Diagnosis and treatment of primary thyroid lymphoma from a surgical perspective: a multi-institutional study.

PURPOSE: Surgery of primary thyroid lymphoma (PTL) has been mostly limited to diagnostic work-up. This study aimed to further study its potential role. METHODS: This was a retrospective study from a multi-institutional registry of PTL patients. Clinical, diagnostic work-up (fine needle aspiration, FNA; core needle biopsy, CoreNB), contribution of surgery (open surgical biopsy, OpenSB; thyroidectomy), histology subtype, and outcome data were evaluated. RESULTS: Some 54 patients were studied. Diagnostic work-up included FNA in 47 patients, CoreNB in 11, and OpenSB in 21. CoreNB yielded the best sensitivity (90.9%). Thyroidectomy was performed in 14 patients with other diagnosis (incidental PTL), in 4 for diagnosis and in 4 for elective treatment of PTL. Incidental PTL was associated with not performed FNA nor CoreNB (OR 52.5; P = 0.008), mucosa-associated lymphoid tissue (MALT) subtype (OR 24.3; P = 0.012), and Hashimoto's thyroiditis (OR 11.1; P = 0.032). Lymphoma-related death (10 cases) mostly occurred within the first year after diagnosis and was associated with diffuse large B-cell (DLBC) subtype (OR 10.3; P = 0.018) and older patients (OR 1.08 for every 1-year increase; P = 0.010). There was a trend towards lower mortality rate in patients receiving thyroidectomy (2/22 versus 8/32, P = 0.172). CONCLUSION: Incidental PTL accounts for most of thyroid surgery cases and are associated with incomplete diagnostic work-up, Hashimoto's thyroiditis and MALT subtype. CoreNB appears to be the best tool for diagnosis. Most of PTL deaths occurred during the first year after diagnosis and mostly related to systemic treatment. Age and DLBC subtype are poor prognostic factors.

Differential involvement of synovial adipokines in pain and physical function in female patients with knee osteoarthritis. A cross-sectional study.

OBJECTIVE: Adipokines have been reported to play a role in the development, progression and severity of knee osteoarthritis but the influence of the different adipokines are not well known. The aim of this study was to evaluate the association between different synovial fluid adipokines with pain and disability knee osteoarthritis patients. METHODS: Cross-sectional study with systematic inclusion of 115 symptomatic primary knee osteoarthritis female patients with ultrasound-confirmed joint effusion. Age, physical exercise, symptoms duration and different anthropometric measurements were collected. Radiographic severity was evaluated according to Kellgren-Lawrence scale. Pain and disability were assessed by WOMAC-total, -pain, -function subscales and Knee injury and Osteoarthritis Outcome Score (KOOS) pain and function scales. Seven adipokines and three inflammatory markers were measured by ELISA in synovial fluid. Partial Correlation Coefficient (PCC) and corresponding 95% confidence interval were used as a measure of association. RESULTS: Leptin, osteopontin and inflammatory factors, especially TNF-alpha, were associated to pain and function. After adjustment for potential confounders including inflammatory factors and all adipokines, an association was found for adiponectin with pain (PCC 0.240 [0.012, 0.444]) and for resistin and visfatin with function (PCC 0.336 [0.117, 0.524] and -0.262 [-0.463, -0.036]). No other adipokines or inflammatory markers were statistically and independently associated. An association between physical exercise and pain and disability remained after adjustment, whereas an attenuation of the influence of anthropometric measurements was observed. CONCLUSIONS: Different patterns of association between synovial fluid adipokines were observed regarding pain and disability in knee osteoarthritis patients. Specifically, adiponectin was associated to pain while resistin and visfatin were mainly related to function.

High prevalence of cardiovascular co-morbidities in patients with symptomatic knee or hand osteoarthritis.

OBJECTIVES: To evaluate the frequency of cardiovascular events (CVEs) and metabolic syndrome (MetS) in patients with symptomatic knee or hand osteoarthritis (OA). METHOD: A cross-sectional study conducted by rheumatologists in a primary care setting. Consecutive symptomatic patients with primary knee or hand OA were included and patients with soft tissue conditions served as the control group. Hypertension, diabetes mellitus, obesity, dyslipidaemia, and CVEs consisting of myocardial infarction, angina, or cerebrovascular disease were recorded. RESULTS: A total of 254 OA patients (184 with knee OA and 70 with hand OA) and 254 control patients were included. The frequency of obesity was higher in all OA groups and hypertension was more frequent in knee OA. MetS was significantly more frequent in patients with OA as a whole group and in knee or hand OA groups separately (p < 0.001, p = 0.002, and p = 0.007, respectively, vs. control group), with odds ratio (OR) 2.4, 95% confidence interval (CI) 1.26-4.55 in the OA group, OR 2.29, 95% CI 1.15-4.54 in the knee OA group, and OR 2.67, 95% CI 1.15-6.19 in the hand OA group. A higher prevalence of CVEs in the three OA groups was observed compared with the control group. CONCLUSIONS: A high frequency of MetS and CVEs was observed in OA patients in a primary care setting.

Experiencia de 4 años de funcionamiento de una unidad multidisciplinar de psoriasis y artritis psoriásica / Multidisciplinary Psoriasis and Psoriactic Arthritis Unit: Report of 4 years’ Experience

INTRODUCCIÓN Y OBJETIVOS: La afectación articular en los pacientes con psoriasis puede llegar hasta el 30%. El diagnóstico y tratamiento precoz de la artropatía puede influenciar su evolución. El objetivo de nuestro trabajo es describir la experiencia de la unidad multidisciplinar de psoriasis y artritis psoriásica de nuestro hospital en el periodo 2009-2012. MATERIAL Y MÉTODOS: Elaboración de un programa asistencial y docente. En una primera fase se consensuaron los criterios de derivación a la futura unidad y se realizaron varias reuniones conjuntas para formar y concienciar a los especialistas. En una segunda fase se estableció una agenda de visitas conjunta psoriasis-reumato-dermato (PSORD) con periodicidad mensual. A partir de 2011 se desarrolló un programa formativo abierto a dermatólogos y reumatólogos interesados en crear un modelo de colaboración similar. RESULTADOS: Durante el periodo revisado se han efectuado 259 visitas (71% primeras, 8% no presentados) con una media de 8 (2-14) visitas por sesión. El 63% de visitas eran derivaciones de reumatología. En un 32% de casos hubo algún cambio en el diagnóstico y en un 47% cambios en el tratamiento. También se han hecho 3 cursos con participación de 15 médicos de 6 hospitales, y en 3 de ellos se han creado unidades parecidas. CONCLUSIONES: Este modelo ha comportado una mejora en el manejo de los pacientes que presentan problemas diagnósticos y/o de control de la enfermedad. También ha aumentado el diagnóstico precoz de la artritis y ha permitido indicar un tratamiento precoz. Además ha aumentado la colaboración entre ambas especialidades y el modelo creado se ha podido exportar a otros hospitales

INTRODUCTION AND OBJECTIVES: Up to 30% of patients with psoriasis develop joint disease, the course of which can be improved by early diagnosis and treatment. The aim of this study was to describe our experience with a new multidisciplinary psoriasis and psoriatic arthritis unit over a period of 4 years (2009-2012). MATERIAL AND METHODS: Implementation of a PSOriasis Rheumatology and Dermatology unit (PSORD) to provide patient care and physician training. In the first phase of the project, referral criteria for the unit were defined and several meetings were organized to train and prepare the specialists involved in the program. In the second phase, a schedule was drawn up for monthly patient visits with the PSORD team. Starting in 2011, training was offered to dermatologists and rheumatologists from other hospitals interested in implementing a similar model. RESULTS: A total of 259 visits (71% first visits, 8% no-shows) were scheduled during the period analyzed, with a median of 8 visits (range, 2-14 visits) per session. Sixty-three percent of the patients were referred from the rheumatology department. Diagnosis and treatment were modified in 32% and 47% of cases, respectively. Three training courses were held with 15 physicians from 6 hospitals, 3 of which created similar units. CONCLUSIONS: The PSORD model improved the management of difficult-to-diagnose and/or uncontrolled disease, the early diagnosis and treatment of psoriatic arthritis, and collaboration between dermatologists and rheumatologists. Finally, the model lends itself to being exported to other settings

Multidisciplinary psoriasis and psoriatic arthritis unit: report of 4 years' experience.

INTRODUCTION AND OBJECTIVES: Up to 30% of patients with psoriasis develop joint disease, the course of which can be improved by early diagnosis and treatment. The aim of this study was to describe our experience with a new multidisciplinary psoriasis and psoriatic arthritis unit over a period of 4 years (2009-2012). MATERIAL AND METHODS: Implementation of a PSOriasis Rheumatology and Dermatology unit (PSORD) to provide patient care and physician training. In the first phase of the project, referral criteria for the unit were defined and several meetings were organized to train and prepare the specialists involved in the program. In the second phase, a schedule was drawn up for monthly patient visits with the PSORD team. Starting in 2011, training was offered to dermatologists and rheumatologists from other hospitals interested in implementing a similar model. RESULTS: A total of 259 visits (71% first visits, 8% no-shows) were scheduled during the period analyzed, with a median of 8 visits (range, 2-14 visits) per session. Sixty-three percent of the patients were referred from the rheumatology department. Diagnosis and treatment were modified in 32% and 47% of cases, respectively. Three training courses were held with 15 physicians from 6 hospitals, 3 of which created similar units. CONCLUSIONS: The PSORD model improved the management of difficult-to-diagnose and/or uncontrolled disease, the early diagnosis and treatment of psoriatic arthritis, and collaboration between dermatologists and rheumatologists. Finally, the model lends itself to being exported to other settings.

Sudomotor function assessment as a screening tool for microvascular complications in type 2 diabetes.

Sudoscan, a non invasive, quick, and simple method to measure sweat function, was evaluated as a screening tool for microvascular complications in type 2 diabetes. AUC of the ROC curve for detection of microvascular complication was 0.75 for an autonomic risk score, with a sensitivity of 82% and a specificity of 61%.

Screening of cardiovascular autonomic neuropathy in patients with diabetes using non-invasive quick and simple assessment of sudomotor function.

AIM: Cardiovascular autonomic neuropathy (CAN) is a common but often overlooked complication of diabetes. Sympathetic C-fibers innervating sweat glands can be impaired early on in patients with diabetes. In this study, SUDOSCAN, a new non-invasive device that assesses sudomotor function was compared to methods generally used for the investigation of CAN. PATIENTS: A total of 232 patients with diabetes were measured for heart rate variability (HRV) at rest and during moderate activity. Time and frequency domain analysis techniques, including measurement of the low-frequency (LF) domain component, were assessed during HRV testing. Ewing tests, as recommended by the French Health Authority, were also done. Electrochemical sweat conductance (ESC) was measured on the hands and feet, and a risk-score was calculated. RESULTS: Using two abnormal Ewing tests as a reference for the area under the curve (AUC) of the receiver operating characteristics (ROC) curve for SUDOSCAN, the risk-score was 0.74, with a sensitivity of 92% and specificity of 49% for a risk-score cut-off value of 35%. For the ROC curve analysis using the LF power component during moderate activity at a threshold of 90 ms(2) (first quartile) as reference, the AUC was higher for the SUDOSCAN risk-score (0.77) compared with the standard Ewing tests [E:I ratio (0.62), 30:15 ratio (0.76) and blood pressure change on standing (0.55)]. Using a cut-off value of 35%, risk-score sensitivity and specificity were 88 and 54%, respectively. CONCLUSION: SUDOSCAN, which allows quick quantitative assessment of sudomotor function, may be used for early screening of CAN in everyday clinical practice before resorting to the more sophisticated and specific, but ultimately more time-consuming, Ewing tests.

Assessment of small fiber neuropathy through a quick, simple and non invasive method in a German diabetes outpatient clinic.

INTRODUCTION: Sudomotor dysfunction is one of the earliest neurophysiologic abnormalities to manifest in distal small fiber neuropathy. SUDOSCAN® was developed to provide a non invasive, quick, simple and quantitative measurement of sweat function. The aim of this observational study was to assess sweat function in a diabetes outpatient consult clinic in Germany. METHODS: The study was conducted from February 2009 to March 2011 on patients of a diabetes outpatient clinic in Germany with type 1 and type 2 diabetes, and was conducted parallel to standard care. Sweat function was evaluated by measuring the electrochemical conductance (ESC) of the hands and feet. The method's reproducibility between 2 devices and a follow-up according to insulin administration were also assessed. RESULTS: 52 patients with type 1 diabetes and 115 patients with type 2 diabetes (69 receiving insulin) were involved in this observational study. Hand and foot conductances were lower in patients with type 2 diabetes when compared to patients with type 1 diabetes. A slight decrease in hand and foot conductances was observed in patients with type 2 diabetes without insulin, while an increase was observed in patients receiving insulin (-3.8±9.7 vs. 1.0±9.7 µS, p=0.02 for the hands and -2.2±7.5 vs. 4.1±8.8 µS, p<0.001 for the feet). Coefficient of correlation between measurements performed with the 2 different devices was 0.85 for hands and 0.93 for feet, p<0.001. No safety concern was reported and none of the subjects experienced discomfort during the tests. CONCLUSION: This preliminary study shows that the assessment of small C fiber neuropathy can be performed non invasively, quickly and effectively in standard diabetes outpatient practice with very good reproducibility. The observation that electrochemical skin conductance improves with intensified insulin treatment must be confirmed in a clinical study performed on a larger population.

Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-α blocker agents: Report of five cases and review of the literature.

BACKGROUND: Tumour necrosis factor antagonists (anti-TNF-α) have demonstrated the efficacy in different chronic immune inflammatory disorders. Within the spectrum of adverse events, autoimmune diseases have been observed, including cases of alopecia areata (AA). OBJECTIVES: The objective of the study is to characterize AA developed during anti-TNF-α therapy. METHODS: We present five new cases and review all the cases reported in the literature (eleven). RESULTS: One third of the cases had a positive (personal or family) history of AA. Most of them presented with rapid extensive AA, usually involving the ophiasis area. Prognosis was usually poor, with slight response to treatments. In the cases where anti-TNF-α therapy was maintained, the course did not seem to change. CONCLUSIONS: Although rare, AA developed during anti-TNF-α therapy might be more frequent than suggested by reports of isolated cases. Personal and family history of autoimmune disease might alert clinicians to their possible development or relapse once the anti-TNF-α therapy is started.

Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+ rat.

In polycystic kidney disease, abnormal epithelial cell proliferation is the main factor leading to cyst formation and kidney enlargement. Cyclic AMP (cAMP) is mitogenic in cystic but antimitogenic in normal human kidney cells, which is due to reduced steady-state intracellular calcium levels in cystic compared to the normal cells. Inhibition of intracellular calcium entry with channel blockers, such as verapamil, induced cAMP-dependent cell proliferation in normal renal cells. To determine if calcium channel blockers have a similar effect on cell proliferation in vivo, Cy/+ rats, a model of dominant polycystic kidney disease, were treated with verapamil. Kidney weight and cyst index were elevated in verapamil-treated Cy/+ rats. This was associated with increased cell proliferation and apoptosis, elevated expression, and phosphorylation of B-Raf with stimulation of the mitogen-activated protein kinase MEK/ERK (mitogen-activated protein kinase kinase/extracellular-regulated kinase) pathway. Verapamil had no effect on kidney morphology or B-Raf stimulation in wild-type rats. We conclude that treatment of Cy/+ rats with calcium channel blockers increases activity of the B-Raf/MEK/ERK pathway accelerating cyst growth in the presence of endogenous cAMP, thus exacerbating renal cystic disease.

Massive intraperitoneal stromal tumour: two-year follow-up.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare. Few cases of such tumours are reported in the literature. Until recently, they were only treated surgically but, nowadays, for high grade tumours, we can consider wide excision, not only as a palliative measure, but also to enable subsequent treatment with Imatinib mesylate. METHODS: We describe the case of a patient with a high-grade GIST, who, two years after undergoing surgery and medical treatment, is still in remission. Computerised axial tomography (CT) of the abdomen detected the presence of multiple heterogeneous solid masses of various sizes but no localised retroperitoneal adenopathies. MAIN FINDINGS: Median laparotomy was performed and revealed multiple intraperitoneal tumours. The larger masses were excised and the smaller residual implants are currently being treated with Imatinib mesylate. The patient had visceral, parietal and peritoneal dissemination. One of them, located in the supramesocolic area, had a maximal diameter of 20cm. Another one, at the level of the retro-gastric space, had a diameter of 22cm. The other tumours were smaller and spread over the parietal and visceral peritoneum, mainly between the loops of the small intestine and pelvis. Two years after cytoreduction surgery, the patient is well and free of obvious disease and has shown a good tolerance to pharmacological treatment. CONCLUSIONS: Imatinib mesylate has revolutionised the treatment of GIST and offers good palliation and prolongation of overall survival.

Morbid obesity: postsurgical predictive factors and prioritization of the waiting list.

AIM: To study a sample of patients with morbid obesity who are on the waiting list for a surgical intervention, to establish various scores of surgical risk (Possum and severity score), and to assess potential criteria for list prioritization. DESIGN: We calculated physiological and surgical Possum scores for every patient, and analysed comorbidities and other associated factors to calculate the severity score. Likewise, we calculated the predictive rates of morbimortality. Differences between associated comorbidities in body mass index (BMI) were also analyzed. The correlation between Possum score, prediction rates, and severity score were analyzed. PATIENTS: Fifty-two patients on the surgical waiting list in our institution (San Juan University Hospital, Reus) from 26/4/02 to 5/03/04. RESULTS: The mean qualitative score is significantly higher in the female sex. Invalidating arthropathy and socio-occupational and/or psychiatric criteria are significantly higher in women. There is a significant correlation between the severity score and Possum score. Age does not correlate with any of the variables studied. CONCLUSIONS: Possum scores are significantly related to BMI, particularly in terms of morbidity rates. The degree of correlation between the Possum score and the qualitative score tells how useful the latter is to cover other determinant factors in the severity of this condition. Socio-occupational and psychiatric criteria, and invalidating arthropathy are the main variables to be taken into account for postsurgical prediction, and are directly related to BMI degree.

Induction of acute lung injury after intranasal administration of toxin botulinum a complex.

The inhalation of aerozolized botulinum toxin may represent a potential significant hazard to both military and civilian personnel. Since the lung is the primary target organ for inhaled toxin, the investigation reported herein was conducted to examine lung function in mice exposed to botulinum toxin A complex by intranasal route. Data includes lethality, symptomatology, measurement of respiratory function (minute ventilation, respiratory frequency, and tidal volume), and histopathology of the lungs. The clinical signs of intoxication are similar to those observed in foodborne botulism. Plethysmography revealed severe impairment of all respiratory parameters tested from 7 hours postexposure. Severe lung lesions, possibly secondary to the intoxication, were observed in mice who survived 14 days after the toxin challenge. These included intra-alveolar hemorrhage and interstitial edema. Mice immunized by the pentavalent (ABCDE) toxoid were protected against the neurotoxin (4 LD50) as revealed by the decrease of lethality and severity of nervous signs of intoxication, but not against histopathological changes in the lungs. These effects are nonspecific and require further experiments in order to specify the relationships between the pathology and the inflammatory process in the lung due to mediators such as cytokines,and possibly permanent physiological sequelae.

Obesidad mórbida: factores predictivos postquirúrgicos y priorización de la lista de espera / Morbid obesity: postsurgical predictive factors and priorization of the waiting list

Objetivo: estudio de una muestra de pacientes afectos deobesidad mórbida y en lista de espera para intervención quirúrgica,determinar el riesgo quirúrgico según diferentes scores (Possumy score de gravedad) y valorar los posibles criterios en la priorizaciónde dicha lista. Diseño: cálculo del Possum fisiológico y quirúrgico para cadapaciente y análisis de las comorbilidades y otros factores asociadospara el cálculo del score de gravedad. Cálculo de los ratiospredictivos de morbi-mortalidad. Análisis de las diferencias observadas,según el índice de masa corporal (IMC), de las comorbilidadesasociadas. Análisis del grado de correlación entre el Possum,los ratios de predicción y el score de gravedad. Pacientes: Cincuenta y dos pacientes incluidos en la lista deespera quirúrgica de nuestro centro (Hospital Universitario SanJoan de Reus) durante el periodo del 26/4/02 al 5/03/04.Resultados: el score cualitativo tiene una media superior significativaen el sexo masculino. La artropatía invalidante y los criteriossocio-laborales y/o psiquiátricos son significativamente superioresen el sexo femenino. Existe una correlación significativaentre el score de gravedad y el Possum. La edad no se correlacionaen nuestra serie con ninguna de las variables estudiadas.Conclusiones: los valores del Possum están relacionados significativamentecon el IMC, en especial en base al ratio de morbilidad.El grado de correlación entre el Possum y el score cualitativonos indica la utilidad de este para cubrir otros factoresdeterminantes en la gravedad de esta patología. Los criterios socio-laborales y psiquiátricos y la artropatía invalidante, son lasprincipales variables a tener en cuenta en la predicción postquirúrgica,estando directamente relacionados con el grado de IMC

Aim: to study a sample of patients with morbid obesity whoare on the waiting list for a surgical intervention, to establish variousscores of surgical risk (Possum and severity score), and to assesspotential criteria for list prioritization.Design: we calculated physiological and surgical Possumscores for every patient, and analysed comorbidities and other associatedfactors to calculate the severity score. Likewise, we calculatedthe predictive rates of morbimortality. Differences betweenassociated comorbidities in body mass index (BMI) were also analyzed.The correlation between Possum score, prediction rates,and severity score were analyzed.Patients: fifty-two patients on the surgical waiting list in ourinstitution (San Juan University Hospital, Reus) from 26/4/02 to5/03/04.Results: the mean qualitative score is significantly higher inthe female sex. Invalidating arthropathy and socio-occupationaland/or psychiatric criteria are significantly higher in women.There is a significant correlation between the severity score andPossum score. Age does not correlate with any of the variablesstudied.Conclusions: possum scores are significantly related to BMI,particularly in terms of morbidity rates. The degree of correlationbetween the Possum score and the qualitative score tells how usefulthe latter is to cover other determinant factors in the severity ofthis condition. Socio-occupational and psychiatric criteria, and invalidatingarthropathy are the main variables to be taken into accountfor postsurgical prediction, and are directly related to BMIdegree

Prosopagnosia y simultagnosia aisladas debidas a infarto isquémico en territorio occipito-temporal derecho / Isolated prosopagnosia and simultagnosia due to ischemic infarction in right occipitotemporal territory

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Comparative efficacy of diazepam and avizafone against sarin-induced neuropathology and respiratory failure in guinea pigs: influence of atropine dose.

This investigation compared the efficacy of diazepam and the water-soluble prodiazepam-avizafone-in sarin poisoning therapy. Guinea pigs, pretreated with pyridostigmine 0.1 mg/kg, were intoxicated with 4LD(50) of sarin (s.c. route) and 1 min after intoxication treated by intramuscular injection of atropine (3 or 33.8 mg/kg), pralidoxime (32 mg/kg) and either diazepam (2 mg/kg) or avizafone (3.5 mg/kg). EEG and pneumo-physiological parameters were simultaneously recorded. When atropine was administered at a dose of 3 mg/kg, seizures were observed in 87.5% of the cases; if an anticonvulsant was added (diazepam (2 mg/kg) or avizafone (3.5 mg/kg)), seizure was prevented but respiratory disorders were observed. At 33.8 mg/kg, atropine markedly increased the seizure threshold and prevented early respiratory distress induced by sarin. When diazepam was administered together with atropine, seizures were not observed but 62.5% of the animals displayed respiratory difficulties. These symptoms were not observed when using avizafone. The pharmacokinetic data showed marked variation of the plasma levels of atropine and diazepam in different antidote combination groups, where groups receiving diazepam exhibited the lowest concentration of atropine in plasma. Taken together, the results indicate that avizafone is suitable in therapy against sarin when an anticonvulsant is judged necessary.