Modified Pneumatic Reduction Protocol for Intussusception: A Retrospective Cohort Study in an Ultrahigh Volume Center.

BACKGROUND: This study aims to assess the long-term outcomes of a modified pneumatic reduction protocol for intussusception at the Vietnam National Hospital of Pediatrics, an institution with a significant patient load in a lower-middle-income country. PATIENTS AND METHODS: A single center, retrospective cohort observational study was conducted to examine patients who underwent modified fluoroscopic-guided air-enema reduction (FGAR) for intussusception from January 2016 to December 2017. Data on patient demographics, complication rates, and the incidence of long-term recurrence was collected. RESULTS: Between January 2016 and December 2017, a total of 3562 patients underwent modified FGAR at our institution, including 2313 males (64.9%) and 1249 females (35.1%). The median age was 19 months (range: 1-170), and the median FGAR procedure duration was 4 min (range: 2-24). The median hospital stay was 1 day (range: 1-31). Successful reduction was achieved in 98.7% of cases, with 43 unsuccessful cases and 4 cases of perforated bowel requiring surgery. Twenty patients, presenting with severe symptoms due to delayed treatment seeking, were admitted to the pediatric intensive care unit (ICU) post-FGAR. No mortality or severe morbidity was reported. Over a median 6-year follow-up, intussusception recurred in 198 patients, accounting for 5.6% of the cohort, with 97% of recurrences occurring within the first year post-reduction. Infants and children under 12 months of age had the highest complication rates, including failed FGAR, complicated intussusception, ICU admission, or recurrence, compared to other age groups, and this difference was statistically significant (p < 0.05). CONCLUSION: The modified FGAR protocol has been demonstrated to be safe and feasible, with a very high success rate, low complication rate, and low recurrence rate. Although further comparative studies are needed to confirm its reproducibility, it should be considered a promising approach for children in low-to middle-income countries. LEVEL OF EVIDENCE: Level III.

The Reconstruction of the Nasal Columella Defect Using Domino Flaps.

Skin defects of the total nasal columella can significantly impact both nasal respiratory function and aesthetics. The reconstruction of total columella is a complex process and represents a significant challenge for plastic surgeons. Various factors can cause the loss of the columella. Numerous columella reconstruction procedures have been proposed, each with their own set of advantages and disadvantages. The main issues to address include the need for regional flaps from the forehead or nasofacial sulcus, a long pedicle to reach the columella, and the double angular folding that causes a risk of malnutrition or venous congestion. Additionally, using horizontal nasolabial flaps may lead to deformation of the upper lip. In this study, we present a new procedure to reconstruct the nasal columella using "Domino flaps" with two flaps (the horizontal upper lip island flap and nasocheek island flap). This new procedure ensures adequate skin for reconstruction of nasal columella and partial tip, minimizes rotation angle, reduces the angular folding of the pedicle, furthermore limits deformation of the upper lip. "Domino flaps" are a valuable option for surgeons when reconstructing the total nasal columella. However, it is important to consider whether the patient has a beard at the donor sites.

Arteriovenous malformation in the kidney allograft: A rare cause of hematuria in the post-transplant patient.

Gross hematuria is one of the most common complications in postrenal transplant patients, accounting for 12% of all renal recipients. The management plan in these cases varies depending on different entities, including infection, renal cell carcinoma, chronic graft rejection, kidney calculus, or recurrence of primary disease. On the other hand, vascular malformation like arteriovenous malformation was less likely to be mentioned due to a lack of consensus in the natural history, pathogenesis, and current management. In this article, we report a 62-year-old man presenting with spontaneous hematuria for a week and 2 days of anuria after 3 years of renal transplantation. Abdominal ultrasound and abdominopelvic computed tomography noted an obstruction of the renal pelvis due to blood clots without signs of vascular injuries. An emergency operation was performed to remove blood clots in the renal pelvis, but after that, hematuria was still recurrence. A digital renal graft subtraction angiography (DSA) revealed an arteriovenous malformation (AVM)in the kidney allograft. This lesion was then successfully selective embolized with glue. Given the high accuracy of DSA, our case highlights the potential role of this imaging modality in diagnosing and treating AVM after failure with other modalities.

CAR memory-like NK cells targeting the membrane proximal domain of mesothelin demonstrate promising activity in ovarian cancer.

Epithelial ovarian cancer (EOC) remains one of the most lethal gynecological cancers. Cytokine-induced memory-like (CIML) natural killer (NK) cells have shown promising results in preclinical and early-phase clinical trials. In the current study, CIML NK cells demonstrated superior antitumor responses against a panel of EOC cell lines, increased expression of activation receptors, and up-regulation of genes involved in cell cycle/proliferation and down-regulation of inhibitory/suppressive genes. CIML NK cells transduced with a chimeric antigen receptor (CAR) targeting the membrane-proximal domain of mesothelin (MSLN) further improved the antitumor responses against MSLN-expressing EOC cells and patient-derived xenograft tumor cells. CAR arming of the CIML NK cells subtanstially reduced their dysfunction in patient-derived ascites fluid with transcriptomic changes related to altered metabolism and tonic signaling as potential mechanisms. Lastly, the adoptive transfer of MSLN-CAR CIML NK cells demonstrated remarkable inhibition of tumor growth and prevented metastatic spread in xenograft mice, supporting their potential as an effective therapeutic strategy in EOC.

The quassinoids bruceines A-M: pharmacology, mechanism of action, synthetic advance, and pharmacokinetics-a review.

Bruceines A-L are among the quassinoid representatives found in the medicinal plant Brucea javanica (L.). An overview of their pharmacological activities is still unknown. The given research deals with highlights in their pharmacological result, molecular mechanism of action, synthetic progress, and pharmacokinetics. From previous evidence, bruceine derivatives are potential agents for anticancer treatments, as well as they are appropriate to treat inflammation, diabetes, and parasitic infections, and protect the neurons, kidneys, and lungs. Cytokine inhibitions, oxidative stress responses, and various signaling pathways, such as MAPK (mitogen-activated protein kinase) and NF-κB (nuclear factor-kappa B), have been proposed as the underlying mechanisms of action. Synthetic approaches to synthesize new derivatives with enhancement activities are based on free hydroxyl group modifications. Bruceines seem to be promptly absorbed by both oral and intravenous administrations, but their bioavailability is not high (less than 6%). Pre-clinical and clinical studies to prove their anticancer potential and other activities are urgent. Structural modifications, nano-combinations, and synergistic effects are necessary.

[18F]F-AraG imaging reveals association between neuroinflammation and brown- and bone marrow adipose tissue.

Brown and brown-like adipose tissues have attracted significant attention for their role in metabolism and therapeutic potential in diabetes and obesity. Despite compelling evidence of an interplay between adipocytes and lymphocytes, the involvement of these tissues in immune responses remains largely unexplored. This study explicates a newfound connection between neuroinflammation and brown- and bone marrow adipose tissue. Leveraging the use of [18F]F-AraG, a mitochondrial metabolic tracer capable of tracking activated lymphocytes and adipocytes simultaneously, we demonstrate, in models of glioblastoma and multiple sclerosis, the correlation between intracerebral immune infiltration and changes in brown- and bone marrow adipose tissue. Significantly, we show initial evidence that a neuroinflammation-adipose tissue link may also exist in humans. This study proposes the concept of an intricate immuno-neuro-adipose circuit, and highlights brown- and bone marrow adipose tissue as an intermediary in the communication between the immune and nervous systems. Understanding the interconnectedness within this circuitry may lead to advancements in the treatment and management of various conditions, including cancer, neurodegenerative diseases and metabolic disorders.

The association of magnetic resonance imaging features with five molecular subtypes of breast cancer.

Objective: To identify the association of magnetic resonance imaging (MRI) features with molecular subtypes of breast cancer (BC). Materials and methods: A retrospective study was conducted on 112 invasive BC patients with preoperative breast MRI. The confirmed diagnosis and molecular subtypes of BC were based on the postoperative specimens. MRI features were collected by experienced radiologists. The association of MRI features of each subtype was compared to other molecular subtypes in univariate and multivariate logistic regression analyses. Results: The proportions of luminal A, luminal B HER2-negative, luminal B HER2-positive, HER2-enriched, and triple-negative BC were 14.3 %, 52.7 %, 12.5 %, 10.7 %, and 9.8 %, respectively. Luminal A was associated with hypo-isointensityon T2-weighted images (OR=6.214, 95 % CI: 1.163-33.215) and non-restricted diffusion on DWI-ADC (OR=6.694, 95 % CI: 1.172-38.235). Luminal B HER2-negative was related to the presence of mass (OR=7.245, 95 % CI: 1.760-29.889) and slow/medium initial enhancement pattern (OR=3.654, 95 % CI: 1.588-8.407). There were no associations between MRI features and luminal B HER2-positive. HER2-enriched tended to present as non-mass enhancement lesions (OR=20.498, 95 % CI: 3.145-133.584) with fast uptake in the initial postcontrast phase (OR=9.788, 95 % CI: 1.689-56.740), and distortion (OR=11.471, 95 % CI: 2.250-58.493). Triple-negative were associated with unifocal (OR=7.877, 95 % CI: 1.180-52.589), hyperintensityon T2-weighted images (OR=14.496, 95 % CI: 1.303-161.328), rim-enhanced lesions (OR=18.706, 95 % CI: 1.915-182.764), and surrounding tissue edema (OR=5.768, 95 % CI: 1.040-31.987). Conclusion: Each molecular subtype of BC has distinct features on breast MRI. These characteristics can serve as an adjunct to immunohistochemistry in diagnosing molecular subtypes, particularly in cases, where traditional methods yield equivocal results.

Obesogenic High-Fat Diet and MYC Cooperate to Promote Lactate Accumulation and Tumor Microenvironment Remodeling in Prostate Cancer.

Cancer cells exhibit metabolic plasticity to meet oncogene-driven dependencies while coping with nutrient availability. A better understanding of how systemic metabolism impacts the accumulation of metabolites that reprogram the tumor microenvironment (TME) and drive cancer could facilitate development of precision nutrition approaches. Using the Hi-MYC prostate cancer mouse model, we demonstrated that an obesogenic high-fat diet (HFD) rich in saturated fats accelerates the development of c-MYC-driven invasive prostate cancer through metabolic rewiring. Although c-MYC modulated key metabolic pathways, interaction with an obesogenic HFD was necessary to induce glycolysis and lactate accumulation in tumors. These metabolic changes were associated with augmented infiltration of CD206+ and PD-L1+ tumor-associated macrophages (TAM) and FOXP3+ regulatory T cells, as well as with the activation of transcriptional programs linked to disease progression and therapy resistance. Lactate itself also stimulated neoangiogenesis and prostate cancer cell migration, which were significantly reduced following treatment with the lactate dehydrogenase inhibitor FX11. In patients with prostate cancer, high saturated fat intake and increased body mass index were associated with tumor glycolytic features that promote the infiltration of M2-like TAMs. Finally, upregulation of lactate dehydrogenase, indicative of a lactagenic phenotype, was associated with a shorter time to biochemical recurrence in independent clinical cohorts. This work identifies cooperation between genetic drivers and systemic metabolism to hijack the TME and promote prostate cancer progression through oncometabolite accumulation. This sets the stage for the assessment of lactate as a prognostic biomarker and supports strategies of dietary intervention and direct lactagenesis blockade in treating advanced prostate cancer. SIGNIFICANCE: Lactate accumulation driven by high-fat diet and MYC reprograms the tumor microenvironment and promotes prostate cancer progression, supporting the potential of lactate as a biomarker and therapeutic target in prostate cancer. See related commentary by Frigo, p. 1742.

Pure estrogen receptor antagonists potentiate capecitabine activity in ESR1-mutant breast cancer.

The ESR1 ligand binding domain activating mutations are the most prevalent genetic mechanism of acquired endocrine resistance in metastatic hormone receptor-positive breast cancer. These mutations confer endocrine resistance that remains estrogen receptor (ER) dependent. We hypothesized that in the presence of the ER mutations, continued ER blockade with endocrine therapies that target mutant ER is essential for tumor suppression even with chemotherapy treatment. Here, we conducted comprehensive pre-clinical in vitro and in vivo experiments testing the efficacy of adding fulvestrant to fluorouracil (5FU) and the 5FU pro-drug, capecitabine, in models of wild-type (WT) and mutant ER. Our findings revealed that while this combination had an additive effect in the presence of WT-ER, in the presence of the Y537S ER mutation there was synergy. Notably, these effects were not seen with the combination of 5FU and selective estrogen receptor modulators, such as tamoxifen, or in the absence of intact P53. Likewise, in a patient-derived xenograft (PDX) harboring a Y537S ER mutation the addition of fulvestrant to capecitabine potentiated tumor suppression. Moreover, multiplex immunofluorescence revealed that this effect was due to decreased cell proliferation in all cells expressing ER and was not dependent on the degree of ER expression. Taken together, these results support the clinical investigation of the combination of ER antagonists with capecitabine in patients with metastatic hormone receptor-positive breast cancer who have experienced progression on endocrine therapy and targeted therapies, particularly in the presence of an ESR1 activating mutation.

Gastrointestinal Perforation After Solid Organ Transplantation: A Case Series.

Although organ transplantation is associated with significant survival rates and cost benefits, postoperative complications still occur. Gastrointestinal complications, including those involving the stomach and intestines, account for 1-6% of posttransplant complications, with intestinal perforation specifically accounting for approximately 9%, depending on the center. In Vietnam, there are no comprehensive reports on these complications. Therefore, we report three clinical cases of gastrointestinal perforation following transplantation. Three cases of intestinal perforation are described in this case series. In 2023, a 16-year-old female patient who underwent heart transplantation for congenital heart disease was diagnosed with intestinal perforation on the 12th day. The patient required continued blood filtration support after surgery. In 2018, six days after liver transplantation, a 56-year-old male patient was diagnosed with intestinal perforation, which was subsequently repaired, and the ends of his intestines were removed. The patient was discharged in stable condition after 30 days. In 2017, five days after kidney transplantation, a 46-year-old female patient was diagnosed with intestinal perforation, which was repaired, and the perforation site was left open. The patient was discharged in stable condition after 40 days. Intestinal perforation is a relatively rare, but not uncommon, complication. Early diagnosis is challenging due to nonspecific clinical symptoms and signs. Considering the possibility of intestinal perforation and obtaining early abdominal computed tomography imaging can help prevent delayed diagnosis.

Managing and treating COVID-19 in patients with hematological malignancies: a narrative review and expert insights.

Patients with hematologic malignancies (HMs) are at a significantly higher risk of contracting COVID-19 and experiencing severe outcomes compared to individuals without HMs. This heightened risk is influenced by various factors, including the underlying malignancy, immunosuppressive treatments, and patient-related factors. Notably, immunosuppressive regimens commonly used for HM treatment can lead to the depletion of B cells and T cells, which is associated with increased COVID-19-related complications and mortality in these patients. As the pandemic transitions into an endemic state, it remains crucial to acknowledge and address the ongoing risk for individuals with HMs. In this review, we aim to summarize the current evidence to enhance our understanding of the impact of HMs on COVID-19 risks and outcomes, identify particularly vulnerable individuals, and emphasize the need for specialized clinical attention and management. Furthermore, the impaired immune response to COVID-19 vaccination observed in these patients underscores the importance of implementing additional mitigation strategies. This may include targeted prophylaxis and treatment with antivirals and monoclonal antibodies as indicated. To provide practical guidance and considerations, we present two illustrative cases to highlight the real-life challenges faced by physicians caring for patients with HMs, emphasizing the need for individualized management based on disease severity, type, and the unique circumstances of each patient.

Central Lymphatic Imaging in Adults with Spontaneous Chyluria.

Purpose: Chyluria is a rare condition primarily prevalent in developing countries in tropical regions. In chyluria, there exists the communication between lymphatic vessels and the urinary tract, but the specific mechanism of this communication remains undocumented. The objective of this study was to assess the morphology of the main lymphatic vessels including the uro-lymphatic fistula, the thoracic duct using Magnetic Resonance Lymphangiography (MRL) and Intranodal Lymphangiography (IL). Materials and Methods: A retrospective study spanning five years, from January 2020 to January 2024, included 43 patients diagnosed with chyluria through cystoscopy and quantitative urine testing for triglycerides. These patients underwent MRL and then IL for uro-lymphatic fistula embolization. Results: The study involved 43 patients with an average age of 66.1 ± 19.5 years, with a male-to-female ratio of 1:2. Uro-lymphatic fistula occurred predominantly in the left kidney (72.1%), followed by the right kidney (20.9%), and both sides (7%). MRL imaging showed the thoracic duct in 100% of cases but visualized only 84.5% of the uro-lymphatic fistulas. In contrast, IL imaging showed the thoracic duct in 51.5% of patients but visualized uro-lymphatic fistulas in 100% of cases. In the procedure of IL, the average visualization time of the thoracic duct was 45 minutes, with a range of 35 to 69 minutes. Conclusion: MRL and IL complement each other in diagnosing the main lymphatic vessels in chyluria patients. The observed circulatory stasis in the thoracic duct supports the hypothesis that it contributes to increased pressure in the thoracic duct and the formation uro-lymphatic fistula as collateral circulations.

Improving Laryngoscopy Image Analysis Through Integration of Global Information and Local Features in VoFoCD Dataset.

The diagnosis and treatment of vocal fold disorders heavily rely on the use of laryngoscopy. A comprehensive vocal fold diagnosis requires accurate identification of crucial anatomical structures and potential lesions during laryngoscopy observation. However, existing approaches have yet to explore the joint optimization of the decision-making process, including object detection and image classification tasks simultaneously. In this study, we provide a new dataset, VoFoCD, with 1724 laryngology images designed explicitly for object detection and image classification in laryngoscopy images. Images in the VoFoCD dataset are categorized into four classes and comprise six glottic object types. Moreover, we propose a novel Multitask Efficient trAnsformer network for Laryngoscopy (MEAL) to classify vocal fold images and detect glottic landmarks and lesions. To further facilitate interpretability for clinicians, MEAL provides attention maps to visualize important learned regions for explainable artificial intelligence results toward supporting clinical decision-making. We also analyze our model's effectiveness in simulated clinical scenarios where shaking of the laryngoscopy process occurs. The proposed model demonstrates outstanding performance on our VoFoCD dataset. The accuracy for image classification and mean average precision at an intersection over a union threshold of 0.5 (mAP50) for object detection are 0.951 and 0.874, respectively. Our MEAL method integrates global knowledge, encompassing general laryngoscopy image classification, into local features, which refer to distinct anatomical regions of the vocal fold, particularly abnormal regions, including benign and malignant lesions. Our contribution can effectively aid laryngologists in identifying benign or malignant lesions of vocal folds and classifying images in the laryngeal endoscopy process visually.

Physicochemical Characterization, Antioxidant and Tyrosinase Inhibitory Activities of Coffea Robusta Monofloral Honey from Dak Lak Province, Vietnam.

Robusta coffee blossom honey stands as a key regional product in Dak Lak province, Vietnam. Despite its significance, there exists a dearth of scientific data for assessing its quality. This study aims to fill this gap by characterizing the physicochemical properties and biological activities of coffee blossom honeys from three distinct sub-regions within Dak Lak province, Vietnam. These activities include ferric reducing power (FRP), DPPH and ABTS radical scavenging, as well as tyrosinase inhibitory activities. Moreover, the study compares these honey samples with other popular varieties in Vietnam, such as Lychee and Longan honeys. The physicochemical parameters of the honey samples meet the standards set by Codex Alimentarius 2001. Through UPLC analysis, eleven compounds were identified, with caffeine serving as a marker for coffee honey. Furthermore, by employing multiple factor analysis (MFA), it was observed that certain physicochemical properties correlate positively with tyrosinase inhibitory, DPPH, ABTS free radicals scavenging activities, and FRP. Notably, tyrosinase inhibitory activity exhibited a positive correlation with antioxidant activity. These findings underscore the high quality of Coffea robusta honey, showcasing its potent antioxidant and tyrosinase inhibitory activities.

Partitioning recombinant chitinase from Nicotiana benthamiana by an aqueous two-phase system based on polyethylene glycol and phosphate salts.

The objectives of this study were to purify 42 kDa chitinase derived from Trichoderma asperellum SH16 produced in Nicotiana benthamiana by a polyethylene glycol (PEG)/salt aqueous two-phase system (ATPS). The specific activities of the crude chitinase and the partially purified chitinase from N. benthamiana were about 251 unit/mg and 386 unit/mg, respectively. The study found the 300 g/L PEG 6000 + 200 g/L potassium phosphate (PP) and 300 g/L PEG 6000 + 150 g/L sodium phosphate (SP) systems had the highest partitioning efficiency for each salt in primary extraction. However, among the two types of salt, PP displayed higher efficiency than SP, with a partitioning coefficient K of 4.85 vs. 3.89, a volume ratio V of 2.94 vs. 2.68, and a partitioning yield Y of approximately 95 % vs. 83 %. After back extraction, the enzymatic activity of purified chitinase was up to 834 unit/mg (PP) and 492 unit/mg (SP). The purification factors reached 3.32 (PP) and 1.96 (SP), with recovery yields of about 59 % and 61 %, respectively. SDS-PAGE and zymogram analysis showed that the recombinant chitinase was significantly purified by using ATPS. The purified enzyme exhibited high chitinolytic activity, with the hydrolysis zone's diameter being around 2.5 cm-3 cm. It also dramatically reduced the growth of Sclerotium rolfsii; the colony diameter after treatment with 60 unit of enzyme for 104 spores was only about 1 cm, compared to 3.5 cm in the control. The antifungal effect of chitinase suggests that this enzyme has great potential for applications in agricultural production as well as postharvest fruit and vegetable preservation.

BM-BronchoLC - A rich bronchoscopy dataset for anatomical landmarks and lung cancer lesion recognition.

Flexible bronchoscopy has revolutionized respiratory disease diagnosis. It offers direct visualization and detection of airway abnormalities, including lung cancer lesions. Accurate identification of airway lesions during flexible bronchoscopy plays an important role in the lung cancer diagnosis. The application of artificial intelligence (AI) aims to support physicians in recognizing anatomical landmarks and lung cancer lesions within bronchoscopic imagery. This work described the development of BM-BronchoLC, a rich bronchoscopy dataset encompassing 106 lung cancer and 102 non-lung cancer patients. The dataset incorporates detailed localization and categorical annotations for both anatomical landmarks and lesions, meticulously conducted by senior doctors at Bach Mai Hospital, Vietnam. To assess the dataset's quality, we evaluate two prevalent AI backbone models, namely UNet++ and ESFPNet, on the image segmentation and classification tasks with single-task and multi-task learning paradigms. We present BM-BronchoLC as a reference dataset in developing AI models to assist diagnostic accuracy for anatomical landmarks and lung cancer lesions in bronchoscopy data.

Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects.

One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues. A Tet-On doxycycline-inducible CAIX expressing cell line was established to mimic various CAIX densities, providing coverage from CAIX-high skrc-59 tumor cells to CAIX-low MMNK-1 cholangiocytes. Assessing the killing of CAR-T cells, we demonstrated that low-affinity/high-avidity fine-tuned G9 CAR-T has a wider therapeutic window compared to high-affinity/high-avidity G250 that was used in the first anti-CAIX CAR-T clinical trial but displayed serious OTOT effects. To assess the therapeutic effect of G9 on patient samples, we generated ccRCC patient derived organotypic tumor spheroid (PDOTS) ex vivo cultures and demonstrated that G9 CAR-T cells exhibited superior efficacy, migration and cytokine release in these miniature tumors. Moreover, in an RCC orthotopic mouse model, G9 CAR-T cells showed enhanced tumor control compared to G250. In summary, G9 has successfully mitigated OTOT side effects and in doing so has made CAIX a druggable immunotherapeutic target.

Milk fat globule-epidermal growth factor 8 (MFGE8) prevents intestinal fibrosis.

OBJECTIVE: Intestinal fibrosis is considered an inevitable consequence of chronic IBD, leading to stricture formation and need for surgery. During the process of fibrogenesis, extracellular matrix (ECM) components critically regulate the function of mesenchymal cells. We characterised the composition and function of ECM in fibrostenosing Crohn's disease (CD) and control tissues. DESIGN: Decellularised full-thickness intestinal tissue platforms were tested using three different protocols, and ECM composition in different tissue phenotypes was explored by proteomics and validated by quantitative PCR (qPCR) and immunohistochemistry. Primary human intestinal myofibroblasts (HIMFs) treated with milk fat globule-epidermal growth factor 8 (MFGE8) were evaluated regarding the mechanism of their antifibrotic response, and the action of MFGE8 was tested in two experimental intestinal fibrosis models. RESULTS: We established and validated an optimal decellularisation protocol for intestinal IBD tissues. Matrisome analysis revealed elevated MFGE8 expression in CD strictured (CDs) tissue, which was confirmed at the mRNA and protein levels. Treatment with MFGE8 inhibited ECM production in normal control HIMF but not CDs HIMF. Next-generation sequencing uncovered functionally relevant integrin-mediated signalling pathways, and blockade of integrin αvß5 and focal adhesion kinase rendered HIMF non-responsive to MFGE8. MFGE8 prevented and reversed experimental intestinal fibrosis in vitro and in vivo. CONCLUSION: MFGE8 displays antifibrotic effects, and its administration may represent a future approach for prevention of IBD-induced intestinal strictures.

Immune-restoring CAR-T cells display antitumor activity and reverse immunosuppressive TME in a humanized ccRCC mouse model.

One of the major barriers that have restricted successful use of chimeric antigen receptor (CAR) T cells in the treatment of solid tumors is an unfavorable tumor microenvironment (TME). We engineered CAR-T cells targeting carbonic anhydrase IX (CAIX) to secrete anti-PD-L1 monoclonal antibody (mAb), termed immune-restoring (IR) CAR G36-PDL1. We tested CAR-T cells in a humanized clear cell renal cell carcinoma (ccRCC) orthotopic mouse model with reconstituted human leukocyte antigen (HLA) partially matched human leukocytes derived from fetal CD34+ hematopoietic stem cells (HSCs) and bearing human ccRCC skrc-59 cells under the kidney capsule. G36-PDL1 CAR-T cells, haploidentical to the tumor cells, had a potent antitumor effect compared to those without immune-restoring effect. Analysis of the TME revealed that G36-PDL1 CAR-T cells restored active antitumor immunity by promoting tumor-killing cytotoxicity, reducing immunosuppressive cell components such as M2 macrophages and exhausted CD8+ T cells, and enhancing T follicular helper (Tfh)-B cell crosstalk.

Minimally Invasive Treatment of Chyle Leak After Thyroidectomy and Cervical Lymph Node Dissection in Patients with Thyroid Carcinoma: Results of a Study Involving 36 Patients.

Objective: Chyle leak (CL) after head and neck surgery is a rare but well-known complication. In patients with high-output leakage, the treatment can be complicated. This study aims to report on a recent innovation in lymphatic intervention for treating such patients. Materials and Methods: A retrospective review of 36 patients with chyle leak after neck surgery for thyroid cancer was conducted to assess the efficacy of percutaneous lymphatic embolization and thoracic duct (TD) disruption. Results: Antegrade catheterization of the thoracic duct was achieved in 31 of 36 patients (86.1%). Therefore, embolization of the thoracic duct and thoracic duct branches was performed in 26 and 5 patients, respectively. In 5 cases of unsuccessful antegrade catheterization into the thoracic duct, transcervical access embolization was performed in 2 patients, and TD disruption (TDD) was performed in 3 patients. The pooled overall technical success rate of lymphatic embolization was 33/36 patients (91.7%). One patient who underwent thoracic duct embolization (TDE) with technical success (1/33 patients) but clinical failure had additional treatment directly sclerosing the TD under computed tomography scan. Cervical fluid collection sclerotherapy was done in 7 patients as an additional treatment. Resolution of the chyle leak after procedures was observed in all patients (100%). The mean time to resolution was 3 days (1-7 days). There was no complication intra and after procedures. Conclusion: TDE, selective TD branches embolization and TDD are safe and effective minimally invasive treatments for CL post-surgery for thyroid carcinoma. Sclerosing cervical fluid collection contributes to clinical success.