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1.
J Invasive Cardiol ; 34(10): E709-E719, 2022 10.
Article in English | MEDLINE | ID: mdl-36001457

ABSTRACT

In this review, the authors discuss a brief history of the Impella mechanical circulatory support device, a mechanistic role for the device in the context of the underlying pathophysiology of acute myocardial infarction cardiogenic shock (AMI-CS), the current body of literature evaluating its role in AMI-CS, and upcoming efforts to identify a role more clearly for the device in AMI-CS.


Subject(s)
Heart-Assist Devices , Myocardial Infarction , Heart-Assist Devices/adverse effects , Humans , Myocardial Infarction/complications , Myocardial Infarction/diagnosis , Shock, Cardiogenic/diagnosis , Shock, Cardiogenic/etiology , Shock, Cardiogenic/therapy , Treatment Outcome
2.
Cardiovasc Revasc Med ; 40: 42-47, 2022 07.
Article in English | MEDLINE | ID: mdl-35210188

ABSTRACT

BACKGROUND: The role of revascularization in patients with stable ischemic heart disease (SIHD) has been controversial, more so in the present era of drug-eluting stents. AIMS: To examine the absolute risk difference (ARD) between revascularization plus optimal medical therapy (OMT) versus OMT alone among patients with SIHD using Bayesian approach. METHODS: PubMed/MEDLINE and Cochrane citation indices were utilized to identify randomized controlled trials (RCTs) through March 31, 2020. Among trials comparing initial revascularization plus OMT with initial OMT alone, revascularization arm must have comprised >50% of patients receiving either percutaneous or surgical revascularization, and >50% of patients must have received aspirin and statin as OMT in both arms. RESULTS: Seven RCTs (12,494) were included in the final analysis. The ARD of all-cause mortality for revascularization with respect to OMT was centred at -0.002 (95% CrI: -0.01; 0.01, Tau: 0.01, 67% probability of ARD of revascularization vs. OMT < 0). The ARD for cardiac mortality was centred at -0.0025 (95%CrI: -0.01; 0.01, Tau: 0.01, 77% probability of ARD of revascularization vs. OMT < 0). The ARD for MI was -0.02 (95% CrI: -0.06; 0.00, Tau: 0.02, 97% probability of ARD for revascularization vs. OMT < 0). There was 96% probability of ARD for unstable angina with revascularization vs. OMT < 0, 4.5% probability of ARD for freedom from angina with revascularization vs. OMT < 0, and 6% probability of ARD for stroke with revascularization vs. OMT < 0. CONCLUSIONS: Bayesian analysis demonstrated minimal probability of difference in all-cause mortality and cardiac mortality in patients with SIHD who underwent revascularization compared with OMT alone. However, revascularization was associated with lower probability of MI, unstable angina, and increased freedom from angina, but a higher risk of stroke compared with OMT alone. PROSPERO: The protocol of this systematic review and meta-analysis was registered in PROSPERO [CRD42020160540].


Subject(s)
Coronary Artery Disease , Drug-Eluting Stents , Myocardial Ischemia , Percutaneous Coronary Intervention , Stroke , Angina Pectoris , Angina, Unstable , Bayes Theorem , Humans , Myocardial Ischemia/therapy , Stroke/therapy , Treatment Outcome
3.
EuroIntervention ; 17(15): 1227-1237, 2022 Feb 18.
Article in English | MEDLINE | ID: mdl-34521614

ABSTRACT

BACKGROUND: Limited data are available regarding clinical outcomes of valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) following the United States Food and Drug Administration approval of ViV TAVI in 2015. AIMS: The aim of this study was to evaluate in-hospital, 30-day, and 6-month outcomes of ViV TAVI versus repeat surgical aortic valve replacement (SAVR) in patients with a failed aortic bioprosthetic valve. METHODS: This retrospective cohort study identified patients who underwent ViV TAVI or repeat SAVR utilising the Nationwide Readmission Database from 2016 to 2018. Primary outcomes were all-cause readmission (at 30 days and 6 months) and in-hospital death. Secondary outcomes were in-hospital stroke, pacemaker implantation, 30-day/6-month major adverse cardiac events (MACE), and mortality during readmission. Propensity score-matching (inverse probability of treatment weighting) analyses were implemented. RESULTS: Out of 6,769 procedures performed, 3,724 (55%) patients underwent ViV TAVI, and 3,045 (45%) underwent repeat SAVR. ViV TAVI was associated with lower in-hospital all-cause mortality (odds ratio [OR] 0.42, 95% confidence interval [CI]: 0.20-0.90, p=0.026) and a higher rate of 30-day (hazard ratio [HR] 1.46, 95% CI: 1.13-1.90, p=0.004) and 6-month all-cause readmission (HR 1.54, 95% CI: 1.14-2.10, p=0.006) compared with repeat SAVR. All secondary outcomes were comparable between the two groups. CONCLUSIONS: ViV TAVI was associated with lower in-hospital mortality but higher 30-day and 6-month all-cause readmission. However, there was no difference in risk of in-hospital stroke, post-procedure pacemaker implantation, MACE, and mortality during 30-day and 6-month readmission compared with repeat SAVR, suggesting that ViV TAVI can be performed safely in carefully selected patients.


Subject(s)
Aortic Valve Stenosis , Bioprosthesis , Heart Valve Prosthesis Implantation , Transcatheter Aortic Valve Replacement , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Bioprosthesis/adverse effects , Heart Valve Prosthesis Implantation/adverse effects , Heart Valve Prosthesis Implantation/methods , Hospital Mortality , Humans , Retrospective Studies , Risk Factors , Transcatheter Aortic Valve Replacement/adverse effects , Transcatheter Aortic Valve Replacement/methods , Treatment Outcome , United States
4.
Respir Med ; 185: 106492, 2021.
Article in English | MEDLINE | ID: mdl-34139578

ABSTRACT

Fungal pneumonia is a dreaded complication encountered after kidney transplantation, complicated by increased mortality and often associated with graft failure. Diagnosis can be challenging because the clinical presentation is non-specific and diagnostic tools have limited sensitivity and specificity in kidney transplant recipients and must be interpreted in the context of the clinical setting. Management is difficult due to the increased risk of dissemination and severity, multiple comorbidities, drug interactions and reduced immunosuppression which should be applied as an important adjunct to therapy. This review will focus on the main causes of fungal pneumonia in kidney transplant recipients including Pneumocystis, Aspergillus, Cryptococcus, mucormycetes and Histoplasma. Epidemiology, clinical presentation, laboratory and radiographic features, specific characteristics will be discussed with an update on diagnostic procedures and treatment.


Subject(s)
Aspergillus/pathogenicity , Cryptococcus/pathogenicity , Histoplasma/pathogenicity , Kidney Transplantation/adverse effects , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Mucorales/pathogenicity , Pneumocystis/pathogenicity , Pneumonia/diagnosis , Pneumonia/microbiology , Antifungal Agents/administration & dosage , Antifungal Agents/adverse effects , Drug Interactions , Female , Humans , Immunocompromised Host , Lung Diseases, Fungal/drug therapy , Lung Diseases, Fungal/epidemiology , Male , Pneumonia/drug therapy , Pneumonia/epidemiology
5.
J Cardiovasc Magn Reson ; 23(1): 44, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33794918

ABSTRACT

The Society for Cardiovascular Magnetic Resonance (SCMR) is an international society focused on the research, education, and clinical application of cardiovascular magnetic resonance (CMR). The SCMR web site ( https://www.scmr.org ) hosts a case series designed to present case reports demonstrating the unique attributes of CMR in the diagnosis or management of cardiovascular disease. Each clinical presentation is followed by a brief discussion of the disease and unique role of CMR in disease diagnosis or management guidance. By nature, some of these are somewhat esoteric, but all are instructive. In this publication, we provide a digital archive of the 2019 Case of the Week series as a means of further enhancing the education of those interested in CMR and as a means of more readily identifying these cases using a PubMed or similar search engine.


Subject(s)
Churg-Strauss Syndrome/diagnostic imaging , Magnetic Resonance Imaging , Thrombosis/diagnostic imaging , Ventricular Dysfunction, Left/diagnostic imaging , Antineoplastic Agents/adverse effects , Cardiotoxicity , Churg-Strauss Syndrome/physiopathology , Churg-Strauss Syndrome/therapy , Diagnosis, Differential , Female , Heart Neoplasms/diagnostic imaging , Humans , Middle Aged , Predictive Value of Tests , Thrombosis/physiopathology , Thrombosis/therapy , Ventricular Dysfunction, Left/chemically induced , Ventricular Dysfunction, Left/physiopathology , Ventricular Dysfunction, Left/therapy , Ventricular Function, Left/drug effects , Young Adult
6.
J Am Geriatr Soc ; 69(5): 1363-1369, 2021 05.
Article in English | MEDLINE | ID: mdl-33570174

ABSTRACT

IMPORTANCE: The impact of pre-existing cognitive dysfunction on outcomes after transcatheter aortic valve replacement (TAVR) remains unclear. OBJECTIVE: To study the association between dementia and post-TAVR outcomes. DESIGN: Cohort study with propensity-score matching was conducted using the Nationwide Inpatient Sample. EXPOSURES: History of dementia at the time of undergoing TAVR. MAIN OUTCOMES: All-cause in-hospital mortality, stroke, bleeding requiring transfusion, acute kidney injury, post-procedural vascular complications, post-procedural pacemaker implantation, length of stay, in-hospital delirium, and discharge disposition in patients with and without dementia undergoing TAVR. RESULTS: Of 57,805 patients undergoing TAVR, 2910 (5.0%) had a diagnosis of dementia. Propensity-score matching yielded 2895 matched pairs of patients. TAVR was associated with an increased risk of bleeding requiring transfusion (14.7% vs 8.6%, odd ratio (OR) 1.82 [95% confidence interval (CI) 1.26-2.63]; p < 0.01), discharge to a rehabilitation facility (45.8% vs 31.6%, OR 2.27 [95% CI 1.67-3.08]; p < 0.001), in-hospital delirium (7.4% vs 3.6%, OR 2.13 [95% CI 1.26-3.61]; p < 0.01), increased length of stay (6.75 ± 0.07 days vs 6.11 ± 0.06 days, slope = 1.11 [95% CI 1.03-1.19]; p < 0.01), but comparable in-hospital mortality (2.1% vs 2.6%, OR 1.26 [95% CI 0.57-2.79]; p = 0.57] in patients with dementia compared with patients without dementia. CONCLUSIONS AND RELEVANCE: This study found that patients with dementia undergoing TAVR had a longer hospital stay as well as higher rates of discharge to a rehabilitation facility and in-hospital delirium, which may indicate debility and functional decline during hospitalization; however, in-hospital mortality and other outcomes were comparable between the two groups. TAVR candidates should be subjected to a comprehensive geriatric and cognitive assessment to help risk-stratify them for potential post-procedural functional decline. Prospective studies aimed at standardizing cognitive scoring and evaluating the post-procedural quality of life are needed.


Subject(s)
Aortic Valve Disease/surgery , Cognitive Dysfunction/mortality , Dementia/mortality , Postoperative Complications/mortality , Transcatheter Aortic Valve Replacement/mortality , Aged , Aged, 80 and over , Aortic Valve Disease/psychology , Cognitive Dysfunction/complications , Cohort Studies , Dementia/complications , Female , Hospital Mortality , Humans , Male , Odds Ratio , Postoperative Complications/psychology , Preoperative Period , Propensity Score , Risk Assessment , Risk Factors , Treatment Outcome
8.
JAMA Netw Open ; 3(7): e2014780, 2020 07 01.
Article in English | MEDLINE | ID: mdl-32644140

ABSTRACT

Importance: The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe psychological, social, and economic stress in people's lives. It is not known whether the stress of the pandemic is associated with an increase in the incidence of stress cardiomyopathy. Objective: To determine the incidence and outcomes of stress cardiomyopathy during the COVID-19 pandemic compared with before the pandemic. Design, Setting, and Participants: This retrospective cohort study at cardiac catheterization laboratories with primary percutaneous coronary intervention capability at 2 hospitals in the Cleveland Clinic health system in Northeast Ohio examined the incidence of stress cardiomyopathy (also known as Takotsubo syndrome) in patients presenting with acute coronary syndrome who underwent coronary arteriography. Patients presenting during the COVID-19 pandemic, between March 1 and April 30, 2020, were compared with 4 control groups of patients with acute coronary syndrome presenting prior to the pandemic across 4 distinct timelines: March to April 2018, January to February 2019, March to April 2019, and January to February 2020. Data were analyzed in May 2020. Exposures: Patients were divided into 5 groups based on the date of their clinical presentation in relation to the COVID-19 pandemic. Main Outcomes and Measures: Incidence of stress cardiomyopathy. Results: Among 1914 patient presenting with acute coronary syndrome, 1656 patients (median [interquartile range] age, 67 [59-74]; 1094 [66.1%] men) presented during the pre-COVID-19 period (390 patients in March-April 2018, 309 patients in January-February 2019, 679 patients in March-April 2019, and 278 patients in January-February 2020), and 258 patients (median [interquartile range] age, 67 [57-75]; 175 [67.8%] men) presented during the COVID-19 pandemic period (ie, March-April 2020). There was a significant increase in the incidence of stress cardiomyopathy during the COVID-19 period, with a total of 20 patients with stress cardiomyopathy (incidence proportion, 7.8%), compared with prepandemic timelines, which ranged from 5 to 12 patients with stress cardiomyopathy (incidence proportion range, 1.5%-1.8%). The rate ratio comparing the COVID-19 pandemic period to the combined prepandemic period was 4.58 (95% CI, 4.11-5.11; P < .001). All patients during the COVID-19 pandemic had negative reverse transcription-polymerase chain reaction test results for COVID-19. Patients with stress cardiomyopathy during the COVID-19 pandemic had a longer median (interquartile range) hospital length of stay compared with those hospitalized in the prepandemic period (COVID-19 period: 8 [6-9] days; March-April 2018: 4 [3-4] days; January-February 2019: 5 [3-6] days; March-April 2019: 4 [4-8] days; January-February: 5 [4-5] days; P = .006). There were no significant differences between the COVID-19 period and the overall pre-COVID-19 period in mortality (1 patient [5.0%] vs 1 patient [3.6%], respectively; P = .81) or 30-day rehospitalization (4 patients [22.2%] vs 6 patients [21.4%], respectively; P = .90). Conclusions and Relevance: This study found that there was a significant increase in the incidence of stress cardiomyopathy during the COVID-19 pandemic when compared with prepandemic periods.


Subject(s)
Acute Coronary Syndrome/epidemiology , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Takotsubo Cardiomyopathy/epidemiology , Aged , Betacoronavirus , COVID-19 , Cohort Studies , Comorbidity , Female , Humans , Incidence , Length of Stay/statistics & numerical data , Male , Middle Aged , Ohio/epidemiology , Pandemics , Retrospective Studies , SARS-CoV-2
9.
Cardiovasc Revasc Med ; 21(9): 1157-1163, 2020 09.
Article in English | MEDLINE | ID: mdl-31959561

ABSTRACT

Recurrent in-stent restenosis (R-ISR) refers to the re-occlusion of a successfully treated in-stent restenosis. Much of the present understanding of this condition stems from studies on in-stent restenosis, as literature on R-ISR is sparse. Compounded by multiple previous struts, narrower luminal diameters and worse patient profiles, R-ISR is a clinical challenge that demands urgent attention. Recent studies have explored various diagnostic and therapeutic strategies to identify and suitably manage R-ISR. In this review, we discuss our understanding of the risk factors, invasive and non-invasive imaging techniques, therapeutic options and gaps in present knowledge for the management of R-ISR.


Subject(s)
Coronary Restenosis , Drug-Eluting Stents , Coronary Angiography , Humans , Risk Factors , Stents , Treatment Outcome
10.
Ann Thorac Surg ; 110(1): 152-157, 2020 07.
Article in English | MEDLINE | ID: mdl-31770505

ABSTRACT

BACKGROUND: The "weekend effect" is a purported phenomenon whereby patients admitted for time-sensitive medical and surgical conditions on a weekend suffer worse outcomes than those admitted on a weekday. There are limited data on the weekend effect for nonelective coronary artery bypass grafting (CABG). METHODS: We studied outcomes for weekend vs weekday operations for all adult patients in the 2013 to 2014 National Inpatient Sample (NIS) undergoing nonelective CABG. RESULTS: Of 101,510 patients undergoing nonelective CABG, 12,795 patients (12.6%) underwent CABG on the day of admission (n = 1230 for weekend and 11,565 for weekday admission, respectively). Patients undergoing surgical procedures on a weekend were more likely to have a diagnosis of ST-elevation acute coronary syndrome (47.2% vs 20.2%, P < .001), require intraaortic balloon pump support (46.3% vs 23.1%, P < .001), and undergo same-day coronary angiography (66.7% vs 41.8%; P < .001) or same-day percutaneous coronary intervention (11.8% vs 7.1%; P = .01). Weekend admission was associated with increased mortality in unadjusted analysis (6.1% vs 3.2%; odds ratio, 1.99; 95% confidence interval, 1.13-3.52; P = .02), but this effect was attenuated in the adjusted model (adjusted odds ratio, 1.22; 95% confidence interval, 0.63-2.33; P = .47). CONCLUSIONS: Patients undergoing CABG on a weekend had higher crude mortality but similar risk-adjusted mortality compared with their weekday counterparts. Some of the excess mortality observed for weekend operations is likely attributable to a sicker cohort of patients undergoing CABG on the weekend.


Subject(s)
Coronary Artery Bypass/adverse effects , Coronary Artery Disease/mortality , Coronary Artery Disease/surgery , Hospitalization/statistics & numerical data , Postoperative Complications/epidemiology , Aged , Coronary Artery Disease/etiology , Female , Humans , Male , Middle Aged , Retrospective Studies , Survival Rate , Time Factors , Treatment Outcome
11.
Respir Med ; 137: 89-94, 2018 04.
Article in English | MEDLINE | ID: mdl-29605219

ABSTRACT

Bacterial pathogens are the most frequent cause of pneumonia after transplantation. Early after transplantation, recipients are at higher risk for nosocomial infections. The most commonly encountered pathogens during this period are gram-negative bacilli (Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa …), but gram-positive coccus such as Staphylococcus aureus or Streptococcus pneumoniae and anaerobic bacteria can also be found. Empirical antibiotic therapy should be guided by previous colonisation of the recipient and bacterial resistance pattern in the hospital. Six months after transplantation, pneumonias are mostly due to community-acquired bacteria (S. pneumonia, H. influenza, Mycoplasma, Chlamydia and others). Opportunistic pathogens take advantage of the state of immunosuppression which is usually highest from one to six months after transplantation. During this period, but also occurring many years later in the setting of a chronically depressed immune system, bacterial pathogens with low intrinsic virulence can cause pneumonia. The diagnosis of pneumonia caused by opportunistic pathogens can be challenging. The delay in diagnosis preventing the early instauration of adequate treatment in kidney transplant recipients with a depressed immune system, frequently coupled with co-morbid conditions and a state of frailty, will affect prognosis and outcome, increasing morbidity and mortality. This review will focus on the most common opportunistic bacterial pathogens causing pneumonia in kidney transplant recipients: Legionella, Nocardia, Mycobacterium tuberculosis/nontuberculous, and Rhodococcus. Recognition of their specificities in the setting of immunosuppression will allow early diagnosis, crucial for initiation of effective therapy and successful outcome. Interactions with immunosuppressive therapy should be considered as well as reducing immunosuppression if necessary.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Immunosuppression Therapy/adverse effects , Kidney Transplantation/adverse effects , Opportunistic Infections/microbiology , Pneumonia, Bacterial/microbiology , Transplant Recipients/statistics & numerical data , Aged , Anti-Bacterial Agents/administration & dosage , Bacteria/isolation & purification , Cross Infection/drug therapy , Cross Infection/mortality , Humans , Legionella/isolation & purification , Male , Middle Aged , Mycobacterium/isolation & purification , Nocardia/isolation & purification , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Opportunistic Infections/mortality , Pneumonia, Bacterial/complications , Pneumonia, Bacterial/diagnostic imaging , Pneumonia, Bacterial/drug therapy , Prognosis , Rhodococcus/isolation & purification
12.
Transplant Proc ; 49(9): 2065-2069, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29149962

ABSTRACT

BACKGROUND: Tacrolimus is metabolized by members of the cytochrome p450 3A subfamily, and its bioavailability depends also on P-glycoprotein. We have observed that some patients admitted for infection presented with increased tacrolimus trough levels (TLs). The aim of the study was to assess the impact of infection on tacrolimus TLs and to determine the factors involved in TL fluctuations. METHODS: This retrospective cohort study included patients transplanted with a kidney between 2009 and 2011 who were hospitalized for an acute infection. Tacrolimus TLs and dosages were recorded before hospitalization, at admission, and 1 month after discharge. Increased levels of tacolimus were defined as TL 25% higher on admission than those recorded at the last visit before hospitalization. RESULTS: Seventy-seven patients were hospitalized 138 times for infection. More than two thirds of first hospitalizations occurred during the first post-transplant year. Causes of hospitalization were urinary (33%), cytomegalovirus (27%), digestive (15%), and pulmonary (12%) infections. Thirty-five percent of kidney transplant recipients had increased tacrolimus TLs (27/77 patients) in 24% of the hospitalizations (34/138). In 34 hospitalizations occurring in 27 patients, TL at admission was ≥25% compared with the last visit before admission. Comparing these 34 hospitalizations with the other 104, no significant differences were noted, except for a greater fraction of digestive infections in the group with elevated tacrolimus TLs, independent of diarrhea occurrence. CONCLUSIONS: Up to 35% of kidney transplant recipients admitted for acute infection present with high tacrolimus TLs, requiring a dose reduction. How acute infection precisely affects metabolism and bioavailability of tacrolimus remains to be investigated.


Subject(s)
Immunosuppressive Agents/blood , Infections/metabolism , Kidney Transplantation , Tacrolimus/blood , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Acute Disease , Adult , Aged , Cytochrome P-450 CYP3A/metabolism , Female , Hospitalization , Humans , Immunosuppressive Agents/metabolism , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Retrospective Studies , Tacrolimus/metabolism , Tacrolimus/therapeutic use
13.
J Viral Hepat ; 24(5): 430-435, 2017 05.
Article in English | MEDLINE | ID: mdl-27917563

ABSTRACT

Kidney transplant recipients (KTR) are subjected to immunosuppressive therapy that can enhance hepatitis B and C virus replication, leading to cirrhosis and hepatocellular carcinoma (HCC). The aim of this study was to assess the prevalence and outcome of HCC in KTR. Case-control study. Patients with chronic HBV and/or HCV infection who underwent kidney transplantation between 1976 and 2011 and subsequently developed HCC were compared to a control group of patients with chronic HBV and/or HCV infection, matched for gender and age at HCC diagnosis, who did not receive kidney transplantation. Among 2944 KTR, 330 had hepatitis B and/or C. Fourteen developed HCC, a period prevalence of 4.2%. Age at HCC diagnosis was 52.6 ± 6.5 years (53.5 ± 5.7 in controls, P=.76). Time between transplantation and HCC diagnosis was 16.7 ± 2.7 years. Six HCCs were related to HBV, six to HCV and two to co-infection with HBV and HCV. Immunosuppressive therapy was comparable in HBV, HCV and HBV+HCV patients. At diagnosis, 71% of patients met Milan criteria (65% in the control group, P=.4). Alpha-fetoprotein levels, tumour characteristics and treatment modalities were comparable between both groups. Patient survival 2 years after HCC diagnosis was 28% in KTR, compared to 68% in controls (P=.024). Survival after HCC diagnosis is significantly worse in KTR compared to nontransplanted patients with HBV and/or HCV. Prevention is crucial and should be based on viral eradication/suppression before or after transplantation.


Subject(s)
Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/mortality , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Kidney Transplantation , Transplant Recipients , Adult , Case-Control Studies , Female , Humans , Male , Middle Aged , Survival Analysis , Treatment Outcome
14.
Sci Rep ; 6: 19393, 2016 Jan 20.
Article in English | MEDLINE | ID: mdl-26786552

ABSTRACT

Non-fibrillar soluble oligomeric forms of amyloid-ß peptide (oAß) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAß initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aß, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAß levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAß to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aß on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aß and tau pathology.


Subject(s)
Long-Term Potentiation , Memory , Protein Aggregates , Protein Aggregation, Pathological , Protein Multimerization , tau Proteins/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Alzheimer Disease/psychology , Amyloid beta-Peptides/metabolism , Animals , Disease Models, Animal , Extracellular Space/metabolism , Hippocampus/metabolism , Hippocampus/pathology , Mice , Neurons/metabolism , tau Proteins/chemistry
15.
J Clin Endocrinol Metab ; 100(12): 4669-76, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26505822

ABSTRACT

CONTEXT: Vascular calcification (VC) is prevalent and progressive in renal transplant recipients (RTRs). Recent cross-sectional data suggest that activated Wnt signaling contributes to VC. OBJECTIVE: The objective was to investigate whether circulating levels of the Wnt antagonist sclerostin associate with progression of VC. DESIGN: This was a post hoc analysis of the longitudinal observational Brussels Renal Transplant Cohort study. SETTING: The setting was a tertiary care academic hospital. PATIENTS: Coronary artery calcification and aorta calcification were measured by multislice spiral computerized tomography in 268 prevalent RTRs (age, 53 ± 13 y; 61% male) at baseline and remeasured in 189 patients after a median follow-up of 4.4 years. Baseline serum sclerostin levels were assessed on stored blood samples. Regression analysis was performed to identify determinants of baseline VC and progression. MAIN OUTCOME MEASURE: The main outcome measure was progression of VC. RESULTS: VC was present in up to 84% of participants at baseline. Almost half of the patients showed progression of VC, according to Hokanson criteria. The cross-sectional analysis at baseline demonstrated a direct association between sclerostin levels and VC score in univariate analysis, which became inverse after adjustment for age, gender and PTH level. Remarkably, a lower sclerostin level was identified as an independent determinant of a higher baseline aorta calcification score in the final regression model. Moreover, baseline sclerostin levels showed an inverse association with VC progression, at least after adjustment for traditional risk factors. CONCLUSIONS: Serum sclerostin levels inversely associated with VC burden and progression in prevalent RTRs after adjustment for traditional risk factors. Our data corroborate previous findings in nontransplanted chronic kidney disease patients and support the notion that sclerostin may be up-regulated in the vascular wall during the VC process as part of a local counterregulatory mechanism directed to suppress VC. Additional clinical and experimental data are required for confirmation.


Subject(s)
Bone Morphogenetic Proteins/blood , Kidney Transplantation , Transplant Recipients , Vascular Calcification/blood , Adaptor Proteins, Signal Transducing , Adult , Aged , Aorta/pathology , Cohort Studies , Disease Progression , Female , Genetic Markers , Humans , Longitudinal Studies , Male , Middle Aged , Risk Factors , Tomography, X-Ray Computed , Vascular Calcification/pathology
16.
Med Dosim ; 40(3): 210-7, 2015.
Article in English | MEDLINE | ID: mdl-25595492

ABSTRACT

Radiation pneumonitis is a well-documented side effect of radiation therapy for breast cancer. The purpose of this study was to compare combined photon-electron, photon-only, and electron-only plans in the radiation treatment of the supraclavicular lymph nodes. In total, 13 patients requiring chest wall and supraclavicular nodal irradiation were planned retrospectively using combined photon-electron, photon-only, and electron-only supraclavicular beams. A dose of 50Gy over 25 fractions was prescribed. Chest wall irradiation parameters were fixed for all plans. The goal of this planning effort was to cover 95% of the supraclavicular clinical target volume (CTV) with 95% of the prescribed dose and to minimize the volume receiving ≥ 105% of the dose. Comparative end points were supraclavicular CTV coverage (volume covered by the 95% isodose line), hotspot volume, maximum radiation dose, contralateral breast dose, mean total lung dose, total lung volume percentage receiving at least 20 Gy (V(20 Gy)), heart volume percentage receiving at least 25 Gy (V(25 Gy)). Electron and photon energies ranged from 8 to 18 MeV and 4 to 6 MV, respectively. The ratio of photon-to-electron fractions in combined beams ranged from 5:20 to 15:10. Supraclavicular nodal coverage was highest in photon-only (mean = 96.2 ± 3.5%) followed closely by combined photon-electron (mean = 94.2 ± 2.5%) and lowest in electron-only plans (mean = 81.7 ± 14.8%, p < 0.001). The volume of tissue receiving ≥ 105% of the prescription dose was higher in the electron-only (mean = 69.7 ± 56.1 cm(3)) as opposed to combined photon-electron (mean = 50.8 ± 40.9 cm(3)) and photon-only beams (mean = 32.2 ± 28.1 cm(3), p = 0.114). Heart V(25 Gy) was not statistically different among the plans (p = 0.999). Total lung V(20 Gy) was lowest in electron-only (mean = 10.9 ± 2.3%) followed by combined photon-electron (mean = 13.8 ± 2.3%) and highest in photon-only plans (mean = 16.2 ± 3%, p < 0.001). As expected, photon-only plans demonstrated the highest target coverage and total lung V(20 Gy). The superiority of electron-only beams, in terms of decreasing lung dose, is set back by the dosimetric hotspots associated with such plans. Combined photon-electron treatment is a feasible technique for supraclavicular nodal irradiation and results in adequate target coverage, acceptable dosimetric hotspot volume, and slightly reduced lung dose.


Subject(s)
Breast Neoplasms/radiotherapy , Lymph Nodes/radiation effects , Lymphatic Metastasis/radiotherapy , Organ Sparing Treatments/methods , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, High-Energy/methods , Combined Modality Therapy , Electrons/therapeutic use , Humans , Organs at Risk/radiation effects , Photons/therapeutic use , Radiation Protection/methods , Radiotherapy Dosage , Retrospective Studies , Treatment Outcome
17.
Acta Clin Belg ; 70(3): 218-22, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25541210

ABSTRACT

Although post-transplant lymphoproliferative disorder is a classical complication encountered after kidney transplantation, its diagnosis can still be challenging and its outcome life-threatening. Most cases are related to Epstein-Barr virus (EBV) infection and occur mainly in the first year post-transplant, favoured by the seronegative EBV status of the recipient transplanted with a kidney from a seropositive donor, and strong immunosuppression. We report the case of a young kidney-pancreas transplant recipient who developed post-transplant lymphoproliferative disorder (PTLD) early after transplantation, with a rapid fatal issue. We review the pathogenesis, clinical presentation, and management of PTLD with a focus on prevention.


Subject(s)
Epstein-Barr Virus Infections , Immunosuppressive Agents/adverse effects , Kidney Transplantation , Lymphoproliferative Disorders , Pancreas Transplantation , Postoperative Complications , Adult , Diabetes Mellitus, Type 1/complications , Diagnosis, Differential , Epstein-Barr Virus Infections/diagnosis , Epstein-Barr Virus Infections/etiology , Epstein-Barr Virus Infections/physiopathology , Fatal Outcome , Female , Humans , Immunosuppressive Agents/administration & dosage , Kidney Failure, Chronic/etiology , Kidney Failure, Chronic/surgery , Kidney Transplantation/methods , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/etiology , Lymphoproliferative Disorders/physiopathology , Lymphoproliferative Disorders/therapy , Pancreas Transplantation/adverse effects , Pancreas Transplantation/methods , Positron-Emission Tomography/methods , Postoperative Complications/diagnosis , Postoperative Complications/physiopathology , Postoperative Complications/therapy
19.
Transplant Proc ; 44(9): 2814-7, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23146530

ABSTRACT

BACKGROUND: Disseminated varicella zoster virus (VZV) infection, whether due to primary infection or reactivation, may be life threatening in renal transplant recipients. The aims of this study were to assess the outcome of disseminated VZV infection in renal transplant recipients and to determine potential risk factors for mortality. METHODS: A search of the English literature from 1985 to 2011 using PUBMED was performed. Reports involving renal transplant recipients younger than 16 years of age were excluded. RESULTS: A total of 56 adult patients presenting with a disseminated cutaneous or visceral VZV infection was included. Seventy percent of cases occurred within 5 years after transplantation, and 89% within 10 years. Visceral complications including disseminated intravascular coagulation occurred in two thirds of patients. Mortality decreased significantly from 47% in the era before 1995 to 17% after 1995 (P = .04). Risk factors for mortality included visceral involvement, use of azathioprine as immunosuppressant, and longer time between transplantation and VZV infection. VZV seropositivity did not influence fatal outcome. CONCLUSION: Disseminated VZV infection can be life threatening in renal transplant recipients with a global mortality rate of 30%. This rate seems to have decreased since 1995. Seropositive VZV patients with disseminated infection are not protected from fatal outcome.


Subject(s)
Chickenpox/virology , Herpes Zoster/virology , Herpesvirus 3, Human/pathogenicity , Kidney Transplantation/adverse effects , Adult , Chickenpox/diagnosis , Chickenpox/immunology , Chickenpox/mortality , Female , Herpes Zoster/diagnosis , Herpes Zoster/immunology , Herpes Zoster/mortality , Herpesvirus 3, Human/immunology , Humans , Immunosuppressive Agents/adverse effects , Kaplan-Meier Estimate , Kidney Transplantation/immunology , Kidney Transplantation/mortality , Male , Risk Factors , Time Factors , Treatment Outcome , Virus Activation
20.
Transpl Infect Dis ; 14(1): 99-102, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22093456

ABSTRACT

Hepatitis E virus (HEV) infection can evolve to chronic hepatitis in immunocompromised patients leading to rapidly progressive cirrhosis. Proper diagnosis is therefore important, as reducing immunosuppressive therapy can allow clearance of the virus. We report a case of chronic HEV infection in a renal transplant recipient that went undiagnosed for many years, discuss the therapeutic options, and review the current available literature.


Subject(s)
Hepatitis E virus/isolation & purification , Hepatitis E/diagnosis , Hepatitis, Chronic/virology , Kidney Transplantation/adverse effects , Adult , Female , Hepatitis E/virology , Hepatitis, Chronic/diagnosis , Humans , Immunosuppression Therapy
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