Laser-mediated osteoblast ablation triggers a pro-osteogenic inflammatory response regulated by reactive oxygen species and glucocorticoid signaling in zebrafish.

In zebrafish, transgenic labeling approaches, robust regenerative responses and excellent in vivo imaging conditions enable precise characterization of immune cell behavior in response to injury. Here, we monitored osteoblast-immune cell interactions in bone, a tissue which is particularly difficult to in vivo image in tetrapod species. Ablation of individual osteoblasts leads to recruitment of neutrophils and macrophages in varying numbers, depending on the extent of the initial insult, and initiates generation of cathepsin K+ osteoclasts from macrophages. Osteoblast ablation triggers the production of pro-inflammatory cytokines and reactive oxygen species, which are needed for successful macrophage recruitment. Excess glucocorticoid signaling as it occurs during the stress response inhibits macrophage recruitment, maximum speed and changes the macrophage phenotype. Although osteoblast loss is compensated for within a day by contribution of committed osteoblasts, macrophages continue to populate the region. Their presence is required for osteoblasts to fill the lesion site. Our model enables visualization of bone repair after microlesions at single-cell resolution and demonstrates a pro-osteogenic function of tissue-resident macrophages in non-mammalian vertebrates.

Axial skeleton anterior-posterior patterning is regulated through feedback regulation between Meis transcription factors and retinoic acid.

Vertebrate axial skeletal patterning is controlled by co-linear expression of Hox genes and axial level-dependent activity of HOX protein combinations. MEIS transcription factors act as co-factors of HOX proteins and profusely bind to Hox complex DNA; however, their roles in mammalian axial patterning remain unknown. Retinoic acid (RA) is known to regulate axial skeletal element identity through the transcriptional activity of its receptors; however, whether this role is related to MEIS/HOX activity remains unknown. Here, we study the role of Meis in axial skeleton formation and its relationship to the RA pathway in mice. Meis elimination in the paraxial mesoderm produces anterior homeotic transformations and rib mis-patterning associated to alterations of the hypaxial myotome. Although Raldh2 and Meis positively regulate each other, Raldh2 elimination largely recapitulates the defects associated with Meis deficiency, and Meis overexpression rescues the axial skeletal defects in Raldh2 mutants. We propose a Meis-RA-positive feedback loop, the output of which is Meis levels, that is essential to establish anterior-posterior identities and patterning of the vertebrate axial skeleton.

Enteral nutrition in septic shock: a call for a paradigm shift.

PURPOSE OF REVIEW: The purpose of this review is to identify contemporary evidence evaluating enteral nutrition in patients with septic shock, outline risk factors for enteral feeding intolerance (EFI), describe the conundrum of initiating enteral nutrition in patients with septic shock, appraise current EFI definitions, and identify bedside monitors for guiding enteral nutrition therapy. RECENT FINDINGS: The NUTRIREA-2 and NUTRIREA-3 trial results have better informed the dose of enteral nutrition in critically ill patients with circulatory shock. In both trials, patients with predominant septic shock randomized to receive early standard-dose nutrition had more gastrointestinal complications. Compared to other contemporary RCTs that included patients with circulatory shock, patients in the NUTRIREA-2 and NUTRIREA-3 trials had higher bowel ischemia rates, were sicker, and received full-dose enteral nutrition while receiving high baseline dose of vasopressor. These findings suggest severity of illness, vasopressor dose, and enteral nutrition dose impact outcomes. SUMMARY: The provision of early enteral nutrition preserves gut barrier functions; however, these benefits are counterbalanced by potential complications of introducing luminal nutrients into a hypo-perfused gut, including bowel ischemia. Findings from the NUTRIREA2 and NUTRIREA-3 trials substantiate a 'less is more' enteral nutrition dose strategy during the early acute phase of critical illness. In the absence of bedside tools to guide the initiation and advancement of enteral nutrition in patients with septic shock, the benefit of introducing enteral nutrition on preserving gut barrier function must be weighed against the risk of harm by considering dose of vasopressor, dose of enteral nutrition, and severity of illness.

Long-term efficacy of percutaneous tibial nerve stimulation for faecal incontinence and a new approach for partial responders.

BACKGROUND: The aim of the present study was to evaluate the long-term efficacy of percutaneous tibial nerve stimulation (PTNS) for patients with faecal incontinence (FI) refractory to conservative treatment. Secondary aims were to identify predictors of response and validate new treatment pathways for partial responders. METHODS: A prospective, interventional study was carried out in a specialist defecatory disorder unit from a university hospital between January 2010 and June 2017 on patients > 18 years old with FI refractory to conservative treatment. Thirty-minute PTNS sessions were performed in three phases (weekly, biweekly and monthly) up to a year, with clinical reassessment at 3, 6, 12 and 36 months. Patients were classified as optimal responders when their pretreatment Wexner score decreased > 50%; partial responders when it decreased 25-50%; and insufficient responders if it decreased < 25%. Only optimal and partial responders progressed into successive phases. RESULTS: Between 2010 and 2017, 139 patients (110 women, median age 63 years [range 22-82 years]) were recruited. After the first phase, 4 patients were optimal responders, 93 were partial responders and 36 were insufficient responders. At 6 and 12 months, 66 and 89 patients respectively were optimal responders, with an optimal response rate of 64% at the end of treatment. A total of 93.3% patients with a partial response initially finally became optimal responders. Furthermore, at 36 months, 71.9% of patients were still optimal responders without supplementary treatment, although their quality of life did not improve significantly. Baseline Wexner scores ≤ 10 and symptom duration < 1 year were identified as predictive factors for positive responses to PTNS. CONCLUSIONS: Patients undergoing PTNS for 1 year following this protocol had optimal long-term responses. PTNS sessions for up to 1 year in patients who were partial responders prevents a high percentage of them from needing more invasive treatments, and maintains long-term continence in patients who were optimal responders.

History or demography? Determining the drivers of genetic variation in North American plants.

Understanding the impact of historical and demographic processes on genetic variation is essential for devising conservation strategies and predicting responses to climate change. Recolonization after Pleistocene glaciations is expected to leave distinct genetic signatures, characterised by lower genetic diversity in previously glaciated regions. Populations' positions within species ranges also shape genetic variation, following the central-marginal paradigm dictating that peripheral populations are depauperate, sparse and isolated. However, the general applicability of these patterns and relative importance of historical and demographic factors remains unknown. Here, we analysed the distribution of genetic variation in 91 native species of North American plants by coupling microsatellite data and species distribution modelling. We tested the contributions of historical climatic shifts and the central-marginal hypothesis on genetic diversity and structure on the whole data set and across subsets based on taxonomic groups and growth forms. Decreased diversity was found with increased distance from potential glacial refugia, coinciding with the expected make-up of postglacially colonised localities. At the range periphery, lower genetic diversity, higher inbreeding levels and genetic differentiation were reported, following the assumptions of the central-marginal hypothesis. History and demography were found to have approximately equal importance in shaping genetic variation.

Osteogenic capacity of mesenchymal stem cells from patients with osteoporotic hip fractures in vivo.

PURPOSE: Human mesenchymal stem cells (MSCs) have the ability to differentiate into bone-forming osteoblasts. The aim of this study was to elucidate if MSCs from patients with OP show a senescent phenotype and explore their bone-forming ability in vivo. MATERIALS AND METHODS: MSCs from patients with OP and controls with osteoarthritis (OA) were implanted into the subcutaneous tissue of immunodeficient mice for histological analysis and expression of human genes by RT-PCR. The expression of senescence-associated phenotype (SASP) genes, as well as p16, p21, and galactosidase, was studied in cultures of MSCs. RESULTS: In vivo bone formation was evaluated in 103 implants (47 OP, 56 OA). New bone was observed in 45% of the implants with OP cells and 46% of those with OA cells (p = 0.99). The expression of several bone-related genes (collagen, osteocalcin, alkaline phosphatase, sialoprotein) was also similar in both groups. There were no differences between groups in SASP gene expression, p16, and p21 expression, or in senescence-associated galactosidase activity. CONCLUSION: Senescence markers and the osteogenic capacity in vivo of MSCs from patients with OP are not inferior to that of cells from controls of similar age with OA. This supports the interest of future studies to evaluate the potential use of autologous MSCs from OP patients in bone regeneration procedures.

Homomorphic Asymmetric Encryption Applied to the Analysis of IoT Communications.

In this paper, we describe the use of homomorphic encryption techniques in order to not only ensure the data are transmitted in a confidential way, but also to use the encrypted data to provide the manager with statistics that allow them to detect the incorrect functioning of a sensor node or a group of sensors due to either malicious data injection, data transmission, or simply sensor damage (miscalibration, faulty sensor functioning). Obtaining these statistical values does not need decryption, so the process is sped up and can be developed in real time. Operating the data in this way ensures privacy and removes the need to maintain a shared key infrastructure between the sensor nodes and the manager nodes that are part of the blockchain infrastructure. In this work, we focus on operations with the sensor nodes that provide data that will be, later, treated as part of the business logic in the agribusiness sector (for example), hence the importance of having fast checking mechanisms in terms of data quality. The results obtained on conventional configurations of sensor nodes encourage the use of this technique in the aforementioned infrastructure.

Point-of-care lung ultrasound assessment for risk stratification and therapy guiding in COVID-19 patients: a prospective noninterventional study.

BACKGROUND: Lung ultrasound is feasible for assessing lung injury caused by coronavirus disease 2019 (COVID-19). However, the prognostic meaning and time-line changes of lung injury assessed by lung ultrasound in COVID-19 hospitalised patients are unknown. METHODS: Prospective cohort study designed to analyse prognostic value of lung ultrasound in COVID-19 patients by using a quantitative scale (lung ultrasound Zaragoza (LUZ)-score) during the first 72 h after admission. The primary end-point was in-hospital death and/or admission to the intensive care unit. Total length of hospital stay, increase of oxygen flow and escalation of medical treatment during the first 72 h were secondary end-points. RESULTS: 130 patients were included in the final analysis; mean±sd age was 56.7±13.5 years. Median (interquartile range) time from the beginning of symptoms to admission was 6 (4-9) days. Lung injury assessed by LUZ-score did not differ during the first 72 h (21 (16-26) points at admission versus 20 (16-27) points at 72 h; p=0.183). In univariable logistic regression analysis, estimated arterial oxygen tension/inspiratory oxygen fraction ratio (PAFI) (hazard ratio 0.99, 95% CI 0.98-0.99; p=0.027) and LUZ-score >22 points (5.45, 1.42-20.90; p=0.013) were predictors for the primary end-point. CONCLUSIONS: LUZ-score is an easy, simple and fast point-of-care ultrasound tool to identify patients with severe lung injury due to COVID-19, upon admission. Baseline score is predictive of severity along the whole period of hospitalisation. The score facilitates early implementation or intensification of treatment for COVID-19 infection. LUZ-score may be combined with clinical variables (as estimated by PAFI) to further refine risk stratification.

Long-term Evaluation of Fistulotomy and Immediate Sphincteroplasty as a Treatment for Complex Anal Fistula.

BACKGROUND: Fistulotomy with immediate sphincteroplasty is a technique that can heal fistulas and decrease fecal incontinence more effectively than fistulotomy alone, in selected patients. OBJECTIVE: We aimed to perform a long-term evaluation of fecal incontinence after fistulotomy and immediate sphincteroplasty in patients with complex anal fistula. DESIGN: This prospective study included patients undergoing fistulotomy and immediate sphincteroplasty for complex anal fistula from January 2000 to December 2010. SETTINGS: The study was conducted by 2 colorectal surgeons in the coloproctology unit of the General Hospital of Elche. PATIENTS: We included patients aged ≥18 years with complex anal fistulas of cryptoglandular origin. MAIN OUTCOME MEASURES: Main outcomes were recurrence and continence after fistulotomy and immediate sphincteroplasty, according to fistula tract height and preoperative continence status. RESULTS: A total of 107 patients were included; 68.2% were men, with a mean age of 48 years and mean fistula duration of 12.8 months. The range and median follow-up period were 84 to 204 and 96 months. Thirty-seven fistulas were not primary. The overall healing rate was 84.1%. Primary fistulas healed by the end of follow-up in 58 (82.9%) of 70 patients; recurrent fistulas healed in 32 (86.5%) of 37; high tracts healed in 31 (83.8%) of 37, and nonhigh fistulas healed in 59 (84.3%) of 70. Male sex (OR = 0.66 (95% CI, 0.20-2.13); p > 0.05) and recurrent fistulas (OR = 0.43 (95% CI, 0.11-1.68); p > 0.05) could have a protective effect against postoperative fecal incontinence; however, more studies with larger sample sizes are necessary to confirm this result, whereas high fistulas showed a 4-fold increased risk of incontinence (range, 1.22-13.06; p < 0.01). One in 5 high-tracts patients experienced continence deterioration. LIMITATIONS: This was a prospective study, and randomized clinical trials with more patients and longer follow-up are needed to compare fistulotomy and immediate sphincteroplasty with other sphincter-preserving techniques. CONCLUSIONS: Fistulotomy and immediate sphincteroplasty are good options for treating complex anal fistulas, especially for recurrent fistulas, men, and patients with nonhigh tracts, with acceptable recurrence and incontinence rates. See Video Abstract at http://links.lww.com/DCR/B498. EVALUACIN A LARGO PLAZO DE LA FISTULOTOMA Y LA ESFINTEROPLASTIA INMEDIATA COMO TRATAMIENTO PARA LA FSTULA ANAL COMPLEJA: ANTECEDENTES:La fistulotomía y la esfinteroplastia inmediata es una técnica que puede curar las fístulas y disminuir la incontinencia fecal de manera más efectiva que la fistulotomía sola, en pacientes seleccionados.OBJETIVO:Nuestro objetivo fue realizar una evaluación a largo plazo de la incontinencia fecal después de la fistulotomía y la esfinteroplastia inmediata en pacientes con fístula anal compleja.DISEÑO:Este estudio prospectivo incluyó pacientes sometidos a fistulotomía y esfinteroplastia inmediata por fístula anal compleja, desde enero de 2000 hasta diciembre de 2010.ENTORNO CLINICO:El estudio fue realizado por dos cirujanos colorrectales de la Unidad de Coloproctología del Hospital General de Elche.PACIENTES:Se incluyeron pacientes ≥ 18 años con fístulas anales complejas de origen criptoglandular.PRINCIPALES MEDIDAS DE VALORACION:Los principales resultados fueron la recurrencia y la continencia después de la fistulotomía y la esfinteroplastia inmediata, de acuerdo con la altura del trayecto de la fístula y el estado de continencia preoperatoria.RESULTADOS:Se incluyeron un total de 107 pacientes; El 68,2% eran varones, con una edad media de 48 años y una duración media de la fístula de 12,8 meses. El rango y la mediana del período de seguimiento fue de 84-204 y 96 meses, respectivamente. Treinta y siete fístulas no fueron primarias. La tasa de curación general fue del 84,1%. Las fístulas primarias cicatrizaron al final del seguimiento en 58/70 (82,9%) pacientes; las fístulas recurrentes cicatrizaron en 32/37 (86,5%); los tractos altos cicatrizaron en 31/37 (83,8%) y las fístulas no altas cicatrizaron en 59/70 (84,3%). El sexo masculino (razón de posibilidades: 0,66 [0,20-2,13], p > 0,05) y las fístulas recurrentes (razón de posibilidades: 0,43 [0,11-1,68], p > 0,05) podrían tener un efecto protector contra la incontinencia fecal postoperatoria, sin embargo, más estudios con una muestra más grande son necesarios para confirmar este resultado. Fistulas altas mostraron un riesgo cuatro veces mayor de incontinencia ([1.22-13.06], p < 0.01). Uno de cada cinco pacientes con tractos altos experimentó un deterioro de la continencia.LIMITACIONES:Este fue un estudio prospectivo y se necesitan ensayos clínicos aleatorios con más pacientes y un seguimiento más prolongado para comparar la fistulotomía y la esfinteroplastia inmediata con otras técnicas de preservación del esfínter.CONCLUSIÓN:La fistulotomía y la esfinteroplastia inmediata son buenas opciones para el tratamiento de fístulas anales complejas, especialmente para fístulas recurrentes, varones y pacientes con tractos no altos, con tasas aceptables de recurrencia e incontinencia. Consulte Video Resumen en http://links.lww.com/DCR/B498.

A case report of severe dermatitis, allergies, and metabolic wasting (SAM syndrome).

The presence of eczema and elevated IgE in pediatric patients does not always indicate atopic dermatitis. Rare genodermatoses may share this clinical presentation and should be considered in the differential diagnosis for patients with congenital immunodeficiency and severe refractory dermatitis. We describe a case of severe dermatitis, allergies, and metabolic wasting syndrome, due to a novel mutation in DSG1 gene, an additional example of this uncommon genetic disorder of desmosome function.

The Effect of Vitamin C on Clinical Outcome in Critically Ill Patients: A Systematic Review With Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The effects of vitamin C administration on clinical outcome in critically ill patients remain controversial. DATA SOURCES: Online databases were searched up to October 1, 2018. STUDY SELECTION: We included randomized controlled trials on the use of vitamin C (any regimen) in adult critically ill patients versus placebo or no therapy. DATA EXTRACTION: Risk ratio for dichotomous outcome and standardized mean difference for continuous outcome with 95% CI were calculated using random-effects model meta-analysis. DATA SYNTHESIS: Forty-four randomized studies, 16 performed in ICU setting (2,857 patients) and 28 in cardiac surgery (3,598 patients), published between 1995 and 2018, were included in the analysis. In ICU patients, vitamin C administration was not associated with a difference in mortality (risk ratio, 0.90; 95% CI, 0.74-1.10; p = 0.31), acute kidney injury, ICU or hospital length of stay compared with control. In cardiac surgery, vitamin C was associated to a reduction in postoperative atrial fibrillation (risk ratio, 0.64; 95% CI, 0.52-0.78; p < 0.0001), ICU stay (standardized mean difference, -0.28 d; 95% CI, -0.43 to -0.13 d; p = 0.0003), and hospital stay (standardized mean difference, -0.30 d; 95% CI, -0.49 to -0.10 d; p = 0.002). Furthermore, no differences in postoperative mortality, acute kidney injury, stroke, and ventricular arrhythmia were found. CONCLUSIONS: In a mixed population of ICU patients, vitamin C administration is associated with no significant effect on survival, length of ICU or hospital stay. In cardiac surgery, beneficial effects on postoperative atrial fibrillation, ICU or hospital length of stay remain unclear. However, the quality and quantity of evidence is still insufficient to draw firm conclusions, not supporting neither discouraging the systematic administration of vitamin C in these populations. Vitamin C remains an attractive intervention for future investigations aimed to improve clinical outcome.

Blood Purification and Mortality in Sepsis and Septic Shock: A Systematic Review and Meta-analysis of Randomized Trials.

BACKGROUND: Sepsis and septic shock are severe inflammatory conditions related to high morbidity and mortality. We performed a systematic review with meta-analysis of randomized trials to assess whether extracorporeal blood purification reduces mortality in this setting. METHODS: Electronic databases were searched for pertinent studies up to January 2019. We included randomized controlled trials on the use of hemoperfusion, hemofiltration without a renal replacement purpose, and plasmapheresis as a blood purification technique in comparison to conventional therapy in adult patients with sepsis and septic shock. The primary outcome was mortality at the longest follow-up available. We calculated relative risks and 95% CIs. The grading of recommendations assessment, development and evaluation methodology for the certainty of evidence was used. RESULTS: Thirty-seven trials with 2,499 patients were included in the meta-analysis. Hemoperfusion was associated with lower mortality compared to conventional therapy (relative risk = 0.88 [95% CI, 0.78 to 0.98], P = 0.02, very low certainty evidence). Low risk of bias trials on polymyxin B immobilized filter hemoperfusion showed no mortality difference versus control (relative risk = 1.14 [95% CI, 0.96 to 1.36], P = 0.12, moderate certainty evidence), while recent trials found an increased mortality (relative risk = 1.22 [95% CI, 1.03 to 1.45], P = 0.02, low certainty evidence); trials performed in the United States and Europe had no significant difference in mortality (relative risk = 1.13 [95% CI, 0.96 to 1.34], P = 0.15), while trials performed in Asia had a positive treatment effect (relative risk = 0.57 [95% CI, 0.47 to 0.69], P < 0.001). Hemofiltration (relative risk = 0.79 [95% CI, 0.63 to 1.00], P = 0.05, very low certainty evidence) and plasmapheresis (relative risk = 0.63 [95% CI, 0.42 to 0.96], P = 0.03, very low certainty evidence) were associated with a lower mortality. CONCLUSIONS: Very low-quality randomized evidence demonstrates that the use of hemoperfusion, hemofiltration, or plasmapheresis may reduce mortality in sepsis or septic shock. Existing evidence of moderate quality and certainty does not provide any support for a difference in mortality using polymyxin B hemoperfusion. Further high-quality randomized trials are needed before systematic implementation of these therapies in clinical practice.

Nutrition in Adult Cardiac Surgery: Preoperative Evaluation, Management in the Postoperative Period, and Clinical Implications for Outcomes.

The perioperative nutritional status of patients undergoing cardiac surgery influences outcomes; therefore nutritional support is essential for these patients. Owing to the lack of solid evidence, no protocols have been established for the nutritional management of this specific population, and most of the recommendations are based on other critically ill populations. In this review of the main studies performed in this population, the importance of preoperative evaluation of nutritional status, the management of nutritional support immediately after cardiac surgery, the influence of nutrition on outcomes, and the importance of nutrition after hospital discharge are discussed. In addition, the possible influence of glycemic control and pharmaconutrition in the outcomes of these patients are described briefly.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality.

OBJECTIVE: Reducing mortality is a key target in critical care and perioperative medicine. The authors aimed to identify all nonsurgical interventions (drugs, techniques, strategies) shown by randomized trials to increase mortality in these clinical settings. DESIGN: A systematic review of the literature followed by a consensus-based voting process. SETTING: A web-based international consensus conference. PARTICIPANTS: Two hundred fifty-one physicians from 46 countries. INTERVENTIONS: The authors performed a systematic literature search and identified all randomized controlled trials (RCTs) showing a significant increase in unadjusted landmark mortality among surgical or critically ill patients. The authors reviewed such studies during a meeting by a core group of experts. Studies selected after such review advanced to web-based voting by clinicians in relation to agreement, clinical practice, and willingness to include each intervention in international guidelines. MEASUREMENTS AND MAIN RESULTS: The authors selected 12 RCTs dealing with 12 interventions increasing mortality: diaspirin-crosslinked hemoglobin (92% of agreement among web voters), overfeeding, nitric oxide synthase inhibitor in septic shock, human growth hormone, thyroxin in acute kidney injury, intravenous salbutamol in acute respiratory distress syndrome, plasma-derived protein C concentrate, aprotinin in high-risk cardiac surgery, cysteine prodrug, hypothermia in meningitis, methylprednisolone in traumatic brain injury, and albumin in traumatic brain injury (72% of agreement). Overall, a high consistency (ranging from 80% to 90%) between agreement and clinical practice was observed. CONCLUSION: The authors identified 12 clinical interventions showing increased mortality supported by randomized controlled trials with nonconflicting evidence, and wide agreement upon clinicians on a global scale.

A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Reducing Mortality.

The authors aimed to identify interventions documented by randomized controlled trials (RCTs) that reduce mortality in adult critically ill and perioperative patients, followed by a survey of clinicians' opinions and routine practices to understand the clinicians' response to such evidence. The authors performed a comprehensive literature review to identify all topics reported to reduce mortality in perioperative and critical care settings according to at least 2 RCTs or to a multicenter RCT or to a single-center RCT plus guidelines. The authors generated position statements that were voted on online by physicians worldwide for agreement, use, and willingness to include in international guidelines. From 262 RCT manuscripts reporting mortality differences in the perioperative and critically ill settings, the authors selected 27 drugs, techniques, and strategies (66 RCTs, most frequently published by the New England Journal of Medicine [13 papers], Lancet [7], and Journal of the American Medical Association [5]) with an agreement ≥67% from over 250 physicians (46 countries). Noninvasive ventilation was the intervention supported by the largest number of RCTs (n = 13). The concordance between agreement and use (a positive answer both to "do you agree" and "do you use") showed differences between Western and other countries and between anesthesiologists and intensive care unit physicians. The authors identified 27 clinical interventions with randomized evidence of survival benefit and strong clinician support in support of their potential life-saving properties in perioperative and critically ill patients with noninvasive ventilation having the highest level of support. However, clinician views appear affected by specialty and geographical location.

Abnormal bone turnover in individuals with low serum alkaline phosphatase.

The clinical spectrum of hypophosphatasia (HPP) is broad and variable within families. Along severe infantile forms, adult forms with mild manifestations may be incidentally discovered by the presence of low alkaline phosphatase (ALP) activity in serum. However, it is still unclear whether individuals with persistently low levels of ALP, in the absence of overt manifestations of HPP, have subclinical abnormalities of bone remodeling or bone mass. The aim of this study was to obtain a better understanding of the skeletal phenotype of adults with low ALP by analyzing bone mineral density (BMD), bone microarchitecture (trabecular bone score, TBS), and bone turnover markers (P1NP and ß-crosslaps). We studied 42 individuals with persistently low serum ALP. They showed lower levels of P1NP (31.4 ± 13.7 versus 48.9 ± 24.4 ng/ml; p = 0.0002) and ß-crosslaps (0.21 ± 0.17 versus 0.34 ± 0.22 ng/ml, p = 0.0015) than individuals in the control group. There were no significant differences in BMD, bone mineral content, or TBS. These data suggest that individuals with hypophosphatasemia have an overall reduction of bone turnover, even in the absence of overt manifestations of HPP or low BMD. We evaluated bone mineral density (BMD), bone microarchitecture, and bone turnover markers in patients with low serum levels of alkaline phosphatase. Our results show that these patients have low bone remodeling even in the absence of BMD abnormalities, thus supporting the recommendation of avoiding antiresorptives such as bisphosphonates in these subjects.

A PCR-free technology to detect and quantify microRNAs directly from human plasma.

A novel sensitive, specific and rapid method for the detection and quantification of microRNAs without requiring extraction from their biological sources is now available using a novel chemical based, PCR-free technology for nucleic acid testing. In this study, we both demonstrate how this method can be used to profile miR-451a, an important miRNA in erythropoiesis, and compare with the gold standard RT-qPCR.

Epigenetics of Skeletal Diseases.

PURPOSE OF REVIEW: Epigenetic mechanisms modify gene activity in a stable manner without altering DNA sequence. They participate in the adaptation to the environment, as well as in the pathogenesis of common complex disorders. We provide an overview of the role of epigenetic mechanisms in bone biology and pathology. RECENT FINDINGS: Extensive evidence supports the involvement of epigenetic mechanisms (DNA methylation, post-translational modifications of histone tails, and non-coding RNAs) in the differentiation of bone cells and mechanotransduction. A variety of epigenetic abnormalities have been described in patients with osteoporosis, osteoarthritis, and skeletal cancers, but their actual pathogenetic roles are still unclear. A few drugs targeting epigenetic marks have been approved for neoplastic disorders, and many more are being actively investigated. Advances in the field of epigenetics underscore the complex interactions between genetic and environmental factors as determinants of osteoporosis and other common disorders. Likewise, they help to explain the mechanisms by which prenatal and post-natal external factors, from nutrition to psychological stress, impact our body and influence the risk of later disease.

Surgical site infection in critically ill patients with secondary and tertiary peritonitis: epidemiology, microbiology and influence in outcomes.

BACKGROUND: Surgical site infection (SSI) remains a significant problem in the postoperative period that can negatively affect clinical outcomes. Microbiology findings are typically similar to other nosocomial infections, with differences dependent on microbiology selection due to antibiotic pressure or the resident flora. However, this is poorly understood in the critical care setting. We therefore aimed to assess the incidence, epidemiology and microbiology of SSI and its association with outcomes in patients with severe peritonitis in the intensive care unit (ICU). METHODS: We prospectively studied 305 consecutive patients admitted to our surgical ICU from 2010 to 2014 with a diagnosis of secondary or tertiary peritonitis. We collected the following data: SSI diagnosis, demographics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II score, type of surgery, microbiology, antibiotic treatment and outcomes. Microbiological sampling was done by means of swabs. RESULTS: We identified 269 episodes of SSI in 162 patients (53.1%) aged 64.4 ± 14.3 years, of which 200 episodes occurred in men (64.6%). The mean APACHE II and SAPS II scores were 19.7 ± 7.8 and 36.5 ± 16.1 respectively. The mean ICU and hospital stays were 19.8 ± 24.8 and 21.7 ± 30 days respectively. Pseudomonas spp. (n = 52, 19.3%), Escherichia coli (n = 55, 20.4%) and Candida spp. (n = 46, 17.1%) were the most frequently isolated microorganisms, but gram-positive cocci (n = 80, 29.7%) were also frequent. Microorganisms isolated from SSIs were associated with a higher incidence of antibiotic resistance (64.9%) in ICU patients, but not with higher in-hospital mortality. However, patients who suffered from SSI had longer ICU admissions (odds ratio = 1.024, 95% confidence interval 1.010-1.039, P = 0.001). CONCLUSIONS: The incidence of SSI in secondary or tertiary peritonitis requiring ICU admission is very high. Physicians may consider antibiotic-resistant pathogens, gram-positive cocci and fungi when choosing empiric antibiotic treatment for SSI, although more studies are needed to confirm our results due to the inherent limitations of the microbiological sampling with swabs performed in our research. The presence of SSI may be associated with prolonged ICU stays, but without any influence on overall mortality.