A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions / Serie de 69 dermatosis relacionadas con la COVID con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19

Background Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. Material and method We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. Results After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. Conclusions Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions (AU)

Antecedentes A pesar del gran número de artículos publicados sobre las lesiones cutáneas relacionadas con la COVID-19, no se ha realizado una correlación clinicopatológica de manera consistente, y no ha sido validado el estudio de inmunohistoquímica para demostrar la expresión de la proteína spike 3 mediante RT-PCR. Material y métodos Recopilamos 69 casos de pacientes con COVID-19 confirmada, en los que se estudiaron las lesiones cutáneas a nivel clínico e histopatológico, habiéndose realizado la prueba inmunohistoquímica (IHQ) y RT-PCR en las biopsias cutáneas. Resultados Tras una revisión detallada de los casos, en 15 de ellos se encontró que la dermatosis no guardaba relación con la COVID-19, mientras que el resto de las lesiones podrían clasificarse de acuerdo con sus características clínicas como vesiculares (4), erupciones maculopapulares (41), urticariformes (9), livedo y necrosis (10) y de tipo perniosis (5). Aunque las características histopatológicas fueron similares a los resultados previamente reportados, encontramos dos hallazgos no reportados previamente: erupciones maculopapulares con siringometaplasia ecrina escamosa y epiteliotropismo neutrofílico. La IHQ reflejó en ciertos casos tinción endotelial y epidérmica, pero la prueba RT-PCR fue negativa en todos los casos probados. Por ello no pudo demostrarse el compromiso viral directo. Conclusiones A pesar de presentar la mayor serie de pacientes con COVID-19 confirmada y manifestaciones cutáneas histopatológicamente estudiadas, el compromiso viral directo fue difícil de establecer. Las lesiones vasculopáticas e urticariformes parecen ser las más claramente relacionadas con la infección viral, a pesar de que los resultados negativos de la IHQ o RT-PCR no pudieron demostrar la presencia viral (AU)

[Articulo traducido] Serie de 69 dermatosis relacionadas con la COVID-19 con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19 / A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions

Antecedentes A pesar del gran número de artículos publicados sobre las lesiones cutáneas relacionadas con la COVID-19, no se ha realizado una correlación clinicopatológica de manera consistente, y no ha sido validado el estudio de inmunohistoquímica para demostrar la expresión de la proteína spike 3 mediante RT-PCR. Material y métodos Recopilamos 69 casos de pacientes con COVID-19 confirmada, en los que se estudiaron las lesiones cutáneas a nivel clínico e histopatológico, habiéndose realizado la prueba inmunohistoquímica (IHQ) y RT-PCR en las biopsias cutáneas. Resultados Tras una revisión detallada de los casos, en 15 de ellos se encontró que la dermatosis no guardaba relación con la COVID-19, mientras que el resto de las lesiones podrían clasificarse de acuerdo con sus características clínicas como vesiculares (4), erupciones maculopapulares (41), urticariformes (9), livedo y necrosis (10) y de tipo perniosis (5). Aunque las características histopatológicas fueron similares a los resultados previamente reportados, encontramos dos hallazgos no reportados previamente: erupciones maculopapulares con siringometaplasia ecrina escamosa y epiteliotropismo neutrofílico. La IHQ reflejó en ciertos casos tinción endotelial y epidérmica, pero la prueba RT-PCR fue negativa en todos los casos probados. Por ello no pudo demostrarse el compromiso viral directo. Conclusiones A pesar de presentar la mayor serie de pacientes con COVID-19 confirmada y manifestaciones cutáneas histopatológicamente estudiadas, el compromiso viral directo fue difícil de establecer. Las lesiones vasculopáticas e urticariformes parecen ser las más claramente relacionadas con la infección viral, a pesar de que los resultados negativos de la IHQ o RT-PCR no pudieron demostrar la presencia viral (AU)

Background Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. Material and method We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. Results After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. Conclusions Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions (AU)

A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions. / [Articulo traducido] Serie de 69 dermatosis relacionadas con la COVID-19 con biopsia, estudio inmunohistoquímico con anti-spike 3, hibridación in situ y PCR: Una revisión crítica de la afectación cutánea relacionada con la COVID-19.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

A Series of 69 COVID-related Dermatoses With Biopsy, Immunohistochemistry With Anti-spike 3, in situ Hybridization and PCR: A Critical Reappraisal of Viral Involvement in COVID-19 Skin Lesions.

BACKGROUND: Despite the large number of articles published on skin lesions related to COVID-19, clinicopathological correlation has not been performed consistently and immunohistochemistry to demonstrate spike 3 protein expression has not been validated through RT-PCR. MATERIAL AND METHODS: We compiled 69 cases of patients with confirmed COVID-19, where skin lesions were clinically and histopathologically studied. Immunohistochemistry (IHC) and RT-PCR was performed in skin biopsies. RESULTS: After a careful review of the cases, 15 were found to be dermatosis not related to COVID-19, while the rest of the lesions could be classified according to their clinical characteristics as vesicular (4), maculopapular eruptions (41), urticariform (9), livedo and necrosis (10) and pernio-like (5). Although histopathological features were similar to previously reported results, we found two previously unreported findings, maculopapular eruptions with squamous eccrine syringometaplasia and neutrophilic epitheliotropism. IHC showed in some cases endothelial and epidermal staining but RT-PCR was negative in all the tested cases. Thus, direct viral involvement could not be demonstrated. CONCLUSIONS: Despite presenting the largest series of confirmed COVID-19 patients with histopathologically studied skin manifestations, direct viral involvement was difficult to establish. Vasculopathic and urticariform lesions seem to be those more clearly related to the viral infection, despite IHC or RT-PCR negative results failed to demonstrate viral presence. These findings, as in other dermatological areas, highlight the need of a clinico-pathological correlation to increase knowledge about viral involvement in COVID-19 skin-related lesions.

SARS-CoV-2 endothelial infection causes COVID-19 chilblains: histopathological, immunohistochemical and ultrastructural study of seven paediatric cases.

BACKGROUND: Chilblains ('COVID toes') are being seen with increasing frequency in children and young adults during the COVID-19 pandemic. Detailed histopathological descriptions of COVID-19 chilblains have not been reported, and causality of SARS-CoV-2 has not yet been established. OBJECTIVES: To describe the histopathological features of COVID-19 chilblains and to explore the presence of SARS-CoV-2 in the tissue. METHODS: We examined skin biopsies from seven paediatric patients presenting with chilblains during the COVID-19 pandemic. Immunohistochemistry for SARS-CoV-2 was performed in all cases and electron microscopy in one. RESULTS: Histopathology showed variable degrees of lymphocytic vasculitis ranging from endothelial swelling and endotheliitis to fibrinoid necrosis and thrombosis. Purpura, superficial and deep perivascular lymphocytic inflammation with perieccrine accentuation, oedema, and mild vacuolar interface damage were also seen. SARS-CoV-2 immunohistochemistry was positive in endothelial cells and epithelial cells of eccrine glands. Coronavirus particles were found in the cytoplasm of endothelial cells on electron microscopy. CONCLUSIONS: Although the clinical and histopathological features were similar to other forms of chilblains, the presence of viral particles in the endothelium and the histological evidence of vascular damage support a causal relation of the lesions with SARS-CoV-2. Endothelial damage induced by the virus could be the key mechanism in the pathogenesis of COVID-19 chilblains and perhaps also in a group of patients severely affected by COVID-19 presenting with features of microangiopathic damage. What is already known about this topic? Despite the high number of cases of chilblains seen during the COVID-19 pandemic, a definite causative role for SARS-CoV-2 has not yet been proven. Different pathogenetic hypotheses have been proposed, including coagulation anomalies, interferon release and external factors. What does this study add? The demonstration of SARS-CoV-2 in endothelial cells of skin biopsies by immunohistochemistry and electron microscopy confirms that these lesions are part of the spectrum of COVID-19. Virus-induced vascular damage and secondary ischaemia could explain the pathophysiology of COVID-19 chilblains. Our findings support the hypothesis that widespread endothelial infection by SARS-CoV-2 could have a pathogenetic role in the severe forms of COVID-19. Linked Comment: Wetter. Br J Dermatol 2020; 183:611.

[Guideline: Auditory Processing and Perception Disorders: Differential Diagnosis : S1 guideline of the German Society of Phoniatrics and Pediatric Audiology]. / Leitlinie "Auditive Verarbeitungs- und Wahrnehmungsstörungen": Differenzialdiagnose : S1-Leitlinie der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie.

As a prerequisite for diagnosing auditory processing disorders (APD), differential diagnostic considerations are essential, especially with regard to language comprehension disorders, attention deficit hyperactivity disorder, specific cognitive impairments (e. g., in memory or multi-modal perception performance), specific learning disorders affecting reading and/or spelling, and autistic-type diseases. The current clinical management is presented in detail in the updated APD guidelines, as are the resulting conclusions for the interpretation of individual test results.

[Auditory processing and perception disorders (APPD): summary and updated overview]. / Auditive Verarbeitungs- und Wahrnehmungsstörungen (AVWS): Zusammenfassung und aktualisierter Überblick.

The APD guideline of 2009 was supplemented by the statements listed here. The addition is based on current knowledge and findings. Otherwise, the Guideline 2009 remains valid. Here, a summary of the updated APD guideline is given, thus proving an overview of the definition of APD, diagnosis, differential diagnosis and recommended for APD management.

[Morphological and genetic aspects of Spitz tumors]. / Morphologische und genetische Aspekte bei Spitz-Tumoren.

BACKGROUND: Spitzoid melanocytic neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) are a clinical, histopathological and molecular genetic heterogeneous group of melanocytic skin tumors. OBJECTIVES: Correlation of the histological features of spitzoid neoplasms with molecular genetic aberrations. MATERIAL AND METHODS: A review and summary of the scientific literature. RESULTS: Several histopathological and molecular genetic distinct subtypes of spitzoid lesions have been defined. Epithelioid Spitz tumors commonly show a loss of the BAP1 gene and BRAF mutations and are associated with a hereditary tumor predisposition syndrome. Desmoplastic Spitz tumors frequently harbor HRAS mutations and gains of the chromosome arm 11p. Plexiform Spitz tumors often display ALK translocations. The morphology of Spitz tumors with ROS1, NTRK1, RET and BRAF fusion genes seems to be unspecific and is currently not well characterized. CONCLUSION: Morphological features offer valuable clues to the underlying genetic aberrations in spitzoid neoplasms. Genetic aberrations can be found in the entire biological spectrum of spitzoid neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) and are, therefore, probably not useful for distinguishing benign from malignant tumors; however, genetic aberrations represent important targets for therapeutic interventions and offer investigational treatment options for patients with metastatic disease. The appearance of multiple epithelioid melanocytic tumors with BAP1 loss indicates a hereditary tumor syndrome and warrants genetic counseling and preventive screening of affected individuals.

[Objective hearing tests in pediatric audiology: AGERA recommendations for follow-up diagnosis in infants that fail newborn hearing screening tests]. / Empfehlungen der AGERA zum Einsatz objektiver Hörprüfmethoden im Rahmen der pädaudiologischen Konfirmationsdiagnostik (Follow-up) nach nicht bestandenem Neugeborenen-Hörscreening.

This paper presents the recommendations compiled by the German Electric Response Audiometry Working Group (Arbeitsgruppe Elektrische Reaktions-Audiometrie, AGERA) and the Association of German Audiologists and Neuro-otologists (Arbeitsgemeinschaft Deutschsprachiger Audiologen und Neurootologen, ADANO) for infants that fail newborn hearing screening (NHS) tests. Outlined are procedures for follow-up diagnosis using objective hearing tests to rule out or confirm a therapeutically relevant auditory defect and assessment of the severity thereof.

Absence of BRAF and HRAS mutations in eruptive Spitz naevi.

BACKGROUND: Eruptive Spitz naevi have been reported rarely in the literature. In solitary Spitz naevi, BRAF and HRAS mutations, as well as increased copy numbers of chromosome 11p have been identified. OBJECTIVES: To investigate the genetic changes underlying eruptive Spitz naevi. METHODS: We report on a 16-year-old boy who developed multiple disseminated eruptive Spitz naevi within a few months. We analysed BRAF, HRAS, KRAS and NRAS genes in 39 naevi from this patient for hotspot mutations. Furthermore, comparative genomic hybridization analysis was performed in three lesions. RESULTS: None of the Spitz naevi displayed a mutation in the analysed genes, and no chromosomal imbalances were observed. Conclusions Our results indicate that the typical genetic alterations described in solitary Spitz naevi appear to be absent in eruptive Spitz naevi. Yet unknown alternative genetic alterations must account for this rare syndrome.

Circulating endocannabinoids and N-acyl-ethanolamides in patients with sleep apnea--specific role of oleoylethanolamide.

OBJECTIVE: The endocannabinoid system promotes diverse effects on fat and glucose metabolism as well as on energy balance and sleep regulation. The role of N-acylethanolamides like oleoylethanolamide (OEA) and other endocannabinoids such as anandamide (AEA) and 2-arachidonyl-glycerol (2-AG) has not yet been investigated in patients with sleep apnea. DESIGN AND METHODS: We measured circulating OEA, AEA and 2-AG in patients with sleep apnea (n = 20) and healthy control subjects (n = 57). Respiratory distress index (RDI) as measured by polysomnography was used as a quantitative index of sleep apnea. RESULTS: In patients with sleep apnea OEA serum concentrations were significantly higher than in control subjects (8.4 pmol/ml (95% CI 6.9;9.9) vs. 4.0 (3.5;4.5); p<0.0001, adjusted for body mass index (BMI), fasting insulin, HDL and LDL cholesterol). In contrast, AEA (2.9 (95% CI 1.9;3.9) vs. 1.8 (1.4;2.1), p = 0.09) and 2-AG (20.0 (-14.5;54.5) vs. 32.8 (21.4;44.2), p = 0.56) were not significantly different between patients with sleep apnea and control subjects after adjustment. In the sleep apnea group, OEA serum concentrations were associated with RDI (r (2) = 0.28, p = 0.02) and BMI (r (2) = 0.32, p = 0.01). However, OEA was not associated with BMI in the control group (p = 0.10). CONCLUSIONS: These results indicate that among the three analyzed fatty acid derivatives, OEA plays a specific role in patients with sleep apnea. Together with animal data, the 2-fold elevation of OEA serum concentrations could be interpreted as a neuroprotective mechanism against chronic oxidative stressors and a mechanism to promote wakefulness in patients with nocturnal sleep deprivation and daytime hypersomnolence.

Cutaneous Lymphomas: from Morphology to Chip Technology / Llnfomas cutáneos: de la morfología a la tecnología de microprocesador

Cutaneous lymphomas represent a heterogenous group of malignant lymphoid diseases with particular tropism for the skin. Prognosis and treatment depend on the type of lymphoma, thus precise diagnosis and classification are of paramount importance. Classification of cutaneous lymphomas relies on a synthesis of all available information, including clinical history and presentation, histopathology, immunophenotype, and molecular data. Thanks to the efforts of the lymphoma groups of both the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC), a joint WHO-EORTC classification for primary cutaneous Iymphomas has been proposed in 2005. The WHO-EORTC classification has been adsorbed with minor changes in the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues, thus including for the first time primary cutaneous lymphomas as distinct subtypes of extranodal lymphomas in a general classification of lymphomas (AU)

Los linfomas cutáneos representan un grupo heterogéneo de neoplasias linfoides con un tropismo particular por la piel. El pronóstico y el tratamiento dependen del tipo de linfoma, por tanto son de suma importancia un diagnóstico y clasificación precisos. La clasificación de los linfomas cutáneos se basa en un compendio de toda la información disponible, incluyendo la historia clínica y la presentación, la histopatología, el inmunofenotipo y los datos moleculares. Gracias a los esfuerzos de los grupos de linfoma, tanto de la Organización Mundial de la Salud (siglas en inglés WHO) como de la Organización Europea para la Investigación y el Tratamiento del Cáncer (siglas en inglés EORTC), se ha propuesto una clasificación conjunta WHO-EORTC para los linfomas cutáneos primarios en 2005. La clasificación de la WHO de 2008 de los tumores de los tejidos hematopoyéticos y linfoides ha incorporado la clasificación de la WH0-EORTC con cambios mínimos incluyendo, por primera vez, a los linfomas cutáneos primarios como subtipos distintos de linfomas extraganglionares en una clasificación general de linfomas (AU)

[Quality assurance of a universal newborn hearing screening. Recommendations of the German Society of Phoniatrics and Pediatric Audiology]. / Qualitätssicherung eines universellen Neugeborenen-Hörscreenings. Empfehlungen der Deutschen Gesellschaft für Phoniatrie und Pädaudiologie.

Statutory implementation of a universal newborn hearing screening requires a continuous quality assurance monitoring. Therefore, at the Annual Meeting in 2007, the members of the German Society of Phoniatrics and Pediatric Audiology passed a recommendation on measures of quality assurance applied to newborn hearing screening. This recommendation describes the procedures, performance, location, time frame, and technical prerequisites of the screening and of potentially necessary follow-ups, the definition of hearing loss to be detected, the performing and responsible professional groups and their qualifications for the screening, the regulation of repeat and control screenings, the confirmation diagnostics and initiation of therapy, the information of parents, the documentation of screening results, the aims and organization of a tracking system, the tasks of regional screening centers and of a supraregional institution for the quality assurance of the hearing screening, the central collection of person and screening-related quality relevant data, and the accessibility of defined data sets as predisposition for cost analyses and quality reports.

Cutaneous lymphomas: from morphology to chip technology.

Cutaneous lymphomas represent a heterogeneous group of malignant lymphoid diseases with particular tropism for the skin. Prognosis and treatment depend on the type of lymphoma, thus precise diagnosis and classification are of paramount importance. Classification of cutaneous lymphomas relies on a synthesis of all available information, including clinical history and presentation, histopathology, immunophenotype, and molecular data. Thanks to the efforts of the lymphoma groups of both the World Health Organization (WHO) and the European Organization for Research and Treatment of Cancer (EORTC), a joint WHO-EORTC classification for primary cutaneous lymphomas has been proposed in 2005. The WHO-EORTC classification has been adsorbed with minor changes in the 2008 WHO classification of tumours of haematopoietic and lymphoid tissues, thus including for the first time primary cutaneous lymphomas as distinct subtypes of extranodal lymphomas in a general classification of lymphomas.

Impact of the Thr789Ala variant of the von Willebrand factor levels, on ristocetin co-factor and collagen binding capacity and its association with coronary heart disease in patients with diabetes mellitus type 2.

A Thr789Ala variant in the von Willebrand Factor (vWF) gene is associated with increased vWF plasma concentrations and might therefore affect the risk of coronary heart disease (CHD) in the general population. Patients with type 2 diabetes have an increased risk for premature atherosclerosis and are characterized by alterations of the coagulation system. However, it is not known whether the Thr789Ala variant in the vWF gene contributes to the increased CHD risk in patients with type 2 diabetes. We therefore investigated the potential relationship between the Thr789Ala variant in the vWF gene and the occurrence of CHD in 356 patients with type 2 diabetes, either with (DM+/CHD+, n = 204) or without evidence for CHD (DM+/CHD-, n = 152). In addition, two control groups without type 2 diabetes, with (DM-/CHD+, n = 22) or without CHD (DM-/CHD-, n = 100), were investigated. Individuals with the vWF Thr789Ala variant have significantly higher von Willebrand factor plasma concentrations (p < 0.001). In addition, ristocetin co-factor was significantly increased in vWF Thr789Ala variant carriers (p < 0.05). Ristocetin co-factor levels and collagen binding capacity were also increased in individuals affected with either type 2 diabetes, CHD or both (DM+/CHD+, DM+/CHD-, DM-/CHD+) as compared to healthy controls (DM-/CHD-) (p < 0.001). However, we did not find an association between the vWF Thr789Ala variant and the occurrence of CHD in patient with type 2 diabetes (p = 0.34). In conclusion, although the Thr789Ala vWF gene variant is associated with increased plasma concentrations of vWF, ristocetin co factor levels and collagen binding capacity in patients with type 2 diabetes and CHD, a direct effect of this variant on the occurrence of CHD in patients with type 2 diabetes, could not be detected.