Search for small-bowel capsule diagnostic yield optimization conducted through observational analysis. / Búsqueda de optimización de la cápsula endoscópica mediante análisis observacional.

OBJECTIVES: To search for parameters susceptible to optimization when performing capsule endoscopy (CE) in a third level hospital with high volume and experience in this test. PATIENTS AND METHODS: Retrospective observational study, including 1325 CEs performed between 2017 and 2022. Overall diagnostic yield, effective diagnostic yield, by indication, place of request and waiting list, as well as complete examination rate and cleansing degree were analyzed. RESULTS: The overall diagnostic yield was 70.99%, while the effective diagnostic yield was 72.7%. Diagnostic yields varied between 60.2% and 77.9% depending on the indication and between 64.7% and 74.3% depending on the requesting center. The mean waiting list was 101.15 days, with a tendency to worse results when the waiting list was longer. A total of 77.8% of the examinations were complete. Completion rates were lower in patients >70 years of age (p=0.001), as well as in those with gastric transit >60minutes (p=0.000). A total of 77.3% were clean, with debris that did not impede diagnosis being found in 16.9% and debris that did impede diagnosis in 5.8%. There was a relationship, although not significant, between cleansing degree and age. CONCLUSIONS: The diagnostic yields of CE in our center are in line with those previously reported. Differences were found according to the place of request. Waiting list could also influence diagnostic yield. Completion rates are lower in >70 years of age and when gastric transit is >60minutes. Cleansing degree achieved is acceptable.

Recommendations for the future management of thrombocytopenia in patients with liver cirrhosis: A modified RAND/UCLA appropriateness method.

OBJECTIVE: The lack of consensus and specific guidelines, and the introduction of new treatments in thrombocytopenia management in liver cirrhosis patients, required a series of recommendations by experts to improve knowledge on this disease. This study's aim was to improve the knowledge around thrombocytopenia in liver cirrhosis patients, in order to contribute to the generation of future evidence to improve the management of this disease. PATIENTS AND METHODS: A modified version of the RAND/UCLA appropriateness method was used. The scientific committee, a multidisciplinary team of 7 experts in managing thrombocytopenia in liver cirrhosis patients, identified the expert panel, and participated in elaborating the questionnaire. Thirty experts from different Spanish institutions were invited to answer a 48-item questionnaire covering 6 areas on a nine-point Likert scale. Two rounds were voted. The consensus was obtained if >77.7% of panelists reached agreement or disagreement. RESULTS: A total of 48 statements were developed by the scientific committee and then voted by the experts, resulting in 28 defined as appropriate and completely necessary, relating to evidence generation (10), care circuit, (8), hemorrhagic risk assessment, decision-making and diagnostic tests (14), professionals' role and multidisciplinary coordination (9) and patient education (7). CONCLUSIONS: This is the first consensus in Spain on the management of thrombocytopenia in liver cirrhosis patients. Experts indicated several recommendations to be carried out in different areas that could help physicians make better decisions in their clinical practice.

Advanced fibrosis associated with non-alcoholic steatohepatitis (NASH) in Spain: results of a Delphi study. / Fibrosis avanzada asociada a esteatohepatitis no alcohólica (NASH) en España: resultados de un estudio Delphi.

OBJECTIVE: To describe in detail the epidemiology, diagnosis, clinical management, treatment options, impact on quality of life and unmet needs of patients with advanced liver fibrosis (F3-F4) associated with non-alcoholic steatohepatitis (NASH) in Spain. METHODOLOGY: Delphi study of two rounds of consultation rounds with 41 expert hepatologists from 16 autonomous communities to collect their experience in clinical practice. RESULTS: The estimated prevalence of adult patients diagnosed with F3-F4 fibrosis associated with NASH in Spain is 0.019% (95% confidence interval [CI]: 0.019-0.020%). Approximately 7,588 adults with this condition are currently diagnosed and managed in the Digestive System Services of Spanish hospitals, and around 1,881 new patients are diagnosed each year. Management is multidisciplinary and includes the specialties of Digestive System, Endocrinology and Internal Medicine, considering the frequently associated metabolic comorbidities (obesity, type 2 diabetes mellitus or dysmetabolic iron overload). Despite a clear impact on quality of life, this it is not routinely evaluated in clinical practice. The most widely used non-invasive diagnostic techniques are transitional elastography and liver fibrosis index 4 (FIB-4). The absence of effective and safe treatments appears as the main unmet need for the management of these patients. CONCLUSIONS: This study provides a representation of the current situation of patients diagnosed with F3-F4 fibrosis associated with NASH in Spain, increasing the evidence available and contributing to informed decision-making by professionals and the health system.

Assessment of the quality, diagnosis, and therapeutic recommendations of clinical practice guidelines on patients with Helicobacter pylori infection: A systematic review.

We conducted this study to systematically review and assess the current clinical practice guidelines (CPGs) related to the diagnosis and treatment of Helicobacter pylori (H. pylori) infection. The aim was to evaluate the quality of these included CPGs and provide clinicians with a convenient and comprehensive reference for updating their own CPGs. We searched four databases to identify eligible CPGs focusing on H. pylori diagnosis and treatment recommendations. The results were presented using evidence mappings. Quality and clinical applicability were assessed comprehensively using AGREE-II and AGREE-REX. Statistical tests, specifically Bonferroni tests, were employed to compare the quality between evidence-based guidelines and consensus. A total of 30 eligible CPGs were included, comprising 17 consensuses and 13 guidelines. The quality showed no statistical significance between consensuses and guidelines, mainly within the moderate to low range. Notably, recommendations across CPGs exhibited inconsistency. Nevertheless, concerning diagnosis, the urea breath test emerged as the most frequently recommended method for testing H. pylori. Regarding treatment, bismuth quadruple therapy stood out as the predominantly recommended eradication strategy, with high-dose dual therapy being a newly recommended option. Our findings suggest the need for specific organizations to update their CPGs on H. pylori or refer to recently published CPGs. Specifically, CPGs for pediatric cases require improvement and updating, while a notable absence of CPGs for the elderly was observed. Furthermore, there is a pressing need to improve the overall quality of CPGs related to H. pylori. Regarding recommendations, additional evidence is essential to elucidate the relationship between H. pylori infection and other diseases and refine test indications. Clinicians are encouraged to consider bismuth quadruple or high-dose dual therapy, incorporating locally sensitive antibiotics, as empirical radical therapy. .

Prevalence of diagnosed and undiagnosed osteoarthrosis and associated factors in the adult general Spanish population.

OBJECTIVE: To determine the prevalence and related factors of diagnosed osteoarthrosis (DO) and undiagnosed osteoarthrosis (UO) in the general Spanish adult population. SETTING: Cross-sectional study with data from the Spanish National Health Survey 2017. PARTICIPANTS: N=23,089 adults. Three groups of people were defined: DO, UO, and no osteoarthrosis (NO). MAIN MEASUREMENTS: Sociodemographic information, lifestyle (tobacco, alcohol, physical activity, body mass index) and health factors (intensity of pain, pain drug consumption, mental health, self-perceived health status, pain involvement in daily living) were collected. Descriptive and bivariate analyses were performed, and a multinomial logistic regression model for the factors associated with each group. RESULTS: The prevalence of DO was 22.4% (95%CI=21.8;22.9) and 0.9% (95%CI=0.8;1) of UO. With respect to NO, risk factors for DO and UO included higher pain levels and pain drug consumption. Better self-perceived health status was inversely related with both. More pain involvement in daily living was associated with increased risk of DO, but reduced risk of UO. CONCLUSIONS: The prevalence of DO and UO was similar to that reported in Europe, but slightly higher than in low/middle-income countries. It was more prevalent in females, older people, people with worse perceived health status and worse mental health. Higher pain levels and pain drug consumption were risk factors for DO and UO. Better self-perceived health status was protective. Pain involvement in daily living was a risk factor for DO, but protective for UO. Different public health strategies should be considered in view of this.

Ten Years of HIV Diagnosis in a Dermatology and Venereology Department: A Retrospective Study on Demographic, Clinical, and Laboratory Characteristics.

Human immunodeficiency virus (HIV) transmission remains an important health issue, with a high burden that is felt across the world. This work aims to analyze the demographic, clinical, and laboratory characteristics of newly diagnosed patients with HIV in a Department of Dermatology and Venereology. A retrospective observational study was conducted from all health records of newly diagnosed patients with HIV from a Dermatology unit from January 2011 to December 2020. A total of 134 patients with new HIV diagnoses were included in the analysis. Concurrent dermatological or venereal diseases were diagnosed in 91.0% of the patients (n=122), being the most common conditions syphilis (22.4%, n=30) and urethritis (14.9%, n=20). Out of all the patients with diagnoses of concurrent sexually transmitted infection (STI) (41.0%, n=55), syphilis was reported in 81.8% of the patients (n=45), gonorrhea in 9.1% (n=5), and chlamydia in 5.5% (n=3). We present a large patient database on the clinical conditions associated with newly diagnosed HIV, concluding that infectious diseases were the most common conditions associated with newly diagnosed HIV.

Ten Years of HIV Diagnosis in a Dermatology and Venereology Department: A Retrospective Study on Demographic, Clinical, and Laboratory Characteristics. / [Artículo traducido] Diez años de diagnóstico de VIH en un Departamento de Dermatología y Venereología: un estudio retrospectivo sobre características demográficas, clínicas y de laboratorio.

Human immunodeficiency virus (HIV) transmission remains an important health issue, with a high burden that is felt across the world. This work aims to analyze the demographic, clinical, and laboratory characteristics of newly diagnosed patients with HIV in a Department of Dermatology and Venereology. A retrospective observational study was conducted from all health records of newly diagnosed patients with HIV from a Dermatology unit from January 2011 to December 2020. A total of 134 patients with new HIV diagnoses were included in the analysis. Concurrent dermatological or venereal diseases were diagnosed in 91.0% of the patients (n=122), being the most common conditions syphilis (22.4%, n=30) and urethritis (14.9%, n=20). Out of all the patients with diagnoses of concurrent sexually transmitted infection (STI) (41.0%, n=55), syphilis was reported in 81.8% of the patients (n=45), gonorrhea in 9.1% (n=5), and chlamydia in 5.5% (n=3). We present a large patient database on the clinical conditions associated with newly diagnosed HIV, concluding that infectious diseases were the most common conditions associated with newly diagnosed HIV.

[Translated article] Reticulate Skin Lesions: Practical Color-Based Algorithm for Initial Clinical Assessment.

Reticular patterns are observed in a great variety of skin diseases. While these morphologic patterns are often highly distinctive, they are seldom discussed or studied in clinical contexts or recognized as a diagnostic category in their own right. Diseases presenting with reticulate skin lesions have multiple etiologies (tumors, infections, vascular disorders, inflammatory conditions, and metabolic or genetic alterations) and can range from relatively benign conditions to life-threatening ones. We review a selection of these diseases and propose a clinical diagnostic algorithm based on predominant coloring and clinical features to aid in their initial assessment.

Reticulate Skin Lesions: Practical Color-Based Algorithm for Initial Clinical Assessment. / Lesiones cutáneas reticulares: algoritmo clínico práctico basado en el color de la lesión para el abordaje inicial.

Reticular patterns are observed in a great variety of skin diseases. While these morphologic patterns are often highly distinctive, they are seldom discussed or studied in clinical contexts or recognized as a diagnostic category in their own right. Diseases presenting with reticulate skin lesions have multiple etiologies (tumors, infections, vascular disorders, inflammatory conditions, and metabolic or genetic alterations) and can range from relatively benign conditions to life-threatening ones. We review a selection of these diseases and propose a clinical diagnostic algorithm based on predominant coloring and clinical features to aid in their initial assessment.

Diagnosis of Onychomycosis: Utility of an Immunochromatography Strip Test Compared with Conventional Culture. / Diagnóstico de onicomicosis. La utilidad del test rápido de detección antigénica en comparación con el cultivo.

BACKGROUND: Ringworm is highly prevalent in our setting and is frequently observed in our routine clinical practice. Diagnostic confirmation depends on techniques that are not always accessible (PCR), with highly variable sensitivity depending on the observer (direct microscopy) or delayed results (culture, histopathology). Recently, an immunochromatography-based rapid test (Diafactory®) for the antigenic detection of dermatophytes has been developed. This diagnostic tool can help diagnose ringworm, allowing early initiation of treatment and fewer consultation visits. OBJECTIVE: To determine the sensitivity and specificity of the rapid antigen detection test compared to conventional culture. MATERIAL AND METHODS: For a full year, 333 nail samples were collected from patients with suspected onychomycosis. The rapid test and the conventional culture were simultaneously performed on each sample. Those with a positive antigenic test result began treatment early. The remaining patients had appointments for serial cultures and subsequent medical consultation to evaluate the results. RESULTS: Compared to conventional culture, the sensitivity and specificity rates of the rapid antigen detection test are 97.2% and 80.7%, respectively. CONCLUSION: The effectiveness of the rapid antigen detection test is similar to that of conventional culture for the detection of dermatophytes in nail samples. It is a quick and simple diagnostic technique that reduces the number of patient visits to the hospital, and allows early treatment start.

Validation of the Spanish Version of the PURE-4 Questionnaire for the Early Detection of Psoriatic Arthritis in Psoriatic Patients. / Validación de la versión española del cuestionario PURE-4 para la detección precoz de la artritis psoriásica en pacientes con psoriasis.

BACKGROUND AND OBJECTIVE: Psoriasis often precedes the onset of psoriatic arthritis (PsA), so dermatologists often face the challenge of early identifying signs of PsA in patients with psoriasis. Our aim was to validate the Spanish version of the PURE-4 questionnaire as a screening tool for PsA, evaluate its performance in terms of sensitivity, specificity, feasibility, reliability, and build validity. METHODS: This was a cross-sectional, observational, multicenter trial of adult patients with psoriasis. Initially, patients were assessed by a dermatologist and completed 2 self-administered versions (in print and online) of the PURE-4 questionnaire. Afterwards, the rheumatologist, blinded to the PURE-4 results, assessed the presence/absence of PsA, being the reference to determine the performance of the PURE-4 questionnaire. RESULTS: A total of 268 patients were included (115 [42.9%] women; mean age, 47.1±12.6). The prevalence of PsA according to rheumatologist diagnosis was 12.7% (34 patients). The mean PURE-4 score for patients with psoriasis diagnosed with PsA was 2.3±1.1, and 1.3±1.3 for patients without PsA (P<.001). The cutoff value ≥2 demonstrated the best performance for detecting PsA, with a negative predictive value of 95.1% (95% confidence interval, 90.3-97.6). CONCLUSIONS: The PURE-4 questionnaire demonstrated good performance in detecting PsA, with an optimal cutoff point ≥2. This simple tool could facilitate early referral of patients to the rheumatology unit.

Consensus on the diagnostic algorithm for chronic nodular prurigo. / Consenso sobre el algoritmo diagnóstico del prurigo crónico nodular.

Chronic nodular prurigo (CNP) is a chronic dermatological disease characterized by the presence of chronic pruritus and pruritic nodular lesions. The aim of this study was to reach consensus among a group of experts based on a non-systematic literature review and an algorithm for the clinical diagnosis of CNP. The resulting algorithm is structured in 3 blocks: 1) early identification of the patient with a possible diagnosis of CNP; 2) diagnosis and assessment of CNP; and 3) categorization of CNP (identification of the underlying causes or associated comorbidities). We believe that this clinical algorithm can facilitate the correct diagnosis of patients with CNP. Additionally, it raises awareness on the need for a multidisciplinary approach and specific treatment of CNP, steps of paramount importance to make better therapeutic decisions.

AEDV Expert Consensus for the Management of Syphilis. / Documento de expertos de la AEDV para el manejo de la sífilis.

Syphilis -the "great simulator" for classical venereologists-is re-emerging in Western countries despite adequate treatment; several contributing factors have been identified, including changes in sexual behaviour, which won't be the topic of this article though. In 2021, a total of 6613 new cases of syphilis were reported in Spain, representing an incidence of 13.9×100 000 inhabitants (90.5%, men). Rates have increased progressively since 2000. The clinical presentation of syphilis is heterogeneous. Although chancroid, syphilitic roseola and syphilitic nails are typical lesions, other forms of the disease can be present such as non-ulcerative primary lesions like Follmann balanitis, chancres in the oral cavity, patchy secondary lingual lesions, or enanthema on the palate and uvula, among many others. Regarding diagnosis, molecular assays such as PCR have been replacing dark-field microscopy in ulcerative lesions while automated treponemal tests (EIA, CLIA) are being used in serological tests, along with classical tests (such as RPR and HAART) for confirmation and follow-up purposes. The interpretation of these tests should be assessed in the epidemiological and clinical context of the patient. HIV serology and STI screening should be requested for anyone with syphilis. Follow-up of patients under treatment is important to ensure healing and detect reinfection. Serological response to treatment should be assessed with the same non-treponemal test (RPR/VDRL); 3-, 6-, 12-, and 24-month follow-up is a common practice in people living with HIV (PLHIV). Sexual contacts should be assessed and treated as appropriate. Screening is advised for pregnant women within the first trimester of pregnancy. Pregnant women with an abortion after week 20 should all be tested for syphilis. The treatment of choice for all forms of syphilis, including pregnant women and PLHIV, is penicillin. Macrolides are ill-advised because of potential resistance.

Recommendations for the integral diagnosis of chronic viral hepatitis in a single analytical extraction. / Recomendaciones para el diagnóstico integral de las hepatitis virales crónicas en una única extracción analítica.

The Spanish Society of Digestive Pathology (SEPD), the Spanish Association for the Study of the Liver (AEEH), the Spanish Society of Infections and Clinical Microbiology (SEIMC) and its Viral Hepatitis Study Group (GEHEP), and with the endorsement of the Alliance for the Elimination of Viral Hepatitis in Spain (AEHVE), have agreed on a document to carry out a comprehensive diagnosis of viral hepatitis (B, C and D), from a single blood sample; that is, a comprehensive diagnosis, in the hospital and/or at the point of care of the patient. We propose an algorithm, so that the positive result in a viral hepatitis serology (B, C and D), as well as human immunodeficiency virus (HIV), would trigger the analysis of the rest of the virus, including the viral load when necessary, in the same blood draw. In addition, we make two additional recommendations. First, the need to rule out a previous hepatitis A virus (VHA) infection, to proceed with its vaccination in cases where IgG-type studies against this virus are negative and the vaccine is indicated. Second, the determination of the HIV serology. Finally, in case of a positive result for any of the viruses analyzed, there must be an automated alerts and initiate epidemiological monitoring.

Endoscopic diagnosis of H. pylori infection. / Diagnóstico endoscópico de la infección por H. pylori.

Helicobacter pylori (H. pylori) infection is highly prevalent in our environment and is associated with highly relevant gastric disease, both benign and malignant. The gold standard for diagnosis is histological confirmation by biopsy. However, there is increasing evidence that optical endoscopic diagnosis could have a fundamental role in avoiding unnecessary biopsies in certain cases. Specifically, the regular distribution of the collecting venules (RAC pattern) seems to have a high negative predictive value (NPV) to rule out infection. This review describes the most outstanding endoscopic findings with the best diagnostic potential for H. pylori infection after an exhaustive search comparing the most relevant studies that have been carried out in Europe and the East.

Prevalence of hepatitis C virus infection in patients with chronic mental disorders: The relevance of dual disorders.

OBJECTIVE: The prevalence of hepatitis C virus (HCV) infection is higher in people with psychiatric disorders compared to the general population. In addition, patients with severe mental illness are frequently affected by substance abuse, which increases the risk of blood-borne viral infections. Epidemiological studies in samples of hospitalised individuals with chronic mental disorders and dual diagnosis (DD) are lacking. The objective of this study was to investigate the prevalence of HCV infection in a sample of in-patients with severe mental illness. PATIENTS AND METHODS: This was a retrospective observational study. All patients meeting selection criteria admitted to the Medium-Term Psychiatric Unit of the University of Salamanca Health Care Complex between 2007 and 2018 were included. The primary endpoint was the prevalence of HCV infection. The secondary endpoint comprised the characteristics influencing the occurrence of HCV infection in these patients. RESULTS: A total of 497 admissions were included and patients' last admission data were considered for analyses (n=345). The overall prevalence of HCV infection was 3.8% and reached 14.3% among DD patients, who showed a higher prevalence than those without this condition (14.3% versus 3.1%, p=0.009). HCV RNA was detected in 6 individuals at diagnosis who received DAA treatment reaching sustained virological response. CONCLUSIONS: The prevalence of HCV infection in our sample was higher than in the general population, especially among DD patients. Despite the multiple barriers to access healthcare by patients with chronic mental illness, efforts to include this population in screening and treatment are mandatory.

Recommendations and quality criteria to improve the early diagnosis of primary biliary cholangitis. / Recomendaciones y criterios de calidad para mejorar el diagnóstico precoz de la colangitis biliar primaria.

OBJECTIVE: The study aimed to establish recommendations and quality criteria to enhance the healthcare process of PBC. PATIENTS AND METHODS: It was conducted using qualitative techniques, preceded by a literature review. A consensus conference involving five specialists in the field was held, followed by a Delphi process developed in two waves, in which 30 specialist physicians in family and community medicine, digestive system and internal medicine were invited to participate. RESULTS: Seven recommendations and 15 sets of quality criteria, indicators and standards were obtained. Those with the highest consensus were «Know the impact on the patient's quality of life. Consider their point of view and agree on recommendations and care¼ and «Evaluate possible fibrosis at the time of diagnosis and during PBC follow-up, assessing the evolution of factors associated with poor disease prognosis: noninvasive fibrosis (elastography > 2.1 kPa/year), GGT, ALP and bilirubin annually¼, respectively. CONCLUSIONS: The implementation of the consensus recommendations and criteria would provide better patient care. The need for multidisciplinary follow-up and an increased role of primary care is emphasized.

Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) survey on the management of patients with inflammatory bowel disease. / Encuesta Sociedad Española de Médicos de Atención Primaria (SEMERGEN) y Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el manejo de pacientes con enfermedad inflamatoria intestinal.

INTRODUCTION: Collaboration between Primary Care (PC) and Gastroenterology in inflammatory bowel disease (IBD) is crucial to provide high-quality healthcare. The aim of this study is to analyse the relationship between PC and gastroenterologists at a national level in order to identify areas for improvement in the management of patients with inflammatory bowel disease (IBD) and how to address them, with the aim of subsequently developing concrete proposals and projects between SEMERGEN and GETECCU. METHODS: Descriptive, observational, cross-sectional study, was carried out using an anonymous online questionnaire between October 2021 and March 2022. RESULTS: A total of 157 surveys from Gastroenterology and 222 from PC were collected. 43.8% and 34.3% of gastroenterologists and family practitioners, respectively, considered that there was a good relationship between the units. The level of knowledge from family practitioners regarding different aspects of IBD out of 10 was: clinical 6.67±1.48, diagnosis 6.47±1.46, treatment 5.63±1.51, follow-up 5.53±1.68 and complications 6.05±1.54. The perception of support between both units did not exceed 4.5 on a scale from 0 to 10 in either of the surveys. The most highly voted improvement proposals were better coordination between the units, implementation of IBD units, and nursing collaboration. CONCLUSION: There are deficiencies in the relationship between PC and Gastroenterology with special dedication to IBD that require the efforts of the scientific societies that represent them for greater coordination with the development of joint protocols and agile, fast, and effective communication channels.

The application of artificial intelligence in improving colonoscopic adenoma detection rate: Where are we and where are we going.

Colorectal cancer (CRC) is one of the common malignant tumors in the world. Colonoscopy is the crucial examination technique in CRC screening programs for the early detection of precursor lesions, and treatment of early colorectal cancer, which can reduce the morbidity and mortality of CRC significantly. However, pooled polyp miss rates during colonoscopic examination are as high as 22%. Artificial intelligence (AI) provides a promising way to improve the colonoscopic adenoma detection rate (ADR). It might assist endoscopists in avoiding missing polyps and offer an accurate optical diagnosis of suspected lesions. Herein, we described some of the milestone studies in using AI for colonoscopy, and the future application directions of AI in improving colonoscopic ADR.

Significant heterogeneity in the diagnosis and long-term management of Wilson disease: Results from a large multicenter Spanish study.

There is uncertainty regarding Wilson's disease (WD) management. OBJECTIVES: To assess, in a multicenter Spanish retrospective cohort study, whether the approach to WD is homogeneous among centers. METHODS: Data on WD patients followed at 32 Spanish hospitals were collected. RESULTS: 153 cases, 58% men, 20.6 years at diagnosis, 69.1% hepatic presentation, were followed for 15.5 years. Discordant results in non-invasive laboratory parameters were present in 39.8%. Intrahepatic copper concentration was pathologic in 82.4%. Genetic testing was only done in 56.6% with positive results in 83.9%. A definite WD diagnosis (Leipzig score ≥4) was retrospectively confirmed in 92.5% of cases. Chelating agents were standard initial therapy (75.2%) with frequent modifications (57%), particularly to maintenance zinc. Enzyme normalization was not achieved by one third, most commonly in the setting of poor compliance, lack of genetic mutations and/or presence of cardiometabolic risk factors. Although not statistically significant, there were trends for sex differences in number of diagnosed cases, age at diagnosis and biochemical response. CONCLUSIONS: Significant heterogeneity in diagnosis and management of WD patients emerges from this multicenter study that includes both small and large reference centers. The incorporation of genetic testing will likely improve diagnosis. Sex differences need to be further explored.