Ipercolesterolemia familiare: dal genotipo al fenotipo ed implicazione terapeutiche dei nuovi farmaci biologici ipocolesterolemizzanti

AIMS: Familial Hypercholesterolemia (FH) is a frequent genetic cause of early coronary artery disease, and is still under-diagnosed and under-treated. With the advent of PCSK9 inhibitors as adjunctive therapy to maximal lipid-lowering therapy, a significant reduction in cholesterol levels of low-density lipoprotein (LDL-C) and cardiovascular events was observed, while maintaining a good safety and tolerance profile. Ultrasonography (US) detects Achilles tendon (AT) xanthomas in patients (pts) with FH. Given the recent introduction of new therapies, there are no studies in the literature that evaluate the efficacy and safety of this therapy over a period of more than 3 years. We analysed the potential associations between FH genotype, clinical phenotype and ultrasonographic AT findings, evaluating the contribution of AT US to identify individuals with an FH-causing mutation. We also analysed the long-term efficacy and safety of additional therapy with PCSK9 inhibitors, comparing treatment with evolocumab and that with alirocumab. SUBJECTS AND METHODS: Genetic screening, clinical and biochemical parameters in 194 pts with possible, probable or definite clinical diagnosis of FH according to the Dutch Lipid Clinic Network Score (DLCNS); 71 pts underwent bilateral AT US. RESULTS: 43 pts carriers of null allele (NA) and 62 of defective (DEF) allele for LDL receptor while 33 pts with no known mutations (NM) for FH. Presence of xanthomas and gerontoxon, total and LDL-cholesterol (NA vs DEF vs NM: 326.5+97.7 mg/dl, 316.9+93.9 mg/dl, 211.1+76.3mg/dl, p<0.000) at diagnosis were significantly higher in NA pts than other subgroups. AT thickness was significantly different among the three groups (p< 0,005) and 78.2%, 72.4% and 31.6% had USX in NA, DEF and NM carriers respectively (p=0.002). Among the 52 pts positive for FH-causing mutations, 16 pts had a clinical diagnosis either possible or probable and in nine pts the presence of USX was clinically undetected and thereby not considered for DLCNS calculation. Tendon ultrasound was able to show a prevalence of 51% of tendon xanthomas in comparison to the prevalence of alterations detected only by physical examination, which was 10,2%. Following the addition of treatment with PCSK9 inhibitors, a mean reduction in LDL-C levels from 169 ± 30 mg / dl to 46 ± 16 was obtained, compared to the traditional maximal lipid-lowering treatment, ie in percentage terms a reduction of 72.4%. Compared to baseline LDL-C levels, this corresponds to an average reduction of 86.9%. There were no statistically significant differences between treatment with evolocumab and that with alirocumab in terms of reduction of LDL-C levels. In the course of traditional maximal lipid-lowering therapy, the goal of LDL cholesterol was obtained based on the personal level of cardiovascular risk in 0% of cases, while with the addition of PCSK9 inhibitors, 100% of subjects achieved therapeutic goal. No statistically significant differences were found following the introduction of PCSK9 inhibitor treatment with regard to CPK and transaminase levels. Over the years we have observed that LDL-C levels remained substantially stable. CONCLUSIONS: Genotypic functional characterization is associated with different phenotypic clinical features, AT thickness and presence of US xanthomas. AT ultrasonography may help reclassifying as definite FH, patients with DLCN score of possible/probable FH. Achilles tendon ultrasound has a greater sensibility than standard physical exam. It discloses a noticeable higher prevalence of tendon xanthomas (51%) in comparison to clinical evaluation (10,2%). This exam allows to look in a more integrated way at the cardiovascular and tendon complications in everyeach patient. It also suggests, when xanthomas are found, the necessity to adopt a stronger lipid-lowering therapy. In our study, in subjects with FH, it emerged that PCSK9 inhibitor therapy (evolocumab or alirocumab), in addition to maximal lipid-lowering therapy, results in a significant reduction of LDL-C levels, allowing the totality of patients to achieve the therapeutic goal of LDL-C related to its cardiovascular risk. Further studies are needed to confirm mainly the persistence of long-term efficacy and safety of PCSK9 inhibitor therapy and to evaluate on a larger scale whether there are differences between evolocumab and alirocumab in terms of efficacy in reducing LDL-C and cardiovascular risk

Fatores associados ao desenvolvimento de alergias de pele em prematuros no primeiro ano de vida

Objetivo: Identificar os fatores associados ao desenvolvimento de alergias de pele no primeiro ano de vida em prematuros moderados e tardios.  Método: Trata-se de uma pesquisa seccional, com 151 prematuros moderados e tardios, nascidos entre maio de 2016 e maio de 2017. Os participantes foram avaliados no 3º, 6º, 9º e 12º mês de vida, por contato telefônico. As análises estatísticas foram realizadas no software SPSS com testes de comparação de frequência e regressão logística. Resultados: A prevalência de alergia de pele, na percepção dos cuidadores, entre prematuros tardios e moderados foi de 16%. Fatores como ser egresso da terapia intensiva neonatal (p=0,006) e não estar em aleitamento materno (p=0,041) mostrou associação significativa no 3º e 12ª mês de vida, respectivamente. Conclusão: A alergia de pele, na percepção dos cuidadores, é uma característica mais intensa naqueles que apresentam manifestações clínicas respiratórias e gastrointestinais, seja ela condicionante ou de causa-efeito. O aleitamento materno mostrou-se um fator protetor no 1º ano de vida. Palavras-chave: Recém-nascido prematuro. Lactente. Pele. Manifestações cutâneas. Fatores de risco

Ipercolesterolemia familiare: dal genotipo al fenotipo ed implicazione terapeutiche dei nuovi farmaci biologici ipocolesterolemizzanti

AIMS: Familial Hypercholesterolemia (FH) is a frequent genetic cause of early coronary artery disease, and is still under-diagnosed and under-treated. With the advent of PCSK9 inhibitors as adjunctive therapy to maximal lipid-lowering therapy, a significant reduction in cholesterol levels of low-density lipoprotein (LDL-C) and cardiovascular events was observed, while maintaining a good safety and tolerance profile. Ultrasonography (US) detects Achilles tendon (AT) xanthomas in patients (pts) with FH. Given the recent introduction of new therapies, there are no studies in the literature that evaluate the efficacy and safety of this therapy over a period of more than 3 years. We analysed the potential associations between FH genotype, clinical phenotype and ultrasonographic AT findings, evaluating the contribution of AT US to identify individuals with an FH-causing mutation. We also analysed the long-term efficacy and safety of additional therapy with PCSK9 inhibitors, comparing treatment with evolocumab and that with alirocumab. SUBJECTS AND METHODS: Genetic screening, clinical and biochemical parameters in 194 pts with possible, probable or definite clinical diagnosis of FH according to the Dutch Lipid Clinic Network Score (DLCNS); 71 pts underwent bilateral AT US. RESULTS: 43 pts carriers of null allele (NA) and 62 of defective (DEF) allele for LDL receptor while 33 pts with no known mutations (NM) for FH. Presence of xanthomas and gerontoxon, total and LDL-cholesterol (NA vs DEF vs NM: 326.5+97.7 mg/dl, 316.9+93.9 mg/dl, 211.1+76.3mg/dl, p<0.000) at diagnosis were significantly higher in NA pts than other subgroups. AT thickness was significantly different among the three groups (p< 0,005) and 78.2%, 72.4% and 31.6% had USX in NA, DEF and NM carriers respectively (p=0.002). Among the 52 pts positive for FH-causing mutations, 16 pts had a clinical diagnosis either possible or probable and in nine pts the presence of USX was clinically undetected and thereby not considered for DLCNS calculation. Tendon ultrasound was able to show a prevalence of 51% of tendon xanthomas in comparison to the prevalence of alterations detected only by physical examination, which was 10,2%. Following the addition of treatment with PCSK9 inhibitors, a mean reduction in LDL-C levels from 169 ± 30 mg / dl to 46 ± 16 was obtained, compared to the traditional maximal lipid-lowering treatment, ie in percentage terms a reduction of 72.4%. Compared to baseline LDL-C levels, this corresponds to an average reduction of 86.9%. There were no statistically significant differences between treatment with evolocumab and that with alirocumab in terms of reduction of LDL-C levels. In the course of traditional maximal lipid-lowering therapy, the goal of LDL cholesterol was obtained based on the personal level of cardiovascular risk in 0% of cases, while with the addition of PCSK9 inhibitors, 100% of subjects achieved therapeutic goal. No statistically significant differences were found following the introduction of PCSK9 inhibitor treatment with regard to CPK and transaminase levels. Over the years we have observed that LDL-C levels remained substantially stable. CONCLUSIONS: Genotypic functional characterization is associated with different phenotypic clinical features, AT thickness and presence of US xanthomas. AT ultrasonography may help reclassifying as definite FH, patients with DLCN score of possible/probable FH. Achilles tendon ultrasound has a greater sensibility than standard physical exam. It discloses a noticeable higher prevalence of tendon xanthomas (51%) in comparison to clinical evaluation (10,2%). This exam allows to look in a more integrated way at the cardiovascular and tendon complications in everyeach patient. It also suggests, when xanthomas are found, the necessity to adopt a stronger lipid-lowering therapy. In our study, in subjects with FH, it emerged that PCSK9 inhibitor therapy (evolocumab or alirocumab), in addition to maximal lipid-lowering therapy, results in a significant reduction of LDL-C levels, allowing the totality of patients to achieve the therapeutic goal of LDL-C related to its cardiovascular risk. Further studies are needed to confirm mainly the persistence of long-term efficacy and safety of PCSK9 inhibitor therapy and to evaluate on a larger scale whether there are differences between evolocumab and alirocumab in terms of efficacy in reducing LDL-C and cardiovascular risk.INTRODUZIONE e SCOPI dello STUDIO: L’Ipercolesterolemia Familiare (FH) è un disordine del metabolismo lipidico su base genetica, rara in omozigosi (1/250000) ma coinvolgente 1 soggetto ogni 250 abitanti nella forma eterozigote. Il fenotipo lipidico è caratterizzato da livelli molto elevati di colesterolo delle lipoproteine a bassa densità (LDL) dalla nascita e da un rischio elevato di aterosclerosi che predispone ad eventi clinici cardiovascolari (CHD) precoci. La FH è causata da mutazioni nei geni che codificano per proteine chiave coinvolte nelle vie metaboliche che riguardano il recettore delle LDL (LRL-R) e il suo ciclo metabolico, con conseguente diminuzione dell’uptake cellulare delle LDL e conseguente aumento delle concentrazioni plasmatiche del colesterolo LDL (LDL-C). Tra i geni coinvolti sono note mutazioni con perdita di funzione nel gene LDLR, mutazioni nel gene dell’apolipoproteina B (ApoB) che alterano il dominio di legame dell’ApoB con LDL-R, mutazioni con guadagno di funzione nel gene per la proteina convertasisubtilisina/kexina tipo 9 (PCSK9). Tra le mutazioni del LDL-R si riconoscono cinque classi funzionali, una delle quali è chiamata allele nullo e normalmente determina un difetto nella sintesi del recettore con conseguente funzione recettoriale quasi completamente abolita (<5% rispetto alla norma). Le restanti sono legate un’alterata sintesi della proteina dovuta ad alterazioni della sequenza amminoacidica che comporta difetti nel trasporto del recettore, nel legame tra ligando e recettore, nella localizzazione dello stesso a livello della superficie cellulare e infine nel riciclaggio. Allo scopo di stabilire una diagnosi clinica, sono raccomandati i criteri del Dutch Lipid Clinic Network (DLCN) che permettono di fare diagnosi di FH considerando cinque aspetti anamnestici, clinici e bioumorali. La formazione precoce di gerontoxon, xantelasmi e xantomi sono markers clinici suggestivi per indirizzare verso la diagnosi di FH. L’utilizzo dell’ecografia consente di valutare con maggiore accuratezza lo spessore tendineo, aumentato nel caso in cui siano presenti accumuli lipidici. Dal momento che il tendine di Achille si è rivelato essere la più comune localizzazione per lo sviluppo di xantomi, la valutazione ecografica di questo distretto consente di aumentare notevolmente la sensibilità (fino al 75%) nella diagnosi di FH, a discapito di una relativa perdita di specificità nei confronti di altre forme di ipercolesterolemia. Con l’avvento degli inibitori di PCSK9 come terapia aggiuntiva a una terapia ipolipemizzante massimale, si è osservata una riduzione significativa dei livelli di colesterolo delle lipoproteine a bassa densità (LDL-C) e degli eventi cardiovascolari, mantenendo un buon profilo di sicurezza e tolleranza. In tale contesto si inserisce il nostro studio con la valutazione della mappatura genetica dell’Ipercolesterolemia Familiare in relazione al fenotipo clinico, l’approfondimento dell’utilità dell’impiego dell’ecografia dei tendini achillei come strumento di approfondimento diagnostico, l’analisi di dati di efficacia e sicurezza della terapia addizionale con inibitori di PCSK9. SOGGETTI e METODI:194 soggetti con diagnosi possibile, probabile o certa di FH, in accordo con i criteri del DLCN, sono stati sottoposti a screening genetico e valutazione delle caratteristiche cliniche e bioumorali; di 168 pazienti (pz) ad ora è disponibile il risultato dello screening genetico; 101 pz sono stati sottoposti ad ecografia bilaterale dei tendini achillei; gli xantomi ecografici sono stati definiti come presenza di uno spessore tendineo >6,15 mm in almeno un tendine e/o presenza di formazioni ipoecogene; 20 pazienti con FH eterozigote in trattamento con nuovi farmaci biologici ipocolesterolemizzanti (inibitori PCSK9). RISULTATI: Dei 168 pz con risultato dello screening genetico in particolare 105 pz presentavano mutazione del gene per il recettore delle LDL in forma eterozigote, di cui 43 portatori di allele nullo (NA) e 62 di allele difettivo (DEF); in 33 pz non sono state individuate mutazioni per FH (NM). La prevalenza di xantomi obiettivi e gerontoxon, insieme ai livelli di colesterolo totale e LDL basali sono risultati significativamente maggiori nei soggetti NA rispetto agli altri sottogruppi (xantomi obiettivi: NA vs DEF vs NM 71,4 vs 48,5 vs 30,7 %: p<0,001 Anova; LDL: NA vs DEF vs NM 326,5+97,7 vs 316,9+93,9 vs 211,1+76,3 mg/dl: p<0,001 Anova). Dei 101 pazienti di cui si disponeva del risultato degli esami bioumorali e dell’ecografia tendinea la prevalenza di xantomi obiettivi e gerontoxon, insieme ai livelli di colesterolo totale e LDL basali sono risultati significativamente maggiori nei soggetti NA rispetto agli altri sottogruppi (xantomi obiettivi: NA vs DEF vs NM 26,1 vs 13,8 vs 0,0 %: p=0,054 Anova; LDL: NA vs DEF vs NM 316+117 vs 321+109 vs 199+44 mg/dl: p<0,001 Anova). Lo spessore dei tendini achillei è risultato significativamente diverso tra i tre gruppi (NA vs DEF vs NM 7,64±2,06 vs 7,65±4,02 vs 5,67±0,75 mm: p<0,005 Anova) e la prevalenza di xantomi ecografici era del 78,2%, 72,4% e 31,6% nei soggetti portatori di NA, DEF e NM rispettivamente (p=0,002). Il solo esame obiettivo rilevava la presenza di xantomi tendinei achillei nel 10,2% dei soggetti, mentre l’ecografia tendinea rivelava una prevalenza di lesioni tendinee pari al 51%. Nell’ambito dei 74 pz sottoposti ad ecografia dei tendini achillei di cui si dispone attualmente del risultato dello screening genetico, sono stati considerati i 52 pz con mutazioni responsabili di FH; tra questi 36 pz avevano una diagnosi clinica certa di FH secondo i criteri DLCN (punteggio >8), mentre vi erano 16 pz con diagnosi possibile (punteggio tra 3 e 5) o probabile (punteggio tra 6 e 8). Di questi 16 pz 1 mostrava xantomi evidenziabili clinicamente mentre 10 presentavano lo xantoma ecografico. Nel sottogruppo dei 20 pz trattati con PCSK9, in seguito all’aggiunta di trattamento con inibitori di PCSK9 si è ottenuta, rispetto al trattamento ipolipemizzante tradizionale massimale, una riduzione media dei livelli di LDL-C da 169 ± 30 mg/dl a 46 ± 16, ossia in termini percentuali una riduzione del 72,4% (valore minimo 41,5% e massimo 87,5%). Rispetto ai livelli basali di LDL-C, ciò corrisponde a una riduzione media pari all’86,9%. Non sono emerse differenze statisticamente significative tra il trattamento con evolocumab e quello con alirocumab in termini di riduzione dei livelli di LDL-C. In corso di terapia ipolipemizzante tradizionale massimale si otteneva l’obiettivo di colesterolo delle LDL previsto in base al personale livello di rischio cardiovascolare nello 0% dei casi, mentre con l’aggiunta della terapia con inibitori di PCSK9 il 100% dei soggetti raggiungeva l’obiettivo terapeutico. Non si sono dimostrate differenze statisticamente significative in seguito all’introduzione del trattamento con inibitori di PCSK9 per quanto riguarda i livelli di CPK e di transaminasi. Nel corso degli anni abbiamo osservato che i livelli di LDL-C si mantenevano sostanzialmente stabili. CONCLUSIONI: La caratterizzazione genotipica funzionale si conferma essere associata a fenotipi clinici diversi, anche in termini di spessori tendinei e prevalenza di xantomi ecografici, confermando come il paziente con allele nullo presenti una maggiore aggressività clinica della patologia. L’ecografia del tendine di Achille risulta più sensibile rispetto all’esame obiettivo classico, rilevando una prevalenza di xantomi tendinei notevolmente maggiore rispetto a quella rilevata mediante il solo esame obiettivo. Tale esame consente di guardare in modo integrato alle complicanze tendinee e vascolari nel singolo paziente, suggerendo, ove siano presenti xantomi, un trattamento ipolipemizzante più intensivo. I risultati preliminari di questo studio suggeriscono inoltre come l’ecografia dei tendini di Achille possa essere uno strumento da considerare nell’aiutare a riclassificare quei pazienti per in cui il DLCN score è compatibile con diagnosi possibile o probabile di FH. Tale strumento potrebbe inoltre rivelarsi un valido alleato per il clinico, aiutandolo nel raggiungimento di una diagnosi sempre più precoce, ed una garanzia per il paziente di ricevere quanto prima il trattamento farmacologico più adeguato alla sua fascia di rischio. L’utilizzo degli anticorpi monoclonali anti-PCSK9, evolocumab ed alirocumab, rappresenta un approccio terapeutico innovativo, caratterizzato da elevato profilo di sicurezza ed altamente efficacie in associazione alla terapia massimale attualmente disponibile nei pazienti eterozigoti per FH. Ulteriori studi sono necessari per confermare principalmente la persistenza di efficacia e sicurezza a lungo termine della terapia con inibitori di PCSK9 e per valutare su larga scala se vi siano differenze tra evolocumab e alirocumab in termini di efficacia nella riduzione dei livelli di LDL-C e del rischio cardiovascolare

Multidisciplinary Care for the Prevention and Treatment of Venous Thromboembolism in Patients with Cancer-Associated Thrombosis (CAT): Impact of Educational Interventions on CAT-Related Events and on Patients&rsquo; and Clinicians&rsquo; Awareness

Cancer is a leading cause of death. Venous thromboembolism (VTE) is an often-overlooked cause of morbidity and mortality in cancer patients that can be readily prevented and treated. Actions are needed to reduce the morbidity and mortality of patients with cancer-associated thrombosis (CAT). There is a need to increase awareness of the impact of CAT on cancer patients&rsquo; morbidity and mortality, on their quality of life and to understand the importance of more effective preventions and treatments of VTE in cancer patients. Moreover, it is of great importance to systematically assess the risk of VTE in regard to patients, cancer and treatment-related factors. Unfortunately, there are unmet clinical needs in the prevention and treatment of cancer-associated VTE. In this review, we discuss an action plan to ensure an increased awareness of and education on the issues that need to be addressed in order to improve the provision of appropriate prevention, early diagnosis and effective and safe treatment of VTE to all cancer patients and, ultimately, to reduce morbidity and mortality

I farmaci che riducono la mortalit\ue0: gli ipolipemizzanti

Cardiovascular disease (CVD) is the leading cause of death in Italy and in the 28 countries of the European Union. Low-density lipoprotein cholesterol (LDL-C) is a key CVD risk factor. Results from the randomized intervention clinical trials with lipid-lowering agents strongly suggest that the reduction of fatal and non-fatal CVD events is associated with the absolute LDL-C reduction, in mg/dl or mmol/L, regardless of the lipid-lowering agent studied. Statins, by decreasing cholesterol synthesis in the liver, are associated with a large LDL-C reduction and with robust and convincing evidence of a significant reduction of all-cause, CVD and coronary heart disease (CHD) mortality. An LDL-C reduction by 39 mg/dl (1 mmol/L) on statin therapy is associated with a decrease by 10% (p<0.0001) in all-cause mortality, by 20% (p<0.0001) in CHD deaths and by 24% (p<0.0001) in major cardiovascular events. These results were often observed in secondary CVD prevention patients (4S, HPS and LIPID trials), independently of patients\u2019 gender and age, in patients on primary CVD prevention at high CV risk and in patients with type two diabetes. In patients with diabetes a 39 mg/dl (1 mmol/L) LDL-C reduction is associated with a decrease by 9% (p=0.02) in all-cause mortality, by 12% (p=0.03) and 13% (p=0.008) in deaths due to CHD and CVD causes respectively, and by 21% (p<0.0001) in major cardiovascular events. Data on CVD and CHD mortality regarding ezetimibe, fibrates and PCSK9 inhibitors are not nearly as robust as those with statin therapy: a significant reduction with these lipid-lowering agents has been observed in combined clinical endpoints including fatal and non-fatal CVD events while no significant reduction in all-cause, CVD or CHD mortality has been reported. This lack of positive results on CVD and CHD mortality should be interpreted in the light of remarkable changes in the background therapy to prevent CVD events seen in patients enrolled in the more recent trials where aggressive antihypertensive, antiplatelet and lipid-lowering therapy are common enrollment criteria for both control and active treatment groups

Vascular risk assessment and management

&lt;b&gt;&lt;/b&gt; Background: Atherosclerotic cardiovascular disease remains the leading cause of morbidity and mortality globally. Methods: the integrated care pathways (ICPs) are tools through which evidence-based guidelines (GLs) on a specific disease or clinical topic can be implemented in a clinical process. Aim: This study aims to facilitate decision making for health professionals in their daily practice. Results: This model, according with the European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) Guidelines, supports the multifactorial evaluation of global cardiovascular (CV) risk and suggests using algorithms and revised cardiovascular risk stratification, specifically for high- and very-high-risk patients. Conclusions: Multidimensional and integrated actions are aimed at eliminating and/or minimizing the impact of cardiovascular disease, improving the quality and consistency of vascular prevention, and leading to optimal clinical decisions

Factores asociados al seguimiento del cuidado de niños menores de dos años

Objetivo: analizar los factores asociados al seguimiento adecuado del cuidado infantil en niños meno­res de dos años. Materiales y métodos: estu­dio analítico-transversal desarrolla­do entre noviembre de 2019 y marzo de 2020 en las diez unidades básicas de salud de un municipio del interior de Rio Grande do Sul, Brasil. Partici­paron 71 familiares de niños menores de dos años. Los datos se recopilaron a través de la Herramienta para la Evaluación de la Atención Primaria, versión infantil (PCATool Infantil), e instrumentos de perfil clínico y socioeconómico. Se utilizó estadís­tica analítica, con comparación de frecuencias entre variables. Resultados: el 72 % de los niños menores de dos años tuvieron un seguimien­to adecuado durante las consultas. Los hijos de madres que asistieron a una serie de consultas prenata­les adecuadas tuvieron un número significativamente mayor de consul­tas de cuidado infantil de forma adecuada (p = 0,02). Las familias que no han vivido en medio de vulnera­bilidades sociales y de salud brindan mejor cuidado a los niños (p > 0,05). Cuidadores más jóvenes mostraron mayor adhesión a las consultas. Conclusiones: la adhesión adecua­da de las mujeres gestantes a la aten­ción prenatal, estar bajo la responsa­bilidad de cuidadores jóvenes y no asistir a guarderías o escuelas fueron los factores significativamente más asociados al seguimiento de puericul­tura en niños menores de dos años

Fatores associados ao desenvolvimento de alergias de pele em prematuros no primeiro ano de vida

Objetivo: Identificar os fatores associados ao desenvolvimento de alergias de pele no primeiro ano de vida em prematuros moderados e tardios.  Método: Trata-se de uma pesquisa seccional, com 151 prematuros moderados e tardios, nascidos entre maio de 2016 e maio de 2017. Os participantes foram avaliados no 3º, 6º, 9º e 12º mês de vida, por contato telefônico. As análises estatísticas foram realizadas no software SPSS com testes de comparação de frequência e regressão logística. Resultados: A prevalência de alergia de pele, na percepção dos cuidadores, entre prematuros tardios e moderados foi de 16%. Fatores como ser egresso da terapia intensiva neonatal (p=0,006) e não estar em aleitamento materno (p=0,041) mostrou associação significativa no 3º e 12ª mês de vida, respectivamente. Conclusão: A alergia de pele, na percepção dos cuidadores, é uma característica mais intensa naqueles que apresentam manifestações clínicas respiratórias e gastrointestinais, seja ela condicionante ou de causa-efeito. O aleitamento materno mostrou-se um fator protetor no 1º ano de vida. Palavras-chave: Recém-nascido prematuro. Lactente. Pele. Manifestações cutâneas. Fatores de risco

Evaluation of the performance of Dutch Lipid Clinic Network score in an Italian FH population: The LIPIGEN study

Background and aims: Familial hypercholesterolemia (FH) is an inherited disorder characterized by high levels of blood cholesterol from birth and premature coronary heart disease. Thus, the identification of FH patients is crucial to prevent or delay the onset of cardiovascular events, and the availability of a tool helping with the diagnosis in the setting of general medicine is essential to improve FH patient identification. Methods: This study evaluated the performance of the Dutch Lipid Clinic Network (DLCN) score in FH patients enrolled in the LIPIGEN study, an Italian integrated network aimed at improving the identification of patients with genetic dyslipidaemias, including FH. Results: The DLCN score was applied on a sample of 1377 adults (mean age 42.9 ± 14.2 years) with genetic diagnosis of FH, resulting in 28.5% of the sample classified as probable FH and 37.9% as classified definite FH. Among these subjects, 43.4% had at least one missing data out of 8, and about 10.0% had 4 missing data or more. When analyzed based on the type of missing data, a higher percentage of subjects with at least 1 missing data in the clinical history or physical examination was classified as possible FH (DLCN score 3–5). We also found that using real or estimated pre-treatment LDL-C levels may significantly modify the DLCN score. Conclusions: Although the DLCN score is a useful tool for physicians in the diagnosis of FH, it may be limited by the complexity to retrieve all the essential information, suggesting a crucial role of the clinical judgement in the identification of FH subjects