Gout Activity Score has predictive validity and is sensitive to change: results from the Nottingham Gout Treatment Trial (Phase II).

OBJECTIVES: To examine the predictive validity of the Gout Activity Score (GAS), its correlation with the Gout Impact Scale (GIS) and their sensitivity to change. METHODS: Data from a clinical trial in which participants with one or more gout flares in the previous year were recruited from primary care and randomized to nurse-led or continuing usual care were used in this study. GAS and GIS were calculated as described, with higher scores indicating worse disease activity and quality of life, respectively. The correlation between GAS and GIS was examined using Spearman's correlation. Standardized response means (SRMs) were calculated to assess sensitivity to change. The association between GAS at baseline and the number of flares in the next 12 months was evaluated using Poisson regression. Data analyses were performed using STATA version 14, with P-values <0.05 being statistically significant. RESULTS: There was low positive correlation between GAS and gout concern overall and unmet treatment need subscales of GIS (r = 0.34-0.45). Female sex associated independently with fewer gout flares, while increasing GAS, BMI and age associated independently with frequent flares. Of all the outcome measures examined, GAS was the most responsive to change (SRM 0.89 to -0.53). Of the GIS domains, the gout concern overall domain had the best sensitivity to change (SRM 1.06-0.01). CONCLUSION: GAS is sensitive to change, has predictive validity and correlates with relevant domains of GIS such as gout concern overall. Additional independent validation of GAS is required before it can be adopted in clinical practice.

Increase in thyroid stimulating hormone levels in patients with gout treated with inhibitors of xanthine oxidoreductase.

Increase in thyroid stimulating hormone (TSH) levels over the upper normal limit has been reported in a small percentage of patients treated with febuxostat in clinical trials, but a mechanistic explanation is not yet available. In an observational parallel longitudinal cohort study, we evaluated changes in TSH levels in patients with gout at baseline and during urate-lowering treatment with febuxostat. Patients to be started on allopurinol who had a measurement of TSH in the 6-month period prior to baseline evaluation were used for comparison. TSH levels and change in TSH levels at 12-month follow-up were compared between groups. Patients with abnormal TSH levels or previous thyroid disease or on amiodarone were not included for analysis. Eighty-eight patients treated with febuxostat and 87 with allopurinol were available for comparisons. Patients to be treated with febuxostat had higher urate levels and TSH levels, more severe gout, and poorer renal function, but were similar regarding other characteristics. A similar rise in TSH levels was observed in both groups (0.4 and 0.5 µUI/mL for febuxostat and allopurinol, respectively); at 12-mo, 7/88 (7.9 %) of patients on febuxostat and 4/87 (3.4 %) of patients on allopurinol showed TSH levels over 0.5 µUI/mL. Doses prescribed (corrected for estimated glomerular filtration rate in the case if patients on allopurinol) and baseline TSH levels were determinants of TSH levels at 12-month follow-up. No impact on free T4 (fT4) levels was observed. Febuxostat, but also allopurinol, increased TSH levels in a dose-dependent way, thus suggesting rather a class effect than a drug effect, but with no apparent impact on either clinical or fT4 levels.

Renal clearance of uric acid is linked to insulin resistance and lower excretion of sodium in gout patients.

Inefficient renal excretion of uric acid is the main pathophysiological mechanism for hyperuricemia in gout patients. Polymorphisms of renal tubular transporters linked with sodium and monosaccharide transport have yet to be demonstrated. We intended to evaluate the impact of insulin resistance, evaluated with the homeostasis model assessment (HOMA), through a transversal study of non-diabetic patients with gout, with normal renal function, not treated with any medication but colchicine as prophylaxis. One hundred and thirty-three patients were evaluated. Clearance of uric acid was inversely correlated with insulin resistance and directly correlated with fractional excretion of sodium. In multivariate analysis, hypertension and hyperlipidemia, in addition to insulin resistance and fractional excretion of sodium, were associated with renal clearance of uric acid. HOMA cutoff for efficient versus inefficient renal handling of uric acid was 2.72, close to that observed in studies of reference population. The impact of insulin resistance and renal handling of sodium on renal clearance of uric acid may help to explain why hyperuricemia is more commonly associated with diabetes and hypertension.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

PET/CT F18-FDG with soft tissue plasmacytomas in multiple myeloma.

Multiple myeloma is characterized by malignant proliferation of clonal plasma cells. Usually, appears as a generalized disease but it can present as solitary bone plasmacytoma or a solitary soft tissue mass or extramedullary plasmacytoma. In the case of extramedullary involvement, it could present as soft tissue plasmacytomas and the prognosis is poor. The 18F-FDG PET/CT could be a valuable tool for characterization of the medullary and extramedullary involvement. We present a case of F18-FDG PET/CT with extramedullary involvement with soft tissue plasmacytomas in the setting of MM.

Secondary cluster headache and numb chin syndrome as initial manifestation of high-grade B-lymphoma: a case report.

BACKGROUND: Cluster headache is a primary condition characterized by severe headache accompanied by trigeminal autonomic signs. By definition, it is not attributed to underlying etiologies; however, under certain clinical characteristics, secondary etiologies must be ruled out. CASE PRESENTATION: We present the case of a 48-year-old Hispanic man with a history of episodic right orbital pain, lasting 30 minutes, associated with ipsilateral tearing, who prior to the onset of his symptoms reported loss of appetite, weight loss, and paresthesias in the right chin region. After work-up studies, high-grade lymphoma with infiltration to the right submental nerve was diagnosed, in which numb chin syndrome was the initial presentation. Despite initiation of treatment, the patient died 3 weeks after the diagnosis. CONCLUSIONS: In the study of cluster headache, underlying etiologies must be considered when there are atypical clinical manifestations. Within these etiologies, metastases to pericranial nerves must be included, which, besides generating localized symptoms, can activate the trigeminal vascular system simulating headaches of primary etiology.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Febuxostat for the chronic management of hyperuricemia in patients with gout.

Febuxostat is a non-purine, selective inhibitor of both isoforms of xanthine oxido-reductase (XOR), and a major alternative to the scarce number of urate-lowering medications available in the last decades. Its inhibition of XOR is more potent than allopurinol in a mg to mg comparison, what is associated to achievement of serum urate target more frequently than allopurinol at doses tested in clinical trials, especially in patients with the highest baseline serum urate levels. Its pharmacokinetics is not greatly dependent on renal clearance, contrary to allopurinol, what may be an advantage in patients with chronic kidney disease. Several trials are further evaluating both the cardiovascular safety of febuxostat and its possible beneficial effect on renal function preservation. Still scarce, but clinically interesting, evidence on its use in transplant patients has been recently released.

Hyperuricaemia with deposition: latest evidence and therapeutic approach.

This article reviews recent evidence on urate deposition and the opportunity for a therapeutic approach. We reviewed Pubmed 2013-2015 literature using the search terms 'deposition' with 'hyperuricaemia', 'gout', 'ultrasonography', 'DECT' (dual-energy computed tomography), 'radiography', 'CT'(computed tomography), 'MRI' (magnetic resonance imaging), or 'cardiovascular', in addition to a digital bibliographic library compiled by the authors with 2072 papers on hyperuricaemia and gout. Relevant papers on the topic were selected. Recent evidence, mostly based on imaging studies, showed a continuum from hyperuricaemia to deposition and clinical manifestations. Chronic inflammation and structural damage may be present even in asymptomatic patients with crystal-proved deposition. The impact of early intervention in patients with asymptomatic deposition either on vascular outcomes or further structural joint damage has not been demonstrated yet. In conclusion, a worldwide definition of gout is still lacking, stages from hyperuricaemia to clinical gout not being definitively defined. Although there is increasing interest on the impact of early deposits on joint damage and cardiovascular outcomes, robust evidence is still lacking to fully support interventions.

Canakinumab for gout: a specific, patient-profiled indication.

The role of interleukin-1 (IL-1) in inflammation induced by crystals, and especially by monosodium urate crystals (MSUCs), has raised much interest in both basic and clinical investigation. Several drugs have been developed, and more are still in development, to block IL-1 driven inflammation, though to date only canakinumab (blocking IL-1ß) has been labelled, yet limited to the European Union, with a restricted indication to treat episodes of acute inflammation (EAIs) in patients with gout in whom other therapeutic choices are unacceptable. Other medications developed for IL-1 blocking, such as anakinra and rilonacept, have been tested in gout patients in clinical trials, but lack label approval and may be further restricted to orphan indication in gout. Notwithstanding, the use of IL-1 blockade to prevent EAIs in gout looks promising, but no drug has yet obtained approval for such an indication.

Clinical manifestations and diagnosis of gout.

Gout has been academically considered to be a step-up disease consisting of different stages: acute gout, intercritical gout, and chronic gout. This simple approach may lead to misinterpretation and misdiagnosis. In clinical practice, we should consider gout as a single disease with either or both acute (most commonly, episodes of acute inflammation) and persistent clinical manifestations, but not restricted to chronic synovitis. In this article, an innovative, practical, and rational approach to the clinical manifestations and diagnosis of gout is presented, which may be supportive for clinicians involved in everyday care and management of patients with gout.

Follicular thyroid carcinoma with signet ring cell morphology: fine-needle aspiration cytology, histopathology, and immunohistochemistry.

Thyroid follicular neoplasms with signet ring cell morphology represent a challenging cytological and histopathologic diagnosis. The low frequency of these neoplasms and their broad differential diagnosis contribute to this difficult scenario. Here, we present an exceptionally rare case of thyroid follicular carcinoma with signet ring cell morphology in a 62-year-old female. We analyze the characteristics in fine-needle aspiration cytology, histopathology, and immunohistochemistry and compare our results in a discussion with previous literature reports.

Tumor de Sertoli variante célula grande calcificante asociado a síndrome de peutz-jeghers / Large cell calcifying sertoli cell tumor associated with peutz-jeghers syndrome

El tumor de células de Sertoli calcificante de células grandes (TCSCCG) es una neoplasia testicular muy rara, con 60 casos descritos en todo el mundo; en Latinoamérica y Colombia son escasos los casos reportados en la literatura. Esta neoplasia se origina en el estroma gonadal/cordones sexuales, y, en general, tiende a mostrar un comportamiento biológico benigno. Se piensa que estos tumores tienen características de presentación diferente, dependiendo de si se presentan en el contexto de un síndrome congénito complejo, en cuyo caso tienden a ser bilaterales y multifocales, en contraposición a los no asociados a síndromes, que tienden a ser unilaterales y focales. El estudio de inmunohistoquímica es fundamental para el diagnóstico; en especial, para diferenciar estos tumores de neoplasias germinales. Se reportan en esta investigación tres casos de esta neoplasia, uno de ellos asociado al síndrome de Peutz-Jeghers, y haciendo énfasis en los criterios histológicos para definir malignidad.

The large cell calcifying Sertoli cell tumor (LCCSCT) is a very rare testicular tumor with 60 cases reported worldwide; in Latin America and Colombia, few cases are reported in the literature. This neoplasm originates in the gonadal stromal/sex cord, and, in general, tends to display benign biological behavior. It is thought that these tumors may display differing characteristics: depending upon whether they occur in the context of a complex congenital syndrome, in which case they tend to be bilateral and multifocal; as opposed to those not associated with syndromes, which tend to be unilateral and focal. Immunohistochemical study is essential for diagnosis, in particular, to differentiate these tumors from germ cell tumors. This study reports on three cases of this tumor--one associated with Peutz-Jeghers Syndrome—and emphasis is given to histological criteria to define malignancy.

Carcinoma adenoescamoso primario de vesícula biliar: reporte de un nuevo caso y consideraciones sobre su etiología / Primary adenosquamous carcinoma of gallbladder: a case report and considerations on its etiology

El carcinoma adenoescamoso primario de vesícula biliar (CAEVB), es una neoplasia infrecuente cuya etiología y comportamiento biológico no están totalmente aclarados. Describimos un caso de un paciente masculino con un carcinoma adenoescamoso infiltrante primario de vesícula biliar diagnósticado en una colecistectomía por colelitiasis. Morfológicamente se encontró asociado a los elementos glandulares y escamosos malignos, la presencia de displasia de bajo y alto grado del epitelio glandular y metaplasia escamosa entre las zonas glandulares y escamocelulares, que permiten hacer el diagnostico de este tipo de carcinoma. El estudio de inmunohistoquímica mostraba marcadores tanto de diferenciación glandular como escamosa. Por tratarse de una variante infrecuente de Carcinoma de vesícula biliar reportamos este caso por las dificultades que genera su diagnóstico. Nuestras observaciones sugieren que se trata de un adenocarcinoma con áreas de metaplasia escamosa y posterior transformación maligna de los elementos escamosos.

The adeno-squamous gallbladder carcinoma is a frequent neoplasm with blurred etiology and biological course. A case report is presented from a male with an incidental finding of a gallbladder carcinoma diagnosed during a cholecystectomy. Associated to malignant glandular and squamous morphological findings, low grade dysplasia and squamous metaplasia were observed, allowing the final diagnosis. Immunohistochemistry analyses revealed both glandular and squamous differentiation biomarkers. The report of a rare gallbladder carcinoma illustrates difficulties for proper diagnosis. The analysis suggests an adenocarcinoma with squamous metaplasia areas that evolved towardsthe malignant transformation of squamous components.

Carcinoma folicular de tiroides mínimamente invasivo en edad pediátrica / Minimally invasive follicular thyroid carcinoma in pediatric age

Los carcinomas de la glándula tiroides son poco usuales en edad pediátrica, pero su presencia ha aumentado durante los últimos años; posiblemente, debido al incremento en la irradiación de la cabeza, cuello y mediastino. Entre estas neoplasias, el carcinoma papilar es el más habitual, y los carcinomas foliculares verdaderos son, por el contrario, bastante raros y se asocian al bocio endémico, a alteraciones genéticas y al incremento de los niveles de TSH. Sus características morfológicas son particulares y ayudan a su diagnóstico, el cual ha sido redefinido recientemente. Describiremos el caso de una adolescente de 13 años con carcinoma folicular de tiroides mínimamente invasivo, con nódulo tiroideo hipocaptante en el polo inferior del lóbulo izquierdo, de 6 meses de evolución. La punción aspiración con aguja fina demostró una lesión de células foliculares sospechosa de neoplasia. Se realizó lobectomía tiroidea, con reporte de carcinoma folicular mínimamente invasivo.

Thyroid carcinomas are rare during childhood and adolescence. They have increased recently probably due to a higher frequency radiation over the head, neck and mediastinum. The papillary carcinoma is the most common and true follicular carcinoma is far less common. Follicular thyroid carcinoma is associated with endemic goiter, genetic disorders, and increased TSH levels. Its morphological characteristics are peculiar and have been recently redefined, thus helping the diagnosis. A minimally invasive follicular thyroid carcinoma in 13 years old girl is described, presenting a hypocaptant thyroid nodule in the left lobe lower pole. The fine needle aspiration biopsy revealed a follicular cell lesion suspicious of malignancy. Thyroid lobectomy was performed reporting minimally invasive follicular carcinoma.