ABSTRACT
Reverse left ventricular (LV) remodeling after aortic valve replacement (AVR), in patients with aortic stenosis, is well-documented as an important prognostic factor. With this systematic review and meta-analysis, we aimed to characterize the response of the unloaded LV after AVR. We searched on MEDLINE/PubMed and Web of Science for studies reporting echocardiographic findings before and at least 1 month after AVR for the treatment of aortic stenosis. In total, 1,836 studies were identified and 1,098 were screened for inclusion. The main factors of interest were structural and dynamic measures of the LV and aortic valve. We performed a random-effects meta-analysis to compute standardized mean differences (SMD) between follow-up and baseline values for each outcome. Twenty-seven studies met the eligibility criteria, yielding 11,751 patients. AVR resulted in reduced mean aortic gradient (SMD: - 38.23 mmHg, 95% CI: - 39.88 to - 36.58 , I 2 = 92 % ), LV mass (SMD: - 37.24 g, 95% CI: - 49.31 to - 25.18 , I 2 = 96 % ), end-diastolic LV diameter (SMD: - 1.78 mm, 95% CI: - 2.80 to - 0.76 , I 2 = 96 % ), end-diastolic LV volume (SMD: - 1.6 ml, 95% CI: - 6.68 to 3.51, I 2 = 91 % ), increased effective aortic valve area (SMD: 1.10 cm2, 95% CI: 1.01 to 1.20, I 2 = 98 % ), and LV ejection fraction (SMD: 2.35%, 95% CI: 1.31 to 3.40%, I 2 = 94.1 % ). Our results characterize the extent to which reverse remodeling is expected to occur after AVR. Notably, in our study, reverse remodeling was documented as soon as 1 month after AVR.
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Surgical antimicrobial prophylaxis (SAP) is widely used to reduce the risk of surgical site infections (SSI), but there is uncertainty as to what the proportion of SSI reduction is. Therefore, it is difficult for surgeons to properly weigh the costs, risks and benefits for individual patients when deciding on the use of SAP, making it challenging to promote antimicrobial stewardship in primary practice settings. The objective of this study was to map the veterinary evidence focused on assessing the effect of SAP on SSI development and in order to identify surgical procedures with some research evidence and possible knowledge gaps. In October 2021 and December 2022, Scopus, CAB Abstracts, Web of Science Core Collection, Embase and MEDLINE were systematically searched. Double blinded screening of records was performed to identify studies in companion animals that reported on the use of SAP and SSI rates. Comparative data were available from 34 out of 39123 records screened including: eight randomised controlled trials (RCT), 23 cohort studies (seven prospective and 16 retrospective) and three retrospective case series representing 12476 dogs and cats in total. Extracted data described peri- or post-operative SAP in nine, and 25 studies, respectively. In the eight RCTs evaluating SAP in companion animals, surgical procedure coverage was skewed towards orthopaedic stifle surgeries in referral settings and there was large variation in SAP protocols, SSI definitions and follow-up periods. More standardized data collection and agreement of SSI definitions is needed to build stronger evidence for optimized patient care.
Subject(s)
Antibiotic Prophylaxis , Surgical Wound Infection , Animals , Surgical Wound Infection/veterinary , Surgical Wound Infection/prevention & control , Cats/surgery , Dogs , Antibiotic Prophylaxis/veterinary , Pets , Practice Guidelines as Topic , Cat Diseases/prevention & control , Cat Diseases/drug therapy , Cat Diseases/surgery , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/administration & dosage , Europe , Dog Diseases/prevention & control , Dog Diseases/surgery , Dog Diseases/drug therapy , Antimicrobial StewardshipABSTRACT
Weather radiosondes play a crucial role in gathering atmospheric data for weather modeling and forecasting. However, their impact on marine wildlife, particularly seabirds, has raised concerns regarding the potential threats posed by these instruments. This study aims to assess the adverse effects of weather balloons on albatrosses, with a focus on the Southwest Atlantic region. The research reveals seven cases of entanglement of radiosonde equipment, leading to severe injuries and mortality along the Southern and Southeastern coasts of Brazil. Recommendations for mitigating the environmental impact of weather balloons include the adoption of biodegradable materials in their design and the implementation of improved retrieval protocols. Furthermore, the study stresses the importance of continued monitoring and research to address the interaction of weather radiosondes with marine animals. This approach is vital for ensuring the sustainable collection of scientific data while minimizing harm to marine life and ecosystems.
Subject(s)
Birds , Ecosystem , Animals , Brazil , Weather , Animals, Wild , Environmental MonitoringABSTRACT
BACKGROUND: Carbapenem-resistant Acinetobacter baumannii is a common pathogen associated with healthcare-acquired infections, and robust infection prevention and control protocols exist in human healthcare settings. In contrast, infection prevention and control (IPC) standards are limited in veterinary medicine, necessitating further investigation. AIM: Examine the possible transmission of carbapenem-resistant Acinetobacter spp. in a veterinary practice where a cat was diagnosed with an OXA-23-producing A. baumannii ST2 strain. METHODS: Environmental samples together with nasal and hand swabs from the veterinary personnel were collected. All swabs were screened for the presence of extended-spectrum-ß-lactamase- and carbapenemase-producing Enterobacterales, meticillin-resistant staphylococcus and multi-drug-resistant Acinetobacter spp. Whole-genome sequencing was performed for carbapenemase-producing strains. RESULTS: Of the veterinary staff, 60% carried meticillin-resistant Staphylococcus epidermidis. Environmental evaluation showed that 40% (N=6/15) of the surfaces analysed by contact plates and 40% (N=8/20) by swabs failed the hygiene criteria. Assessment of the surfaces revealed contamination with five OXA-23-producing Acinetobacter spp. strains: an OXA-23-producing Acinetobacter schindleri on the weight scale in the waiting room; and four OXA-23-producing Acinetobacter lwoffii strains, on different surfaces of the treatment room. The blaOXA-23 gene was located on the same plasmid-carrying Tn2008 across the different Acinetobacter spp. strains. These plasmids closely resemble a previously described OXA-23-encoding plasmid from a human Portuguese nosocomial Acinetobacter pittii isolate. Distinctly, the OXA-23-producing A. baumannii ST2 clinical strain had the resistant gene located on Tn2006, possibly inserted on the chromosome. CONCLUSION: The detection of an OXA-23-producing A. baumannii ST2 veterinary clinical strain is of concern for companion animal health and infection, prevention and control. This study established the dynamic of transmission of the plasmid-mediated blaOXA-23 gene on critical surfaces of a small animal veterinary practice. The genetic resemblance to a plasmid found in human nosocomial settings suggests a potential One Health link.
Subject(s)
Acinetobacter Infections , Acinetobacter baumannii , Cross Infection , Methicillin-Resistant Staphylococcus aureus , One Health , Animals , Humans , Interleukin-1 Receptor-Like 1 Protein , Methicillin , Acinetobacter Infections/epidemiology , Acinetobacter Infections/prevention & control , Acinetobacter Infections/veterinary , Microbial Sensitivity Tests , Bacterial Proteins/genetics , beta-Lactamases/genetics , beta-Lactamases/analysis , Acinetobacter baumannii/genetics , Carbapenems , Cross Infection/prevention & control , Cross Infection/veterinary , Anti-Bacterial AgentsABSTRACT
BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients. AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients. METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil's subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%. RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups. CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection. TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials - REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.
Subject(s)
Antirheumatic Agents , Axial Spondyloarthritis , COVID-19 , Male , Humans , Adult , Middle Aged , Female , HLA-B27 Antigen , Brazil/epidemiology , Prospective Studies , COVID-19 Testing , SARS-CoV-2 , Antirheumatic Agents/therapeutic use , RegistriesABSTRACT
The androgens/androgen receptor (AR) axis is the main therapeutic target in prostate cancer (PCa). However, while initially responsive, a subset of tumors loses AR expression through mechanisms putatively associated with epigenetic modifications. In this study, we assessed the link between the presence of CpG methylation in the 5'UTR and promoter regions of AR and loss of AR expression. Hence, we characterized and compared the methylation signature at CpG resolution of these regulatory regions in vitro, both at basal levels and following treatment with 5-aza-2-deoxycytidine (DAC) alone, or in combination with Trichostatin A (TSA). Our results showed heterogeneity in the methylation signature of AR negative cell lines and pinpointed the proximal promoter region as the most consistently methylated site in DU-145. Furthermore, this region was extremely resistant to the demethylating effects of DAC and was only significantly demethylated upon concomitant treatment with TSA. Nevertheless, no AR re-expression was detected at the mRNA or protein level. Importantly, after treatment, there was a significant increase in repressive histone marks at AR region 1 in DU-145 cells. Altogether, our data indicate that AR region 1 genomic availability is crucial for AR expression and that the inhibition of histone methyltransferases might hold promise for AR re-expression.
Subject(s)
Androgens , Prostatic Neoplasms , Male , Humans , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , DNA Methylation , Cell Line, Tumor , Promoter Regions, Genetic , Prostatic Neoplasms/metabolism , Epigenesis, Genetic/genetics , Gene Expression Regulation, NeoplasticSubject(s)
Cost-Effectiveness Analysis , Papillomavirus Vaccines , Humans , Cost-Benefit Analysis , Vaccines, Combined , EuropeABSTRACT
The placenta is a temporary organ that is essential for supporting mammalian embryo and fetal development. Understanding the molecular mechanisms underlying trophoblast differentiation and placental function may contribute to improving the diagnosis and treatment of obstetric complications. Epigenetics plays a significant role in the regulation of gene expression, particularly at imprinted genes, which are fundamental in the control of placental development. The Ten-Eleven-Translocation enzymes are part of the epigenetic machinery, converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). DNA hydroxymethylation is thought to act as an intermediate in the DNA demethylation mechanism and potentially be a stable and functionally relevant epigenetic mark on its own. The role of DNA hydroxymethylation during differentiation and development of the placenta is not fully understood but increasing knowledge in this field will help to evaluate its potential role in pregnancy complications. This review focuses on DNA hydroxymethylation and its epigenetic regulators in human and mouse placental development and function. Additionally, we address 5hmC in the context of genomic imprinting mechanism and in pregnancy complications, such as intrauterine growth restriction, preeclampsia and pregnancy loss. The cumulative findings show that DNA hydroxymethylation might be important for the control of gene expression in the placenta and suggest a dynamic role in the differentiation of trophoblast cell types during gestation.
Subject(s)
Abortion, Spontaneous , Pregnancy Outcome , Pregnancy , Female , Humans , Animals , Mice , DNA Methylation , Placentation , Placenta/metabolism , 5-Methylcytosine/metabolism , DNA/metabolism , MammalsABSTRACT
PURPOSE: Adequate staging of early rectal neoplasms is essential for organ-preserving treatments, but magnetic resonance imaging (MRI) frequently overestimates the stage of those lesions. We aimed to compare the ability of magnifying chromoendoscopy and MRI to select patients with early rectal neoplasms for local excision. METHODS: This retrospective study in a tertiary Western cancer center included consecutive patients evaluated by magnifying chromoendoscopy and MRI who underwent en bloc resection of nonpedunculated sessile polyps larger than 20 mm, laterally spreading tumors (LSTs) [Formula: see text] 20 mm, or depressed-type lesions of any size (Paris 0-IIc). Sensitivity, specificity, accuracy, and positive and negative predictive values of magnifying chromoendoscopy and MRI to determine which lesions were amenable to local excision (i.e., [Formula: see text] T1sm1) were calculated. RESULTS: Specificity of magnifying chromoendoscopy was 97.3% (95% CI 92.2-99.4), and accuracy was 92.7% (95% CI 86.7-96.6) for predicting invasion deeper than T1sm1 (not amenable to local excision). MRI had lower specificity (60.5%, 95% CI 43.4-76.0) and lower accuracy (58.3%, 95% CI 43.2-72.4). Magnifying chromoendoscopy incorrectly predicted invasion depth in 10.7% of the cases in which the MRI was correct, while magnifying chromoendoscopy provided a correct diagnosis in 90% of the cases in which the MRI was incorrect (p = 0.001). Overstaging occurred in 33.3% of the cases in which magnifying chromoendoscopy was incorrect and 75% of the cases in which MRI was incorrect. CONCLUSION: Magnifying chromoendoscopy is reliable for predicting invasion depth in early rectal neoplasms and selecting patients for local excision.
Subject(s)
Colonoscopy , Rectal Neoplasms , Humans , Colonoscopy/methods , Retrospective Studies , Rectal Neoplasms/diagnostic imaging , Rectal Neoplasms/surgery , Predictive Value of Tests , Neoplasm StagingABSTRACT
Chyloperitoneum is a rare manifestation of gastric carcinoma, generally occurring late in the course of the disease with a poor prognosis. We report an unusual case of chyloperitoneum in a patient with gastric carcinoma. A 61-year-old male patient presented with postprandial fullness, nausea and weight loss. The upper gastrointestinal endoscopy demonstrated a stenosing lesion of the esophagogastric junction. A biopsy was made and revealed a signet-ring cell gastric adenocarcinoma. The staging CT scan showed multiple abdominal lymphadenopathies and mild ascites. The patient underwent a staging laparoscopy that revealed a large carcinoma of the gastric cardia and a milky-appearing peritoneal fluid. A peritoneal washing and abdominal drainage were performed. The fluid analysis showed a high concentration of triglycerides, compatible with a chyloperitoneum. The patient started medium chain triglycerides-based diet with good response. This case report emphasizes that chyloperitoneum should be considered when assessing patients with gastric carcinoma.
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TET enzymes (TET1-3) are dioxygenases that oxidize 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and are involved in the DNA demethylation process. In line with the observed 5hmC abundance in the brain, Tet genes are highly transcribed, with Tet3 being the predominant member. We have previously shown that Tet3 conditional deletion in the brain of male mice was associated with anxiety-like behavior and impairment in hippocampal-dependent spatial orientation. In the current study, we addressed the role of Tet3 in female mice and its impact on behavior, using in vivo conditional and inducible deletion from post-mitotic neurons. Our results indicate that conditional and inducible deletion of Tet3 in female mice increases anxiety-like behavior and impairs both spatial orientation and short-term memory. At the molecular level, we identified upregulation of immediate-early genes, particularly Npas4, in both the dorsal and ventral hippocampus and in the prefrontal cortex. This study shows that deletion of Tet3 in female mice differentially affects behavioral dimensions as opposed to Tet3 deletion in males, highlighting the importance of studying both sexes in behavioral studies. Moreover, it contributes to expand the knowledge on the role of epigenetic regulators in brain function and behavioral outcome.
Subject(s)
Cognitive Dysfunction , Dioxygenases , Animals , Anxiety/genetics , Basic Helix-Loop-Helix Transcription Factors/genetics , Behavior, Animal , Brain/metabolism , Cognitive Dysfunction/genetics , DNA Methylation/genetics , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Male , Mice , Neurons/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolismABSTRACT
INTRODUCTION AND AIMS: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. MATERIALS AND METHODS: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. RESULTS: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. CONCLUSION: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.
Subject(s)
Hepatic Encephalopathy , Animals , Caffeine/pharmacology , Caffeine/therapeutic use , Hepatic Encephalopathy/drug therapy , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/prevention & control , Liver Cirrhosis , Male , Rats , Rats, WistarABSTRACT
To demonstrate the efficacy of radiofrequency for pancreatic stump closure in reducing the incidence of postoperative pancreatic fistula (POPF) in distal pancreatectomy (DP) compared with mechanical transection methods. Despite all the different techniques of pancreatic stump closure proposed for DP, best practice for avoiding POPF remains an unresolved issue, with an incidence of up to 30% regardless of center volume or surgical expertise. DP was performed in a cohort of patients by applying radiofrequency to stump closure (RF Group) and compared with mechanical closure (Control Group). A propensity score (PS) matched cohort study was carried out to minimize bias from nonrandomized treatment assignment. Cohorts were matched by PS accounting for factors significantly associated with either undergoing RF transection or mechanical closure through logistic regression analysis. The primary end-point was the incidence of clinically relevant POPF (CR-POPF). Of 89 patients included in the whole cohort, 13 case patients from the RF-Group were 1:1 matched to 13 control patients. In both the first independent analysis of unmatched data and subsequent adjustment to the overall propensity score-matched cohort, a higher rate of CR-POPF in the Control Group compared with the RF-Group was detected (25.4% vs 5.3%, p = 0.049 and 53.8% vs 0%; p = 0.016 respectively). The RF Group showed better outcomes in terms of readmission rate (46.2% vs 0%, p = 0.031). No significant differences were observed in terms of mortality, major complications (30.8% vs 0%, p = 0.063) or length of hospital stay (5.7 vs 5.2 days, p = 0.89). Findings suggest that the RF-assisted technique is more efficacious in reducing CR-POPF than mechanical pancreatic stump closure.
Subject(s)
Pancreatectomy , Pancreatic Fistula , Cohort Studies , Humans , Pancreas/surgery , Pancreatectomy/adverse effects , Pancreatectomy/methods , Pancreatic Fistula/epidemiology , Pancreatic Fistula/etiology , Pancreatic Fistula/prevention & control , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Complications/surgery , Propensity Score , Retrospective Studies , Risk FactorsABSTRACT
This paper analyses the influence of European Law on Brazilian Consumer Law. It starts by describing the general features of Brazilian Consumer Protection law, including the constitutional dimension of consumer protection, and the introduction of the Brazilian Consumer Protection and Defence Code (CDC). It also highlights product liability, product safety, and product warranties. Some of these topics are illustrated by the case of the telecommunications sector.
ABSTRACT
Quasiparticle interference (QPI) imaging is well established to study the low-energy electronic structure in strongly correlated electron materials with unrivalled energy resolution. Yet, being a surface-sensitive technique, the interpretation of QPI only works well for anisotropic materials, where the dispersion in the direction perpendicular to the surface can be neglected and the quasiparticle interference is dominated by a quasi-2D electronic structure. Here, we explore QPI imaging of galena, a material with an electronic structure that does not exhibit pronounced anisotropy. We find that the quasiparticle interference signal is dominated by scattering vectors which are parallel to the surface plane however originate from bias-dependent cuts of the 3D electronic structure. We develop a formalism for the theoretical description of the QPI signal and demonstrate how this quasiparticle tomography can be used to obtain information about the 3D electronic structure and orbital character of the bands.
ABSTRACT
BACKGROUND: P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are short (21 to 35 nucleotides in length) and noncoding and are found almost exclusively in germ cells, where they regulate aberrant expression of transposable elements and postmeiotic gene expression. Critical to the processing of piRNAs is the protein poly(A)-specific RNase-like domain containing 1 (PNLDC1), which trims their 3' ends and, when disrupted in mice, causes azoospermia and male infertility. METHODS: We performed exome sequencing on DNA samples from 924 men who had received a diagnosis of nonobstructive azoospermia. Testicular-biopsy samples were analyzed by means of histologic and immunohistochemical tests, in situ hybridization, reverse-transcriptase-quantitative-polymerase-chain-reaction assay, and small-RNA sequencing. RESULTS: Four unrelated men of Middle Eastern descent who had nonobstructive azoospermia were found to carry mutations in PNLDC1: the first patient had a biallelic stop-gain mutation, p.R452Ter (rs200629089; minor allele frequency, 0.00004); the second, a novel biallelic missense variant, p.P84S; the third, two compound heterozygous mutations consisting of p.M259T (rs141903829; minor allele frequency, 0.0007) and p.L35PfsTer3 (rs754159168; minor allele frequency, 0.00004); and the fourth, a novel biallelic canonical splice acceptor site variant, c.607-2AâT. Testicular histologic findings consistently showed error-prone meiosis and spermatogenic arrest with round spermatids of type Sa as the most advanced population of germ cells. Gene and protein expression of PNLDC1, as well as the piRNA-processing proteins PIWIL1, PIWIL4, MYBL1, and TDRKH, were greatly diminished in cells of the testes. Furthermore, the length distribution of piRNAs and the number of pachytene piRNAs was significantly altered in men carrying PNLDC1 mutations. CONCLUSIONS: Our results suggest a direct mechanistic effect of faulty piRNA processing on meiosis and spermatogenesis in men, ultimately leading to male infertility. (Funded by Innovation Fund Denmark and others.).
Subject(s)
Azoospermia/genetics , Exoribonucleases/genetics , Infertility, Male/genetics , Meiosis/physiology , Mutation , RNA, Small Interfering/metabolism , Testis/pathology , Adult , Azoospermia/physiopathology , Biopsy , Gene Expression , Humans , Male , Phenotype , Polymerase Chain Reaction , RNA, Small Interfering/ultrastructure , Sequence Analysis, RNA , Testis/metabolism , Exome SequencingABSTRACT
Introducción y objetivo: La mayoría de los cánceres de próstata (CP) se clasifican como adenocarcinoma acinar. El carcinoma intraductal de la próstata (CIDP) es una entidad histológica distinta que se cree que representa la propagación retrógrada del adenocarcinoma acinar invasivo en los conductos prostáticos y acinos.Hemos analizado el impacto del CIDP en pacientes con cáncer de próstata resistente a la castración metastásico (CPRCm) y sin tratamiento hormonal previo (hormone-naïve).Pacientes y métodosEvaluamos retrospectivamente a 118 pacientes con CPRCm con diagnóstico inicial de cáncer de prostata metastásico (CPM) desde mayo del 2010 hasta septiembre del 2018. El grupo uno incluyó 81 personas con CPM con adenocarcinoma acinar y el grupo dos estuvo compuesto por 37 pacientes con CPM con CIDP.ResultadosLa edad media de presentación fue de 76 años (IQR 73,4 a 78,7) en el grupo uno y de 74 años (68,5 a 80,6) en el grupo dos. El valor medio del PSA en el momento del diagnóstico fue de 619 ng/mL (IQR 85 a 1.113) y 868 ng/mL (IQR 186 a 1.922), respectivamente. El tiempo hasta la resistencia a la castración fue de 24,7 meses (IQR 16,7 a 32,7) en el grupo uno y 10,2 meses (IQR 4,2 a 16,2) en el grupo dos (p = 0,007). El tiempo hasta la progresión en los pacientes con cáncer de próstata resistente a la castración (CPRC) fue: 10,6 meses (IQR 5,6 a 15,6) y 6,2 meses (3,2 a 9,2), respectivamente (p = 0,05). La supervivencia global fue de 57,9 meses en el grupo uno (IC 95% 56,4 a 59,5) y de 38 meses (IC 95% 19,9 a 48,06) en el grupo dos (p = 0,001). En el análisis multivariante, el subtipo de adenocarcinoma fue estadísticamente significativo p 0,014, IC 95% (Hazard Ratio [HR] 0,058, 0,006 a 0,56).ConclusionesEl CIDP parece ser un subtipo de CP que se asocia con una respuesta más corta al tratamiento hormonal cuando se compara con el adenocarcinoma acinar en pacientes con cáncer metastásico. (AU)
Introduction and objective: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini.We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients.Patients and methodsWe retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P.ResultsMean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619 ng/mL (IQR 85-1113) and 868 ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (p = 0.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (p = 0.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (p = 0.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant p 0.014, CI 95% (HR 0.058, 0.006-0.56).ConclusionsIDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. In daily clinical practice it might be interesting to take into account that patients with IDC-P may present shorter responses to first and second line hormonal treatments. (AU)
Subject(s)
Humans , Carcinoma, Intraductal, Noninfiltrating , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant/drug therapy , Retrospective StudiesABSTRACT
INTRODUCTION AND OBJECTIVE: Most prostate cancers are classified as acinar adenocarcinoma. Intraductal carcinoma of the prostate (IDC-P) is a distinct histologic entity that is believed to represent retrograde spread of invasive acinar adenocarcinoma into prostatic ducts and acini. We have analyzed the impact of IDC-P in hormonal naïve and castration resistant metastatic prostate cancer patients. PATIENTS AND METHODS: We retrospectively evaluated 118 metastatic castration resistant prostate cancer (mCRPC) patients who were initially diagnosed with distant metastases from May 2010 to September 2018. Group 1 patients included 81 metastatic PCa patients with acinar adenocarcinoma and Group 2 included 37 metastatic PCa patients with IDC-P. RESULTS: Mean age at presentation was 76 years (IQR 73.4-78.7) in group 1 and 74 years (68.5-80.6) in group 2. Mean PSA at diagnosis was 619â¯ng/mL (IQR 85-1113) and 868â¯ng/mL (IQR 186-1922), respectively. Time to castration resistance was 24.7 months (IQR 16.7-32.7) in group 1 and 10.2 months (IQR 4.2-16.2) in group 2 (Pâ¯=â¯.007). Time to progression in CPRC patients was: 10.6 months (IQR 5.6-15.6) and at 6.2 months (3.2-9.2), respectively (Pâ¯=â¯.05). Overall survival was 57.9 months in group 1(CI 95% 56.4-59.5) and 38 months (CI 95% 19.9-48.06) in group 2 (Pâ¯=â¯.001). In the multivariate analysis, adenocarcinoma subtype was statistically significant P .014, CI 95% (HR 0.058, 0.006-0.56) CONCLUSIONS: IDC-P seems to be a subtype of prostate cancer that is associated with a shorter response to hormonal treatment when compared to acinar adenocarcinoma in metastatic patients. New drugs in CRPC scenario as abiraterone and enzalutamide also obtained less response in IDC-P patients. Once IDC-P is identified, clinicians could extrapolate the relative poor response to hormonal therapy. Consequently, follow-up of these patients in this scenario should be more strict.
Subject(s)
Carcinoma, Intraductal, Noninfiltrating , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Phenylthiohydantoin , Prostatic Neoplasms, Castration-Resistant/drug therapy , Retrospective StudiesABSTRACT
Caecal volvulus represent the 20-40% of colonic volvulus, being the second most frequent localization. It causes intestinal occlusion symptomatology (nausea, vomiting, abdominal distension). We present a case of 45-year-old women with feeding jejunostomy tube due to connatal anoxia. She arrives at A&E after 12 h of vomits and abdominal pain. The CT scan shows a small intestine dilation that suggested a small intestine volvulus. A laparotomy is performed showing a caecal volvulus, so ileo-cequectomy with primary anastomosis is performed. After several complications, she was discharged after 60 days of hospital stay. Caecal volvulus can be challenging to diagnose by clinic, because it can be hardly differenced from other intestinal occlusion causes. CT scan can be useful to reach the diagnostic and see signs of tissue suffering. In contrast with sigma volvulus, endoscopic treatment has not shown any benefit to solve it.