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.

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.

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.

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.

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.

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.

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.

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.

KIR and KIR ligand polymorphism: a new area for clinical applications?

Killer immunoglobulin-like receptors (KIRs) play an essential role in the regulation of natural killer (NK) activity, allowing NK cells to sense and respond to human leukocyte antigen (HLA) class I downregulation, an important hallmark for viral infections and tumor transformation. KIR and HLA genes are located on different chromosomes and KIR/HLA class I interaction represents an example of genetic epistasis in which the presence of receptor/ligand pairs is necessary for the induction of functional activity, while the presence of one in the absence of the other is not sufficient to influence NK cell function. Due to the high degree of HLA class I and KIR gene variability, KIR/KIR-ligand (KIR-L) interactions are extraordinarily diverse. KIR polymorphism arises from both haplotypic and allelic variations and was shaped by natural selection. KIR variability affects NK cell education influencing the KIR repertoire, KIR expression, the strength of KIR/KIR-L interactions and the capability to deliver signals. Moreover, it may influence NK cell function during infections, autoimmune diseases, pregnancy and allogeneic transplantation. This review summarizes the genetic and functional features of KIR/KIR-L interactions and gives an overview of their potential relevance in clinical studies.

PLP1 gene analysis in 88 patients with leukodystrophy.

Pelizaeus-Merzbacher disease (PMD) is caused in most cases by either duplications or point mutations in the PLP1 gene. This disease, a dysmyelinating disorder affecting mainly the central nervous system, has a wide clinical spectrum and its causing mutations act through different molecular mechanisms. Eighty-eight male patients with leukodystrophy were studied. PLP1 gene analysis was performed by the Multiplex Ligation-dependent Probe Amplification technique and DNA sequencing, and, in duplicated cases of PLP1, gene dosage was completed by using array-CGH. We have identified 21 patients with mutations in the PLP1 gene, including duplications, short and large deletions and several point mutations in our cohort. A customized array-CGH at the Xq22.2 area identified several complex rearrangements within the PLP1 gene region. Mutations found in the PLP1 gene are the cause of PMD in around 20% of the patients in this series.

Schnitzler's syndrome: diagnosis, treatment, and follow-up.

Schnitzler's syndrome is characterized by recurrent urticarial rash and monoclonal gammopathy, associated with clinical and biological signs of inflammation and a long-term risk of AA amyloidosis and overt lymphoproliferation. An extensive literature review was performed, and the following questions were addressed during an expert meeting: In whom should Schnitzler's syndrome be suspected? How should the diagnosis of Schnitzler's syndrome be established? How should a patient with Schnitzler's syndrome be treated? How should a patient with Schnitzler's syndrome be followed up?. A diagnosis of Schnitzler's syndrome is considered definite in any patient with two obligate criteria: a recurrent urticarial rash and a monoclonal IgM gammopathy, and two of the following minor criteria: recurrent fever, objective signs of abnormal bone remodeling, elevated CRP level or leukocytosis, and a neutrophilic infiltrate on skin biopsy. It is considered probable, if only 1 minor criterion is present. In patients with monoclonal IgG gammopathies, diagnosis is definite if three minor criteria are present and possible if two are present. First-line treatment in patients with significant alteration of quality of life or persistent elevation of markers of inflammation should be anakinra. Follow-up should include clinical evaluation, CBC and CRP every 3 months and MGUS as usually recommended.

Actinic keratosis in the en-face and slice imaging mode of high-definition optical coherence tomography and comparison with histology.

BACKGROUND: Optical coherence tomography (OCT) allows real-time, in vivo examination of nonmelanoma skin cancer. An innovative high-definition (HD)-OCT with a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of actinic keratosis (AK) and may potentially replace invasive diagnostic biopsies. OBJECTIVES: To define the characteristic morphological features of AK by using HD-OCT in the two imaging modes compared with histopathology as gold standard. METHODS: In total, 20 AKs were examined by HD-OCT in the en-face and slice imaging modes and characteristic features were described and evaluated in comparison with the histopathological findings. Furthermore, the HD-OCT images of a subgroup of AKs were compared with those of the clinically normal adjacent skin. RESULTS: The preoperative in vivo diagnostics showed the following features in the en-face imaging mode of HD-OCT: disruption of stratum corneum, architectural disarray, cellular/nuclear polymorphism in the stratum granulosum/stratum spinosum, and bright irregular bundles in the superficial dermis. In the vertical slice imaging mode the following characteristics were found: irregular entrance signal, destruction of layering, white streaks and dots, and grey areas. In contrast, the clinically healthy adjacent skin showed mainly a regular epidermal 'honeycomb' pattern in the en-face mode and distinct layering of the skin in the slice mode. CONCLUSIONS: HD-OCT with both the en-face and slice imaging modes offers additional information in the diagnosis of AK compared with conventional OCT and might enhance the possibility of the noninvasive diagnosis of AK prior to treatment procedures and possibly in the monitoring of noninvasive treatment strategies.

Morphology of basal cell carcinoma in high definition optical coherence tomography: en-face and slice imaging mode, and comparison with histology.

BACKGROUND: Optical coherence tomography (OCT) allows real-time, in vivo examination of basal cell carcinoma (BCC). A new high definition OCT with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode offers additional information in the diagnosis of BCC and may potentially replace invasive diagnostic biopsies. OBJECTIVES: To define the characteristic morphologic features of BCC by using high definition optical coherence tomography (HD-OCT) compared to conventional histology. METHODS: A total of 22 BCCs were examined preoperatively by HD-OCT in the en-face and slice imaging mode and characteristic features were evaluated in comparison to the histopathological findings. RESULTS: The following features were found in the en-face mode of HD-OCT: lobulated nodules (20/22), peripheral rimming (17/22), epidermal disarray (21/22), dilated vessels (11/22) and variably refractile stroma (19/22). In the slice imaging mode the following characteristics were found: grey/dark oval structures (18/22), peripheral rimming (13/22), destruction of layering (22/22), dilated vessels (7/22) and peritumoural bright stroma (11/22). In the en-face mode the lobulated structure of the BCC was more distinct than in the slice mode compared to histology. CONCLUSION: HD-OCT with a horizontal and vertical imaging mode offers additional information in the diagnosis of BCC compared to conventional OCT imaging and enhances the feasibility of non-invasive diagnostics of BCC.

Reflectance confocal microscopy in the diagnosis of partially and completely amelanotic melanoma: report on seven cases.

BACKGROUND: The clinical diagnosis of amelanotic melanoma is often challenging, because the classical clinical and dermoscopic features of pigmented melanoma are usually missing. The reflectance confocal microscopy (RCM) offers an additional possibility of an in vivo diagnosis of both pigmented and amelanotic melanoma lesions. OBJECTIVES: To test the value of RCM in vivo in the preoperative prediction of melanoma lesions lacking significant pigment and to compare the results with the evaluation by dermoscopy and histopathology. METHODS: We examined seven patients with the clinically uncertain differential diagnosis of partially or completely amelanotic melanoma by RCM and dermoscopy prior to surgical excision of the lesions according to the previously suggested dermoscopy algorithm and RCM score for melanoma. The following RCM features were evaluated: major criteria scored +2 (non-edged papillae, cytological atypia at the dermo-epidermal junction) and minor criteria +1 (roundish pagetoid cells, widespread pagetoid infiltration, nucleated cells within dermal papillae, cerebriform cell clusters). The dermoscopic evaluation included the following criteria: polymorphous vessels, dotted and linear irregular vessels, hairpin vessels, pink-erythematous colour, milky red areas, irregularly shaped depigmentation, blue-grey dots and subtle pigmentation. RESULTS: The preoperative in vivo RCM analysis revealed common features of melanoma also found in pigmented melanoma lesions. All lesions showed a score above three in the applied RCM algorithm which was proposed earlier as the threshold for malignancy. In dermoscopy, five of seven lesions showed characteristic vascular changes. CONCLUSION: In vivo RCM is a valuable tool in the preoperative diagnosis of partially and completely amelanotic tumours suspicious for melanoma in addition to dermoscopic evaluation.

Fatigue in patients undergoing radiation therapy: an observational study.

AIM: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer. METHODS: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 g / day for the first 10 days of radiation treatment and then 10 g/day for the following 20 days without considering the terms of the radiation oncology treatment [corrected]. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother. RESULTS: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue. CONCLUSION: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.

High-definition optical coherence tomography for the in vivo detection of demodex mites.

BACKGROUND: Demodex mites are involved in different skin diseases and are commonly detected by skin scrape tests or superficial biopsies. A new high-definition optical coherence tomography (HD-OCT) with high lateral and axial resolution in a horizontal (en-face) and vertical (slice) imaging mode might offer the possibility of noninvasive and fast in vivo examination of demodex mites. METHODS: Twenty patients with demodex-related skin diseases and 20 age- and gender-matched healthy controls were examined by HD-OCT. Mites per follicle and follicles per field of view were counted and compared to skin scrape tests. RESULTS: HD-OCT images depicted mites in the en-face mode as bright round dots in groups of 3-5 mites per hair follicle. In the patients with demodex-related disease, a mean number of 3.4 mites per follicle were detected with a mean number of 2.9 infested follicles per area of view compared to a mean of 0.6 mites in 0.4 infested follicles in the controls. The skin scrape tests were negative in 21% of the patients. CONCLUSION: The innovative HD-OCT enables fast and noninvasive in vivo recognition of demodex mites and might become a useful tool in the diagnosis and treatment monitoring of demodex-related skin diseases.

[The role of molecular genetics in dermatologic diagnosis]. / Molekulargenetik in der dermatologischen Diagnostik.

Modern molecular techniques have tremendously expanded our knowledge about the biologic processes in healthy individuals as well as our understanding about the pathologic events in an increasing number of dermatological diseases. These technologies initially came from basic molecular biology and genetic research but have become firmly anchored in clinical diagnosis approaches. Included in this group are immunohistochemistry (IHC), polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), chromogen in situ hybridization (CISH), comparative genomic hybridization (CGH), and microarray technology. IHC and PCR already belong to the armamentarium for routine daily diagnostics due to their high degree of standardization and reproducibility, ease of use and relatively low costs. Others like FISH and CISH are currently employed for specific indications in a growing number of larger laboratories, whereas CGH and microarray technology still remain in the hands of a few highly specialized laboratories. These new ancillary methods will help to improve diagnostic accuracy particularly in cases in which conventional histopathology is ambiguous. In addition, they will provide new and important information concerning the prognosis, progression and response rate to therapies in several particular malignant diseases.

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.