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Acute superficial thrombophlebitis is a venous system disease. Animal models with mannitol induced phlebitis were treated with an orally administered "phlebitis ointment." 24 rabbits were randomly divided into 4 groups. The therapy group was treated with "phlebitis ointment" and a control group received "Mai Luo Shu Tong granules." Levels of blood TNF-α, IL-6, CRP, and IL-1β were measured. The tissue expression levels of NF-КBp65 and PKC genes were evaluated. The therapy group showed a better improvement of the clinical status and similar vascular morphology than the control group. A blank group showed no vascular changes through pathological investigation. In contrast, significant vascular changes were seen in the model group. The control group showed slight vascular modifications. Small thrombi could be found in the lumen despite the intact tunica intima. Both control and therapy group showed less inflammatory cells infiltration than the model group and upregulation of NF-КBp65 and PKC genes. The phlebitis ointment reduced the levels of necrosis factor-α, interleukin-6, C-reactive protein, and interleukin-1ß. The expressions of NF-КBp65 and PKC genes, which are the primary mechanisms underlying the development of thrombophlebitis, were improved significantly in tissues of both therapy group and control group.
Lemierre's syndrome is typically caused by Fusobacterium necrophorum where an oropharyngeal infection is followed by septic internal jugular vein thrombophlebitis with subsequent septic embolization. Yet, the pathogenesis of septic thrombophlebitis, differences dependent on the presence of jugular vein thrombosis, and the role of anticoagulant therapy are insufficiently understood.
We retrospectively evaluated off-label use of dalbavancin as secondary therapy in 32 patients with serious Staphylococcus aureus infections (endocarditis, osteomyelitis, septic thrombophlebitis, epidural infection) who were also persons who use drugs. The majority of patients (56%) had a clinical response to treatment. Only 1 patient who completed the intended dalbavancin course experienced a treatment failure.
Few studies have focused on the risks of peripheral intravenous catheters (PIVs) as sources for Staphylococcus aureus bacteremia (SAB), a life-threatening complication. We identified 34 PIV-related infections (7.6%) in a cohort of 445 patients with SAB. Peripheral intravenous catheter-related SAB was associated with significantly longer bacteremia duration and thrombophlebitis at old PIV sites rather than current PIVs.
Pylephlebitis is a septic thrombophlebitis of the portal vein that is associated with multiple suppurative abdominal infections, such as diverticulitis, appendicitis, cholangitis, and cholecystitis. We describe a case of pylephlebitis in a patient with fever and diffuse, poorly localized abdominal pain who was eventually diagnosed with appendicitis. We aim to increase awareness of this condition among emergency physicians, as timely initiation of antibiotics and expedited surgical resection may improve outcomes in this potentially fatal disease.
Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of antineoplastic agents. Several treatment regimens are used to address this problem. Fosaprepitant is a neurokinin-1 receptor blocker used in the prevention and treatment of CINV, especially for moderately and severely emetogenic chemotherapy. It is highly effective in the treatment of delayed CINV. Data from previous studies show that fosaprepitant is noninferior to aprepitant in the management of CINV. Fosaprepitant is given as a single-dose intravenous infusion, thus offering better patient compliance. The dose-limiting side effect of fosaprepitant is an infusion-related reaction, ranging from pain at the infusion site to thrombophlebitis. This side effect has been reported with coadministration of anthracycline agents.
Catheter-related infections (CRI) are a major cause of morbidity and mortality in chronic hemodialysis (HD) patients. In this paper, we share our experience with CRI in HD patients. We recorded 49 cases of CRI among 167 patients during a period of 40 months (January 2018-April 2021). The incidence of CRI was 3.7 per 1000 catheter-days. The revealing symptoms were dominated by fever or chills (90%). Inflammatory signs were observed in 74% of cases with respectively concurrent exit-site (51%) and tunnel infection (6%). The biological inflammatory syndrome was found in 74% of patients (average CRP level = 198.9 mg/l). Blood cultures were performed in all cases and were positive in 65% of cases. Thirteen patients have been diagnosed with Infection complications, which were respectively infective endocarditis in 7 cases, septic arthritis in 3 cases, infective myositis in one case, cerebral thrombophlebitis in 1 case and mediastinitis in 1 case. The death occurred in eleven patients, it was due to septic shock in 9 cases, pulmonary embolism in one case and neurologic alterations related to cerebral thrombophlebitis. The mean seniority in HD was 16.5 months in the group with CRI and 3.7 months in the group without CRI (p < 0.04). We did not notice significant difference in mortality between tunnelled and non-tunnelled catheters. CRI does not seem to be more severe in patients with diabetes. Duration of use of the HD catheter (p < 0.007) and ferritin level (p < 0.0001) were independent factors that predispose to CRI in our population.
Superficial venous thrombosis (SVT) or superficial thrombophlebitis is characterized by thrombi within superficial veins, with partial involvement or occlusion of the lumen and inflammatory reaction along the course of the vein. Clinical diagnosis tends to be straightforward, but supplementary tests and examinations are needed to confirm thrombosis extension and possible thromboembolic complications. SVT can be associated with deep venous thrombosis in 6 to 40% of cases, with asymptomatic pulmonary embolism (PE) in 20 to 33%, and with symptomatic PE in 2 to 13%. Despite the morbidity and complications, there are currently no Brazilian guidelines for SVT. These guidelines cover the most important issues related to SVT definition, terminology, and etiology, and set out recommendations for diagnosis and treatment.
Baker's cysts, commonly incidental findings, can occasionally present as intramuscular dissecting cysts within the medial gastrocnemius muscle. This case report highlights the ultrasound features and differential diagnoses of intramuscular dissecting Baker's cysts through the examination of three distinct cases: a 64-year-old woman with severe osteoarthritis, an 80-year-old man with a palpable mass in the popliteal fossa, and a 37-year-old man with early degenerative arthropathy. Each case was investigated using ultrasound, revealing fusiform hypoechoic fluid collections with heterogeneous echostructure parallel to the medial gastrocnemius muscle bundle and lacking posterior reinforcement. The clinical context and ultrasound findings were critical in differentiating these cases from other conditions, such as superficial thrombophlebitis, intramuscular seroma, and intramuscular myxoma. These cases emphasize the role of ultrasound in diagnosing intramuscular dissecting Baker's cysts. Accurate diagnosis requires careful consideration of ultrasound features in conjunction with clinical findings.
This study investigated the pharmacodynamic and pharmacokinetic equivalence of 1% and 2% propofol emulsions when used for total intravenous anaesthesia for intracranial surgery. The same infusion rate (6.7 mg.kg-1 x h-1) of the two preparations was administered. Induction doses, recovery times, and haemodynamic profiles were identical. Similar propofol concentration profiles were produced and total body clearance of propofol was identical. Both preparations were associated with a similar incidence of injection pain but neither resulted in venous thrombosis or thrombophlebitis at 24 h. Plasma triglyceride concentrations were significantly higher with the 1% solution, but there were no differences in cholesterol concentrations. The 1% and 2% emulsions appeared to be pharmacologically equivalent with similar minor effects on arterial blood pressure and heart rate. Two percent propofol may be preferable to the 1% solution for maintenance of anaesthesia in patients in whom a large lipid load might be considered undesirable.
The structure of protein-protein interaction (PPI) networks has already been successfully used as a source of new biological information. Even though cardiovascular diseases (CVDs) are a major global cause of death, many CVD genes still await discovery. We explore ways to utilize the structure of the human PPI network to find important genes for CVDs that should be targeted by drugs. The hope is to use the properties of such important genes to predict new ones, which would in turn improve a choice of therapy. We propose a methodology that examines the PPI network wiring around genes involved in CVDs. We use the methodology to identify a subset of CVD-related genes that are statistically significantly enriched in drug targets and "driver genes." We seek such genes, since driver genes have been proposed to drive onset and progression of a disease. Our identified subset of CVD genes has a large overlap with the Core Diseasome, which has been postulated to be the key to disease formation and hence should be the primary object of therapeutic intervention. This indicates that our methodology identifies "key" genes responsible for CVDs. Thus, we use it to predict new CVD genes and we validate over 70% of our predictions in the literature. Finally, we show that our predicted genes are functionally similar to currently known CVD drug targets, which confirms a potential utility of our methodology towards improving therapy for CVDs.
Short peripheral catheters are ubiquitous in today's healthcare environment enabling effective delivery of fluids and medications directly into a patient's vasculature. However, complications related to their use, such as short peripheral catheter thrombophlebitis (SPCT), affect up to 80% of hospitalized patients. While indwelling within the vein, the catheters exert prolonged constant pressure upon the endothelium which can trigger inflammation processes. We have developed and studied an in-vitro model of cultured endothelial cells subjected to mechanical compression of modular self-designed weights, and explored their inflammatory response by quantification of two key biomarkers- vWF and IL-8. Evaluation was performed by ELISA immunoassay and processing of vWF-labeled immunofluorescence images. We found that application of weights correspond to 272 Pa yielded increased release of vWF and IL-8 up to 150% and 250% respectively, comparing to the exertion of 136 Pa. Analyses of the immunofluorescence images revealed significantly longer and more extracellular vWF-strings as well as higher intensity stained-pixels in cells exposed to elevated pressures. The release of both factors found to be significantly dependent on the extent of the exerted pressure. The research shed a light on the relationship between induced mechanical compression and the pathogenesis of SPCT. Minimizing, let alone eliminating the contact between the catheter and the vein wall will mitigate the pressure acting on the endothelium, thereby reducing the secretion of inflammatory factors and lessen the incidence of SPCT.
Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau's syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau's syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.
The efficacy and safety of ticarcillin plus clavulanic acid in the treatment of patients with infections of soft tissue, bone, and joint were evaluated in this open study. Clinical diagnoses included osteomyelitis, soft tissue abscess or ulcer, cellulitis, bite wound, traumatic or postoperative cellulitis, necrotizing fasciitis, septic arthritis, septic bursitis, and septic thrombophlebitis. Trauma or underlying disease such as diabetes mellitus or vascular insufficiency was common (more than 50 percent) in the patient population. Clinical efficacy was evaluable in 66 patients who received 3 g of ticarcillin and 0.1 g of clavulanic acid every four or six hours for a mean of 23.4 days. A satisfactory clinical response was observed in 92 percent of the patients. Major pathogens isolated were Enterobacteriaceae, anaerobic cocci, Staphylococcus aureus, and beta-hemolytic Streptococcus. Of the 143 isolates recovered from 55 bacteriologically evaluable cases, 87 percent were eradicated by therapy. Overall, a satisfactory bacteriologic outcome occurred in 93 percent of the patients, and the pathogen(s) persisted in 7 percent. More than 98 percent of the isolates were susceptible to ticarcillin plus clavulanic acid in vitro. Emergence of resistance during therapy occurred with three strains of Pseudomonas aeruginosa. Adverse drug-related reactions required discontinuation of treatment in two patients, although other minor abnormal laboratory findings were common. These results indicate that ticarcillin plus clavulanic acid offers safe and effective therapy for infections of soft tissue, bone, and joint.
Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.
Human genome sequencing has resulted in a great body of data, including a stunningly large number of single nucleotide polymorphisms (SNPs) with unknown phenotypic manifestations. Identification and comprehensive analysis of regulatory SNPs in human gene promoters will help quantify the effects of these SNPs on human health. Based on our experimental and computer-aided study of SNPs in TATA boxes and the use of literature data, we have derived an equation for TBP/TATA equilibrium binding in three successive steps: TATA-binding protein (TBP) sliding along DNA due to their nonspecific affinity for each other ↔ recognition of the TATA box ↔ stabilization of the TBP/TATA complex. Using this equation, we have analyzed TATA boxes containing SNPs associated with human diseases and made in silico predictions of changes in TBP/TATA affinity. An electrophoretic mobility shift assay (EMSA)-based experimental study performed under the most standardized conditions demonstrates that the experimentally measured values are highly correlated with the predicted values: the coefficient of linear correlation, r, was 0.822 at a significance level of α<10⁻⁷ for equilibrium K(D) values, (-ln K(D)), and 0.785 at a significance level of α<10⁻³ for changes in equilibrium K(D) (δ) due to SNPs in the TATA boxes (δ= -ln[K(D,TATAMut)]-(-ln[K(D,TATAMut)])). It has been demonstrated that the SNPs associated with increased risk of human diseases such as α-, β- and δ-thalassemia, myocardial infarction and thrombophlebitis, changes in immune response, amyotrophic lateral sclerosis, lung cancer and hemophilia B Leyden cause 2-4-fold changes in TBP/TATA affinity in most cases. The results obtained strongly suggest that the TBP/TATA equilibrium binding equation derived can be used for analysis of TATA-box sequences and identification of SNPs with a potential of being functionally important.
We aimed to understand relationships of the weather as biometeorological and hospital admissions due to diseases of arteries and veins by subtypes, which have been scarcely studied, in a national setting in recent years. This is an ecological study. Ten percent of daily hospital admissions from the included hospitals (n = 1,618) across Germany that were available between 1 January 2009 and 31 December 2011 (n = 5,235,600) were extracted from Statistisches Bundesamt, Germany. We identified I70-I79 Diseases of arteries, arterioles and capillaries and I80-I89 Diseases of veins, lymphatic vessels and lymph nodes by International Classification of Diseases version 10 as the study outcomes. Daily weather data from 64 weather stations that covered 13 German states including air temperature, humidity, wind speed, cloud cover, radiation flux and vapour pressure were obtained and generated into physiologically equivalent temperature (PET). Two-way fractional-polynomial prediction was plotted with 95 % confidence intervals. For most of the subtypes from diseases of arteries and veins, hospital admissions slightly peaked in spring and dropped when PET was at 10 °C. There were no other large differences across 12 months. Admissions of peripheral vascular diseases, arterial embolism and thrombosis, phlebitis and thrombophlebitis, oesophageal varices and nonspecific lymphadenitis peaked when PET was between 0 and -10 °C, while others peaked when PET was between 0 and 10 °C. More medical resources could have been needed on days when PETs were at -10 to 10 °C than on other days. Adaptation to such weather change for health professionals and the general public would seem to be imperative.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombotic manifestations and/or pregnancy-related complications in patients with persistent antiphospholipid (aPL) antibodies. The introduction of Sapporo's classification criteria allowed uniformity in the classification of this pathology, representing a considerable advance in its diagnosis. However, currently some doubts about the application of these criteria still persist. The aim of this study was to contribute to the better understanding of APS by the assessment of aPL prevalence, the association between clinical and laboratory tests, and evaluation of the aPL confirmatory profile. In this study, 1,179 samples from patients with suspected APS of both genders, without age restrictions, who were advised to test for complete aPL's profile were analyzed. The samples were tested for lupus anticoagulant (LAC), anticardiolipin immunoglobulin (Ig) G/IgM and anti-β-2-glycoprotein I IgG/IgM antibodies. Patient samples with isolated test requests for analysis and samples from patients under the influence of anticoagulants or in an infectious process were excluded. The overall positivity found was 17.9% and the most frequent aPL was LAC. The antibodies were determined in isolation and in association. The prevalence of triple positivity was 0.8% and double positivity was 1.8%. Positivity was higher in inpatient/emergency services compared with outpatient services. There was a higher positivity in individuals over 41 years, males, patients with systemic lupus erythematosus, kidney complications, and deep vein thrombosis/thrombophlebitis. The positivity confirmation with second sample was 39.5% and the confirmation profile shows that 50.6% of samples confirmed with same positivity profile; 17.3% with a different profile and regarding to these, 2.5% of the samples confirmed positivity with a different antibody from the previously detected. This study suggests that the aPL's positivity tends to increase with age, showing that the aPL's testing should be avoided during an acute event and reinforces the need for complete aPL laboratory profile in the second sample and subsequent determinations.
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