Maximal Aerobic Power, Quality of Life, and Ejection Fraction in Survivors of Childhood Cancer Treated with Anthracyclines.

BACKGROUND: Anthracycline-induced cardiotoxicity is a frequent complication that can occur at any stage of treatment, even in survivors. OBJECTIVE: To determine maximum aerobic power, quality of life, and left ventricular ejection fraction in childhood cancer survivors treated with anthracyclines. DESIGN: Cross-sectional, observational study. METHODS: The left ventricular ejection fraction was obtained from the transthoracic echocardiogram report in the medical records. Each patient underwent a 6-minute walk test, assessment of maximum aerobic power on a cycle ergometer, and evaluation of perceived exertion using the EPInfant scale, and finally, their quality of life was evaluated using the pediatric quality of life inventory model. RESULTS: A total of 12 patients were studied, with an average of 16.2 years of age. All patients exhibited a left ventricular ejection fraction >60%, the mean distance covered in the 6-minute walk test was 516.7 m, and the mean of the maximum aerobic power was 70 W. Low quality of life scores were obtained in the physical and psychosocial aspects. In the Pearson test, a weak correlation without statistical significance was found between all the variables studied. CONCLUSIONS: Simultaneously with the detection of cardiotoxicity in childhood cancer survivors, it is pertinent to perform physical evaluations as physical condition and cardiotoxicity seem to be issues that are not necessarily dependent.

Transverse colon volvulus in a young patient with wandering liver.

We present the case of a 26-year-old male patient with no history of interest who consulted the emergency department due to occlusive symptoms. Urgent CT showed the presence of a transverse colonic volvulus in the context of a heterotopic liver, located in the left hypochondrium. There were no clinical or radiological signs of perforation or ischemia, so urgent endoscopic decompression was performed with subsequent elective surgery with a favorable resolution of the condition. Transverse colonic volvulus is rare (<1%) and wandering liver is an exceptional predisposing factor, with less than a hundred published cases. In these patients, endoscopic decompression carries a risk of perforation with high recurrence rates, and surgical treatment should be considered. However, in this case, in the absence of severity criteria, decompressive colonoscopy was considered an urgent treatment and subsequent elective surgery with favorable results.

Complications after breast augmentation with dermal fillers containing copolyamide: A systematic review.

Background: Dermal fillers containing copolyamide are used for breast augmentation and are marketed under different labels, such as Aquafilling, Los Deline, Aqualift, and Activegel. In recent years, the number of publications reporting complications after use of these fillers has increased. Methods: Through a computerized search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of published studies on complications, treatment options, and radiological findings related to breast augmentation with dermal fillers containing copolyamide was performed. Publications between January 1, 2007, and January 23, 2023, were included. Retrieved studies were screened for inclusion and quality assessment. The Joanna Briggs checklist for case reports and the Strengthening the Reporting of Observational Studies in Epidemiology checklist for cross-sectional studies were used. Results: Sixteen studies met the inclusion criteria: 14 case reports and 2 retrospective cohort studies, including 196 women and 333 complications. Long-term complications (≥30 days after surgery) were described in 15 studies. The most commonly reported complications were nodules in the breast (130 patients), pain (92 patients), inflammation and/or infection (43 patients), breast deformities (35 patients), and migration of the filler to the pectoralis muscle, abdominal wall, thoracic wall, pubic area, back, or upper extremity (27 patients). The median time between injection of the dermal filler and any complication was 18 months, and the majority of patients with complications required surgical intervention. Conclusion: Given the reports of severe complications months to years after injection of dermal fillers containing copolyamide and the lack of studies evaluating long-term safety, our interpretation is that dermal fillers containing copolyamide should not be used for breast augmentation.

Myeloid deletion of talin-1 reduces mucosal macrophages and protects mice from colonic inflammation.

The intestinal immune response is crucial in maintaining a healthy gut, but the enhanced migration of macrophages in response to pathogens is a major contributor to disease pathogenesis. Integrins are ubiquitously expressed cellular receptors that are highly involved in immune cell adhesion to endothelial cells while in the circulation and help facilitate extravasation into tissues. Here we show that specific deletion of the Tln1 gene encoding the protein talin-1, an integrin-activating scaffold protein, from cells of the myeloid lineage using the Lyz2-cre driver mouse reduces epithelial damage, attenuates colitis, downregulates the expression of macrophage markers, decreases the number of differentiated colonic mucosal macrophages, and diminishes the presence of CD68-positive cells in the colonic mucosa of mice infected with the enteric pathogen Citrobacter rodentium. Bone marrow-derived macrophages lacking expression of Tln1 did not exhibit a cell-autonomous phenotype; there was no impaired proinflammatory gene expression, nitric oxide production, phagocytic ability, or surface expression of CD11b, CD86, or major histocompatibility complex II in response to C. rodentium. Thus, we demonstrate that talin-1 plays a role in the manifestation of infectious colitis by increasing mucosal macrophages, with an effect that is independent of macrophage activation.

Targeting hypoxia-inducible factor-1 alpha suppresses Helicobacter pylori-induced gastric injury via attenuation of both cag-mediated microbial virulence and proinflammatory host responses.

Helicobacter pylori-induced inflammation is the strongest known risk factor for gastric adenocarcinoma. Hypoxia-inducible factor-1 (HIF-1α) is a key transcriptional regulator of immunity and carcinogenesis. To examine the role of this mediator within the context of H. pylori-induced injury, we first demonstrated that HIF-1α levels were significantly increased in parallel with the severity of gastric lesions in humans. In interventional studies targeting HIF-1α, H. pylori-infected mice were treated ± dimethyloxalylglycine (DMOG), a prolyl hydroxylase inhibitor that stabilizes HIF-1α. H. pylori significantly increased proinflammatory chemokines/cytokines and inflammation in vehicle-treated mice; however, this was significantly attenuated in DMOG-treated mice. DMOG treatment also significantly decreased function of the H. pylori type IV secretion system (T4SS) in vivo and significantly reduced T4SS-mediated NF-κB activation and IL-8 induction in vitro. These results suggest that prolyl hydroxylase inhibition protects against H. pylori-mediated pathologic responses, and is mediated, in part, via attenuation of H. pylori cag-mediated virulence and suppression of host proinflammatory responses.

Developing a Multi-Tiered System of Support-Based Plan for Bullying Prevention Among Students with Disabilities: Perspectives from General and Special Education Teachers During Professional Development.

Students with disabilities or at risk for disability identification (SWD) are disproportionately affected by the bullying dynamic; however, professional development and educator-focused training on preventing bullying for this population is lacking. To address this gap, this study presents an analysis of qualitative data collected from general and special education teachers (n = 33) participating in an online professional development training using Multi-Tiered System of Supports (MTSS) to prevent bullying among students with disabilities. Braun and Clarke's six-step process was used to identify key themes and exemplar quotes from qualitative reflections collected as knowledge check responses embedded within two training modules. Three themes were identified and examined based on MTSS tiers: (1) teacher perceptions of SWD and their inclusion in a MTSS-based bullying prevention plan; (2) identifying key stakeholders for preventing bullying within a MTSS-based bullying prevention plan; and (3) potential challenges and solutions of implementing a MTSS-based bullying prevention plan within the individual, classroom, and school contexts. Findings highlight the need to educate teachers on how to use MTSS, especially for bullying prevention and interventions that are inclusive of SWD. Implications from this work extend to all students including those with mental health considerations, regardless of disability status. Supplementary Information: The online version contains supplementary material available at 10.1007/s12310-023-09589-8.

Hypusination Maintains Intestinal Homeostasis and Prevents Colitis and Carcinogenesis by Enhancing Aldehyde Detoxification.

BACKGROUND & AIMS: The amino acid hypusine, synthesized from the polyamine spermidine by the enzyme deoxyhypusine synthase (DHPS), is essential for the activity of eukaryotic translation initiation factor 5A (EIF5A). The role of hypusinated EIF5A (EIF5AHyp) remains unknown in intestinal homeostasis. Our aim was to investigate EIF5AHyp in the gut epithelium in inflammation and carcinogenesis. METHODS: We used human colon tissue messenger RNA samples and publicly available transcriptomic datasets, tissue microarrays, and patient-derived colon organoids. Mice with intestinal epithelial-specific deletion of Dhps were investigated at baseline and in models of colitis and colon carcinogenesis. RESULTS: We found that patients with ulcerative colitis and Crohn's disease exhibit reduced colon levels of DHPS messenger RNA and DHPS protein and reduced levels of EIF5AHyp. Similarly, colonic organoids from colitis patients also show down-regulated DHPS expression. Mice with intestinal epithelial-specific deletion of Dhps develop spontaneous colon hyperplasia, epithelial proliferation, crypt distortion, and inflammation. Furthermore, these mice are highly susceptible to experimental colitis and show exacerbated colon tumorigenesis when treated with a carcinogen. Transcriptomic and proteomic analysis on colonic epithelial cells demonstrated that loss of hypusination induces multiple pathways related to cancer and immune response. Moreover, we found that hypusination enhances translation of numerous enzymes involved in aldehyde detoxification, including glutathione S-transferases and aldehyde dehydrogenases. Accordingly, hypusination-deficient mice exhibit increased levels of aldehyde adducts in the colon, and their treatment with a scavenger of electrophiles reduces colitis. CONCLUSIONS: Hypusination in intestinal epithelial cells has a key role in the prevention of colitis and colorectal cancer, and enhancement of this pathway via supplementation of spermidine could have a therapeutic impact.

Treatment of orbital fractures - a critical analysis of ophthalmic outcomes and scenarios for re-intervention.

BACKGROUND: Malplaced implants in orbital reconstruction may lead to serious complications and necessitate re-intervention. The aim of this study was to describe outcomes, complications and scenarios of re-intervention in a historical case series of orbital fractures treated with free-hand orbital wall reconstruction. The main hypothesis was that early re-interventions are mainly because of malplaced implants in the posterior orbit. METHODS: Retrospective review of 90 patients with facial fractures involving the orbit, reconstructed with radiopaque orbital wall implants, from 2011 to 2016. Data were obtained from medical records and computed tomography images. Recorded parameters were fracture type, ocular injury, ocular motility, diplopia, eye position, complications and re-interventions. Secondary reconstructions because of enophthalmos were volumetrically evaluated. RESULTS: Early complications requiring re-intervention within 1 month were seen in 12 (13%) patients, where all except two were because of malplaced implants. The implant incongruence was without exception found in the posterior orbit. Late complications consisted of four (4%) cases of ectropion and five (5%) cases of entropion that needed corrective surgery. The majority of the patients with eye-lid complications had undergone repeated surgeries. Secondary orbital surgeries were performed in nine (10%) patients. Five of these patients had secondary reconstruction for enophthalmos and associated diplopia. None of these patients became completely free from either enophthalmos or diplopia after the secondary surgery. CONCLUSION: Re-intervention after orbital reconstruction is mainly related to malplaced implants in the posterior orbit. Incomplete results in patients requiring secondary surgery for enophthalmos infer the importance of accurate restoration of the orbit at primary surgery. Abstract presented at: Swedish surgery Week 2021 and SCAPLAS 2022.

Patient Reported Outcome Following the Skoog Unilateral Cleft Lip Repair among Adults- a Long-Term Cohort Study and Comparison to a Non-cleft Population.

OBJECTIVE: The study primarily aimed to compare satisfaction with lip appearance among adults treated for unilateral cleft lip and palate (UCLP) with Skoog's primary lip repair procedure to those without clefts. The secondary aim was to determine whether satisfaction with lip appearance and the desire to change the lip/face appearance correlated with the number of secondary lip revisions performed. DESIGN: Long-term follow-up. PATIENTS/SETTINGS: All UCLP patients treated at the Uppsala University Hospital born between 1960- and 1987 (n = 109) were invited. At an average of 37 years following the primary lip repair, the participation rate was 76% (n = 83). A control group of adults without cleft (n = 67) completed the same study protocol for comparison. MAIN OUTCOME MEASURES: Satisfaction with appearance was measured with The Satisfaction with Appearance Questionnaire (SWA) and a modified version of the Body Cathexis -Scale was used to assess the desire to change the lip and facial appearance. RESULTS: UCLP patients were less satisfied with their lip, face, and overall appearance and reported a greater desire to change the appearance of their lips and face than non-cleft controls (p < 0.001). Dissatisfaction with lip appearance correlated to a greater willingness to change the appearance of the lip and face. No correlation was found between satisfaction with appearance and the number of the previously performed secondary lip revisions. CONCLUSION: Adults treated for UCLP are less satisfied with the appearance of their lips compared to the non-cleft population. The number of secondary revisions does not necessarily correlate to greater satisfaction with lip appearance.

Electrophilic reactive aldehydes as a therapeutic target in colorectal cancer prevention and treatment.

Colorectal cancer (CRC) is a major health problem worldwide. Dicarbonyl electrophiles, such as isolevuglandins (isoLGs), are generated from lipid peroxidation and form covalent adducts with amine-containing macromolecules. We have shown high levels of adducts of isoLGs in colonic epithelial cells of patients with CRC. We thus investigated the role of these reactive aldehydes in colorectal cancer development. We found that 2-hydroxybenzylamine (2-HOBA), a natural compound derived from buckwheat seeds that acts as a potent scavenger of electrophiles, is bioavailable in the colon of mice after supplementation in the drinking water and does not affect the colonic microbiome. 2-HOBA reduced the level of isoLG adducts to lysine as well as tumorigenesis in models of colitis-associated carcinogenesis and of sporadic CRC driven by specific deletion of the adenomatous polyposis coli gene in colonic epithelial cells. In parallel, we found that oncogenic NRF2 activation and signaling were decreased in the colon of 2-HOBA-treated mice. Additionally, the growth of xenografted human HCT116 CRC cells in nude mice was significantly attenuated by 2-HOBA supplementation. In conclusion, 2-HOBA represents a promising natural compound for the prevention and treatment of CRC.

Epithelial talin-1 protects mice from citrobacter rodentium-induced colitis by restricting bacterial crypt intrusion and enhancing t cell immunity.

Pathogenic enteric Escherichia coli present a significant burden to global health. Food-borne enteropathogenic E. coli (EPEC) and Shiga toxin-producing E. coli (STEC) utilize attaching and effacing (A/E) lesions and actin-dense pedestal formation to colonize the gastrointestinal tract. Talin-1 is a large structural protein that links the actin cytoskeleton to the extracellular matrix though direct influence on integrins. Here we show that mice lacking talin-1 in intestinal epithelial cells (Tln1Δepi) have heightened susceptibility to colonic disease caused by the A/E murine pathogen Citrobacter rodentium. Tln1Δepi mice exhibit decreased survival, and increased colonization, colon weight, and histologic colitis compared to littermate Tln1fl/fl controls. These findings were associated with decreased actin polymerization and increased infiltration of innate myeloperoxidase-expressing immune cells, confirmed as neutrophils by flow cytometry, but more bacterial dissemination deep into colonic crypts. Further evaluation of the immune population recruited to the mucosa in response to C. rodentium revealed that loss of Tln1 in colonic epithelial cells (CECs) results in impaired recruitment and activation of T cells. C. rodentium infection-induced colonic mucosal hyperplasia was exacerbated in Tln1Δepi mice compared to littermate controls. We demonstrate that this is associated with decreased CEC apoptosis and crowding of proliferating cells in the base of the glands. Taken together, talin-1 expression by CECs is important in the regulation of both epithelial renewal and the inflammatory T cell response in the setting of colitis caused by C. rodentium, suggesting that this protein functions in CECs to limit, rather than contribute to the pathogenesis of this enteric infection.

Use of the Cephalic Vein in DIEP Breast Reconstruction Does Not Increase Risk of Lymphedema of the Ipsilateral Arm.

SUMMARY: Flap failure is a rare but devastating complication in deep inferior epigastric perforator (DIEP) flap reconstructions. Common causes of partial or complete flap failure are related to venous congestion. Although the cephalic vein is usually a safe and reliable recipient vein for additional venous outflow, there is a hypothesized risk of donor-arm lymphedema secondary to lymphatic vessel damage in the vicinity of the cephalic vein or related to scarring and reduced venous backflow of the arm. The aim was to assess whether the cephalic vein as an additional recipient vessel, by means of the superficial inferior epigastric vein in DIEP flap breast reconstruction, was associated with long-term volume changes of the arm and/or symptoms of lymphedema. Arm volume was assessed preoperatively in patients scheduled to undergo unilateral delayed DIEP flap breast reconstruction at Uppsala University Hospital, Sweden, between 2001 and 2007. Long-term postoperative assessments were performed in 2015 to 2016. Water displacement and circumferential measurement were assessed preoperatively and postoperatively by the same lymphedema therapists. Patients were divided into two groups: DIEP reconstruction with the cephalic vein or without. Fifty-four patients fulfilled the inclusion criteria and completed the study, with a mean follow-up time of 136 months. There was no increased occurrence of lymphedema in the group undergoing DIEP flap reconstruction with the cephalic vein as extra venous drainage, based on an analysis of change from baseline in arm volume difference.This study shows that the cephalic vein can be used for secondary venous outflow in DIEP breast reconstruction without long-term risk of ipsilateral arm volume increase or symptoms of lymphedema. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The nutraceutical electrophile scavenger 2-hydroxybenzylamine (2-HOBA) attenuates gastric cancer development caused by Helicobacter pylori.

Stomach cancer is a leading cause of cancer death. Helicobacter pylori is a bacterial gastric pathogen that is the primary risk factor for carcinogenesis, associated with its induction of inflammation and DNA damage. Dicarbonyl electrophiles are generated from lipid peroxidation during the inflammatory response and form covalent adducts with amine-containing macromolecules. 2-hydroxybenzylamine (2-HOBA) is a natural compound derived from buckwheat seeds and acts as a potent scavenger of reactive aldehydes. Our goal was to investigate the effect of 2-HOBA on the pathogenesis of H. pylori infection. We used transgenic FVB/N insulin-gastrin (INS-GAS) mice as a model of gastric cancer. First, we found that 2-HOBA is bioavailable in the gastric tissues of these mice after supplementation in the drinking water. Moreover, 2-HOBA reduced the development of gastritis in H. pylori-infected INS-GAS mice without affecting the bacterial colonization level in the stomach. Further, we show that the development of gastric dysplasia and carcinoma was significantly reduced by 2-HOBA. Concomitantly, DNA damage were also inhibited by 2-HOBA treatment in H. pylori-infected mice. In parallel, DNA damage was inhibited by 2-HOBA in H. pylori-infected gastric epithelial cells in vitro. In conclusion, 2-HOBA, which has been shown to be safe in human clinical trials, represents a promising nutritional compound for the chemoprevention of the more severe effects of H. pylori infection.

Underwater versus conventional EMR of large nonpedunculated colorectal lesions: a multicenter randomized controlled trial.

BACKGROUND AND AIMS: Underwater EMR (UEMR) is an alternative procedure to conventional EMR (CEMR) to treat large, nonpedunculated colorectal lesions (LNPCLs). In this multicenter, randomized controlled clinical trial, we aimed to compare the efficacy and safety of UEMR versus CEMR on LNPCLs. METHODS: We conducted a multicenter, randomized controlled clinical trial from February 2018 to February 2020 in 11 hospitals in Spain. A total of 298 patients (311 lesions) were randomized to the UEMR (n = 149) and CEMR (n = 162) groups. The main outcome was the lesion recurrence rate in at least 1 follow-up colonoscopy. Secondary outcomes included technical aspects, en bloc resection rate, R0 resection rates, and adverse events, among others. RESULTS: There were no differences in the overall recurrence rate (9.5% UEMR vs 11.7% CEMR; absolute risk difference, -2.2%; 95% CI, -9.4 to 4.9). However, considering polyp sizes between 20 and 30 mm, the recurrence rate was lower for UEMR (3.4% UEMR vs 13.1% CEMR; absolute risk difference, -9.7%; 95% CI, -19.4 to 0). The R0 resection showed the same tendency, with significant differences favoring UEMR only for polyps between 20 and 30 mm. Overall, UEMR was faster and easier to perform than CEMR. Importantly, the techniques were equally safe. CONCLUSIONS: UEMR is a valid alternative to CEMR for treating LNPCLs and could be considered the first option of treatment for lesions between 20 and 30 mm due to its higher en bloc and R0 resection rates. (Clinical trial registration number: NCT03567746.).

Angiosarcoma de aorta diagnosticado mediante ecoendoscopia / Angiosarcoma of the aorta diagnosed via endoscopic ultrasound

Varón de 54 años que consulta por lumbalgia de 5 semanas de evolución refractaria a analgésicos habituales y pérdida de peso significativa. El PET-TAC evidenció una masa retroperitoneal en contacto con la pared anterior de la aorta abdominal. Tras comentarlo con la Unidad de Endoscopias, se decide realizar ecoendosocopia y PAAF por la accesibilidad y el carácter menos invasivo con resultado anatomopatológico de angiosarcoma de aorta. (AU)

"Location of cutaneous malignant melanoma in Sweden 2004-2018 - mortality and sex differences".

BACKGROUND: Cutaneous malignant melanoma (CMM) is one of the most common causes of cancer-related death in Sweden. There is increasing evidence that localisation of the primary CMM lesion differs between sexes and is associated with different outcomes. However, definitive convincing data is lacking. AIMS: To describe changes in the distribution of CMM anatomical location over time according to sex and determine differences in mortality by location. METHOD: This is a retrospective nation-wide cohort study of all patients diagnosed with CMM in Sweden between 2004 and 2018. Hazard ratios (HRs) were calculated using a multivariate cox regression model adjusting for age, sex, T-stage, multiple melanomas and comorbidities. RESULTS: A total of 68,666 patients were included. In males, trunk CMM was the most common location (51% of all male CMM), with an increasing proportion over time. In females, lower extremity CMM had the largest proportion in 2004 (33%) followed by trunk CMM (27%). By 2018, trunk CMM became more common than lower extremity CMM in females. Upper and lower extremity CMMs had lower HR for all-cause mortality compared with trunk CMM (0.896 and 0.887, respectively, p<0.001), while head and neck CMM had higher HR compared with trunk CMM (1.090, p<0.001). Males had greater risk than females (HR 1.352, p<0.001). CONCLUSIONS: Head and neck CMMs were associated with increased risk of all-cause mortality, while both upper and lower extremity CMMs were associated with decreased risk. Both sexes had increasing proportions of trunk and upper extremity CMM over time, with corresponding decreases in lower extremity and, head and neck CMM.

Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis of Helicobacter pylori Infection.

Colonization by Helicobacter pylori is associated with gastric diseases, ranging from superficial gastritis to more severe pathologies, including intestinal metaplasia and adenocarcinoma. The interplay of the host response and the pathogen affect the outcome of disease. One major component of the mucosal response to H. pylori is the activation of a strong but inefficient immune response that fails to control the infection and frequently causes tissue damage. We have shown that polyamines can regulate H. pylori-induced inflammation. Chemical inhibition of ornithine decarboxylase (ODC), which generates the polyamine putrescine from l-ornithine, reduces gastritis in mice and adenocarcinoma incidence in gerbils infected with H. pylori However, we have also demonstrated that Odc deletion in myeloid cells enhances M1 macrophage activation and gastritis. Here we used a genetic approach to assess the specific role of gastric epithelial ODC during H. pylori infection. Specific deletion of the gene encoding for ODC in gastric epithelial cells reduces gastritis, attenuates epithelial proliferation, alters the metabolome, and downregulates the expression of immune mediators induced by H. pylori Inhibition of ODC activity or ODC knockdown in human gastric epithelial cells dampens H. pylori-induced NF-κB activation, CXCL8 mRNA expression, and IL-8 production. Chronic inflammation is a major risk factor for the progression to more severe pathologies associated with H. pylori infection, and we now show that epithelial ODC plays an important role in mediating this inflammatory response.

Helicobacter pylori actively suppresses innate immune nucleic acid receptors.

Chronic mucosal pathogens have evolved multiple strategies to manipulate the host immune response; consequently, microbes contribute to the development of >2 million cases of cancer/year. Gastric adenocarcinoma is the fourth leading cause of cancer-related death and Helicobacter pylori confers the highest risk for this disease. Gastric innate immune effectors can either eliminate bacteria or mobilize adaptive immune responses including Toll-like receptors (TLRs), and cytosolic DNA sensor/adaptor proteins (e.g., stimulator of interferon genes, STING). The H. pylori strain-specific cag type IV secretion system (T4SS) augments gastric cancer risk and translocates DNA into epithelial cells where it activates the microbial DNA sensor TLR9 and suppresses injury in vivo; however, the ability of H. pylori to suppress additional nucleic acid PRRs within the context of chronic gastric inflammation and injury remains undefined. In this study, in vitro and ex vivo experiments identified a novel mechanism through which H. pylori actively suppresses STING and RIG-I signaling via downregulation of IRF3 activation. In vivo, the use of genetically deficient mice revealed that Th17 inflammatory responses are heightened following H. pylori infection within the context of Sting deficiency in conjunction with increased expression of a known host immune regulator, Trim30a. This novel mechanism of immune suppression by H. pylori is likely a critical component of a finely tuned rheostat that not only regulates the initial innate immune response, but also drives chronic gastric inflammation and injury.

Angiosarcoma of the aorta diagnosed via endoscopic ultrasound.

A 54-year-old man consulted for low back pain of 5 weeks of evolution, refractory to regular analgesics, and significant weight loss. The PET-CT revealed a retroperitoneal mass in contact with the anterior wall of the abdominal aorta. After consulting with the Endoscopy Unit, an endoscopic ultrasound-guided FNAP was performed due to the accessibility of the lesion and the less invasive nature of these procedures. The anatomopathological result was angiosarcoma of the aorta.

Cystathionine γ-lyase exacerbates Helicobacter pylori immunopathogenesis by promoting macrophage metabolic remodeling and activation.

Macrophages play a crucial role in the inflammatory response to the human stomach pathogen Helicobacter pylori, which infects half of the world's population and causes gastric cancer. Recent studies have highlighted the importance of macrophage immunometabolism in their activation state and function. We have demonstrated that the cysteine-producing enzyme cystathionine γ-lyase (CTH) is upregulated in humans and mice with H. pylori infection. Here, we show that induction of CTH in macrophages by H. pylori promoted persistent inflammation. Cth-/- mice had reduced macrophage and T cell activation in H. pylori-infected tissues, an altered metabolome, and decreased enrichment of immune-associated gene networks, culminating in decreased H. pylori-induced gastritis. CTH is downstream of the proposed antiinflammatory molecule, S-adenosylmethionine (SAM). Whereas Cth-/- mice exhibited gastric SAM accumulation, WT mice treated with SAM did not display protection against H. pylori-induced inflammation. Instead, we demonstrated that Cth-deficient macrophages exhibited alterations in the proteome, decreased NF-κB activation, diminished expression of macrophage activation markers, and impaired oxidative phosphorylation and glycolysis. Thus, through altering cellular respiration, CTH is a key enhancer of macrophage activation, contributing to a pathogenic inflammatory response that is the universal precursor for the development of H. pylori-induced gastric disease.