Repeated Plastic Stentings of Common Hepatic Duct for Portal Vein Aneurysm Compression in a Patient Unsuitable for Surgery

Portal vein aneurysms are rare vascular malformations with unclear etiologies and optimal treatment guidelines. Although Doppler ultrasonography is the most commonly used diagnostic tool, there is no gold standard imaging modality. Despite recommendations of surgical treatment for symptomatic aneurysms, there are limited options in the management of portal vein aneurysm-related complications in patients unfit for surgical intervention. We describe an 85-year-old man who presented with abdominal pain and low-grade fever with clinical signs consistent with cholangitis. Endoscopic retrograde cholangiopancreatography revealed a common hepatic duct stricture and concomitant intraductal ultrasonography identified adjacent aneurysmal portal vein dilatation. The final diagnosis of portal vein aneurysm was made using contrast computerized tomography scan. The patient was considered unsuitable for surgery due to his advanced age and multiple comorbidities. Instead, an endoscopic biliary plastic stent was inserted as a therapeutic alternative, which successfully achieved complete resolution of symptoms 3 days after the procedure. The patient was regularly followed at the outpatient clinic with repeated stent replacements every 3 to 4 months. After a follow-up of over 3.5 years, the patient remained symptom-free without signs of portal vein aneurysm compression. The result suggests that repeated stent replacements may be a therapeutic option for biliary compression by portal vein aneurysm in patients contraindicated for surgical intervention

Adipose-derived mesenchymal stem cells markedly attenuate brain infarct size and improve neurological function in rats

<p>Abstract</p> <p>Background</p> <p>The therapeutic effect of adipose-derived mesenchymal stem cells (ADMSCs) on brain infarction area (BIA) and neurological status in a rat model of acute ischemic stroke (IS) was investigated.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 30) were divided into IS plus intra-venous 1 mL saline (at 0, 12 and 24 h after IS induction) (control group) and IS plus intra-venous ADMSCs (2.0 × 10⁶) (treated interval as controls) (treatment group) after occlusion of distal left internal carotid artery. The rats were sacrificed and brain tissues were harvested on day 21 after the procedure.</p> <p>Results</p> <p>The results showed that BIA was larger in control group than in treatment group (p < 0.001). The sensorimotor functional test (Corner test) identified a higher frequency of turning movement to left in control group than in treatment group (p < 0.05). mRNA expressions of Bax, caspase 3, interleukin (IL)-18, toll-like receptor-4 and plasminogen activator inhibitor-1 were higher, whereas Bcl-2 and IL-8/Gro were lower in control group than in treatment group (all p < 0.05). Western blot demonstrated a lower CXCR4 and stromal-cell derived factor-1 (SDF-1) in control group than in treatment group (all p < 0.01). Immunohistofluorescent staining showed lower expressions of CXCR4, SDF-1, von Willebran factor and doublecortin, whereas the number of apoptotic nuclei on TUNEL assay was higher in control group than in treatment group (all p < 0.001). Immunohistochemical staining showed that cellular proliferation and number of small vessels were lower but glial fibrillary acid protein was higher in control group than in treatment group (all p < 0.01).</p> <p>Conclusions</p> <p>ADMSC therapy significantly limited BIA and improved sensorimotor dysfunction after acute IS.</p

The efficacy and safety of cuttlebone for lowering serum phosphate in patients with end-stage renal disease: a meta-analysis of randomized controlled trials

Background: The efficacy of cuttlebone for treating hyperphosphatemia in patients with end-stage renal disease and its safety remained unclear.Methods: Randomized controlled trials comparing the efficacy of cuttlebone with conventional interventions were retrieved from MEDLINE, EMBASE, Cochrane Library, Airiti Library, and other major Chinese databases until 1 February 2023. The primary outcome was circulating phosphate concentration, while secondary outcomes included circulating calcium and intact parathyroid hormone levels, calcium–phosphorus product, and treatment-related side-effects.Results: Analysis of nine studies published between 2000 and 2019 including 726 participants showed a lower circulating phosphate concentration in the cuttlebone group than in controls [mean difference (MD) = −0.23, 95% CI: −0.39 to −0.06, p = 0.006, I2 = 94%, 726 patients] and a dose-dependent effect of cuttlebone against hyperphosphatemia. Therapeutic benefits were noted after both short-term (1–2 months) and long-term (3–6 months) treatments. Besides, patients receiving hemodialysis showed a better response to cuttlebone than those receiving peritoneal dialysis. There was no difference in circulating calcium level (mean difference = 0.03, 95% CI: −0.01 to 0.07, p = 0.17, I2 = 34%, 654 patients), while patients receiving cuttlebone showed lower circulating iPTH level and calcium-phosphorus product (MD = −43.63, 95% CI: −74.1 to −13.16, p = 0.005, I2 = 76%, 654 patients), (MD = −0.38, 95% CI: −0.38 to −0.01, p = 0.04, I2 = 83%, 520 patients). No difference in the risks of constipation, gastrointestinal discomfort, and elevated blood calcium was noted between the two groups.Conclusion: Compared with conventional phosphate-binding agents, cuttlebone more efficiently suppressed hyperphosphatemia with a dose-dependent effect. The limited number of included studies warrants further clinical investigations to verify our findings.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023396300

Involvement of the nuclear high mobility group B1 peptides released from injured hepatocytes in murine hepatic fibrogenesis

AbstractThis study investigated the pro-fibrogenic role of high mobility group box 1 (HMGB1) peptides in liver fibrogenesis. An animal model of carbon tetrachloride (CCl4)-induced liver fibrosis was used to examine the serum HMGB1 levels and its intrahepatic distribution. The increased serum HMGB1 levels were positively correlated with elevation of transforming growth factor-β1 (TGF-β1) and collagen deposition during fibrogenesis. The cytoplasmic distribution of HMGB1 was noted in the parenchymal hepatocytes of fibrotic livers. In vitro studies confirmed that exposure to hydrogen peroxide and CCl4 induced an intracellular mobilization and extracellular release of nuclear HMGB1 peptides in clone-9 and primary hepatocytes, respectively. An uptake of exogenous HMGB1 by hepatic stellate cells (HSCs) T6 cells indicated a possible paracrine action of hepatocytes on HSCs. Moreover, HMGB1 dose-dependently stimulated HSC proliferation, up-regulated de novo synthesis of collagen type I and α-smooth muscle actin (α-SMA), and triggered Smad2 phosphorylation and its nuclear translocation through a TGF-β1-independent mechanism. Blockade with neutralizing antibodies and gene silencing demonstrated the involvement of the receptor for advanced glycation end-products (RAGE), but not toll-like receptor 4, in cellular uptake of HMGB1 and the HMGB1-mediated Smad2 and ERK1/2 phosphorylation as well as α-SMA up-regulation in HSC-T6 cells. Furthermore, anti-RAGE treatment significantly ameliorated CCl4-induced liver fibrosis. In conclusion, the nuclear HMGB1 peptides released from parenchymal hepatocytes during liver injuries may directly activate HSCs through stimulating HSC proliferation and transformation, eventually leading to the fibrotic changes of livers. Blockade of HMGB1/RAGE signaling cascade may constitute a therapeutic strategy for treatment of liver fibrosis

A systematic review and meta-analysis comparing the efficacy and safety of ciprofol (HSK3486) versus propofol for anesthetic induction and non-ICU sedation

Background: Ciprofol (HSK3486) is a novel intravenous anesthetic agent that bears structural similarity to propofol and displays favorable pharmacodynamic characteristics such as rapid onset and offset. The meta-analysis aimed at comparing the efficacy and safety of ciprofol versus propofol in clinical practice.Methods: Medline, EMBASE, Google Scholar, Cochrane Library were searched from inception to April 2023. The primary outcome was success rate of sedation/anesthetic induction and differences in sedation/induction time. The secondary outcomes included risks of hemodynamic instability, respiratory complications, and pain on injection, as well as recovery profiles, satisfaction score, and top-up dose requirement.Results: Twelve RCTs (sedation: n = 6, anesthetic induction, n = 6, all conducted in China) involving 1,793 patients (age: 34–58 years) published from 2021 to 2023 were analyzed. Pooled results revealed no differences in success rate [risk ratio (RR) = 1, 95% confidence interval (CI): 0.99 to 1.01, I2 = 0%, 1,106 patients, p = 1] and time required for successful anesthetic induction/sedation [mean difference (MD) = 7.95 s, 95% CI: −1.09 to 16.99, I2 = 97%, 1,594 patients, p = 0.08]. The risks of top-up dose requirement (RR = 0.94, p = 0.48), cardiopulmonary complications [i.e., bradycardia (RR = 0.94, p = 0.67), tachycardia (RR = 0.83, p = 0.68), hypertension (RR = 1.28, p = 0.2), hypoxemia/pulmonary depression (RR = 0.78, p = 0.24)], and postoperative nausea/vomiting (RR = 0.85, p = 0.72), as well as discharge time (MD = 1.39 min, p = 0.14) and satisfaction score (standardized MD = 0.23, p = 0.16) did not differ significantly between the two groups. However, the ciprofol group had lower risks of hypotension (RR = 0.85, p = 0.02) and pain on injection (RR = 0.17, p &lt; 0.00001) than the propofol group. The time to full alertness was statistically shorter in the propofol group (i.e., 0.66 min), but without clinical significance.Conclusion: Our results demonstrated similar efficacy between ciprofol and propofol for sedation and anesthetic induction, while ciprofol was associated with lower risks of hypotension and pain on injection. Future studies are warranted to evaluate the efficacy and safety of ciprofol in pediatric or the elderly populations.Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/), identifier (CRD42023421278)

Association of vitamin D deficiency with post-stroke depression: a retrospective cohort study from the TriNetX US collaborative networks

BackgroundPost-stroke depression (PSD) affects up to one-third of patients who survive stroke. This matched cohort study aimed to investigate the relationship between vitamin D deficiency (VDD) and PSD using a global health research network.MethodsAdult patients with first-ever stroke were eligible for inclusion if their circulating vitamin D levels were available within 3 months before the onset of stroke. Patients were subdivided into those with VDD [VDD group, 25(OH) D &lt; 20 ng/mL] and those with normal vitamin D levels [control group, 25(OH) D: 30–80 ng/mL]. By using propensity score matching (PSM), potential confounding factors were adjusted. The primary outcomes were the association of VDD with the risk of PSD at the 3-month and 12-month follow-ups, while the secondary outcomes were the relationships between VDD and the risk of pneumonia as well as emergency department visits at the 12-month follow-up.ResultsAfter PSM, 758 individuals were included in each group, with no significant differences in baseline characteristics. Musculoskeletal diseases, metabolic disorders, and hypertension were the three leading comorbidities in both the groups. The incidence of PSD was not significantly different between the two groups at the 3-month (5.8% vs. 4.7%, p = 0.358) and 12-month (11.6% vs. 10.2%, p = 0.364) follow-up. VDD was not associated with an increased risk of PSD at the 3-month [hazard ratio (HR) = 1.258, p = 0.358] or 12-month follow-up (HR = 1.210, p = 0.364). In addition, VDD was not associated with an increased risk of pneumonia (HR = 1.053, p = 0.823) or emergency visits at the 12-month follow-up (HR = 1.206, p = 0.148).ConclusionThe results revealed no significant link between VDD and PSD risk during the 3-month and 12-month follow-up periods, suggesting that VDD might not play a substantial role in PSD risk. However, further extensive studies employing a prospective design are necessary to explore the potential protective effects of vitamin D against PSD and validate these findings

Impact of intravenous vitamin C as a monotherapy on mortality risk in critically ill patients: A meta-analysis of randomized controlled trials with trial sequential analysis

BackgroundThis meta-analysis aimed at investigating the pooled evidence regarding the effects of intravenous vitamin C (IVVC) on mortality rate in critically ill patients.MethodsDatabases including Medline, Embase, and Cochrane Library were searched from inception to October, 2022 to identify RCTs. The primary outcome was the risk of overall mortality. Subgroup analyses were performed based on IVVC dosage (i.e., cut-off value: 100 mg/kg/day or 10000 mg/day). Trial sequential analysis (TSA) was used to examine the robustness of evidence.ResultsA total of 12 trials including 1,712 patients were analyzed. Although meta-analysis demonstrated a lower risk of mortality in patients with IVVC treatment compared to those without [risk ratio (RR): 0.76, 95% CI: 0.6 to 0.97, p = 0.02, I2 = 36%, 1,711 patients), TSA suggested the need for more studies for verification. Moreover, subgroup analyses revealed a reduced mortality risk associated with a low IVVC dosage (RR = 0.72, p = 0.03, 546 patients), while no beneficial effect was noted with high IVVC dosage (RR = 0.74, p = 0.13, I2 = 60%, 1,165 patients). The durations of vasopressor [mean difference (MD): −37.75 h, 404 patients) and mechanical ventilation (MD: −47.29 h, 388 patients) use were shorter in the IVVC group than those in the controls, while there was no significant difference in other prognostic outcomes (e.g., length of stay in intensive care unit/hospital) between the two groups.ConclusionAlthough intravenous vitamin C as a monotherapy reduced pooled mortality, durations of vasopressor use and mechanical ventilation, further research is required to support our findings and to identify the optimal dosage of vitamin C in the critical care setting.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42022371090

Myocardium-derived conditioned medium improves left ventricular function in rodent acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>We investigated whether myocardium-derived conditioned medium (MDCM) is effective in preserving left ventricular (LV) function in a rat acute myocardial infarction (AMI) model.</p> <p>Methods</p> <p>Adult male Sprague-Dawley (SD) rats (n = 36) randomized to receive either left coronary artery ligation (AMI induction) or thoracotomy only (sham procedure) were grouped as follows (n = 6 per group): Group I, II, and III were sham-controls treated by fresh medium, normal rat MDCM, and infarct-related MDCM, respectively. Group IV, V, and VI were AMI rats treated by fresh medium, normal MDCM, and infarct-related MDCM, respectively. Either 75 μL MDCM or fresh medium was administered into infarct myocardium, followed by intravenous injection (3 mL) at postoperative 1, 12, and 24 h.</p> <p>Results</p> <p>In vitro studies showed higher phosphorylated MMP-2 and MMP-9, but lower α-smooth muscle actin and collagen expressions in neonatal cardiac fibroblasts treated with MDCM compared with those in the cardiac fibroblasts treated with fresh medium (all p < 0.05). Sirius-red staining showed larger collagen deposition area in LV myocardium in Group IV than in other groups (all p < 0.05). Stromal cell-derived factor-1α and CXCR4 protein expressions were higher in Group VI than in other groups (all p < 0.05). The number of von Willebrand factor- and BrdU-positive cells and small vessels in LV myocardium as well as 90-day LV ejection fraction were higher, whereas oxidative stress was lower in Group VI than in Group IV and Group V (all p < 0.05).</p> <p>Conclusion</p> <p>MDCM therapy reduced cardiac fibrosis and oxidative stress, enhanced angiogenesis, and preserved 90-day LV function in a rat AMI model.</p