Novel Local Chimeric Flap Based on Tunnelized Facial Artery Myomucosal Island Flap and Submandibular Gland Flap for Reconstructions After Oral Squamous Cell Carcinoma Surgery.

The reconstruction of oral tongue and floor of mouth defects after resections of squamous cell carcinoma is a challenging task in reconstructive surgery aiming for appropriate restoration of oral function and quality of life improvement. In this study, the authors introduce the innovative reconstruction technique of medium-sized defects consisting of tunnelized facial artery myomucosal island flap and submandibular gland flap as the local chimeric flap pedicled on facial vessels. A retrospective case series evaluation of 4 patients suffering from oral cavity cancer (stages III and IVa), who underwent transoral tumor excision with neck dissection and immediate reconstruction in the time period September 2020 to July 2021, was conducted. No flap losses or flap-related complications were identified. No recurrences occurred during the follow-up at 11.0±4.5 months (range: 6-16 mo, median=11 mo). Tunnelized facial artery myomucosal island flap and submandibular gland flap local chimeric flap expands the reconstruction options of medium-sized defects after ablative oral cancer surgery in carefully selected patients primarily not suitable for free flap reconstructions.

Moving from the Trial to the Real World: Improving Medication Adherence Using Insights of Implementation Science.

Medication nonadherence is a serious public health concern. Although there are promising interventions that improve medication adherence, most interventions are developed and tested in tightly controlled research environments that are dissimilar from the real-world settings where the majority of patients receive health care. Implementation science methods have the potential to facilitate and accelerate the translation shift from the trial world to the real world. We demonstrate their potential by reviewing published, high-quality medication adherence studies that could potentially be translated into clinical practice yet lack essential implementation science building blocks. We further illustrate this point by describing an adherence study that demonstrates how implementation science creates a junction between research and real-world settings. This article is a call to action for researchers, clinicians, policy makers, pharmaceutical companies, and others involved in the delivery of care to adopt the implementation science paradigm in the scale-up of adherence (research) programs.

Influence of Digital Intervention Messaging on Influenza Vaccination Rates Among Adults With Cardiovascular Disease in the United States: Decentralized Randomized Controlled Trial.

BACKGROUND: Seasonal influenza affects 5% to 15% of Americans annually, resulting in preventable deaths and substantial economic impact. Influenza infection is particularly dangerous for people with cardiovascular disease, who therefore represent a priority group for vaccination campaigns. OBJECTIVE: We aimed to assess the effects of digital intervention messaging on self-reported rates of seasonal influenza vaccination. METHODS: This was a randomized, controlled, single-blind, and decentralized trial conducted at individual locations throughout the United States over the 2020-2021 influenza season. Adults with self-reported cardiovascular disease who were members of the Achievement mobile platform were randomized to receive or not receive a series of 6 patient-centered digital intervention messages promoting influenza vaccination. The primary end point was the between-group difference in self-reported vaccination rates at 6 months after randomization. Secondary outcomes included the levels of engagement with the messages and the relationship between vaccination rates and engagement with the messages. Subgroup analyses examined variation in intervention effects by race. Controlling for randomization group, we examined the impact of other predictors of vaccination status, including cardiovascular condition type, vaccine drivers or barriers, and vaccine knowledge. RESULTS: Of the 49,138 randomized participants, responses on the primary end point were available for 11,237 (22.87%; 5575 in the intervention group and 5662 in the control group) participants. The vaccination rate was significantly higher in the intervention group (3418/5575, 61.31%) than the control group (3355/5662, 59.25%; relative risk 1.03, 95% CI 1.004-1.066; P=.03). Participants who were older, more educated, and White or Asian were more likely to report being vaccinated. The intervention was effective among White participants (P=.004) but not among people of color (P=.42). The vaccination rate was 13 percentage points higher among participants who completed all 6 intervention messages versus none, and at least 2 completed messages appeared to be needed for effectiveness. Participants who reported a diagnosis of COVID-19 were more likely to be vaccinated for influenza regardless of treatment assignment. CONCLUSIONS: This personalized, evidence-based digital intervention was effective in increasing vaccination rates in this population of high-risk people with cardiovascular disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584645; https://clinicaltrials.gov/ct2/show/NCT04584645.

Effects of inorganic nitrate on ischaemia-reperfusion injury after coronary artery bypass surgery: a randomised controlled trial.

BACKGROUND: Nitric oxide (NO) is an important signalling molecule in the cardiovascular system with protective properties in ischaemia-reperfusion injury. Inorganic nitrate, an oxidation product of endogenous NO production and a constituent in our diet, can be recycled back to bioactive NO. We investigated if preoperative administration of inorganic nitrate could reduce troponin T release and other plasma markers of injury to the heart, liver, kidney, and brain in patients undergoing cardiac surgery. METHODS: This single-centre, randomised, double-blind, placebo-controlled trial included 82 patients undergoing coronary artery bypass surgery with cardiopulmonary bypass. Oral sodium nitrate (700 mg×2) or placebo (NaCl) were administered before surgery. Biomarkers of ischaemia-reperfusion injury and plasma nitrate and nitrite were collected before and up to 72 h after surgery. Troponin T release was our predefined primary endpoint and biomarkers of renal, liver, and brain injury were secondary endpoints. RESULTS: Plasma concentrations of nitrate and nitrite were elevated in nitrate-treated patients compared with placebo. The 72-h release of troponin T did not differ between groups. Other plasma biomarkers of organ injury were also similar between groups. Blood loss was not a predefined outcome parameter, but perioperative bleeding was 18% less in nitrate-treated patients compared with controls. CONCLUSION: Preoperative administration of inorganic nitrate did not influence troponin T release or other plasma biomarkers of organ injury in cardiac surgery. CLINICAL TRIAL REGISTRATION: NCT01348971.

Will high-dose heparin affect blood loss and inflammatory response in patients undergoing cardiopulmonary bypass?

INTRODUCTION: We performed a randomized study to investigate if a high versus a standard dose of heparin dose during cardiopulmonary bypass could affect intra- and post-operative bleeding and reduce the inflammatory response. METHODS: A total of 30 patients undergoing elective coronary artery bypass grafting were randomized into high or standard dose of heparin during cardiopulmonary bypass. Blood loss was documented peri- and post-operatively, and interleukin-6, tumor necrosis factor-α, and C3 were measured in conjunction with cardiopulmonary bypass. RESULTS: Data from 29 patients were analyzed after exclusion of one patient. The mean initial bolus and total heparin doses were 43,000 ± 5,800 IU versus 35,000 ± 4,100 IU, (p < 0.001), and 58,000 ± 9,500 IU versus 45,000 ± 7,900 IU, (p < 0.001) in the intervention and the control group, respectively. The median intra-operative bleeding was 150 mL (interquartile range 100-325) in the control versus 225 mL (IQR 200-350) in the intervention group, p = 0.15. The median chest tube blood loss 12 hour post-operatively was 300 mL (interquartile range 250-385) in the control versus 450 mL (IQR 315-505) in the intervention group, p = 0.029. There was no significant difference between the control group and the intervention group during cardiopulmonary bypass for the measured inflammatory markers interleukin-6 (p = 0.98), tumor necrosis factor-α (p = 0.72), or C3 (p = 0.13). CONCLUSION: This small study showed a small increase of post-operative bleeding associated with higher heparin dosage in conjunction with cardiopulmonary bypass but did not demonstrate an effect of heparin on the inflammatory response to cardiopulmonary bypass.

Intraspinal characteristics of thoracic spinal nerve roots anomalies.

Purpose: The anomalous anatomical arrangement of the thoracic spinal nerve roots within the spinal canal can complicate the surgical treatment of several pathologies. The aim of this work was to reveal intraspinal anatomical variations of the thoracic spinal nerve roots.Methods: Anatomical study on 43 cadavers with a mean age of 53.7. After opening the spinal canal and dural sac, intradural and extradural anomalies of the thoracic spinal nerve roots were documented. Extradural communicating branches were excised, histologically processed and examined for the presence of nervous tissue.Results: We found 14 cases (32.6%) of intraspinal thoracic nerve root variations: intradural in 8 cases (18.6%), intradural communicating branches in 3 cases (6.97%), extradural anatomical variations occurred 6 cases (13.95%), 2 cases (4.65%) had extradural communicating branches between the nerve roots, 1 case had simultaneous occurrence of intradural and extradural communications (0.23%). All the results are differentiated according to the plexus type. In macroscopic extradural thoracic communicating branch had no nervous tissue on microscopy.Conclusions: This study describes intraspinal anatomical variations of thoracic spinal nerve roots. Knowledge of these variables should help prevent the failure of several medical procedures.

Outcomes of aortic arch repair with extended (≥ 90 minutes) antegrade cerebral perfusion.

OBJECTIVES: To analyze outcomes with extended duration of antegrade cerebral perfusion (ACP) during hypothermic circulatory arrest (HCA) for total arch repair (TAR). DESIGN: Retrospective study of consecutive patients undergoing TAR with HCA and ACP. Patients were divided into group A (ACP ≥ 90 min, n = 12) and group B (ACP < 90 min, n = 17) and compared regarding in-hospital mortality and neurological complications (primary outcome measures) and major complications, biochemical markers of organ damage, and blood product use (secondary outcome measures). Complications were analyzed according to standards of the International Aortic Arch Surgery Study Group. RESULTS: Overall in-hospital mortality was 4/29 (14%); 1/12 (8.3%) in group A versus 3/17 (18%) in group B, p = 0.62. No grade-V (lethal) neurological complication occurred, but five patients (all in group B) had grade-IV neurological complications: one general and two each focal and spinal neurological deficit (p = 0.047, overall). Prevalence of grade-II (temporary) general neurological deficit was 17% (group A) versus 27% (group B), p = 0.66. None of the patients suffered ≥ grade-IV respiratory or renal complications. Other complications, biochemical markers, and blood product usage were not significantly different. CONCLUSION: Outcomes in TAR with HCA and extended (≥ 90 min) three-vessel ACP were encouraging and could be contemplated with anticipated time-consuming TAR.

Introducing intravascular microdialysis for continuous lactate monitoring in patients undergoing cardiac surgery: a prospective observational study.

INTRODUCTION: Lactate is a marker of hypoperfusion and may be used for risk assessment in critically ill patients. Although evidence suggests that repeated lactate measurements are of clinical interest, how and when lactate should be analyzed is controversial. Intravascular microdialysis provides a novel method for the continuous monitoring of lactate, which may be clinically beneficial in critically ill patients. METHODS: Circulating lactate levels were continuously monitored in 80 patients undergoing cardiac surgery using either a separate single-lumen microdialysis catheter or a triple-lumen central venous catheter with an integrated microdialysis function. The catheter was placed with the tip positioned in the superior vena cava. Arterial blood gas samples were taken every hour to obtain reference values, and the lactate levels were analyzed in a blood gas analyzer. RESULTS: A total of 1,601 paired microdialysis-arterial blood gas lactate samples were obtained. Bland-Altman analysis showed a bias (mean difference) ± limits of agreement (±1.96 SD) of 0.02 ± 0.42 mmol/L. The regression coefficient was 0.98 (P = 0.0001). CONCLUSIONS: Central venous microdialysis is an accurate and reliable method for continuous blood lactate monitoring in patients undergoing cardiac surgery. The system may be useful for early lactate-guided therapy in critically ill patients.

Mapping the Cardiometabolic Patient Experience and Self-Care Behaviors to Inform Design, Implementation, and Persistent Use of Digital Health Care Solutions: Mixed Methods Study.

BACKGROUND: Cardiometabolic conditions including acute coronary syndrome (ACS) and type 2 diabetes (T2D) require comprehensive care and patient engagement in self-care behaviors, and the drivers of those behaviors at the individual and health system level are still poorly understood. OBJECTIVE: We aim to gain insights into self-care behaviors of individuals with cardiometabolic conditions. METHODS: A convenience sample of 98 adult patients with ACS and T2D was recruited in the United States, Germany, and Taiwan to participate in a mixed methods study using ethnographic methods. All participants completed 7-day web-based diaries tracking their level of engagement, and 48 completed 90-minute web-based semistructured interviews between February 4, 2021, and March 27, 2021, focusing on themes including moments of engagement. Qualitative analysis identified factors influencing self-care practices and a Patient Mind States Model prototype. RESULTS: Patient reports indicate that many patients feel social pressure to adhere to treatment. Patients' experience can be understood within 5 categories defined in terms of their degree of engagement and adherence ("ignoring," "struggling," "juggling," "controlling," and "reframing"). CONCLUSIONS: For people living with ACS and T2D, the self-care journey is defined by patterns of patient experiences, which can identify areas that tailored digital health care interventions may play a meaningful role.

Behavioral Engagement and Activation Model Study (BEAMS): A latent class analysis of adopters and non-adopters of digital health technologies among people with Type 2 diabetes.

Many people with Type 2 diabetes (T2D) who could benefit from digital health technologies (DHTs) are either not using DHTs or do use them, but not for long enough to reach their behavioral or metabolic goals. We aimed to identify subgroups within DHT adopters and non-adopters and describe their unique profiles to better understand the type of tailored support needed to promote effective and sustained DHT use across a diverse T2D population. We conducted latent class analysis of a sample of adults with T2D who responded to an internet survey between December 2021 and March 2022. We describe the clinical and psychological characteristics of DHT adopters and non-adopters, and their attitudes toward DHTs. A total of 633 individuals were characterized as either DHT "Adopters" (n = 376 reporting any use of DHT) or "Non-Adopters" (n = 257 reporting never using any DHT). Within Adopters, three subgroups were identified: 21% (79/376) were "Self-managing Adopters," who reported high health activation and self-efficacy for diabetes management, 42% (158/376) were "Activated Adopters with dropout risk," and 37% (139/376) were "Non-Activated Adopters with dropout risk." The latter two subgroups reported barriers to using DHTs and lower rates of intended future use. Within Non-Adopters, two subgroups were identified: 31% (79/257) were "Activated Non-Adopters," and 69% (178/257) were "Non-Adopters with barriers," and were similarly distinguished by health activation and barriers to using DHTs. Beyond demographic characteristics, psychological, and clinical factors may help identify different subgroups of Adopters and Non-Adopters.

In this study, we characterized subgroups of adopters and non-adopters of digital health technologies (DHTs) for managing Type 2 diabetes, such as apps to track nutrition, continuous glucose monitors, and activity monitors like Fitbit. Self-efficacy for diabetes management, health activation, and perceived barriers to use DHT emerged as characteristics that distinguished subgroups. Notably, subgroups of adopters differed in their interest to use these technologies in the next 3 months; groups with low levels of self-efficacy and health activation were least interested in using them and thus at risk of discontinuing use. The ability to identify these subgroups can inform strategies tailored to each subgroup that motivate adoption of DHTs and promote long-term engagement.

Mortality and reoperations in survivors operated on for acute type A aortic dissection and implications for catheter-based or hybrid interventions.

OBJECTIVE: This study investigated late outcomes (mortality, reoperations) and their associated predictors after operations for acute type A aortic dissection. The role catheter-based and hybrid interventions is discussed. METHODS: All hospital survivors operated on for acute type A aortic dissection from 1990 through 2009 were reviewed, with cross-sectional follow-up. Mortality (overall and aortic) and freedom from reoperations (proximal and distal) were estimated using actuarial methods. Preoperative, intraoperative, and postoperative variables (n = 44) associated with late outcomes were analyzed with univariable and multivariable (Cox) statistical methods. RESULTS: Of 360 operated-on patients, 291 hospital survivors (81%) were monitored for a median of 5.5 years (1864 patient-years). Total late mortality was 30% (n = 86), with estimated (standard error) survival of 82% (3%), 64% (4%), and 48% (6%) at 5, 10, and 15 years, respectively. Aortic events accounted for at least 27% (up to 42% including unknown causes) of late deaths. In Cox analysis, variables independently related (hazard ratios [95% confidence limits]) to late mortality were increased age (1.6 per 10 years [1.3, 2.0]), earlier operation (<2005; 2.3 [1.2, 4.6]), permanent neurologic damage (2.6 [1.6, 4.2]), and respiratory insufficiency (3.4 [1.8, 6.4]). Thirty-four patients underwent 46 reoperations, 21 on the proximal and 25 on the distal aorta, up to 19 years after the primary operation; respective in-hospital reoperative mortality was 14% and 12%. Estimated freedom (standard error) from aortic reoperation was 95% (2%), 87% (4%), and 61% (5%) at 5, 10, and 15 years, respectively. In multivariable Cox analysis (hazard ratios [95% confidence limits]), use of surgical adhesive at the primary operation (4.2 [1.6, 11]) and temporary neurologic damage (3.2l [1.2, 8.9]) were independently related to proximal reoperation, and DeBakey type I dissection (10.5 [1.4, 80]) was related to late distal reoperation. Catheter-based (endovascular, percutaneous) or hybrid procedures were not used in any patients but could have been used in up to 74% of reoperations, including in four of six of those that resulted in in-hospital death and putatively in 10 of 17 patients who sustained lethal aortic events without reoperation. CONCLUSIONS: Despite close follow-up, aortic-related death after a successful operation for acute type A aortic dissection is prevalent, and overall mortality remains substantial. Reoperations are not uncommon, may be indicated very late as well as repeatedly in the same patient, and are associated with a significant mortality. Increased use of applicable but seemingly under-used catheter-based or hybrid treatment approaches could benefit this growing patient population by offering repeat intervention to more patients and as substitute for reoperative open surgery in selected cases.

Predicting Chronic Hyperplastic Candidiasis Retro-Angular Mucosa Using Machine Learning.

Chronic hyperplastic candidiasis (CHC) presents a distinctive and relatively rare form of oral candidal infection characterized by the presence of white or white-red patches on the oral mucosa. Often mistaken for leukoplakia or erythroleukoplakia due to their appearance, these lesions display nonhomogeneous textures featuring combinations of white and red hyperplastic or nodular surfaces. Predominant locations for such lesions include the tongue, retro-angular mucosa, and buccal mucosa. This paper aims to investigate the potential influence of specific anatomical locations, retro-angular mucosa, on the development and occurrence of CHC. By examining the relationship between risk factors, we present an approach based on machine learning (ML) to predict the location of CHC occurrence. In this way, we employ Gradient Boosting Regression (GBR) to classify CHC lesion locations based on important risk factors. This estimator can serve both research and diagnostic purposes effectively. The findings underscore that the proposed ML technique can be used to predict the occurrence of CHC in retro-angular mucosa compared to other locations. The results also show a high rate of accuracy in predicting lesion locations. Performance assessment relies on Mean Squared Error (MSE), Root Mean Squared Error (RMSE), R-squared (R2), and Mean Absolute Error (MAE), consistently revealing favorable results that underscore the robustness and dependability of our classification method. Our research contributes valuable insights to the field, enhancing diagnostic accuracy and informing treatment strategies.

Clinical Experience with Autofluorescence Guided Oral Squamous Cell Carcinoma Surgery.

In our study, the effect of the use of autofluorescence (Visually Enhanced Lesion Scope-VELscope) on increasing the success rate of surgical treatment in oral squamous carcinoma (OSCC) was investigated. Our hypothesis was tested on a group of 122 patients suffering from OSCC, randomized into a study and a control group enrolled in our study after meeting the inclusion criteria. The preoperative checkup via VELscope, accompanied by the marking of the range of a loss of fluorescence in the study group, was performed before the surgery. We developed a unique mucosal tattoo marking technique for this purpose. The histopathological results after surgical treatment, i.e., the margin status, were then compared. In the study group, we achieved pathological free margin (pFM) in 55 patients, pathological close margin (pCM) in 6 cases, and we encountered no cases of pathological positive margin (pPM) in the mucosal layer. In comparison, the control group results revealed pPM in 7 cases, pCM in 14 cases, and pFM in 40 of all cases in the mucosal layer. This study demonstrated that preoperative autofluorescence assessment of the mucosal surroundings of OSCC increased the ability to achieve pFM resection 4.8 times in terms of lateral margins.

Tracheobronchial transplantation with a stem-cell-seeded bioartificial nanocomposite: a proof-of-concept study.

BACKGROUND: Tracheal tumours can be surgically resected but most are an inoperable size at the time of diagnosis; therefore, new therapeutic options are needed. We report the clinical transplantation of the tracheobronchial airway with a stem-cell-seeded bioartificial nanocomposite. METHODS: A 36-year-old male patient, previously treated with debulking surgery and radiation therapy, presented with recurrent primary cancer of the distal trachea and main bronchi. After complete tumour resection, the airway was replaced with a tailored bioartificial nanocomposite previously seeded with autologous bone-marrow mononuclear cells via a bioreactor for 36 h. Postoperative granulocyte colony-stimulating factor filgrastim (10 µg/kg) and epoetin beta (40,000 UI) were given over 14 days. We undertook flow cytometry, scanning electron microscopy, confocal microscopy epigenetics, multiplex, miRNA, and gene expression analyses. FINDINGS: We noted an extracellular matrix-like coating and proliferating cells including a CD105+ subpopulation in the scaffold after the reseeding and bioreactor process. There were no major complications, and the patient was asymptomatic and tumour free 5 months after transplantation. The bioartificial nanocomposite has patent anastomoses, lined with a vascularised neomucosa, and was partly covered by nearly healthy epithelium. Postoperatively, we detected a mobilisation of peripheral cells displaying increased mesenchymal stromal cell phenotype, and upregulation of epoetin receptors, antiapoptotic genes, and miR-34 and miR-449 biomarkers. These findings, together with increased levels of regenerative-associated plasma factors, strongly suggest stem-cell homing and cell-mediated wound repair, extracellular matrix remodelling, and neovascularisation of the graft. INTERPRETATION: Tailor-made bioartificial scaffolds can be used to replace complex airway defects. The bioreactor reseeding process and pharmacological-induced site-specific and graft-specific regeneration and tissue protection are key factors for successful clinical outcome. FUNDING: European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, StratRegen, Vinnova Foundation, Radiumhemmet, Clinigene EU Network of Excellence, Swedish Cancer Society, Centre for Biosciences (The Live Cell imaging Unit), and UCL Business.

Impaired splicing of fibronectin is associated with thoracic aortic aneurysm formation in patients with bicuspid aortic valve.

OBJECTIVE: Thoracic aortic aneurysm is a common complication in patients with bicuspid aortic valve (BAV). Alternatively spliced extra domain A (EDA) of fibronectin (FN) has an essential role in tissue repair. Here we analyze the expression of FN spliceforms in dilated and nondilated ascending aorta of tricuspid aortic valve (TAV) and BAV patients. METHODS AND RESULTS: The mRNA expression was analyzed in the ascending aorta by Affymetrix Exon arrays in patients with TAV (n=40) and BAV (n=69). EDA and extra domain B (EDB) expression was increased in dilated aorta from TAV patients compared with nondilated aorta (P<0.001 and P<0.05, respectively). In contrast, EDA expression was not increased in dilated aorta from BAV patients (P=0.25), whereas EDB expression was upregulated (P<0.01). The expression of EDA correlated with maximum aortic diameter in TAV (ρ=0.58) but not in BAV (ρ=0.15) patients. Protein analyses of EDA-FN showed concordant results. Transforming growth factor-ß treatment influenced the splicing of FN and enhanced the formation of EDA-containing FN in cultured medial cells from TAV patients but not in cells derived from BAV patients. Gene set enrichment analysis together with multivariate and univariate data analyses of mRNA expression suggested that differences in the transforming growth factor-ß signaling pathway may explain the impaired EDA inclusion in BAV patients. CONCLUSIONS: Decreased EDA expression may contribute to increased aneurysm susceptibility of BAV patients.

Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue.

BACKGROUND: Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. METHODS: Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. RESULTS: Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. CONCLUSIONS: Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue.

Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.

Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10(-27 and-30)). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.

Oral presentation of paraneoplastic pemphigus as the first sign of tonsillar HPV associated squamous cell carcinoma. A case report.

BACKGROUND: Paraneoplastic pemphigus (PNP) in the oral cavity is a rare variant of blistering pemphigus disease closely associated with mostly malignant tumors. The diagnosis may even precede an underlying malignancy enabling early detection. Here, we describe a previously unreported case of PNP associated with HPV-related tonsillar squamous cell carcinoma. METHODS AND RESULTS: A 50-year-old woman was referred to a dentist because of painful oral lesions resembling aphthae major and minor. Later, blisters appeared and an incisional biopsy was performed. Histological examination revealed an unusual coexistence of subepithelial and intraepithelial blisters raising suspicion of paraneoplastic pemphigus. The patient underwent 18F-FDG PET/MRI, showing a metabolically active process in the left palatal tonsil. Diagnostic biopsy revealed HPV type 16 associated tonsillar squamous cell carcinoma. A left tonsillectomy with elective left-sided neck dissection was performed. The postoperative period was complicated by bilateral fluidothorax. Two weeks after radical tumor removal, the mucosal and skin lesions of PNP disappeared. The patient currently shows no evidence of recurrence either of malignancy or PNP eight months after the surgery. CONCLUSION: PNP is a rare autoimmune blistering disease characterized by polymorphous cutaneous and mucosal lesions associated with internal neoplasms including HPV associated squamous cell carcinoma of a tonsil. In order to identify an occult malignancy, a whole-body PET/CT or PET/MRI scan is recommended. Rarely, accurate patient management may depend on the dentist being familiar with this entity and on interdisciplinary cooperation involving dermatologist, radiologist, pathologist, and pneumologist. A strict patient follow-up is indicated.

Brief Digital Solutions in Behavior Change Interventions for Type 2 Diabetes Mellitus: A Literature Review.

INTRODUCTION: With the advent of the COVID-19 pandemic, health systems increasingly look to digital health solutions to provide support for self-management to people with type 2 diabetes (T2D). This review aimed to assess brief digital behavior change solutions (i.e., solutions that require limited engagement or contact) for T2D, including use of behavior change techniques (BCTs) and their impact on self-care and glycemic control. METHODS: A review was conducted by searching Embase and gray literature using a predefined search strategy to identify randomized controlled trials (RCT) published between January 1, 2015, and March 21, 2021. BCTs were coded using an internationally established BCT taxonomy v1 (BCTTv1). RESULTS: Out of 1426 articles identified, 10 RCTs were included in qualitative synthesis. Of these, six reported significant improvements in primary outcome(s), including improved patient engagement, glycemic control, self-efficacy, and physical activity. Interventions as short as 12 min were found to be effective, and users' ability to control their preferences was noted as conducive to engagement. Almost three quarters of BCTs targeted by interventions were under the hierarchical clusters of "Feedback and monitoring," "Goals and planning," and "Shaping knowledge." Interventions that targeted fewer BCTs were at least as effective as interventions that were more comprehensive in their goals. DISCUSSION: Digital behavior change solutions can successfully improve T2D self-care support and outcomes in a variety of populations including patients with low incomes, limited educational attainment, or living in rural areas. Easy-to-use interventions tailored to patient needs may be as effective as lengthy, complex, and more generalized interventions. CONCLUSIONS: Brief digital solutions can improve clinical and behavioral outcomes while reducing patient burden, fitting more easily in patients' lives and potentially improving usability. As T2D patients increasingly expect access to self-care assistance between face-to-face encounters, digital support tools will play a greater role in effective diabetes management programs.

Cervical lymphocele: A rare complication following salvage surgery for ocular adnexal apocrine adenocarcinoma. A case report and review of the literature.

BACKGROUND: An ocular adnexal apocrine adenocarcinoma (OAAA) is an extremely rare, but potentially aggressive and life-threatening tumor with ill-defined management based only on recommendations from a limited number of reported cases. The development of cervical lymphocele following neck dissection is a very rare complication, but one with well established methods for prevention and treatment. Here we describe a previously unreported case of salvage surgery including neck dissection for OAAA in addition to an emergence of cervical lymphocele. A literature review of current knowledge on both pathological conditions is included. METHODS AND RESULTS: A 58-year-old man suffering from OAAA, previously treated with multiple eye-sparing excisions and adjuvant proton therapy, underwent salvage surgery for locoregional recurrence of the tumor. A partial orbitectomy with orbital exenteration, primary reconstruction and left-sided neck dissection was performed. The procedure was complicated by a cervical lymphocele resolved after the surgical therapy. The patient remained disease-free during the one-year follow-up. CONCLUSION: OAAA is a locally aggressive tumor with potential to local or distant metastatic spread. Whole-body staging, regular clinico-radiological follow-up and stage-dependent therapy with surgery as the first-choice treatment is required. A cervical lymphocele as a complication of especially left-sided neck dissection is managed with a conservative or surgical therapy according to the level of lymph leakage, extent and localization of lesions, presence of local or systemic disorders and the period from primary surgery.