Trastornos del sueño en niños con epilepsia / Sleep disorders in children with epilepsy

Introducción: Los niños con epilepsia tienen más trastornos del sueño (TS) que la población sana. Es fundamental su diagnóstico, ya que la epilepsia y los TS tienen una relación bidireccional. Objetivo: Determinar la incidencia de TS y malos hábitos de sueño en niños con epilepsia. Método: Estudio transversal de pacientes menores de 18 años con epilepsia sobre TS, mediante la versión española de Sleep Disturbance Scale for Children (SDSC), y sobre hábitos de sueño, mediante cuestionario de elaboración propia. Resultados: La muestra incluyó 153 pacientes. El 84% de la población estudiada presentaba alterado algún aspecto del sueño. Lo más frecuente fueron las alteraciones en la transición sueño-vigilia (53%), en el inicio-mantenimiento del sueño (47,7%) y la somnolencia diurna (44,4%). Un 70% de los padres de los pacientes referían que su hijo «dormía bien», pero en este grupo se detectaron TS hasta en el 75,7%. Muchos de los pacientes tenían hábitos de sueño poco saludables, como dormirse con dispositivos electrónicos (16,3%), precisar presencia familiar para dormirse (39%) o dormir en colecho o cohabitación (23,5 y 30,5%, respectivamente). Aquellos con epilepsias generalizadas, refractarias, crisis nocturnas y discapacidad intelectual presentaron mayor probabilidad de presentar TS. En cambio, los malos hábitos de sueño fueron frecuentes independientemente de las características de la epilepsia. Conclusiones: Los TS y los malos hábitos de sueño son frecuentes en niños con epilepsia. Su tratamiento puede conllevar una mejoría en la calidad de vida del paciente y su familia, así como una mejoría en el pronóstico de la epilepsia.(AU)

Introduction: Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship. Objective: Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy. Methods: We conducted a cross-sectional study of patients under 18 years of age with epilepsy, assessing sleep disorders using the Spanish-language version of the Sleep Disturbance Scale for Children (SDSC), and sleep habits using an original questionnaire. Results: The sample included 153 patients. Eighty-four percent of our sample presented some type of sleep alteration. The most frequent alterations were sleep-wake transition disorders (53%), sleep initiation and maintenance disorders (47.7%), and daytime sleepiness (44.4%). In 70% of cases, the patients’ parents reported that their child “slept well,” although sleep disorders were detected in up to 75.7% of these patients. Many patients had poor sleep habits, such as using electronic devices in bed (16.3%), requiring the presence of a family member to fall asleep (39%), or co-sleeping or sharing a room (23.5% and 30.5%, respectively). Those with generalised epilepsy, refractory epilepsy, nocturnal seizures, and intellectual disability were more likely to present sleep disorders. In contrast, poor sleep habits were frequent regardless of seizure characteristics. Conclusions: Sleep disorders and poor sleep habits are common in children with epilepsy. Their treatment can lead to an improvement in the quality of life of the patient and his/her family, as well as an improvement in the prognosis of epilepsy.(AU)

Sleep disorders in children with epilepsy.

INTRODUCTION: Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship. OBJECTIVE: Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy. METHODS: We conducted a cross-sectional study of patients under 18 years of age with epilepsy, assessing sleep disorders using the Spanish-language version of the Sleep Disturbance Scale for Children (SDSC), and sleep habits using an original questionnaire. RESULTS: The sample included 153 patients. Eighty-four percent of our sample presented some type of sleep alteration. The most frequent alterations were sleep-wake transition disorders (53%), sleep initiation and maintenance disorders (47.7%), and daytime sleepiness (44.4%). In 70% of cases, the patients' parents reported that their child "slept well," although sleep disorders were detected in up to 75.7% of these patients. Many patients had poor sleep habits, such as using electronic devices in bed (16.3%), requiring the presence of a family member to fall asleep (39%), or co-sleeping or sharing a room (23.5% and 30.5%, respectively). Those with generalised epilepsy, refractory epilepsy, nocturnal seizures, and intellectual disability were more likely to present sleep disorders. In contrast, poor sleep habits were frequent regardless of seizure characteristics. CONCLUSIONS: Sleep disorders and poor sleep habits are common in children with epilepsy. Their treatment can lead to an improvement in the quality of life of the patient and his/her family, as well as an improvement in the prognosis of epilepsy.

Endocrine system involvement in patients with RASopathies: A case series.

Background and Objectives: Endocrine complications have been described in patients affected by RASopathies but no systematic assessment has been reported. In this study, we investigate the prevalence of endocrine disorders in a consecutive unselected cohort of patients with RASopathies. Study Design: 72 patients with a genetically confirmed RASopathy (Noonan syndrome [NS], N=53; 29 LEOPARD syndrome [LS], N=2; cardiofaciocutaneous syndrome [CFCS], N=14; subjects showing co-occurring pathogenic variants in PTPN11 and NF1, N=3) and an age- and sex-matched healthy controls were included in the study. Endocrine system involvement was investigated by assessing the thyroid function, pubertal development, auxological parameters, adrenal function and bone metabolism. Results: Short stature was detected in 40% and 64% of the NS and CFCS subcohorts, respectively. Patients showed lower Z-scores at DXA than controls (p<0.05) when considering the entire case load and both NS and CFCS groups. Vitamin D and Calcitonin levels were significantly lower (p< 0.01), Parathormone levels significantly higher (p<0.05) in patients compared to the control group (p<0.05). Patients with lower BMD showed reduced physical activity and joint pain. Finally, anti-TPO antibody levels were significantly higher in patients than in controls when considering the entire case load and both NS and CFCS groups. Conclusions: The collected data demonstrate a high prevalence of thyroid autoimmunity, confirming an increased risk to develop autoimmune disorders both in NS and CFCS. Reduced BMD, probably associated to reduced physical activity and inflammatory cytokines, also occurs. These findings are expected to have implications for the follow-up and prevention of osteopenia/osteoporosis in both NS and CFCS.

Sleep disorders in children with epilepsy. / Trastornos del sueño en niños con epilepsia.

INTRODUCTION: Children with epilepsy present greater prevalence of sleep disorders than the general population. Their diagnosis is essential, since epilepsy and sleep disorders have a bidirectional relationship. OBJECTIVE: Determine the incidence of sleep disorders and poor sleep habits in children with epilepsy. METHODS: We conducted a cross-sectional study of patients under 18 years of age with epilepsy, assessing sleep disorders using the Spanish-language version of the Sleep Disturbance Scale for Children (SDSC), and sleep habits using an original questionnaire. RESULTS: The sample included 153 patients. Eighty-four percent of our sample presented some type of sleep alteration. The most frequent alterations were sleep-wake transition disorders (53%), sleep initiation and maintenance disorders (47.7%), and daytime sleepiness (44.4%). In 70% of cases, the patients' parents reported that their child "slept well," although sleep disorders were detected in up to 75.7% of these patients. Many patients had poor sleep habits, such as using electronic devices in bed (16.3%), requiring the presence of a family member to fall asleep (39%), or co-sleeping or sharing a room (23.5% and 30.5%, respectively). Those with generalised epilepsy, refractory epilepsy, nocturnal seizures, and intellectual disability were more likely to present sleep disorders. In contrast, poor sleep habits were frequent regardless of seizure characteristics. CONCLUSIONS: Sleep disorders and poor sleep habits are common in children with epilepsy. Their treatment can lead to an improvement in the quality of life of the patient and his/her family, as well as an improvement in the prognosis of epilepsy.

Improving dose delivery accuracy with EPID in vivo dosimetry: results from a multicenter study.

PURPOSE: To investigate critical aspects and effectiveness of in vivo dosimetry (IVD) tests obtained by an electronic portal imaging device (EPID) in a multicenter and multisystem context. MATERIALS AND METHODS: Eight centers with three commercial systems-SoftDiso (SD, Best Medical Italy, Chianciano, Italy), Dosimetry Check (DC, Math Resolution, LCC), and PerFRACTION (PF, Sun Nuclear Corporation, SNC, Melbourne, FL)-collected IVD results for a total of 2002 patients and 32,276 tests. Data are summarized for IVD software, radiotherapy technique, and anatomical site. Every center reported the number of patients and tests analyzed, and the percentage of tests outside of the tolerance level (OTL%). OTL% was categorized as being due to incorrect patient setup, incorrect use of immobilization devices, incorrect dose computation, anatomical variations, and unknown causes. RESULTS: The three systems use different approaches and customized alert indices, based on local protocols. For Volumetric Modulated Arc Therapy (VMAT) treatments OTL% mean values were up to 8.9% for SD, 18.0% for DC, and 16.0% for PF. Errors due to "anatomical variations" for head and neck were up to 9.0% for SD and DC and 8.0% for PF systems, while for abdomen and pelvis/prostate treatments were up to 9%, 17.0%, and 9.0% for SD, DC, and PF, respectively. The comparison among techniques gave 3% for Stereotactic Body Radiation Therapy, 7.0% (range 4.7-8.9%) for VMAT, 10.4% (range 7.0-12.2%) for Intensity Modulated Radiation Therapy, and 13.2% (range 8.8-21.0%) for 3D Conformal Radiation Therapy. CONCLUSION: The results obtained with different IVD software and among centers were consistent and showed an acceptable homogeneity. EPID IVD was effective in intercepting important errors.

Efficacy of third-party chimeric antigen receptor modified peripheral blood natural killer cells for adoptive cell therapy of B-cell precursor acute lymphoblastic leukemia.

We developed an innovative and efficient, feeder-free culture method to genetically modify and expand peripheral blood-derived NK cells with high proliferative capacity, while preserving the responsiveness of their native activating receptors. Activated peripheral blood NK cells were efficiently transduced by a retroviral vector, carrying a second-generation CAR targeting CD19. CAR expression was demonstrated across the different NK-cell subsets. CAR.CD19-NK cells display higher antileukemic activity toward CD19+ cell lines and primary blasts obtained from patients with B-cell precursor ALL compared with unmodified NK cells. In vivo animal model data showed that the antileukemia activity of CAR.CD19-NK cell is superimposable to that of CAR-T cells, with a lower xenograft toxicity profile. These data support the feasibility of generating feeder-free expanded, genetically modified peripheral blood NK cells for effective "off-the-shelf" immuno-gene-therapy, while their innate alloreactivity can be safely harnessed to potentiate allogeneic cell therapy.

Hippocampal sparing in stereotactic radiotherapy for brain metastases: To contour or not contour the hippocampus?

PURPOSE: The aim of our study was to evaluate hippocampal irradiation in patients treated with fractionated stereotactic brain radiotherapy. PATIENTS AND METHODS: Retrospective hippocampal dosimetric analysis performed on 22 patients with one to four brain metastases treated with fractionated stereotactic radiotherapy using volumetric intensity-modulated arc therapy. Original plans did not include hippocampus as avoidance structure in optimization criteria; hippocampus was retrospectively delineated on magnetic resonance coregistered with planning CT and using as reference the RTOG 0933 atlas. Hippocampus was defined both as a single and as pair organ. Constraints analysed were: Dmax<16Gy, D40%<7.3Gy, D100%=Dmin<9Gy. Assuming a α/ß ratio of 2Gy, biologically equivalent dose in 2Gy fractions was calculated. Hippocampal-sparing plans were developed in cases where hippocampal constraints were not respected in the original plan. RESULTS: Among constraints analysed Dmax and D40% have been exceeded in ten out of 22 cases. The constraints were not respected in patients with more than one metastatic lesion and in three patients with only one lesion. Considering all exceeded constraints values in non-hippocampal sparing plans, the 50% of them was respected after replanning. No significant differences were found among conformity and homogeneity index between non-hippocampal sparing and hippocampal sparing plans. CONCLUSION: Volumetric intensity-modulated arc therapy hippocampal sparing plans significantly decreases dose to hippocampus assuring an equal target coverage and organs at risk avoiding.

Serum selenium levels predict survival after breast cancer.

BACKGROUND: Studies have reported an inverse relationship between serum selenium levels and cancer incidence, but the impact of low serum selenium status on survival after a diagnosis of breast cancer has not been established. METHODS: We obtained a blood sample from 546 women diagnosed with a first primary invasive breast cancer between 2008 and 2015 in the region of Szczecin, Poland. Blood was collected after diagnosis, but prior to treatment. Serum selenium was quantified by mass spectroscopy and each patient was assigned to one of four categories (quartiles) based on the distribution in the entire cohort. Patients were followed from diagnosis to death over a mean follow-up of 3.8 years. Vital status was obtained by linkage to the Polish National Death Registry. RESULTS: The 5-year overall actuarial survival was 68.1% for women in the lowest (< 64.4 µg/L) and 82.5% for those in the highest (> 81.0 µg/L) quartile of serum selenium. In an adjusted analysis, the hazard ratio for death was 2.49 (95%CI 1.53-4.04; P = 0.0002) for patients in the lowest quartile of serum selenium, compared to those in all other quartiles. The effect of low selenium on breast cancer-specific mortality was stronger for women who were past smokers (HR 6.03; 95%CI 1.96-18.6; P = 0.0002). CONCLUSIONS: This study suggests that a selenium level in excess of 64.4 µg//L might be beneficial for women undergoing treatment for breast cancer and that selenium supplementation to achieve this level may favorably impact the outcome. Further studies are needed to confirm this association and to evaluate the impact of selenium supplementation on breast cancer survival among women with low post-diagnostic selenium levels.

Radioguided thyroidectomy for follicular tumors: Multicentric experience.

BACKGROUND: The diagnosis of thyroid nodular diseases requires an integrated approach that has been widely established over the past years. This strategy includes: ultrasonography (US) with; implemented Color-Power-Doppler, conventional scintigraphy also with positive indicators, specific pathological studies targeted by immunohistochemically-assays, and the fine needle; aspiration biopsy (FNAB), which, usually, in case of "Follicular Lesions" (10-20%) findings is; unable to distinguish carcinoma from follicular adenoma, then indicating the necessity of surgery to; obtain a correct diagnosis. The aim of this study was to evaluate the role of the scintigraphy with; positive indicators, both preoperatively in diagnostic approach of the thyroid nodules and; intraoperatively as a guide to the extension of the surgical excision. METHODS: On 4482 Thyroidectomy performed, we selected 360 cases of follicular neoplasms (192; females and 168 males). In the preoperative phase, these patients underwent 99 m Tc-sestaMIBI; scintigraphy with both early (10 min) and late (2 h) image acquisition, which were later; compared to the ones obtained by image subtraction of means 99 m Tc-pertechnetate. Following the; sestamibi administration before intervention, we selected the most up-taking nodularity with the; assistance of a specific surgical probe (Neoprobe), quantifying uptake with relation to the surgical pathology, for an amount of 324 total thyroidectomies and 36 hemi thyroidectomies. RESULTS: In all cases of multinodular goiter the benign nodules showed an intraoperative low sestamibi uptake whereas follicular carcinomas showed both a high preoperative uptake and, as a; percentage, the highest values of intraoperative uptake; on the other hand, follicular adenomas had; both pre-and intraoperative mean values of uptake. On the contrary, papillary carcinomas only; showed a mild uptake. CONCLUSIONS: Preoperative sestamibi scintigraphy confirmed its importance in improving the information obtained through different diagnostic investigations. Also intraoperatively, it pointed; out high-risk nodules more accurately. Therefore, radio (Sestamibi) guided surgery could have an; interesting rule in the thyroid follicular lesion treatment.

Placental histopathology associated with pre-eclampsia: systematic review and meta-analysis.

OBJECTIVE: Pre-eclampsia (PE) is associated with impaired trophoblastic invasion and typical villous and vascular placental lesions. The primary aim of this study was to quantify the prevalence of placental histopathological lesions in pregnancies complicated by PE. METHODS: MEDLINE, EMBASE and CINAHL were searched electronically, and relevant articles reporting on placental histopathological lesions were assessed according to the following criteria: study design, number of pregnancies included, severity of PE and whether the pathologist was blinded to the clinical information. Prospective and retrospective case-control studies including ≥ 100 pregnancies were included in the systematic review. The incidence of each type of histological lesion according to the Perinatal Section of the Society for Pediatric Pathology classification in pre-eclamptic and normal pregnancies was identified, and lesions were categorized into two main groups: villous lesions and vascular lesions. Random-effects meta-analysis of proportions was used for analysis. Between-study heterogeneity was assessed using the I2 statistic. RESULTS: The search yielded 717 citations, and a total of eight studies (four blinded and four non-blinded) were included in the review. In unblinded studies, the pooled prevalence of villous lesions was 11.6% and 48.2% in normal and pre-eclamptic pregnancies, respectively, giving a pooled odds ratio (OR) of 7.59. In blinded studies, the pooled prevalence of villous lesions was 18.5% and 42.0% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 4.28. In unblinded studies, the pooled prevalence of vascular lesions was 8.1% and 37.3% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 20.34. In blinded studies, the pooled prevalence of vascular lesions was 9.8% and 38.9%, in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 7.08. CONCLUSIONS: In blinded studies, the incidence of both placental villous and vascular histopathological lesions is four- to seven-fold higher in pre-eclamptic than in normal pregnancies. Greater differences are reported in unblinded studies. Despite the higher probability (point prevalence) of finding abnormal placental pathology in pregnancies with PE, placental lesions are not specific to the diagnosis of PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome.

The impact of oophorectomy on survival after breast cancer in BRCA1-positive breast cancer patients.

The aim of the study is to identify treatments which predict survival for women with a BRCA1 mutation, including oophorectomy and chemotherapy. 476 women with stage I to stage III breast cancer who carried a BRCA1 mutation were followed from diagnosis until April 2015. Information on treatment was obtained from chart review and patient questionnaires. Dates of death were obtained from the Poland vital statistics registry. Survival curves were compared for different subgroups according to treatment received. Predictors of overall survival were determined using the Cox proportional hazards model. The ten-year overall survival was 78.3 % (95 % CI 74.2-82.6 %) and the ten-year breast cancer-specific survival was 84.2 % (95 % CI 80.5-88.0 %). Sixty-two patients died of breast cancer, 14 patients died of ovarian cancer, and 2 patients died of peritoneal cancer. Oophorectomy was associated with a significant reduction in all-cause mortality in the entire cohort (adjusted HR = 0.41; 95 % CI 0.24-0.69; p = 0.0008) and in breast cancer-specific mortality among ER-negative breast cancer patients (HR = 0.44; 95 % CI 0.22-0.89; p = 0.02). Among women with breast cancer and a BRCA1 mutation, survival is greatly improved by oophorectomy due to the prevention of deaths from both breast and ovarian cancer.

Unveiling iodine-based electrolytes chemistry in aqueous dye-sensitized solar cells.

Aqueous dye-sensitized solar cells (DSSCs) have recently emerged as promising systems, which can combine low cost and environmental compatibility with appreciable efficiency, long-term durability and enhanced safety. In the present study, we thoroughly investigate the chemistry behind the iodide/triiodide-based redox mediator, which presents - in a completely aqueous environment - several differences when compared to the behavior observed in the conventionally used organic solvents. The speciation of ions, the effect of the concentration of the redox mediator and the type of counter-ion are characterized from the electrochemical, spectroscopic, photovoltaic and analytical viewpoints. Furthermore, we demonstrate that aqueous DSSCs, often assumed as unstable, hold the potential to assure unparalleled stability after five months of aging without any addition of stabilizers or gelling agents, thus envisaging the construction of eco-friendly photovoltaic devices free of expensive, flammable and toxic solvents.

Non-invasive diagnosis of sweat gland dysplasia using optical coherence tomography and reflectance confocal microscopy in a family with anhidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome).

BACKGROUND: Anhidrotic ectodermal dysplasia (AED) is an inherited syndrome, which originates mainly from genetic alteration of the ectodysplasin A (EDA) gene. It regularly affects the adnexa of the skin which results in a characteristic phenotype of the patients including hypo- or anhidrosis leading to severe disturbances in the regulation of body temperature. OBJECTIVES: To prevent the development of the symptoms in early childhood promising therapeutic approaches are currently under clinical investigation. In this context, timely diagnosis of this genetic syndrome is crucial. The purpose of our study was the investigation of modern non-invasive imaging methods such as optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) in the immediate diagnosis of AED. METHODS: We examined a 3-year-old boy with the suspicion for an AED syndrome and his family members with RCM and OCT to document presence and characteristic features of sweat glands in comparison to non-affected individuals. RESULTS: The patient and the affected brother showed significantly reduced sweat glands in the imaging compared to the controls. The genetic analysis revealed a mutation of the EDA gene for hemizygosity previously associated with AED and the mother was revealed as the conductor of the genetic alteration. CONCLUSIONS: With the help of non-invasive imaging, we were able to detect sweat gland dysplasia in the affected family members without performing a biopsy which led us to the diagnosis of an AED. The application of modern dermatological imaging techniques might serve as valuable supplementary tools in the immediate, non-invasive diagnosis of genetic syndromes especially in newborns when early therapeutic approaches are planned.

A novel synthetic single crystal diamond device for in vivo dosimetry.

PURPOSE: Aim of the present work is to evaluate the synthetic single crystal diamond Schottky photodiode developed at the laboratories of "Tor Vergata" University in Rome in a new dosimeter configuration specifically designed for offline wireless in vivo dosimetry (IVD) applications. METHODS: The new diamond based dosimeter, single crystal diamond detector (SCDD-iv), consists of a small unwired detector and a small external reading unit that can be connected to commercial electrometers for getting the detector readout after irradiation. Two nominally identical SCDD-iv dosimeter prototypes were fabricated and tested. A basic dosimetric characterization of detector performances relevant for IVD application was performed under irradiation with (60)Co and 6 MV photon beams. Preirradiation procedure, response stability, short and long term reproducibility, leakage charge, fading effect, linearity with dose, dose rate dependence, temperature dependence, and angular response were investigated. RESULTS: The SCDD-iv is simple, with no cables linked to the patient and the readout is immediate. The range of response with dose has been tested from 1 up to 12 Gy; the reading is independent of the accumulated dose and dose rate independent in the range between about 0.5 and 5 Gy/min; its temperature dependence is within 0.5% between 25 and 38 °C, and its directional dependence is within 2% from 0° to 90°. The combined relative standard uncertainty of absorbed dose to water measurements is estimated lower than the tolerance and action level of 5%. CONCLUSIONS: The reported results indicate the proposed novel offline dosimeter based on a synthetic single crystal diamond Schottky photodiode as a promising candidate for in vivo dosimetry applications with photon beams.

Characterization of a microDiamond detector in high-dose-per-pulse electron beams for intra operative radiation therapy.

PURPOSE: To characterize a synthetic diamond dosimeter (PTW Freiburg microDiamond 60019) in high dose-per-pulse electron beams produced by an Intra Operative Radiation Therapy (IORT) dedicated accelerator. METHODS: The dosimetric properties of the microDiamond were assessed under 6, 8 and 9 MeV electron beams by a NOVAC11 mobile accelerator (Sordina IORT Technologies S.p.A.). The characterization was carried out with dose-per-pulse ranging from 26 to 105 mGy per pulse. The microDiamond performance was compared with an Advanced Markus ionization chamber and a PTW silicon diode E in terms of dose linearity, percentage depth dose (PDD) curves, beam profiles and output factors. RESULTS: A good linearity of the microDiamond response was verified in the dose range from 0.2 Gy to 28 Gy. A sensitivity of 1.29 nC/Gy was measured under IORT electron beams, resulting within 1% with respect to the one obtained in reference condition under (60)Co gamma irradiation. PDD measurements were found in agreement with the ones by the reference dosimeters, with differences in R50 values below 0.3 mm. Profile measurements evidenced a high spatial resolution of the microDiamond, slightly worse than the one of the silicon diode. The penumbra widths measured by the microDiamond resulted approximately 0.5 mm larger than the ones by the Silicon diode. Output factors measured by the microDiamond were found within 2% with those obtained by the Advanced Markus down to 3 cm diameter field sizes. CONCLUSIONS: The microDiamond dosimeter was demonstrated to be suitable for precise dosimetry in IORT applications under high dose-per-pulse conditions.

Successful treatment of PASH syndrome with infliximab, cyclosporine and dapsone.

BACKGROUND: The group of autoinflammatory syndromes associated with Pyoderma gangrenosum, Acne, and Suppurative Hidradenitis are poorly defined and difficult to control with currently available treatment modalities. OBJECTIVES: We describe a patient with PASH syndrome and report about the successful multimodal treatment with infliximab, cyclosporine, and dapsone. METHODS: A review of the available literature to date about this group of autoinflammatory diseases was performed. We performed genetic analysis for PSTPIP1 mutations associated with PAPA syndrome. RESULTS: A 22-year-old woman presented to our department with pyoderma gangrenosum, concomitant acne, and suppurative hidradenitis. She had previously been treated unsuccessfully with etanercept, adalimumab, fumaric acid and the IL-1 receptor antagonist (IL-1RA) anakinra without prolonged remission. Treatment with intravenous infliximab in combination with cyclosporine and dapsone lead to sudden and prolonged improvement of the clinical symptoms that we classified as PASH syndrome. We review the literature about this group of diseases and report the third case of PASH syndrome to date. CONCLUSION: PASH syndrome and associated diseases should be considered whenever hidradenitis suppurativa is found in association with pyoderma gangrenosum. We provide a systematic overview about PASH syndrome and suggest a novel multimodal therapeutic regimen beyond isolated inhibition of TNF or IL-1.