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1.
Case Rep Nephrol Dial ; 14(1): 15-19, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38298244

RESUMEN

Introduction: During the last year, the features of peritoneal dialysis patients have changed, and the cases in which there is a need to perform abdominal surgery are growing. Reports of abdominal surgery in patients who are able to continue peritoneal dialysis are increasing. The minimally invasive techniques represent the preferred and safest approach. Such techniques are associated with reduced hospitalization time, less invasiveness, peritoneal integrity preservation, and reduced intra-abdominal inflammation due to regenerative processes. Case Presentation: In this case report, we present a case of major abdominal surgery, in the form of hepatic metastasectomy, performed with the robotic-assisted technique, which allowed catheter and intracorporeal dialysis preservation. The patient showed a strong determination to continue with peritoneal dialysis as long as possible. During the switch to hemodialysis, he performed prophylactic antibiotic therapy to preserve the peritoneal catheter, and the patient was instructed to have a reduced water intake, avoiding excessive ultrafiltration potentially deteriorating the residual renal function. Special care was also taken to avoid any nephrotoxic drug. The peritoneal treatment was restarted after 3 weeks with low volume exchange for the first 10 days, and the pre-surgery dialysis volumes were then re-established. After surgery, the patient showed adequate clearance of solutes and ultrafiltration similar to the preoperative period. The patient did not encounter any wound complications. Conclusion: Robotic surgery represents a further aid in peritoneal dialysis preservation after abdominal surgery. A detailed communication with the patient before performing this kind of procedure and a strong will to preserve the peritoneal method are essential.

2.
G Ital Nefrol ; 40(2)2023 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-37179476

RESUMEN

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased. We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient's vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis.


Asunto(s)
Acidosis , Terapia de Reemplazo Renal Híbrido , Insuficiencia Renal Crónica , Humanos , Masculino , Persona de Mediana Edad , Creatinina , Diálisis Renal/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Topiramato
3.
Atherosclerosis ; 366: 32-39, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36696749

RESUMEN

BACKGROUND AND AIMS: Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. METHODS: All data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. RESULTS: 798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. CONCLUSIONS: PCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.


Asunto(s)
Anticolesterolemiantes , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Inhibidores de PCSK9 , LDL-Colesterol , Proproteína Convertasa 9 , Anticuerpos Monoclonales/efectos adversos , Anticolesterolemiantes/efectos adversos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico
4.
J Vasc Access ; 24(2): 300-304, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34213371

RESUMEN

Guidelines for vascular access recommend that the distal autogenous arteriovenous fistula (AVF) should be the first choice-access procedure for patients starting dialysis. Arteriosclerosis of radial artery may cause early failure, as well as failure of maturation of distal arteriovenous fistulas. To increase the incidence of distal AVFs, our team, specialized in vascular access surgery from 2004 onwards, has introduced Intraoperative Transluminal Angioplasty (ITA) under ultrasound (UG) or fluoroscopic guidance, to recruit inadequate arterials for creating distal fistulas. Intravascular lithotripsy (IL) is a novel approach to treat luminal and medial calcifications in patients with peripheral arterial disease and coronary disease. We believe that intraoperative IL may be an opportunity to recruit calcified radial arteries for creating distal radio-cephalic fistulas. Purpose of this study is to describe the intraoperative IL technical applied in our clinical experience. A 37-year-old diabetic patient with distal radio-cephalic fistula was recruited for the first IL experience. One year ago, a wrist radio-cephalic fistula was created in the right upper limb, with intraoperative UG radial artery angioplasty for extensive calcifications. The fistula was functioning but showed a delay in maturation. An angioplasty was unsuccessfully attempted to facilitate the maturation. Subsequently, a surgical revision of the fistula was performed, creating a new anastomosis immediately upstream of the previous one by performing an intraoperative IL UG of the radial artery. The fistula was immediately well functioning, and was cannulated with two needles after 1 month. It is currently being used with intradialytic adequate blood flow. The positive outcome of the case described in this paper, even if only anecdotal, could act as a trigger for further experiences with IL.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Fístula , Humanos , Adulto , Arteria Radial/diagnóstico por imagen , Arteria Radial/cirugía , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/métodos , Resultado del Tratamiento , Diálisis Renal/métodos , Grado de Desobstrucción Vascular , Estudios Retrospectivos
5.
BMC Nephrol ; 23(1): 390, 2022 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-36476330

RESUMEN

BACKGROUND: Hepatitis C virus (HCV) may play a pathogenic role in several forms of immune complex glomerulonephritis (GN). We present a patient whose initial clinical presentation instilled suspicion of HCV-related renal involvement. Yet, histopathologic data oriented towards a different diagnosis. CASE PRESENTATION: A 68-year old man presented with kidney dysfunction, cryoglobulins, low C4 level, high HCV-RNA and cutaneous vasculitis. The first hypothesis was a hepatitis C-related cryoglobulinemic glomerulonephritis. Renal biopsy revealed endocapillary and mesangial cells hypercellularity with complement C3 and IgM deposits. The echocardiography showed an infectious endocarditis (IE) on aortic valve. Appropriate antibiotic therapy and a prosthetic valve replacement were performed, obtaining recovery of renal function. CONCLUSION: HCV infection may be linked to multiple renal manifestations, often immune-complex GN such as cryoglobulinemic membrano-proliferative GN. Renal disease due to IE is usually associated to focal, segmental or diffuse proliferative GN, with prominent endocapillary proliferation. The most common infectious agents are Staphylococcus aureus and Streptococcus species. This case report may be relevant because the renal dysfunction was highly suggestive of a cryoglobulinemic GN on a clinical ground, but the histologic pattern after performing the renal biopsy oriented towards a different cause of the underlying disease, that required a specific antibiotic treatment. The renal biopsy is always required to confirm a clinical suspicious in patients affected by multiple comorbidities.


Asunto(s)
Hepatitis C , Humanos , Anciano , Hepatitis C/complicaciones
6.
Exp Clin Endocrinol Diabetes ; 130(6): 415-422, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34384121

RESUMEN

INTRODUCTION: Multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII) are two modalities of treating type 1 diabetes mellitus (T1DM). The benefits of CSII on long-term metabolic control and outcomes compared to those of MDI are still debated. We investigated both vascular function and myocardial performance in T1DM adolescents on MDI or CSII treatment. METHODS: One hundred twenty-three T1DM subjects (mean age 14.16±2.55 years), 63 on MDI regimen, 60 on CSII, and 57 controls were enrolled. Anthropometric and biochemical characteristics were evaluated. Ultrasound assessments of carotid intima-media thickness (cIMT), flow-mediated dilatation of brachial artery, anteroposterior diameter of the infrarenal abdominal aorta (APAO), and transthoracic echocardiography were performed. RESULTS: T1DM subjects on the CSII regimen showed better glycemic control than those on MDI, expressed as glycated haemoglobin (HbA1c). c-IMT and APAO were higher in MDI than CSII patients (0.61±0.11 mm vs. 0.56±0.07 mm, p=0.04; 13.61±3.29 mm vs. 11.65±1.84 mm, p=0.01, respectively). Left and right Tei index and left E/e' ratio were higher in MDI than CSII subjects (0.82±0.40 vs. 0.52±0.19, p=0.002; 0.86±0.41 vs. 0.64±0.1, p=0.02; 5.89±2.0 vs. 4.73±1.59, p=0.02, respectively). Multiple regression analyses showed that glucose level, HbA1c and diabetes onset were significantly related to vascular and echocardiographic parameters in MDI and CSII patients. CONCLUSIONS: CSII regimen in T1DM adolescents improves glycemic control and seems to ameliorate endothelial function and global myocardial performance as compared to MDI therapy.


Asunto(s)
Diabetes Mellitus Tipo 1 , Adolescente , Grosor Intima-Media Carotídeo , Niño , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes , Inyecciones Subcutáneas , Insulina , Sistemas de Infusión de Insulina
7.
J Vasc Access ; 23(2): 257-264, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33482698

RESUMEN

Maturation failure remains a major clinical problem of distal arteriovenous fistula (AVF). Early failure (EF) is associated with the small size of the veins. For about 10 years we have used in more than 1000 fistulas, the Vessels Pre-Dilatation (VPD) to increase the recruitment of small veins for creating distal AVFs. The purpose of this study is to highlight if the VPD can reduce the incidence of EF or failure to mature (FTM) in AVFs created with small veins. Data of all the consecutive patients directly admitted to our Department for their first distal AVF from January to December 2019 were collected. The patients were divided in two groups, one with a vein diameter after the tourniquet ⩽2.0 mm (G1) and one >2 mm (G2). Both in G1 then in G2 the vessels had undergone VPD. Immediate failure (IF), EF, FTM, delayed or arrested maturation rate (DAM), unassisted AVFs and matured AFVs were evaluated. The patients recruited totalled 104, 37 in G1, and 67 in G2. The two groups were homogeneous in age, incidence of diabetes, obesity, heart disease, peripheral vasculopathy, and race. Female were more numerous in G1 (51% vs 12%, p < 0.001). In G1 and G2 occurred respectively 3 IF versus zero (p < 0.05), 10 EF (29%) versus 6 (9%) (p < 0.05), 6 DAM (16%) versus 6 (9%), 21 unassisted AVFs (57%) versus 57 (85%) (p < 0.01). Dividing the patients into groups of unassisted and assisted AVFs, female and low vein diameter are more represented in the assisted group. There were 32 matured AVFs (86%) in G1 and 65 (97%) in G2. In order to increase the incidence of the distal AVF, the PDV allows to include small veins. However, more patients require further interventions to achieve maturation of the fistula.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Fístula , Derivación Arteriovenosa Quirúrgica/efectos adversos , Derivación Arteriovenosa Quirúrgica/métodos , Dilatación , Dilatación Patológica , Femenino , Humanos , Diálisis Renal/métodos , Grado de Desobstrucción Vascular
8.
Int J Mol Sci ; 24(1)2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36613485

RESUMEN

Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.


Asunto(s)
Enfermedades Renales , Proteinuria , Humanos , Proteinuria/orina , Proteína de Bence Jones , Enfermedades Renales/terapia , Dieta
9.
J Vasc Access ; 22(1_suppl): 91-96, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34278873

RESUMEN

Autogenous (AVF) and prosthetic (AVG) arteriovenous fistulas are the vascular accesses (VA) of choice for hemodialysis thanks to their improved patency, reduced costs, and lower rate of infections relative to catheters.In an effort to maximize the number of primary AVF and AVG, shorten maturation times for AVF, and reduce the number of indwelling catheters, several new techniques have been developed within the context of an overall program designed to optimize access care.This approach includes: (a) Primary Intraoperative Balloon Angioplasty on the vessels selected for AV creation whether small-sized or altered by pre-existing lesions; (b) Percutaneous Transluminal Angioplasty (PTA) on AVF and AVG stenosis, performed under ultrasonographic (UG) or fluoroscopic guide (FG).We report the experience of two Center in performing the above mentioned procedures on even complex VA. The wise adoption of these techniques may avail to meet the stringent demands for reliable VA placement as defined by KDOQI and, thereby, expand the duration and quality of life for hemodialysis patients.


Asunto(s)
Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Derivación Arteriovenosa Quirúrgica/efectos adversos , Humanos , Calidad de Vida , Diálisis Renal , Ultrasonografía Intervencional
10.
G Ital Nefrol ; 38(3)2021 Jun 24.
Artículo en Italiano | MEDLINE | ID: mdl-34169693

RESUMEN

Proteinuria is a well-known marker of renal damage and, at the same time, an important factor in the progression of chronic kidney disease itself. The scientific community has always sought to investigate and provide answers on how nutritional therapy can influence and modify proteinuria and therefore limit its impact on progression to end-stage renal disease. However, despite the importance of the topic, the studies rarely take the form of randomized and controlled trials; in any case, they are often limited to protein intake only, conducted on very heterogeneous populations and, finally, they rarely indicate the precise values of proteinuria. The aim of this work is to explore the different nutritional approaches and their implications in the pathological conditions associated with proteinuria.


Asunto(s)
Fallo Renal Crónico , Insuficiencia Renal Crónica , Biomarcadores , Progresión de la Enfermedad , Humanos , Riñón , Proteinuria/etiología , Proteinuria/terapia , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia
11.
G Ital Nefrol ; 37(6)2020 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-33295709

RESUMEN

Background: Distal arterio-venous fistula (AVF) is considered the gold standard for vascular access in hemodialysis. The aim of this retrospective study is to report our experience on two innovative techniques, Intraoperative Transluminal Angioplasty (ITA) and Vessel Pre-Dilatation (VPD). Methods: We collected data from all the consecutive patients directly admitted to our Department from January 2014 to October 2018 in order to create or repair an AVF. Early Failure (EF), Failure to Mature (FTM), Late Failure (LF), Primary and Secondary patency rate were evaluated. Results: All patients underwent VPD; of the total 647 AFVs, 128 received an ITA for the presence of suboptimal vessels. 98.3% of AVFs were located on the forearm. EF occurred in 83 cases; in 67 of these a new AVF was successfully created upstream from the previous one. LF occurred in 100 cases; of these, the access was abandoned in 32 cases and we performed a new AVF upstream from the previous one in 68 cases. FTM occurred in 57 cases, 31 of which were treated with Percutaneous Transluminal Angioplasty (PTA) whilst 26 were resolved performing a new anastomosis upstream. Primary and secondary patency at 1, 2, 3 and 4 years were, respectively, 80%, 74%, 68%, 64% and 94%, 91%, 89%, 88%. By dividing patients into an ITA group and a control group, we did not find any difference in primary and secondary patency. Conclusions: VPD and ITA could be useful to increase the incidence and the prevalence of distal AVF.


Asunto(s)
Derivación Arteriovenosa Quirúrgica , Diálisis Renal , Derivación Arteriovenosa Quirúrgica/métodos , Humanos , Estudios Retrospectivos
13.
G Ital Nefrol ; 35(5)2018 Sep.
Artículo en Italiano | MEDLINE | ID: mdl-30234233

RESUMEN

Fabry disease (also known as Anderson-Fabry disease, angiocheratoma corporis diffusum, diffuse angiocheratoma) is a rare tesaurismosis linked to the deficiency of the lysosomal enzyme alpha-galactosidase A, required for the physiological catabolism of glycosphingolipids. The related clinical signs show a multisystemic feature and define a degenerative and disabling pathology, whose approach requires a close multidisciplinary specialist collaboration. Currently, the renewed interest in the disease is aimed at the need to provide an early diagnosis, in order to early begin the enzyme replacement therapy and to slow down or avoid the establishment of irreparable organ damage. For this reason, the diagnostic suspicion becomes crucial and arises from the careful observation and research of the symptoms, together with the anamnesis and the overall clinical evaluation of the patient.


Asunto(s)
Enfermedad de Fabry/diagnóstico , Hemorragia Cerebral/etiología , Diagnóstico Precoz , Terapia de Reemplazo Enzimático , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/tratamiento farmacológico , Pruebas Genéticas , Humanos , Hipertrofia Ventricular Izquierda/etiología , Fallo Renal Crónico/etiología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Mutación Puntual , alfa-Galactosidasa/genética , alfa-Galactosidasa/uso terapéutico
14.
G Ital Nefrol ; 35(3)2018 May.
Artículo en Italiano | MEDLINE | ID: mdl-29786185

RESUMEN

We describe the case of a 74-year-old man admitted to our Nephrology Unit with nephrotic syndrome and mild kidney disease. A complete panel of laboratoristic and instrumental tests did not provide useful information for diagnosis. No specific signs or symptoms suggested the presence of AL amyloidosis. As a matter of fact, diagnosis was reached thanks to the hystopathologic examination of renal tissue and bone marrow, since the associated B-cell lymphoproliferative disorder had not revealed itself through serum and urine electrophoresis and immunofixation. This recent case provides the opportunity to review about the disease and to revaluate the renal biopsy as a first line exam in a clinical context where laboratoristic and instrumental tests offer us poor information.


Asunto(s)
Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/diagnóstico , Síndrome Nefrótico/etiología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia con Aguja , Médula Ósea/patología , Bortezomib/administración & dosificación , Dexametasona/administración & dosificación , Errores Diagnósticos , Insuficiencia Cardíaca Diastólica/complicaciones , Humanos , Biopsia Guiada por Imagen , Cadenas Ligeras de Inmunoglobulina/análisis , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/complicaciones , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/tratamiento farmacológico , Amiloidosis de Cadenas Ligeras de las Inmunoglobulinas/patología , Riñón/patología , Glomérulos Renales/química , Glomérulos Renales/patología , Masculino , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Células Plasmáticas/química , Células Plasmáticas/patología
15.
Mol Immunol ; 71: 131-142, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26895476

RESUMEN

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of chronic nephropathy recently reclassified into immunoglobulin-associated MPGN (Ig-MPGN) and C3 glomerulopathy (C3G). In this study we aimed: (1) to evaluate the complement genetic and biochemical profile in patients with Ig-MPGN/C3G; (2) to investigate whether genetic variants and different patterns of complement activation (i.e., fluid versus solid phase) correlate with disease manifestations and outcomes. METHODS: In 140 patients with idiopathic Ig-MPGN or C3G we performed complement biochemical and genetic screening and correlated genetic, biochemical and histology data with clinical features. RESULTS: Mutations in genes encoding alternative pathway complement proteins were found in both Ig-MPGN and C3G, and mutations in the two components of the C3 convertase are the most prevalent. We also report a mutation in THBD encoding thrombomodulin in a C3G patient. The presence of mutations alone does not significantly increase the risk of Ig-MPGN or C3G, but it does so when combined with common susceptibility variants (CD46 c.-366A in Ig-MPGN; CFH V62 and THBD A473 in C3G). Finally, patients without complement gene mutations or C3NeFs--autoantibodies that stabilize the alternative pathway C3 convertase--have a higher risk of progressing to end-stage renal disease than patients with identified mutations and/or C3NeFs, suggesting the existence of different pathogenetic mechanisms that lead to renal disease. CONCLUSIONS: We provide new insights into the pathogenesis of Ig-MPGN/C3G that underscore the complex nature of these diseases and suggest that the current C3G classification may miss many cases associated with abnormalities of the complement alternative pathway.


Asunto(s)
Vía Alternativa del Complemento/genética , Variación Genética , Glomerulonefritis Membranoproliferativa/clasificación , Glomerulonefritis Membranoproliferativa/genética , Trombomodulina/genética , Adolescente , Factor Nefrítico del Complemento 3/genética , Femenino , Técnica del Anticuerpo Fluorescente , Predisposición Genética a la Enfermedad , Glomerulonefritis Membranoproliferativa/patología , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Inmunoglobulinas , Fallo Renal Crónico/etiología , Masculino , Reacción en Cadena de la Polimerasa Multiplex , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Adulto Joven
16.
J Pathol ; 237(1): 72-84, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25925804

RESUMEN

Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss. To uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of peripheral blood mononuclear cells (PBMCs) and, separately, of CD4(+) T lymphocytes isolated from CAMR patients, compared to kidney transplant recipients with normal graft function and histology. We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls), and 8 transplant recipients with clinical and histological evidence of interstitial fibrosis/tubular atrophy. Messenger RNA and microRNA profiling of PBMCs and CD4(+) T lymphocytes was performed using Agilent microarrays in eight randomly selected patients per group from CAMR and control subjects. Results were evaluated statistically and by functional pathway analysis (Ingenuity Pathway Analysis) and validated in the remaining subjects. In PBMCs, 45 genes were differentially expressed between the two groups, most of which were up-regulated in CAMR and were involved in type I interferon signalling. In the same patients, 16 microRNAs were down-regulated in CAMR subjects compared to controls: four were predicted modulators of six mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signalling. To further confirm this result, we investigated the transcriptomic profiles of CD4(+) T lymphocytes in an independent group of patients, observing that the activation of type I interferon signalling was a specific hallmark of CAMR. In addition, in CAMR patients, we detected a reduction of circulating BDCA2(+) dendritic cells, the natural type I interferon-producing cells, and their recruitment into the graft along with increased expression of MXA, a type I interferon-induced protein, at the tubulointerstitial and vascular level. Finally, interferon alpha mRNA expression was significantly increased in CAMR compared to control biopsies. We conclude that type I interferon signalling may represent the molecular signature of CAMR.


Asunto(s)
Rechazo de Injerto/inmunología , Interferón Tipo I/inmunología , Trasplante de Riñón/efectos adversos , Riñón/inmunología , Riñón/cirugía , Leucocitos Mononucleares/inmunología , Adulto , Anciano , Biomarcadores/metabolismo , Biopsia , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Estudios de Casos y Controles , Enfermedad Crónica , Femenino , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica , Redes Reguladoras de Genes , Estudios de Asociación Genética , Rechazo de Injerto/sangre , Rechazo de Injerto/genética , Humanos , Interferón Tipo I/genética , Interferón Tipo I/metabolismo , Riñón/metabolismo , Riñón/patología , Leucocitos Mononucleares/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/metabolismo , Transducción de Señal , Transcripción Genética , Transcriptoma , Resultado del Tratamiento
17.
Curr Pharm Des ; 21(13): 1672-89, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25633118

RESUMEN

The treatment of older and oldest old patients with COPD poses several problems and should be tailored to specific outcomes, such as physical functioning. Indeed, impaired homeostatic mechanisms, deteriorated physiological systems, and limited functional reserve mainly contribute to this complex scenario. Therefore, we reviewed the main difficulties in managing therapy for these patients and possible remedies. Inhaled long acting betaagonists (LABA) and anticholinergics (LAMA) are the mainstay of therapy in stable COPD, but it should be considered that pharmacological response and safety profile may vary significantly in older patients with multimorbidity. Their association with inhaled corticosteroids is recommended only for patients with severe or very severe airflow limitation or with frequent exacerbations despite bronchodilator treatment. In hypoxemic patients, long-term oxygen therapy (LTOT) may improve not only general comfort and exercise tolerance, but also cognitive functions and sleep. Nonpharmacological interventions, including education, physical exercise, nutritional support, pulmonary rehabilitation and telemonitoring can importantly contribute to improve outcomes. Older patients with COPD should be systematically evaluated for the presence of risk factors for non-adherence, and the inhaler device should be chosen very carefully. Comorbidities, such as cardiovascular diseases, chronic kidney disease, osteoporosis, obesity, cognitive, visual and auditory impairment, may significantly affect treatment choices and should be scrutinized. Palliative care is of paramount importance in end-stage COPD. Finally, treatment of COPD exacerbations has been also reviewed. Therapeutic decisions should be founded on a careful assessment of cognitive and functional status, comorbidity, polypharmacy, and agerelated changes in pharmacokinetics and pharmacodynamics in order to minimize adverse drug events, drug-drug or drug-disease interactions, and non-adherence to treatment.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Factores de Edad , Anciano de 80 o más Años , Humanos
18.
Arch Ital Biol ; 153(2-3): 204-13, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26742674

RESUMEN

Menopause in the female life cycle is a special period due to important hormonal, physical and psychological changes. Sleep disruption represents a common complaint for midlife and menopausal women, related to primary sleep disorders, including insomnia, sleep disordered breathing, restless legs syndrome (RLS), mood and anxiety disorder, other medical illness, hormonal-related vasomotor symptoms, and aging per se. Aims of our study were to evaluate the prevalence of sleep disorders in a sample of pre and post menopausal women, and to investigate the relationship between sleep and other medical disorders, and life habits. Among workers in the six participant centers, we enrolled 334 women, aged between 40 and 60 years, that completed a questionnaire that included screening on menarche, menstrual cycle, fertility, parity, menopause, life habits, personal medical and sleep history and related treatment, and self-administered scales for sleep quality (PSQI), excessive daytime sleepiness [Epworth Sleepiness Scale (ESS)], mood disorder [Beck Depression Inventory (BDI)], Berlin Questionnaire for sleep disordered breathing (SDB), IRLS diagnostic interview and Rating Scale. Menopausal and perimenopausal women showed an increased prevalence of poor sleep, high risk of SDB, and mood disorder; menopausal women also reported increased RLS severity. Mood disorder had a significant impact on night sleep measures and excessive daytime sleepiness, as well as on RLS severity, and had a greater prevalence in hypertensive women. Sleep disturbances are frequent in menopausal women. Their aetiology is unclear, but probably multifactorial, and many factors contribute to the sleep disruption. Our data suggest the importance of correctly investigate and address sleep problems associated with menopause, through sleep history, and a sleep study could be obtained if clinically warranted. Pharmacological and behavioural treatment strategies should then be aimed at improving sleep and life quality in perimenopausal and menopausal women.


Asunto(s)
Menopausia , Trastornos del Sueño-Vigilia/epidemiología , Adulto , Femenino , Humanos , Persona de Mediana Edad
20.
J Med Screen ; 20(4): 220-6, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24174512

RESUMEN

BACKGROUND: Polysomnography remains the diagnostic gold standard for obstructive sleep apnea syndrome (OSAS), but it is time consuming and requires dedicated personnel and setting. It may be more useful to plan a polysomnogram based on a preliminary screening. OBJECTIVE: To verify whether a questionnaire of general quality of sleep, the Pittsburgh Sleep Quality Index (PSQI), could outperform a dedicated questionnaire (Epworth Sleep Scale: ESS) in targeting OSAS patients in an at risk population. METHODS: 254 consecutive subjects attending the outpatient clinic for respiratory diseases were clinically evaluated for sleep apnea and referred to a 12 channel night-time polysomnography. All patients were administered the ESS and the PSQI before the procedure. The correlation between the Apnoea/Hypopnoea Index (AHI) and the global score of the PSQI was calculated; Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), Diagnostic accuracy and the area under the receiver operating characteristic curve (AUC) were calculated. ESS performance was used as a control reference. RESULTS: The mean age was 65.8 (standard deviation: 12.1) and the study group was 68.4% male. The mean BMI was 38.5; SD 7.7. Prevalence of OSAS in the study population was 55.5%; OSAS was severe in 60.5% of OSAS patients. ESS was significantly, but weakly, correlated with the AHI (AHI vs ESS: R = 0.308; p < 0.001), whereas PSQI was not (R = 0.037; p = 0.581). Both PSQI and ESS, however, performed unsatisfactorily: sensitivity 37.8% and 69.7%; Specificity 76.1% and 31.0%; Diagnostic Accuracy 57.5% and 49.8%; PPV 60% and 48.7%; NPV 56.3% and 52.2%; AUC 0.589 and 0.509, respectively. CONCLUSIONS: The PSQI score is not helpful in the pre-polysomnographic assessment of people with suspected OSAS. Further studies are required to provide reliable pre-clinical instruments targeting patients amenable to polysomnography.


Asunto(s)
Polisomnografía/estadística & datos numéricos , Apnea Obstructiva del Sueño/diagnóstico , Encuestas y Cuestionarios , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
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