Predicting treatment recommendations in postmenopausal osteoporosis.

We designed, implemented, and tested a clinical decision support system at the Research Center for the Study of Menopause and Osteoporosis within the University of Ferrara (Italy). As an independent module of our system, we implemented an original machine learning system for rule extraction, enriched with a hierarchical extraction methodology and a novel rule evaluation technique. Such a module is used in everyday operation protocol, and it allows physicians to receive suggestions for prevention and treatment of osteoporosis. In this paper, we design and execute an experiment based on two years of data, in order to evaluate and report the reliability of our suggestion system. Our results are encouraging, and in some cases reach expected accuracies of around 90%.

Clinical value of negative 68Ga-PSMA PET/CT in the management of biochemical recurrent prostate cancer patients.

PURPOSE: To evaluate the clinical value of 68Ga-PSMA PET/CT negativity in patients with biochemical recurrent prostate cancer (BCR). METHODS: One hundred three BCR patients (median age, 70 years; median PSA, 0.47 ng/mL) with negative 68Ga-PSMA PET/CT, followed up for at least 1 year, were retrospectively identified in a database of 1003 consecutive patients undergoing 68Ga-PSMA PET/CT for BCR. Clinical recurrence (CR) was determined or excluded on follow-up imaging selected as per clinical practice. Clinical recurrence-free survival (CRFS) was computed from the date of negative 68Ga-PSMA PET/CT to the date of evident disease; frequencies of CRFS were described as per ISUP patient subset (subset 1: ISUP grades 1 and 2; subset 2: ISUP grade 3; subset 3: ISUP grades 4 and 5) and other conventional variables. RESULTS: In 57 patients out of 103 (55.3%), CR was detected in the prostatic fossa (45.6%), nodes (38.6%), and bone (15.8%). The median CRFS was 15.4 months (range, 12.1-20.5), with a CRFS at 12 months in 61.4% of cases (range, 50.9-70.4) whereas the 24-month CRFS was 34.8% (range, 24-45.8). ISUP subset 1 benefited from significantly longer CRFS compared to subset 2 and subset 3 (median CRFS, 20.5 months, 12.6 months, and 12.1 months, respectively). ISUP subset 3 had significantly poorer 24-month CRFS (9.3%) compared to subset 1 (47.8%) and subset 2 (33.5%). At the univariate and multivariate analyses, the ISUP subset was the only significant risk factor for clinical relapse; ISUP subset 3 and subset 2 patients held a higher risk of CR compared to subset 1 patients (HR of 2.75 [1.35-5.57] for subset 3 versus subset 1; HR of 2.08 [1.11-3.88] for subset 2 versus subset 1). CONCLUSION: 68Ga-PSMA PET/CT negativity in early BCR patients (PSA < 0.5 ng/mL) with low-grade primary prostate cancer (ISUP1 and 2) may support the exploration of a clinical surveillance approach in future prospective studies.

Effect of external cervical orthoses on clinical and radiological outcome of patients undergoing anterior cervical discectomy and fusion.

BACKGROUND: The current use of external cervical orthoses (ECO) after cervical discectomy is still based on a common practice than a solid scientific literature. The aim of this study is to evaluate the impact of ECO on radiological and functional outcomes in patients undergoing anterior cervical discectomy and fusion (ACDF). METHODS: We compared two cohorts of consecutive patients who underwent ACDF with and without ECO after surgery. Thirty-six patients operated from January 2015 to June 2016 received an ECO whereas 36 patients, operated from July 2016 to December 2017, did not. Each patient underwent radiological and functional evaluation using plain x-ray at 1, 6, and 12 months after surgery and Neck Disability Index (NDI) at 2 weeks and 3, 6, and 12 months after surgery, respectively. RESULTS: In the ECO group, 5 patients (13.9%) presented an incomplete fusion and 31 patients (86.1%) presented a complete fusion (CI 0.705-0.953). In the non-ECO group, 8 patients (22.2%) presented an incomplete fusion and 28 patients (77.8% [CI 0.608-0.899]) had a complete fusion, with no statistically significant differences between two groups. No statistically significant differences were also observed regarding the NDI neither at 2 weeks nor at 3-, 6-, and 12-month follow-up. At multivariate analysis, patients who underwent two-level ACDF showed a five-fold increased risk of worse NDI at 3-, 6-, 12-month (p = 0.003, CI 1.770-14.584) follow-up. CONCLUSIONS: We advise against the routine use of ECO after single- or two-level ACDF as we did not find out any significant statistical differences between the two groups.

Percutaneous Lung Tumor Biopsy Under CBCT Guidance with PET-CT Fusion Imaging: Preliminary Experience.

PURPOSE: The aim of this study is to evaluate the feasibility of percutaneous lung tumor biopsy under cone beam-computed tomography (CBCT) with PET-CT imaging fusion. MATERIALS AND METHODS: Eleven patients (four women and seven men) underwent C-arm CBCT lung biopsy with PET-CT fusion imaging. A preprocedural PET-CT scan was manually fused with procedural CBCT based on anatomical landmarks; using real-time fluoroscopy, the coregistered PET-CT and CBCT images were overlaid to guide the needle trajectory. Technical success, accuracy, sensibility and specificity were evaluated. Mean total procedure time and time required for image elaboration were recorded. RESULTS: Technical success, diagnostic accuracy, sensitivity and specificity were 100%. The mean procedure time was 38 min. The average time of PET-CT/CBCT image fusion elaboration was 3.53 min for planning and 3.42 min for needle positioning check. CONCLUSION: CBCT-guided percutaneous lung biopsy with PET-CT fusion imaging is a feasible and effective procedure, with the potential to further improve diagnostic yield by targeting the most metabolically active portion of a lesion, whether it is morphologically altered or normal.

Trends in proportion of older HIV-infected people in care in Latin America and the Caribbean: a growing challenge.

We aimed to quantify the proportion of people receiving care for HIV-infection that are 50 years or older (older HIV patients) in Latin America and the Caribbean between 2000 and 2015 and to estimate the contribution to the growth of this population of people enrolled before (<50yo) and after 50 years old (yo) (⩾50yo). We used a series of repeated, cross-sectional measurements over time in the Caribbean, Central and South American network (CCASAnet) cohort. We estimated the percentage of patients retained in care each year that were older HIV patients. For every calendar year, we divided patients into two groups: those who enrolled before age 50 and after age 50. We used logistic regression models to estimate the change in the proportion of older HIV patients between 2000 and 2015. The percentage of CCASAnet HIV patients over 50 years had a threefold increase (8% to 24%) between 2000 and 2015. Most of the growth of this population can be explained by the increasing proportion of people that enrolled before 50 years and aged in care. These changes will impact needs of care for people living with HIV, due to multiple comorbidities and high risk of disability associated with aging.

On the antiquity of Legg-Calvé-Perthes disease: Skeletal evidence in Iron Age Italy.

Legg-Calvé-Perthes is a very rare disease involving childhood osteochondrosis of the femoral head due to interruption of its blood supply. The etiology is unknown. The signs of the pathology are well described in the literature but few paleopathological cases have been reported, mostly dating from Late Antiquity to Early Middle Ages. Here we report on morphometric and radiological analyses of a skeleton from the Etruscan necropolis of Spina (Ferrara, Italy, 6th-3rd century BCE), to our knowledge the most ancient case of Legg-Calvé-Perthes disease published thus far.

Femoroacetabular impingement: role of imaging.

The femoroacetabular impingement (FAI) is an impingement characterized by repetitive abutment between the femur and the acetabular rim during hip motion due to loss of joint clearance (Imam and Khanduja in Int Orthop 35(10):1427-1435, 2011; James et al. in AJR Am J Roentgenol 187(6):1412-1419, 2006). Femoroacetabular impingement (FAI) can be classified as either cam or pincer type, and it can be differentiated on the basis of a predominance of either a femoral or an acetabular abnormality (Pfirrmann et al. in Radiology 244(2):626, 2007; Ganz et al. in Clin Orthop Relat Res 466(2):264-272, 2008). In cases of cam FAI, the nonspherical shape of the femoral head at the femoral head-neck junction and reduced depth of the femoral waist lead to abutment of the femoral head-neck junction against the acetabular rim. In cases of pincer FAI, acetabular overcoverage limits the range of motion and leads to a conflict between the acetabulum and the femur. The most important role of preoperative MR evaluation in patients affected by FAI is the accurate assessment of the damage's extension.

Atraumatic vertebral compression fractures: differential diagnosis between benign osteoporotic and malignant fractures by MRI.

Atraumatic vertebral compression fractures are a common clinical problem, especially in elderly population. Metastases are the most frequent source of bone tumors, and the spine is a common site of metastatic disease; in case of cortical involvement or osteolysis, they may result in pathological compression fractures. Atraumatic compression fractures may result from other primary neoplasms of vertebrae and also from osteomyelitis, Paget's disease, hyperparathyroidism and other metabolic processes. Osteoporosis is a common source of vertebral compression fractures in elderly population, which may be indistinguishable from those of metastatic origin. The differentiation between osteoporotic compression fractures and malignant fracture is necessary to establish an appropriate staging and a therapeutic planning, especially in the acute and subacute stages. Anamnestic data about preexisting disease can be useful to individuate the potential cause of vertebral collapse. Plain radiography shows some difficulties in distinguishing whether the fracture represents a consequence of osteoporosis, a metastatic lesion or some other primary bone neoplasm. Computed tomography is one of the most suitable imaging techniques for the evaluation of bone structure and fragments and to establish the degree of cortical bone destruction; MR imaging (MRI) is the most helpful radiological investigation in order to provide the basis for the distinction between metastatic and acute osteoporotic compression fractures. The most relevant MRI findings to establish a differential diagnosis are described.

Rehabilitation and surgical management of ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease which, if untreated, may progress to severe damage of the spine with functional impairment, disability and poor quality of life. An increased mortality has been reported in AS patients compared to the general population. AS requires combined management (pharmacological and non-pharmacological) and advice by different health professionals. Even the pharmacological treatment in the last decade has dramatically changed the outcome, the severity of the disease might require a surgical approach for the hip involvement with total hip replacement, or the corrective spinal surgery. However, this surgery deserves some careful approaches since the complexity of the disease. Rehabilitation still represents a cornerstone of the global management of AS patients. The present review summarizes the state of art of surgical management of these two diseases.

Gastrointestinal perforation: ultrasonographic diagnosis.

Gastrointestinal tract perforations can occur for various causes such as peptic ulcer, inflammatory disease, blunt or penetrating trauma, iatrogenic factors, foreign body or a neoplasm that require an early recognition and, often, a surgical treatment.Ultrasonography could be useful as an initial diagnostic test to determine, in various cases the presence and, sometimes, the cause of the pneumoperitoneum.The main sonographic sign of perforation is free intraperitoneal air, resulting in an increased echogenicity of a peritoneal stripe associated with multiple reflection artifacts and characteristic comet-tail appearance.It is best detected using linear probes in the right upper quadrant between the anterior abdominal wall, in the prehepatic space.Direct sign of perforation may be detectable, particularly if they are associated with other sonographic abnormalities, called indirect signs, like thickened bowel loop and air bubbles in ascitic fluid or in a localized fluid collection, bowel or gallbladder thickened wall associated with decreased bowel motility or ileus.Neverthless, this exam has its own pitfalls. It is strongly operator-dependant; some machines have low-quality images that may not able to detect intraperitoneal free air; furthermore, some patients may be less cooperative to allow for scanning of different regions; sonography is also difficult in obese patients and with those having subcutaneous emphysema. Although CT has more accuracy in the detection of the site of perforation, ultrasound may be particularly useful also in patient groups where radiation burden should be limited notably children and pregnant women.

Changes in serum levels of TNF-alpha, IL-6, OPG, RANKL and their correlation with radiographic and clinical assessment in fragility fractures and high energy fractures.

Stages of bone turnover during fracture repair can be assessed employing serum markers of osteoblastic and osteoclastic activity, inflammatory cytokines, clinical evaluation and imaging instruments. Our study compare the fracture healing process in fragility fractures and high energy fractures by evaluating serum changes of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), osteoprotegerin (OPG) and receptor activator of the nuclear factor-kB ligand (RANKL) in combination with radiographic (Radiographic Union Scale for Tibial fractures, RUST) and clinical (Lower extremity measure, LEM) assessments. We enrolled 56 patients divided into four corresponding groups: group A with high energy trauma fracture (tibial/femoral shaft); group B with low energy trauma fracture (femoral fractures); healthy (control A) and osteoporotic subjects (control B). Blood samples were collected before surgery (T0) and after 10 weeks (T10). Serum concentrations of IL-6, TNF-alpha, RANKL and OPG were quantified using commercial enzyme-linked immunosorbent assay (ELISA) kits. Our results show that RANKL values are significantly higher at T10 than at T0 in low energy trauma fractures (group B). OPG is significantly lower in each control group than that of the respective fractured group and its concentration at T0 and at T10 is significantly lower in high than in low energy fractures. RANKL/OPG ratio is significantly higher in both controls than in fractured groups, and significantly increases after 10 weeks. IL-6 and TNF-alpha concentrations significantly decrease during fracture healing and are higher in high (group A) than in low energy fractures (group B). Significant differences were also found in both RUST score and LEM between groups A and B. Changes in TNF-alpha and IL-6 levels correlate with RUST and LEM in fragility and high energy fractures, while RANKL/OPG ratio is associated with these clinical parameters only in fragility fractures. These findings suggest that serum levels of IL-6, TNF-alpha, RANKL and OPG might be used to monitor the stages of fracture repair. Further studies will be needed to confirm the role of these cytokines in fracture repair.

A pilot study on the transcriptional response of androgen- and insulin-related genes in peripheral blood mononuclear cells induced by testosterone administration in hypogonadal men.

The aim of the present study is to determine whether testosterone (T) administration changes the expression profile of androgen- and insulin-related genes in peripheral blood mononuclear cells (PBMC). To this end, we evaluated the gene expression profile of 19 genes (AKT2, CCND1, GSK3ALPHA, IGF1, GSK3BETA, FOXO3, IL6, IGFBP2, UGT2B17, ARA55, CREBBP, CYP11A, HSD17B1, HSD17B7, UGT2B7, SELADIN 1, CLU, PGC1, AKR1C1) selected according their function in the androgen pathways, in a series of 11 hypogonadal men pharmacologically treated with T. We noted that 7 genes were differentially expressed, five of them were up-regulated (AKT2 FC=2.39, CREBBP FC=11.2, GSK3beta FC=5.6, UGT2B7 FC=4.49, UGT2B17 FC=2.88) and two were down-regulated (ARA55 FC= -2.0, CYP11A FC= -2.47). This experience suggests that androgen- and insulin-related genes can be considered useful blood genomic biomarkers for specific steroid drugs.

Androgen- and insulin-related gene signature using a specific low density oligoarray AndroChip 2 in peripheral blood mononuclear cells in agonists, recreational athletes and sedentary subjects.

The early detection of genomic biomarkers (e.g. RNAs) through analysis of circulating blood cells could have a substantial impact on biomedicine, particularly in monitoring clinical trials, drug toxicity and doping in athletes. To achieve this goal, it is essential to develop methods that are sufficiently sensitive to detect biomarker alterations during normal biologic processes, pathogenic processes, and or in response to therapeutic or other intervention. Using a low density microarray (AndroChip 2) we detected a transcriptional profiling signature of 190 genes related to androgen and insulin metabolism pathway, in peripheral blood mononuclear cell (PBMC) in subjects with different intensities of sports activities. We demonstrated that androgen and insulin gene transcriptional levels are independent to sports activity and therefore potentially suitable for drug monitoring and/or drug doping (such as anabolic androgen steroid AAS abuse) and or gene doping.

Degenerate PCR method for identification of an antiapoptotic gene in BHV-1.

To investigate on the hypothetical presence of an antiapoptotic gene, we utilized the CODEHOP (COnsensus-DEgenerate Hybrid Oligonucleotide Primers) strategy amplifying unknown sequences from a background of genomic (bovine herpesvirus type-1) BHV-1 DNA. An alignment of carboxyl-terminal domains belonging to three proteins encoded by gamma34.5, MyD116 and GADD34 genes, was carried out to design degenerate PCR primers in highly conserved regions. This allowed the amplification of a 110 bp fragment. This fragment was subjected to automatic sequencing and DNA sequence analysis revealed that its position resided between the nt 14363 and the nt 14438 in bovine herpesvirus type-1 (BHV-1) Cooper strain sharing an identity of 86% (UL14). Transient transfections showed that UL14 protein is efficient in protecting MDBK and K562 cells from sorbitol induced apoptosis. The protein's anti-apoptotic function may derive from its heat shock protein-like properties.

[Metastatic bone disease. Strategies for imaging]. / La malattia ossea metastatica. Strategia della diagnostica per immagini.

Skeletal metastases represent the most common malignant bone tumor. They occur mainly in adults and even more frequently in the elderly. The most common metastases in men are from prostate cancer (60%) and in women from breast cancer (70%). Other primitive tumors responsible for bone metastases are: lung, kidney, thyroid, alimentary tract, bladder, and skin. The spine and pelvis are the most common metastatic sites, due to the presence of red (haematopoietic active) bone marrow in a high amount. As a general rule, the radiographic pattern was lytic type; other aspects were osteosclerotic, mixed, lytic vs mixed and osteosclerotic vs lytic patterns. The main symptom is pain, although many bone metastases are asymptomatic. The most severe consequences are pathologic fractures and cord compression. Clinical evaluation of patients with skeletal metastases needs multimodal diagnostic imaging, able to detect lesions, to assess their extension and localization, and eventually drive the biopsy (for histo-morphological diagnosis). These techniques give different performances in terms of sensitivity and specificity; but none of the modalities alone seems to be adequate to yield a reliable diagnostic outcome. Therefore multidisciplinary cooperation is required to optimize the screening, clinical management and follow-up of the patients. In other terms, what is the efficacy of these new diagnostic tests compared to the "older" diagnostic tests? Frequently the new procedures do not replace the older one, but it is added to the diagnostic workup, thereby increasing costs without impacting the "patient's condition". The aim of the present work is to propose an "algorithm" for the detection and diagnosis of skeletal metastases, which may be applied differently in symptomatic and asymptomatic oncologic patients. Bone scintigraphy remains the first choice technique in the evaluation of asymptomatic patients, in whom skeletal metastases are supposed. Although it has a high sensitivity, scintigraphy is unspecific. So that a negative scan response has to be re-evaluated with other methods: if clinical status remains "negative", the diagnostic route can stop. On the contrary, in patients with "positive" scan or with local symptoms and pain, the screening of metastatic lesions must be accomplished by a combination of radiography and CT: the result may be negative (for low sensitivity of conventional radiology), not conclusive (in this case bone biopsy is necessary) or symptoms are not due to metastatic lesions (i.e., osteoarthritis). CT represents an excellent mean of defining the extent of any metastatic lesions, especially those located at sites difficult to evaluate (vertebral column and pelvis). Before bone biopsy is carried out, MRI must be performed, because it is the only technique that makes it possible to distinguish between bone marrow components. It has been used most extensively in the evaluation of spine metastases. The limitation of MRI is the unspecificity of its findings, which may lead to an equivocal diagnosis, and because only part of the skeleton can be studied.

Air embolism: diagnosis with single-photon emission tomography and successful hyperbaric oxygen therapy.

Venous air embolism may occur when the surgical field is above the level of the heart. We present a case of venous air embolism in a patient undergoing percutaneous nephrolithotripsy in the prone position and presenting with blindness and neurological deficits 8 h later. The clinical diagnosis of paradoxical air embolism was confirmed by early single-photon emission tomography (SPET), whereas magnetic resonance imaging including diffusion-weighted imaging (DW-MRI) was diagnostic only 30 h later. Hyperbaric oxygen therapy was successful. In this case, early DW-MRI scan was inconclusive, but a SPET study of the brain appeared to be useful in confirming the clinical diagnosis. Early hyperbaric oxygen was demonstrated to be a successful therapy.

A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer.

A multicentre observational study was conducted by the Italian Association of Nuclear Medicine between 1996 and 1998. Twenty-nine Nuclear Medicine Departments participated. The aims of the study were to systematically evaluate the efficacy, toxicity and repeatability of radionuclide therapy of painful bone metastases (RTBM) in a large number of patients and to assess its incidence in patients with prostate cancer. Out of 818 treatments performed with a single i.v. dose of 148 MBq of strontium-89 chloride or 1,295 MBq of rhenium-186 hydroxyethylidene diphosphonate (HEDP), 610 could be evaluated (527 with 89Sr and 83 with 186Re-HEDP). Eighty-one patients received multiple (up to five) RTBM. The total number of retreatments was 100. Patients were followed up for a period of 3-24 months. Results, assessed according to pain relief and consumption of analgesic drugs, were expressed at four levels: 1, no response; 2, mild response; 3, good response; 4, excellent response. Responses were: level 1 in 19%, level 2 in 21.3%, level 3 in 33.3% and level 4 in 26.4% of cases. Retreatments showed significantly (P<0.01) worse responses (48% levels 3+4), in comparison to first RTBM. Duration of palliation was 5.0+/-3.5 months, and was longer in cases of excellent response, in first RTBM, in patients with limited metastases and when 89Sr was used. Better responses were found in cases of limited skeletal disease, under good clinical conditions, when life expectancy exceeded 3 months, and in radiologically osteoblastic or mixed bone lesions. The only statistically significant predictive factor was life expectancy (P<0.001). Flare phenomenon (14.1% of cases) did not correlate with the response. Haematological toxicity (mild to moderate in most cases) mainly affected platelets, and was observed in 25.5% of cases overall and in 38.9% of retreatments. RTBM did not seem to prolong life, though in some cases scintigraphic regression of bone metastases was observed. The two radiopharmaceuticals did not show any statistically significant differences in palliative efficacy and toxicity, either in first RTBM or in retreatments.

Radionuclide therapy for painful bone metastases. An Italian multicentre observational study. Writing Committee of an Ad Hoc Study Group.

BACKGROUND: It has been affirmed that observational studies give analogous results to randomised controlled ones. METHODS: A multicentre observational trial was conducted between 1996-1998 in order to evaluate the efficacy of palliative radionuclide therapy for bone metastases in a large number of patients. An evaluation was made on 510 patients with prostate cancer and painful bone metastases, treated with a single iv. dose of 89Sr-chloride (527 treatments) or 186Re-HEDP (83 treatments), in 29 Italian Nuclear Medicine Departments. Eighty-one patients received up to five injections, totalling 100 retreatments. Patients were followed up for a period of 3 months-2 years. Results were expressed at four levels of response: excellent, good, mild, and nil. RESULTS: Responses were excellent in 26.4%, good in 33.3%, mild in 21.3% and nil in 19% of all treatments, while good and excellent responses were obtained in 48% of retreatments. No statistically significant correlations were found between response and age of patients, skeletal extension of tumour, pretherapeutic PSA levels, evidence of non-bony metastases, previous chemotherapy and/or external-beam radiotherapy; osteolytic lesions responded worse than osteoblastic or mixed ones. Hematological toxicity (mild to moderate), mainly affecting platelets, was observed in 25.5% of all treatments and in 38.9% of retreatments. No clear differences were found between the two radiopharmaceuticals employed. CONCLUSIONS: Bearing in mind that observational studies can provide just as accurate results as randomised controlled trials, this study confirms the main findings of various limited monocentre trials.

The immunosuppressive cytokines influence the fetal survival in patients with pregnancy-induced hypertension.

PROBLEM: The present study examines the hypothesis that the elevated levels of transforming growth factor (TGF)-beta1 and interleukin (IL)-10 would be protective for the fetus survival during pregnancy-induced hypertension (PIH). Moreover, we evaluate the IL-12 and IL-15 serum concentrations and their relationships with PIH. METHOD OF STUDY: Serum samples were obtained before the onset of labor from control and PIH groups. Cytokine concentrations were determined by Enzyme-Linked Immunoadsorbent Assay. RESULTS: Our data show that PIH women have significantly higher TGF-beta1 and IL-10 concentrations with respect to control groups (P = 0.0001). Similarly, macrophages from the PIH placentas produce in vitro more elevated TGF-beta1 and IL-10 levels compared to normal pregnant ones (P = 0.02), also in the absence of LPS stimulation. IL-12 and IL-15 serum concentrations were not detectable in all pregnant groups. CONCLUSION: We have found that PIH women have elevated concentrations of anti-inflammatory/immunosuppressive cytokines, suggesting their important role in fetal allograft protection during the normal and pathological pregnancy.

An uncommon case of fluid retention simulating a congestive heart failure after aspirin consumption.

Nonsteroidal anti-inflammatory drugs are widely used and relatively safe medications. We report here an uncommon case of fluid retention simulating acute congestive heart failure, secondary to aspirin consumption, promptly reversible after discontinuation of therapy, and triggered again by pharmacological challenge test.