Value of multidetector computed tomography angiography in severe non-variceal upper gastrointestinal bleeding: a retrospective study in a referral bleeding unit.

BACKGROUND: Non-variceal upper gastrointestinal bleeding is a common gastroenterological emergency associated with significant morbidity and mortality. Upper gastrointestinal endoscopy is currently recommended as the gold standard modality for both diagnosis and treatment. As historically played a limited role in the diagnosis of acute non-variceal upper gastrointestinal bleeding, multidetector-row computed tomography angiography is emerging as a promising tool in the diagnosis of non-variceal upper gastrointestinal bleeding, especially for severe cases. However, to date, evidence concerning the role of multidetector-row computed tomography angiography in the non-variceal upper gastrointestinal bleeding diagnosis is still lacking. AIM: The purpose of this study was to retrospectively investigate the diagnostic performance of emergent multidetector-row computed tomography angiography performed prior to any diagnostic modality or following urgent upper endoscopy to identify the status, the site, and the underlying etiology of severe non-variceal upper gastrointestinal bleeding. METHODS: Institutional databases were reviewed in order to identify severe acute non-variceal upper gastrointestinal bleeding patients who were admitted to our bleeding unit and were referred for emergent multidetector-row computed tomography angiography prior to any hemostatic treatment (< 3 h) or following (< 3 h) endoscopy, between December 2019 and October 2022. The study aim was to evaluate the diagnostic performance of multidetector-row computed tomography angiography to detect the status, the site, and the etiology of severe non-variceal upper gastrointestinal bleeding with endoscopy, digital subtraction angiography, surgery, pathology, or a combination of them as reference standards. RESULTS: A total of 68 patients (38 men, median age 69 years [range 25-96]) were enrolled. The overall multidetector-row computed tomography angiography sensitivity, specificity, and accuracy to diagnose bleeding status were 77.8% (95% CI: 65.5-87.3), 40% (95% CI: 5.3-85.3), and 75% (95% CI: 63.0-84.7), respectively. Finally, the overall multidetector-row computed tomography angiography sensitivity to identify the bleeding site and the bleeding etiology were 92.4% (95% CI: 83.2-97.5) and 79% (95% CI: 66.8-88.3), respectively. CONCLUSION: Although esophagogastroduodenoscopy is the mainstay in the diagnosis and treatment of most non-variceal upper gastrointestinal bleeding cases, multidetector-row computed tomography angiography seems to be a feasible and effective modality in detecting the site, the status, and the etiology of severe acute non-variceal upper gastrointestinal bleeding. It may play a crucial role in the management of selected cases of non-variceal upper gastrointestinal bleeding, especially those clinically severe and/or secondary to rare and extraordinary rare sources, effectively guiding timing and type of treatment. However, further large prospective studies are needed to clarify the role of multidetector-row computed tomography angiography in the diagnostic process of acute non-variceal upper gastrointestinal bleeding.

Enhanced molecular release from elderly bone samples using collagenase I: insights into fatty acid metabolism alterations.

BACKGROUND: Bone is a metabolically active tissue containing different cell types acting as endocrine targets and effectors. Further, bone is a dynamic depot for calcium, phosphorous and other essential minerals. The tissue matrix is subjected to a constant turnover in response to mechanical/endocrine stimuli. Bone turnover demands high energy levels, making fatty acids a crucial source for the bone cells. However, the current understanding of bone cell metabolism is poor. This is partly due to bone matrix complexity and difficulty in small molecules extraction from bone samples. This study aimed to evaluate the effect of metabolite sequestering from a protein-dominated matrix to increase the quality and amount of metabolomics data in discovering small molecule patterns in pathological conditions. METHODS: Human bone samples were collected from 65 to 85 years old (the elderly age span) patients who underwent hip replacement surgery. Separated cortical and trabecular bone powders were treated with decalcifying, enzymatic (collagenase I and proteinase K) and solvent-based metabolite extraction protocols. The extracted mixtures were analyzed with the high-resolution mass spectrometry (HRMS). Data analysis was performed with XCMS and MetaboAnalystR packages. RESULTS: Fast enzymatic treatment of bone samples before solvent addition led to a significantly higher yield of metabolite extraction. Collagenase I and proteinase K rapid digestion showed more effectiveness in cortical and trabecular bone samples, with a significantly higher rate (2.2 folds) for collagenase I. Further analysis showed significant enrichment in pathways like de novo fatty acid biosynthesis, glycosphingolipid metabolism and fatty acid oxidation-peroxisome. CONCLUSION: This work presents a novel approach for bone sample preparation for HRMS metabolomics. The disruption of bone matrix conformation at the molecular level helps the molecular release into the extracting solvent and, therefore, can lead to higher quality results and trustable biomarker discovery. Our results showed ß-oxidation alteration in the aged bone sample. Future work covering more patients is worthy to identify the effective therapeutics to achieve healthy aging.

Effects of AIDiet intervention to improve diet quality, immuno-metabolic health in normal and overweight PCOS girls: a pilot study.

This study was conducted in two groups of girls with PCOS (polycystic ovary syndrome) categorized as slim (group N) and overweight-to-obese (group Ov/Ob). The study's primary outcome was to assess the impact of a 12-week anti-inflammatory diet (AIDiet) intervention, without energy deficit, on daily diet quality improvement, evaluated according to the KIDMED index. The secondary outcome was improving inflammatory, redox, hormonal, and metabolic statuses. In the study, which was completed by 13 girls from the Ov/Ob group and 19 girls from the N group, a significant improvement in the mean KIDMED score was obtained. Moreover, the intervention significantly improves concentration of total antioxidant capacity (TAC), fasting insulin, and the homeostatic model assessment for insulin resistance (HOMA-IR) index, in the Ov/Ob group, while both groups experienced a reduction in the concentration of interleukin (IL)-1 and IL-6, tumour necrosis factor (TNF-α), and androstenedione. The AIDiet intervention effectively improved the quality of the subjects' diets, which was associated with the improvement of hormonal and immuno-metabolic markers. However, these changes in normal-weight patients were observed regardless of body weight reduction. ClinicalTrials.gov Identifier NCT04738409.

Plasma microRNA signature associated with skeletal muscle wasting in post-menopausal osteoporotic women.

BACKGROUND: Skeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post-menopausal osteoporotic women. METHODS: One hundred seventy-nine miRNAs were assayed by quantitative real-time polymerase chain reaction in plasma samples from 28 otherwise healthy post-menopausal osteoporotic women (73.4 ± 6.6 years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n = 9, ASMMI = 4.88 ± 0.40 kg·m-2; second tertile: n = 10, ASMMI = 5.73 ± 0.23 kg·m-2; third tertile: n = 9, ASMMI = 6.40 ± 0.22 kg·m-2). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change ≥ ±1.5 and area under the curve (AUC) > 0.800 (P < 0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total-body dual-energy X-ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo-myokines were evaluated by bead-based immunofluorescent assays and enzyme-linked immunosorbent assays. RESULTS: Five miRNAs (hsa-miR-221-3p, hsa-miR-374b-5p, hsa-miR-146a-5p, hsa-miR-126-5p and hsa-miR-425-5p) resulted down-regulated and two miRNAs (hsa-miR-145-5p and hsa-miR-25-3p) were up-regulated in the first tertile (relative-low ASMMI) compared with the third tertile (relative-high ASMMI) (fold change ≥ ±1.5; P-value < 0.05). All the corresponding ROC curves had AUC > 0.8 (P < 0.05). Two signatures hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p showed the highest AUC, 0.914 (sensitivity = 77.78%; specificity = 100.00%) and 0.901 (sensitivity = 88.89%; specificity = 100.00%), respectively. CONCLUSIONS: In this study, we identified, for the first time, two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p, specifically associated with muscle mass wasting in post-menopausal osteoporotic women.

Definition of malnutrition from routinely-collected data for orthopedic surgery research: the global leadership initiative on malnutrition (GLIM) tool and others.

The correct identification of malnourished patients in the context of hip, knee, or spine surgery research would enhance the quality of analytical studies investigating the prediction potential of preoperative nutritional disorders on postoperative recovery. However, accurate malnutrition screening and diagnostic assessment rely on parameters that were not routinely collected in routine practice until a few years ago. The authors of this article present substitute literature-based equations that can be built up using historical routinely collected data to classify patients that had been at risk of malnutrition or malnourished. For what concerns the risk screening, several methods are available to identify patients at risk of over- or undernutrition, encompassing the BWd (body weight difference from the ideal weight), GNRI (geriatric nutritional risk index), INA (instant nutritional assessment), LxA (combination of lymphocyte count and albumin), PMA (protein malnutrition with acute inflammation), PMAC (protein malnutrition with acute and chronic inflammation), IDM (iron deficit malnutrition), and VBD (vitamin B deficit malnutrition). Conversely, the GLIM (global leadership initiative on malnutrition) criteria can be used to assess malnutrition and diagnose subclasses of undernutrition. Rational use of these tools can facilitate the conduction of efficient prospective studies in the future, as well as bespoke retrospective cohort studies and database research.

Evaluating safety risks of whole-body cryotherapy/cryostimulation (WBC): a scoping review from an international consortium.

Over the two last decades, whole-body cryotherapy/cryostimulation (WBC) has emerged as an exciting non-pharmacological treatment influencing inflammatory events at a cellular and physiological level, which can result in improved sleep quality, faster neuromuscular recovery after high-intensity exercise, and chronic pain relief for patients suffering different types of diseases (fibromyalgia, rheumatism, arthritis). Some evidence even suggests that WBC has benefits on mental health (depression, anxiety disorders) and cognitive functions in both adults and older adults, due to increased circulating BDNF levels. Recently, some safety concerns have been expressed by influential public health authorities (e.g., FDA, INSERM) based on reports from patients who developed adverse events upon or following WBC treatment. However, part of the data used to support these claims involved individuals whose entire body (except head) was exposed to extreme cold vaporized liquid nitrogen while standing in a narrow bathtub. Such a procedure is known as partial-body cryotherapy (PBC), and is often erroneously mistaken to be whole-body cryotherapy. Although having similarities in terms of naming and pursued aims, these two approaches are fundamentally different. The present article reviews the available literature on the main safety concerns associated with the use of true whole-body cryotherapy. English- and French-language reports of empirical studies including case reports, case series, and randomized controlled trials (RCTs) were identified through searches of PubMed, Scopus, Cochrane, and Web of Science electronic databases. Five case reports and two RCTs were included for a total of 16 documented adverse events (AEs). A critical in-depth evaluation of these AEs (type, severity, context of onset, participant's medical background, follow-up) is proposed and used to illustrate that WBC-related safety risks are within acceptable limits and can be proactively prevented by adhering to existing recommendations, contraindications, and commonsense guidelines.

Rare causes of acute non-variceal upper gastrointestinal bleeding: A comprehensive review.

Non-variceal upper gastrointestinal bleeding (NVUGIB) is a common gastroenterological emergency associated with significant morbidity and mortality. Gastroenterologists and other involved clinicians are generally assisted by international guidelines in its management. However, NVUGIB due to peptic ulcer disease only is mainly addressed by current guidelines, with upper gastrointestinal endoscopy being recommended as the gold standard modality for both diagnosis and treatment. Conversely, the management of rare and extraordinary rare causes of NVUGIB is not covered by current guidelines. Given they are frequently life-threatening conditions, all the involved clinicians, that is emergency physicians, diagnostic and interventional radiologists, surgeons, in addition obviously to gastroenterologists, should be aware of and familiar with their management. Indeed, they typically require a prompt diagnosis and treatment, engaging a dedicated, patient-tailored, multidisciplinary team approach. The aim of our review was to extensively summarize the current evidence with regard to the management of rare and extraordinary rare causes of NVUGIB.

Long non-coding RNAs in bone metastasis: progresses and perspectives as potential diagnostic and prognostic biomarkers.

In a precision medicine perspective, among the biomarkers potentially useful for early diagnosis of cancers, as well as to define their prognosis and eventually to identify novel and more effective therapeutic targets, there are the long non-coding RNAs (lncRNAs). The term lncRNA identifies a class of non-coding RNA molecules involved in the regulation of gene expression that intervene at the transcriptional, post-transcriptional, and epigenetic level. Metastasis is a natural evolution of some malignant tumours, frequently encountered in patients with advanced cancers. Onset and development of metastasis represents a detrimental event that worsen the patient's prognosis by profoundly influencing the quality of life and is responsible for the ominous progression of the disease. Due to the peculiar environment and the biomechanical properties, bone is a preferential site for the secondary growth of breast, prostate and lung cancers. Unfortunately, only palliative and pain therapies are currently available for patients with bone metastases, while no effective and definitive treatments are available. The understanding of pathophysiological basis of bone metastasis formation and progression, as well as the improvement in the clinical management of the patient, are central but challenging topics in basic research and clinical practice. The identification of new molecular species that may have a role as early hallmarks of the metastatic process could open the door to the definition of new, and more effective, therapeutic and diagnostic approaches. Non-coding RNAs species and, particularly, lncRNAs are promising compounds in this setting, and their study may bring to the identification of relevant processes. In this review, we highlight the role of lncRNAs as emerging molecules in mediating the formation and development of bone metastases, as possible biomarkers for cancer diagnosis and prognosis, and as therapeutic targets to counteract cancer spread.

Osteocalcin modulates parathyroid cell function in human parathyroid tumors.

Introduction: The bone matrix protein osteocalcin (OC), secreted by osteoblasts, displays endocrine effects. We tested the hypothesis that OC modulates parathyroid tumor cell function. Methods: Primary cell cultures derived from parathyroid adenomas (PAds) and HEK293 cells transiently transfected with the putative OC receptor GPRC6A or the calcium sensing receptor (CASR) were used as experimental models to investigate γ-carboxylated OC (GlaOC) or uncarboxylated OC (GluOC) modulation of intracellular signaling. Results: In primary cell cultures derived from PAds, incubation with GlaOC or GluOC modulated intracellular signaling, inhibiting pERK/ERK and increasing active ß-catenin levels. GlaOC increased the expression of PTH, CCND1 and CASR, and reduced CDKN1B/p27 and TP73. GluOC stimulated transcription of PTH, and inhibited MEN1 expression. Moreover, GlaOC and GluOC reduced staurosporin-induced caspase 3/7 activity. The putative OC receptor GPRC6A was detected in normal and tumor parathyroids at membrane or cytoplasmic level in cells scattered throughout the parenchyma. In PAds, the membrane expression levels of GPRC6A and its closest homolog CASR positively correlated; GPRC6A protein levels positively correlated with circulating ionized and total calcium, and PTH levels of the patients harboring the analyzed PAds. Using HEK293A transiently transfected with either GPRC6A or CASR, and PAds-derived cells silenced for CASR, we showed that GlaOC and GluOC modulated pERK/ERK and active ß-catenin mainly through CASR activation. Conclusion: Parathyroid gland emerges as a novel target of the bone secreted hormone osteocalcin, which may modulate tumor parathyroid CASR sensitivity and parathyroid cell apoptosis.

The benefits of grape seed extract in neurological disorders and brain aging.

Common neurological disorders, including neurodegenerative diseases, stroke, epilepsy, autism and psychiatric disorders, affect many people worldwide and threaten their lives and health by inducing movement disorders, behavioral disorders, or a combination of both. Oxidative stress and neuroinflammation play a central role in neuronal damage and neurological diseases induction and progression. In addition, protein homeostasis (proteostasis) impairment occurs in many neurodegenerative diseases, which plays a critical role in the progression of the pathology. Grape seed contains several flavonoids and non-flavonoids and exerts potent antioxidant and anti-inflammatory effects. In addition, polyphenols and flavanols can maintain cellular proteostasis. Since impaired proteostasis is closely involved in all amyloid diseases, particularly neurodegenerative diseases, grape seeds extract can be a valuable therapeutic agent. Therefore, this review discusses the protective and therapeutic mechanisms of grape seed against neurological disorders and, in the end, links GSE to microRNAs as future therapeutic developments.

Severe Stenosis of Mitral Bioprosthetic Valve Thrombosis in a Patient with HCV-Related Cirrhosis and Duodenal Variceal Bleeding: The Deadly Triad.

Bioprosthetic valve thrombosis (BPVT) is considered a relatively rare but life-threatening clinical entity. Thus, there is the need of high clinical suspicion in order to make a timely diagnosis and related appropriate therapeutic interventions. In this regard, the management of BPVT is high risk, whatever the option taken (surgery and/or systemic fibrinolysis). The presence of severe comorbidities-as decompensated cirrhosis-further complicates the clinical decision-making process, calling for a patient-tailored integrated multidisciplinary approach. We report a challenging case of a 45-year-old patient with mitral bioprosthetic valve thrombosis and hepatitis C virus (HCV)-related cirrhosis complicated by active duodenal variceal bleeding.

Quality performance measures in upper gastrointestinal endoscopy for lesion detection: Italian AIGO-SIED-SIGE joint position statement.

Esophagogastroduodenoscopy (EGD) plays a crucial role in the management of gastroduodenal diseases by allowing a direct and accurate evaluation of the mucosa and the execution of several operative maneuvers. Despite a constant development of new imaging tools and operative devices, the widespread use of EGD has not resulted in a significant reduction of mortality for patients affected by esophageal/gastric cancer during the last three decades in Western countries. Evidence indicates that this disheartening scenario derives from a high variability of execution of EGD which determines its quality and diagnostic yield, delaying the diagnosis of neoplastic diseases. Based on this evidence, in recent years many scientific societies have produced different position papers aimed at defining quality performance measures in EGD. Thus, the Italian Association of Gastroenterologists and Endoscopists, the Italian Society of Digestive Endoscopy and the Italian Society of Gastroenterology have produced this joint document based on the review of ASGE, ACG, BSG, ESGE and Asian Consensus EGD position papers with the aim of indicating the quality standards of EGD (pre-, intra- and post-procedure) focused on lesion detection to be adopted in the Italian context.

SUMOylation and NEDDylation in Primary and Metastatic Cancers to Bone.

Post-translational modifications comprise series of enzymatically-driven chemical modifications, virtually involving the entire cell proteome, that affect the fate of a target protein and, in turn, cell activity. Different classes of modifications can be established ranging from phosphorylation, glycosylation, ubiquitination, acetylation, methylation, lipidation and their inverse reactions. Among these, SUMOylation and NEDDylation are ubiquitin-like multi-enzymatic processes that determine the bound of SUMOs and NEDD8 labels, respectively, on defined amino acidic residues of a specific protein and regulate protein function. As fate-determinants of several effectors and mediators, SUMOylation and NEDDylation play relevant roles in many aspects of tumor cell biology. Bone represents a preferential site of metastasis for solid tumors (e.g., breast and prostate cancers) and the primary site of primitive tumors (e.g., osteosarcoma, chondrosarcoma). Deregulation of SUMOylation and NEDDylation affects different aspects of neoplastic transformation and evolution such as epithelial-mesenchymal transition, adaptation to hypoxia, expression and action of tumor suppressors and oncogenic mediators, and drug resistance. Thereby, they represent potential therapeutic targets. This narrative review aims at describing the involvement and regulation of SUMOylation and NEDDylation in tumor biology, with a specific focus on primary and secondary bone tumors, and to summarize and highlight their potentiality in diagnostics and therapeutic strategies.

Exposed endoscopic full-thickness resection for duodenal submucosal tumors: Current status and future perspectives.

Exposed endoscopic full-thickness resection (EFTR), with or without laparoscopic assistance, is an emergent natural orifice transluminal endoscopic surgery technique with promising safety and efficacy for the management of gastrointestinal submucosal tumors (SMTs) arising from the muscularis propria (MP), especially of the gastric wall. To date, evidence concerning duodenal exposed EFTR is lacking, mainly due to both the technical difficulty involved because of the special duodenal anatomy and concerns about safety and effectiveness of transmural wall defect closure. However, given the non-negligible morbidity and mortality associated with duodenal surgery, the recent availability of dedicated endoscopic tools for tissue-approximation capable to realize full-thickness defect closure could help in promoting the adoption of this endosurgical technique among referral centers. The aim of our study was to review the current evidence concerning exposed EFTR with or without laparoscopic assistance for the treatment of MP-arising duodenal SMTs.

Lipocalin 2 increases after high-intensity exercise in humans and influences muscle gene expression and differentiation in mice.

Lipocalin 2 (LCN2) is an adipokine that accomplishes several functions in diverse organs. However, its importance in muscle and physical exercise is currently unknown. We observed that following acute high-intensity exercise ("Gran Sasso d'Italia" vertical run), LCN2 serum levels were increased. The Wnt pathway antagonist, DKK1, was also increased after the run, positively correlating with LCN2, and the same was found for the cytokine Interleukin 6. We, therefore, investigated the involvement of LCN2 in muscle physiology employing an Lcn2 global knockout (Lcn2-/- ) mouse model. Lcn2-/- mice presented with smaller muscle fibres but normal muscle performance (grip strength metre) and muscle weight. At variance with wild type (WT) mice, the inflammatory cytokine Interleukin 6 was undetectable in Lcn2-/- mice at all ages. Intriguingly, Lcn2-/- mice did not lose gastrocnemius and quadriceps muscle mass and muscle performance following hindlimb suspension, while at variance with WT, they lose soleus muscle mass. In vitro, LCN2 treatment reduced the myogenic differentiation of C2C12 and primary mouse myoblasts and influenced their gene expression. Treating myoblasts with LCN2 reduced myogenesis, suggesting that LCN2 may negatively affect muscle physiology when upregulated following high-intensity exercise.

Exposed endoscopic full-thickness resection without laparoscopic assistance for gastric submucosal tumors: A systematic review and pooled analysis.

BACKGROUND: Exposed endoscopic full-thickness resection (Eo-EFTR) is emerging as a promising minimally invasive alternative to surgery for the treatment of deep gastric submucosal tumors (G-SMTs). However, literature concerning this subject is heterogeneous and data mostly come from relatively small retrospective studies. AIMS: We aimed to perform a pooled analysis of published data with regard to gastric Eo-EFTR, providing a pooled estimate of technical and clinical outcomes. METHODS: The protocol was registered in PROSPERO. MEDLINE and EMBASE databases were searched for studies published from 1998 to 2020. The primary outcomes were complete resection and surgical conversion rates. The secondary outcomes were overall and selected major adverse events rates. The Forest plots on primary and secondary endpoints were produced based on fixed and random effect models. RESULTS: Nineteen studies including 952 Eo-EFTR-treated G-SMTs were included. The pooled estimate of the complete resection rate and surgical conversion rates was 99.3% and 0.09%, respectively. The pooled estimate of overall major adverse events, delayed bleeding, delayed perforation and peritonitis, abdominal abscess and/or abdominal infection was 0.29%, 0.14%, 0.14%, and 0.12%, respectively. CONCLUSION: Gastric Eo-EFTR has a high rate of complete resection with a low surgical conversion rate. It appears to be relatively safe and might represent a non-inferior minimally invasive alternative to surgery in selected cases.

Acute upper gastrointestinal bleeding caused by esophageal right bronchial artery fistula: A case report.

BACKGROUND: Fistula between the esophagus and bronchial artery is an extremely rare and potentially life-threatening cause of acute upper gastrointestinal bleeding. Here, we report a case of fistula formation between the esophagus and a nonaneurysmal right bronchial artery (RBA). CASE SUMMARY: An 80-year-old woman with previous left pneumonectomy and recent placement of an uncovered self-expandable metallic stent for esophageal adenocarcinoma was admitted due to hematemesis. Emergent computed tomography showed indirect signs of fistulization between the esophagus and a nonaneurysmal RBA, in the absence of active bleeding. Endoscopy revealed the esophageal stent correctly placed and a moderate amount of red blood within the stomach, in the absence of active bleeding or tumor ingrowth/overgrowth. After prompt multidisciplinary evaluation, a step-up approach was planned. The bleeding was successfully controlled by esophageal restenting followed by RBA embolization. No signs of rebleeding were observed and the patient was discharged home with stable hemoglobin level on postoperative day 7. CONCLUSION: This was a previously unreported case of an esophageal RBA fistula successfully managed by esophageal restenting followed by RBA embolization.

Sclerostin and bone remodeling biomarkers responses to whole-body cryotherapy (- 110 °C) in healthy young men with different physical fitness levels.

We investigated the effects of single and repeated exposures to whole-body cryotherapy on biomarkers of bone remodeling and osteo-immune crosstalk: sclerostin, osteocalcin (OC), C-terminal cross-linked telopeptide of type I collagen (CTx-I), osteoprotegerin (OPG) and free soluble receptor activator for nuclear factor κ B ligand (sRANKL). The study included 22 healthy males, grouped in high physical fitness level (HPhL) and low physical fitness level (LPhL), all undergone 10 consecutive sessions in a cryogenic chamber (- 110 °C). We observed a significant time-effect on sclerostin (p < 0.05), OC (p < 0.01), CTx-I (p < 0.001), OC/CTx-I (p < 0.05), and significant differences in sRANKL between the groups (p < 0.05) after the 1st cryostimulation; a significant time-effect on OC (p < 0.001) and OC/CTx-I (p < 0.001) after the 10th cryostimulation, and a significant time-effect on CTx-I (p < 0.001) and OC/CTx-I (p < 0.01) after 10 sessions of WBC. In conclusion, in young men, the first exposure to extreme cold induced significant changes in serum sclerostin. The changes in sRANKL, between groups, suggest that fitness level may modify the body's response to cold. The effects of the first stimulus and the whole session are not identical, probably due to the physiological development of habituation to cold.

Closure techniques in exposed endoscopic full-thickness resection: Overview and future perspectives in the endoscopic suturing era.

Exposed endoscopic full-thickness resection (EFTR) without laparoscopic assistance is a minimally invasive natural orifice transluminal endoscopic surgery technique that is emerging as a promising effective and safe alternative to surgery for the treatment of muscularis propria-originating gastric submucosal tumors. To date, various techniques have been used for the closure of the transmural post-EFTR defect, mainly consisting in clip- and endoloop-assisted closure methods. However, the recent advent of dedicated tools capable of providing full-thickness defect suture could further improve the efficacy and safety of the exposed EFTR procedure. The aim of our review was to evaluate the efficacy and safety of the different closure methods adopted in gastric-exposed EFTR without laparoscopic assistance, also considering the recent advent of flexible endoscopic suturing.