Improving hemocompatibility of decellularized vascular tissue by structural modification of collagen fiber.

Decellularized vascular tissue has high potential as a tissue-engineered vascular graft because of its similarity to native vessels in terms of mechanical strength. However, exposed collagen on the tissue induces blood coagulation, and low hemocompatibility is a major obstacle to its vascular application. Here we report that freeze-drying and ethanol treatment effectively modify collagen fiber structure and drastically reduce blood coagulation on the graft surface without exogenous chemical modification. Decellularized carotid artery of ostrich was treated with freeze-drying and ethanol solution at concentrations ranging between 5 and 99.5 %. Collagen fiber distance in the graft was narrowed by freeze-drying, and the non-helical region increased by ethanol treatment. Although in vitro blood coagulation pattern was similar on the grafts, platelet adhesion on the grafts was largely suppressed by freeze-drying and ethanol treatments. Ex vivo blood circulation tests also indicated that the adsorption of platelets and Von Willebrand Factor was largely reduced to approximately 80 % by ethanol treatment. These results indicate that structural modification of collagen fibers in decellularized tissue reduces blood coagulation on the surface by inhibiting platelet adhesion.

A rare case of schwannoma of the small intestine discovered during intussusception.

A woman in her 60s with anemia was diagnosed with a small intestinal intussusception on computed tomography. She underwent a double-balloon endoscopy, which revealed submucosal tumor in the ileum. Suspected to be the cause of anemia and intussusception, surgical intervention was carried out, revealing it to be a schwannoma. Schwannomas of the small intestine are very rare, and because exophytic growths are common, intussusception due to luminal side development is even rarer.

Central subfield thickness of diabetic macular edema: Correlation with the aqueous humor proteome.

Purpose: Diabetic macular edema (DME) is a sight-threatening complication of diabetes. Consequently, studying the proteome of DME may provide novel insights into underlying molecular mechanisms. Methods: In this study, aqueous humor samples from eyes with treatment-naïve clinically significant DME (n = 13) and age-matched controls (n = 11) were compared with label-free liquid chromatography-tandem mass spectrometry. Additional aqueous humor samples from eyes with treatment-naïve DME (n = 15) and controls (n = 8) were obtained for validation by enzyme-linked immunosorbent assay (ELISA). Best-corrected visual acuity (BCVA) was evaluated, and the severity of DME was measured as central subfield thickness (CST) employing optical coherence tomography. Control samples were obtained before cataract surgery. Significantly changed proteins were identified using a permutation-based calculation, with a false discovery rate of 0.05. A human donor eye with DME and a control eye were used for immunofluorescence. Results: A total of 101 proteins were differentially expressed in the DME. Regulated proteins were involved in complement activation, glycolysis, extracellular matrix interaction, and cholesterol metabolism. The highest-fold change was observed for the fibrinogen alpha chain (fold change = 17.8). Complement components C2, C5, and C8, fibronectin, and hepatocyte growth factor-like protein were increased in DME and correlated with best-corrected visual acuity (BCVA). Ceruloplasmin and complement component C8 correlated with central subfield thickness (CST). Hemopexin, plasma kallikrein, monocyte differentiation antigen CD14 (CD14), and lipopolysaccharide-binding protein (LBP) were upregulated in the DME. LBP was correlated with vascular endothelial growth factor. The increased level of LBP in DME was confirmed using ELISA. The proteins involved in desmosomal integrity, including desmocollin-1 and desmoglein-1, were downregulated in DME and correlated negatively with CST. Immunofluorescence confirmed the extravasation of fibrinogen at the retinal level in the DME. Conclusion: Elevated levels of pro-inflammatory proteins, including the complement components LBP and CD14, were observed in DME. DME was associated with the loss of basal membrane proteins, compromised desmosomal integrity, and perturbation of glycolysis.

Real-world efficacy and safety of tofacitinib treatment in Asian patients with ulcerative colitis.

BACKGROUND: Real-world data on tofacitinib (TOF) covering a period of more than 1 year for a sufficient number of Asian patients with ulcerative colitis (UC) are scarce. AIM: To investigate the long-term efficacy and safety of TOF treatment for UC, including clinical issues. METHODS: We performed a retrospective single-center observational analysis of 111 UC patients administered TOF at Hyogo Medical University as a tertiary inflammatory bowel disease center. All consecutive UC patients who received TOF between May 2018 and February 2020 were enrolled. Patients were followed up until August 2020. The primary outcome was the clinical response rate at week 8. Secondary outcomes included clinical remission at week 8, cumulative persistence rate of TOF administration, colectomy-free survival, relapse after tapering of TOF and predictors of clinical response at week 8 and week 48. RESULTS: The clinical response and remission rates were 66.3% and 50.5% at week 8, and 47.1% and 43.5% at week 48, respectively. The overall cumulative clinical remission rate was 61.7% at week 48 and history of anti-tumor necrosis factor-alpha (TNF-α) agents use had no influence (P = 0.25). The cumulative TOF persistence rate at week 48 was significantly lower in patients without clinical remission than in those with remission at week 8 (30.9% vs 88.1%; P < 0.001). Baseline partial Mayo Score was significantly lower in responders vs non-responders at week 8 (odds ratio: 0.61, 95% confidence interval: 0.45-0.82, P = 0.001). Relapse occurred in 45.7% of patients after TOF tapering, and 85.7% of patients responded within 4 wk after re-increase. All 6 patients with herpes zoster (HZ) developed the infection after achieving remission by TOF. CONCLUSION: TOF was more effective in UC patients with mild activity at baseline and its efficacy was not affected by previous treatment with anti-TNF-α agents. Most relapsed patients responded again after re-increase of TOF and nearly half relapsed after tapering off TOF. Special attention is needed for tapering and HZ.

A new surgical approach for the treatment of a refractory foveal microaneurysm: A case report.

Purpose: To report a case of a refractory foveal microaneurysm (MA) that was successfully treated by use of a new surgical procedure. Observations: This study involved a 79-year-old female with an active foveal MA associated with branch retinal vein occlusion in her left eye. Despite anti-vascular endothelial growth factor treatments, the MA remained active without closure, and best-corrected visual acuity (VA) gradually decreased from 20/20 to 20/200. After our new surgical procedure was explained in detail to the patient, written informed consent was obtained from the patient and the surgery was performed. Briefly, following pars plana vitrectomy, the internal limiting membrane in her left eye was peeled and the retina of the external wall of the MA was then gently incised. The exposed MA was then directly grabbed and pulled up onto the retina using 27-gauge microforceps, and photocoagulation was performed. At 3-months postoperative, closure of the MA and improvement in the retinal findings were observed, and best-corrected VA improved to 20/67. Conclusions and importance: We report a case of a refractory foveal MA that was successfully treated with a novel surgical technique that closed the MA, avoided thermal damage to the surrounding tissue, and resulted in improved postoperative VA.

Steroid refractory severe ulcerative colitis after kidney transplantation successfully treated with infliximab.

A 54-year-old man underwent kidney transplantation at the age of 50 for end-stage renal failure owing to diabetic nephropathy. The patient was subsequently treated with three immunosuppressive drugs (tacrolimus, mycophenolate mofetil, and methylprednisolone) to prevent organ rejection, and no renal failure was noted. He visited our department with bloody stools and diarrhea, and a colonoscopy revealed mucosal edema and redness of the entire colon. After excluding infection and drug-induced enteritis based on the endoscopic and pathological findings, he was diagnosed with ulcerative colitis (UC). He was admitted and received a high dose of steroids, but did not demonstrate improvement. We initiated infliximab (IFX), and his symptoms improved within 3 days. After the second IFX treatment, the patient achieved clinical remission and was discharged. After the third IFX dose, the biomarker level became normal, and a colonoscopy after the fourth IFX dose revealed that all ulcers had become scarred and achieved endoscopic remission. The patient continued all medications to prevent organ rejection after the onset of UC and had no graft dysfunction or infection for 1 year.

Anti-nuclear matrix protein 2 antibody-positive dermatomyositis with gastrointestinal ulcers: A case report.

Gastrointestinal manifestations are a very rare complication of dermatomyositis (DM) and are much less frequent in adult cases than in juvenile cases. Only a few previous papers have reported adult patients who had DM with anti-nuclear matrix protein 2 (anti-NXP2) antibodies and who developed gastrointestinal ulcers. Herein, we report a similar case of a 50-year-old man who had DM with anti-NXP2 antibodies followed by relapsing multiple gastrointestinal ulcers. Even after the administration of prednisolone, his muscle weakness and myalgia deteriorated and gastrointestinal ulcers relapsed. In contrast, intravenous immunoglobulin and azathioprine improved his muscle weakness and gastrointestinal ulcers. Based on the parallel disease activity of the muscular and gastrointestinal symptoms, we considered that his gastrointestinal ulcers were a complication of DM with anti-NXP2 antibodies. We also propose that early intensive immunosuppressive therapy would be required for the muscular and gastrointestinal symptoms in DM with anti-NXP2 antibodies.

Reply to Marino et al. Does Subretinal Fluid Influence Choroidal Thickness (ChT) and Structure in Preeclampsia with Serous Retinal Detachment? Comment on "Fukui et al. Changes in Choroidal Thickness and Structure in Preeclampsia with Serous Retinal Detachment. J. Clin. Med. 2023, 12, 609".

We thank the authors for the interesting comments [...].

Short-term clinical evaluation of teduglutide for patients with Crohn's disease on home parenteral support for postoperative short bowel syndrome with intestinal failure.

BACKGROUND & AIM: The short-term effects of teduglutide (TED) for short bowel syndrome with chronic intestinal failure (SBS-IF) in patients with Crohn's disease (CD) remain unknown. The aim of this study was to investigate the effects of TED in patients with CD on home parenteral support (PS) for SBS-IF. METHODS: We retrospectively investigated the medical records of patients with CD associated with SBS-IF who initiated TED between 2020 and 2021. The primary outcomes were the change in PS volume and proportion of patients with a reduction of PS volume by ≥ 20% at week 8. Secondary outcomes were the change in PS volume in patients with CD without/with colon in continuity and adverse events during the observation period. RESULTS: Eighteen patients with CD who underwent home PS for SBS-IF were included in this study. Two patients were excluded owing to intolerable abdominal pain or vomiting within 8 weeks (11%). Sixteen patients continued TED throughout the observation period. The median PS duration was 10.5 years. The median observation period was 22 weeks after starting TED. TED significantly reduced the PS volume from 15,825.0 mL/week to 10,700.0 mL/week (p = 0.0038), and the PS volume decreased by ≥ 20% in 7 patients (43.8%) at week 8. The PS volume was significantly reduced at week 4 (p = 0.0078) in 11 patients without colon in continuity but not in 5 patients with colon in continuity. Two patients successfully stopped home PS. No serious adverse events occurred. CONCLUSIONS: TED administration significantly reduced PS volume at week 8 in patients with CD associated with SBS-IF, and at week 4 in patients without colon in continuity.

Macular Edema in Central Retinal Vein Occlusion Correlates With Aqueous Fibrinogen Alpha Chain.

Purpose: The global protein profile of the aqueous humor has been found to correlate with the severity of retinal vascular disease. Studying the aqueous humor in central retinal vein occlusion (CRVO) with proteomic techniques may bring insights to the molecular mechanisms underlying the condition. Methods: Aqueous humor samples from treatment naïve patients with CRVO complicated by macular edema (n = 28) and age-matched controls (n = 20) were analyzed by label-free quantification liquid chromatography - tandem mass spectrometry. Best corrected visual acuity (BCVA) was measured as logMAR, and the severity of macular edema was evaluated as central retinal thickness (CRT) with optical coherence tomography. Control samples were obtained prior to cataract surgery. Significantly changed proteins were identified by a permutation-based calculation with a false discovery rate of 0.05. Results: A total of 177 proteins were differentially expressed in CRVO. Regulated proteins were involved in complement activation, innate immune response, blood coagulation, and cell adhesion. Upregulated proteins that correlated with BCVA and CRT included fibrinogen alpha, beta, and gamma chains, fibronectin, Ig lambda-6 chain C region, Ig alpha-1 chain C region, and complement C7. Downregulated proteins that correlated negatively with BCVA, and CRT, included procollagen C-endopeptidase enhancer 1, clusterin, opticin, reelin, fibrillin-1, and cadherin-2. Monocyte differentiation antigen CD14 and lipopolysaccharide-binding protein were increased in CRVO. Conclusions: Fibrinogen chains, fibronectin, and immunoglobulin components correlated with BCVA and CRT, suggesting a multifactorial response. Protective anti-angiogenic proteins, including procollagen C-endopeptidase enhancer 1, clusterin, and opticin, were downregulated in CRVO and correlated negatively with BCVA and CRT.

Changes in Choroidal Thickness and Structure in Preeclampsia with Serous Retinal Detachment.

Preeclampsia is a pregnancy-specific syndrome characterized by hypertension and proteinuria. We retrospectively investigated the clinical features, including choroidal layer thickness and luminal area to stromal area ratio, in a case series of preeclampsia with serous retinal detachment (SRD). The subjects were pregnant women with SRD during hospitalization for preeclampsia from October 2014 to June 2021. Based on medical records, affected eyes, time of onset, fundus examination findings, and subfoveal choroidal thickness (SCT), the choroidal layer thickness and choroidal vascular index (CVI) in each patient was examined. Thirteen eyes from seven patients (mean age 30.7 ± 4.7 years) were included in the study. In all cases, SRD improved without topical ocular treatment. The mean SCT at the initial visit was 424.4 ± 70.5 µm, and all patients had choroidal thickening, which significantly decreased to 286.0 ± 57.9 µm (p < 0.01) at the last visit. The mean choroidal inner layer was 162.7 ± 69.4 µm at the initial visit and 122.3 ± 35.5 µm at the final follow-up visit (p = 0.06), showing no significant difference; however, the mean choroidal outer layer was 261.7 ± 47.6 µm at the initial visit and 163.7 ± 37.1 µm at the final follow-up visit (p < 0.01), thus showing a significant decrease. The mean CVI was 67.2 ± 1.3% at the initial visit, yet it had significantly decreased to 65.4 ± 1.1% (p < 0.01) at the final follow-up visit. The findings of this study show that SRD with preeclampsia is associated with increased thickening of the choroidal outer layer, especially in the choroidal luminal area.

Progression of Myopic Maculopathy: A Systematic Review and Meta-Analysis.

PURPOSE: The purpose of this study was to elucidate the risk factors for the progression of myopic maculopathy (MM) based on severity. METHODS: In this study, we conducted a systematic review and meta-analysis of the literature published before December 2020 on the risk factors for the progression of MM in patients with pathologic myopia (PM) and high myopia (HM). Odds ratios (ORs) for different stages of myopic maculopathy categorized based on the International Meta-Analysis for PM (META-PM) classification were calculated using fixed and random effects models. RESULTS: A total of 12,070 affected eyes derived from 5 cohort studies were included in the systematic review. The presence of PM at baseline was found to be significantly associated with an increased risk of MM progression (pooled ORs: 7.17, 95% confidence interval [CI]: 3.29-15.6), and the greater category of MM at baseline was found to be significantly associated with an increased risk of MM progression, that is, eyes with MM category 3 or more compared with eyes with MM category 2 (pooled OR: 10.95, 95% CI: 6.07-19.76) and eyes with MM category 4 compared with eyes with MM category 3 (pooled ORs: 2.45, 95% CI: 0.28-21.37). CONCLUSIONS: The findings in this systematic review and meta-analysis indicate that the progression of MM is associated with more severe MM at baseline.

Fingolimod-associated severe bilateral cystoid macular edema.

Purpose: To report a rare case in which a patient undergoing long-term oral fingolimod treatment for multiple sclerosis (MS) developed late-onset severe bilateral cystoid macular edema (ME) at 3-weeks post cataract surgery. Observations: This study involved a 61-year-old female undergoing long-term oral fingolimod treatment for MS in whom at 4-years post initiation of treatment and the treatment being tapered to a 0.5 mg twice-weekly dose severe bilateral cystoid ME occurred at 3-weeks post cataract surgery. Although the patient was administered the proper treatments for pseudophakic ME, including a 20-mg sub-Tenon's-capsule triamcinolone acetonide injection, it took 13 months for the ME to ultimately resolve with continued oral fingolimod treatment. Conclusions and importance: The findings in this study show that severe bilateral cystoid ME can occur even several years after initiating fingolimod treatment, thus indicating that detailed follow-up is necessary post cataract surgery.

Accelerated tissue regeneration in decellularized vascular grafts with a patterned pore structure.

Decellularized tissue is expected to be utilized as a regenerative scaffold. However, the migration of host cells into the central region of the decellularized tissues is minimal because the tissues are mainly formed with dense collagen and elastin fibers. This results in insufficient tissue regeneration. Herein, it is demonstrated that host cell migration can be accelerated by using decellularized tissue with a patterned pore structure. Patterned pores with inner diameters of 24.5 ± 0.4 µm were fabricated at 100, 250, and 500 µm intervals in the decellularized vascular grafts via laser ablation. The grafts were transplanted into rat subcutaneous tissue for 1, 2, and 4 weeks. All the microporous grafts underwent faster recellularization with macrophages and fibroblast cells than the non-porous control tissue. In the case of non-porous tissue, the cells infiltrated approximately 50% of the area four weeks after transplantation. However, almost the entire area was occupied by the cells after two weeks when the micropores were aligned at a distance of less than 250 µm. These results suggest that host cell infiltration depends on the micropore interval, and a distance shorter than 250 µm can accelerate cell migration into decellularized tissues.

Surgical creation of multiple drainage holes versus local injection of corticosteroids for treatment of aural hematomas in dogs: 51 dogs with 71 aural hematomas (2000-2017).

OBJECTIVE: To investigate the outcome of surgical creation of multiple drainage holes (MDHs) versus local corticosteroid injection (LCI) for treatment of aural hematomas (AHs) in dogs and identify risk factors for recurrence and development of new AHs. ANIMALS: 51 dogs with 71 AHs. PROCEDURES: Medical records were reviewed, and information on signalment, clinical findings, and outcome was recorded. Recurrence was defined as development of an AH at the primary site after the first month of treatment. Development of a new AH was defined as an AH occurring at a site different from the treated site. RESULTS: The recurrence rate after the first month of treatment was significantly higher following the LCI procedure (17/48 AHs [33%]) than after the MDH procedure (1/24 AHs [4%]). The odds of recurrence increased as the numbers of LCI in the first month increased (OR, 2.414). Recurrent AHs after LCI resolved with additional LCIs; only 1 AH (2%) required a change to MDHs. No recurrence was observed after the eighth month, and the cosmetic results were good. Sixteen of 51 (31%) dogs had multiple or new AHs. The risk of new AHs was higher in Golden Retrievers and Labrador Retrievers and in dogs with allergic dermatitis. CONCLUSIONS AND CLINICAL RELEVANCE: Long-term outcomes suggested that both creation of MDHs and LCI can be therapeutic options for dogs with AHs. However, the risk of new AH development should be considered, especially in retriever breeds and dogs with allergic dermatitis.

Risk factors of poor prognosis and impairment of activities of daily living in patients with hemorrhagic gastroduodenal ulcers.

BACKGROUND: Impairment of activities of daily living (ADL) due to hemorrhagic gastroduodenal ulcers (HGU) has rarely been evaluated. We analyzed the risk factors of poor prognosis, including mortality and impairment of ADL, in patients with HGU. METHODS: In total, 582 patients diagnosed with HGU were retrospectively analyzed. Admission to a care facility or the need for home adaptations during hospitalization were defined as ADL decline. The clinical factors were evaluated: endoscopic features, need for interventional endoscopic procedures, comorbidities, symptoms, and medications. The risk factors of outcomes were examined with multivariate analysis. RESULTS: Advanced age (> 75 years) was a significant predictor of poor prognosis, including impairment of ADL. Additional significant risk factors were renal disease (odds ratio [OR] 3.43; 95% confidence interval [CI] 1.44-8.14) for overall mortality, proton pump inhibitor (PPIs) usage prior to hemorrhage (OR 5.80; 95% CI 2.08-16.2), and heart disease (OR 3.05; 95% CI 1.11-8.43) for the impairment of ADL. Analysis of elderly (> 75 years) subjects alone also revealed that use of PPIs prior to hemorrhage was a significant predictor for the impairment of ADL (OR 8.24; 95% CI 2.36-28.7). CONCLUSION: In addition to advanced age, the presence of comorbidities was a risk of poor outcomes in patients with HGU. PPI use prior to hemorrhage was a significant risk factor for the impairment of ADL, both in overall HGU patients and in elderly patients alone. These findings suggest that the current strategy for PPI use needs reconsideration.

Risk Factors for Acute Cholangitis Caused by Enterococcus faecalis and Enterococcus faecium.

Background/Aims: Acute cholangitis (AC) is a potentially life-threatening bacterial infection, and timely antimicrobial treatment, faster than that achieved with bacterial cultures, is recommended. Although the current guidelines refer to empirical antimicrobial treatment, various kinds of antimicrobial agents have been cited because of insufficient analyses on the spectrum of pathogens in AC. Enterococcus spp. is one of the most frequently isolated Gram-positive bacteria from the bile of patients with AC, but its risk factors have not been extensively studied. This study aimed to analyze the risk factors of AC caused by Enterococcus faecalis and Enterococcus faecium. Methods: Patients with AC who were hospitalized in a Japanese tertiary center between 2010 and 2015 were retrospectively analyzed. Patients' first AC episodes in the hospital were evaluated. Results: A total of 266 patients with AC were identified. E. faecalis and/or E. faecium was isolated in 56 (21%) episodes of AC. Prior endoscopic sphincterotomy (EST), the presence of a biliary stent, prior cholecystectomy, and past intensive care unit admission were more frequently observed in AC patients with E. faecalis and/or E. faecium than in those without such bacteria. Prior EST was identified as an independent risk factor for AC caused by E. faecalis and/or E. faecium in the multivariate analysis. Conclusions: Given the intrinsic resistance of E. faecalis and E. faecium to antibiotics, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with prior EST.

Prediction Error of Intraocular Lens Power Calculation in Very Elderly Patients over 90 Years Old.

BACKGROUND: To investigate the influence of age on prediction error (PE) after cataract surgery in very elderly (VE) patients aged more than 90 years. METHODS: We retrospectively analyzed 66 eyes of patients aged ≥90 years (VE group) who underwent phacoemulsification and intraocular lens (IOL) implantation. As the control group (CG), we investigated 121 eyes of patients aged 70-89 years who underwent the same surgery. PE was calculated 1 month post-surgery as the actual postoperative spherical equivalent minus the target diopter, which was calculated using the Sanders-Retzlaff-Kraff/T formula. The absolute and arithmetic PE were compared between the two groups. The factors affecting absolute PE outside ±0.5 diopter (D) and ±1.0 D were determined through logistic regression analysis with the variables age, sex, axial length (AL), average corneal power, preoperative best-corrected visual acuity, target diopter, and coexisting pseudoexfoliation syndrome. RESULTS: The absolute PE was significantly larger in the VE group than that in the CG (0.60 ± 0.52 D and 0.34 ± 0.25 D, respectively; P < .001). There was no significant difference in terms of arithmetic PE between the two groups (-0.06 ± 0.79 D and -0.07 ± 0.42 D, respectively; P = .653). In the logistic regression analysis, age was significantly associated with absolute PE outside ±0.50 D (Odds ratio [OR]: 1.05). Age and AL were significantly associated with absolute PE outside ±1.0 D (OR: 1.24 and 0.20, respectively). CONCLUSIONS: Absolute PE tended to increase in the cataract surgery of VE patients.