Albuminuria promotes tubular injury and cell death, and is associated with faster progression of chronic kidney disease (CKD) to end-stage renal disease. However, the molecular mechanisms regulating ...tubular cell death in response to albuminuria are not fully understood. Brain abundant signal protein 1 (BASP1) was recently shown to mediate glucose-induced apoptosis in tubular cells. We have studied the role of BASP1 in albumin-induced tubular cell death. BASP1 expression was studied in experimental puromycin aminonucleoside-induced nephrotic syndrome in rats and in human nephrotic syndrome. The role of BASP1 in albumin-induced apoptosis was studied in cultured human HK2 proximal tubular epithelial cells. Puromycin aminonucleoside induced proteinuria and increased total kidney BASP1 mRNA and protein expression. Immunohistochemistry localized the increased BASP1 to tubular cells. BASP1 expression colocalized with deoxynucleotidyl-transferase-mediated dUTP nick-end labeling staining for apoptotic cells. Increased tubular BASP1 expression was observed in human proteinuric nephropathy by immunohistochemistry, providing evidence for potential clinical relevance. In cultured tubular cells, albumin induced apoptosis and increased BASP1 mRNA and protein expression at 6-48 h. Confocal microscopy localized the increased BASP1 expression in albumin-treated cells mainly to the perinuclear area. A peripheral location near the cell membrane was more conspicuous in albumin-treated apoptotic cells, where it colocalized with actin. Inhibition of BASP1 expression by a BASP1 siRNA protected from albumin-induced apoptosis. In conclusion, albumin-induced apoptosis in tubular cells is BASP1-dependent. This information may be used to design novel therapeutic approaches to slow CKD progression based on protection of tubular cells from the adverse consequences of albuminuria.
ABSTRACTUrinary tract infections (UTIs) are common bacterial infections. Women are 8 to 30 times more likely to have this infection than men. The majority of women report at least 1 UTI in their ...lifetime. Within a year, about 25% or more of these patients will have a recurrence, and 22% will have recurrent UTIs (RUTIs). Continuous prophylaxis with antibiotics is commonly recommended as initial treatment for RUTIs. However, there is high risk for the development of multiresistance with their continuous use; in some regions of the world, more than 40% of the bacterial strains are already resistant to available antibiotics. Moreover, there is a high incidence of adverse reactions. To address these problems, preventive strategies such as vaccine use have been investigated that reinforce the natural mechanisms of pathogen defense. One such vaccine, Uromune, is an inactivated bacterial cell suspension composed of selected strains of Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus faecalis.The aim of this multicenter retrospective observational study was to compare the clinical benefit of prophylactic use of Uromune with that of the currently accepted prophylactic treatment, sulfamethoxazole/trimethoprim (SMX/TMP) to prevent RUTIs. The authors reviewed the clinical history of 319 women who presented with RUTIs (defined as at least 2 episodes of UTI in the last 6 months or 3 in the last 12 months).Data collected before the initiation of the corresponding treatment and after 3, 9, and 15 months included number of UTIs and time of evolution of RUTIs before initiation of treatment. Patients in group A (n = 159) received prophylactic treatment with Uromune for a period of 3 months, and patients in group B (n = 160) received oral doses of SMX/TMP (200/40 mg/d) as prophylactic treatment for a period of 6 months.The data showed that patients in group A experienced a highly significant reduction in the mean number of infections in the first 3 months compared with patients in group B0.36 versus 1.60, P < 0.0001, respectively. There was also a significant reduction after 9 and 15 months (P < 0.0001). Significantly more patients in group A than in group B did not suffer any UTI at 3, 9, and 15 months101, 77, and 55 patients in group A versus 9, 4, and 0 patients in group B (P < 0.000).These data show that the use of this bacterial-based therapeutic vaccine could be an effective strategy to reduce frequency, duration, severity, and costs of RUTIs.
INTRODUCTIONProstate cancer is the most common visceral neoplasm in men and the second one in the United States with the highest mortality behind lung cancer and ahead of colorectal cancer. While ...prostate cancer mortality rates have been reduced in the United States, Austria, United Kingdom and France, 5-year survival rates have been incremented in Sweden, probably due to a higher diagnostic activity and non-lethal tumor detection. TRPB usually has low rates of serious complications, with a not negligible number of minor complications. Mortality directly associated with this procedure is low and usually related to septic shock. The main complications derived from prostate biopsy can be infectious (mild or severe) and non-infectious (hematuria consistent with hemorrhage, urethral bleeding, rectal bleeding or hemospermia, acute urinary retention, pain or vasovagal reactions). MATERIAL AND METHODThe objective of the study is to compare three usual TRPB protocols and their relationship with the incidence of complications. Retrospective multicenter observational study conducted in three countries (Spain, Italy and Portugal). We have reviewed the medical records of 3350 men who underwent TRPB to evaluate the existence of prostate cancer, with a minimum evolutionary control of 6months. RESULTSThe mean age was 65,50years, median 66, range 43-79. The subgroup analysis showed that younger patients had higher rates of acute urine retention (AUR) (P=.0000001). Likewise, our results revealed that younger patients presented more procedural pain (P=.0000001) than older patients. Regarding PSA, the mean value was 10.44, SD 7.73, median 8.15, range 0.98-68.09. A higher body mass index (BMI) was not associated with further infection (P=.000004). When performing the multivariate analysis, it was found that the significant variables in the general group were: age (P=.0013), PSA (P=.0402), local infiltration anesthesia (P=.0001) and prophylaxis with metronidazole +tobramycin +amoxicillin/clavulanic acid +gentamicin (P=.0001), presenting a normal distribution with high confidence interval (95%) and significant correlation. Prophylaxis is the most significant variable for no complications and pain (P=.0001), age (P=.0013) and prophylaxis (P=.0001) are for bleeding, age (P=.0013), prophylaxis and PSA (P=.0001) are for infection, and finally, age (P=.0013), anesthesia with local infiltration and prophylaxis (P=.0001) and PSA (P=.0402) are for AUR. CONCLUSIONSSedation has fewer side effects and complications related to the transrectal prostate biopsy procedure with respect to transrectal local anesthesia. The choice of the antibiotic prophylaxis scheme is decisive in the onset of complications arising from the performance of a transrectal prostate biopsy.
Abstract
Aims
The prevalence of advanced heart failure (HF) is increasing due to the growing number of patients with HF and their better treatment and survival. There is a scarcity of data on the ...accuracy of HF web‐based risk scores in this selected population.
This study aimed to assess mortality prediction performance of the Meta‐Analysis Global Group in Chronic HF (MAGGIC‐HF) risk score and the model of the Barcelona Bio‐HF Risk Calculator (BCN‐Bio‐HF) containing N terminal pro brain natriuretic peptide in HF patients receiving intermittent inotropic support with levosimendan as destination therapy.
Methods and results
Four hundred and three advanced HF patients from 23 tertiary hospitals in Spain receiving intermittent inotropic support with levosimendan as destination therapy were included. Discrimination for all‐cause mortality was compared by area under the curve (AUC) and Harrell's C‐statistic at 1 year. Calibration was assessed by calibration plots comparing observed versus expected events based on estimated risk by each calculator. The included patients were predominantly men, aged 71.5 interquartile range 64–78 years, with reduced left ventricular ejection fraction (27.5 ± 9.4%); ischaemic heart disease was the most prevalent aetiology (52.5%). Death rate at 1 year was 26.8%, while the predicted 1‐year mortality by BCN‐Bio‐HF and MAGGIC‐HF was 17.0% and 22.1%, respectively. BCN‐Bio‐HF AUC was 0.66 (Harrell's C‐statistic 0.64), and MAGGIC‐HF AUC was 0.62 (Harrell's C‐statistic 0.61).
Conclusions
The two evaluated risk scores showed suboptimal discrimination and calibration with an underestimation of risk in advanced HF patients receiving levosimendan as destination therapy. There is a need for specific scores for advanced HF.
Abstract Objectives Since 1999, we have performed implantations of Remeex® adjustable prosthetics as rescue treatment for complex or persistent stress urinary incontinence (SUI) after failure of ...other surgical treatments (Burch colposuspension, Marshall-Marchetti-Krantz (MMK) or tension-free transvaginal tape TVT until 2003 and transobturator tape TOT since 2003). We present the results of our series, which include cases with severe complications. Material and method Retrospective study of women diagnosed with complex or refractory SUI who underwent Remeex® implantation between October 1999 and December 2013. In 5 cases, we conducted cystocele correction in the same operation as the placement of the Remeex®. Results Sixty women, with a mean age of 66.87 years (range 39–85), underwent operations. The procedure was successful in 68.33% of the cases. The failures consisted of the following: 10% of the women had mixed urinary incontinence (UI) with multiple bladder diverticula; 8.33% had mild SUI; and 13.33% had urgency urination without UI. Thirty-five percent required adjustments. We recorded 3 cases with severe complications: disabling severe UI in a patient who underwent multiple operations, massive pelvic hemorrhage in a patient undergoing standard antiplatelet therapy and infected vaginal calculi measuring 7 cm on an extruding Remeex thread in a paraplegic patient 4 years after the implantation. Conclusions Remeex® is an effective and safe procedure for achieving continence in cases of complex or refractory SUI, although it is not exempt from severe complications. Following rigorous protocols can help detect complications and treat them in a timely manner.
Rheumatoid arthritis is a chronic inflammatory disease characterized by polyarthritis with progressive articular wear, immunologic abnormalities and increasing physical limitation. Surgical ...correction with hip replacement comes as a successful solution for patients with advanced articular destruction. Following intervention, surgical site infection (SSI), venous thromboembolism, sepsis, renal and major cardiovascular complications are among the most cited in the literature. No consensus exists as to the detection of preoperative hypoalbuminemia in patients with rheumatoid arthritis.
This study retrospectively evaluated the preoperative serum albumin of 75 patients with rheumatoid arthritis and analyzed its relevance in terms of appearance of postoperative complications with a six-month follow-up. Complications in the group of patients with low serum albumin and the group of patients with normal serum albumin were reviewed to identify the effect of each variable. Odds ratio for each variable was calculated (hospital readmission, surgical site infection, renal and cardiac complications, non-infectious wound complications and the presence of residual hip pain), as well as p-value and confidence intervals.
Surgical site infection showed a statistically significant relation with low serum albumin (OR: 6.125, p = 0.018) as did non-infectious wound complications (OR: 3.714, p = 0.026) and residual hip pain (OR: 3.149, p = 0.022).
Preoperative low serum albumin has a direct relation with the rate of postoperative complications including SSI, non-infectious wound complications (seroma formation, wound dehiscence) and residual hip pain. Preoperative serum albumin is a reliable marker of nutrition, which may establish preventive strategies to reduce postoperative complications in patients with rheumatoid arthritis.
Hepatic biomarker responses were measured in two demersal fish species (
Lepidorhombus boscii and
Callionymus lyra) from the northern Iberian shelf associated with the massive
Prestige oil spill ...(POS), five months after the accident. The biomarkers selected were 7-ethoxyresorufin-
O-deethylase (EROD), glutathione-
S-transferase (GST), glutathione reductase (GR), catalase (CAT), and DNA integrity. Interspecies differences and spatial variations in biomarker responses were observed along the shelf. GST, GR and CAT activities were significantly elevated in
L. boscii in the most oil impacted area (Finisterre) and positively correlated (
p
<
0.05) with POS tar aggregate densities. The lack of previous data from the area together with the existence of chronic background pollution of the shelf implies that the observed biomarker responses cannot be solely attributed to the petroleum hydrocarbon components of the spilled oil. This first biological effect assessment showed that
L. boscii is a potentially suitable target species to be used in future biomonitoring programmes along the northern Iberian shelf.
Background
Age is a major risk factor for venous thromboembolism (VTE), yet patients aged ≥90 years are under‐represented in clinical trials of anticoagulant therapy. The objectives were to describe ...and compare patient clinical characteristics, treatments, and outcomes (VTE recurrence, bleeding, and mortality) during the first 3 months of anticoagulation between VTE patients aged ≥90 years and those aged <90 years.
Methods
We analyzed data from the Registro Informatizado Enfermedad TromboEmbὀlica (RIETE), an ongoing global observational registry of patients with objectively confirmed acute VTE.
Results
From January 2001 to October 2022, 96,701 patients were registered in RIETE, of whom 3262 (3.4%) were aged ≥90 years. Patients aged ≥90 years were less likely to be men, and to have experienced cancer or recent surgery, but more likely to manifest immobility, chronic heart failure, anemia, renal insufficiency, or dementia than those aged <90 years. Most (99.6%) patients aged ≥90 years were receiving anticoagulant therapy. During the first 3 months, 26 patients aged ≥90 years developed VTE recurrences, 116 experienced major bleeding, and 564 died. Among patients initially presenting with pulmonary embolism (PE), deaths due to PE exceeded those due to fatal bleeding (76 vs. 19). Among those initially presenting with isolated deep‐vein thrombosis (DVT), it was the reverse (2 vs. 11 deaths).
Conclusions
In patients aged ≥90 years, the difference in the outcome of anticoagulant treatment depending on the initial presentation of VTE could suggest a need for different management approaches. Clinical trials evaluating the optimal duration of anticoagulation according to initial VTE presentation are warranted to limit excess deaths in this particular population.
Free‐living (FL) and particle‐attached (PA) bacterial assemblages in the Northwest Mediterranean Sea were studied using pyrosequencing data of the 16S rRNA. We have described and compared the ...richness, the distribution of Operational Taxonomic Units (OTUs) within the two fractions, the spatial distribution, and the taxonomic composition of FL and PA bacterial assemblages. The number of OTUs in the present work was two orders of magnitude higher than in previous studies. Only 25% of the total OTUs were common to both fractions, whereas 49% OTUs were exclusive to the PA fraction and 26% to the FL fraction. The OTUs exclusively present in PA or FL assemblages were very low in abundance (6% of total abundance). Detection of the rare OTUs revealed the larger richness of PA bacteria that was hidden in previous studies. Alpha‐Proteobacteria dominated the FL bacterial assemblage and gamma‐Proteobacteria dominated the PA fraction. Bacteroidetes were important in the PA fraction mainly at the coast. The high number of sequences in this study detected additional phyla from the PA fraction, such as Actinobacteria, Firmicutes, and Verrucomicrobia.
Particle‐attached (PA) and free‐living (FL) bacterial assemblages are analyzed by pyrosequencing of the 16S rRNA for the first time. This technique has allowed revisiting the question of how similar are the FL and PA bacterial assemblages that has been studied before using conventional molecular techniques. We have shown several new findings with respect to the previous studies: richness is higher in PA than in FL bacterial assemblages, pyrosequencing has allowed the incorporation of rare species into our analyses, we provide the taxonomic composition of both assemblages as well as their spatial distribution. New bacterial taxa have been added to the PA bacterial pool and differences in the taxonomic composition of the PA bacterial assemblages have been found depending on the location of the samples.
Macroporous scaffolds made of a SiO
2
-CaO-P
2
O
5
mesoporous bioactive glass (MBG) and ε-polycaprolactone (PCL) have been prepared by robocasting. These scaffolds showed an excellent
in vitro
...biocompatibility in contact with osteoblast like cells (Saos 2) and osteoclasts derived from RAW 264.7 macrophages.
In vivo
studies were carried out by implantation into cavitary defects drilled in osteoporotic sheep. The scaffolds evidenced excellent bone regeneration properties, promoting new bone formation at both the peripheral and the inner parts of the scaffolds, thick trabeculae, high vascularization and high presence of osteoblasts and osteoclasts. In order to evaluate the effects of the local release of an antiosteoporotic drug, 1% (%wt) of zoledronic acid was incorporated to the scaffolds. The scaffolds loaded with zoledronic acid induced apoptosis in Saos 2 cells, impeded osteoclast differentiation in a time dependent manner and inhibited bone healing, promoting an intense inflammatory response in osteoporotic sheep.
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