Neural injury markers in intrauterine growth restriction and their relation to perinatal outcomes.

BACKGROUNDThe aims of this study were to (i) compare the concentrations of two neural injury markers, S100B protein and neuron-specific enolase (NSE), in intrauterine growth-restricted (IUGR) fetuses and in fetuses with appropriate growth-for-gestational-age (AGA), and (ii) investigate potential relationships between concentrations of these markers, Doppler abnormalities, and adverse perinatal or neonatal outcomes.METHODSThis was a case-controlled, cooperative, prospective study among Spanish Maternal and Child Health Network (Retic SAMID) hospitals. At inclusion, biometry for estimated fetal weight and feto-placental Doppler were measured. At the time of delivery, maternal venous blood and fetal umbilical arterial blood samples were collected. S100B and NSE concentrations were determined from these samples.RESULTSIn total, 254 pregnancies were included. Among these, 147 were classified as IUGR and 107 as AGA. There were no differences between the groups in S100B concentrations. However, levels of NSE in maternal and umbilical cord serum differed significantly between these groups (2.31 in AGA vs. 2.51 in IUGR in (P<0.05); and 2.89 in AGA vs. 3.25 in IUGR (P<0.05), respectively). No differences were observed in these neurological markers when stratified by perinatal or neonatal complications.CONCLUSIONAlthough some variations exist in these neurological markers, they did not correlate with perinatal or neonatal complications.

Evaluation of the bedside Quikread go® CRP test in the management of febrile infants at the emergency department.

Recently C-reactive protein (CRP) point-of-care tests have been developed. We aimed to validate a bedside CRP test (QuikRead go® CRP), to compare it with the laboratory CRP (ARCHITECT c8000 Abbott, Germany) test in children with fever without source (FWS), and to evaluate the optimal CRP cut-off value to identify those patients at a high risk for serious bacterial infection (SBI). The CRP bedside test was prospectively performed in capillary blood samples concurrently with the laboratory CRP testing for 283 well-appearing infants aged 1 to 24 months with FWS attending the emergency department (ED) between May 2013 and August 2015. The mean difference between the laboratory CRP and the QuikRead go CRP values was 0.71 mg/L (p = 0.444). Pearson's correlation coefficient between the CRPs was r = 0.929 (p < 0.001). SBI was diagnosed in 34 patients (12.0%). The area under the receiver operating characteristics (ROC) curve obtained was 0.87 (95%CI: 0.82-0.90) for an optimal CRP cut-off value of > 10 mg/L (sensitivity: 94.1%, specificity: 49.0%, positive predictive value: 20.1%, negative predictive value: 98.4%), as a predictor of SBI. Nearly 45% of the patients were at a low risk for SBI according to CRP value; thus, additional laboratory tests would have been hypothetically avoided. There was a very strong, positive correlation between the QuikRead go CRP test and laboratory CRP determination. The QuikRead go CRP test provides reliable results to rule out SBI. Its implementation at the ED would improve the management of infants with FWS.

Outcomes and infectious etiologies of febrile neutropenia in non-immunocompromised children who present in an emergency department.

There are no unified protocols governing the management of healthy children with febrile neutropenia in the emergency department (ED). Conservative management is the norm, with admission and empirical broad-spectrum antibiotics prescribed, although viral infections are considered the most frequent etiology. The aim of this study was to describe the clinical outcomes and identified etiologies of unsuspected neutropenia in febrile immunocompetent children assessed in the ED. This was a retrospective study: well-appearing healthy children <18 years old with febrile moderate [absolute neutrophil count (ANC) 500-999 neutrophils ×10(9)/l] or severe (ANC <500 neutrophils ×10(9)/l) neutropenia diagnosed in ED between 2005 and 2013 were included. Patients newly diagnosed with hematologic or oncologic disease were excluded. We included 190 patients: 158 (83.2 %) with moderate and 32(16.8 %) with severe neutropenia. One hundred and one (53.2 %) were admitted; 48(47.5 %) with broad-spectrum antibiotics. The median length of stay was 3 days (IQR 3-5) and the median duration of neutropenia was 6 days (IQR 3-12). An infectious agent was identified in 23(12.1 %); 21 (91.3 %) were viruses. Four (2.1 %) children had a serious bacterial infection (SBI): urinary tract infection and lobar pneumonia (two cases each). All blood cultures performed (144; 75.8 %) were negative. Over the 1-year follow-up, one or several blood tests were performed on 167 patients (87.9 %); two (1.2 %) were diagnosed with autoimmune chronic neutropenia. Previously healthy children with moderate or severe febrile neutropenia have a low risk of SBI and a favorable clinical outcome. Less aggressive management could be carried out in most of them. Although chronic hematological diseases are infrequently diagnosed, serial ANC are necessary to detect them.

Frontal Fibrosing Alopecia in Men: Presentations in 12 Cases and a Review of the Literature. / Alopecia frontal fibrosante en el varón: presentación de 12 casos y revisión de la literatura.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring disease in which the hairline recedes and the eyebrows can be affected. Usually seen in postmenopausal women, FFA is much less common in men. OBJECTIVE: To describe the clinical characteristics of FFA in a case series of men and compare this series to those reported in the literature. MATERIAL AND METHODS: Men with FFA being treated in our dermatology department from January 2010 to December 2015 were included prospectively for this descriptive study. We collected patient information and clinical and treatment characteristics. RESULTS: Twelve men (mean age, 75 years) were recruited. Alopecia was the reason for seeking medical care in only 4 cases. The hairline had receded 3cm on average. Half the patients had facial papules, and 83% had androgenetic alopecia or hair loss on eyebrows or extremities. Follicular hyperkeratosis and erythema were present in 66%, and only 25% of the men reported pruritus. The most commonly prescribed treatments were topical: corticosteroids in 8 patients (66%) and minoxidil in 4 (33%). CONCLUSIONS: Facial papules, androgenetic alopecia, and loss of body hair are more often observed in men with FFA than in women. The men in this series were older on average than in other FFA case series in the literature, possibly accounting for the higher prevalence of associated androgenetic alopecia and the fact that most of these men were seeking care for conditions other than hair loss.

Autochthonous cutaneous larva migrans infection in Guipúzcoa. / Larva migrans cutánea de origen autóctono en Guipúzcoa.

INTRODUCTION: Cutaneous larva migrans (LM) infection forms a serpiginous eruption caused by the migration of nematode helminths through the epidermis. The parasites are acquired when the skin comes into contact with soil contaminated by the feces of infected animals. Until now, infections have been believed to be imported from tropical and subtropical regions. Our aim was to study cases of cutaneous LM diagnosed in residents of the Spanish province of Guipúzcoa who had not recently traveled to such regions. MATERIAL AND METHODS: Cross-sectional observational study of LM cases diagnosed in Hospital Universitario Donostia from 2011 to 2015 in patients who had not visited a region where this nematode infection is endemic. Clinical diagnoses were based on characteristic lesions. We studied the following variables: age, sex, site of lesions, date of onset of symptoms, possible source of contagion, pathologic findings, treatment, and clinical course. RESULTS: We found 4 cases, all in men (mean age, 60 years). Lesions were on the lower extremities in 3 patients and on the trunk in 1 patient. All had been in contact with soil that could have been contaminated by feces and was the most likely source of the parasite. The lesions disappeared after treatment with oral albendazole. CONCLUSIONS: The appearance of cases of autochthonous LM in Europe requires investigation of the culprit species, a review of the epidemiology of this infection, which was once considered imported, and the planning of public health measures to prevent it from becoming endemic.

Diamine oxidase levels in different chronic urticaria phenotypes.

BACKGROUND: Diamine oxidase (DAO) is a polyamine-degrading enzyme also implicated in histamine metabolism. Chronic urticaria (CU) has a wide spectrum of clinical presentations and causes. Anisakis sensitisation associated chronic urticaria (CU+) has been characterised as a phenotype with different clinical and immunological characteristics and possibly associated with previous acute parasitism. We aimed to analyse serum DAO levels in different CU phenotypes. We further analysed the possible association of DAO with fish eating habits. METHODS: We studied 35 CU+ patients and 39 non-sensitised CU patients (CU-) as well as 19 controls. We analysed fish-eating frequency as well as fish intake associated exacerbation of CU (FIAE) or gastro-intestinal complaints (GI). DAO levels were further analysed with respect to lymphoproliferative responses, cytokine and specific IgE production. RESULTS: DAO levels were not different between CU and controls, but were significantly higher in CU+ than in CU-. CU+ patients with FIAE had lower DAO levels, but no differences were detected in patients with GI. DAO levels correlated positively with oily and canned fish consumption in CU-. In CU+, DAO levels correlated positively with specific Anisakis IgE, percentages of proliferation in Anisakis stimulated peripheral blood lymphocytes, serum IL-2 and IL-6, but correlated negatively with mitogen stimulated TGF-ß in supernatants. CONCLUSIONS: DAO levels in CU depend on fish-eating habits and in CU+ on the amount of specific IgE production. In the CU+ phenotype, lower levels of DAO predispose to urticaria exacerbation after fish intake, probably due to a relative insufficient enteric availability of this enzyme.

Positive associations between infections of Toxoplasma gondii and seropositivity with Anisakis simplex in human patients suffering from chronic urticaria.

Toxoplasma gondii is a food-borne and orofecal microorganism which produces chronic infection, and attempts have been made to prove its negative association with atopy in the context of the hygiene hypothesis. Anisakis simplex is a fish parasite associated with chronic urticaria (CU) in endemic regions. We analysed the relationship between both infectious agents in CU. We included 42 patients with chronic urticaria (18 patients with CU associated with A. simplex sensitization and 24 not sensitized CU patients). Patients were assessed for atopy by a skin prick test (SPT) against common aeroallergens and for respiratory symptoms. Anisakis simplex sensitization was assessed by SPT and specific IgE by CAP fluoro-enzyme immunoassay (CAP-FEIA). Anti-T. gondii IgG levels were measured by enzyme-linked immunosorbent assay (ELISA). CU patients were analysed with respect to T. gondii seropositivity, A. simplex sensitization, atopy and immigrant status. The seroprevalence of T. gondii was 40.5% in CU patients and 42.1% in the control group. Immigrants were more frequently infected by T. gondii (41.2% versus 12%; P =0.036). Anti-T. gondii IgG antibodies were associated with past A. simplex parasitism (odds ratio 6.73; P =0.03) and independently with atopic sensitization (odds ratio 5.85; P =0.04). In CU patients, T. gondii has no protective effect on atopic sensitization or A. simplex sensitization.

Treatment of Sézary Syndrome With Alemtuzumab: A Series of 5 Cases and a Review of the Literature.

Alemtuzumab is a monoclonal antibody that has been used to treat refractory cases of Sézary syndrome (SS) and advanced mycosis fungoides. We present 5 patients with SS who were treated with alemtuzumab between 2008 and 2012, with an overall response rate of 80% (40% partial response and 40% complete response). A regimen of 10mg administered subcutaneously was well tolerated with acceptable toxicity. The median duration of response was 13 months. However, one patient remains in complete remission after 67 months, a remarkable outcome given the low survival rate associated with SS. In conclusion, we believe that alemtuzumab may be useful in cases of SS refractory to other treatments. As there are no curative treatments for SS, alemtuzumab should be considered as a therapeutic option.

Specific IgG4: possible role in the pathogenesis and a new marker in the diagnosis of Anisakis-associated allergic disease.

IgG4 and IgE are immunoglobulin isotypes which are mediated by the same Th2-mediated mechanism. The postulated pathogenic and protective function of IgE or IgG4, respectively, in allergic disease is opposite in parasitic infection. The possible role of IgG4 against recombinant major allergens on the appearance of different forms of Anisakis simplex-associated allergic disease was studied. Gastro-allergic anisakiasis (GAA) and Anisakis-sensitization-associated chronic urticaria (CU+) were compared for specific IgE, IgG4 and the respective recognition of Ani s 1 and Ani s 7. Gastro-allergic anisakiasis showed higher IgE and IgG4 levels against crude extract and both recombinant allergens. Whereas IgE recognition of Ani s 7 did not differ and supports both clinical entities to be associated with previous acute parasitism, the IgE recognition rates of Ani s 1 and IgG4 recognition of both Ani s 1 and Ani s 7 were higher in GAA. IgG4 levels were associated with IgE, but also with age, time to last parasitic episode and frequency of fish intake. Logistic regression analysis showed that the presence of specific IgG4 against Ani s 7 was an independent marker associated with GAA. In the diagnosis of Anisakis-associated allergic disease phenotypes (GAA versus CU+), measurement of specific IgG4 against recombinant allergens could be useful. Further, evaluation of specific IgE and IgG4 facilitates more insight into the protective versus pathogenic potential of IgE and IgG4.

Adverse skin effects of imatinib, a tyrosine kinase inhibitor.

Imatinib mesylate is a tyrosine kinase inhibitor that targets the BCR-ABL, c-kit, and PDGF (platelet-derived growth factor) receptors. Imatinib is mainly indicated for chronic myeloid leukemia and gastrointestinal stromal tumors but is also prescribed by dermatologists for dermatofibrosarcoma protuberans, systemic sclerosis, and systemic mastocytosis, among other conditions. Most adverse effects are mild or moderate and therapy is generally well tolerated. Adverse skin effects are very common and include nonspecific manifestations such as edema and maculopapular rashes or eruptions of diverse types (lichenoid or psoriasiform lesions, acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and more). Identifying and properly treating these reactions can help optimize adherence to treatment and improve the prognosis of the underlying disease.

Wolf's isotopic response: a series of 9 cases.

INTRODUCTION: The term Wolf's isotopic response refers to the appearance of a new skin disease at the site of an already healed, unrelated disease. In most cases, the initial disease is herpes zoster. Different diseases may subsequently develop on the same site. The most common isotopic responses are granulomatous and lichenoid reactions, infiltrations of hematologic diseases, skin tumors, and infections. The pathogenesis of these skin reactions is unknown. It has been suggested that viral infection may alter local skin immunity; this would favor hyperreactivity, leading to inflammatory processes, or local immunosuppression, leading to tumor infiltrations or infections. MATERIALS AND METHODS: We performed a retrospective study of 9 patients diagnosed with Wolf's isotopic response in the dermatology department of Hospital Donostia in San Sebastian, Spain. Five patients had B-cell chronic lymphocytic leukemia, 2 had a non-Hodgkin lymphoma, and 1 had ovarian carcinoma. RESULTS: The initial disease was herpes zoster in 7 cases, and chickenpox and herpes simplex in the other 2 cases. The second disease was granulomatous dermatitis in 4 cases, lichenoid dermatitis in 2 cases, infiltration by B-cell chronic lymphatic leukemia in 2 cases, and infiltration by systemic non-Hodgkin lymphoma in 1 case. In the last case, the skin lesions were the first sign of the lymphoma. CONCLUSIONS: We highlight the need to biopsy these second lesions in order to rule out tumor infiltrations, which were more frequent than expected in our series.

Different serum cytokine levels in chronic vs. acute Anisakis simplex sensitization-associated urticaria.

The knowledge on immune mechanisms of chronic urticaria (CU) at the cytokine level is widely scarce. We compared pro- and anti-inflammatory as well as Th1- and Th2-associated serum cytokine levels in two phenotypes of CU: associated with (CU+) and without (CU⁻) sensitization against Anisakis simplex, a ubiquitous fish parasite, that has been associated with acute urticaria in gastro-allergic anisakiasis (GAA) and with CU+. Thirteen CU+ and 19 CU⁻ patients were compared with 13 GAA patients and 15 control subjects for cytokines, measured by cytometric bead array. Urticaria activity score was positively correlated with IL-6 in CU⁻. Serum levels of IL-10 were lower in CU+ and CU⁻ with respect to the control group. Median IFN-γ was lower in all urticaria groups. Patients with previous parasitism by A. simplex displayed higher TGF-ß levels than subjects without previous parasitism. The main finding was lower levels of IL-17 in CU+ with respect to GAA or controls, with a further tendency to even lower levels in CU⁻. Different urticaria phenotypes are associated with distinct serum cytokine levels.

[Chondroblastic osteosarcoma over a total hip prosthesis]. / Osteosarcoma condroblástico sobre una artroplastia total de cadera.

Malignant transformation in the area of joint prostheses is very rare. We present the case of a woman who developed a chondroblastic osteosarcoma in the area where a total hip prosthesis had been implanted.

3D printed soft surgical planning prototype for a biliary tract rhabdomyosarcoma.

Biliary tract rhabdomyosarcoma is a soft tissue malignant musculoskeletal tumor which is located in the biliary tract. Although this tumor represents less than 1% of the total amount of childhood cancers, when localized, a >70% overall 5-year survival rate, the resection is clinically challenging and complications might exist during the biliary obstruction. Although surgery remains a mainstay, complete tumor resection is generally difficult to achieve without mutilation and severe long-term sequelae. Therefore, manufacturing multi-material 3D surgical planning prototypes of the case provides a great opportunity for surgeons to learn beforehand what they can expect. Additionally, practicing before the operation enhances the probability of success. That is why different compositions of materials have been characterized to match the mechanical properties of the liver. To do this, Dynamic Mechanical Analysis (DMA) tests and Shore hardness tests have been carried out. Amongst the material samples produced, 6%wt PVA (poly vinyl alcohol)/1%wt PHY (Phytagel)-1FT (Freeze-Thaw cycles) and 1%wt agarose appear as the best options for mimicking the liver tissue in terms of viscoelasticity. Regarding the Shore hardness, the best solution is 1%wt agarose. Additionally, a surgical planning prototype using this last material mentioned was manufactured and validated using a CT (Computed Tomography) scanner. In most of the structures the difference between the 3D model and the organ in terms of dimensions is less than 3.35 mm, which represents a low dimensional error, around 1%. On the other hand, the total manufacturing cost of the 3D physical model was €513 which is relatively low in comparison with other technologies.