Accelerated corneal crosslinking with 20'-soaking hydroxypropyl methyl cellulose/riboflavin vs conventional crosslinking with 30'-soaking dextran/riboflavin.

PURPOSE: To evaluate and compare functional and structural outcomes of accelerated corneal crosslinking (A-CXL) using riboflavin with hydroxypropyl methyl cellulose (HPMC) vs conventional corneal crosslinking (C-CXL) using riboflavin with dextran. SETTING: American University of Beirut Medical Center, Beirut, Lebanon. DESIGN: Retrospective analysis. METHODS: Retrospective analysis of 83 eyes of 73 patients with mild to moderate keratoconus. First group (n = 44 eyes) underwent C-CXL using a 30-minute riboflavin/dextran soaking between June 2014 and March 2016. Second group (n = 39 eyes) underwent A-CXL using a 20-minute riboflavin/HPMC soaking between April 2016 and December 2017. Patients were evaluated preoperatively and at 1, 3, and 12 months postoperatively. Main outcome measures were simulated keratometry (simK), maximum axial keratometry (Kmax), demarcation line depth, and haze intensity measured using optical coherence tomography-based image analysis software. RESULTS: Demarcation line (DL) was 298.30 ± 64.60 µm and 335.61 ± 99.76 µm for C-CXL and A-CXL groups, respectively ( P = .04). Haze profile was similar for both groups. The mean simK values were reduced from 46.93 ± 3.50 and 46.44 ± 2.93 preoperatively to 46.18 ± 3.65 and 45.54 ± 2.78 at 12 months postoperatively, for C-CXL and A-CXL, respectively ( P = .003 for both groups). The mean Kmax decreased from 52.46 ± 4.82 and 51.50 ± 3.87 preoperatively to 51.30 ± 4.42 and 50.30 ± 3.52 postoperatively, for the C-CXL and A-CXL, respectively ( P < .001 for both groups). There was no difference in the simK and Kmax changes between the C-CXL and A-CXL groups ( P = .814 and P = .913), visual acuity, and refraction between the 2 groups ( P > .05). CONCLUSIONS: A-CXL with a 20-minute riboflavin/HPMC soaking produced deeper DL and similar corneal haze, topographic, refractive, and visual results to C-CXL with a 30-minute riboflavin/dextran soaking.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

The Effectiveness of Deflux® Treatment for Vesicoureteral Reflux Following Pediatric Renal Transplantation: A Single-Institution Challenging Experience.

PURPOSE: To validate the effectiveness of Deflux® treatment for vesicoureteral reflux (VUR) following pediatric renal transplantation (RT), based on our single-institution experience. METHOD: A retrospective study was conducted using the medical records of pediatric patients who underwent Deflux® treatment for VUR after RT from April 2008 to March 2022. RESULTS: Sixty-eight pediatric patients underwent RT. VUR was subsequently detected in 22 (32 %) of these patients. Seven of the 22 patients (32 %) underwent Deflux® treatment to avoid renal dysfunction due to urinary infection (UTI). The median age at the time of RT was 4 years (range:2-12). All 7 patients had urinary UTIs before Deflux® treatment. The median estimated glomerular filtration rate (eGFR) before Deflux® treatment was 67 ml/min/1.73 m2 (range:42-138 ml/min/1.73 m2). After Deflux® treatment, VUR was downgraded in three cases (43 %). Four patients (57 %) experienced postoperative UTI, two of who underwent a second Deflux® treatment, one underwent submuscular tunnel reconstruction, and the other one experienced UTI without VUR after 1st Deflux® treatment but did not reoccur. All seven patients continued prophylactic medication after Deflux® treatment, without any history of recurrent UTIs during the observation period after treatment (median 37 months [range 7-86 months]). Furthermore, the eGFRs did not significantly decrease after Deflux® treatment (median eGFR 58 ml/min/1.73 m2 [range:33-99 ml/min/1.73 m2], p > 0.1). CONCLUSION: Deflux® treatment for VUR after RT is technically challenging because the new ureteral orifice is ventrally anastomosed at the bladder. We believe our results indicate the possibility of reducing the frequency of UTIs and contributing to preservation of the renal function after RT. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: Level III.

Whey Protein Hydrolysate Exerts Anti-Inflammatory Effects to Alleviate Dextran Sodium Sulfate (DSS)-Induced Colitis via Microbiome Restoration.

Whey protein hydrolysate (WPH) has been shown to have a variety of bioactivities. This study aimed to investigate the preventive effect of WPH on dextran sodium sulfate (DSS)-induced colitis in C57BL/6J mice. The results indicated that WPH intervention for 37 days was effective in delaying the development of colonic inflammation, and high doses of WPH significantly inhibited weight loss (9.16%, n = 8, p < 0.05), protected the colonic mucosal layer, and significantly reduced the levels of inflammatory factors TNF-α, IL-6, and IL-1ß in mice with colitis (n = 8, p < 0.05). In addition, WPH intervention was able to up-regulate the short-chain fatty acids secretion and restore the gut microbiome imbalance in mice with colitis. Notably, high-dose WPH intervention increased the relative abundance of norank_f_Muribaculaceae by 1.52-fold and decreased the relative abundance of Romboutsia and Enterobacter by 3.77-fold and 2.45-fold, respectively, compared with the Model group. WPH intervention protected colitis mice mainly by reversing the microbiome imbalance and regulating the major histocompatibility complex (MHC) class I pathway. This study showed that WPH has anti-inflammatory activity and a promising colitis management future.

Management of priming fluids in cardiopulmonary bypass for adult cardiac surgery: network meta-analysis.

BACKGROUND: Cardiopulmonary bypass (CPB) is frequently employed for cardiac surgery, and selecting a suitable priming fluid is a prerequisite for CPB. Currently, the commonly used priming fluids in clinics are classified as crystalloids and colloids, including balanced crystalloids, albumin, dextran, gelatin and hydroxyethyl starch (HES). This network meta-analysis compared the effects of eight fluids used during CPB in adults to determine optimal priming fluid during CPB surgery. METHODS: Randomised controlled trials assessing priming fluids for CPB in adult cardiac surgery published before 13 April 2023 were searched across Ovid MEDLINE(R) ALL, OVID EMbase, and Cochrane Central Register of Controlled Trials. Various priming fluids were classified into eight categories, including balanced crystalloids, 0.9% NaCl, iso-oncotic human albumin, hyperoncotic human albumin, HES with molecular weight 130k, HES with molecular weight 200k, gelatin and dextran. RESULTS: The NMA of platelet counts revealed no significant differences in any result. In direct comparison results, only the comparison of HES with molecular weight 130k vs. gelatin (standard mean difference = -0.40, 95% confidence interval [95%CI: -0.63, -0.16) revealed a significant difference. According to the SUCRA, balanced crystalloids had the highest platelet count, followed by gelatin, and HES with a molecular weight of 130k had the lowest platelet, followed by HES with a molecular weight of 200k. CONCLUSION: Patients using dextran have a low mortality rate and a short mean CPB time, the use of balanced crystalloids is beneficial in terms of platelet count, and HES with molecular weight 130k is beneficial for postoperative urine volume at 24h. However, all priming fluids have pros and cons quite, and the optimal choice of priming fluids remains unsupported by current evidences. When performing CPB surgery, the type of priming fluid should be selected according to the actual situation in CPB for adult cardiac surgery.

When dextran was used as the CPB priming fluid, patients had the lowest mortality and shortest mean CPB time.With iso-oncotic HA, patients had the shortest length of ICU stay, the least blood loss 24h after surgery, and the lowest chest tube output 24h after surgery.The use of balanced crystalloids was beneficial for platelet count, the use of L-HES was beneficial for urine output 24h after surgery, and the use of H-HES resulted in the shortest hospital stay.In summary, each of these fluids has pros and cons quite, and an optimal choice of priming fluids during CPB surgery remains unsupported by current evidence.When performing CPB surgery, the type of priming fluids should be selected according to the actual condition of the patient's body.

Dietary Supplementation of Ancientino Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

Ancientino, a complex dietary fiber supplement mimicking the ancient diet, has improved chronic heart failure, kidney function, and constipation. However, its effect on ulcerative colitis is unknown. This study explores the impact of Ancientino on colitis caused by dextran sulfate sodium (DSS) and its mechanisms. Data analyses showed that Ancientino alleviated bodyweight loss, colon shortening and injury, and disease activity index (DAI) score, regulated levels of inflammatory factors (tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), interleukin-1 beta (IL-1ß), and interleukin 6 (IL-6)), reduced intestinal permeability (d-lactate and endotoxin), fluorescein isothiocyanate-dextran (FITC-dextran), and diamine oxidase (DAO), repaired colonic function (ZO-1 and occludin), and suppressed oxidative stress (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA)) in vivo and in vitro. In short, this study demonstrated that Ancientino alleviates colitis and exerts an anticolitis effect by reducing inflammatory response, suppressing oxidative stress, and repairing intestinal barrier function. Thus, Ancientino may be an effective therapeutic dietary resource for ulcerative colitis.

Ferroptosis-Enhanced Immunotherapy with an Injectable Dextran-Chitosan Hydrogel for the Treatment of Malignant Ascites in Hepatocellular Carcinoma.

Malignant ascites in advanced hepatocellular carcinoma (HCC) is a complex clinical problem that lacks effective treatments. Due to the insensitivity of advanced HCC cells to traditional chemotherapies, low drug accumulation, and limited drug residence time in the peritoneal cavity, the therapeutic effects of malignant ascites in HCC are not satisfactory. In this study, an injectable hydrogel drug delivery system based on chitosan hydrochloride and oxidized dextran (CH-OD) is designed to load sulfasalazine (SSZ), an FDA-approved drug with ferroptosis-inducing ability, for effective tumor-killing and activation of anti-tumor immunity. Compared to free SSZ, SSZ-loaded CH-OD (CH-OD-SSZ) hydrogel exhibits greater cytotoxicity and induces higher levels of immunogenic ferroptosis. In the preclinical model of hepatoma ascites, intraperitoneal administration of CH-OD-SSZ hydrogel can significantly suppress tumor progression and improve the immune landscape. Both in vitro and in vivo, CH-OD-SSZ hydrogel induces the repolarization of macrophages to an M1-like phenotype and promotes the maturation and activation of dendritic cells. Combination treatment with CH-OD-SSZ hydrogel and anti-programmed cell death protein 1 (PD-1) immunotherapy achieves more than 50% ascites regression and generates long-term immune memory. Collectively, CH-OD-SSZ hydrogel exhibits promising therapeutic potential in the treatment of peritoneal dissemination and malignant ascites in advanced HCC, especially when combined with anti-PD-1 immunotherapy.

Pomegranate Extract Affects Gut Biofilm Forming Bacteria and Promotes Intestinal Mucosal Healing Regulating the Crosstalk between Epithelial Cells and Intestinal Fibroblasts.

Background: Pomegranate (Punica granatum) can be used to prepare a bioactive extract exerting anti-inflammatory activities. Clinical studies demonstrated an improvement in clinical response in inflammatory bowel disease (IBD) patients when pomegranate extract (PG) was taken as a complement to standard medications. However, the molecular mechanisms underlying its beneficial effects are still scarcely investigated. This study investigates the effect of PG on bacterial biofilm formation and the promotion of mucosal wound healing. Methods: The acute colitis model was induced in C57BL/6N mice by 3% dextran sodium sulfate administration in drinking water for 5 days. During the recovery phase of colitis, mice received saline or PG (200 mg/kg body weight) by oral gavage for 11 days. Colitis was scored daily by evaluating body weight loss, bleeding, and stool consistency. In vivo intestinal permeability was evaluated by fluorescein isothiocyanate-conjugated dextran assay, bacterial translocation was assessed by fluorescence in situ hybridization on tissues, whereas epithelial and mucus integrity were monitored by immunostaining for JAM-A and MUC-2 markers. Bacterial biofilm formation was assessed using microfluidic devices for 24 or 48 h. Primary fibroblasts were isolated from healthy and inflamed areas of 8 IBD patients, and Caco-2 cells were stimulated with or without PG (5 µg/mL). Inflammatory mediators were measured at the mRNA and protein level by RT-PCR, WB, or Bio-plex multiplex immunoassay, respectively. Results: In vivo, PG boosted the recovery phase of colitis, promoting a complete restoration of the intestinal barrier with the regeneration of the mucus layer, as also demonstrated by the absence of bacterial spread into the mucosa and the enrichment of crypt-associated fibroblasts. Microfluidic experiments did not highlight a specific effect of PG on Enterobacterales biofilm formation, even though Citrobacter freundii biofilm was slightly impaired in the presence of PG. In vitro, inflamed fibroblasts responded to PG by downregulating the release of metalloproteinases, IL-6, and IL-8 and upregulating the levels of HGF. Caco-2 cells cultured in a medium supplemented with PG increased the expression of SOX-9 and CD44, whereas in the presence of HGF or plated with a fibroblast-conditioned medium, they displayed a decrease in SOX-9 and CD44 expression and an increase in AXIN2, a negative regulator of Wnt signaling. Conclusions: These data provide new insight into the manifold effects of PG on promoting mucosal homeostasis in IBD by affecting pathogen biofilm formation and favoring the regeneration of the intestinal barrier through the regulation of the crosstalk between epithelial and stromal cells.

A kaolin/calcium incorporated shape memory and antimicrobial chitosan-dextran based cryogel as an efficient haemostatic dressing for uncontrolled hemorrhagic wounds.

Increased mortalities associated with uncontrolled and excessive bleeding is still of paramount concern in the clinics, caregivers and military medics. Herein, we designed a shape memory cryogel based on chitosan (C) and functionalized-dextran (D), incorporated with Kaolin (K) and calcium (Ca2+) as haemostatic agents. The developed cryogel (CDKCa) exhibits a uniform interconnected porous architecture with profound fluid absorption ability, rapid blood clotting, stable clot formation and good antibacterial activity. The CDKCa elucidates significantly less clotting time (~30 s; in-vitro) and increased aggregation and activation of platelets/red blood cells in comparison to the control groups and commercial dressings (Axiostat and QuikClot). The developed CDKCa also significantly reduced the aPTT and PT values by ~58 % and 31 % respectively, leading to the activation of intrinsic and extrinsic coagulation cascades. The CDKCa cryogel displays enhanced mechanical stability, flexibility and a good shape memory, a property quintessential to cease uncontrolled bleeding in irregular and non-compressible wounds. Further, the Kaolin and Ca2+ incorporated shape memory CDKCa cryogel demonstrates a rapid blood coagulation and stable clot formation in different compressible and non-compressible rat liver and femur hemorrhagic models. In summary, the endorsed results of CDKCa suggest that the design, fabrication and excellent clotting ability may attribute to high haemostatic efficiency of CDKCa dressing and have a great potential to prevent uncontrollable hemorrhages.

Long-term Safety and Efficacy of Corneal Collagen Crosslinking in a Pediatric Group With Progressive Keratoconus: A 7-year Follow-up.

PURPOSE: To assess effectiveness and safety of corneal crosslinking (CXL) to reduce keratoconus (KC) progression and improve visual acuity among children with progressive KC and to analyze the use of 20% dextran-based (Dextran) and 1% hydroxypropyl methylcellulose-based (HPMC) riboflavin. DESIGN: Prospective, clinical cohort study METHODS: Standard CXL (SCXL) was performed in 74 eyes (58 patients, 45 males, mean age 13.0 ± 2.1 years): 53 eyes with HPMC and 21 with Dextran. Examinations were performed at baseline, 3 and 6 months, and 1, 2, 3, 4, 5, and 7 years of follow-up, including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), a complete ophthalmologic examination, anterior segment ocular coherence tomography, Scheimpflug corneal tomography, and specular microscopy. RESULTS: UDVA and CDVA improved at all periods with statistically significant differences in CDVA at 1, 2, and 3 years. Compared with baseline, maximum K (Max K) reduced throughout the 7-year follow-up. Mean thinnest pachymetry (Th Pachy) decreased significantly at 3 months and remained low; in the Dextran group, the Th Pachy mean value returned to baseline 6 months postoperatively. After CXL, 1.5 diopter progression in max K was 1.4% to 14.6% of eyes; worsening was found at 4 to 7 years postoperatively. CONCLUSION: SCXL reduced KC progression in children up to 7 years of follow-up and revealed improvement and stability of UDVA and CDVA in 82% of eyes. For visual acuity and KC stability, no statistically significant difference was observed between Dextran-HPMC. The HPMC group showed persistent cornea thinning, raising concerns about its use in SCXL.

The usage and outcomes of dextran in the treatment of acute deep venous thrombosis.

OBJECTIVES: In this study, we retrospectively compared the outcomes of patients with acute deep vein thrombosis treated with dextran 40 infusion and unfractionated heparin with those of patients treated with unfractionated heparin alone. METHODS: We evaluated 104 patients with the diagnosis of acute deep vein thrombosis. The pain complaints of the patients at the time of admission and the pain complaints in the calf with dorsiflexion of the foot were evaluated with the visual analogue pain scale, and the calf diameter of affected limbs was measured. Fifty five patients had dextran 40 infusion and unfractionated heparin treatment concomitantly (Group HD), while 49 patients had unfractionated heparin treatment (Group H). Heparin dose was adjusted to obtain 1.5- to 2.5-fold of normal activated partial thromboplastin time in both groups. Oral anticoagulant, warfarin sodium, was administered in the first day and resumed. Unfractionated heparin infusion therapy was resumed until international normalized ratio values of 2-2.5 were obtained. Dextran 40 infusion therapy was administered for 3 days. Calf diameters, current pain, and calf pain at foot dorsiflexion were recorded at 48 h and 72 h. 65 patients were distal, and 39 patients were proximal and popliteal acute DVT. None of the patients had phlegmasia. All were acute DVT. RESULTS: At 48 and 72 h of therapy, it was determined that the decrease of the calf diameter and the pain were more significant both at 48th and 72nd hours in the Group HD. The calf circumference change, especially at 72 h, was 2.58 ± 0.39 cm in the group receiving heparin + dextran, while it was 1.76 ± 0.56 cm in the group receiving only heparin. (p = 0.000). While there were only 1.24 ± 1.02 people in the group that received dextran at 72 h, leg pain persisted in 3.35 ± 1.11 people in the other group. (p = 0.000). Evaluation was made only with calf vein diameter measurement. When patients with Homan's sign were evaluated for their calf pain at foot dorsiflexion; both groups had decreased pain at 48th and 72nd hours. CONCLUSION: In this study, we observed that the use of dextran 40 infusion therapy concomitantly with unfractionated heparin accelerates recovery substantially and decreases patient complaints significantly in early stages. In particular, reduction in leg pain and calf circumference reduction were more adequate in the dextran group. The early decrease in the calf circumference will have clinical consequences such as less heparin intake, earlier return to normal life, and a decrease in the total cost of treatment. Since the antithrombotic and anticoagulant effects of dextran are well known, we think that its use in this treatment as well as venous thromboembolism prophylaxis should be discussed.

Ginsenoside Rg1 attenuates dextran sodium sulfate-induced ulcerative colitis in mice.

Ulceration colitis (UC) is a chronic and recurrent inflammatory disorder in the gastro-intestinal tract. The purpose of our study is to explore the potential mechanisms of ginsenoside Rg1 (GS Rg1) on dextran sulfate sodium (DSS)-induced colitis in mice and lipopolysaccharide (LPS)-induced RAW 264.7 cells. Acute colitis was induced in male C57BL/6 mice. In vitro model of LPS-induced RAW 264.7 cells to simulate enteritis model. The disease activity index (DAI), colon length, body weight and histopathological analysis were performed in vivo. Pro-inflammatory cytokines and markers for oxidative and anti-oxidative stress, MPO level were measured in vivo and in vitro. Nuclear erythroid 2-related factor 2 (Nrf2) and NF-?B p65 protein levels were analyzed using western blotting. Our results indicated that the UC models were established successfully by drinking DSS water. GS Rg1 significantly attenuated UC-related symptoms, including preventing weight loss, decreasing DAI scores, and increasing colon length. GS Rg1 ameliorated the DSS-induced oxidative stress. IL-1beta, IL-6, and TNF-alpha levels were significantly increased in serum and cell supernatant effectively, while treatment with the GS Rg1 significantly reduced these factors. GS Rg1 reduced MPO content in the colon. GS Rg1 treatment increased SOD and decreased MDA levels in the serum, colon, and cell supernatant. GS Rg1 restored the Nrf-2/HO-1/NF-?B pathway in RAW 264.7 cells and UC mice, and these changes were blocked by Nrf-2 siRNA. Overall, GS Rg1 ameliorated inflammation and oxidative stress in colitis via Nrf-2/HO-1/NF-kappaB pathway. Thus, GS Rg1 could serve as a potential therapeutic agent for the treatment of UC.

Comparison of polyacrylate polyalcohol copolymer (PPC) and dextranomer/hyaluronic acid (Dx/HA) for treatment of vesicoureteral reflux. A systematic review and meta-analysis.

PURPOSE: Our study aimed to compare the efficacy of polyacrylate polyalcohol copolymer and Dextranomer-Hyaluronic Acid for endoscopic treatment of vesicoureteral reflux. MATERIAL AND METHODS: MEDLINE, EMBASE, Scopus, Web of science, Ovid, Cochrane databases, Google scholar have been searched for studies published until January 2022 in any language. Studies that compared the success rate for endoscopic treatment of vesicoureteral reflux in children with two bulking agents, namely, "polyacrylate polyalcohol copolymer." and "Dextranomer-Hyaluronic Acid" were included for this analysis. RESULTS: Nine studies were included in data synthesis for this meta-analysis. Pooled data with a total of 763 ureters in PPC group and 718 ureters in Dx/HA group indicated that ureters in PPC group were more likely to undergo complete reflux resolution than Dx/HA (OR 3.80, 95% CI: 2.71; 5.31). Among subgroup of patients with high grade reflux, PPC injection had more resolution rate compared to Dx/HA patients (OR: 2.92, 95% CI: 1.19-7.16). In total, 95.81% of the PPC group and 86.52% of the Dx/HA group experienced success after the third injection. However a concerning complication of endoscopic treatment which is ureterovesical junction obstruction (UVJO) was more prevalent in PPC group. So the possible benefits arising from endoscopic treatment with PPC could be offset by the costs of re-implantation surgery or stenting in the case of UVJO. CONCLUSION: These data indicate that PPC injection for vesicoureteral reflux treatment was associated with a higher success rate, but concerningly, UVJO incidence was higher in the PPC group which might negate the possible benefits of PPC injection However, due to the lack of studies with long-term follow-up, we couldn't reach a definitive conclusion about the superiority of one of the bulking agents over the other.

Association of iron infusion reactions with ABO blood type.

OBJECTIVES: We sought to determine risk factors for iv iron infusion-related reactions (IRR), and identify strategies for iron repletion after IRR. METHODS: We conducted a retrospective chart review of patients treated in the classical hematology clinic at Yale Cancer Center (n = 330 consecutive patients) from 2016 to 2021, who received iv ferumoxytol (60.3%), iron sucrose (14.8%), or iron dextran (10.9%). RESULTS: The iv iron IRR was noted in 58 (17.6%) patients, 62.1% of whom had previously tolerated iv iron. The severity of IRR was mild in 22, moderate in 23, and severe in 11 patients. Most (72.4%) patients who experienced IRR tolerated a subsequent iv iron infusion. On multivariable analysis, a history of non-medication allergies was associated with greater odds of IRR (odds ratio [OR] 2.12, 95% confidence interval (CI): 1.16-3.87, p = .01). No patients with type AB blood, and few with type A blood (n = 6), had IRR; compared to type A or AB together, patients with type B (OR 5.00, 95% CI: 1.56-16.06, p = .007) or type O (OR 3.71, 95% CI: 1.44-9.55, p = .007) blood had greater odds of IRR. CONCLUSIONS: This study highlights a possible association of blood type with iv iron IRR; prospective studies with larger patient numbers are warranted to explore this association.

A short- and long-term follow-up study of intersphincteric NASHA Dx implants for fecal incontinence.

BACKGROUND: The bulking agent NASHA Dx injected into the submucosal layer is effective in the treatment of fecal incontinence (FI) at short-and medium-term follow-up but efficacy after injection in the intersphincteric location is unknown. The aim of this study was to determine the short- and long-term efficacy and safety of NASHA Dx injected into the intersphincteric location for FI. METHODS: Patients were recruited from referrals to our Department for treatment of FI in November 2008-January 2010. Eligible patients were injected with 8 ml of NASHA Dx. Patients with a subtotal treatment effect were retreated after 2-4 weeks. The change in number of fecal incontinence episodes, the proportion of responders defined as at least 50% decrease in number of FI episodes and side effects were the main outcome measures. RESULTS: Sixteen patients, 15 women and 1 man with a median age of 68, 5 (range 44-80) years and a median CCFIS of 15 (range 10-19) were included in the study. The median number of incontinence episodes decreased from 21.5 (range 8-61) at baseline to 10 (range 0-30) at 6 months (p = 0.003) and 6 (range 0-44) at 12 months (p = 0.05). The median number of incontinence episodes in the 11 patients completing the 10-year follow-up was 26.5 (range 0-68). The percentage of responders at 12 months and 10 years were 56% and 27%, respectively. Mild to moderate pain at the injection site was described by 69%. There was one case of mild infection, successfully treated with antibiotics and one implant had to be removed due to dislocation. CONCLUSIONS: NASHA Dx as an intersphincteric implant improves incontinence symptoms in the short term with moderate side effects and can be used alone or as an adjunct to other treatment modalities. Long-term efficacy was observed in 27%.

The Impact of Methenamine Hippurate Treatment on Urothelial Integrity and Bladder Inflammation in Aged Female Mice and Women With Urinary Tract Infections.

IMPORTANCE: Antibiotics are commonly used to treat and prevent urinary tract infection (UTI), but resistance is growing. Nonantibiotic prophylaxis such as methenamine hippurate (MH) shows clinical promise, but its impact on bladder factors influencing recurrent UTIs (rUTIs) is not well described. OBJECTIVE: The aim of the study was to examine the effect of MH on bladder inflammation and barrier function in aged mice and women with rUTI. STUDY DESIGN: This study included urine samples from an experimental study involving aged female mice with and without methenamine treatment as well as women with rUTI who received either no prophylaxis, MH alone, vaginal estrogen therapy and/or d-mannose alone, or MH in addition to vaginal estrogen therapy and/or d-mannose. We performed a comprehensive cytopathological analysis, which included enzyme-linked immunosorbent assay for immunoglobulin A (IgA), interleukin 6 (in human samples), and fluorescein isothiocyanate-conjugated-dextran permeability assay (in mice) to assess for urothelial permeability. RESULTS: In the aged mice model, there was a decreased urothelial permeability (as seen by retention of fluorescein isothiocyanate-conjugated-dextran fluorescence in superficial cells) and increased urinary IgA in mice treated with MH compared with controls. There was no significant difference in urothelial shedding (P > 0.05). In human samples, there was significantly increased urinary IgA in those taking MH alone compared with no prophylaxis (830.1 vs 540.1 ng/mL, P = 0.04), but no significant difference in interleukin 6. CONCLUSIONS: Methenamine hippurate seems to enhance barrier function as evidenced by decreased urothelial permeability and increased urinary IgA levels, without worsening inflammation. This may reflect another beneficial mechanism by which MH helps prevent rUTI.

Macrophage targeted triptolide micelles capable of cGAS-STING pathway inhibition for rheumatoid arthritis treatment.

The abundant M1 macrophages in the joint synovium were the main factors that exacerbate rheumatoid arthritis (RA) by secreting various types of inflammatory cytokines. Here, we note that cGAS-STING, an important pro-inflammatory pathway, was significantly up-regulated in RA, enabling it be the potential target for RA therapy. Therefore, in this work, we developed M1 macrophages targeted micelles capable of cGAS-STING pathway inhibition for the smart treatment of RA. The folic acid (FA) and lauric acid (LA) were modified on dextran to obtain an amphiphilic polymer (FDL). Then, FDL was subsequently applied to encapsulate triptolide (TP) to form FDL@TP nanomicelles. The FDL@TP could target the joint and enhance the cell uptake of TP by M1 macrophages (overexpressing folate receptor-ß), which also reduced the side effects of TP on normal tissues. In M1 macrophages, the released TP, acted as an anti-inflammatory and immunosuppressant, obviously down-regulated the expressions of cGAS and STING protein, and thus reduced the secretion of TNF-α, IL-1ß and IL-6. Importantly, compared with the same dose of free TP, FDL@TP could significantly enhance the anti-inflammatory effect. Therefore, FDL@TP nanomicelles were believed to be superior candidates for the clinical treatment of RA.

A systematic review & meta-analysis comparing outcomes of endoscopic treatment of primary vesico ureteric reflux in children with polyacrylate poly alcohol copolymer versus dextranomer hyaluranic acid.

BACKGROUND & AIMS: There are conflicting reports on the efficacy of bulking agents for vesico ureteric reflux (VUR). In this meta-analysis we have compared the outcomes of endoscopic treatment with polyacrylate polyalcohol copolymer (PPC) and dextranomer hyaluronic acid (DxHA). METHODS: A systematic review of publications between 2010 and 2020 was conducted covering databases like PUBMED, MEDLINE etc. for (endoscopic treatment) AND (VUR) AND (PPC OR DxHA) AND (recurrence OR complications). PRISMA guidelines were followed and only comparative studies were included. Outcomes were early success defined as absence of VUR in voiding cystourethrogram at 3-months followup, urinary tract infections (UTI) and occurrence of vesico-ureteric-junction obstruction (VUJO). Risk of bias was analysed with Robvis tool and odds-ratios were compared with Revman-3.0. RESULTS: Among nine studies (heterogeneity; I 2 69-79%) all cleared the risk of bias assessment. There was no significant difference in high grade VUR (p = 0.94) between PPC (40%) and DxHA (43%). Success rate after single injection was significantly higher (p = 0.0001) at 86% (477/555) for PPC vs 69% (474/685) for DxHA. UTI rate between PPC (12%) and DxHA (14.6%) was not statistically significant (p = 0.54). VUJO rate between PPC (3.9%) and DxHA (0.8%) was also not significantly different (p = 0.47). Significantly lesser volume (p = 0.02) was used for PPC (0.7 ml) compared to DxHA (0.9 ml). CONCLUSION: Reflux resolution was significantly higher with PPC than DxHA. Postinjection UTI/VUJO incidence was not significantly different between them. Limitation of this meta-analysis was heterogeneity & small number of articles. Further studies should focus on long-term outcomes and cost-effectiveness.

Fabrication of anionic dextran-coated micelles for aptamer targeted delivery of camptothecin and survivin-shRNA to colon adenocarcinoma.

In this study, we synthesized PLA-PEI micelles which was co-loaded with an anticancer drug, camptothecin (CPT), and survivin-shRNA (sur-shRNA). The hydrophobic CPT was encapsulated in the core of the polymeric micelles while sur-shRNA was adsorbed on the shell of the cationic micelles. Then, the positively-charged sur-shRNA-loaded micelles were coated with poly carboxylic acid dextran (PCAD) to form PLA/PEI-CPT-SUR-DEX. To selectively target the system to colon cancer cells, AS1411 aptamer was covalently attached to the surface of the PCAD-coated nanoparticles (PLA/PEI-CPT-SUR-DEX-APT). PLA/PEI-CPT-SUR-DEX-APT enhanced cellular uptake through receptor-mediated endocytosis followed by increased CPT accumulation, downregulation of survivin, and thereby 38% cell apoptosis. In C26 tumor-bearing mice models, after administered intravenously, PLA/PEI-CPT-SUR-DEX-APT and PLA/PEI-CPT-SUR-DEX formulations resulted in a significant inhibition of the tumor growth with tumor inhibition rate of 93% and 87%, respectively. Therefore, PLA/PEI-CPT-SUR-DEX-APT could be a versatile co-delivery vehicle for promising therapy of colorectal cancer.

Synthesis, characterization, and cytotoxicity evaluation of dextran-myristoyl-ECGKRK peptide conjugate.

CGKRK is a well-known tumor homing peptide with significant specificity for many types of cancer tissues. Herein, we describe the synthesis of a novel drug delivery system based on dextran decorated with myristoyl-ECGKRK peptide. The myristoylated peptide was synthesized and conjugated to dextran via an ester bond followed by purification. FT-IR and NMR confirmed the success of the conjugation reaction, while the surface morphology examination revealed that the conjugate has a characteristic porous network-like structure. Dynamic-light scattering measurements indicated the ability of the conjugate to self-assemble into nanoparticles with an average size of 248 ± 6.33 nm, and zeta potential of 10.7 mV. The cytotoxicity profiles for the peptide, dextran (Dex0), and dextran-peptide conjugate (Dex1) were evaluated against triple-negative breast cancer cells (MDA-MB-231), breast cancer cells (MCF-7), and human embryonic normal kidney cells (HEK-293). The results revealed that myristoyl-ECGKRK was noncytotoxic on the two different breast cancer cell lines up to 50 µM, but the cell viability was minimally reduced to 85% at 50 µm in HEK-293 cells. Similarly, Dex0 showed a neglected cytotoxicity profile at all tested concentrations. The Dex1 was not toxic to the cells up to a concentration of 8.3 mg/mL.