Determinant Factors of Disease Severity for Patients With Hidradenitis Suppurativa Evaluated in a Spanish Hospital Over a 5-Year Period. / [Artículo traducido] Factores determinantes de la severidad de la enfermedad en los pacientes con hidradenitis supurativa evaluados en un hospital español durante un periodo de 5 años.

It is necessary to identify which factors or comorbidities are associated with more severe hidradenitis suppurativa, aiming to identify which patients may benefit more from early systemic treatment or a more aggressive approach. A retrospective study was conducted, including patients diagnosed with HS at the dermatology department of a Spanish hospital over a 5-year period. A total of 322 patients were included. A relationship was found between diagnostic delay, the presence of acne conglobata, pilonidal sinus, cardiovascular risk factors (hypertension, dyslipidemia, and/or diabetes mellitus) and more severe HS. No significant relationship was found between psychiatric comorbidities and the severity of the HS. The presence of perianal or truncal involvement was significantly associated with severe HS. Female sex and the presence of a family history of HS were associated with an earlier onset of the disease.

Determinant Factors of Disease Severity for Patients With Hidradenitis Suppurativa Evaluated in a Spanish Hospital Over a 5-Year Period.

It is necessary to identify which factors or comorbidities are associated with more severe hidradenitis suppurativa, aiming to identify which patients may benefit more from early systemic treatment or a more aggressive approach. A retrospective study was conducted, including patients diagnosed with HS at the dermatology department of a Spanish hospital over a 5-year period. A total of 322 patients were included. A relationship was found between diagnostic delay, the presence of acne conglobata, pilonidal sinus, cardiovascular risk factors (hypertension, dyslipidemia, and/or diabetes mellitus) and more severe HS. No significant relationship was found between psychiatric comorbidities and the severity of the HS. The presence of perianal or truncal involvement was significantly associated with severe HS. Female sex and the presence of a family history of HS were associated with an earlier onset of the disease.

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

Congenital and Infantile Hemangiomas: Epidemiological, Clinical, and Treatment Characteristics Based on 3 Years' Experience at a Tertiary Care Hospital - A Retrospective Case Comparison and Review of the Literature. / Características clínico-epidemiológicas y consideraciones terapéuticas de los hemangiomas congénitos e infantiles de un hospital de tercer nivel durante un periodo de 3 años: estudio comparativo y revisión de la literatura.

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment.

Expanding the clinical spectrum of the 'HDAC8-phenotype' - implications for molecular diagnostics, counseling and risk prediction.

Cornelia de Lange syndrome (CdLS) is a clinically heterogeneous disorder characterized by typical facial dysmorphism, cognitive impairment and multiple congenital anomalies. Approximately 75% of patients carry a variant in one of the five cohesin-related genes NIPBL, SMC1A, SMC3, RAD21 and HDAC8. Herein we report on the clinical and molecular characterization of 11 patients carrying 10 distinct variants in HDAC8. Given the high number of variants identified so far, we advise sequencing of HDAC8 as an indispensable part of the routine molecular diagnostic for patients with CdLS or CdLS-overlapping features. The phenotype of our patients is very broad, whereas males tend to be more severely affected than females, who instead often present with less canonical CdLS features. The extensive clinical variability observed in the heterozygous females might be at least partially associated with a completely skewed X-inactivation, observed in seven out of eight female patients. Our cohort also includes two affected siblings whose unaffected mother was found to be mosaic for the causative mutation inherited to both affected children. This further supports the urgent need for an integration of highly sensitive sequencing technology to allow an appropriate molecular diagnostic, genetic counseling and risk prediction.

Clinical onset and course, response to treatment and outcome in 24 patients with the cblE or cblG remethylation defect complemented by genetic and in vitro enzyme study data.

BACKGROUND: The cobalamin E (cblE) (MTRR, methionine synthase reductase) and cobalamin G (cblG) (MTR, methionine synthase) defects are rare inborn errors of cobalamin metabolism leading to impairment of the remethylation of homocysteine to methionine. METHODS: Information on clinical and laboratory data at initial full assessment and during the course of the disease, treatment, outcome and quality of life was obtained in a survey-based, retrospective study from physicians caring for patients with the CblE or CblG defect. In addition, data on enzyme studies in cultured skin fibroblasts and mutations in the MTRR and MTR gene were analysed. RESULTS: In 11 cblE and 13 cblG patients, failure to thrive, feeding problems, delayed milestones, muscular hypotonia, cognitive impairment and macrocytic anaemia were the most frequent symptoms. Delay in diagnosis depended on age at first symptom and clinical pattern at presentation and correlated significantly with impaired communication abilities at follow-up. Eighteen/22 patients presented with brain atrophy or white matter disease. Biochemical response to treatment with variable combinations of betaine, cobalamin, folate was significant. The overall course was considered improving (n = 8) or stable (n = 15) in 96% of patients, however the average number of CNS symptoms per patient increased significantly over time and 16 of 23 patients were classified as developmentally delayed or severely handicapped. In vitro enzyme analysis data showed no correlation with outcome. Predominantly private mutations were detected and no genotype- phenotype correlations evident. CONCLUSIONS: The majority of patients with the cblE and cblG defect show limited clinical response to treatment and have neurocognitive impairment.

Could a patient with SMC1A duplication be classified as a human cohesinopathy?

The disorders caused by mutations in genes encoding subunits and accessory proteins of cohesin complex are collectively termed as cohesinopathies. The best known cohesinopathy is Cornelia de Lange Syndrome (CdLS), which is a multisystem developmental disorder characterized by facial dysmorphism, limb malformations, growth and cognitive impairment. Mutations in five genes, encoding subunits of the cohesin complex (SMC1A, SMC3, RAD21) and its regulators (NIPBL, HDAC8), are responsible for ∼ 70% of CdLS cases. We describe a 16-year-old boy with facial dysmorphism, growth retardation, intellectual disability, hirsutism and small hands, who has a small Supernumerary Marker Chromosome (sSMC) present in mosaic form. sSMC is composed of two duplicated segments encompassing 17 genes including SMC1A gene, at the regions Xp11.22 and Xp11.21q11.1. Clinical comparison between our patient with a previously reported individual with a SMC1A duplication and four male carriers of similar sSMC reported in databases, suggest that they all share clinical features related to cohesinopathies. Although our patient does not have the classical CdLS craniofacial phenotype, he has pre and postnatal growth retardation, intellectual disability and mild musculoskeletal anomalies, features commonly seen in patients with cohesinopathies.

A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.

BACKGROUND: PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer. PATIENTS AND METHODS: Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m(2), irinotecan 300 mg/m(2) or docetaxel (Taxotere) 75 mg/m(2) every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error ß = 0.10, null hypothesis of ORR was 5%). RESULTS: Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%). CONCLUSION: The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting.

Longitudinal study of in-hospital consultations with neurology in a tertiary hospital. A health care activity on the increase.

OBJECTIVE: In-hospital consultation (IHC) is a service that some medical specialties provide to others with the aim of resolving complications in patients admitted to different hospital units. The aim of this study is to perform a descriptive analysis and longitudinal study of IHCs received in our department during the last 5 years. METHOD: A retrospective study was conducted on the IHCs made within the period 2005-2009. The data analysed were as follows: department of origin of the IHC, reason for consult, date, priority of care, definitive diagnosis, need for follow-up, need for transfer, and the demographic data of the patients. RESULTS: There were a total of 1458 IHCs in the period studied. The mean age of the patients was 58.2 ± 19.10 years, and 837 (57.6%) were males. The number of IHCs per year was: 2005: 263; 2006: 226; 2007: 239; 2007: 239, 2008: 329 and 2009: 401. The majority (86.8%) had normal priority, 8.5% high priority, and 4.7% were urgent. The Emergency Department (12%), Cardiology (10.9%), General Medicine (9.8%) and Psychiatry (8.9%) were the services with the highest demand. The most frequent reasons for consulting were loss of consciousness and epileptic seizures (24.6%), cerebral vascular disease (21.1%), and confusional states and cognitive impairment (13.4%). Over one third (36.8%) were resolved in the first consultation, and the remainder (63.8%) required follow up. Of all the cases assessed, 8.4% required transfer to Neurology. CONCLUSIONS: IHC is a complex activity that may not resolve all questions in a single visit. It involves a health care burden which is increasing annually. The increasing diagnostic complexity of the neurology, as well as the increasingly more specific treatments are the factors that lead to this higher demand.