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OBJECTIVE: Restenosis after transcarotid artery revascularization (TCAR) is a known complication. When identified in the early postoperative period, it may be related to technique. We evaluated our TCAR experience to identify potentially modifiable factors impacting restenosis. METHODS: This is a single-institution, retrospective review of patients undergoing TCAR from November 2017 to July 2022. Restenosis was defined as >50% stenosis on duplex ultrasound (DUS) examination or computed tomographic angiography (CTA). Continuous variables were compared using Kruskal-Wallis's test. Categorical variables were compared using the Fisher's exact test. RESULTS: Of 61 interventions, 11 (18%) developed restenosis within the median follow-up of 345 days (interquartile range, 103-623 days). Among these patients, 82% (9/11) had >50% stenosis, and 18% (2/11) had >80% stenosis. Both patients with high-grade restenosis were symptomatic and underwent revascularization. Diagnosis of post-TCAR restenosis was via DUS examination in 45% (5/11), CTA in 18% (2/11), or both CTA/DUS examination in 36% (4/11). Restenosis occurred within 1 month in 54% (6/11) and 6 months in 72% (8/11) of patients. However, three of the six patients with restenosis within 1 month had discordant findings on CTA vs DUS imaging. Patient comorbidities, degree of preoperative stenosis, medical management, balloon size, stent size, lesion characteristics, and predilatation angioplasty did not differ. Patients with restenosis were younger (P = .02), had prior ipsilateral endarterectomy (odds ratio [OR], 6.5; P = .02), had history of neck radiation (OR, 18.3; P = .01), and lower rate of postdilatation angioplasty (OR, 0.11; P = .04), without an increased risk of neurological events. CONCLUSIONS: Although post-TCAR restenosis occurred in 18% of patients, only 3% of patients had critical restenosis and required reintervention. Patient factors associated with restenosis were younger age, prior endarterectomy, and history of neck radiation. Although early restenosis may be mitigated by improved technique, the only technical factor associated with restenosis was less use of postdilatation angioplasty. Balancing neurological risk, this factor may have increased application in appropriate patients. Diagnosis of restenosis was inconsistent between imaging modalities; current surveillance paradigms and diagnostic thresholds may warrant reconsideration.
Subject(s)
Carotid Stenosis , Stroke , Humans , Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Constriction, Pathologic/complications , Treatment Outcome , Risk Factors , Arteries , Retrospective Studies , Stents/adverse effects , Stroke/etiology , Risk AssessmentABSTRACT
OBJECTIVES: Carotid endarterectomy (CEA) and carotid artery stenting (CAS) are available treatment options for stroke prevention in individuals with severe carotid stenosis. This study aims to compare the early postoperative outcomes in patients who underwent CEA or CAS after prior contralateral carotid revascularization. METHODS: We conducted a retrospective review of the Society of Vascular Surgery (SVS) Vascular Quality Initiative (VQI) database, identifying patients who had prior carotid artery revascularization followed by a contralateral CEA or CAS between 2017 and 2023. Based on the sequence of the procedures performed, patients were categorized into four groups: 1) patients who had a prior unilateral CEA followed by a contralateral CEA (CEA-CEA); 2) patients who had a prior unilateral CAS followed by a contralateral CEA (CAS-CEA); 3) patients had a prior unilateral CAS followed by a contralateral CAS (CAS-CAS); and 4) patients had a prior unilateral CEA followed by a contralateral CAS (CEA-CAS). Univariate analysis (Pearson χ 2, Wilcoxon rank sum test) and multivariate logistic regression were employed to assess length of stay, rates of in-hospital stroke, myocardial infarction, new-onset arrhythmia, and 30-day mortality. RESULTS: A total of 20,761 patients with a history of prior unilateral carotid revascularization procedures were identified, of which 12,788 underwent contralateral CEA and another 7,973 underwent contralateral CAS. Compared to the CAS-CAS group, patients who underwent CEA followed by contralateral CAS (CEA-CAS group) were associated with higher rates of postoperative in-hospital stroke (1.8% vs. 1%, P = 0.003), new-onset arrhythmia (2% vs. 1.2%, P=0.006), and 30-day mortality (1.3% vs. 0.8%, P = 0.04). On multivariate analysis, preoperative use of statins and beta-blockers was associated with lower odds of in-hospital stroke (OR 0.42; 95% confidence interval [CI] 0.29 - 0.69; P = 0.0002) and new-onset arrhythmia (OR 0.62; 95% CI 0.49 - 0.9; P = 0.01), respectively, after CAS. There were no significant differences in outcomes for CEA-CEA and CAS-CEA groups. CONCLUSION: Patients with prior CEA undergoing contralateral CAS had higher rates of in-hospital stroke, new-onset arrhythmia, and 30-day mortality. Beta-blockers may reduce postoperative arrhythmia rates in these patients, and established regimens should not be discontinued in the perioperative period; however, further prospective studies are needed to confirm this finding. Optimized medical treatment and appropriate imaging follow-up remain crucial for improvement outcomes.
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PURPOSE: Lumbar musculature has a fundamental role in spine stability and spinal balance. Muscle atrophy and fat infiltration play an important role in pain pathophysiology. Accordingly, the preoperative condition of lumbar muscles may influence clinical outcomes after surgical treatment. In this context, the aim of this study was to evaluate the association between preoperative lumbar paravertebral muscle fat infiltration and clinical outcomes after lumbar interbody fusion. METHODS: A retrospective study of patients with lumbar pathology submitted to lumbar transforaminal (TLIF) or posterior interbody fusion (PLIF) was performed, with a minimum of two years of follow-up. Preoperative lumbar magnetic resonance imaging (MRI) images were classified for fat infiltration in lumbar multifidus muscle and correlated with clinical outcomes. RESULTS: Seventy-five patients were included: 24 submitted to PLIF and 51 to TLIF. Most patients underwent surgery for spondylolisthesis (67%). Higher degrees of fat infiltration were associated with more advanced age (54.8 vs. 49.1 years old, p = 0.04) and more leg pain after surgery (p = 0.04). No statistically significant differences in other clinical outcomes such as Oswestry Disability Index, visual analogue scale for back and leg pain, self-reported back pain relief, return to work and overall satisfaction were found between different groups of fat infiltration. The improvement in leg pain was associated with improvement in self-reported lumbar pain (p < 0.001). CONCLUSION: Age and preoperative degree of fat infiltration may be important to predict improvement in leg pain after lumbar interbody fusion. The absence of solid literature on this topic and universal assessment methodologies reinforce the need for further studies.
Subject(s)
Spinal Fusion , Spondylolisthesis , Humans , Middle Aged , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Treatment Outcome , Spinal Fusion/adverse effects , Spinal Fusion/methods , Back Pain/etiology , Spondylolisthesis/complications , Spondylolisthesis/surgery , Muscles , Minimally Invasive Surgical Procedures/methodsABSTRACT
RATIONALE: Cancer is associated with muscle wasting. However, optimal protein intake has not been determined, limiting the efficacy of nutritional interventions. This systematic review aims to assess the effect of protein intake on muscle mass of patients with cancer types with high prevalence of sarcopenia during treatment, in longitudinal studies. METHODS: MEDLINE, CINAHL, and Scopus databases were searched following PRISMA guidelines. Longitudinal studies written in English, including adults with high sarcopenia prevalence cancer diagnosis, submitted to (chemo)radiotherapy, with assessment of protein intake and muscle changes during treatment, published until 4 October 2020 were included. Studies including supplementation with substances, such as n-3 fatty acids, specific amino acids, or proteins, were excluded. Study appraisal was independently conducted by two reviewers, and a qualitative research synthesis was performed. RESULTS: Overall, 575 records were identified, of which, eight studies were included (one randomized clinical trial and seven uncontrolled before and after studies). Patients with head and neck (n = 5), lung (n = 2), and esophageal cancer (n = 1) were included, comprising a total of 554 participants. The studies presented heterogeneous methodologies, objectives, and methods to assess body composition. Overall, participant groups with a mean protein intake below 1.2 g/kg presented muscle wasting, with one exception, while those reporting a mean intake above 1.4 g/kg, maintained muscle during treatment. CONCLUSIONS: Our findings show that protein intakes below 1.2 g/kg, even when within the recommendations, have been associated with muscle wasting during treatment. Only intakes above 1.4 g/kg have been associated with muscle maintenance. High-quality research is needed to establish an optimal dose response.
Subject(s)
Neoplasms , Sarcopenia , Adult , Humans , Muscles , Muscular Atrophy/epidemiology , Muscular Atrophy/etiology , Neoplasms/complications , Neoplasms/therapy , Prevalence , Randomized Controlled Trials as Topic , Sarcopenia/complications , Sarcopenia/etiologyABSTRACT
PURPOSE: Short-stem prostheses in hip arthroplasty have emerged as an alternative to conventional stems, especially in younger patients. The purpose of this study was to compare functional and radiological results of a short metaphyseal fitting cementless stem versus a conventional stem implant, in patients younger than 60 years. METHODS: All patients operated from January 2006 to April 2013 were included, obtaining a minimum follow-up of 7 years. Harris Hip Score (HHS) and SF-36 (quality of life) questionnaires were applied and the presence of "thigh pain" was specifically assessed. We also compared complication rate, revision rate and average prosthesis survival. Femoral stress shielding (Gruen scale), stem subsidence, varus-valgus tilt and implant stability (Engh scale) were also compared. RESULTS: A total of 101 short-stem and 74 conventional arthroplasties were included, with an average follow-up of 9.82 (7-14) years. HHS functional score and SF-36 were excellent in both implants and no significant difference between them (p > 0.05) was found. However, "thigh pain" was present in 7 patients with conventional stems and none with short-stems (p < 0.001). The survival rate at 13 years was 99%, for both implants, and no significant differences were found between them (χ2(2) = 0.178; p = 0.673). Conventional stems had stress shielding at the greater trochanter in 72% of the cases and 43% at the calcar, being statistically superior (p < 0.001) to the stress shielding observed in the short stems. CONCLUSION: According to our results, this short-stem seems to allow preservation of bone stock, with decreased stress shielding and also a lower incidence of thigh pain compared to conventional stems. LEVEL OF EVIDENCE: Level III retrospective comparative study.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Follow-Up Studies , Humans , Middle Aged , Pain/epidemiology , Quality of Life , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: Cage subsidence is a very common complication after lumbar interbody fusion. It may compromise vertebral interbody fusion through progressive spinal deformity and consequently cause compression of neural elements. Clinical relevance remains, however, unclear, with few studies on this subject and even less information regarding its correlation with clinical findings. The aim of this study was to identify risk factors for cage subsidence and clinical evaluation after transforaminal (TLIF) and posterior (PLIF) lumbar interbody fusion. METHODS: A retrospective study in patients submitted to TLIF and PLIF between 2008 and 2017 was conducted. RESULTS: A total of 165 patients were included (123 TLIF and 42 PLIF). Univariate analysis showed an increased risk of cage subsidence in spondylolisthesis comparing with degenerative disk disease (p = 0.007). A higher preoperative lumbar lordosis angle (p = 0.014) and cage placement in L2-L3 (p = 0.012) were associated with higher risk of subsidence. The posterior cage positioning on vertebral endplate was associated with a higher risk of subsidence (p = 0.028) and significant subsidence (p = 0.005), defined as cage migration > 50% of cage height. PLIF presented a higher risk when comparing with TLIF (p = 0.024). Hounsfield unit (HU) values < 135 (OR6; 95% CI [1.95-34]) and posterior positioning (OR7; 95% CI [1.7-27.3]) were independent risk factors for cage subsidence and significant subsidence, respectively, in multivariate analysis. There was a tendency for significant subsidence in degrees ≥ 2 of Meyerding spondylolisthesis (OR4; 95% CI [0.85-21.5]). Significant cage subsidence was not associated with worse clinical results. Other analyzed factors, such as age (p = 0.008), low bone mineral density (BMD) (p = 0.029) and type of surgery (TLIF) (p = 0.004), were associated with worse results. CONCLUSION: The present study shows that lower BMD and posterior cage positioning are relevant risk factors for lumbar cage subsidence. Low BMD is also a predictor of poor clinical results, so it must be properly evaluated and considered, through HU values measurement in CT scan, a feasible and reliable tool in perioperative planning.
Subject(s)
Ankylosis , Bone Diseases, Metabolic , Spinal Fusion , Spondylolisthesis , Bone Diseases, Metabolic/etiology , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Risk Factors , Spinal Fusion/adverse effects , Spinal Fusion/methods , Spondylolisthesis/etiology , Spondylolisthesis/surgeryABSTRACT
PURPOSE: To evaluate the presence of macular edema secondary to retinal vein occlusion (RVO)-both central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO)-3 years after diagnosis in patients who underwent intravitreal therapy and to identify potential prognostic factors and biomarkers of persistent macular edema. METHODS: National multicenter, observational, exploratory, retrospective cohort study of 104 consecutive patients with macular edema secondary to RVO diagnosed from January 2014 to December 2015 with minimum 3-year follow-up time. Data analyzed included best-corrected visual acuity (BCVA), clinical and demographic data, and spectral domain optical coherence tomography parameters. RESULTS: At final observation, median baseline central retinal thickness significantly improved from baseline 538 to 290 µm (p < 0.001) and complete macular edema resolution was achieved in 51.0% of patients (56.3% and 42.5% in BRVO and CRVO patients, respectively). BCVA also improved (p < 0.01). Logistic regression analysis revealed a relationship between recurrence of macular edema and disorganization of retinal inner layers (DRIL) at baseline (odds ratio = 2.88; p = 0.013). CONCLUSION: Good long-term anatomical and functional outcomes are achieved with intravitreal treatments in RVO patients. Anatomical success and visual gains seen in the first year were maintained throughout the entire follow-up, though DRIL is a major risk factor for recurrence.
Subject(s)
Macular Edema , Retinal Vein Occlusion , Angiogenesis Inhibitors/therapeutic use , Follow-Up Studies , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/epidemiology , Macular Edema/etiology , Retinal Vein Occlusion/complications , Retinal Vein Occlusion/diagnosis , Retinal Vein Occlusion/epidemiology , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Visual AcuityABSTRACT
Many pollinating insects expand their niche to adjacent agricultural areas and are, therefore, exposed to chemical insecticides. Acraea horta L. (Lepidoptera: Nymphalidae) is a pollinator butterfly widely distributed in the Southern African region. The objectives of this work were to evaluate carbohydrate, lipid and chemical elements in the hemolymph of A. horta exposed to pyriproxyfen, a juvenile hormone analog (JHA). Last instar larvae (L6: day 1 or day 2) were topically exposed to an aqueous solution of pyriproxyfen (100 µg of the active ingredient per insect) or to diluent (control group). Hemolymph was collected after adult eclosion to determine total carbohydrate and lipid concentrations: in the control group lipids were present in lower concentrations than carbohydrates and there was no significant difference in metabolite levels between sexes; a similar pattern with similar levels were measured in the treated group, except that lipid concentrations in treated males were lower, and carbohydrate concentrations in treated females were lower than the control values. Morphologically intact adult males from treated larvae were subjected to free flight; their hemolymph carbohydrate levels were significantly reduced and did not recover to starting levels in a 30 min rest period following the exhaustive flight episode. To assess the effect of pyriproxyfen on a different stage of development, 48 h old butterflies were treated in the same way as described for the L6 larvae above; hemolymph samples were taken 48 h later for metabolite measurements and for quantification of chemical elements: carbohydrate levels decreased significantly after pyriproxyfen exposure, while lipid levels increased; inorganic elements measured in untreated adults were more abundant in females, with a general decrease in concentration following pyriproxyfen exposure, except for an increase in Fe levels in males and Cl levels in females. The quantitative changes measured in A. horta hemolymph via biochemical and chemical element analyses may indicate distinct physiological interferences beyond the main mode of action of pyriproxyfen on JH activity. In conclusion, the use and quantification of pyriproxyfen should be carefully evaluated prior to application in areas where A. horta and other pollinator species occur.
Subject(s)
Butterflies , Animals , Female , Hemolymph , Juvenile Hormones , Larva , Male , PyridinesABSTRACT
BACKGROUND: Head and neck cancer patients have the second highest malnutrition prevalence, when compared with other oncological patients. They experience significant weight loss before diagnosis, during and after treatment, and even during the first year of follow-up. However, the prognostic value of weight loss depends on body mass index, and this may be associated with low skeletal muscle mass, masking its loss. Thus, weight loss itself poorly predicts outcome in head and neck cancer patients when compared with depleted skeletal muscle mass, illustrating the inadequacy of body mass index as an accurate method to reflect nutritional status. A synthesis is needed of the body composition changes occurring in head and neck cancer patients during treatment, as well as of the methods to assess it. OBJECTIVE: The aim of this scoping review is to examine and map the body composition changes in head and neck cancer patients under oncological treatment with curative intent. A further objective is to determine which methods are used to assess body composition in these patients. INCLUSION CRITERIA: Types of participants: The current review considered head and neck cancer patients, aged 18 years or older. CONCEPT: This scoping review considered all studies that focused on the body composition changes. CONTEXT: This scoping review considered the studies that evaluated the body composition changes in the context of treatment with curative intent. Surgical treatment approach was excluded to avoid excess heterogeneity in the data. Types of sources: This scoping review considered only published studies, with abstract available. SEARCH STRATEGY: A three-step search strategy was undertaken. This review was limited to studies published in English, Spanish, and Portuguese during 2000-2019. DATA EXTRACTION: The data extracted included author(s)/year of publication, aims and purpose of the study, sample size, study design, type of treatment, measurement points and component(s) of body composition evaluated, body composition assessment methods, and main results/findings. PRESENTATION OF RESULTS: Head and neck cancer patients suffer from serious loss of lean body mass, skeletal muscle, or free fat mass, after treatment compared with baseline. Further, nutritional deterioration is evident and occurs up to 8-12 months after treatment. Bioelectrical impedance analysis is one of the body composition assessment tools that has the great advantage for being available on a regular basis for assessment of body composition in head and neck cancer patients. However, it cannot be recommended for clinical decision making until further validation. CONCLUSION: Head and neck cancer patients experience a significant depletion of lean body mass, fat-free mass, and skeletal muscle, accompanied by body fat mass, while undergoing (chemo)radiotherapy. This can be demonstrated either by triceps skinfold thickness, bioelectrical impedance analysis, dual-energy x-ray absorptiometry, or computed tomography. This loss has a remarkable impact on their survival, on their quality of life, and on the risk for post-operative complications and may result in a reduced response to cancer treatment. Thus, body composition assessment should become an integral component of the care of head and neck cancer patients, beyond weight and body mass index, and should be carried out at different times throughout treatment.
Subject(s)
Body Composition/physiology , Head and Neck Neoplasms/complications , Quality of Life/psychology , Adult , Female , Head and Neck Neoplasms/pathology , Humans , Male , Young AdultABSTRACT
In order to evaluate the differential absorption and toxicity of arsenate (AsV) and arsenite (AsIII), Lemna valdiviana plants were grown in a nutrient solution and subjected to 0.0 (control); 0.5; 1.0; 1.5; 2.0; 3.0; 4.0; 5.0 and 7.5 mg L-1 of AsIII or AsV for three days. Exposure to both chemical forms resulted in As bioaccumulation, although AsIII-grown plants showed higher As content in tissues. In AsV-grown plants, the relative growth rate (RGR) decreased to 50%, at a concentration of 4.0 mg L-1, while for treatments with AsIII, the same decrease was observed at 1.0 mg L-1. The tolerance index decreased with increasing concentrations, with lower values for AsIII. Plants treated with AsIII showed increased superoxide anion levels, whilst higher levels of hydrogen peroxide were present in AsV-treated plants. Moreover, malondialdehyde (MDA) levels were higher for plants subjected to AsIII when compared to AsV at lower concentrations. Concentrations of 1 mg L-1 of AsIII and 4 mg L-1 of AsV showed equivalent MDA levels. Superoxide dismutase and catalase activities were increased at low concentrations and were inhibited at higher concentrations of AsIII and AsV, whereas peroxidase activity was positively modulated by increased AsIII or AsV concentrations. In conclusion, L. valdiviana plants took up and accumulated arsenic as AsIII or AsV, demonstrating the potential for phytoremediation of this metalloid. Furthermore, AsIII-exposed plants showed enhanced toxicity when compared to AsV, at the same applied concentration, although toxicity was more related to internal As concentrations, regardless of the chemical form applied.
Subject(s)
Arsenates/toxicity , Arsenites/toxicity , Environmental Pollutants/toxicity , Plants/drug effects , Araceae/physiology , Biodegradation, Environmental , Malondialdehyde , Superoxide Dismutase/metabolismABSTRACT
OBJECTIVE: Inhibition of mineral crystal formation is a crucial step in ectopic calcification. Serum calciprotein particles (CPPs) have been linked to chronic kidney disease (CKD) calcification propensity, but additional knowledge is required to understand their function, assemblage, and composition. The role of other circulating nanostructures, such as extracellular vesicles (EVs) in vascular calcification is currently unknown. Here, we investigated the association of GRP (Gla-rich protein) with circulating CPP and EVs and the role of CKD CPPs and EVs in vascular calcification. APPROACH AND RESULTS: Biological CPPs and EVs were isolated from healthy and CKD patients and comparatively characterized using ultrastructural, analytic, molecular, and immuno-based techniques. Our results show that GRP is a constitutive component of circulating CPPs and EVs. CKD stage 5 serum CPPs and EVs are characterized by lower levels of fetuin-A and GRP, and CPPs CKD stage 5 have increased mineral maturation, resembling secondary CPP particles. Vascular smooth muscle cell calcification assays reveal that CPPs CKD stage 5 and EVs CKD stage 5 are taken up by vascular smooth muscle cells and induce vascular calcification by promoting cell osteochondrogenic differentiation and inflammation. These effects were rescued by incubation of CPPs CKD stage 5 with γ-carboxylated GRP. In vitro, formation and maturation of basic calcium phosphate crystals was highly reduced in the presence of γ-carboxylated GRP, fetuin-A, and MGP (matrix gla protein), and a similar antimineralization system was identified in vivo. CONCLUSIONS: Uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD. We propose a major role for cGRP as inhibitory factor to prevent calcification at systemic and tissue levels.
Subject(s)
Calcium/blood , Extracellular Vesicles/metabolism , Muscle, Smooth, Vascular/metabolism , Proteins/metabolism , Renal Insufficiency, Chronic/blood , Vascular Calcification/blood , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Case-Control Studies , Cells, Cultured , Crystallization , Extracellular Vesicles/pathology , Female , Humans , Intercellular Signaling Peptides and Proteins , Intracellular Signaling Peptides and Proteins , Male , Middle Aged , Muscle, Smooth, Vascular/pathology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/pathology , Uremia/blood , Uremia/pathology , Vascular Calcification/etiology , Vascular Calcification/pathology , Vascular Calcification/prevention & control , Young Adult , alpha-2-HS-Glycoprotein/metabolismABSTRACT
The treatment against leishmaniasis presents problems, since the currently used drugs are toxic and/or have high costs. In addition, parasite resistance has increased. As a consequence, in this study, a chloroquinolin derivative, namely 7-chloro-N,N-dimethylquinolin-4-amine or GF1059, was in vitro and in vivo tested against Leishmania parasites. Experiments were performed to evaluate in vitro antileishmanial activity and cytotoxicity, as well as the treatment of infected macrophages and the inhibition of infection using pre-treated parasites. This study also investigated the GF1059 mechanism of action in L. amazonensis. Results showed that the compound was highly effective against L. infantum and L. amazonensis, presenting a selectivity index of 154.6 and 86.4, respectively, against promastigotes and of 137.6 and 74.3, respectively, against amastigotes. GF1059 was also effective in the treatment of infected macrophages and inhibited the infection of these cells when parasites were pre-incubated with it. The molecule also induced changes in the parasites' mitochondrial membrane potential and cell integrity, and caused an increase in the reactive oxygen species production in L. amazonensis. Experiments performed in BALB/c mice, which had been previously infected with L. amazonensis promastigotes, and thus treated with GF1059, showed that these animals presented significant reductions in the parasite load when the infected tissue, spleen, liver, and draining lymph node were evaluated. GF1059-treated mice presented both lower parasitism and low levels of enzymatic markers, as compared to those receiving amphotericin B, which was used as control. In conclusion, data suggested that GF1059 can be considered a possible therapeutic target to be tested against leishmaniasis.
Subject(s)
Antiprotozoal Agents/pharmacology , Chloroquinolinols/pharmacology , Leishmania infantum/drug effects , Leishmania mexicana/drug effects , Leishmaniasis, Cutaneous/parasitology , Leishmaniasis, Visceral/parasitology , Amphotericin B/pharmacology , Amphotericin B/therapeutic use , Amphotericin B/toxicity , Animals , Antiprotozoal Agents/therapeutic use , Antiprotozoal Agents/toxicity , Chloroquinolinols/therapeutic use , Chloroquinolinols/toxicity , Disease Models, Animal , Erythrocytes/drug effects , Female , Inhibitory Concentration 50 , Leishmania infantum/growth & development , Leishmania mexicana/growth & development , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Visceral/drug therapy , Liver/parasitology , Lymph Nodes/parasitology , Macrophages/drug effects , Macrophages/parasitology , Macrophages, Peritoneal/drug effects , Macrophages, Peritoneal/parasitology , Membrane Potential, Mitochondrial/drug effects , Mice , Mice, Inbred BALB C , Parasite Load , Reactive Oxygen Species/metabolism , Spleen/parasitologyABSTRACT
PURPOSE: The purpose of this study was to evaluate the 2-year outcome of ranibizumab for diabetic macular oedema (DME) in the real-life clinical practice of five ophthalmology departments of the National Health Service (NHS) in Portugal. METHODS: This is a retrospective multicentre study. The clinical records on consecutive patients with DME from clinical practice treated with 0.5 mg intravitreal ranibizumab and followed up for 24 months were reviewed. Efficacy outcomes comprised the change in best corrected visual acuity (BCVA) and central macular thickness (CMT) evaluated by SD-OCT. Multivariate regression analysis was performed to explore predictors of BCVA. RESULTS: A total of 122 eyes of 93 patients were included. The median BCVA change by 24 months was +5.0 letters (IQR 12.0) (p < 0.001) and the CMT change was -89.0 µm (IQR 165.0) (p < 0.001). By 24 months, 21.4% of the eyes had gained ≥15 letters and 8.6% had lost ≥15 letters. The median number of injections given during follow-up was 5.0 (IQR 4.0). A greater baseline CMT and a more disrupted status of the external limiting membrane were predictive of worse BCVA at 24 months (p ≤ 0.015). CONCLUSION: DME treatment with ranibizumab in the Portuguese NHS is associated with anatomic and functional improvement by 2 years; however, our results are below those reported in major clinical trials, and undertreatment is probably the cause.
Subject(s)
Diabetic Retinopathy/complications , Macula Lutea/pathology , Macular Edema/drug therapy , Ranibizumab/administration & dosage , Visual Acuity , Aged , Angiogenesis Inhibitors/administration & dosage , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/drug therapy , Dose-Response Relationship, Drug , Female , Follow-Up Studies , Humans , Intravitreal Injections , Macular Edema/diagnosis , Macular Edema/etiology , Male , Portugal , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Vascular Endothelial Growth Factor A/antagonists & inhibitorsABSTRACT
BACKGROUND: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. METHODS: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2â»3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. RESULTS: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). CONCLUSIONS: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.
Subject(s)
Cardiovascular Diseases/blood , Cardiovascular Diseases/complications , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Fibroblast Growth Factors/blood , Glucuronidase/blood , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/complications , Adult , Aged , Biomarkers/blood , Cardiovascular Diseases/mortality , Female , Fibroblast Growth Factor-23 , Hospitalization , Humans , Kaplan-Meier Estimate , Klotho Proteins , Linear Models , Male , Middle Aged , ROC CurveABSTRACT
N-Heptane and 2,2,4-trimethylpentane (isooctane) are the key species in the modeling of ignition of hydrocarbon-based fuel formulations. Isooctane is knock-resistant whereas n-heptane is a very knock-prone hydrocarbon. It has been suggested that interconversion of their associated alkylperoxy and hydroperoxyalkyl species via hydrogen-transfer isomerization reaction is the key step to understand their different knocking behavior. In this work, the kinetics of unimolecular hydrogen-transfer reactions of n-heptylperoxy and isooctylperoxy are determined using canonical variational transition-state theory and multidimensional small curvature tunneling. Internal rotation of involved molecules is taken explicitly into account in the molecular partition function. The rate coefficients are calculated in the temperature range 300-900 K, relevant to low-temperature autoignition. The concerted HO2 elimination is an important reaction that competes with some H-transfer and is associated with chain termination. Thus, the branching ratio between these reaction channels is analyzed. We show that variational and multidimensional tunneling effects cannot be neglected for the H-transfer reaction. In particular, the pre-exponential Arrhenius fitting parameter derived from our rate constants shows a strong dependence on the temperature, because tunneling increases quickly at temperatures below 500 K. On the basis of our results, the existing qualitative model for the reasons for different knock behavior observed for n-heptane and isooctane is quantitatively validated at the molecular level.
ABSTRACT
BACKGROUND/AIMS: Peritoneal protein loss (PPL) is associated with cardiovascular disease and mortality in peritoneal dialysis (PD). Controversial results have been published about the effect of paricalcitol in PPL among PD patients. This study intends to analyze the relationship between paricalcitol and PPL in PD. METHODS: In a retrospective study, prevalent PD patients were divided into 2 groups: "with paricalcitol" and "without paricalcitol". X2-test, Student's t test, Pearson correlation coefficient and Logistic Regression analysis were applied. RESULTS: Eighty-two patients were included. PPL was lower among patients medicated with paricalcitol (5.17 ± 1.71 vs. 6.79 ± 2.10 g/24 h, p = 0.0001). In multivariate analysis, paricalcitol and dialysate/plasma ratio of creatinine (D/P creatinine) were independently related to PPL (OR 4.270 [1.437-12.684], p = 0.009 and OR 0.205 [0.064-0.659], p = 0.008, respectively), adjusted for diabetes. CONCLUSION: Paricalcitol and D/P creatinine were independently related to PPL. Paricalcitol may have an effect on PPL in PD patients.
Subject(s)
Ergocalciferols/deficiency , Peritoneal Dialysis/adverse effects , Protein Deficiency/etiology , 25-Hydroxyvitamin D 2/analogs & derivatives , Aged , Creatinine/analysis , Ergocalciferols/pharmacology , Female , Humans , Male , Middle Aged , Retrospective Studies , Vitamin D Deficiency/complicationsABSTRACT
AIM: Evaluate the real-life experience with ocriplasmin on vitreomacular traction (VMT) release and full-thickness macular hole (FTMH) closure in Portugal. METHODS: Multicentric, retrospective study of 83 eyes of 78 patients who were treated with intravitreal ocriplasmin for VMT with and without FTMH. Primary outcomes were VMT release and FTMH closure. Secondary outcomes included visual acuity changes and structural features on spectral-domain ocular coherence tomography. RESULTS: VMT resolved in 47 of the 83 eyes (56.6%) and 6 of the 12 FTMH were closed (50.0%). Mean best-corrected visual acuity (BCVA) improved from 65.1 at baseline to 70.8 ETDRS letters at the end of follow-up (p < 0.0001) with a mean follow-up of 138.8 days. Improvement in BCVA was significantly better in eyes with VMT release (p = 0.021). Approximately 73% of patients had normal ellipsoid zone integrity at the end of follow-up, 87% had no neurosensorial detachment and 40% had no intra- or subretinal fluid. CONCLUSION: VMT release and FTMH closure were achieved in more than half of the treated eyes and were correlated with significant BCVA improvements and favorable baseline characteristics. In fact, if a careful patient selection is carried out, VMT resolution with ocriplasmin can be optimized, tailoring the best approach to each patient.
Subject(s)
Fibrinolysin/administration & dosage , Peptide Fragments/administration & dosage , Tomography, Optical Coherence/methods , Vitreous Detachment/drug therapy , Aged , Female , Follow-Up Studies , Humans , Intravitreal Injections , Male , Retrospective Studies , Time Factors , Treatment Outcome , Visual Acuity , Vitreous Detachment/diagnosis , Vitreous Detachment/physiopathologyABSTRACT
AIMS AND OBJECTIVES: To establish primary features of training programmes designed to assist family caregivers of people with dementia living at home and to propose a model programme based on literature findings. BACKGROUND: Due to dementia's distinctive progression, there is a widely felt need to train family members who undertake the responsibility of caring for relatives diagnosed with this condition to provide positive care, particularly during the early and middle stages of the disease. DESIGN: Integrative review. METHODS: Literature reviews were carried out in the Pubmed, CINAHL, Mediclatina and Medline databases, using the following describers: training programme, family caregivers, dementia and aged. Such searches encompassed publications between 2004-2014, together with eight articles for review due to their positive identification with the inclusion criteria. Relevant results were extracted, the subsequent analysis performed and the presentation carried out in a descriptive manner. RESULTS: The prevailing length of a training programme for a family caregiver of people with dementia is of six sessions over a six-week period, with one weekly session load, and an average duration of 100 minutes each. Methodologies most commonly used include discussion, problem-solving models as well as skills and strategies training. The themes discussed comprehend caring for the individual with dementia, information about the illness and the use of health and community resources. Regarding the assessment of the family caregiver, the most widely used instruments are demographic assessment questionnaires, self-efficiency and caregiver's burnout scales, as well as depression and quality of life measures. Three assessment instances of family caregivers' needs during the training programme are commonly encountered: initial, final and follow-up. CONCLUSIONS: This review has identified a set of features transversal to training programmes for family members who undertake the care for individuals with dementia living at home, which will bolster the construction and validation of other programmes in the area. More studies about such programmes need to be implemented, particularly engaged in their conceptual and experimental validation. RELEVANCE TO CLINICAL PRACTICE: The results of this review assist nurses by increasing their awareness of the basic assumptions supporting training programmes for family members responsible for individuals with dementia living at home and subsequently enforce them during their interventions with such population.
Subject(s)
Caregivers/psychology , Dementia/nursing , Patient Education as Topic , Quality of Life , Family , Health Services for the Aged , Humans , Surveys and QuestionnairesABSTRACT
Periprosthetic joint infection is a frequent complication after total hip replacement. Two-stage exchange with the use of a temporary cement spacer is commonplace. Several complications are possible with its use. In addition to infection persistence, mechanical complications such as dislocation or fractures are among the most common. Several risk factors can and should be addressed during first stage or spacer implantation surgery in order to minimize complications. Technical aspects as well as practical tips and pearls to overcome common nuisances such as spacer instability or femoral and acetabular bone loss will be discussed.