Impact of perioperative low-molecular-weight heparin therapy on clinical events of elderly patients with prior coronary stents implanted > 12 months undergoing non-cardiac surgery: a randomized, placebo-controlled trial.

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo. The primary efficacy endpoint was cardiac or cerebrovascular events. The primary safety endpoint was major bleeding. RESULTS: Among 2476 randomized patients, the variables (sex, age, body mass index, comorbidities, medications, and procedural characteristics) and percutaneous coronary intervention information were not significantly different between the bridging and non-bridging groups. During the follow-up period, the rate of the combined endpoint in the bridging group was significantly lower than in the non-bridging group (5.79% vs. 8.42%, p = 0.012). The incidence of myocardial injury in the bridging group was significantly lower than in the non-bridging group (3.14% vs. 5.19%, p = 0.011). Deep vein thrombosis occurred more frequently in the non-bridging group (1.21% vs. 0.4%, p = 0.024), and there was a trend toward a higher rate of pulmonary embolism (0.32% vs. 0.08%, p = 0.177). There was no significant difference between the groups in the rates of acute myocardial infarction (0.81% vs. 1.38%), cardiac death (0.24% vs. 0.41%), stroke (0.16% vs. 0.24%), or major bleeding (1.22% vs. 1.45%). Multivariable analysis showed that LMWH bridging, creatinine clearance < 30 mL/min, preoperative hemoglobin < 10 g/dL, and diabetes mellitus were independent predictors of ischemic events. LMWH bridging and a preoperative platelet count of < 70 × 109/L were independent predictors of minor bleeding events. CONCLUSIONS: This study showed the safety and efficacy of perioperative LMWH bridging therapy in elderly patients with coronary stents implanted > 12 months undergoing non-cardiac surgery. An alternative approach might be the use of bridging therapy with half-dose LMWH. TRIAL REGISTRATION: ISRCTN65203415.

Predicting perioperative myocardial injury/infarction after noncardiac surgery in patients under surgical and medical co-management: a prospective cohort study.

BACKGROUND: Perioperative myocardial injury/infarction (PMI) following noncardiac surgery is a frequent cardiac complication. This study aims to evaluate PMI risk and explore preoperative assessment tools of PMI in patients at increased cardiovascular (CV) risk who underwent noncardiac surgery under the surgical and medical co-management (SMC) model. METHODS: A prospective cohort study that included consecutive patients at increased CV risk who underwent intermediate- or high-risk noncardiac surgery at the Second Medical Center, Chinese PLA General Hospital, between January 2017 and December 2022. All patients were treated with perioperative management by the SMC team. The SMC model was initiated when surgical intervention was indicated and throughout the entire perioperative period. The incidence, risk factors, and impact of PMI on 30-day mortality were analyzed. The ability of the Revised Cardiac Risk Index (RCRI), frailty, and their combination to predict PMI was evaluated. RESULTS: 613 eligible patients (mean [standard deviation, SD] age 73.3[10.9] years, 94.6% male) were recruited consecutively. Under SMC, PMI occurred in 24/613 patients (3.9%). Patients with PMI had a higher rate of 30-day mortality than patients without PMI (29.2% vs. 0.7%, p = 0.00). The FRAIL Scale for frailty was independently associated with an increased risk for PMI (odds ratio = 5.91; 95% confidence interval [CI], 2.34-14.93; p = 0.00). The RCRI demonstrated adequate discriminatory capacity for predicting PMI (area under the curve [AUC], 0.78; 95% CI, 0.67-0.88). Combining frailty with the RCRI further increased the accuracy of predicting PMI (AUC, 0.87; 95% CI, 0.81-0.93). CONCLUSIONS: The incidence of PMI was relatively low in high CV risk patients undergoing intermediate- or high-risk noncardiac surgery under SMC. The RCRI adequately predicted PMI. Combining frailty with the RCRI further increased the accuracy of PMI predictions, achieving excellent discriminatory capacity. These findings may aid personalized evaluation and management of high-risk patients who undergo intermediate- or high-risk noncardiac surgery.

A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Isolated left ventricular noncompaction: clinical profile and prognosis in 106 adult patients.

This study was undertaken to evaluate the clinical course of isolated left ventricular noncompaction (ILVNC) and to identify the predictors for adverse outcomes in an adult cohort with ILVNC. Between March 2003 and April 2012, 106 adult patients diagnosed with ILVNC at Fuwai Hospital were included in this study. The medical history, electrocardiograms, and echocardiograms of these patients were retrospectively analyzed by chart review. Of these patients, 64 (60 %) were in New York Heart Association (NYHA) functional class III/IV and 84 (79 %) had systolic dysfunction (left ventricular ejection fraction (LVEF) <50 %). During a follow-up of 2.9 ± 2.1 years, 28 (26 %) patients died or underwent heart transplantation. The annual incidence of death or transplantation was 9.1 %. The determinants of death or heart transplantation included NYHA functional class III/IV (hazard ratio (HR) 4.52; 95 % confidence interval (CI) 1.57-13.04; P = 0.005), decreased left ventricular ejection fraction (HR 0.94; 95 % CI 0.90-0.97; P = 0.001), dilated left ventricular end-diastolic diameter (HR, 1.06; 95 % CI, 1.02-1.09; P = 0.001), increased left atrial diameter (HR 1.08; 95 % CI 1.03-1.14; P = 0.001), reduced systolic blood pressure (HR 0.96; 95 % CI 0.94-0.99; P = 0.003), the presence of pulmonary hypertension (HR 3.50; 95 % CI 1.63-7.51; P = 0.001), and right bundle branch block (HR 7.79; 95 % CI 2.56-23.76; P < 0.001). In conclusion, this study demonstrates that ILVNC is related to a high incidence of death or heart transplantation. Advanced heart failure, a dilated left heart with systolic dysfunction, reduced systolic blood pressure, pulmonary hypertension, and right bundle branch block predict adverse outcomes of ILVNC.

Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study.

Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan-Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423-1.262) in the azvudine group 0.802 (0.435-1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805-3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546-3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the "National Key R&D Program of China" (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

A family with Liddle syndrome caused by a novel missense mutation in the PY motif of the beta-subunit of the epithelial sodium channel.

OBJECTIVE: To identify the gene mutation in ß and γ subunits of the epithelial sodium channel (ENaC) in an adolescent and family members with Liddle syndrome, an autosomal dominant form of secondary hypertension. STUDY DESIGN: We screened an adolescent with severe hypertension who was clinically diagnosed with Liddle syndrome for mutations in the C-terminus of the SCNN1B and SCNN1G genes. We also screened for these mutations in his family members, in 100 hypertensive patients, and in 100 controls. RESULTS: The index case, a 14-year-old boy, was diagnosed with Liddle syndrome by the identification of a novel missense mutation, P614L, in the PY motif of the ß subunit of the ENaC. Testing of relatives considered at risk revealed 6 subjects heterozygous for the mutation. All genetically affected subjects had a history of severe hypertension as well as hypokalemia. No other variants in the ß or γ subunits of the ENaC were detected. CONCLUSION: Based on direct DNA sequencing, we have detected a novel mutation that causes Liddle syndrome. This confirms the diagnosis and helps guide effective therapy for this adolescent and his affected relatives. These findings provide further evidence that the conserved PY motif is critical to regulation of ENaC activity.

Genotype-phenotype analysis of F-helix mutations at the kinase domain of TGFBR2, including a type 2 Marfan syndrome familial study.

PURPOSE: Transforming growth factor beta receptor II (TGFBR2) gene mutations are associated with Marfan syndrome; however, the relationship between the mutations and clinical phenotypes are not clear. METHODS: Genomic DNA from peripheral blood leukocytes of a Chinese proband with Marfan syndrome, five of the proband's relatives, and 100 unrelated Chinese control subjects were isolated and screened for fibrillin-1 (FBN1) and TGFBR2 gene mutations by direct sequencing, and a genotype-phenotype study was performed following a review of the literature on TGFBR2 mutations in the search area. Also, the structure of TGFBR2 protein before and after gene mutation was analyzed. RESULTS: The results identified a novel missense TGFBR2 mutation p.V453E (c.1358T>A) in the proband and two relatives that was located in the F-helix in the kinase domain of TGFBR2. No such genetic change was observed in the unrelated controls. No FBN1 mutation was detected in any of the subjects. Genotype-phenotype analyses indicated that F-helix mutations are related to type 2 Marfan syndrome and Loeys-Dietz syndrome, and these mutations can lead to severe cardiovascular (93.8%) and skeletal (81.3%) lesions and minor ocular lesions (25%). Losartan treatment can slow-down the progression of aortic lesions. CONCLUSIONS: The findings extend the mutation spectrum of Marfan syndrome, and that mutations at the F-helix in the kinase domain of TGFBR2 may be associated with the development of severe cardiovascular and skeletal lesions and minor ocular lesions. These findings have implications for genetic testing, diagnosis, and treatment in individuals with transforming growth factor beta (TGF-ß) signaling-related disorders.

Management of Postoperative Myocardial Injury After Non-cardiac Surgery in Patients Aged ≥ 80 Years: Our 10 Years' Experience.

Background: Postoperative myocardial injury (PMI) is associated with short- and long-term mortality. The incidence of PMI in very old patients is currently unknown. There is currently neither known effective prophylaxis nor a uniform strategy for the elderly with PMI. Objective: To share our 10 years of experience in the comprehensive management of PMI after non-cardiac surgery in patients aged ≥ 80 years. Methods: In this case series, we retrospectively collected and assessed the 2,984 cases aged ≥ 80 years who accepted non-cardiac surgery from 2011 to 2021 at the second Medical Center, Chinese PLA General Hospital. The incidence, risk factors, management strategy, and prognosis of surgical patients with PMI were analyzed. Results: A total of 2,984 patients met our inclusion criteria. The overall incidence of PMI was 14%. In multivariable analysis, coronary artery disease, chronic heart failure, and hypotension were independently associated with the development of PMI. The patients with PMI were at a higher risk of death (OR, 2.69; 95% CI, 1.78-3.65). They were more likely to have received low molecular heparin, anti-plantlet therapy, beta-blocker, early coronary angiography, and statin than patients without PMI. The 30-day (0.96% vs. 0.35%; OR 3.46; 95% CI, 1.49-7.98; P < 0.001) and 1-year mortality (5.37% vs. 2.60%; OR 2.35; 95% CI, 1.12-6.53; P < 0.001) was significantly higher in patients with PMI compared with those without PMI. Conclusions: The incidence of PMI in very old patients was high. The PMI is associated with an increased risk of 30 days and 1-year mortality. These patients can benefit from intensification of assessment and individualized care of multi-morbidities during the perioperative period. Especially cardiovascular medical treatments, such as antiplatelet, anticoagulation, ß-blockers, and statins are very important for patients with PMI.

Perioperative Myocardial Injury/Infarction After Non-cardiac Surgery in Elderly Patients.

At present, we have entered an aging society. Many diseases suffered by the elderly, such as malignant tumors, cardiovascular diseases, fractures, surgical emergencies and so on, need surgical intervention. With the improvement of Geriatrics, surgical minimally invasive technology and anesthesia level, more and more elderly patients can safely undergo surgery. Elderly surgical patients are often complicated with a variety of chronic diseases, and the risk of postoperative myocardial injury/infarction (PMI) is high. PMI is considered to be the increase of cardiac troponin caused by perioperative ischemia, which mostly occurs during operation or within 30 days after operation, which can increase the risk of short-term and long-term death. Therefore, it is suggested to screen troponin in elderly patients during perioperative period, timely identify patients with postoperative myocardial injury and give appropriate treatment, so as to improve the prognosis. The pathophysiological mechanism of PMI is mainly due to the increase of myocardial oxygen consumption and / the decrease of myocardial oxygen supply. Preoperative and postoperative risk factors of myocardial injury can be induced by mismatch of preoperative and postoperative oxygen supply. The treatment strategy should first control the risk factors and use the drugs recommended in the guidelines for treatment. Application of cardiovascular drugs, such as antiplatelet ß- Receptor blockers, statins and angiotensin converting enzyme inhibitors can effectively improve postoperative myocardial ischemia. However, the risk of perioperative bleeding should be fully considered before using antiplatelet and anticoagulant drugs. This review is intended to describe the epidemiology, diagnosis, pathophysiology, risk factors, prognosis and treatment of postoperative myocardial infarction /injury.

Clinical characteristics and outcomes in patients with Takayasu arteritis coexisting with myocardial ischemia and neurological symptoms: A multicenter, long-term, follow-up study.

Background: The incidence of coexisting myocardial ischemia and neurological symptoms in Takayasu arteritis (TA) is currently unknown. There is no standardized treatment algorithm in complex cases involving the coronary and intracranial arteries. Objective: This study aimed to describe the clinical characteristics and outcomes in patients with TA coexisting with myocardial ischemia and neurological symptoms. Methods: We retrospectively collected and assessed 1,580 patients with TA, and enrolled patients with myocardial ischemia and neurological symptoms from January 2002 to December 2021 in several hospitals. The incidence, clinical features, management strategy, and prognosis of these patients were evaluated. Results: Ninety-four (5.9%, 94/1,580) patients with TA coexisting with myocardial ischemia and neurological symptoms were included in the present study. Imaging results showed that the subclavian arteries were the most frequently affected arteries and 37 patients had intracranial vascular abnormalities, comprising the basilar artery (6.1%, 17/279), middle cerebral artery (2.5%, 7/279), anterior cerebral artery (2.9%, 8/279), and posterior cerebral artery (1.9%, 5/279). Among patients with neurological symptoms, 25 patients underwent percutaneous transluminal angioplasty and 20 patients underwent stent implantation. The most common site of stenosis was the ostial and proximal segments of the coronary artery, with 142 lesions among 188 (75.5%) lesions. Thirty-eight patients adopted interventional therapy, 21 patients underwent surgical treatment, and the remaining 35 patients received conservative treatment. There were 20 (21.27%, 20/94) late deaths during a mean follow-up of 57.79 months. The mortality rate in the conservative treatment group was significantly higher than that in the interventional therapy and surgical treatment groups. Conclusion: Patients with TA involving both the coronary and intracranial vessels are not rare. Stenosis and occlusion lesions most frequently involve the ostia and proximal segment of the arteries. Severe vascular lesions should be revascularized as soon as possible. These patients should be supplemented with glucocorticoids, antiplatelet, nitrates, and statins.

Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.

Objective: Liddle syndrome (LS) is a monogenic hypertension consistent with autosomal dominant inheritance, often with early onset high blood pressure in childhood or adolescence. This study aimed to identify the pathogenicity of a nonsense mutation in SCNN1G in a Chinese family with LS and the long-term outcomes of tailored treatment with amiloride. Methods: To explore the pathogenicity of candidate variant reported in 2015 by our team, we constructed mutant and wild-type models in vitro and measured amiloride-sensitive current in Chinese Hamster Ovary (CHO) cells using patch clamp technique. Participants were followed up for 7 years after tailored treatment with amiloride. Results: A nonsense variant was detected in six members, two of whom were pediatric patients. This mutation resulted in a termination codon at codon 572, truncating the Pro-Pro-Pro-X-Tyr motif. The mutant epithelial sodium channels displayed higher amiloride-sensitive currents than the wild-type channels (P < 0.05). Tailored treatment with amiloride achieved ideal blood pressure control in all patients with normal cardiorenal function, and no adverse events occurred during follow-up. Conclusion: We found the pathogenicity of a nonsense SCNN1G mutation (p.Glu571*) with enhanced amiloride-sensitive currents in a LS family with young patients. Tailored treatment with amiloride may be an effective strategy for the long-term control of blood pressure and protection from target organ damage or cardiovascular events, including children and youth patients with LS.

Corrigendum: Pathogenicity and Long-Term Outcomes of Liddle Syndrome Caused by a Nonsense Mutation of SCNN1G in a Chinese Family.

[This corrects the article DOI: 10.3389/fped.2022.887214.].

The effect of beta-blocker therapy on progressive aortic dilatation in children and adolescents with Marfan's syndrome: a meta-analysis.

AIM: To assess the effect of beta-blockade therapy on progressive aortic dilatation and on clinical outcome in children and adolescents with Marfan's syndrome (MFS). METHODS: The meta-analysis was instituted, which included studies identified by a systematic review of MEDLINE of peer-reviewed publications. Echocardiogram measurements of the aortic root dimension and outcome measures of mortality and major morbidity were compared between patients who were treated and untreated with beta-blockade therapy. RESULTS: Five studies were included. A total of 224 young patients treated with beta-blocker therapy and 168 patients did not accept medical management. Compared with non-beta-blockade treatment, beta-blockade therapy significantly decreased the rate of aortic dilatation (SMD = -1.30 with 95% CI -2.11 to -0.49). A tendency of clinical outcome beneficial was observed in the beta-blocker treatment group when compared with no beta-blocker treatment group (odds ratio = 0.87 with 95% CI 0.37-2.04). CONCLUSION: There is evidence that beta-blockade therapy can slow down the rate of dilatation of the aorta and has clinical benefits on children and adolescents with MFS.

Factors influencing prognosis in patients with marfan syndrome after aortic surgery.

OBJECTIVE: Aortic aneurysm formation leading eventually to aortic rupture or dissection in early adult life is a fatal outcome of Marfan syndrome (MFS). Advances in the treatment of the syndrome have improved prognosis, but the long-term reoperation rate is still high. It remains unknown which factors influence the long-term prognosis, including the reoperation and mortality rates, in surgically treated Chinese patients with MFS. The authors studied 125 such patients to investigate factors influencing prognosis after aortic surgery. DESIGN: A retrospective clinical investigation. SETTING: An academic medical center. SUBJECTS: One hundred twenty-five Marfan patients who had undergone aortic surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The indications for aortic surgery were aortic aneurysm and/or dissection in the 125 Marfan patients. The most commonly performed procedure was the Bentall in 92 patients. Sixteen patients underwent total arch replacement combined with stented elephant trunk implantation. Ten patients underwent the David procedure. Overall in-hospital and 30-day mortality rate was 1.6%. The survival rate was 97.5%, 91.4%, and 74.2% at 1, 5, and 10 years after surgery, respectively. The reoperation rate was 2.5%, 12.9%, and 32.9% at 1, 5, and 10 years after surgery, respectively. Multivariate analysis revealed that increased systolic blood pressure (Sys BP) was the predictor of death (p < 0.05), and body mass index and smoking were significant predictors of reoperation (p < 0.05). CONCLUSIONS: The present findings report the factors influencing the prognosis of Chinese patients with MFS after aortic surgical procedures. Managing these risk factors may enable health care professionals to improve the prognosis of MFS patients after aortic surgical procedures.

Cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout: A systematic and meta-analysis.

The cardiovascular safety of febuxostat compared to allopurinol for the treatment of gout remains equivocal. Febuxostat had a better safety outcome compared with allopurinol. In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2000 and April 4, 2021, without any language restrictions. We did a systematic review and meta-analysis of included clinical trials to evaluate the cardiovascular safety of febuxostat compared to allopurinol for treatment of chronic gout. Two reviewers independently selected studies, assessed study quality, and extracted data. Risk ratios were calculated with random effects and were reported with corresponding 95% confidence intervals (CI). From 240 potentially relevant citations, 224 papers were excluded; 16 studies were ultimately included in the analysis. Febuxostat had a better safety outcome compared with allopurinol，which was the composite of urgent coronary revascularization (OR: 0.84, 95% CI: 0.77-0.90, p < .0001) and stroke (OR: 0.87, 95% CI: 0.79-0.97, p = .009). However, that difference was not found in nonfatal myocardial infarction (OR: 0.99, 95% CI: 0.80-1.22, p = .91), cardiovascular related mortality (OR: 0.98, 95% CI: 0.69-1.38, p = .89) and all-cause mortality (OR: 0.93, 95% CI: 0.75-1.15, p = .52). No significant differences in cardiovascular related mortality and all-cause mortality were observed across any subgroup. This meta-analysis adds new evidence regarding the cardiovascular safety of febuxostat in patients. Initiation of febuxostat in patients was not associated with an increased risk of death or serious cardiovascular related adverse events compared with allopurinol.

Detection of ten novel FBN1 mutations in Chinese patients with typical or incomplete Marfan syndrome and an overview of the genotype-phenotype correlations.

OBJECTIVE: The aim of this study is to identify the mutation spectrum of FBN1 in patients with Marfan syndrome (MFS) or Marfan-Like Phenotypes and to analyze the genotype-phenotype correlations of existing literature. METHODS AND RESULTS: A total of 21 unrelated patients with a definite or suspected clinical diagnosis of MFS were recruited for research. Eleven FBN1 mutations were identified in 12 patients who strictly fulfilled the Ghent criteria for MFS, and 1 FBN1 mutations were detected in 9 patients with suspected MFS by screening the mutations of FBN1. These FBN1 mutations include 10 novel mutations (c.357 C>A, c.493 C>T, c.1374 T>A, c.4143 delG, c. 6987 C>G, c.7238 G>A, c. 7765 A>G, c.8200 A>G, c. 8431 G>A, c.8547 T>G,) and 2 previously reported mutations (c.4567 C>T, c.4615 C>T). By searching PubMed and Embase (from 1990 up to December 2018), twenty nine studies (including the present study) with 890 subjects with MFS or Marfan-like phenotypes were included to analyze the genotype-phenotype correlations. Several genotype-phenotype correlations were founded. Firstly, mutations of premature termination codons (PTC) were associated with an increased risk of major cardiovascular involvements. Secondly, the frequency of patients with major cardiovascular involvement in exons 43-65 group was as high as that in exons 24-32 group (71.4% vs. 77.0%; p = 0.238). Finally, cysteine missense mutations might be associated with major cardiovascular involvements. CONCLUSIONS: These results extended the FBN1 mutation spectrum of this rare disease and revealed the genotype-phenotype correlations in MFS by analyzing existing literature.

The clinicopathological features and prognosis of signet ring cell carcinoma of the esophagus: A 10-year retrospective study in China.

OBJECTIVES: The aim of this study was to analyze the clinicopathological features and prognosis of esophageal signet ring cell (SRC) carcinoma in China. METHODS: Patients with poorly differentiated adenocarcinoma were identified in two hospitals from January 2006 to June 2016. The patients were divided into three groups according to component of SRCs: SRC≥50% group, SRC < 50% group and non-SRC poorly differentiated adenocarcinoma group. RESULTS: Fifty-seven patients had carcinoma (SRC≥50%), and 79 patients had tumors containing <50% SRCs, and 535 patients was in non-SRC poorly differentiated adenocarcinoma group. There were no significant differences among the three groups in clinicopathological characteristics. Patients in SRC≥50% group had a lower overall survival rate (at 3-year 37.6%versus71.1%; at 5-year 0% versus 43.3%; p<0.001) compared with the control group. Even survival outcome of patients in SRC < 50%was inferior to that of in control group (at 3-year 53.0%versus71.1%; at 5-year 25.9% versus 43.3%; p<0.001). Female sex, large tumor size and increasing TNM stage were independent prognostic factors for SRC ≥50% esophageal carcinoma patients. CONCLUSIONS: The incidence of esophageal SRC carcinoma is relatively rare and the worst outcome is observed in the SRC≥ 50% group. It is necessary to explore new therapeutic modalities to achieve further improvements in the clinical outcome of these patients.

Minimally invasive esophagectomy for esophageal cancer according to the location of the tumor: Experience of 251 patients.

BACKGROUND: Minimally invasive esophagectomy (MIE) is increasingly used for the treatment of esophageal cancer. However, the ideal approach of MIE is not yet standardized. We explore the ideal approach of MIE according to the location of the tumor and compare the clinical outcomes between patients with cancer arising in the upper third of the esophagus and those with tumors involving the middle and lower third of the esophagus. METHODS: We included patients with esophageal carcinoma and had clear indications for MIE. For cancer arising in the upper third of the esophagus, MIE McKeown approach was performed. For tumors involving the middle and lower third of the esophagus, MIE Ivor Lewis approach was adopted. RESULTS: Of the 251 patients included in this analysis, 200 patients underwent Ivor-Lewis MIE and 51 patients underwent McKeown MIE. The incidence of anastomotic leak, anastomotic stenosis and recurrent laryngeal nerve injury was significantly higher in the McKeown MIE group than that in the Ivor Lewis MIE group. The 30-day postoperative mortality rate was 1.2% (n = 1) in the McKeown MIE group. Lymph nodes harvested were significantly more in the MIE-McKeown group than in Ivor Lewis MIE group (P < 0.05). The median follow-up period was 15 months (1-25 months) and the overall survival rate at 1 year stratified by pathologic stage at esophagectomy was 95.9% (stage 1), 83.8% (stage II), 73.4% (stage III). CONCLUSIONS: MIE for esophageal cancer according to the location and clinical stage of the tumor will decrease all postoperative complications and may yield the greatest benefit from surgery.

Clinical characteristics, target organ damage and associate risk factors of resistant hypertension determined by ambulatory blood pressure monitoring in patients aged ≥ 80 years.

OBJECTIVES: To investigate clinical characteristics, target organ damage, and the associated risk factors of the patients aged ≥ 80 years with true resistant hypertension (RH). METHODS: Patients aged ≥ 80 years with hypertension (n = 1163) were included in this study. The included participants attended a structured clinical examination and an evaluation of RH was carried out. The prevalence, clinical characteristics and target organ damage of patients with RH were assessed. The associated clinical risk factors were analyzed by using logistic regression. RESULTS: The prevalence of RH diagnosis by 24-h ambulatory blood pressure monitoring assessment was 21.15%. End-diastolic left ventricular internal dimension, left ventricular mass index as well as prevalence of left ventricular hypertrophy were significantly greater in patients with RH than in control group. The common carotid artery intimal media thickness, carotid walls thickness, common carotid artery diameter and relative wall thickness were significant greater in RH group than in control. A relatively higher level of creatinine, estimated glomerular filtration rate, microalbuminuria and retinal changes was found in RH group than in control. A multivariate analysis showed that patients with a history of diabetes, higher body mass index (BMI) and lipid profiles were independent risk factors of RH. CONCLUSIONS: The prevalence of RH in patients aged ≥ 80 years was within the range of reported rates of the general population. Subjects with RH diagnosis showed a higher occurrence of target organ damage than patients with well controlled blood pressure. Patients with diabetes, higher BMI and serum lipid profiles were independent risk factors for RH in patients aged ≥ 80 years.