ACUTE VENOUS THROMBOEMBOLISM IS COMMON FOLLOWING ACUTE NECROTIZING PANCREATITIS AND IS ASSOCIATED WITH WORSE CLINICAL OUTCOMES.

OBJECTIVES: While splanchnic vein thrombosis (SVT) is a well-known local complication of acute pancreatitis, extra-splanchnic VTE (ESVT) is inadequately studied. Here, we aim to explore the incidence of VTE in acute necrotizing pancreatitis (ANP) and the associated mortality. METHODS: This is a retrospective cohort study utilizing an electronic health record database. Adults with a diagnosis of ANP from January 2017 to December 2022 were identified using appropriate ICD-10-CM codes. The primary outcome was development of acute ESVT within one month of ANP. Secondary outcomes were 90-day mortality, 30-day rehospitalization, and oral anticoagulant (OAC) use in patients with ESVT. Propensity score matching (1:1) was performed for baseline characteristics and common comorbidities. RESULTS: 17,942 (7.11%) patients were diagnosed with ANP during the study period and about 10% (1,737) of them had a diagnosis of ESVT. Of all VTE, 61% were ESVT with or without SVT, and 63% (N = 1,799) were SVT. 90-day mortality (16.3% vs. 5.7%, risk ration, RR 2.86 [95% CI 2.29-3.56]) and 30-day rehospitalization (31% Vs 19%, RR 1.63 [95% CI 1.49-1.79]) were higher in patients with ESVT compared to non-VTE patients. 60% of patients with ESVT were on OAC and OAC use was associated with lower 90-day mortality (8.9% vs. 19.4%, RR 0.46) without increased risk of adverse events, like - acute gastrointestinal bleeding, intracranial bleeding, or need for packed red cell transfusion. CONCLUSIONS: Systemic VTE is common in patients with ANP and may contribute to increased mortality and risk of readmissions. Prospective studies can confirm our findings and explore the role of aggressive VTE prophylaxis in patients with ANP during hospital stay, and in the immediate ambulatory period.

TRPV4 Activator-Containing CMT-Hy Hydrogel Enhances Bone Tissue Regeneration In Vivo by Enhancing Mitochondrial Health.

Treating different types of bone defects is difficult, complicated, time-consuming, and expensive. Here, we demonstrate that transient receptor potential cation channel subfamily V member 4 (TRPV4), a mechanosensitive, thermogated, and nonselective cation channel, is endogenously present in the mesenchymal stem cells (MSCs). TRPV4 regulates both cytosolic Ca2+ levels and mitochondrial health. Accordingly, the hydrogel made from a natural modified biopolymer carboxymethyl tamarind CMT-Hy and encapsulated with TRPV4-modulatory agents affects different parameters of MSCs, such as cell morphology, focal adhesion points, intracellular Ca2+, and reactive oxygen species- and NO-levels. TRPV4 also regulates cell differentiation and biomineralization in vitro. We demonstrate that 4α-10-CMT-Hy and 4α-50-CMT-Hy (the hydrogel encapsulated with 4αPDD, 10 and 50 nM, TRPV4 activator) surfaces upregulate mitochondrial health, i.e., an increase in ATP- and cardiolipin-levels, and improve the mitochondrial membrane potential. The same scaffold turned out to be nontoxic in vivo. 4α-50-CMT-Hy enhances the repair of the bone-drill hole in rat femur, both qualitatively and quantitatively in vivo. We conclude that 4α-50-CMT-Hy as a scaffold is suitable for treating large-scale bone defects at low cost and can be tested for clinical trials.

Modulation of calcium-influx by carboxymethyl tamarind­gold nanoparticles promotes biomineralization for tissue regeneration.

Gold nanoparticles (AuNPs) have been reported to modulate bone tissue regeneration and are being extensively utilized in biomedical implementations attributable to their low cytotoxicity, biocompatibility and simplicity of functionalization. Lately, biologically synthesized nanoparticles have acquired popularity because of their environmentally acceptable alternatives for diverse applications. Here we report the green synthesis of AuNPs by taking the biopolymer Carboxymethyl Tamarind (CMT) as a unique reducing as well as a stabilizing agent. The synthesized CMT-AuNPs were analyzed by UV-vis spectrophotometer, DLS, FTIR, XRD, TGA, SEM and TEM. These results suggest that CMT-AuNPs possess an average size of 19.93 ± 8.52 nm and have long-term stability. Further, these CMT-AuNPs promote the proliferation together with the differentiation and mineralization of osteoblast cells in a "dose-dependent" manner. Additionally, CMT-AuNPs are non-toxic to SD rats when applied externally. We suggest that the CMT-AuNPs have the potential to be a suitable and non-toxic agent for differentiation and mineralization of osteoblast cells in vitro and this can be tested in vivo as well.

Biocompatible quaternary pullulan functionalized 2D MoS2 glycosheet-based non-leaching and infection-resistant coatings for indwelling medical implants.

Medical implants are frequently used in medicine and reconstructive surgery to treat various pathological and anatomical conditions. However, over time, biofilm formation on the surface of these implants can cause recurrent infections and subsequent inflammatory responses in the host, resulting in tissue damage, necrosis, and re-hospitalization. To address these implant-associated infections, the best approach is to create antimicrobial coatings. Here, we report the fabrication of a biocompatible, non-leaching, and contact-based antibacterial coating for implants using quaternary pullulan functionalized MoS2 (MCP) glycosheets. The cationic MCP glycosheets were coated on the surfaces of polydopamine-modified stainless steel and polyvinyl fluoride substrates through a simple process of electrostatic interaction. The developed coating showed excellent antibacterial activity (>99.5%) against E. coli and S. aureus that remained stable over 30 days without leaching out of the substrates and retained its antibacterial activity. MCP-coated implants did not induce any acute or sub-chronic toxicity to mammalian cells, both in vitro and in vivo. Furthermore, MCP coating prevented S. aureus colonization on stainless steel implants in a mouse model of implant-associated infection. The MCP coating developed in this study represents a simple, safe, and effective antibacterial coating for preventing implant-associated infections.

Palladium Nanocapsules for Photothermal Therapy in the Near-Infrared II Biological Window.

Recent developments in nanomaterials with programmable optical responses and their capacity to modulate the photothermal effect induced by an extrinsic source of light have elevated plasmonic photothermal therapy (PPTT) to the status of a favored treatment for a variety of malignancies. However, the low penetration depth of near-infrared-I (NIR-I) lights and the need to expose the human body to a high laser power density in PPTT have restricted its clinical translation for cancer therapy. Most nanostructures reported to date exhibit limited performance due to (i) activity only in the NIR-I region, (ii) the use of intense laser, (iii) need of large concentration of nanomaterials, or (iv) prolonged exposure times to achieve the optimal hyperthermia state for cancer phototherapy. To overcome these shortcomings in plasmonic nanomaterials, we report a bimetallic palladium nanocapsule (Pd Ncap)─with a solid gold bead as its core and a thin, perforated palladium shell─with extinction both in the NIR-I as well as the NIR-II region for PPTT applications toward cancer therapy. The Pd Ncap demonstrated exceptional photothermal stability with a photothermal conversion efficiency of ∼49% at the NIR-II (1064 nm) wavelength region at a very low laser power density of 0.5 W/cm2. The nanocapsules were further surface-functionalized with Herceptin (Pd Ncap-Her) to target the breast cancer cell line SK-BR-3 and exploited for in vitro PPTT applications using NIR-II light. Pd Ncap-Her caused more than 98% cell death at a concentration of just 50 µg/mL and a laser power density of 0.5 W/cm2 with an output power of only 100 mW. Flow cytometric and microscopic analyses revealed that Pd Ncap-Her-induced apoptosis in the treated cancer cells during PPTT. Additionally, Pd Ncaps were found to have reactive oxygen species (ROS) scavenging ability, which can potentially reduce the damage to cells or tissues from ROS produced during PPTT. Also, Pd Ncap demonstrated excellent in vivo biocompatibility and was highly efficient in photothermally ablating tumors in mice. With a high photothermal conversion and killing efficiency at very low nanoparticle concentrations and laser power densities, the current nanostructure can operate as an effective phototherapeutic agent for the treatment of different cancers with ROS-protecting ability.

Quaternary Pullulan-Functionalized 2D MoS2 Glycosheets: A Potent Bactericidal Nanoplatform for Efficient Wound Disinfection and Healing.

Rapid emergence of multidrug-resistant bacterial strains has posed a global threat to public health. Hospital-acquired infections, especially in diabetic and burn patients, severely impede the process of wound healing, thereby causing high mortality. This calls for developing a new biomaterial that synergistically destroys pathogenic strains and also helps in promoting wound healing without causing any resistance generation. A new and highly potent antibacterial agent has been developed by integrating the bactericidal and wound healing properties of MoS2 nanosheets and a recently developed quaternized polysaccharide, pullulan (CP), into a single nanoplatform for accelerated wound therapy. MoS2 nanosheets are noncovalently functionalized with quaternized pullulan to yield glycosheets (MCP) that efficiently eradicate both Gram-negative Escherichia coli (5 µg/mL) and Gram-positive Staphylococcus aureus (10 µg/mL) within a short period of 4 h, through a synergistic action of membrane damage and chemical oxidation. MoS2 nanosheets coupled with CP exert a membrane-directed bactericidal action through distinct mechanisms of "pore-forming" and "non-pore-forming" pathways, respectively, whereas oxidative stress is induced by MoS2 nanosheets alone to collectively kill the pathogens. The MCP glycosheets have good biocompatibility and are also capable of disrupting and eradicating mature biofilms. Rapid and highly efficient in vivo wound disinfection and healing occurred upon MCP treatment through the reduction of inflammation and promotion of cellular proliferation and tissue remodeling. Thus, MCP glycosheets can emerge as a safe and potential biomaterial for better wound care management.

Hemostatic spray (TC-325) vs. standard endoscopic therapy for non-variceal gastrointestinal bleeding: A meta-analysis of randomized controlled trials.

Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I 2 %. Results Five RCTs with 362 patients (TC-325 178, SET 184) - 123 females and 239 males with a mean age 65 ±â€Š16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95-1.25; I 2 43), P =  0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98-1.3; I 2 35), P =  0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12-0.77, I 2 0), P =  0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 - 0.63, I 2 0), P =  0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62-2.07, I 2 26), P =  0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, -0.20-0.74; I 2 62), P =  0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5-0.94; I 2 0), P =  0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.

Reduced FRG1 expression promotes angiogenesis via activation of the FGF2-mediated ERK/AKT pathway.

Identifying novel targets that control both tumorigenesis and angiogenesis can aid in developing a more potent anti-angiogenic therapeutic strategy. We previously reported that reduction of FRG1 is associated with increased p38-MAPK signaling in prostate cancer and with elevated MEK-ERK signaling in breast cancer. Here, we reveal the role of FRG1 in tumor angiogenesis. Our findings demonstrate that depleted FRG1 levels enhance the proliferation, migration, and tubule formation of HUVECs in a paracrine manner, and this was further substantiated in multiple animal models. Mechanistically, FRG1 depletion activated the expression of FGF2 in breast cancer cells, which triggered the ERK/AKT cascade in endothelial cells. As FRG1 affects multiple tumorigenic properties and it is upstream of FGF2, it can be explored as a therapeutic target that is less prone to resistance.

Efficacy & safety of EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) in Roux-en-Y gastric bypass anatomy: a systematic review & meta-analysis.

BACKGROUND: In patients with Roux-en-Y gastric bypass (RYGB) anatomy, laparoscopic endoscopic retrograde cholangiopancreatography (LA-ERCP) and enteroscopy-assisted ERCP (E-ERCP) have been utilized to achieve pancreaticobiliary access. Endoscopic ultrasound-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE) has recently emerged as an alternate and efficient approach. As data regarding EDGE continues to evolve, concerns about safety and efficacy remain, limiting wide adoptability. We performed a systematic review and meta-analysis to assess the safety and efficacy of EDGE and compare it to the current standard of care. METHODS: A comprehensive search of major databases (inception to Nov 2022) identified published studies on EDGE. A random-effects model was used to calculate the pooled rates and heterogeneity (I2). Risk ratio (RR) and standardized difference in means (SMD) were utilized for head-to-head comparison analysis between EDGE vs. LA-ERCP and EDGE vs. E-ERCP. Primary outcomes assessed pooled EDGE safety (adverse events) and efficacy (technical/clinical success). Secondary outcomes assessed efficacy and safety profiles via a comparative analysis of EDGE vs. LA-ERCP and EDGE vs. E-ERCP. RESULTS: A total of 16 studies (470 patients) were included. EDGE pooled technical success (TS) rate was 96% (95% CI 92-97.6, I2 = 0), and clinical success was 91% (85-95, I2 = 0). Pooled rate of all adverse events with EDGE was 17% (14-24.6, I2 = 32%). On sub-group analysis, these included failure of fistula closure 17% (10-25.5, I2 = 48%), stent migration 7% (4-12, I2 = 51%), bleeding 5% (3.2-7.9, I2 = 0), post-EDGE weight gain 4% (2-9, I2 = 0), perforation 4% (2.1-5.8, I2 = 0), and post-ERCP pancreatitis 2% (1-5, I2 = 0). EDGE TS was comparable to LA-ERCP (97% vs. 98%; RR, 1.00; CI, 0.85-1.17, p = 0.95) and E-ERCP (100% vs. 66%; RR, 1.26; CI, 0.99-1.6, p = 0.06). No statistical difference was noted in adverse events between EDGE and LA-ERCP (13% vs. 17.6%; RR, 0.61; CI, 0.28-1.35, p = 0.52) and E-ERCP (9.6% vs. 16%; RR, 0.61; CI, 0.28-1.35, p = 0.22). EDGE procedure time and hospital stay were shorter than LA-ERCP and E-ERCP (p < 0.001). CONCLUSION: Our analysis shows that EDGE is safe and efficacious to the current standard of care. Further head-to-head comparative trials are needed to validate our findings.

Formulation of a dual drug-loaded nanoparticulate co-delivery hydrogel system and its validation in rheumatoid arthritis animal model.

Rheumatoid arthritis (RA), a systemic autoimmune disease that dramatically affects patients' quality of life. Given the intricacy of RA's pathophysiology, no single treatment can completely halt the disease progression. Here, we attempted to treat RA holistically and synergistically by co-delivering methotrexate (MTX), a standard slow-acting anti-rheumatic drug, and phenethyl isothiocyanate (PEITC), a bioactive phytochemical, using a sodium alginate (SA)-pluronic F127 (PF-127) in situ hydrogel formulation. Therefore, in the current study, the co-delivery of MTX and PEITC in the nanoparticulate form could help enhance stability and solubility and facilitate greater penetration in the target arthritic tissues. The fabricated MTX NP and PEITC NE were found to have a minimum particle size, PDI, and good zeta potential. Results from in vitro release studies showed that MTX and PEITC were simultaneously released from the DD NP HG matrix over 6-7 days through diffusion and erosion mechanisms. An intra-articular (IA) injection of DD NP HG dramatically reduced chronic inflammation in adjuvant-induced arthritis (AIA) rats, delayed the onset of bone erosion, significantly reduced synovitis, and down-regulated the inflammatory cytokine expression. Most notably, the co-delivery strategy almost entirely restored the morphological features of the ankle joints of RA rats. The hepatic and renal function tests indicated good biological safety for DD NP HG in RA conditions. Taken together, these findings indicated that DD NP HG could achieve good anti-inflammatory activity and reverse cartilage disruption through a synergistic effect between two nanoparticulate forms of MTX and PEITC, which can effectively improve the drawbacks of their free forms.

A nanostructured dual-drug loaded smart hydrogel (DD NP HG) was successfully constructed for the intra-articular delivery of MTX and PEITC to the affected joints of RA.The fabrication of the nanoformulation of both MTX (MTX NP) and PEITC (PEITC NE) aided in mitigating the drawbacks and drug-related side effects of the free form of drugs.DD NP HG markedly suppressed joint inflammation and protect against bone destruction in arthritic rats.This combination approach of PEITC and MTX (DD NP HG) synergistically improved anti-arthritic activity and reduced the adverse side effects in vivo.

Thermosensitive smart hydrogel of PEITC ameliorates the therapeutic efficacy in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune condition that accompanies chronic inflammation of joints with limited therapeutic options. Phenethyl isothiocyanate (PEITC), a bioactive phytochemical, exerts its chemopreventive, anti-oxidant, and anti-inflammatory activity via the Nrf-2 pathway. However, limited water solubility, short half-life, and instability are reasons for the low bioavailability of PEITC that hampers clinical application. From studies in healthy rats, the performance of PEITC-loaded chitosan/pluronic F-127 smart hydrogel (PH) as a thermosensitive injectable demonstrated adequate thermosensitivity (gel formation), injectability (ease of administration), biocompatibility (with prolonged contact), pharmacokinetics (sustained drug release), and biosafety (nontoxic to major organs). In the adjuvant-induced arthritis (AIA) rat model, PEITC-hydrogel (PH50) injected into the knee joint lowered RA-related symptoms significantly (paw edema and arthritis score). Further, a marked reduction in bone erosion and inflammation-specific biomarkers was observed. Finally, this study demonstrates a smart injectable hydrogel optimally loaded with PEITC which is safe, biocompatible and exhibits significant therapeutic efficacy in RA conditions.

Safety evaluation of enriched fraction from leaves of Dillenia indica L. in BALB/c mice.

The enriched fraction derived from Dillenia indica L. (Dilleniaceae), also known as elephant apple was subjected to acute and sub-acute toxicological study to document its safety issues for use as fumigant. The enriched fractions were orally administered to both sexes of BALB/c mice at doses of 200, 800 and 1600 mg/kg bw for acute toxicity, and 50 and 500 mg/kg bw for 14 days of sub-acute toxicity. Experimental results revealed that there were no signs of adverse toxicity, and mortality, with no significant treatment related effect in the percentage weight gain, daily feed and water intake, and haematological parameters. However, at higher dose in sub-acute toxicity study a patch of mild tubular injuries in kidney of female mice were observed as suggested by histopathological studies and mild abnormalities in levels of serum biochemical parameters. In general, it can be considered that the enriched fraction from D. indica leaves on oral feeding does not show any adverse effect on mice of both sexes. Hence, the highest doses 1600 mg/kg bw (acute) and 500 mg/kg bw (sub-acute) can be used as basal dose for the determination of no-observed-adverse-effect level (NOAEL) of enriched fraction from D. indica to calculate its safety margin.

Acute and sub-acute toxicity evaluation of dihydro-p-coumaric acid isolated from leaves of Tithonia diversifolia Hemsl. A. Gray in BALB/c mice.

In present study, the acute and sub-acute toxicities of Dihydro-p-coumaric acid isolated from the leaves of Tithonia diversifolia (Hemsl.) A. Gray was studied for safety issues in mammals. For acute toxicity tests, isolated compound was administered orally in both male and female BALB/c mice at the doses of 200, 800, and 1,600 mg/kg body weight for 7 days. In sub-acute toxicity study 50 and 500 mg/kg bw of the compound was orally administered for 14 days. Toxicity induced behavioural changes, haematological parameters, biochemical markers and histopathological sections were studied after Dihydro-p-coumaric acid administration. The vital organs like heart, kidney, uterus and testis revealed no adverse effects at doses of upto 1,600 mg/kg bw and 500 mg/kg bw. Slight hepatotoxicity was however demonstrated by ALT and AST assay but histopathological section did not concur as much. The study demonstrated insignificant difference in the percentage of feed intake, water intake, weight gain, haematological parameters and histopathological changes, with no toxicity signs and mortality. Dihydro-p-coumaric acid can be regarded as safe in both acute and sub-acute toxicity assay in both sexes. This indicates Dihydro-p-coumaric acid as a viable alternative to synthetic pesticides.

Elevation of TRPV1 expression on T-cells during experimental immunosuppression.

The transient receptor potential vanilloid 1 (TRPV1) channel is a thermo-sensitive, polymodal cation channel. An increase in intracellular calcium (Ca2+) is essential for T-cell responses. Similarly, various immunosuppressive agents are also reported to induce Ca2+ influx. However, the possible involvement of TRPV1 during immunosuppression has not been studied yet. Here, we investigated the possible functional role of TRPV1 in FK506 or B16F10-culture supernatant (B16F10-CS)-driven experimental immunosuppression in T-cells. Intriguingly, it was found that TRPV1 surface expression was further significantly elevated during immunosuppression compared with concanavalin A (ConA) or TCR-activated T-cells. Moreover, in B16F10 tumor-bearing mice, TRPV1 expression was upregulated on splenic T-cells as compared with T-cells derived from control mice. We also observed an immediate increase in intracellular Ca2+ levels in FK506 (marked increase) and B16F10-CS treatment (modest increase) or in combination with T-cell activation as compared with resting and activated T-cells. Likewise, in B16F10 tumor-bearing mice, the basal intracellular calcium level was upregulated in T-cells as compared with controls. The elevated Ca2+ level(s) were found to be significantly downregulated by 5'-iodoresiniferatoxin (50-IRTX) (a TRPV1-specific inhibitor), suggesting an important role of TRPV1 during immune activation and immunosuppression. The current study may have implications for immunosuppressive diseases along with inflammatory disorders associated with the coordinating role of TRPV1 and Ca2+ influx.

Correction to: Elevation of TRPV1 expression on T-cells during experimental immunosuppression.

Correction to: J. Biosci. (2022) 47:42 https://doi.org/10.1007/s12038-022-00279-2 In the Journal of Biosciences article titled ''Elevation of TRPV1 expression on T-cells during experimental immunosuppression'' by P Sanjai Kumar et al. (https://doi.org/10.1007/s12038-022-00279-2; Vol. 47, Art. ID 42), published in July 2022, the affiliation of the authors has been incompletely mentioned as: School of Biological Sciences, National Institute of Science Education and Research, Bhubaneswar 752050, India The correct affiliation should read as: School of Biological Sciences, National Institute of Science Education and Research, an Off-campus Centre (OCC) of Homi Bhabha National Institute, Bhubaneswar 752050, India.

Function and regulation of thermosensitive ion channel TRPV4 in the immune system.

Transient receptor potential vanilloid sub-type 4 (TRPV4) is a six transmembrane protein that acts as a non-selective Ca2+ channel. Notably, TRPV4 is present in almost all animals, from lower eukaryotes to humans and is expressed in diverse tissue and cell types. Accordingly, TRPV4 is endogenously expressed in several types of immune cells that represent both innate and adaptive immune systems of higher organism. TRPV4 is known to be activated by physiological temperature, suggesting that it acts as a molecular temperature sensor and thus plays a key role in temperature-dependent immune activation. It is also activated by diverse endogenous ligands, lipid metabolites, physical and mechanical stimuli. Both expression and function of TRPV4 in various immune cells, including T cells and macrophages, are also modulated by multiple pro- and anti-inflammatory compounds. The results from several laboratories suggest that TRPV4 is involved in the immune activation, a phenomenon with evolutionary significance. Because of its diverse engagement in the neuronal and immune systems, TRPV4 is a potential therapeutic target for several immune-related disorders.

Association of endoscopic variceal treatment with portal venous system thrombosis in liver cirrhosis: a case-control study.

Background: The association of endoscopic variceal treatment (EVT) with portal venous system thrombosis (PVST) in liver cirrhosis is still unclear. Methods: PVST was assessed by contrast-enhanced CT or MRI in 406 cirrhotic patients from our prospective database. Case and control groups, which are defined as patients with and without PVST, respectively, were matched at a ratio of 1:1 according to age, gender, Child-Pugh class, and MELD score. History of EVT was reviewed. Logistic regression analysis was used to identify the risk factors for PVST. Odds ratios (ORs) were calculated. Subgroup analyses were further performed in terms of degree and location of PVST. Results: Overall, 109 patients each were included in case and control groups. The case group had a significantly higher proportion of patients who had undergone EVT than the control group (53.2% versus 18.3%; p < 0.001). In detail, the case group had significantly higher proportions of patients who had undergone EVT for controlling bleeding (45.9% versus 14.7%; p < 0.001), endoscopic variceal ligation (EVL) alone (19.3% versus 9.2%; p = 0.033), and EVL combined with endoscopic cyanoacrylate glue injection (24.8% versus 5.5%; p < 0.001). EVT was independently associated with PVST (OR = 4.258; p < 0.001). In subgroup analyses, EVT remained independently associated with partial PVST (OR = 10.063; p < 0.001), complete PVST/fibrotic cord (OR = 4.889; p = 0.008), thrombosis within main portal vein (OR = 5.985; p < 0.001), and thrombosis within superior mesenteric and splenic veins (OR = 5.747; p < 0.001). Conclusions: EVT may lead to a higher risk of PVST, especially more severe PVST, in liver cirrhosis. Screening for and prophylaxis of PVST after EVT should be further explored.

Direct percutaneous endoscopic jejunostomy (DPEJ) and percutaneous endoscopic gastrostomy with jejunal extension (PEG-J) technical success and outcomes: Systematic review and meta-analysis.

Background and study aims Endoscopic methods of delivering uninterrupted feeding to the jejunum include direct percutaneous endoscopic jejunostomy (DPEJ) or PEG with jejunal extension (PEG-J), validated from small individual studies. We aim to perform a meta-analysis to assess their effectiveness and safety in a variety of clinical scenarios. Methods Major databases were searched until June 2021. Efficacy outcomes included technical and clinical success, while safety outcomes included adverse events (AEs) and malfunction rates. We assessed heterogeneity using I 2 and classic fail-safe to assess bias. Results 29 studies included 1874 patients (983 males and 809 females); mean age of 60 ±â€Š19 years. Pooled technical and clinical success rates with DPEJ were 86.6 % (CI, 82.1-90.1, I 2 73.1) and 96.9 % (CI, 95.0-98.0, I 2 12.7). The pooled incidence of malfunction, major and minor AEs with DPEJ were 11 %, 5 %, and 15 %. Pooled technical and clinical success for PEG-J were 94.4 % (CI, 85.5-97.9, I 2 33) and 98.7 % (CI, 95.5-99.6, I 2  < 0.001). The pooled incidence of malfunction, major and minor AEs with DPEJ were 24 %, 1 %, and 25 %. Device-assisted DPEJ performed better in altered gastrointestinal anatomy. First and second attempts were 87.6 % and 90.2 %. Conclusions DPEJ and PEG-J are safe and effective procedures placed with high fidelity with comparable outcomes. DPEJ was associated with fewer tube malfunction and failure rates; however, it is technically more complex and not standardized, while PEG-J had higher placement rates. The use of balloon enteroscopy was found to enhance DPEJ performance.

Epidemiology of early esophageal adenocarcinoma.

BACKGROUND/AIMS: Endoscopic resection has become the preferred treatment approach for select early esophageal adenocarcinoma (EAC); however, the epidemiology of early stage disease has not been well defined. METHODS: Surveillance Epidemiology and End Results (SEER) data were analyzed to determine age-adjusted incidence rates among major epithelial carcinomas, including EAC, from 1973 to 2017. The percent change in incidence over time was compared according to tumor subtype. Early T-stage, node-negative EAC without metastasis was examined from 2004 to 2017 when precise T-stage data were available. RESULTS: The percent change in annual incidence from 1973 to 2017 was 767% for EAC. Joinpoint analysis showed that the average annual percent change in EAC from 1973 to 2017 was 5.11% (95% confidence interval, 4.66%-5.56%). The annual percent change appeared to plateau between 2004 and 2017; however, early EAC decreased from 2010 to 2017, with an annual percent change of -5.78%. CONCLUSION: There has been a 7-fold increase in the incidence of EAC, which was significantly greater than that of the other major epithelial malignancies examined. More recently, the incidence of early EAC has been decreasing. Approximately one in five patients has node negative, potentially resectable early stage disease.