Multifocal calcific periarthritis with distinctive clinical and radiological features in patients with CD73 deficiency.

OBJECTIVES: Arterial calcification due to deficiency of CD73 (ACDC) is a hereditary autosomal recessive ectopic mineralization syndrome caused by loss-of-function mutations in the ecto-5'-nucleotidase gene. Periarticular calcification has been reported but the clinical characterization of arthritis as well as the microstructure and chemical composition of periarticular calcifications and SF crystals has not been systematically investigated. METHODS: Eight ACDC patients underwent extensive rheumatological and radiological evaluation over a period of 11 years. Periarticular and synovial biopsies were obtained from four patients. Characterization of crystal composition was evaluated by compensated polarized light microscopy, Alizarin Red staining for synovial fluid along with X-ray diffraction and X-ray micro tomosynthesis scanner for periarticular calcification. RESULTS: Arthritis in ACDC patients has a clinical presentation of mixed erosive-degenerative joint changes with a median onset of articular symptoms at 17 years of age and progresses over time to the development of fixed deformities and functional limitations of small peripheral joints with, eventually, larger joint and distinct axial involvement later in life. We have identified calcium pyrophosphate and calcium hydroxyapatite (CHA) crystals in SF specimens and determined that CHA crystals are the principal component of periarticular calcifications. CONCLUSION: This is the largest study in ACDC patients to describe erosive peripheral arthropathy and axial enthesopathic calcifications over a period of 11 years and the first to identify the composition of periarticular calcifications and SF crystals. ACDC should be considered among the genetic causes of early-onset OA, as musculoskeletal disease signs may often precede vascular symptoms.

Pharmacotherapy Pearls in Rheumatology for the Care of Older Adult Patients: Focus on Oral Disease-Modifying Antirheumatic Drugs and the Newest Small Molecule Inhibitors.

Providing safe and effective pharmacotherapy to geriatric patients with rheumatologic disorders is challenging. Multidisciplinary care involving rheumatologists, primary care physicians, and other specialties can optimize benefit and reduce adverse outcomes. Oral disease-modifying antirheumatic drugs, including methotrexate, hydroxychloroquine, sulfasalazine, and leflunomide, and the small molecule inhibitors tofacitinib and apremilast have distinctive monitoring requirements and specific adverse reaction profiles. This article provides clinically relevant pearls for use of these interventions in older patients.

Pulmonary aspergillosis presenting with recurrent haemoptysis.

Pulmonary aspergillosis presents with a variety of clinical forms including invasive pulmonary aspergillosis, chronic necrotising aspergillosis, aspergilloma, chronic cavitary pulmonary aspergillosis and allergic bronchopulmonary aspergillosis. Haemoptysis is a devastating complication of pulmonary aspergillosis and a common indication for surgery. We report a case of a 54-year-old man with a history of pulmonary tuberculosis and diabetes mellitus, who presented with productive cough and haemoptysis for 2 months. Chest CT revealed a 30 mm diameter soft tissue mass in the upper lobe of the right lung. Haemoptysis subsided with conservative measures, but 2 weeks later the patient developed a new episode of persistent haemoptysis, which was only partially controlled with bronchial arterial embolisation. He underwent right upper and middle lobectomy. Histology examination confirmed the presence of a fungal cavitary lesion. The patient was started on voriconazole, and recovered with no recurrence at 18 months follow-up.

Intralesional administration of epidermal growth factor-based formulation (Heberprot-P) in chronic diabetic foot ulcer: treatment up to complete wound closure.

Previous studies have shown that an epidermal growth factor-based formulation (Heberprot-P) can enhance granulation of high-grade diabetic foot ulcers (DFU). The aim of this study was to explore the clinical effects of this administration up to complete wound closure. A pilot study in 20 diabetic patients with full-thickness lower extremity ulcers of more than 4 weeks of evolution was performed. Mean ulcer size was 16.3 +/- 21.3 cm(2). Intralesional injections of 75 microg of Heberprot-P three times per week were given up to complete wound healing. Full granulation response was achieved in all 20 patients in 23.6 +/- 3.8 days. Complete wound closure was obtained in 17 (85%) cases in 44.3 +/- 8.9 days. Amputation was not necessary in any case and only one relapse was notified. The most frequent adverse events were tremors, chills, pain and odour at site of administration and local infection. The therapeutic scheme of intralesional Heberprot-P administration up to complete closure can be safe and suitable to improve the therapeutic goal in terms of healing of chronic DFU.

Intralesional injections of Citoprot-P (recombinant human epidermal growth factor) in advanced diabetic foot ulcers with risk of amputation.

To investigate the efficacy and safety of recombinant human epidermal growth factor (rhEGF) in advanced diabetic foot ulcers (DFU) A double-blind trial was carried out to test two rhEGF dose levels in type 1 or 2 diabetes patients with Wagner's grade 3 or 4 ulcers, with high risk of amputation. Subjects were randomised to receive 75 (group I) or 25 mug (group II) rhEGF through intralesional injections, three times per week for 5-8 weeks together with standardised good wound care. Endpoints were granulation tissue formation, complete healing and need of amputation. Safety was assessed by clinical adverse events (AEs) and laboratory evaluations. Forty-one patients were included. After 5-8 weeks of treatment, 83% patients in the higher dose group and 61% in group II achieved useful granulation tissue covering more than 98% of the wound area. At long-term assessment, 13 (56.5%) patients healed in group I and 9 (50%) in group II. The mean time to complete healing in group I was 20.6 weeks (95% CI: 17.0-24.2) and 19.5 weeks (16.3-22.7) in group II. After 1-year follow-up, only one patient relapsed. Amputation was not necessary in 65% and 66.7% of groups I and II, respectively. The AEs rates were similar. The most frequent were sepsis (33%), burning sensation (29%), tremors, chills and local pain (25% each). rhEGF local injection enhances advanced DFU healing and reduces the risk of major amputation. No dose dependency was observed.

Thrombolysis as first choice therapy in prosthetic heart valve thrombosis. A study of 68 patients.

BACKGROUND AND OBJECTIVES: Valvular thrombosis is a serious complication in patients with prosthetic heart valves. Traditional treatment is emergency surgery, but thrombolysis provides a non invasive alternative. In this paper we evaluate the efficacy and safety of thrombolysis in prosthetic heart valve thrombosis. METHODS: Data of 68 patients diagnosed of prosthetic valve thrombosis, treated at the Institute of Cardiology and Cardiovascular Surgery, Havana during a 6-years period were analyzed. They received thrombolysis with a recombinant streptokinase infusion at 250,000 IU in 30 minutes followed by 100,000 IU/hour during 72 hours or less if the thrombosis resolved before. The evaluation was based on clinical and echocardiographic findings. RESULTS: Affected sites were mitral (50 cases), tricuspid (9), and aortic (9). Mean time of prosthesis implantation was 6.8 years. The presentation form was generally heart failure (NYHA functional class III-IV) in 64 (94.1%) patients. Mean time interval between onset of symptoms and diagnosis was 10.6 days. There was total response to treatment in 58 (85.3%) patients, partial in 4 (5.9%) and failure in 6 (8.8%). Recombinant streptokinase overall dose was 5.1 x 10(6) IU and mean infusion time 50 hours. Major hemorrhagic complications were observed in two patients. Five embolic events occurred during thrombolysis. Four patients died. Rethrombosis was noted in 11 patients; 10 were retreated successfully with thrombolysis. CONCLUSIONS: Thrombolysis with recombinant streptokinase is efficacious and safe for the treatment of prosthetic heart valve thrombosis. It does not contraindicate surgical treatment if there is no total response, because patient goes to surgery in better hemodynamic conditions with lower risk. Nowadays it can be considered as first-line treatment in all patients with prosthetic heart valve thrombosis regardless of functional class unless specific contraindications exist.

Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction.

BACKGROUND: Streptokinase (SK) is an effective fibrinolytic agent for the treatment of acute myocardial infarction (AMI). The objective of the present study was to assess the adverse drug reactions (ADRs) associated with intravenous recombinant SK in patients with AMI in routine clinical practice. METHODS: A national, prospective and spontaneous reporting-based pharmacovigilance program was conducted in Cuba. Patient demographics, suspected ADR description, elements to define causality, and outcomes were documented and analyzed. RESULTS: A total of 1496 suspected ADRs identified in 792 patients out of the 1660 (47.7 %) prescriptions reported in the program, were received from July 1995 to July 2002. Most of the patients (71.3%) were male, 67.2% were white and mean age was 61.6 +/- 13.0 years. The mean time interval between the onset of symptoms and the start of the SK infusion was 4.9 +/- 3.7 h. The most frequently reported ADRs were hypotension, arrhythmias, chills, tremors, vomiting, nauseas, allergy, bleeding and fever. ADR severity was 38% mild, 38% moderate, 10% severe, and 4% very severe. Only 3 patients with hemorrhagic stroke were reported. Seventy-two patients died in-hospital mainly because of cardiac causes associated with the patient's underlying clinical condition. Mortality was 3 times more likely in patients suffering arrhythmias than in those without this event (odds ratio 3.1, 95% CI: 1.8 to 5.1). Most of the reported ADRs were classified as possibly or probably associated with the study medication. CONCLUSION: Recombinant SK was associated with a similar post-marketing safety profile to those suggested in previous clinical trials.

Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction

Background: Streptokinase (SK) is an effective fibrinolytic agent for the treatment of acute myocardial infarction (AMI). The objective of the present study was to assess the adverse drug reactions (ADRs) associated with intravenous recombinant SK in patients with AMI in routine clinical practice. Methods: A national, prospective and spontaneous reporting-based pharmacovigilance program was conducted in Cuba. Patient demographics, suspected ADR description, elements to define causality, and outcomes were documented and analyzed. ResultsA total of 1496 suspected ADRs identified in 792 patients out of the 1660 (47.7 percent) prescriptions reported in the program, were received from July 1995 to July 2002. Most of the patients (71.3percent) were male, 67.2percent were white and mean age was 61.6 ± 13.0 years. The mean time interval between the onset of symptoms and the start of the SK infusion was 4.9 ± 3.7 h. The most frequently reported ADRs were hypotension, arrhythmias, chills, tremors, vomiting, nauseas, allergy, bleeding and fever. ADR severity was 38percent mild, 38percent moderate, 10 percent severe, and 4percent very severe. Only 3 patients with hemorrhagic stroke were reported. Seventy-two patients died in-hospital mainly because of cardiac causes associated with the patient's underlying clinical condition. Mortality was 3 times more likely in patients suffering arrhythmias than in those without this event (odds ratio 3.1, 95percent CI: 1.8 to 5.1). Most of the reported ADRs were classified as possibly or probably associated with the study medication.Conclusion: Recombinant SK was associated with a similar post-marketing safety profile to those suggested in previous clinical trials(AU)

Antecedentes: la estreptoquinasa (SK) es un agente fibrinolítico eficaz para el tratamiento del infarto agudo de miocardio (IAM). El objetivo del presente estudio fue evaluar las reacciones adversas a medicamentos (RAM) se asocia con SK recombinante intravenoso en pacientes con IAM en la práctica clínica habitual. Métodos: Estudio nacional, prospectivo y notificaciones espontáneas de farmacovigilancia basado en el programa se llevó a cabo en Cuba. La demografía del paciente, presuntamente ADR descripción, los elementos para definir la causalidad, y los resultados fueron documentados y analizados. Resultados Un total de 1.496 sospechosos de RAM identificadas en 792 pacientes de los 1.660 (47,7 por ciento) informaron de las recetas en el programa, se recibieron entre julio de 1995 y julio de 2002. La mayoría de los pacientes (71.3percent) eran hombres, eran blancos y 67.2percent edad media fue de 61,6 ± 13,0 años. La media de intervalo de tiempo entre la aparición de los síntomas y el inicio de la infusión de SK fue de 4,9 ± 3,7 h. La RAM más frecuentes fueron hipotensión, arritmias, escalofríos, temblores, vómitos, náuseas, alergias, hemorragias y fiebre. ADR se 38percent gravedad leve, moderada 38percent, el 10 por ciento graves y muy graves 4percent. Sólo 3 pacientes con accidente cerebrovascular hemorrágico se informó. Setenta y dos pacientes fallecieron en el hospital debido principalmente a causas cardíacas asociadas con la del paciente condición clínica subyacente. La mortalidad fue 3 veces más probable en pacientes que sufren arritmias que en aquellos sin este evento (odds ratio: 3.1, 95percent IC: 1,8 a 5,1). La mayoría de los ADR fueron clasificados como posiblemente o probablemente relacionados con la medicación. Conclusión: SK recombinante se asoció con un puesto similar perfil de seguridad de la comercialización a los sugeridos en los ensayos clínicos previos

Angiographic patency study of an albumin-free recombinant streptokinase formulation in acute myocardial infarction.

PURPOSE: Fibrinolytic therapy restores coronary patency and reduces mortality in patients with acute myocardial infarction. Albumin is present in most of the streptokinase formulation as a stabilizer but it is not known whether it plays a role in the product's efficacy and safety profiles. The aim of this study was to assess 90 minutes-coronary patency of a new albumin-free recombinant streptokinase (rSK) formulation. METHODS . Patients with ischemic chest pain and ST-segment elevation, less than 12 hours after symptoms onset, without contraindications for fibrinolytic therapy, were included to receive 1.5 x 10(6) IU of rSK in a one-hour intravenous infusion. Angiography was performed 90 minutes after and coronary patency was classified according to the TIMI flow scales. RESULTS: The study enrolled 25 patients, 59.4 +/- 9.2 years-old, 88% men and 92% white. The mean time interval between the symptoms onset and rSK infusion was 3.0 +/- 2.0 hours. Patency rate (TIMI 2-3) of the infarct-related vessel was 72% (18/25). Partial or complete ST-segment resolution was achieved in 17 patients (68%). Hypotension and nauseas were the most frequent adverse events. Haemorrhage or in-hospital deaths were not reported. CONCLUSIONS: This study suggests that intravenous albumin-free rSK is a safe and appropriate therapy to get early (90-minute) coronary patency in patients with acute myocardial infarction.

Efecto clínico de una formulación de teofilina de liberación sostenida en pacientes asmáticos moderados o severos con intercrisis / Clinic effect of a theophylline of sustained action in asthmatic patients with moderate o severe asthma

Se evaluó el efecto clínico de la formulación de teofilina de acción sostenida (Aristegui 300 mg, cápsulas) a la dosis de 9 mg/kg de peso/día (cada 12 horas) en la consulta de asma bronquial del Hospital Docente Provincial Clínico Quirúrgico de Santa Clara, en el periodo comprendido de febrero a septiembre de 1997. El tiempo de tratamiento fue de un mes y se realizaron cinco consultas. La muestra estuvo constituida por 30 pacientes asmáticos, moderados o severos. Se analizaron las variables: asistencia a cuerpo de guardia, uso de salbutamol en aerosol y se realizaron mediciones objetivas de la función pulmonar a todos los pacientes en las diferentes consultas. Con la utilización de la formulación disminuyeron significativamente el flujo espiratorio pico, el volumen espiratorio forzado en un segundo y el flujo medio espiratorio máximo y existió baja incidencia de efectos adversos (AU)

Efecto clínico de una formulación de teofilina de liberación sostenida en pacientes asmáticos moderados o severos con intercrisis / Clinic effect of a theophylline of sustained action in asthmatic patients with moderate o severe asthma

Se evaluó el efecto clínico de la formulación de teofilina de acción sostenida (Aristegui 300 mg, cápsulas) a la dosis de 9 mg/kg de peso/día (cada 12 horas) en la consulta de asma bronquial del Hospital Docente Provincial Clínico Quirúrgico de Santa Clara, en el periodo comprendido de febrero a septiembre de 1997. El tiempo de tratamiento fue de un mes y se realizaron cinco consultas. La muestra estuvo constituida por 30 pacientes asmáticos, moderados o severos. Se analizaron las variables: asistencia a cuerpo de guardia, uso de salbutamol en aerosol y se realizaron mediciones objetivas de la función pulmonar a todos los pacientes en las diferentes consultas. Con la utilización de la formulación disminuyeron significativamente el flujo espiratorio pico, el volumen espiratorio forzado en un segundo y el flujo medio espiratorio máximo y existió baja incidencia de efectos adversos.