucins in OGC diagnosis. A literature search of MEDLINE, Web of Science, Embase and Cochrane databases was performed following PRISMA protocols for studies published January 1960-December 2022. Demographic data and data on mucin sampling and analysis methods were extracted. The review included 124 studies (n = 11,386 patients). Gastric adenocarcinoma (GAc) was the commonest OG malignancy (n = 101) followed by oesophageal adenocarcinoma (OAc, n = 24) and squamous cell carcinoma (OSqCc, n = 10). Mucins MUC1, MUC2, MUC5AC and MUC6 were the most frequently implicated. High MUC1 expression correlated with poorer prognosis and metastases in OSqCc. MUC2 expression decreases during progression from healthy mucosa to OAc, causing reduced protection from gastric acid. MUC5AC was upregulated, and MUC6 downregulated in GAc. Mucin expression varies in OGC; changes may be epigenetic or mutational. Profiling upper GI mucin expression in OGC, with pre-malignant, benign and healthy controls may identify potential early diagnostic biomarkers.

Recent advances in dosage form design for the elderly: a review.

INTRODUCTION: With the increase in the elderly population and the prevalence of multiple medical conditions, medication adherence, and efficacy have become crucial for the effective management of their health. The aging population faces unique challenges that need to be addressed through advancements in drug delivery systems and formulation technologies. AREAS COVERED: The current review highlights the recent advances in dosage form design for older individuals, with consideration of their specific physiological and cognitive changes. Various dosage forms, such as modified-release tablets/capsules, chewable tablets, and transdermal patches, can be tailored to meet the specific needs of elderly patients. Advancements in drug delivery systems, such as nanotherapeutics, additive manufacturing (three-dimensional printing), and drug-food combinations, improve drug delivery and efficacy and overcome challenges, such as dysphagia and medication adherence. EXPERT OPINION: Regulatory guidelines and considerations are crucial in ensuring the safe utilization of medications among older adults. Important factors to consider include geriatric-specific guidelines, safety considerations, labeling requirements, clinical trial considerations, and adherence and accessibility considerations.

Scrub typus fulminating as liver failure: A rare report.

Scrub typhus is almost an endemic tropical mite-borne, zoonotic illness often cognate with the bacterium Orientia tsutsugamushi. After a typical incubation period of a fortnight, non-specific symptoms including fever, headache, and a specific skin 'eschar' is customary. If untreated after a symptomatic week, scrub typus may precipitate end-organ involvements spiraling into vivid complications. Nevertheless, crub typhus tends to display mild transaminitis, frank liver failure is hardly common in clinical practice. An instance of scrub typus triggering fulminant hepatic failure (FHF) in a middle-aged female is being reported here.

The 2022 FASEB Virtual Catalyst Conference on the Cardiac Interatrial Septum and Stroke Risk, December 7, 2022.

There is emerging evidence that the cardiac interatrial septum has an important role as a thromboembolic source for ischemic strokes. There is little consensus on treatment of patients with different cardiac interatrial morphologies or pathologies who have had stroke. In this paper, we summarize the important background, diagnostic, and treatment considerations for this patient population as presented during the Federation of American Societies for Experimental Biology (FASEB) Virtual Catalytic Conference on the Cardiac Interatrial Septum and Stroke Risk, held on December 7, 2022. During this conference, many aspects of the cardiac interatrial septum were discussed. Among these were the embryogenesis of the interatrial septum and development of anatomic variants such as patent foramen ovale and left atrial septal pouch. Also addressed were various mechanisms of injury such as shunting physiologies and the consequences that can result from anatomic variants, as well as imaging considerations in echocardiography, computed tomography, and magnetic resonance imaging. Treatment options including anticoagulation and closure were addressed, as well as an in-depth discussion on whether the left atrial septal pouch is a stroke risk factor. These issues were discussed and debated by multiple experts from neurology, cardiology, and radiology.

Radiomic applications in upper gastrointestinal cancer surgery.

INTRODUCTION: Cross-sectional imaging plays an integral role in the management of upper gastrointestinal (UGI) cancer, from initial diagnosis and staging to determining appropriate treatment strategies. Subjective imaging interpretation has known limitations. The field of radiomics has evolved to extract quantitative data from medical imaging and relate these to biological processes. The key concept behind radiomics is that the high-throughput analysis of quantitative imaging features can provide predictive or prognostic information, with the goal of providing individualised care. OBJECTIVE: Radiomic studies have shown promising utility in upper gastrointestinal oncology, highlighting a potential role in determining stage of disease and degree of tumour differentiation and predicting recurrence-free survival. This narrative review aims to provide an insight into the concepts underpinning radiomics, as well as its potential applications for guiding treatment and surgical decision-making in upper gastrointestinal malignancy. CONCLUSION: Outcomes from studies to date have been promising; however, further standardisation and collaboration are required. Large prospective studies with external validation and evaluation of radiomic integration into clinical pathways are needed. Future research should now focus on translating the promising utility of radiomics into meaningful patient outcomes.

Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics.

Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.

Chitosan: A Potential Biopolymer in Drug Delivery and Biomedical Applications.

Chitosan, a biocompatible and biodegradable polysaccharide derived from chitin, has surfaced as a material of promise for drug delivery and biomedical applications. Different chitin and chitosan extraction techniques can produce materials with unique properties, which can be further modified to enhance their bioactivities. Chitosan-based drug delivery systems have been developed for various routes of administration, including oral, ophthalmic, transdermal, nasal, and vaginal, allowing for targeted and sustained release of drugs. Additionally, chitosan has been used in numerous biomedical applications, such as bone regeneration, cartilage tissue regeneration, cardiac tissue regeneration, corneal regeneration, periodontal tissue regeneration, and wound healing. Moreover, chitosan has also been utilized in gene delivery, bioimaging, vaccination, and cosmeceutical applications. Modified chitosan derivatives have been developed to improve their biocompatibility and enhance their properties, resulting in innovative materials with promising potentials in various biomedical applications. This article summarizes the recent findings on chitosan and its application in drug delivery and biomedical science.

The importance of social risk factors for patients diagnosed with opioid use disorder.

BACKGROUND: Opioid Use Disorder (OUD) is a major public health concern, with mortality rates in individuals who use opioid medications being up to 30 times greater than those of individuals who do not use such medications. Social risk factors influence one's ability to make healthy choices and pose challenges for individuals recovering from OUD. OBJECTIVE: This study aimed to explore the relationship between OUD and social risk factors for patients who have been prescribed opioid medications. METHODS: Data for this retrospective cohort study were obtained from a health care system's comprehensive data warehouses consisting of electronic health records (EHR) with Social Determinants of Health (SDoH) screening information, and medical and prescription claims data. The study compared patients 18 years of age or older with an opioid prescription who were considered users of opioids to patients who had a documented diagnosis of OUD in the EHR. All patients were screened for SDoH. The analyses were performed using Statistical Analysis System (SAS) (SAS Institute Inc, Cary, NC). RESULTS: The study included patients with an outpatient visit at one of the health care system's primary care or oncology facilities between January 1, 2017 and December 31, 2018. There were 5003 patients with an opioid prescription who were considered users of opioids, and 209 patients with an opioid prescription as well as a diagnosis of OUD. Compared to the opioid use group, patients with OUD were more likely to have a lower educational attainment, encounter financial hardship, or be food insecure. Being female, older than 40, and having a higher Charlson Comorbidity Index score were factors associated with lower rates of opioid misuse. CONCLUSION: Identifying social risk factors and providing appropriate services to individuals with OUD is essential in mitigating challenges to recovery and promoting overall health for these individuals.

Emerging Trends in Lipid-Based Vaccine Delivery: A Special Focus on Developmental Strategies, Fabrication Methods, and Applications.

Lipid-based vaccine delivery systems such as the conventional liposomes, virosomes, bilosomes, vesosomes, pH-fusogenic liposomes, transferosomes, immuno-liposomes, ethosomes, and lipid nanoparticles have gained a remarkable interest in vaccine delivery due to their ability to render antigens in vesicular structures, that in turn prevents its enzymatic degradation in vivo. The particulate form of lipid-based nanocarriers confers immunostimulatory potential, making them ideal antigen carriers. Facilitation in the uptake of antigen-loaded nanocarriers, by the antigen-presenting cells and its subsequent presentation through the major histocompatibility complex molecules, leads to the activation of a cascade of immune responses. Further, such nanocarriers can be tailored to achieve the desired characteristics such as charge, size, size distribution, entrapment, and site-specificity through modifications in the composition of lipids and the selection of the appropriate method of preparation. This ultimately adds to its versatility as an effective vaccine delivery carrier. The current review focuses on the various lipid-based carriers that have been investigated to date as potential vaccine delivery systems, the factors that affect their efficacy, and their various methods of preparation. The emerging trends in lipid-based mRNA vaccines and lipid-based DNA vaccines have also been summarized.

Measurement of Δ9THC and metabolites in the brain and peripheral tissues after intranasal instillation of a nanoformulation.

BACKGROUND: Comparative bioavailability of cannabinoids following their administration by dosing routes has been studied previously, but there are no quantitative reports of distribution of Δ9THC, nor its metabolites, across various brain regions following intranasal (i.n.) administration. The aim of the present study was to determine the time course of Δ9THC transport from nose to brain and to quantify the distribution of Δ9THC and its metabolites in four brain regions. METHODS: Δ9THC was formulated as a lipophilic nano-emulsion and instilled i.n. to three groups of adult mice and euthanized after 2, 4, and 8 h. Brains were dissected into 4 regions. Sensitive analytical methods (HPLC-MS) were utilized to quantify levels of Δ9THC and metabolites in brain regions and peripheral tissues. Data was expressed as mean concentrations (± SEM) of Δ9THC and metabolites in brain regions, blood, plasma, urine, and liver. Two-way analysis of variance was performed followed by post hoc multiple comparisons. RESULTS: Peak concentrations of Δ9THC were reached at 2 h in the brain (15.9 ng/mg), blood (4.54 µg/mL), and plasma (4.56 µg /mL). The percentage of administered dose of Δ9THC transported to the brain (5.9%) was greater than in blood (1.7%), plasma (1.6%), urine (0.4%), and liver (0.1%). Concentrations of Δ9THC and its THC-COOH metabolite in the liver reached their highest levels at 8 h. DISCUSSION: The present study is the first to report the uptake and distribution across brain regions of Δ9THC and its principal metabolites following i.n. administration. The systemic bioavailability (absorption into the blood) of intranasal Δ9THC was 1.7% of the administered dose, much lower than that reported by others after oral ingestion (7-10%) and inhalation (20-35%), but those prior studies did not measure the transport of Δ9THC into brain regions. Others have reported Δ9THC in the whole brain following i.n. instillation in a different species (rats) to be twice (5.9%) that following i.p. injections, while metabolites of Δ9THC in rat brain were lower after i.n. administration. CONCLUSIONS: The intranasal route of a Δ9THC nanoformulation is an effective way to deliver cannabinoids to the brain, especially in those who cannot take the medication orally. Going forward, a metered dosing nasal spray will provide accurate and consistent doses.

The Cancer Hub Approach for Upper Gastrointestinal Surgery During COVID-19 Pandemic: Outcomes from a UK Cancer Centre.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to increase intensive care capacity. Our unit instituted the 'RM Partners Cancer Hub' at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a 'COVID-lite' setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period. METHODS: From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted. RESULTS: A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae. CONCLUSION: Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption.

Shortened Duration of Dual Antiplatelet Therapy Following Percutaneous Coronary Intervention: A Contemporary Clinical Review.

Percutaneous coronary intervention with stent implantation is an integral aspect of minimally interventional cardiac procedures. The technology and techniques behind stent design and implantation have evolved rapidly over several decades. However, continued discourse remains around optimal peri- and post-interventional management with dual antiplatelet therapy to minimise both major cardiovascular or cerebrovascular events and iatrogenic bleeding risk. Standard guidelines around dual antiplatelet therapy historically recommended long-term dual antiplatelet therapy for 12 months (with consideration for >12 months in certain patients); however, emerging data and generational improvements in the safety of drug-eluting stents have ushered in a new era of short-term therapy to reduce the incidence of major bleeding events. This case review will provide an overview of the current state of guidelines around duration of dual antiplatelet therapy and examine recent updates and continued gaps in existing research.