Diagnosis and management of acquired aplastic anemia in childhood. Guidelines from the Marrow Failure Study Group of the Pediatric Haemato-Oncology Italian Association (AIEOP).

Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.

Main biomarkers associated with age-related plasma zinc decrease and copper/zinc ratio in healthy elderly from ZincAge study.

PURPOSE: Zinc (Zn) plays an essential role in many biological processes including immune response. Impaired Zn status promotes immune dysfunction, and it has been associated with enhanced chronic inflammation during aging. It has been suggested that the measurement of circulating Zn by itself could not reflect the real Zn status of an individual. It is therefore necessary to identify other determinants associated with plasma Zn to better understanding how physiopathological conditions during aging may affect the concentration of this metal. METHODS: We have investigated the association between Zn levels and some biomarkers in 1090 healthy elderly from five European countries to increase the accuracy in the assessment of the Zn status. Stepwise multivariate linear regression models were used to analyze the influence of factors such as age, dietary intake, inflammatory mediators, laboratory parameters and polymorphisms previously associated with Zn homeostasis. RESULTS: Plasma Zn decrement was most strongly predicted by age, while positive correlations were found with albumin, RANTES and Zn intake after adjustment for multiple confounders. HSP70 +1267 AA genotype was an independent factor associated with Zn plasma concentrations. Cu/Zn ratio was positively associated with markers of systemic inflammation and age and negatively associated with albumin serum levels. CONCLUSIONS: Our findings show the most important independent determinants of plasma Zn concentration and Cu/Zn ratio variability in elderly population and suggest that the decline with age of Zn circulating levels is more dependent on physiopathological changes occurring with aging rather than to its nutritional intake.

Cost-effectiveness analysis of the temporary percutaneous ileostomy for faecal diversion after colorectal resection in elderly.

BACKGROUND: Conventional loop ileostomy (CLI) is a suitable procedure for transitory faecal diversion after colorectal anastomosis, but it causes relevant morbidities (dehydration, discomfort, peristomal infections) and requires a second operation to be closed. We already described an alternative technique of temporary percutaneous ileostomy (TPI), which can be removed without surgery. AIMS: We analyse the outcomes and the costs of the TPI in protecting low colorectal anastomosis in elderly, compared to the CLI. METHODS: Data of patients underwent elective anterior rectal resection for rectal cancer with extra-peritoneal colorectal anastomosis protected by ileostomy from January 2011 to December 2015 were reviewed. Sixty-one out of 132 patients were older than 70; 35 underwent faecal diversion by TPI and 26 by CLI. RESULTS: The two groups resulted homogenous about age, sex, operative time, short-term post-operative complications. None of the patients reported anastomotic leakage. The hospital stay and the cost for the first surgical procedure did not show statistically significant differences between TPI and CLI. When comparing the overall hospital stay and costs the differences are statistically significant: the TPI showed a shorter hospital stay (12.4 vs 19.3 days, -35.7%) and a lower cost of hospitalization (7954.0 vs 14,372.1€, -44.7%), compared to CLI. DISCUSSION: The limited duration of the faecal diversion and the uselessness of a second surgical procedure to remove the TPI are the most important advantages of TPI, especially in elderly. CONCLUSION: The TPI not only improved the post-operative outcome of the patients, but also allowed a remarkable saving for the National Health System.

Hyaluronan scaffold supports osteogenic differentiation of bone marrow concentrate cells.

Osteochondral lesions are considered a challenge for orthopedic surgeons. Currently, the treatments available are often unsatisfactory and unable to stimulate tissue regeneration. Tissue engineering offers a new therapeutic strategy, taking into account the role exerted by cells, biomaterial and growth factors in restoring tissue damage. In this light, Mesenchymal Stem Cells (MSCs) have been indicated as a fascinating tool for regenerative medicine thanks to their ability to differentiate into bone, cartilage and adipose tissue. However, in vitro-cultivation of MSCs could be associated with some risks such as de-differentiation/reprogramming, infection and contaminations of the cells. To overcome these shortcomings, a new approach is represented by the use of Bone Marrow Concentrate (BMC), that could allow the delivery of cells surrounded by their microenvironment in injured tissue. For this purpose, cells require a tridimensional scaffold that can support their adhesion, proliferation and differentiation. This study is focused on the potentiality of BMC seeded onto a hyaluronan-based scaffold (Hyaff-11) to differentiate into osteogenic lineage. This process depends on the specific interaction between cells derived from bone marrow (surrounded by their niche) and scaffold, that create an environment able to support the regeneration of damaged tissue. The data obtained from the present study demonstrate that BMC grown onto Hyaff-11 are able to differentiate toward osteogenic sense, producing specific osteogenic genes and matrix proteins.

Association among 1267 A/G HSP70-2, -308 G/A TNF-α polymorphisms and pro-inflammatory plasma mediators in old ZincAge population.

Proinflammatory cytokines and heat shock proteins play relevant roles in the pathogenesis of inflammatory diseases. We investigated whether Hsp70 1267 A/G and TNF-α -308 G/A polymorphisms are associated with proinflammatory mediators, zinc status and laboratory parameters in 1,078 healthy elderly from ZincAge study. Hsp70 1267 A/G genotype and allele distribution were similar among various European countries, while a TNF-α genetic heterogeneity was observed between the Northern and the Southern European populations, with a major frequency of the -308 A variant in France, Germany and Poland. We used linear regression models to test additive, dominant or recessive associations of each SNP with proinflammatory mediators, laboratory parameters, metallothioneins and zinc status. Hsp70 1267 A/G SNP, but not TNF-α -308 G/A SNP, influences TNF-α and IL-6 plasma levels under additive, dominant and recessive models (for TNF-α only). An association between Hsp70 1267 A/G SNP and zinc plasma levels was observed in the dominant model. In particular, G allele carriers showed increased circulating pro-inflammatory cytokines and zinc. Moreover, both these SNPs affect creatinine levels suggesting a possible influence on renal function. In conclusion, Hsp70 1267 A/G SNP is associated with pro-inflammatory cytokine production in healthy elderly and might represent a possible determinant of individual susceptibility to inflammatory diseases.

To drain or not to drain extraperitoneal colorectal anastomosis? A systematic review and meta-analysis.

AIM: Anastomotic leakage is the one of the most serious complications in rectal cancer surgery and is associated with high mortality, morbidity and an increased incidence of local recurrence. Although many studies have compared drained and undrained colorectal anastomoses, to date the role of pelvic drainage in extraperitoneal colorectal anastomosis remains undefined. METHOD: We carried out a systematic review of the literature, performing an unrestricted search in MEDLINE and Embase up to 30 October 2012. Reference lists of retrieved articles and review articles were manually searched for other relevant studies. We performed a meta-analysis of the data currently available on the incidence of extraperitoneal anastomotic leakage, according to the presence or absence of pelvic drainage. RESULTS: Overall, eight studies - three randomized clinical trials (RCTs) and five non-RCTs, comprising a total of 2277 patients - were included in the meta-analysis. Pelvic drainage was demonstrated to reduce both the leak rate and the rate of reintervention in patients who underwent anterior rectal resection with extraperitoneal colorectal anastomosis (OR = 0.51, 95% CI: 0.36-0.73; and OR = 0.29, 95% CI: 0.18-0.46, respectively) compared with patients without drainage. Overall mortality and infection rates were also evaluated, but a nonsignificant correlation was found with the presence of drainage. CONCLUSION: The meta-analysis shows that the presence of a pelvic drain reduces the incidence of extraperitoneal colorectal anastomotic leakage and the rate of reintervention after anterior rectal resection.

High hydrostatic pressure activity on the disinfection of clams artificially contaminated with feline calicivirus.

BACKGROUND: The contamination of shellfish with gastroenteric viruses may cause outbreaks because they are often eaten raw or under-cooked. High-hydrostatic pressure treatments have already proven to be effective in reducing high viral load in shellfish samples. The objectives are the assessment of the viral load reduction of contaminated clams using HHP treatments at different pressures and times and the study of the changes caused by these treatments in some food physical parameters. METHODS: Clams were contaminated with a solution containing Feline Calicivirus; they were closed in envelopes and treated with 300, 400, 500, 600 MPa for 1, 3, 5, 7 min for every pressure value. After the treatment the residual viral titre was calculated. The texture parameters were obtained after treating clams samples at the same pressure values but only for 3 and 7 min and analysing them with a TPA test. RESULTS: HHP treatments of 500 and 600 MPa were sufficient to cause a total inactivation at every timelength considered while with 300 and 400 MPa after 1 min, concentrations of 1.13 and 0.55 respectively were found. In general hardness and gumminess tend to increase after the treatment whereas springiness and cohesiveness decrease a bit. CONCLUSIONS: HHP treatments showed good sterilization ability against FCV but it's necessary to consider that FCV has a lower resistance to disinfection than Human norovirus. Texture changes are in line with what is reported in literature.

Rectal washout and local recurrence in rectal resection for cancer: a meta-analysis.

AIM: The effectiveness of rectal washout was compared with no washout for the prevention of local recurrence after anterior rectal resection for rectal cancer. METHOD: The following electronic databases were searched: PubMed, OVID Medline, Cochrane Database of Systematic Reviews, EBM Reviews, CINAHL and EMBASE. RESULTS: Five nonrandomized studies including a total of 5012 patients were identified. Meta-analysis suggested that rectal washout significantly reduced the local recurrence rate (P < 0.0001; OR 0.57; 95% CI 0.43-0.74). It was also significantly lower after washout in patients having radical resection only (P = 0.0004; OR 0.54; 95% CI 0.39-0.76), patients treated by a curative resection (P < 0.0001; OR 0.55; 95% CI 0.42-0.72) and those undergoing preoperative radiotherapy (P = 0.04; OR 0.62; 95% CI 0.39-0.98). CONCLUSION: Taking into account the limitations of the design of the included studies the meta-analysis showed that rectal washout is associated with reduced local recurrence and therefore should be routine during anterior resection for rectal cancer.

Is laparoscopic right colectomy more effective than open resection? A meta-analysis of randomized and nonrandomized studies.

AIM: The aim of this systematic review was to compare laparoscopic and/or laparoscopic-assisted right colectomy (LRC) with open right colectomy (ORC). Many randomized clinical trial have shown that laparoscopic colectomy benefits patients with improved short-term outcomes and comparable overall survival in respect to the open approach. These results, however, could not be applied to right colectomy owing to its wide range of resection and more complicated vascular regional anatomy. METHOD: We performed a meta-analysis of the literature in order to compare LRC vs ORC by examining 21 end-points including operative and recovery outcomes, early postoperative mortality and morbidity, and oncological parameters. A subgroup analysis of patients undergoing right colectomy for cancer was carried out. The meta-analysis was conducted following all aspects of the Cochrane Handbook for systematic reviews and Preferred Reporting Items for Systematic Reviews and Metanalysis (PRISMA) statement. The search strategies were developed using the following electronic databases: PubMed, EMBASE, OVID, Medline, Cochrane Database of Systematic Reviews, EBM reviews and CINAHL until March 2011. We included randomized and non randomized studies that compared the LRC vs ORC for benign disease and malignant neoplasm irrespective of publication status. Only studies in English, French, German, Spanish and Italian languages were considered for inclusion. Emergency right colectomies were excluded. To perform the statistical analysis we used the odds ratio (OR) for categorical variables and the weighted mean difference (WMD) for continuous variables. An intention-to-treat analysis was performed. RESULTS: Seventeen studies, 15 nonrandomized clinical trials and two randomized clinical trials, involving a total of 1489 patients, were identified. The mean operative time was longer in the group of patients undergoing LRC [weighted mean difference (WMD) = 37.94, 95% CI: 25.01 to 50.88; P < 0.00001]. Intra-operative blood loss (WMD = -96.61; 95% CI: -150.68 to -42.54; P = 0.0005), length of hospital stay (WMD = -2.29; 95% CI: -3.96 to -0.63; P = 0.007) and short-term postoperative morbidity (OR = 0.64; 95% CI: 0.49 to 0.83; P = 0.0009) were significantly in favour of LRC. CONCLUSION: Laparoscopic-assisted right colectomy results in less blood loss, a shorter length of hospital stay and lower postoperative short-term morbidity compared with ORC.

Oxidative imbalance in different neurodegenerative diseases with memory impairment.

BACKGROUND: Byproducts of oxidative metabolic reactions could play a role in the pathogenesis of several neurodegenerative diseases (ND) including Alzheimer's disease (AD). We designed a study aimed at investigating a large set of oxidative and antioxidant markers in a sample of patients affected by different forms of dementia or memory impairment. METHODS: Serum levels of coenzyme Q(10), malondialdehyde (MDA), the total, oxidized and reduced forms of glutathione (GStot, GSSG and GSH, respectively), reactive oxygen species, anti-oxidized low-density lipoprotein antibodies and antioxidant power (PAO) were investigated in patients affected by AD, mild cognitive impairment, dementia with Lewy bodies and Parkinson's disease with dementia. The patient sample (n = 66) was compared with healthy subjects (HC; n = 62), and a comparison across pathological subgroups was also performed. A multivariate logistic regression model was implemented in order to calculate an algorithm model for predicting the risk of developing a neurodegenerative disorder. RESULTS: The comparison between the memory deficit (MD) group and HC showed a significant difference for MDA (MD: 6.3 ± 2.8 µg/l; HC: 9.1 ± 4.9 µg/l; p = 1.7 × 10(-6)), GStot (MD: 260.4 ± 62.6 mg/l; HC: 306.5 ± 60.7 mg/l; p = 2.2 × 10(-5)), GSH (MD: 208.9 ± 68.4 mg/l; HC: 295.3 ± 101.3 mg/l; p = 2.2 × 10(-7)) and PAO (MD: 1,066.5 ± 247.7 µmol; HC: 954.9 ± 200.4 µmol; p = 0.8 × 10(-3)). By contrast, no differences in the levels of the studied markers were detected across the different forms of ND. An older age, higher levels of PAO, lower levels of GSH and MDA and the use of cardiovascular or antidepressant drugs were the most important factors associated with the carrier ship of neurodegenerative disorder. CONCLUSION: To our knowledge, this is the first study reporting similar oxidative imbalance in different forms of memory impairment, regardless of the specific etiology. Low GSH levels could be considered as a favorable factor in ND; at the same time it could be suggested that higher levels of PAO represent a counteracting mechanism against an increased oxidative stress. The association between vascular risk factors, depressive status and cognitive impairment is in line with findings in the literature.

Preliminary report of a new technique for temporary faecal diversion after extraperitoneal colorectal anastomosis.

AIM: Loop ileostomy is a suitable procedure for transitory faecal diversion after colorectal or coloanal anastomosis. We describe here an easy alternative technique for ileostomy construction that does not require reintervention for the closure. METHOD: In twenty patients undergoing anterior resection of the extraperitoneal rectum with colorectal and/or coloanal anastomosis, loop ileostomy was performed using a modified jejunotomy tube inflated with 10 ml of normal saline. The tube was deflated on the eighth post-operative day and removed on day 11 after a radiological contrast enema of the anastomosis. RESULTS: Radiological control carried out on day 11 evidenced a premature dislocation of the jejunostomy tube in 1 patient, thus the tube was correctly removed without any complications. In another patient a delayed closure of the ileo cutaneous fistula was recorded that required simple medication over 15 days in the out patient clinic. No signs of anastomotic leakage, either clinical or radiological were evidenced. CONCLUSION: We have described here a safe alternative technique for loop ileostomy with negligible complications related to construction as demonstrated in our results.

Malignant small-bowel neoplasms: spectrum of disease on MR imaging.

Malignant neoplasms of the small bowel are among the rarest types of cancer, accounting for only 2% of all gastrointestinal neoplasms. Owing both to the intrinsic difficulty of common radiographic and endoscopic methods in visualising the entire small bowel and the lack of typical physical findings, a delay in diagnosis is common. Recently, magnetic resonance (MR) imaging has become a widely accepted imaging modality in the study of suspected small-bowel neoplasms due to its ability to depict, without exposure to ionising radiation and with excellent soft-tissue contrast, intraluminal disorders in conjunction with mural, extraparietal and regional abnormalities. The aim of this pictorial review is to illustrate the MR appearance of malignant small-bowel neoplasms.

[Hospital admission of subjects with chronic obstructive bronchopulmonary disease (COPD) and air pollution in the city of Parma (Italy). A preliminary analysis]. / Funzionalità respiratoria in soggetti con Broncopneumopatia Cronica Ostruttiva (BPCO) e inquinamento atmosferico nella città di Parma Analisi preliminare.

A study was conducted in subjects admitted to hospital for chronic obstructive bronchopulmonary disease (COPD) in the city of Parma (Italy). The aim was to evaluate changes in patients' percent vital capacity (VC), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), as a function of changing degrees of atmospheric pollution as measured by PM10, NO2 and O3 concentrations in the outside air. Study results revealed an association between PM10 concentrations and hospital admissions for COPD. Statistically significant differences were found between PM10 concentrations measured three-four days before admission and in days not followed by admission to hospital. Regression analysis between PM10 concentrations at 24, 48, 72, and 96 hours before admission and respiratory function showed a significant association between FVC% and FEV1% and PM10 concentrations at 96 hours. The relative risk was calculated to be 1.016 (95% confidence intervals: 1.001-1.032), which corresponds to a 1.6% increased risk of admission to hospital for COPD for each unit increase in PM10 concentration in the outside air.

Effects of micronutrient supplementation on performance and epigenetic status in dairy cows.

The postpartum period is crucial in dairy cows and is marked by major physiological and metabolic changes that affect milk production, immune response and fertility. Nutrition remains the most important lever for limiting the negative energy balance and its consequences on general health status in highly selected dairy cows. In order to analyze the effect of a commercial micronutrient on intrinsic parameters, performances and the epigenome of dairy cows, 2 groups of 12 Holstein cows were used: 1 fed a standard diet (mainly composed of corn silage, soybean meal and non-mineral supplement) and the other 1 fed the same diet supplemented with the commercial micronutrient (µ-nutrient supplementation) for 4 weeks before calving and 8 weeks thereafter. Milk production and composition, BW, body condition score (BCS), DM intake (DMI) and health (calving score, metritis and mastitis) were recorded over the study period. Milk samples were collected on D15 and D60 post-calving for analyses of casein, Na+ and K+ contents and metalloprotease activity. Milk leukocytes and milk mammary epithelial cells (mMECs) were purified and counted. The viability of mMECs was assessed, together with their activity, through an analysis of gene expression. At the same time points, peripheral blood mononuclear cells (PBMCs) were purified and counted. Using genomic DNA extracted from PBMCs, mMECs and milk leukocytes, we assessed global DNA methylation (Me-CCGG) to evaluate the epigenetic imprinting associated with the µ-nutrient-supplemented diet. The µ-nutrient supplementation increased BCS and BW without modifying DMI or milk yield and composition. It also improved calving condition, reducing the time interval between calving and first service. Each easily collectable cell type displayed a specific pattern of Me-CCGG with only subtle changes associated with lactation stages in PBMCs. In conclusion, the response to the µ-nutrient supplementation improved the body condition without alteration of global epigenetic status in dairy cows.

Crystallographic preferred orientation (CPO) of gypsum measured by electron backscatter diffraction (EBSD).

An investigation by electron backscatter diffraction on gypsum shows that this technique can be used to study the microstructures and crystallographic preferred orientation of gypsum. Presented here are the methods, verification tests and data obtained from a naturally deformed sample of gypsum-rich rock. The electron backscatter diffraction data show the sample has a strong crystallographic preferred orientation.

The Weighted Burgers Vector: a new quantity for constraining dislocation densities and types using electron backscatter diffraction on 2D sections through crystalline materials.

The Weighted Burgers Vector (WBV) is defined here as the sum, over all types of dislocations, of [(density of intersections of dislocation lines with a map) x (Burgers vector)]. Here we show that it can be calculated, for any crystal system, solely from orientation gradients in a map view, unlike the full dislocation density tensor, which requires gradients in the third dimension. No assumption is made about gradients in the third dimension and they may be non-zero. The only assumption involved is that elastic strains are small so the lattice distortion is entirely due to dislocations. Orientation gradients can be estimated from gridded orientation measurements obtained by EBSD mapping, so the WBV can be calculated as a vector field on an EBSD map. The magnitude of the WBV gives a lower bound on the magnitude of the dislocation density tensor when that magnitude is defined in a coordinate invariant way. The direction of the WBV can constrain the types of Burgers vectors of geometrically necessary dislocations present in the microstructure, most clearly when it is broken down in terms of lattice vectors. The WBV has three advantages over other measures of local lattice distortion: it is a vector and hence carries more information than a scalar quantity, it has an explicit mathematical link to the individual Burgers vectors of dislocations and, since it is derived via tensor calculus, it is not dependent on the map coordinate system. If a sub-grain wall is included in the WBV calculation, the magnitude of the WBV becomes dependent on the step size but its direction still carries information on the Burgers vectors in the wall. The net Burgers vector content of dislocations intersecting an area of a map can be simply calculated by an integration round the edge of that area, a method which is fast and complements point-by-point WBV calculations.

Single-injection femoral and sciatic nerve blocks for pain control after total knee arthroplasty.

This study was designed to evaluate the addition of a single-injection sciatic nerve block to a femoral nerve block for analgesia after total knee arthroplasty. Fifty-seven patients undergoing primary total knee arthroplasty were randomized to receive femoral nerve blockade or a sham block. A subsequent 31 patients received both femoral and sciatic nerve blocks (FSNBs) before general anesthesia. Intravenous morphine use and visual analog pain scale scores were recorded at regular intervals. Femoral and sciatic nerve blocks were placed in less than five minutes, on average. Lower visual analog pain scale scores were noted in both femoral nerve blockade and FSNB groups compared to shams through 48 hours. Morphine use was significantly lower in the FSNB group. Femoral and sciatic nerve block can be placed quickly and consistently in the operating room with improved postoperative pain relief and reduced narcotic consumption.

Cumulative Incidence of Revision for a Balanced Knee System at a Mean 8-Year Follow-Up: A Retrospective Review of 500 Consecutive Total Knee Arthroplasties.

PURPOSE: The primary purpose of this study was to evaluate mid-term survival of a Balanced Knee System in the first 500 total knee arthroplasty (TKA) cases using a fully cemented, posterior stabilized TKA at a high-volume private practice. PATIENTS AND METHODS: In this IRB approved retrospective cohort study, data were extracted from a surgical registry at a high-volume orthopaedic practice for the first 500 total knee arthroplasty (TKA) cases performed using the Balanced Knee® System (BKS, Ortho Development®, Draper, Utah, USA). Procedures were performed between June 2000 and September 2003 by one of two orthopaedic surgeons. Follow-up was performed at 6 weeks, 6 months, 1 year, 5 years, and 10 years. 48 patients (9.6%) were considered lost to follow-up. A competing risk analysis was performed to evaluate the cumulative incidence of revision while accounting for the competing risk of death. In the model, failure was defined as revision of any BKS component. Those who failed prior to two years remained in the analysis. RESULTS: The mean age of the population was 69 years (range: 40-94) and 73% were female. The cumulative incidence of revision of any component was approximately 1% at a mean 8-year follow-up (range: 0.11-14.1 years) when accounting for the competing risk of death. When considering all those lost to follow-up as failures, the cumulative incidence of failure at 8 years was approximately 10%. CONCLUSION: Based on the results of the current study, a posterior stabilized primary TKA, implanted using a flexion and extension gap balancing technique, had excellent survivorship and outcomes at a mean 8-year follow-up.