Excision of a large trichilemmal carcinoma of the back with staged reconstruction using biodegradable temporizing matrix (BTM): A case report.

Trichilemmal carcinomas (TC) are rare skin malignancies that arise from the external root sheet of a hair follicle. Their incidence increases with advanced age and they most commonly occur on sun exposed skin or areas of significant hair growth. They vary significantly in size and appearance. Surgical excision is the most common treatment option. We report the case of a large trichilemmal carcinoma of the back occurring in a woman with poorly controlled diabetes mellitus. The lesion was excised resulting in a very large defect, which was reconstructed in a staged process using biodegradable temporising matrix (BTM) and split-skin grafting. There was 95 % graft take at first graft check and the wound was fully healed at 6 weeks post grafting. BTM, already an established adjunct in the reconstruction of burns, degloving injuries and soft tissue infections, provided an enhanced aesthetic outcome and successful wound healing in this complex skin lesion excision.

The Application of a Synthetic Biodegradable Temporizing Matrix in Extensive Burn Injury: A Unicenter Experience of 175 Cases.

Objectives: Addressing extensive and deep burn wounds poses considerable challenges for both patients and surgeons. The NovoSorb® Biodegradable Temporizing Matrix (BTM) emerged as a novel dermal substitute and has been subjected to evaluation in large burn wound cases, with a specific focus on identifying risk factors associated with suboptimal take rates. Methods: All patients with burn wounds greater than 10% body surface that underwent BTM treatment between March 2020 and November 2023 were eligible for inclusion. Univariate analyses and linear regression models were employed to discern risk factors and predictors influencing the take rates of both the BTM and split-thickness skin grafts (STSGs). Results: A total of 175 patients (mean age 56.2 ± 19.8 years, 70.3% male) were evaluated. The mean take rates of the BTM and STSGs were 82.0 ± 24.7% and 87.3 ± 19.0%, respectively. There were significant negative correlations between BTM take and the number of surgeries before BTM application (r = -0.19, p = 0.01), %TBSA and STSG take (r = -0.36, p = <0.001) and significant positive correlations between BTM and STSG take (r = 0.41, p ≤ 0.001) in addition to NPWT and STSG take (r = 0.21, p = 0.01). Multivariate regression analyses showed that a larger number of surgeries prior to BTM application (OR -3.41, 95% CI -6.82, -0.03, p = 0.04) was associated with poorer BTM take. Allograft treatment before BTM application (OR -14.7, 95% CI -23.0, -6.43,p = 0.01) and failed treatment with STSG before BTM application (OR -20.8, 95% CI -36.3, -5.23, p ≤ 0.01) were associated with poorer STSG take, whereas higher BTM take rates were associated with overall higher STSG take (OR -0.15, 95% 0.05, 0.26, p = 0.01). The Meek technique was used in 24 patients and showed similar take rates (BTM: 76.3 ± 28.0%, p = 0.22; STSG: 80.7 ± 21.1, p = 0.07). Conclusions: This study summarizes our findings on the application of a BTM in the context of large burn wounds. The results demonstrate that successful treatment can be achieved even in patients with extensive burns, resulting in satisfying take rates for both the BTM and STSG. The data underscore the importance of promptly applying a BTM to debrided wounds and indicate good results when using Meek.

NovoSorb® Biodegradable Temporizing Matrix: a novel approach for treatment of extremity avulsion injuries in children.

PURPOSE: In pediatric population, large soft tissue defects occur in avulsion injuries. In addition to the challenges of primary surgical therapy, elasticity, appearance and function of the scar in children are of crucial importance, especially in the context of body growth. So far various flaps, plasties, skin grafts and dermal substitutes have become established, although infections and skin shrinkage remain challenging. In 2020, a new skin substitute material-NovoSorb® Biodegradable Temporizing Matrix (BTM)-was introduced in Europe for temporary wound closure and tissue regeneration. The aim of this study was to evaluate the value of BTM in pediatric patients. METHODS: The study included all children treated with BTM after traumatic soft tissue defects following limb avulsion injuries between June 2021 and June 2023 at a university hospital. RESULTS: 7 patients with limb avulsion injuries were treated with BTM, 4 boys, 3 girls. Mean age was 6.5 years (2-11 years) at the time of BTM placement. 4/7 had concomitant fractures. BTM was used successfully in all cases, infection did not occur, skin shrinkage was seen in one case. Split thickness skin graft (STSG) after BTM application was performed in average after 33 days (26 to 39 days). Limitations of this study were highlighted. CONCLUSION: BTM is a promising alternative for reconstruction of complex trauma extremity wounds in children following avulsion injuries, even in cases of concomitant bone injuries. Interpretation may be limited by sample size.

The use of biodegradable temporising matrix (BTM) for facial unit reconstruction with adjuvant radiotherapy-A case study.

Synthetic Biodegradable Temporising Matrix (BTM, NovoSorb; PolyNovo Biomaterials Pty Ltd, Port Melbourne, Victoria, Australia) has proven useful in the resurfacing of large burns,1 necrotising infection debridement2 and tumour excision with exposed bone.3 We present a case report of a large BCC invading three aesthetic subunits of the face which was successfully reconstructed with BTM, split-thickness skin graft with subsequent adjuvant radiotherapy due to the high risk nature of the BCC. We present our series of images illustrating the timeline of BTM, and the ability to achieve a good skin colour match with minimal contour deformity, even in the event of post operative radiotherapy use.

NovoSorb® Biodegradable Temporising Matrix (BTM): What we learned from the first 300 consecutive cases.

INTRODUCTION: Extensive full-thickness soft-tissue defects remain a challenge in reconstructive surgery. NovoSorb® Biodegradable Temporising Matrix (BTM) represents a novel dermal substitute and was evaluated in wounds deriving from different aetiologies and to highlight risk factors for poor take rates. METHODS: All patients treated with BTM at our department between March 2020 and October 2022 were included. Differences in univariate and linear regression models identified predictors and risk factors for take rates of BTM and split-thickness skin grafts (STSG). RESULTS: Three hundred patients (mean age 54.2 ± 20.1 years, 66.3% male, 59.7% burns, 19.7% trauma and 20.6% others) were evaluated. Mean take rates of BTM and STSG after BTM delamination were 82.7 ± 25.2% and 86.0 ± 22.6%, respectively. Multiple regression analyses showed that higher body mass index (BMI, OR 0.43, 95% CI 0.86, -0.01, p = 0.44), prior allograft transplantation (OR 15.12, 95% CI 26.98, -3.31, p = 0.041), longer trauma-to-BTM-application intervals (OR 0.01, 95% CI 0.001, -0.001, p = 0.038), positive wound swabs before BTM (OR 7.15, 95% CI 13.50, -0.80, p = 0.028) and peripheral artery disease (OR 10.80, 95% CI 18.63, -2.96, p = 0.007) were associated with poorer BTM take. Higher BMI (OR 0.40, 95% CI 0.76, -0.08, p = 0.026), increasing BTM graft surface areas (OR 0.58, 95% CI -1.00, -0.17, p = 0.005), prior allograft (OR 12.20, 95% CI -21.99, -2.41, p = 0.015) or autograft transplantations (OR 22.42, 95% CI 38.69, -6.14, p = 0.001), tumour as the aetiology of the wound (OR 37.42, 95% CI 57.41, -17.83, p = 0.001), diabetes (OR 6.64, 95% CI 12.80, -0.48, p = 0.035) and impaired kidney function (OR 5.90, 95% CI 10.94, -0.86, p = 0.021) were associated with poorer STSG take after delamination of BTM, whereas higher BTM take rates were associated with better STSG take (OR 0.40, 95% CI 0.31,0.50, p < 0.001). CONCLUSION: Extensive complex wounds of different aetiologies unsuitable for immediate STSG can be successfully reconstructed by means of two-staged BTM application and subsequent skin grafting. Importantly, presence of wound contamination or infection and prior allograft coverage appear to jeopardise good BTM and STSG take.

How do women perceive their breast image before and after bilateral therapeutic mammoplasty for early breast cancer?

INTRODUCTION: Bilateral therapeutic mammoplasty (BTM) is commonly performed in the UK during treatment for breast cancer, and the available data show oncological safety. This study aims to compare patient-recorded outcome measures before and after surgery, as well as associated patient factors. METHODS: Between March 2018 and December 2019, patients undergoing BTM for breast cancer completed validated BREAST-Q reduction modules before and 3 months after surgery and a radiotherapy domain at 3 months. Scores were correlated with clinical data. For BREAST-Q scales, a higher score (0-100) represents greater satisfaction or quality of life. RESULTS: 28 patients were included, median age 58 years (IQR 52-64), BMI 32.0 (IQR 27.8-34.0). Of these, 1 had bilateral disease, 2 had multifocal disease, and the remaining had unilateral disease. Most (55%) underwent Wise pattern incision. At 3 months post-operatively, the following outcome scores improved based on the Wilcoxon signed-rank test: satisfaction with breasts (median 44 to 84; p < 0.001), psychosocial wellbeing (57.5 to 83; p < 0.001) and sexual wellbeing (48 to 61; p = 0.029). The improvement in satisfaction with breasts score correlated with the preoperative score (p = 0.011), with a larger increase in patients with a lower baseline score. Physical wellbeing was unchanged overall (median 71 to 72). In all solely post-operative domains (satisfaction with information, outcome, nipples and following radiation), patients reported high levels of satisfaction with outcomes. CONCLUSIONS: Patients reported improved levels of patient-related quality of life measures after therapeutic mammoplasty, including satisfaction with breasts and psychosocial and sexual wellbeing, with high post-operative outcomes in satisfaction with outcome, information and nipples, as well as radiation Q-score.

Treatment of Necrotizing Fasciitis With NovoSorb Biodegradable Temporizing Matrix and RECELL Autologous Skin Cell Suspension: A Case Series.

This case series reviews the management of 2 patients who developed a rare, aggressive soft tissue infection, necrotizing fasciitis treated with a synthetic polyurethane dermal regenerative template, Biodegradable Temporizing Matrix (NovoSorb BTM) in conjunction with an off-label use of RECELL device applying autologous skin cell suspension and a split-thickness skin graft for reconstruction. The clinical relevance describes a non-traditional patient's course of treatment and clinical outcome using BTM and RECELL for necrotizing fasciitis. The 2 patients survived with acceptable outcomes and timely healing despite a high chance of mortality and likely amputation secondary to the extensive surface area and anatomical location of the infection.

Using BTM to reconstruct a complex dorsal hand wound with segmental loss of EDC tendon: Case report and review of the literature.

We present the case of a 65 year old man who sustained a complex dorsal hand degloving injury with segmental loss of EDC tendon to middle finger, which was reconstructed using BTM. He returned to near full function despite not having a tendon reconstruction, and the uninjured tendons were able to glide without restriction beneath the BTM. We review the case and the literature surrounding the use of BTM in this clinical scenario.

The use of NovoSorb biodegradable temporising matrix in wound management: a literature review and case series.

OBJECTIVE: NovoSorb (Poly-Novo Ltd, Australia) biodegradable temporising matrix (BTM) is a novel artificial dermal matrix. Previous literature is weighted towards its use in burns reconstruction; however, this paper describes its use within a range of wound aetiologies. The authors present one of the largest and most diverse case series to date, and aim to provide an independent benchmark of clinical practice. METHOD: A retrospective observational study was performed. Patient demographics and clinical data (wound aetiology, site, total body surface area (TBSA), wound bed, number of debridements, time to BTM integration, time to skin grafting) were collected and subgroup analysis preformed. RESULTS: The cohort consisted of 37 patients (acute trauma wounds, n=19; hard-to-heal wounds, n=9; acute infections, n=6; cancer, n=3). Successful BTM integration, allowing subsequent split-thickness skin grafting (STSG), occurred in 70% of cases, despite an overall complication rate of 51%. Mean time from BTM application to STSG was 53 days. There was no difference in STSG outcomes when grafting was performed either before or after the six-week BTM application period. There was no difference when various wound beds (fascia, tendon, periosteum) were compared. Patients >65 years of age were more likely to experience complications; however, this did not affect the speed of integration. The relation of diabetes and smoking to overall integration had no statistical significance. CONCLUSION: In comorbid patients in particular, the time between BTM application and STSG may be longer than the manufacturer's recommendation. Furthermore, data suggest greater wound bed optimisation and closer interval monitoring in hard-to-heal/malignant wounds, and in older patients and patients with comorbidities. However, BTM appears robust (even in infection) and is showing promise as a useful reconstructive tool.

Bone Mineral Density and Serum Bone Turnover Markers among Post-Menarchal Girls from Rural South India.

Background: The data on the bone mineral density (BMD) and bone turnover markers (BTMs) in Indian adolescents are limited. Objectives: To assess BMD at lumbar spine (LS, L1-L4) and femoral neck (FN) in South Indian post-menarchal girls and correlate it with dietary calcium intake (mg/day), physical activity score and post-menarchal years. The study also assessed serum BTMs and their correlation with chronological age in the study population. Methods: This cross-sectional study included apparently healthy post-menarchal adolescent girls aged 12-16 years randomly selected from the community. Participants with vitamin D deficiency were excluded. The data on calcium intake and physical activity were obtained using validated questionnaires. All participants were evaluated with serum calcium, 25-hydroxy vitamin D, parathyroid hormone, N-terminal propeptide of type 1 collagen (P1NP) and Beta-CrossLaps (CTx) and BMD at LS and FN using dual X-ray absorptiometry (DXA). Statistical Analysis: EpiData version 3.1 was used for the data entry. The data analysis was done using Statistical Package for Social Sciences (SPSS) version 21. Continuous variables were expressed as mean ± SD. Pearson's correlation coefficient (r) was calculated, and two-tailed Kendall's tau-b test was used for assessing correlation of all nonparametric measures. Results: A total of 103 participants were screened, and data from 77 were analysed. There was a significant positive correlation of BMD at LS with chronological age (r: +0.235, P = 0.036), but not at FN. Positive correlation of BMD with increase in post-menarchal years was also noted at LS (r: +0.276, P = 0.015). There was no significant association of BMD with calcium intake and physical activity scores at both sites. There was a significant negative correlation of serum BTMs with age CTx (r: -0.596, P = 0.0001) and P1NP (r: -0.505, P = 0.0001). Conclusion: This study provides insight into the reference BMD range at LS spine and FN in South Indian rural post-menarchal adolescent girls. BMD positively correlated, whereas BTMs negatively correlated with age. The study also provides the first Indian reference range for serum BTMs in this age group.

Biodegradable temporising matrix: use of negative pressure wound therapy shows a significantly higher success rate.

OBJECTIVE: The purpose of this case series was to evaluate the efficacy of a synthetic biodegradable temporising matrix (BTM; PolyNovo Biomaterials Pty Ltd, Australia) and compare the outcome of BTM patients with and without negative pressure wound therapy (NPWT). METHOD: A retrospective chart review was conducted on patients admitted with deep full-thickness burns, traumatic or complex wound injuries treated with BTM. Electronic medical records and images were evaluated by a team of clinical professionals. Endpoints included: the measure of successful BTM integration; and comparison between patients treated with and without NPWT. Additional measures were BTM total surface area, BTM sites, timeliness of BTM application and any complications. RESULTS: A total of 28 patients were evaluated and 23 (82.1%) demonstrated overall successful BTM integration. Patients treated with BTM in conjunction with NPWT (n=16) demonstrated a significantly higher (p=0.046) integration rate compared to patients treated without NPWT (n=12) (93.8% versus 58.3%, respectively). Patients treated with BTM with NPWT continued to successfully integrate and sustain favourable outcomes despite the presence of severe infection or the development of haematomas. CONCLUSION: A significantly higher integration rate was demonstrated when BTM was used in conjunction with NPWT. The results of this study further support the efficacy of successful integration of BTM as a replacement for tissue loss in the treatment of deep, full-thickness burns, traumatic and complex wound injuries, and particularly favourable outcomes with the use of NPWT. To the best of our knowledge, this is the first reported case series comparing the clinical outcomes of BTM with and without the use of NPWT.

Treatment of Complex Wounds with NovoSorb® Biodegradable Temporising Matrix (BTM)-A Retrospective Analysis of Clinical Outcomes.

Complex and chronic wounds represent a highly prevalent condition worldwide that requires a multimodal and interdisciplinary treatment approach to achieve good functional and aesthetic outcomes. Due to increasing costs of health care, an aging population and an increase in difficult-to-treat microbial colonization of wounds, complex wounds will become a substantial clinical, social and economic challenge in the upcoming years. In plastic reconstructive surgery, a variety of dermal skin substitutes have been established for clinical use. Since its approval as a dermal skin substitute in Germany, NovoSorb® Biodegradable Temporising Matrix (BTM) has become a valuable therapeutic option for the treatment of full-thickness wound defects. The clinical data published to date are limited to case reports and small-scale case series with the main focus on single wounds. The aim of this single-center study was a retrospective analysis of our own patient collective that has received treatment with BTM for complex wounds. Overall, BTM showed to be a reliable and versatile reconstructive option, especially for patients with multiple co-morbidities and microbiologically colonized wounds. Although the preliminary findings have produced promising results, further investigation and research are warranted regarding long-term outcomes and additional clinical applications.

Differentiating between liver diseases by applying multiclass machine learning approaches to transcriptomics of liver tissue or blood-based samples.

Background & Aims: Liver disease carries significant healthcare burden and frequently requires a combination of blood tests, imaging, and invasive liver biopsy to diagnose. Distinguishing between inflammatory liver diseases, which may have similar clinical presentations, is particularly challenging. In this study, we implemented a machine learning pipeline for the identification of diagnostic gene expression biomarkers across several alcohol-associated and non-alcohol-associated liver diseases, using either liver tissue or blood-based samples. Methods: We collected peripheral blood mononuclear cells (PBMCs) and liver tissue samples from participants with alcohol-associated hepatitis (AH), alcohol-associated cirrhosis (AC), non-alcohol-associated fatty liver disease, chronic HCV infection, and healthy controls. We performed RNA sequencing (RNA-seq) on 137 PBMC samples and 67 liver tissue samples. Using gene expression data, we implemented a machine learning feature selection and classification pipeline to identify diagnostic biomarkers which distinguish between the liver disease groups. The liver tissue results were validated using a public independent RNA-seq dataset. The biomarkers were computationally validated for biological relevance using pathway analysis tools. Results: Utilizing liver tissue RNA-seq data, we distinguished between AH, AC, and healthy conditions with overall accuracies of 90% in our dataset, and 82% in the independent dataset, with 33 genes. Distinguishing 4 liver conditions and healthy controls yielded 91% overall accuracy in our liver tissue dataset with 39 genes, and 75% overall accuracy in our PBMC dataset with 75 genes. Conclusions: Our machine learning pipeline was effective at identifying a small set of diagnostic gene biomarkers and classifying several liver diseases using RNA-seq data from liver tissue and PBMCs. The methodologies implemented and genes identified in this study may facilitate future efforts toward a liquid biopsy diagnostic for liver diseases. Lay summary: Distinguishing between inflammatory liver diseases without multiple tests can be challenging due to their clinically similar characteristics. To lay the groundwork for the development of a non-invasive blood-based diagnostic across a range of liver diseases, we compared samples from participants with alcohol-associated hepatitis, alcohol-associated cirrhosis, chronic hepatitis C infection, and non-alcohol-associated fatty liver disease. We used a machine learning computational approach to demonstrate that gene expression data generated from either liver tissue or blood samples can be used to discover a small set of gene biomarkers for effective diagnosis of these liver diseases.

Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy.

Context: Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy. Objective: The aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl. Methods: This is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA). Results: Men with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (-3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (-4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (-6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (-40.2 ± 35.1 vs. -27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed. Conclusion: T therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Serological, Molecular Prevalence and Genotyping of Coxiella burnetii in Dairy Cattle Herds in Northeastern Algeria.

In Algeria, data on the epidemiology of coxiellosis in cattle are still lacking. In this study, bulk tank milk (BTM) samples from 200 randomly selected dairy cattle herds from Setif province of Algeria were analyzed by an indirect enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). Results highlighted that 37% (95% CI: 30.31-43.69%) and 9% (95% CI: 5.03-12.96%) of BTM samples contained Coxiella burnetii antibodies and DNA, respectively. Based on Cohen's kappa coefficient, a very low agreement between the ELISA and PCR results was found (k = 0.0849) (95% CI: 0.00-0.189). For a second experiment, 186 whole blood samples of cows from farms with reproduction disorders were analyzed by molecular tools to detect C. burnetii. This study revealed an overall prevalence of 6.98% (95% CI: 3.32-10.65%). All positive samples determined by conventional PCR were analyzed by real-time quantitative PCR (qPCR). Eleven samples with cycle threshold (Ct) values lower than 35 were selected for genotyping by the multispacer sequence typing (MST) method. The MST12 genotype in BTM samples, the MST32 genotype and a new MST genotype (partial profile) in whole blood samples were identified. Obtained results have allowed us to better understand the epidemiology of bovine coxiellosis in the region of Setif.

Diagnosis and Management of Osteoporosis in Advanced Kidney Disease: A Review.

Osteoporosis and fractures are common in persons with advanced chronic kidney disease (CKD) and on maintenance dialysis. Although the diagnosis of osteoporosis in this population can be difficult, imaging, especially with dual-energy x-ray absorptiometry (DXA), is helpful in identifying persons with CKD at the highest risk of fracture. Although blood biomarkers including parathyroid hormone and bone-specific alkaline phosphatase concentrations can aid in assessing bone turnover state, bone biopsy remains the gold standard in determining bone turnover in persons with advanced kidney disease and osteoporosis. With the increasing armamentarium of osteoporosis drugs, it now may be possible to prevent many fractures in advanced CKD. Unfortunately, data on these drugs are limited in persons with advanced CKD. Clinicians, aided by advances in imaging, biomarkers, and bone biopsy can now use these novel agents to target bone turnover abnormalities such as adynamic bone disease and high bone turnover disease. This review will discuss the most recent literature surrounding the diagnosis, management, and monitoring of osteoporosis and fractures in persons with advanced CKD or on maintenance dialysis.

Differential blood transcriptome modules predict response to corticosteroid therapy in alcoholic hepatitis.

BACKGROUND & AIMS: In patients with severe alcoholic hepatitis (SAH), little is known about the profile of peripheral blood mononuclear cells (PBMCs) at baseline and during corticosteroid therapy, among those who can be treated successfully with steroids (steroid-responders [R] and those who cannot (steroid-non-responders [NR]); 2 groups with different outcomes. METHODS: We performed RNA-seq analysis in PBMCs from 32 patients with definite SAH, at baseline and after 7 days of corticosteroids. The data were sorted into R and NR (n = 16, each group) using the Lille model and 346 blood transcription modules (BTMs) were identified. BTMs are predefined modules of highly co-expressed PBMC genes, which can determine specific immune cell types and cellular functions. The activity of each BTM was taken as the mean value of its member genes. RESULTS: At baseline, 345 BTMs had higher activity (i.e. were upregulated) in NR relative to R. The 100 most upregulated BTMs in NR, included several modules related to lymphoid lineage (T, B, and natural killer [NK] cells), modules for cell division and mitochondrial respiratory electron transport chain (ETC, relating to energy production), but only a few modules of myeloid cells. Correlation studies of BTM activities found features of significantly greater activation/proliferation and differentiation for T and B cells in NR relative to R. After 7 days of corticosteroids, NR had no significant changes in BTM activities relative to baseline, whereas R had downregulation of BTMs related to innate and adaptive immunity. CONCLUSIONS: At baseline and during corticosteroid therapy, increased activity in the PBMCs of gene modules related to activation/proliferation and differentiation of T and B cells, NK cells, and mitochondrial ETC, is a hallmark of SAH patients who are steroid-non-responders. LAY SUMMARY: Patients with severe alcoholic hepatitis receive steroid therapy as the main line of treatment; however, this treatment is ineffective in some patients. This only becomes apparent after 7 days of steroid therapy. We have developed an approach where it can be estimated if a patient is going to respond or not to steroid therapy using the gene expression information of blood cells. This method will allow clinicians to assess the response of patients to steroids earlier, and will help them in adopting alternate strategies if the treatment is found to be ineffective in a particular patient.

Analysis of the subsequent treatment of osteoporosis by transitioning from bisphosphonates to denosumab, using quantitative computed tomography: A prospective cohort study.

PURPOSE: Denosumab reduces bone resorption and improves bone mineral density (BMD). Studies have analyzed subsequent treatment transitioning from bisphosphonates to denosumab based on dual-energy X-ray absorptiometry scanning (DXA). Quantitative computed tomography (QCT) can help assess cortical and trabecular bones separately in three dimensions without the interference of the surrounding osteophytes. In the present study, we analyzed the subsequent treatment transition from bisphosphonates to denosumab using QCT. METHODS: Thirty-two patients with postmenopausal osteoporosis to be treated with denosumab were recruited. The patients were divided into two groups (15 prior bisphosphonate and 17 naïve) based on their previous treatment. BMD of the lumbar spine and hip were evaluated by DXA and QCT at baseline and 12 months following denosumab treatment. RESULTS: The percentage change in volumetric BMD assessed by QCT at 12 months significantly improved in the naïve group compared with that in the prior bisphosphonate group. The region-specific assessment of femur at 12 months revealed that denosumab treatment was effective in both cortical and trabecular bones except the trabecular region of the prior bisphosphonate group. CONCLUSION: Our study suggests that although denosumab treatment was useful in both treatment groups, BMD increase was significantly higher in the naïve group than in the prior-bisphosphonate group. Interestingly, in the prior-bisphosphonate group, denosumab treatment was more effective in the cortical region than the trabecular region. Our study offers insights into the subsequent treatment and permits greater confidence when switching to denosumab from bisphosphonates.

Coxiella burnetii Shedding in Milk and Molecular Typing of Strains Infecting Dairy Cows in Greece.

Ruminants are considered the commonest animal reservoir for human infection of Coxiella burnetii, the Q fever causative agent. Considering the recently described importance of human Q fever in Greece, we aimed at providing the first comprehensive direct evidence of C. burnetii in dairy cows in Greece, including the genetic characterization of strains. The 462 examined dairy farms represented all geographical areas of Greece. One bulk tank milk sample was collected from every farm and tested for the presence of C. burnetii. Molecular genotyping of strains, performed directly on samples, revealed the existence of two separate clades characterized by single nucleotide polymorphism (SNP) genotypes of type 1 and type 2. The two clades were clearly distinguished in multiple locus variable-number tandem repeat analysis (MLVA) by two discriminative loci: MS30 and MS28. Whereas MLVA profiles of SNP-type 2 clade were closely related to strains described in other European cattle populations, the MLVA profile observed within the SNP type 1 clade highlighted a peculiar genetic signature for Greece, related to genotypes found in sheep and goats in Europe. The shedding of C. burnetii bearing this genotype might have yet undefined human epidemiological consequences. Surveillance of the genetic distribution of C. burnetii from different sources is needed to fully understand the epidemiology of Q fever in Greece.

Skip participates in formation and lipid metabolism of beige adipose and might mediate the effects of SIRT1 activator BTM-0512 on beige remodeling.

Dissipating energy by activating thermogenic adipose to combating obesity attracts many interests. Ski-interacting protein (Skip) has been known to play an important role in cell proliferation and differentiation, but whether it participates in energy metabolism is not known. Our previous study revealed that BTM-0512 could induce beige adipose formation, accompanying with up-regulation of Skip, but the role of Skip in metabolism was unknown. In this study, we mainly investigated whether Skip was involved in beige remodeling of subcutaneous white preadipocytes as well as in lipid metabolism of differentiated beige adipocytes. The results showed that in high fat diet-induced obesity mice, the protein levels of Skip in subcutaneous and visceral white adipose as well as in brown adipose were all down-regulated, especially in subcutaneous white adipose. Then we cultured subcutaneous adipose derived-stem cells (ADSCs) and found knock-down of Skip (siSkip) inhibited the expressions of thermogenic adipose specific genes including PRDM16 and UCP1 in both undifferentiated ADSCs and differentiated beige adipocytes, which could abolish the effects of BTM-0512 on beige remodeling. We further observed that siSkip affected multiple rate-limiting enzymes in lipid metabolism. The expressions of ACC, GPAT-1, HSL and ATGL were down-regulated, while CPT1α expression was up-regulated by siSkip. The expression of AMPK was also decreased by siSkip. In conclusion, our study demonstrated that Skip might play an important role in the beige remodeling of white adipocytes as well as lipid metabolism of beige adipose.