Hereditary transthyretin amyloidosis is a multisystemic autosomal dominant genetic disorder characterized by progressive distal sensory-motor polyneuropathy or restrictive cardiomyopathy, secondary to amyloid deposits. Its pathogenesis lies in the TTR gene mutation, and the Val50Met mutation is the most frequent. Patients have significant differences in the onset and severity of clinical presentation according to their country of origin. The diagnosis of this pathology is complex, even more in countries where it is not considered endemic. However, early suspicion and management are essential to improve survival and avoid unnecessary diagnostic and therapeutic strategies. We report a 69-year-old woman who presented a sensory-motor polyneuropathy, predominantly sensory, associated with distal neuropathic pain and bilateral vitritis. The history of her Italian father with polyneuropathy of unspecified etiology stood out. A vitreous biopsy identified amyloid substance deposits (congo red positive). These were also confirmed on a superficial peroneal nerve biopsy. During the etiological study of her polyneuropathy, an increased Kappa/Lambda index of 2.55 mg/L stood out. Therefore, light chain amyloidosis was suspected, and chemotherapy treatment was indicated without favorable response. After 10 years of progressive neurological and ophthalmological involvement, a genetic study confirmed the first case of late-onset hereditary transthyretin amyloidosis Val50Met with polyneuropathy in Chile.

ABSTRACT Background: Immunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed entity. Aim: To characterize patients with AL amyloidosis in Chilean public health centers. Material and Methods: We conducted a retrospective, multicenter study. Public centers of the Chilean Monoclonal Gammopathies Cooperative Group were asked to search for patients with AL amyloidosis in their databases. Epidemiological, clinical and laboratory characteristics were evaluated. Results: Forty-two patients aged 22 to 84 years were found. Twenty four percent had localized AL amyloidosis; 64% had a lambda light chain clone; 47% were associated with multiple myeloma and 9% with non-Hodgkin lymphoma. The most commonly involved organ was the kidney (76%). Serum free light chains were measured in 31% and an echocardiogram was performed in 74% of patients. Seventeen percent of patients received only palliative care, 17% were treated with bortezomib, 21% with thalidomide, and 40% with melphalan. No patient was transplanted. The mean overall survival (OS) of the group was 19 months. The 5-year OS was 28%. Conclusions: It is important to obtain these realistic, national data to initiate strategies to improve early diagnosis and proper management of this disease.

La amiloidosis AL es una entidad poco frecuente y subdiagnosticada. Mientras todo el mundo discute sobre las nuevas herramientas diagnósticas y terapéuticas, en Chile y en América Latina en general, estamos lejos de esa realidad. El objetivo del presente estudio fue caracterizar a los pacientes con amiloidosis AL en centros del sistema público de nuestro país. Se realizó un estudio retrospectivo, multicéntrico, descriptivo. Los centros públicos del grupo cooperativo hematológico chileno buscaron en sus bases de datos pacientes diagnosticados con amiloidosis AL. Se evaluaron las características epidemiológicas, clínicas y de laboratorio. La edad media fue de 65 años. A 24% de los pacientes se les diagnosticó amiloidosis AL localizada; 64% tuvo paraproteína con cadena ligera lambda; 47% se asoció con mieloma múltiple y 9% con linfoma no Hodgkin. El órgano afectado con mayor frecuencia fue el riñón (76%). Las cadenas ligeras libres de suero se realizaron en 31% y ecocardiograma en 74%. El 17% recibió solo cuidados paliativos, 17% recibió tratamiento con bortezomib, 21% con talidomida y 40% con melfalán. Ningún paciente fue trasplantado. La media de sobrevida global (SG) del grupo fue de 19 meses. La SG a 5 años fue de 28%. Es importante reportar estos resultados nacionales para iniciar estrategias que mejoren tanto el diagnóstico temprano como el tratamiento de esta patología. Por lo tanto, mejorar la sospecha diagnóstica es crucial.

Objective: To report the clinical-functional results of humeral distal fracture treatment with total elbow prosthesis in patients older than 65 years. Methods: Retrospective study performed in two surgical centers. Inclusion criteria: patients with humeral distal fractures, >65 years, operated on with Coonrad-Morrey prostheses, and with a follow-up >1 year. Twenty-one patients were included (20 women) with an average age of 79 years. According to AO classification: 13 type C3 fractures, 7 C2 and 1 A2. All patients were operated on without disinsertion of the extensor mechanism. Average follow-up: 40 months. Results: Flexion-extension: 123-17°, with a total arc of mobility of 106° (80% of the contralateral side). Pain according to visual analogue scale was 1. The Mayo Clinic score was 83 points, results were excellent (8 patients), good (11 patients), regular (one case) and bad (one case). Average DASH score was 24 points. No loosening of the implants was evidenced in 13 patients. Nine complications were reported: 2 reoperations for polyethylene wear, one early decoupling of the prosthesis, 2 ulnar nerve paresthesia, one patient presented a false intraoperative via, one hematoma that needed a local flap and 2 loosening of the prosthesis. Conclusions: Treatment of humeral distal fractures with total elbow arthroplasty in patients older than 65 years may be a good therapeutic option, but indications must be limited to patients with complex fractures, bad bone quality, with osteoporosis and low functional demands.

Objetivo: Comunicar los resultados clínico-radiológicos del tratamiento de las fracturas de húmero distal con prótesis total de codo en pacientes >65 años. Materiales y Métodos: Estudio retrospectivo en dos centros quirúrgicos. Criterios de inclusión: pacientes con fractura de húmero distal, >65 años, operados con prótesis total de Coonrad-Morrey y seguimiento >1 año. Se incluyeron 21 pacientes (20 mujeres), edad promedio: 79 años. Según la clasificación AO, 13 C3, siete C2 y una A2. Todos fueron operados sin desinserción del aparato extensor. Seguimiento promedio: 40 meses. Resultados: La flexo-extensión fue de 123-17°, arco de movilidad de 106° (80% con respecto al lado sano). Dolor según la escala analógica visual: 1 punto. El puntaje de la Clínica Mayo promedio fue 83: resultado excelente (8 pacientes), bueno (11 pacientes), regular (1 caso) y malo (1 caso). El puntaje DASH promedio fue de 24. No hubo aflojamientos en 13 pacientes. Se produjeron nueve complicaciones: dos pacientes fueron operados nuevamente por desgaste del polietileno, uno operado otra vez al mes de la cirugía para la recolocación del perno de ensamble, dos parestesias del nervio cubital, una falsa vía intraoperatoria, un hematoma de la herida que necesitó de un colgajo braquial y dos aflojamientos protésicos. Conclusiones: El tratamiento de las fracturas de húmero distal con prótesis total de codo en pacientes >65 años puede ofrecer una opción terapéutica razonable, pero las indicaciones deben limitarse a fracturas complejas donde la fijación interna puede ser precaria, en pacientes con osteoporosis y con baja demanda funcional.

Background: Minor histocompatibility antigens (mHAgs) play a critical role in the immune responses associated with allogeneic stem cell transplantation, such as graft versus host disease (GVHD) and graft-versus-tumor (GVT). Aim: To determine the gene frequencies of the mHAgs HA-1, HA-2 and HA-8 in Chilean Blood Bank donors. Material and Methods: Blood from 192 blood donors was analyzed. The presence of haplotype HLA-A*02 was determined by flow cytometry. The frequency of mHAgs was determined by allele specific polymerase chain reaction in genomic DNA. Results: Sixty one participants were carriers of the haplotype HLA-A*02. The relative allele frequency HA-1H was 45%, HA-Ir 55%, HA-2V 80.6%, HA-2M 19.4%, HA-8R 49.8% and HA-8P was 50.2%. Based on mHAgs disparity between HA-1, HA-2 or HA-8, the probability to generate a GVT response in HLA-A*02 individuals was 40%. Conclusions: The mHAgs frequency in Chilean population is under Hardy-Weinberg equilibrium and they are similar to those of other ethnic populations in the world.

Background: Development of percutaneous techniques for tracheostomy have facilitated its implementation in the intensive care unit (ICU). Aim: To evaluate the safety of performing percutaneous tracheostomy (PT) using the Ciaglia Blue Rhino thechnique with fiberoptic bronchoscopy assistance in patients with prolonged mechanical ventilation. Patients and methods: Prospective evaluation of 100 consecutive patients aged 62±16 years (38 women) subjected to percutaneous tracheostomy. AU the procedures were performed in the ICU. Demographic variables, APACHE II, days of mechanical ventilation before PT, operative and post operative complications were recorded. Results: Mean APACHE II score was 20±3. Patients required on average 16±7 days of mechanical ventilation before PT. Eight patients (8%) had operative complications. One had an episode of transitory desaturation, one had a transitory hypotension related to sedation and six had mild bleeding not requiríng transfusión. No patient required conversión to surgical tracheostomy. Four patients (4%) presentedpost operative complications. Two had a mild and transitory bleeding ofthe ostomy and two had a displacement ofthe cannula. No other complications were observed. Conclusions: PT using the Ciaglia Blue Rhino technique with fiberoptic bronchoscopy assistance is a safe procedure that can be performed in the ICU by trained intensivists.

Background:Multiple myeloma is rarely curable. Advances in high dose chemotherapy and stem cell transplantation have improved overall survival and event-free disease periods, but relapses are inevitable. Aim: To report our experience with AT in multiple myeloma, between 1994 and 2003. Material and Methods: Retrospective analysis of 20 patients (12 women), with a mean age of 51.1 years. VAD (vincristine, doxorubicin and dexamethasone) was used as initial therapy in 19 patients. High dose cyclophosphamide (11 patients) and variations of VAD regimen (7) associated with granulocyte colony stimulating factor were used for peripheral-blood stem cell harvest. The conditioning regimen consisted of melphalan 200 mg/m² followed by the reinfusion of peripheral-blood stem cells 24 hours later. The median number of CD34 cells infused was 3,3x10(6)/kg. Three patients were subjected to a second auto graft and one to a non-myeloablative transplant. Mean follow up was 35.5 months. Results: Mucositis and febrile neutropenia were common complications. The median number of days for neutrophyl engraftment was 9 (range 8-11) and for platelets, 10 (range 7-13). No patient died. Complete remission was obtained in 60% (12/20), progession-free survival was 30 months and overall median survival, 47 months. Conclusions: The AT with high-dose melphalan is a safe procedure in our hospital, without mortality and engraftment in all the patients. Complete remission and progression free survival were similar to those reported abroad but the overall median survival was lower

In this randomized controlled multicenter trial, we compared endoscopic variceal banding ligation (VBL) with propranolol (PPL) for primary prophylaxis of variceal bleeding. One hundred fifty-two cirrhotic patients with 2 or more esophageal varices (diameter >5 mm) without prior bleeding were randomized to VBL (n=75) or PPL (n=77). The groups were well matched with respect to baseline characteristics (age 56±10 years, alcoholic etiology 51%, Child-Pugh score 7.2±1.8). The mean follow-up was 34±19 months. Data were analyzed on an intention-to-treat basis. Neither bleeding incidence nor mortality differed significantly between the 2 groups. Variceal bleeding occurred in 25% of the VBL group and in 29% of the PPL group. The actuarial risks of bleeding after 2 years were 20% (VBL) and 18% (PPL). Fatal bleeding was observed in 12% (VBL) and 10% (PPL). It was associated with the ligation procedure in 2 patients (2.6%). Overall mortality was 45% (VBL) and 43% (PPL) with the 2-year actuarial risks being 28% (VBL) and 22% (PPL). 25% of patients withdrew from PPL treatment, 16% due to side effects. In conclusion, VBL and PPL were similarly effective for primary prophylaxis of variceal bleeding. VBL should be offered to patients who are not candidates for long-term PPL treatment

We report a 78 year old male with prostatism, that was subjected to a prostate biopsy. The pathological study showed a microvascular lymphocytic infiltration. Four months later, the patients presentd with reduced alertness, cough, dyspnea, fever and elevation of lactic dehydrogenase and erythrocyte sedimentation rate. Chest and abdominal CAT scans, bone marrow aspirate, protein electrophoresis and prostate specific antigen were normal. A re-evaluation of prostate biopsy showed an intravascular lymphoid infiltration, positive for CD45 and CD20, compatible with the diagnosis of intravascular lymphoma. Chemotherapy was started, but it was not tolerated by the patient and the response was partial. Therefore, treatment with monoclonal antibodies anti CD20 (Rituximab) was started. The tumor had a complete and prolonged (24 months) remission after the treatment

An alternative strategy for cancer treatment is the manipulation of the immune system, denominated cancer immunotherapy. The immunotherapeutical use of cells of the immune system, like dendritic cells (DC), is being explored in different clinical protocols. Recently, we finalized a clinical phase I protocol, for the treatment of malignant melanoma, using DCs loaded with tumor lysates. Our results indicate that the subcutaneous application of DCs do not produce adverse effects. We also observed an increase of tumor spe-cific T lymphocytes precursors in the blood, associated to hypersensitivity reactions (DTH) in 60% of the treated patients. In most cases, an stability in the disease was observed, although without a significant association between vaccination and survival. Additionally, therapies based on Interleukin-2 (IL-2) have been used with relative success in the treatment of some kind of tumors since 1985. However, problems associated to the toxicity of IL-2 still restrict its massive use. Our direct experience with the use of IL-2, indicates that low doses and its subcutaneous application, maintains the beneficial effects for patients, eliminating the adverse effects. Based on the accumulated evidence during last the five years, we decided to implement an optimized clinical protocol, which alternatively combines dendritic cells vaccines with the use of low doses of IL-2 for the reinforcement of the immunological system (Rev Méd Chile 2004; 132: 1115-26)