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Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

[This corrects the article DOI: 10.1371/journal.pone.0167358.].

Background: Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Methods and Findings: Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Conclusions: Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

Sudden unexplained death may be the first manifestation of an unknown inherited cardiac disease. Current genetic technologies may enable the unraveling of an etiology and the identification of relatives at risk. The aim of our study was to define the etiology of natural deaths, younger than 50 years of age, and to investigate whether genetic defects associated with cardiac diseases could provide a potential etiology for the unexplained cases. Our cohort included a total of 789 consecutive cases (77.19% males) <50 years old (average 38.6±12.2 years old) who died suddenly from non-violent causes. A comprehensive autopsy was performed according to current forensic guidelines. During autopsy a cause of death was identified in most cases (81.1%), mainly due to cardiac alterations (56.87%). In unexplained cases, genetic analysis of the main genes associated with sudden cardiac death was performed using Next Generation Sequencing technology. Genetic analysis was performed in suspected inherited diseases (cardiomyopathy) and in unexplained death, with identification of potentially pathogenic variants in nearly 50% and 40% of samples, respectively. Cardiac disease is the most important cause of sudden death, especially after the age of 40. Close to 10% of cases may remain unexplained after a complete autopsy investigation. Molecular autopsy may provide an explanation for a significant part of these unexplained cases. Identification of genetic variations enables genetic counseling and undertaking of preventive measures in relatives at risk.

A recent individual patient data (IPD) meta-analysis (MA) of RCTs comparing NSBBs vs. According to another IPD-MA, adding NSBBs to EVL significantly decreases rebleeding risk and improves survival compared with EVL monotherapy, particularly in Child-Pugh B/C [29]. Abbreviations CI, confidence interval; CSPH, clinically significant portal hypertension; FU, follow-up; HVPG, hepatic venous pressure gradient; INR, international normalized ratio; MELD, model for end stage liver disease; NSBBs, non-selective β-blockers; OLT, orthotopic liver transplantation; PH, portal hypertension; RCT, randomized controlled trial; SD, standard deviation; SHR, subdistribution hazard ratio 1. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis.

The objective of this study was to verify the efficacy of cotton fabric, made of serge bonding 2 x 1, as microbial barrier, when new and after multiple laundering and steam sterilization procedures. The power of the microbial barrier was correlated with physical characteristics of the fabric, using standard test methods for evaluation of weight, traction, stretching tearing resistance and microbiological characteristics. The microbiological results evidenced that the microbial barrier was effective when the wrapping material was new or went through a maximum of new 65 reprocessing procedures. As for the alterations in the physical characteristics of the reprocessed material, the decrease in weight seemed to be the event responsible for microbial barrier breaking. The timing of detected alterations in bursting, traction and stretching in the wrap and the reprocessed fabrics did not coincide with the moment of bacterial barrier breaking. The present investigation corroborates that the use double cotton fabric, for wrapping medical and hospital items for steam sterilization, is safe. Re-use number must be controlled, not exceeding 65 times. O objetivo deste estudo foi verificar a efetividade do tecido de ligamento sarja 2 x 1, usado na confecção de campos duplos de algodão para a embalagem de artigos médico-hospitalares como barreira microbiana eficaz, enquanto novos e após múltiplas lavagens e autoclavações e correlacionar a quebra do poder de barreira microbiana com as alterações das características físicas do tecido. Foram utilizados métodos de testes padronizados tanto para a avaliação das características físicas para a determinação da gramatura, resistência a ruptura, resistência a tração e alongamento quanto para as microbiológicas. Os resultados microbiológicos demonstraram a efetividade da barreira microbiana da embalagem em estudo enquanto novos e, na determinação do número máximo de reprocessamentos, indicaram o número limite de 65. Quanto às alterações das características físicas do tecido reprocessado, a diminuição da gramatura foi o acontecimento que sustentou a quebra da barreira microbiana. O momento da alteração constatada nas medidas físicas de estouro, tração e alongamento no urdume e na trama dos tecidos reprocessados não coincidiu com o da quebra de barreira microbiana. A presente investigação sustenta a segurança do uso do tecido de algodão como embalagem de artigos médico hospitalares na esterilização por calor úmido. O número de reusos deverá ser controlado, não excedendo o de 65 vezes.

To evaluate the long-term cumulative probability of intraocular pressure (IOP) elevation with the intravitreal dexamethasone implant (IDI) when used to treat different indications: diabetic macular edema, uveitis, retinal vein occlusion. 705 IDI injections (429 eyes) were assessed and Kaplan-Meier graphs were generated to assess: the probability of different levels of IOP elevation (IOP≥21, ≥25 or ≥35 mmHg), IOP change ≥10 mmHg, initiation of IOP-lowering treatment, glaucoma surgery, IOP change with repeat injections and IOP elevation in eyes with glaucoma and ocular hypertension (OHT). The cumulative probability of IOP ≥21, ≥25 and ≥35 mmHg was 50%-60%, 25%-30% and 6%-7% at 12-24 months, respectively. The probability of initiating IOP-lowering medication was 31%-54% at 12-24 months. Glaucoma and OHT eyes had a higher probability of mild IOP elevation (≥21 mmHg, 65.1%, 75% and 57.8%, p = 0.01), yet a similar moderate (≥25 mmHg, 22.3%, 28% and 30.2%, p = 0.91) and severe elevation of IOP (≥35 mmHg, 3.7%, 7.1% and 4%, p = 0.71) as normal eyes. Glaucoma surgery was required in only 0.9% cases (4/429). At baseline, 8.8% of the treated eyes had glaucoma, 6.7% OHT and 16.9% were already on IOP-lowering medication. In the long-term (24 months), IOP elevation is common, generally mild (30% IOP, ≥25 mmHg) and well-tolerated, resolving with topical treatment (54%) and rarely requiring surgery (0.9%).