DNA损伤在衰老相关疾病中的研究进展

DNA损伤是衰老相关疾病领域的研究热点, 可引起细胞周期停滞、凋亡, 加快个体衰老速度、增加衰老相关疾病的患病风险。本文将从细胞衰老和个体衰老两个层面阐述其与衰老之间的研究进展, 并综述其与衰老常见相关疾病(肿瘤、心血管疾病、阿尔茨海默病)及早衰综合征的关系, 为抗衰老研究和临床干预衰老相关疾病提供理论依据。     

Contemporary Management of Ischemic Mitral Regurgitation at Coronary Artery Bypass Grafting

BackgroundRecent guidelines for the treatment of moderate or severe ischemic mitral regurgitation (IMR) in patients undergoing coronary artery bypass grafting (CABG) have changed. This study assessed the real-world impact of changing guidelines on the management of IMR during CABG over time. We hypothesized that the utilization of mitral valve repair for IMR would decrease over time, whereas mitral valve replacement for severe IMR would increase.MethodsPatients undergoing CABG in a statewide collaborative database (2011-2020) were stratified by severity of IMR. Trends in mitral valve repair or replacement were evaluated. To account for differences of the patients, propensity score–matched analyses were used to compare patients with and without mitral intervention.ResultsA total of 11,676 patients met inclusion criteria, including 1355 (11.6%) with moderate IMR and 390 (3.3%) with severe IMR. The proportion of patients undergoing mitral intervention for moderate IMR decreased over time (2011, 17.7%; 2020, 7.5%; P_trend = .001), whereas mitral replacement for severe IMR remained stable (2011, 11.1%; 2020, 13.3%; P_trend = .14). Major morbidity was higher for patients with moderate IMR who underwent mitral intervention (29.1% vs 19.9%; P = .005). In a propensity analysis of 249 well-matched pairs, there was no difference in major morbidity (29.3% with mitral intervention vs 23.7% without; P = .16) or operative mortality (1.2% vs 2.4%; P = .5).ConclusionsConsistent with recent guideline updates, patients with moderate IMR were less likely to undergo mitral repair. However, the rate of replacement for severe IMR did not change. Mitral intervention during CABG did not increase operative mortality or morbidity.     

Interpretation,pitfalls of biomarkers in diagnosis of invasive fungal diseases

BackgroundInvasive Fungal Diseases (IFD), account for high morbidity and mortality in immunocompromised and seriously ill patients worldwide. Early, faster and accurate diagnosis with timely and appropriate patient management is critical for improved patient outcome and antifungal stewardship. Clinical/radiological presentations in IFD are non-specific and microscopy/culture based tests have low sensitivity and long turnaround time. Biomarkers have clinical utility for diagnosing IFD but their interpretation is not straight forward.ObjectivesThis review discusses the salient characteristics, clinical usefulness and limitations of common biomarkers such as Galactomannan (GM), 1–3, β D glucan (βDG), mannan, anti-mannan antibody (Mn/antiMn), Cryptococcal antigen test (CrAg), Nucleic Acid Amplification (NAA) tests and next generation sequencing for diagnosing IFD.ContentsFungal biomarkers are useful adjuncts as screening and diagnostic tools for IFD and are much more suited for ‘ruling out’ rather than ‘ruling in’ disease. GM, NAA tests are promising biomarkers for screening of invasive Aspergillosis in high risk asymptomatic patients who are not on antifungal therapy and for diagnosis of breakthrough infections in symptomatic patients. 1–3, β D glucan has limitations both as a ‘rule in’ and ‘rule out’ test and is useful in only specific clinical settings. Two consecutive positive 1-3-βDG tests or combined positivity with GM increases its specificity. Mn/antiMn, T2Candida nano diagnostic panel are promising candidates for diagnosing invasive candidiasis. Combining two or more biomarkers improves the sensitivity for prompt initiation of antifungal therapy and the negative predictive value for suspension of empirical treatment.Serum CrAg test is a good ‘rule in’ rather than a ‘rule out’ test in immunocompetent patients but has good diagnostic accuracy in immunocompromised patients. Detection of single nucleotide polymorphisms by next generation sequencing is useful for fungal characterization and identification of host determinants responsible for increased susceptibility to fungal infections but is still in experimental stages.     

Recurrent aseptic liver abscesses in a patient with Crohn’s disease: True infection or a Crohn’s flare?

A liver abscess is identified as a rare extraintestinal manifestation of Crohn’s disease, with an incidence of approximately 150 in 100,000 patients with this condition. In many of these patients, infectious causes are identified, and the patient’s condition is often noted to improve with antibiotics. An aseptic abscess (AA) is an increasingly recognized entity, especially in patients with inflammatory bowel disease, where repetitive evaluations to identify the infectious cause are futile. The average age of diagnosis for an AA is 29 years. The most common site is the spleen, followed by the lymph nodes and then the liver. In this study, we present a unique case of extensive aseptic liver abscesses extending into the pleural cavity in a young patient with Crohn’s disease.     

Orphan drug development: The impact of regulatory and reimbursement frameworks

The enactment of orphan drug-specific legislation pioneered by the USA was subsequently followed by many regions, including the European Union (EU), Australia, Japan, and Taiwan. Here, we discuss the associated regulations established and their impacts in the aforementioned regions, which are among the first with frameworks specific for orphan drugs. Varied scopes of rare diseases or orphan drugs, diverse incentives, and heterogeneous types of reimbursement systems imply the prioritization of the agencies concerned. The numbers of designated and approved drugs reflect the impact of the regulatory and reimbursement frameworks. A comparison of the frameworks and their impact in the respective regions could provide valuable information for developing and improving related frameworks for countries worldwide.     

Anaerobes in cardiac infections: A decade experience from the tertiary care center

PurposeAnaerobic infections are common yet life-threatening. They are being recovered from all sites of the body, including the cardiovascular system. This study was aimed to determine the retrospective analysis on the isolation of anaerobes in cardiovascular samples received for a decade-long duration. It helps in knowing the frequency of isolation of anaerobic causes of cardiovascular infection.MethodsAll cardiovascular samples from the department of Cardio-thoracic vascular surgery from January 2010 to December 2020 were studied.ResultsOf 601 samples received, predominant samples were vegetations and valvular tissues of 258, followed by 98 samples of pericardial tissues, 92 samples of embolus, 90 samples of blood and post-operative collections, and 63 excised aneurysms and vascular grafts. Of the total, 15 samples grew anaerobes where Clostridium species were the predominant isolates. Clostridioides difficile was isolated in 2 samples.ConclusionsAnaerobes in cardiovascular samples are uncommon yet form a significant cause of morbidity and mortality. Most infections are from the contiguous spread, penetrating trauma, and hematogenous causing endocarditis or valvular infections. These conditions and samples form the seat of infectious focus and clinical suspicion towards the anaerobic cause of these conditions, especially in conventional routine culture-negative samples. Timely diagnosis of anaerobic infections plays a vital role in the good prognostic outcome of patients undergoing cardiothoracic and vascular surgery.