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Background: The rate of inpatient mastectomies remains high despite multiple studies reporting favourably on outpatient mastectomies. Outpatient mastectomies do not compromise quality of patient care and are more efficient than inpatient care. The objective of this study was to evaluate the feasibility of outpatient mastectomy. Materials and Methods: Implementation of an outpatient mastectomy program was evaluated in a retrospective study. All patients who underwent mastectomy between January 2019 and September 2021 were included. Results: 213 patients were enrolled in the study: 62.4% (n = 133) outpatient mastectomies versus 37.6% (n = 80) inpatient mastectomies. A steady rise in outpatient mastectomies was observed over time. The second quarter of 2020, coinciding with the first COVID-19 wave, showed a peak in outpatient mastectomies. The only significant barrier to outpatient mastectomy proved to be bilateral mastectomy. Unplanned return to care was observed in 27.8% of the outpatient versus 36.3% of the inpatient mastectomies (P=0.198); the reason for unplanned return of care was similar in both groups. Conclusions: Outpatient mastectomy is shown to be feasible and safe with a steady increase during the study period. A barrier to outpatient mastectomy was bilateral mastectomy. Incidence of unplanned return to care or complications did not differ significantly between the outpatient and inpatient cohorts.
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Neoplasias de la Mama , COVID-19 , Neoplasias de la Mama/cirugía , Femenino , Humanos , Mastectomía , Pacientes Ambulatorios , Estudios RetrospectivosRESUMEN
OBJECTIVES: To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. METHODS: In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10â years. RESULTS: 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10â years was 90.7%. CONCLUSIONS: Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
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Síndrome Antifosfolípido/mortalidad , Lupus Eritematoso Sistémico/mortalidad , Trombosis/mortalidad , Aborto Espontáneo/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/epidemiología , Niño , Preescolar , Estudios de Cohortes , Epilepsia/etiología , Femenino , Retardo del Crecimiento Fetal/epidemiología , Humanos , Lactante , Recién Nacido , Infecciones/etiología , Infecciones/mortalidad , Ataque Isquémico Transitorio/etiología , Livedo Reticularis/etiología , Estudios Longitudinales , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Embarazo , Resultado del Embarazo/epidemiología , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Embolia Pulmonar/etiología , Embolia Pulmonar/mortalidad , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Trombocitopenia/etiología , Trombosis/etiología , Trombosis de la Vena/etiología , Trombosis de la Vena/mortalidad , Adulto JovenRESUMEN
BACKGROUND: Infections are important denominators of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Pneumococcus pneumoniae has been identified as a relatively frequent cause of serious infections in SLE and vaccination against this pathogen is possible. We analysed the incidence of serious infections in a cohort of SLE patients, focussing on Streptococcus pneumoniae. METHODS: We retrospectively screened the medical records of all SLE patients who were regularly seen in the outpatient clinic of our department between January 2010 and December 2012. We registered all infections that necessitated admission to the hospital (serious infection) and compared relevant clinical and laboratory parameters and immunomodulating/immunosuppressive treatment in patients with and without serious infections. RESULTS: In the total cohort of 260 patients, there were 132 episodes of serious infection in 70 patients, with a median follow-up per patient of 11.4 years (range 0 to 50.2 years). S. pneumoniae accounted for 11/132 (8.3%) serious infection episodes and eight of 11 episodes were invasive. With a follow-up of 3970.6 years for the total cohort, this leads to an incidence of 201/100.000 patient-years. In the multivariate analysis neither clinical parameters nor use of immunosuppressive drugs correlated with occurrence of serious infections. CONCLUSIONS: Compared to the incidence of invasive pneumococcal infections in the Dutch population (15.6/100.000 patient years), the incidence in SLE patients is 13 times higher. This, in combination with the absence of a relation to use of immunosuppressive drugs, is a strong argument to recommend vaccination against S. pneumoniae in all SLE patients.
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Infecciones por Escherichia coli/epidemiología , Infecciones/epidemiología , Lupus Eritematoso Sistémico/epidemiología , Neumonía Neumocócica/epidemiología , Infecciones Estafilocócicas/epidemiología , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Inmunosupresores/uso terapéutico , Incidencia , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Países Bajos/epidemiología , Estudios Retrospectivos , Staphylococcus aureus , Adulto JovenRESUMEN
Fungicides are most warranted for control of Fusarium head blight (FHB), a disease of wheat caused by the fungal pathogen Fusarium graminearum, when wet, rainy conditions occur during anthesis. However, it is unclear whether rainfall directly following application affects fungicide efficacy against FHB and its associated toxin, deoxynivalenol (DON). The objective of this study was to determine the rainfastness of the fungicide tebuconazole + prothioconazole and the residual life of tebuconazole when applied to wheat spikes at anthesis in combination with the nonionic surfactant Induce. Three field experiments were conducted during 2012 and 2013 in Wooster, OH. Simulated rainfall of a fixed intensity and duration was applied to separate plots at five different times after the fungicide treatment (0, 60, 105, 150, or 195 min). Spike samples were collected at 4-day intervals after fungicide application and assayed for tebuconazole residue. A similar set of greenhouse experiments was conducted using six post-fungicide-application rainfall timing treatments (0, 15, 30, 60, 120, or 180 min). All experiments were inoculated at anthesis with spores of F. graminearum, and FHB index (IND) and DON were quantified. In four of the five experiments, all fungicide-treated experimental units (EUs) had significantly lower mean IND and DON than the untreated check, regardless of rainfall treatment. Among rainfall treatments, EUs that received the earliest rains after fungicide application tended to have the highest numerical mean IND and DON, but were generally not significantly different from EUs that received later rain or fungicide without rain. In both years, fungicide residue on wheat spikes decreased rapidly with time after application, but the rate of reduction varied somewhat between years, with a half-life of 6 to 9 days. Rainfall treatment did not have a significant effect on the rate of residue reduction or the level of residue at a fixed sampling time after fungicide application. In this study, tebuconazole + prothioconazole mixed with a nonionic surfactant was fairly rainfast for a fixed set of rainfall characteristics, and tebuconazole residue did not persist very long after application on wheat spikes.
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Servicio de Urgencia en Hospital , Fracturas Óseas/diagnóstico , Observación , Radiografía , Luxación del Hombro/diagnóstico , Lesiones del Hombro/diagnóstico , Procedimientos Innecesarios , Adulto , Análisis Costo-Beneficio , Estudios Transversales , Técnicas de Apoyo para la Decisión , Servicio de Urgencia en Hospital/economía , Humanos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radiografía/economía , Procedimientos Innecesarios/economía , Adulto JovenRESUMEN
The antiphospholipid syndrome (APS) is diagnosed when patients with thrombotic complications or foetal losses have elevated levels of antiphospholipid antibodies in their plasmas. The term APS is confusing, because the pathogenic auto-antibodies are not directed against phospholipids but towards a plasma protein, ß(2)-glycoprotein I. For many years the reason why auto-antibodies against ß(2)-glycoprotein I were pro-thrombotic was unclear, because man and mice deficient in ß(2)-glycoprotein I do not express a clear phenotype. Animal models in which passive transfer of patient antibodies into mice resulted in an increased thrombotic response have provided novel insights in the importance of this protein in the pathology of APS.
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Síndrome Antifosfolípido/fisiopatología , Trombosis/inmunología , Animales , Humanos , Trombosis/fisiopatología , beta 2 Glicoproteína I/inmunologíaRESUMEN
Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p ≤ 0.001) than healthy women and more often had below-normal DHEAS levels (p < 0.001). Patients using prednisone with low and normal DHEAS levels reported a similar level of fatigue (p ≥ 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (p ≤ 0.03). Thus, our results indicate that low DHEAS levels in SLE are not - or even inversely - related to fatigue. After our previous finding that DHEA administration does not reduce fatigue, this result further indicates that low serum DHEA(S) levels alone do not offer an explanation for SLE fatigue.
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Sulfato de Deshidroepiandrosterona/sangre , Fatiga/etiología , Lupus Eritematoso Sistémico/fisiopatología , Prednisona/uso terapéutico , Adulto , Anciano , Estudios de Casos y Controles , Fatiga/epidemiología , Femenino , Glucocorticoides/uso terapéutico , Humanos , Mediciones Luminiscentes , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , Persona de Mediana Edad , Psicometría , Adulto JovenRESUMEN
OBJECTIVE: Interaction of advanced glycation end products (AGEs) with their receptors (RAGE) plays an important role in inflammation in auto-immune diseases. Several functional polymorphisms of RAGE have been described. In this study we analysed the role of RAGE polymorphisms in disease susceptibility for systemic lupus erythematosus (SLE). In addition, we investigated whether these polymorphisms in SLE are associated with serum levels of soluble RAGE (sRAGE), renal involvement (lupus nephritis (LN)) and its outcome. METHODS: For this cross-sectional study DNA samples of 97 SLE patients, 114 LN patients and 429 healthy controls (HC) were genotyped for four RAGE polymorphisms: -429 T/C, -374 T/A, 2184 A/G and Gly82Ser. Differences in genotype frequencies and allele frequencies were tested between patients and HCs. In SLE patients, sRAGE was measured by enzyme-linked immunosorbent assay (ELISA). In addition, association of genotypes with sRAGE and disease severity in LN was analysed. RESULTS: The C allele of -429 T/C, the T allele of -374 T/A and the G allele of 2184 A/G were significantly more prevalent in SLE and LN compared with HC. In LN, the C allele of RAGE -429 T/C, the A allele of -374 T/A and the G allele of RAGE 2184 A/G polymorphism were significantly associated with more proteinuria and worse renal function during the first two years of treatment. No association of genotype with sRAGE was found. CONCLUSION: RAGE polymorphisms are associated with susceptibility to SLE and LN. In addition, some of these polymorphisms are likely to be associated with disease severity and initial response to treatment in LN.
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Lupus Eritematoso Sistémico/genética , Nefritis Lúpica/genética , Polimorfismo Genético , Receptores Inmunológicos/genética , Adulto , Anciano , Estudios Transversales , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Receptor para Productos Finales de Glicación AvanzadaRESUMEN
BACKGROUND: Recent guidelines on obesity management promote integrated care. There is little knowledge about local opportunities and barriers, faced by health care professionals and patients, that affect implementation of an integrated national health care standard in a local setting. Our aim is to understand experiences and expectations of health care professionals and patients as part of the local implementation process. METHODS: Eight focus groups and two interviews have been conducted among 24 patients (60+) and 29 professionals from seven different care disciplines. RESULTS: Both patients and professionals have identified serious barriers to implement the national standard: older adults do not feel taken seriously and experience lacking support from professionals. Professionals give contradictory advice and recommendations do not match needs of older adults. Professionals actually feel reluctant to discuss weight-related topics due to several reasons: they do not consider obesity being a chronic disease, lack of qualifications to support self-management and perceived lack of awareness and motivation among patients. CONCLUSION: Focus groups have proven their value to ascertain the opportunities and barriers older adults and professionals foresee while improving obesity care in order to meet the standards as required in a national guideline. Our research provides an emerging picture of health care professionals and patients having contradictory views and expectations about 'the others' role and their notions on the capability to intervene on patient's weight problems. Without this emerging picture, we would have missed important information on barriers to overcome. The likelihood of successful implementation would then have been small.
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Consenso , Grupos Focales , Obesidad/prevención & control , Atención Primaria de Salud/normas , Adulto , Femenino , Humanos , Masculino , Investigación CualitativaRESUMEN
A 35-year old healthy male trauma surgery chief resident, suffered a high-speed motor vehicle collision. The patient sustained the following injuries: a Gustilo-Anderson grade 2 open comminuted intra-articular fracture of the left distal femur (AO 33C3.3), a Hawkins 1A neck fracture of the right talus (AO 81.2A), an undisplaced Lisfranc injury of the right foot comprising avulsion fractures at the base of the 1st, 2nd and 5th metatarsal as well as the cuboid bone suggesting ligament injury and 2nd to 5th carpometacarpal dislocations of the right (non-dominant) hand with comminuted fractures of the capitate, hamate, trapezoid and the base of the fifth metacarpal bone. A staged-treatment approach ensued. An external fixator (ex-fix) was placed over the left knee, followed by definitive fixation of the distal femoral fracture using a Qwix screw, Non-Contact Bridging (NCB) plate and Locking Compression Plate (LCP). An ex-fix was placed over the right wrist, followed by open reduction and k-wire fixation. The talar fracture of the right foot was treated with a single lag screw and the Lisfranc injury was treated non-operatively with four weeks of non-weight bearing cast immobilization. An intensive clinical rehabilitation program was started, including early use of Continuous Passive Motion (CPM), daily non-weightbearing swimming pool exercises, hand, physical and recreational therapy. One year after the injury the patient was rehabilitated and resumed his surgical residency. Two years after the injury, limited flexion and pain in the left leg remains, possibly related to partial union of the femoral fracture. Range of motion (ROM) of the right ankle and wrist remains limited, not causing significant functional impairment. Lessons learned from a patient experience combined with detailed descriptions of injuries, rehabilitation and long term outcomes can be used as a reference for treating patients with comparable injuries.
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PURPOSE: The second-generation multi-electrode catheter, PVAC Gold, was designed to improve the safe delivery of phased radiofrequency energy using a "single shot" approach for pulmonary vein isolation (PVI), while retaining efficacy. This large registry presents long-term performance in a daily practice setting. METHODS: A total of 1011 patients undergoing first time ablation for atrial fibrillation (AF) using PVAC Gold were included, 639 patients with PVI for paroxysmal AF (PAF PVI) and 372 patients with persistent or long-standing persistent AF, divided into 175 patients receiving PVI only (PersAF PVI) and 197 patients receiving PVI with additional substrate ablation (PersAF PVI +). RESULTS: At 24-month follow-up, single procedure freedom from atrial tachyarrhythmia (ATA) was 58% (368/639) in the PAF PVI group, 44% (77/175) in the PersAF PVI group, and 29% (57/197) in the PersAF PVI + group. Allowing one repeat procedure in 33% of patients, 76%, 65%, and 54% were free from ATA at 24 months, respectively. Pulmonary vein reconnection was observed in 98% of patients with recurrent arrhythmia after PVI. CONCLUSIONS: Although phased RF ablation with PVAC Gold is quick and safe, the efficacy outcomes are modest compared to current mainstream ablation strategies.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Humanos , Fibrilación Atrial/cirugía , Oro , Estudios de Seguimiento , Resultado del Tratamiento , Ablación por Catéter/métodos , Venas Pulmonares/cirugía , Catéteres , RecurrenciaRESUMEN
[This corrects the article DOI: 10.1155/2017/2810202.].
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The Antiphospholipid Syndrome (APS) Clinical Research Task Force (CRTF) was one of six Task Forces developed by the 13(th) International Congress on Antiphospholipid Antibodies (aPL) organization committee with the purpose of: a) evaluating the limitations of APS clinical research and developing guidelines for researchers to help improve the quality of APS research; and b) prioritizing the ideas for a well-designed multicenter clinical trial and discussing the pragmatics of getting such a trial done. Following a systematic working algorithm, the Task Force identified five major issues that impede APS clinical research and the ability to develop evidence-based recommendations for the management of aPL-positive patients: (1) aPL detection has been based on partially or non-standardized tests, and clinical (and basic) APS research studies have included patients with heterogeneous aPL profiles with different clinical event risks; (2) clinical (and basic) APS research studies have included a heterogeneous group of patients with different aPL-related manifestations (some controversial); (3) thrombosis and/or pregnancy risk stratification and quantification are rarely incorporated in APS clinical research; (4) most APS clinical studies include patients with single positive aPL results and/or low-titer aPL ELISA results; furthermore, study designs are mostly retrospective and not population based, with limited number of prospective and/or controlled population studies; and (5) lack of the understanding the particular mechanisms of aPL-mediated clinical events limits the optimal clinical study design. The Task Force recommended that there is an urgent need for a truly international collaborative approach to design and conduct well-designed prospective large-scale multi-center clinical trials of patients with persistent and clinically significant aPL profiles. An international collaborative meeting to formulate a good research question using 'FINER' (Feasible; Interesting; Novel; Ethical; and Relevant) criteria took place in November 2010.
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Comités Consultivos , Síndrome Antifosfolípido , Investigación Biomédica , Anticuerpos Antifosfolípidos , Ensayos Clínicos como Asunto , Congresos como Asunto , Femenino , Humanos , EmbarazoRESUMEN
The antiphospholipid syndrome (APS) is defined by the presence of thrombosis and/or pregnancy morbidity in combination with the persistent presence of circulating antiphospholipid antibodies: lupus anticoagulant, anticardiolipin antibodies and/or anti-ß2-glycoprotein I antibodies in medium to high titers. The management of thrombosis in patients with APS is a subject of controversy. This set of recommendations is the result of an effort to produce guidelines for therapy within a group of specialist physicians in Cardiology, Neurology, Hematology, Rheumatology and Internal Medicine, with a clinical and research focus on APS.
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Anticuerpos Antifosfolípidos/sangre , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Trombosis/prevención & control , Trombosis/terapia , Comités Consultivos , Anticuerpos Antifosfolípidos/efectos adversos , Síndrome Antifosfolípido/complicaciones , Ensayos Clínicos como Asunto , Congresos como Asunto , Femenino , Humanos , Embarazo , Texas , Trombosis/sangre , Trombosis/etiologíaRESUMEN
OBJECTIVES: The aim of this study was to compare serum dehydroepiandrosterone sulphate (DHEAS) levels and clinical and laboratory parameters reflecting expression of disease between female patients with primary Sjögren's syndrome (pSS) and age-matched healthy women and to examine in pSS patients the correlation of these variables with fatigue, well-being, and functioning. METHODS: Comparisons were made between 60 female pSS patients and 60 age-matched healthy women. We assessed questionnaire scores of general fatigue, depressed mood, mental wellbeing, and physical functioning, tear production (Schirmer I test), tender point counts, serum DHEAS level, haemoglobin concentration, erythrocyte sedimentation rate, and serum immunoglobulin G. RESULTS: As compared to healthy participants, patients had more fatigue and depressed mood, reduced well-being and functioning, more dryness and pain, lower serum DHEAS levels, and more expression of disease as reflected by laboratory assessments (p≤0.001). In pSS patients, fatigue, well-being, and functioning correlated with tender point counts, but not with the extent of dryness and also not with laboratory assessments including serum DHEAS levels. CONCLUSIONS: The high prevalence of fatigue and reduced functioning in pSS patients might suggest a mediating role of generalised autoimmune processes. In the present study, clinical observations and laboratory assessments are not correlated with persistent fatigue and reduced functioning. Our results suggest that treatment of fatigue, well-being, and functioning, should target other variables than those examined in this study, preferably psychological variables or perhaps specific immunologic parameters.
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Sulfato de Deshidroepiandrosterona/sangre , Fatiga/inmunología , Fatiga/metabolismo , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/metabolismo , Actividades Cotidianas , Adulto , Anciano , Biomarcadores/sangre , Evaluación de la Discapacidad , Fatiga/epidemiología , Femenino , Estado de Salud , Humanos , Persona de Mediana Edad , Prevalencia , Síndrome de Sjögren/epidemiología , Adulto JovenRESUMEN
PURPOSE: The second-generation multi-electrode catheter, pulmonary vein ablation catheter (PVAC) GOLD, was designed to improve the delivery of phased radiofrequency energy and reduce procedure times using a 'single-shot' approach for pulmonary vein isolation (PVI), while retaining efficacy and safety. This large registry presents acute success rates and safety outcomes in a daily practice setting. METHODS: A total of 1017 patients undergoing first-time ablation for atrial fibrillation (AF) using PVAC GOLD were included, 644 patients with paroxysmal AF and 373 patients with non-paroxysmal AF, divided into 175 patients receiving PVI only and 198 patients receiving PVI with additional substrate modification. RESULTS: High and comparable percentages of successful PVI could be achieved in all groups (98%, 95% and 99%; p = 0.108). The median total procedure time for all groups was 90 min [70-100]. As expected, the total procedure, ablation and fluoroscopy time were significantly longer in the PVI + substrate modification group compared with the PVI-only cases (all p < 0.001), but not between the PVI-only groups (p = 0.306, p = 0.088, p = 0.233, respectively). A total of 44 complications were observed in 43 patients (4.2%). Major complications were seen in 19 patients (1.87%) and non-major procedure-related complications were seen in 25 patients (2.46%). Complications leaving permanent sequelae were rare and occurred in only four patients (0.39%). Complications did not differ between groups (p = 0.199, p = 0.438, p = 0.240 and p = 0.465 respectively). CONCLUSION: PVAC GOLD performs successful PVI, while reducing procedure times and retaining safety for paroxysmal, persistent and long-standing persistent AF. Safety was unaffected by additional substrate modification.
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Fibrilación Atrial , Ablación por Catéter , Venas Pulmonares , Fibrilación Atrial/cirugía , Catéteres , Humanos , Venas Pulmonares/diagnóstico por imagen , Venas Pulmonares/cirugía , Resultado del TratamientoRESUMEN
The processes that govern the generation of pathogenic anti-DNA autoantibodies in human systemic lupus erythematosus (SLE) are largely unknown. Autoantibodies may arise as a consequence of polyclonal B cell activation and/or antigen-driven B cell activation and selection. The role of these processes in humoral autoimmunity may be studied by molecular genetic analysis of immunoglobulin (Ig) variable (V) regions of antibodies that are characteristic of SLE. We have analyzed the gene elements that encode a high affinity, IgG anti-double-stranded DNA autoantibody secreted by a monoclonal Epstein-Barr virus (EBV)-transformed cell line derived from a patient with active SLE. In addition, we have identified, cloned, and sequenced the germline counterparts of the VH and VL genes expressed in this autoantibody. The comparison of both sets of gene elements shows that the autoantibody VH and VL regions harbor numerous somatic mutations characteristic of an antigen-driven immune response. The light chain expressed in this autoantibody is a somatically mutated variant of the kv325 germline gene that is frequently associated with paraproteins having autoantibody activity and with Ig molecules produced by malignant B cells that express the CD5 antigen. Furthermore, the utilized DH segment has been repeatedly found in multireactive, low affinity IgM anti-DNA autoantibodies from SLE patients and healthy individuals. These results suggest that pathogenic IgG anti-DNA autoantibodies in human SLE may arise through antigen-driven selection of somatic mutations in the gene elements that frequently encode multireactive IgM autoantibodies.
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Anticuerpos Antinucleares/genética , ADN/inmunología , Inmunoglobulina G/genética , Región Variable de Inmunoglobulina/genética , Lupus Eritematoso Sistémico/inmunología , Secuencia de Aminoácidos , Anticuerpos Antinucleares/inmunología , Anticuerpos Antinucleares/metabolismo , Anticuerpos Monoclonales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Secuencia de Bases , Línea Celular Transformada , Humanos , Inmunoglobulina G/inmunología , Cadenas Pesadas de Inmunoglobulina/genética , Idiotipos de Inmunoglobulinas/inmunología , Cadenas Ligeras de Inmunoglobulina/genética , Lupus Eritematoso Sistémico/genética , Datos de Secuencia Molecular , Mutación , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos B/inmunologíaRESUMEN
OBJECTIVE: Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. METHODS: In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. RESULTS: Patients from the DHEA and placebo group improved on general fatigue (p<0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04). CONCLUSIONS: The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE. Clinical Trials Registration Number NCT00391924.
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Deshidroepiandrosterona/uso terapéutico , Fatiga/tratamiento farmacológico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Anciano , Deshidroepiandrosterona/sangre , Depresión/tratamiento farmacológico , Depresión/etiología , Método Doble Ciego , Fatiga/sangre , Fatiga/etiología , Femenino , Estudios de Seguimiento , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/psicología , Persona de Mediana Edad , Testosterona/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
Thrombosis in the presence of persistently positive tests for antiphospholipid antibodies is termed thrombotic antiphospholipid syndrome (APS). At present, 'standard' secondary thromboprophylaxis in thrombotic APS is treatment with moderate intensity oral anticoagulants for life after a first venous thrombosis and with high intensity oral anticoagulation after non-embolic ischaemic stroke. These recommendations differ from those applied in the general population, where a restricted period of anticoagulation is common practice after venous thrombosis and antiplatelet drugs are the first choice after ischaemic stroke. From an extensive literature review we conclude that the available data are insufficient to apply a different strategy for secondary thromboprophylaxis in patients with thrombotic APS than the one that holds for the general population.
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Anticoagulantes/uso terapéutico , Síndrome Antifosfolípido/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Anticuerpos Antifosfolípidos/inmunología , Anticoagulantes/administración & dosificación , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/inmunología , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/etiología , Isquemia Encefálica/inmunología , Relación Dosis-Respuesta a Droga , Medicina Basada en la Evidencia , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Factores de Riesgo , Prevención Secundaria/métodos , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/inmunología , Trombosis/etiología , Trombosis/inmunologíaRESUMEN
One of the greatest enigmas in thrombosis research is the observation that one can diagnose a person with a thrombotic risk with a prolongation of the clotting time. Our textbooks have taught us that prolongation of clotting correlates with a tendency to bleed. To confuse our textbook knowledge further, the same patients often have a prolonged bleeding time, a diagnostic test to detect a dysfunction in primary haemostasis. In this paper we critically review the literature that tries to explain the contradiction that exists between in-vitro diagnostic tests and the observed clinical manifestations and discuss our current opinion on how antiphospholipid antibodies can disturb the haemostatic balance.