Clinical and demographic features of hidradenitis suppurativa: a multicentre study of 1221 patients with an analysis of risk factors associated with disease severity.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, relapsing and debilitating inflammatory disease associated with profound morbidity. AIM: In this multicentre study, we investigated the demographic and clinical features of HS, and determined risk factors of disease severity. METHODS: In total, 1221 patients diagnosed with HS from 29 centres were enrolled, and the medical records of each patient were reviewed. RESULTS: The mean age of disease onset was 26.2 ± 10.4 years, and almost 70% (n = 849) of patients were current or former smokers. Mean disease duration was 8.9 ± 8.4 years with a delay in diagnosis of 5.8 ± 3.91 years. Just over a fifth (21%; n = 256) of patients had a family history of HS. The axillary, genital and neck regions were more frequently affected in men than in women, and the inframammary region was more frequently affected in women than in men (P < 0.05 for all). Acne (40.8%), pilonidal sinus (23.6%) and diabetes mellitus (12.6%) were the most prevalent associated diseases. Of the various therapies used, antibiotics (76.4%) were most common followed by retinoids (41.7%), surgical interventions (32.0%) and biologic agents (15.4%). Logistic regression analysis revealed that the most important determinants of disease severity were male sex (OR = 2.21) and involvement of the genitals (OR = 3.39) and inguinal region (OR = 2.25). More severe disease was associated with comorbidity, longer disease duration, longer diagnosis delay and a higher number of smoking pack-years. CONCLUSIONS: Our nationwide cohort study found demographic and clinical variation in HS, which may help broaden the understanding of HS and factors associated with disease severity.

Efficacy and safety of 1927 nm fractional Thulium fiber laser for the treatment of melasma: a retrospective study of 100 patients.

Background: Melasma is an acquired hyperpigmentation of the skin that mostly affects areas exposed to the sun. The treatment of melasma can be challenging as it is prone to relapse. Recently, new laser and light-based treatment options have been used; one of these treatment modalities is the 1927 nm fractional Thulium fiber laser.Objective: This study aimed to retrospectively evaluate the efficacy and safety of a 1927 nm fractional Thulium fiber laser for the treatment of melasma.Materials and methods: This study retrospectively evaluated patients who were admitted to the dermatology outpatient clinic between September 2015 and March 2018 and treated with a 1927 nm fractional Thulium fiber laser. The MASI score was used to assess improvements of the lesions.Results: The current study included a total of 100 patients who received 1927 nm fractional Thulium fiber laser treatment. Each patient received two treatments at one month intervals. The mean baseline MASI score was 11.8 ± 6.3, the mean MASI score after the first session was 6.7 ± 4.1, and the mean MASI score after the second session was 3.4 ± 3.8. The differences between these three MASI scores were significant, and the laser treatment had no major side effects.Conclusion: Results of this study indicate that the 1927 nm fractional Thulium fiber laser is a safe and effective treatment option for melasma.

Chemotherapy weakly contributes to predicted neoantigen expression in ovarian cancer.

BACKGROUND: Patients with highly mutated tumors, such as melanoma or smoking-related lung cancer, have higher rates of response to immune checkpoint blockade therapy, perhaps due to increased neoantigen expression. Many chemotherapies including platinum compounds are known to be mutagenic, but the impact of standard treatment protocols on mutational burden and resulting neoantigen expression in most human cancers is unknown. METHODS: We sought to quantify the effect of chemotherapy treatment on computationally predicted neoantigen expression for high grade serous ovarian carcinoma patients enrolled in the Australian Ovarian Cancer Study. In this series, 35 of 114 samples were collected after exposure to chemotherapy; 14 are matched with an untreated sample from the same patient. Our approach integrates whole genome and RNA sequencing of bulk tumor samples with class I MHC binding prediction and mutational signatures extracted from studies of chemotherapy-exposed Caenorhabditis elegans and Gallus gallus cells. We additionally investigated the relationship between neoantigens, tumor infiltrating immune cells estimated from RNA-seq with CIBERSORT, and patient survival. RESULTS: Greater neoantigen burden and CD8+ T cell infiltration in primary, pre-treatment samples were independently associated with improved survival. Relapse samples collected after chemotherapy harbored a median of 78% more expressed neoantigens than untreated primary samples, a figure that combines the effects of chemotherapy and other processes operative during relapse. The contribution from chemotherapy-associated signatures was small, accounting for a mean of 5% (range 0-16) of the expressed neoantigen burden in relapse samples. In both treated and untreated samples, most neoantigens were attributed to COSMIC Signature (3), associated with BRCA disruption, Signature (1), associated with a slow mutagenic process active in healthy tissue, and Signature (8), of unknown etiology. CONCLUSION: Relapsed ovarian cancers harbor more predicted neoantigens than primary tumors, but the increase is due to pre-existing mutational processes, not mutagenesis from chemotherapy.

First report of carglumic acid in a patient with citrullinemia type 1 (argininosuccinate synthetase deficiency).

WHAT IS KNOWN AND OBJECTIVE: Carglumic acid is a structural analogue of human N-acetylglutamate, which has become an alternative therapeutic option for hyperammonaemia in organic acidaemias such as isovaleric acidaemia, methylmalonic acidaemia and propionic acidaemia, and it has been suggested in other urea cycle disorders such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase 1 deficiency. CASE DESCRIPTION: A male newborn was diagnosed with citrullinemia after serum amino acid analyses revealed markedly elevated citrulline concentration together with homozygous p.Gly390Arg mutation in ASS1 gene. The ammonia concentration decreased and blood gas analysis normalized after peritoneal dialysis was performed for three days. Also, sodium benzoate, L-arginine and parenteral nutrition with glucose and lipid therapy were initiated. Until 1 year of age, low adherence to sodium benzoate therapy due to unpleasant taste caused hyperammonaemic episodes and obligated us to initiate carglumic acid (100 mg/kg/day) therapy. During treatment with carglumic acid, the median ammonia level was 45.6 µmol/L. The patient's treatment was switched from carglumic acid to sodium phenylbutyrate when he was 4.5 years old. Currently, the patient is 6.5 years old and remains under follow-up with sodium phenylbutyrate, L-arginine and protein-restricted diet. Plasma ornithine level was found to be significantly lower during the carglumic acid treatment compared to other treatments (P=.039). Also, glutamic acid was found to be higher during the sodium benzoate treatment period compared to other treatment periods (P=.024). WHAT IS NEW AND CONCLUSION: To the best of our knowledge, this is the first report describing the long-term use of carglumic acid in a patient with argininosuccinate synthetase deficiency.

pileup.js: a JavaScript library for interactive and in-browser visualization of genomic data.

UNLABELLED: P: ileup.js is a new browser-based genome viewer. It is designed to facilitate the investigation of evidence for genomic variants within larger web applications. It takes advantage of recent developments in the JavaScript ecosystem to provide a modular, reliable and easily embedded library. AVAILABILITY AND IMPLEMENTATION: The code and documentation for pileup.js is publicly available at https://github.com/hammerlab/pileup.js under the Apache 2.0 license. CONTACT: correspondence@hammerlab.org.

Nutritional status and eating habits of the institutionalised elderly in Turkey: a follow-up study.

BACKGROUND: As the elderly population increases in Turkey, so do the associated health and nutritional problems. The main purpose of the present study was to determine the nutritional status of elderly individuals who live in institutions. METHODS: A total of 102 elderly volunteers was recruited from seven residential homes of the Ministry of Family and Social Policies in Ankara. In the consecutive years of 2007, 2008 and 2009, dietary intake was assessed using a 24-h food recall. Nutritional status was screened using a questionnaire from the Mini-Nutritional Assessment, basic characteristics were determined and anthropometric measurements were assessed. RESULTS: The percentage of elderly participants who were malnourished or at risk for malnutrition increased by the completion of the follow-up (P < 0.05). It was found that energy, total protein, animal proteins, carbohydrates, niacin, vitamin C, vitamin E and zinc intake of men decreased significantly over the years studied (P < 0.05). A significant decrease occurred among women in animal protein, vitamin B1 , niacin and the percentage of energy from proteins (P < 0.05); however, an increase in energy from fat (P < 0.05) was determined. Within the years studied, the percentage of nutrients meeting the Turkish recommended daily allowances decreased from 2007 to 2009 both in men and women. During the years 2007 to 2009, the percentage of waist circumferences >102 cm for men was 46.4%, 45.6% and 48.1%, respectively, and the percentage of waist circumferences for women >88 cm was 75.6%, 75.6% and 81.8%, respectively. CONCLUSIONS: During the follow-up, significant nutritional changes were determined. To prevent malnutrition, periodical screening of nutritional status should be a priority and a standard policy for elderly people, especially for those institutionalised.

The impact of rosacea on quality of life: effects of demographic and clinical characteristics and various treatment modalities.

BACKGROUND: Rosacea has a major psychosocial impact on a patient's life. OBJECTIVES: To determine the impact of rosacea on patient quality of life, the relationship of quality of life scores to clinical and demographic variables, and the change in quality of life following various treatments. METHODS: Patients' demographic and clinical characteristics were recorded at their initial examination and their response to treatment and side-effects were recorded additionally at their follow-up examination. Rosacea severity was scored for each of four signs from 0 to 3. Patients were requested to complete Dermatology Life Quality Index (DLQI) questionnaires. RESULTS: A total of 308 patients took part in this study. Mean ± SD DLQI total score at the initial visit was 6·93 ± 5·18 and was related to patients' age, sex, age at disease onset, subjective symptoms, triggering factors, previous treatments, rosacea severity scores and patients' self-assessment of ease of living with rosacea. Of these 308 patients, 164 completed the DLQI following treatment. Mean ± SD post-treatment DLQI score was 4·36 ± 4·82. Post-treatment scores were also related to sex, type of treatment modality, development of side-effects, improvement of rosacea, rosacea severity scores and patients' self-reported ease of living with rosacea. Topical metronidazole, oral tetracycline and oral isotretinoin were observed to reduce signs and symptoms of rosacea and DLQI scores significantly at this repeat examination. CONCLUSIONS: Rosacea affects patients' lives to a moderate extent, and this can be assessed by using DLQI. DLQI is also sensitive to quality of life changes brought about by treatment of rosacea. As a preliminary result we can say that topical metronidazole, oral tetracycline and oral isotretinoin seem to improve quality of life of patients by improving lesions of rosacea more efficiently than other therapeutic agents.

Mutations in an Innate Immunity Pathway Are Associated with Poor Overall Survival Outcomes and Hypoxic Signaling in Cancer.

Complement-mediated cytotoxicity may act as a selective pressure for tumor overexpression of complement regulators. We hypothesize that the same selective pressure could lead to complement alterations at the genetic level. We find that, when analyzed as a pathway, mutations in complement genes occur at a relatively high frequency and are associated with changes in overall survival across a number of cancer types. Analysis of pathways expressed in patients with complement mutations that are associated with poor overall survival reveals crosstalk between complement and hypoxia in colorectal cancer. The importance of this crosstalk is highlighted by two key findings: hypoxic signaling is increased in tumors harboring complement mutations, and hypoxic tumor cells are resistant to complement-mediated cytotoxicity due, in part, to hypoxia-induced expression of complement regulator CD55. The range of strategies employed by tumors to dysregulate the complement system testifies to the importance of this pathway in tumor progression.

Time-resolved local strain tracking microscopy for cell mechanics.

A uniaxial cell stretching technique to measure time-resolved local substrate strain while simultaneously imaging adherent cells is presented. The experimental setup comprises a uniaxial stretcher platform compatible with inverted microscopy and transparent elastomer samples with embedded fluorescent beads. This integration enables the acquisition of real-time spatiotemporal data, which is then processed using a single-particle tracking algorithm to track the positions of fluorescent beads for the subsequent computation of local strain. The present local strain tracking method is demonstrated using polydimethylsiloxane (PDMS) samples of rectangular and dogbone geometries. The comparison of experimental results and finite element simulations for the two sample geometries illustrates the capability of the present system to accurately quantify local deformation even when the strain distribution is non-uniform over the sample. For a regular dogbone sample, the experimentally obtained value of local strain at the center of the sample is 77%, while the average strain calculated using the applied cross-head displacement is 48%. This observation indicates that considerable errors may arise when cross-head measurement is utilized to estimate strain in the case of non-uniform sample geometry. Finally, the compatibility of the proposed platform with biological samples is tested using a unibody PDMS sample with a well to contain cells and culture media. HeLa S3 cells are plated on collagen-coated samples and cell adhesion and proliferation are observed. Samples with adherent cells are then stretched to demonstrate simultaneous cell imaging and tracking of embedded fluorescent beads.

An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma.

Dysregulated metabolism is a hallmark of cancer, manifested through alterations in metabolites. We performed metabolomic profiling on 138 matched clear cell renal cell carcinoma (ccRCC)/normal tissue pairs and found that ccRCC is characterized by broad shifts in central carbon metabolism, one-carbon metabolism, and antioxidant response. Tumor progression and metastasis were associated with metabolite increases in glutathione and cysteine/methionine metabolism pathways. We develop an analytic pipeline and visualization tool (metabolograms) to bridge the gap between TCGA transcriptomic profiling and our metabolomic data, which enables us to assemble an integrated pathway-level metabolic atlas and to demonstrate discordance between transcriptome and metabolome. Lastly, expression profiling was performed on a high-glutathione cluster, which corresponds to a poor-survival subgroup in the ccRCC TCGA cohort.

Self-assembled micro-structured sensors for food safety in paper based food packaging.

Natural self-assembled microstructured particles (diatomaceous earth) were used to develop a gas sensor paper with detection mechanism based on visible and distinct color changes of the sensor paper when exposed to volatile basic nitrogen compounds. The coating formulation for paper was prepared by applying diatomites, polyvinyl alcohol (PVOH), and pH sensitive dyes on acidic paper substrate. The surface coating was designed to allow a maximum gas flow through the diatomite sensors. The produced sensor paper was tested for sensitivity using different ammonia concentrations and we observed a sensitivity lower limit at 63 ppm. As a comparison, the results show comparable sensitivity levels to carbon nanotube based sensor technologies reported in literature.

Optimal timing and temperature for hyperthermic preconditioning in an animal model of fecal peritonitis.

The impact of immune parameters in the mechanism of hyperthermia is yet to be explained. In this study, the optimal timing and temperature of thermal treatment for reversing the abnormal immunologic parameters obtained in a rat model of peritonitis were planned to be determined. Male Sprague-Dawley rats were grouped as sham, control peritonitis, and thermally treated rats at the time of peritonitis or 4 h prior to induction of peritonitis both at 40 and 42 degrees C. Peritonitis was induced by the cecal ligation and perforation model. Eight hours after the induction of peritonitis, rats were sacrified and samples were taken for measurements of CD4+, CD8+, CD(11b), B cells, NK cells, and tumor necrosis factor alpha (TNFalpha) and thiobarbituric acid-reactive substances (TBARS) levels. CD4+ expression and B cell amount were decreased whereas TNFalpha levels, CD8+ and CD(11b) expression, and NK cell amount were found to be increased in the control peritonitis group when compared to the sham group. Peritonitis induction also increased TBARS levels in liver tissue. Hyperthermic preconditioning at either 40 or 42 degrees C applied 4 h prior to peritonitis induction returned all parameters to their normal levels, which is similar to the results of the sham laparotomy group. The results of TNFalpha values in preconditioned rats were varied according to the temperature that was applied. The levels were increased at 40 degrees C, whereas they showed a decline at 42 degrees C. Hyperthermic preconditioning prevented the oxidative damage in liver as well as TNFalpha elevation, particularly at 42 degrees C. Results from this study suggest that hyperthermic preconditioning 4 h prior to the onset of septic events may improve the adverse outcome in sepsis.

Primary multiple hydatid cysts of the brain: case report.

Primary multiple hydatid cyst in the brain is uncommon. We report two large primary multiple hydatid cysts of the brain in an adult, which were removed without rupture by two separate operations.

Clinical significance of nuclear p53 protein accumulation in bladder cancer.

OBJECTIVES: To investigate the correlation of nuclear p53 accumulation with disease outcome in a cohort of patients with transitional cell carcinoma of the bladder. METHODS: A total of 90 patients (11 female, 79 male) with transitional cell carcinoma of the bladder were included in this study. Tumour samples from the primary tumour were analysed by immunohistochemistry for nuclear accumulation of p53 protein. Outcome of each patient was recorded and investigated for a possible relation with p53 status. RESULTS: Nuclear p53 deposition was determined in 22 specimens. The nuclear p53 deposition was seen in less than 20% of the nuclei examined in 13 and more than 20% in 9 cases. No stromal staining was observed. Nuclear p53 deposition was present in 15.2% (7/46) of grade 2 tumours, and 34% (15/44) of grade 3 tumours (p=0.037). Stage distribution revealed 15.5% (5/33) positivity in stage pTa, 25.8% (8/31) in pT1 and 34% (9/26) in stage pT2-3 tumours. Tumours with p53 nuclear accumulation had a higher rate of recurrence and progression and shorter survival. CONCLUSION: Results of the current study indicate p53 as an important factor in determination of biological behaviour of bladder cancer.

Tenosynovial giant cell tumour of the posterior cruciate ligament and its arthroscopic treatment.

Tenosynovial giant cell tumours originate from synovial tissues of the joints, tendon sheaths, mucosal bursas or fibrous tissues adjacent to tendons. Tenosynovial giant cell tumours are rarely intra-articular. We report a giant cell tumour of the tendon sheath arising from the posterior cruciate ligament diagnosed by magnetic resonance imaging and resected arthroscopically in a 54-year-old woman.

Avulsion of the iliac crest apophysis.

In this paper we report a case concerning an avulsion fracture of the iliac crest in an 18-year-old boy. The fracture happened while he was playing soccer. He reported with a left hip pain to the Accident and Emergency Department about half an hour after the injury had occurred. The diagnosis was made on the basis of radiographs of the pelvis which showed an avulsion fracture of the iliac crest. He was treated conservatively with a nonsteroidal anti-inflammatory drug and rest. Two months later he could play soccer again without any complaint.

Nuclear accumulation of mutant p53 protein: a possible predictor of failure of intravesical therapy in bladder cancer.

OBJECTIVE: To investigate the expression and importance of the nuclear accumulation of p53 in superficial transitional cell carcinoma (TCC) of the bladder and its role as a predictor of response to treatment. PATIENTS AND METHODS: Tumour samples from 30 patients (two women and 28 men, mean age 60.1 years, range 44-75) with pTa/pT1 tumours were assessed immunohistochemically using the Pab1801 monoclonal antibody and standard avidin-biotin peroxidase staining for p53 protein. RESULTS: Tumours from six patients (20%) showed nuclear accumulation of p53; five of these patients failed intravesical therapy with bacille Calmette-Guèrin (BCG) and progressed to muscle invasive and/or metastatic disease, in contrast to six of 24 patients with no detectable nuclear oncoprotein. CONCLUSIONS: The nuclear accumulation of p53 appears to be a prognostic indicator of tumour unresponsive to intravesical treatment, even with the most potent agent (BCG). Therefore, early radical treatment modalities must be seriously considered in this group of patients.