Quantitative MRI evaluation of bone marrow in sickle cell disease: relationship with haemolysis and clinical severity.

AIM: To evaluate bone marrow fat fraction using the Dixon technique (FFDix) of magnetic resonance imaging (MRI) as a potential biomarker of haemolysis and clinical severity in the overall assessment and follow-up of sickle cell disease (SCD) patients. MATERIAL AND METHODS: The present study was a cross-sectional study in which healthy individuals and SCD patients (matched for age, sex, and weight) were subjected to MRI of the lumbar spine and pelvis to quantify FFDix in the bone marrow using the Dixon technique. SCD severity was analysed by clinical and laboratory data, and an online calculator. A high degree of haemolysis was defined using the cut-off values haemoglobin (Hb) ≤10 g/dl, lactate dehydrogenase (LDH) ≥325 U/l, reticulocytes ≥3% and total bilirubin (TB) ≥1.2 mg/dl. Pearson's correlation, receiver operating characteristic (ROC) curve and binary logistic regression analysis were performed. RESULTS: Forty-eight SCD patients (26 homozygous: HbSS and 22 compound heterozygous: HbSC) and 48 healthy individuals participated in the study. FFDix was lower in SCD patients than in the control group, showing even lower values in the HbSS subtype and patients with a higher degree of haemolysis. HbSC patients with a higher degree of haemolysis using hydroxyurea (medium dosage 9.8 mg/kg/day) had lower FFDix. ROC curves and odds ratios for detecting patients with a higher degree of haemolysis at the different FFDix measurement sites demonstrated excellent performance: iliac bones (cut-off ≤16.75%, AUC = 0.824, p<0.001), femoral heads (cut-off ≤46.7%, AUC = 0.775, p=0.001), lumbar vertebrae (cut-off ≤7.8%, AUC = 0.755, p=0.002). CONCLUSION: Decreased FFDix is indicative of higher degree of haemolysis and SCD severity with great potential as a non-invasive biomarker contributing to the overall assessment and follow-up of SCD patients.

Analysis of adrenaline autoinjectors acquisition in Portugal over 15 years.

Summary: Background. The adrenaline autoinjector (AAi) is universally recommended as the first-line treatment for anaphylactic reactions occurring outside the medical setting. The quantification of its acquisition may help estimate the prevalence of patients at risk of anaphylaxis with an indication for AAi. Objective. Evaluation of the global and regional frequency of AAi purchases in Mainland Portugal between 2003-2017 and calculate the inherent costs in 2017. Methods. AAi acquisition distribution analysis along this period. The population was divided in two age groups according to the adrenaline dosage. Results. A total of 10,993 AAi units of 0.15mg/0.3mL and 28,619 of 0.3mg/0.3mL were acquired in these 15 years, with an annual average of 733 and 1908 units, respectively. In cumulative values terms, Lisbon showed the highest number of AAI acquired and higher prevalence per region/100,000 inhabitants in both groups. In 2017, the annual cost for each age group was 64,202.71 € 187,447.70 € for patients and € 37,706.35 / 110,113.30 € for the National Health System. Conclusions. In the last 15 years, there was a progressive increase in AAi acquisition. We estimate a rate of anaphylaxis occurrence in Portugal according to AAi aquisition of 0.165%.

Defining hereditary alpha-tryptasemia as a risk/modifying factor for anaphylaxis: are we there yet?

Summary: Hereditary α-tryptasemia (HαT) is a common autosomal dominant genetic trait with variable penetrance associated with increased serum baseline tryptase (SBT) levels. Clinical manifestations may range from an absence of symptoms to overtly severe and recurrent anaphylaxis. Symptoms have been claimed to result from excessive activation of EGF-like module-containing mucin-like hormone receptor-like 2 (EMR2) and protease-activated receptor 2 (PAR-2) receptors by α/ß-tryptase heterotetramers. Herein, we aimed to review the evidence on whether HαT can be considered a hereditary risk factor or a modifying factor for anaphylaxis.Increased SBT levels have been linked to an increased risk of anaphylaxis. Likewise, recent studies have shown that HαT might be associated with a higher risk of developing anaphylaxis and more severe anaphylaxis. The same has also been shown for patients with clonal mast cell disorders, in whom the co-existence of HαT might lead to a greater propensity for severe, potentially life-threatening anaphylaxis. However, studies leading to such conclusions are generally limited in sample size, while other studies have shown opposing results. As such, further studies investigating the potential association of HαT with anaphylaxis caused by different triggers, and different severity grades, in both patients with clonal mast cell activation syndromes and the general population are still needed.

Clinical experience of a specialized urticaria outpatient clinic from a Portuguese UCARE.

Summary: Background. Chronic urticaria (CU) is a frequent disease, with a prevalence of at least 1%. It is characterized by pruritic wheals, angioedema or both for a period longer than 6 weeks. Objective. Identify the demographic, clinical, laboratory and therapeutic profile of patients treated in a Portuguese Urticaria Center of Reference and Excellence (UCARE) and compare it with international series. Methods. Retrospective analysis of database of patients observed in a specialized urticaria outpatient clinic, from January 2017 through September 2019, of a UCARE center in Portugal. Demographic and clinical features, laboratory findings and pharmacological treatment were obtained from the records. Descriptive analyses were performed for all variables. Chi square and fisher's exact tests were applied to analyze the independence of variables and the fit of distribution. P less than 0.05 was considered significant. Results. During this period, 477 patients were observed, of whom 429 (90%) were diagnosed with chronic urticaria. Mean age (years) at the onset of symptoms was 43.7 (standard deviation (SD) 17.6, range 6-88) and at diagnosis 46.7 (SD 17.8, range 6-88) resulting in an average diagnostic delay of 3 years (range 0-25). Median follow-up period since first attendance in the specialized outpatient clinic was 1.7 years (interquartile range (IQR) 0.79, range 0.1-2.75) . Concerning the whole group of CU patients, 347 (81%) had chronic spontaneous urticaria (CSU) - 79% female, 39 (9%) had isolated chronic inducible urticaria (CIndU) and 43 (10%) had CSU with CIndU. Autologous serum skin test (ASST) was done in 76 patients (positive in 24 (32%)) and basophil activation test (BAT) was done in 38 (positive in 13 (34%)). At the moment of study, 204 (48%) of CU patients were medicated with a second-generation H1-antihistamine (sgAH) daily (first-line therapy), 99 (23%) with sgAH up to four times the standard dose (second-line therapy) and 126 (29%) with omalizumab (third-line therapy). Additionally, 7 (2%) patients were completing a short course of systemic corticosteroids for management of disease exacerbation. Disease control was achieved in 316 of CSU patients (81%). Conclusions. Referral to a specialized urticaria outpatient clinic is important for a proper assessment of the disease and adequately symptom control.

Assessment of the main pathogens associated with clinical and subclinical endometritis in cows by culture and MALDI-TOF mass spectrometry identification.

Clinical endometritis (CE) and subclinical endometritis (SCE) are diseases that affect dairy cows during the puerperium, causing negative effects on the animals' milk production and fertility. The objective of this study was to assess the main bacteria related to cases of CE and SCE from uterine samples of dairy cows in Brazilian herds. Selective and differential media were used for isolation of aerobic and anaerobic bacteria and further MALDI-TOF mass spectrometry (MS) identification. A total of 279 lactating dairy cows with 28 to 33 d in milk from 6 commercial farms were evaluated. Initially, cows were classified in 3 groups: cytologic healthy cows (n = 161), cows with CE (n = 83), and cows with SCE (n = 35). Healthy animals presented 97 species, followed by the CE group with 53 identified species, and SCE cows presented only 21 bacterial species. We found a significantly higher isolation rate of Trueperella pyogenes in CE (26.5%) cows compared with healthy and SCE cows. Some anaerobic species were exclusively isolated from the CE group, even though they presented lower frequency. Interestingly, 18.1% of samples from CE cows and 40% of SCE cows were negative to bacterial isolation. Despite the use of culture-dependent methods instead of molecular methods, the present study enabled the identification of a complex community of 127 different species from 48 genera, composed of aerobic and anaerobic bacterial species among the 3 different animal groups. The method of sample collection, culture, and identification by MALDI-TOF MS were essential for the success of the analyses.

Subcutaneous immunotherapy with aeroallergens: safety profile assessment.

SUMMARY: Introduction. Severe systemic reactions (SR) to allergen subcutaneous immunotherapy (SCIT) are rare but local reactions (LR) are common. We aimed to characterize the type of reactions and safety profile. Methods. Retrospective analysis of medical record from patients under SCIT between 2013-2016. Results. Total of 7372 SCIT injections in 323 patients: 52% female; mean age 30 years (SD 13); mean treatment time 19 months (SD 13). There were 57 patients (17.6% of population, 70% female) with at least one adverse reaction, for 93 reactions described (1.3% injections). There were 79 LR (1.1% injections) in 46(14.2%) patients: 36 in build-up, 43 in maintenance. There were 14 SR (0.19% injections) in 12(3.7%) patients: 12 in build-up, 2 in maintenance. All SR were grade 1. The majority of reactions were caused by mite SCIT (69.9%). Conclusions. SCIT is safe and well tolerated, with no report of SR grade > 1.

Intervertebral disc decellularisation: progress and challenges.

Intervertebral disc (IVD) degeneration and the consequent low-back pain (LBP) affect over 80 % of people in western societies, constituting a tremendous socio-economic burden worldwide and largely impairing patients' life quality. Extracellular matrix (ECM)-based scaffolds, derived from decellularised tissues, are being increasingly explored in regenerative medicine for tissue repair. Decellularisation plays an essential role for host cells and antigen removal, while maintaining native microenvironmental signals, including ECM structure, composition and mechanical properties, which are essential for driving tissue regeneration. With the lack of clinical solutions for IVD repair/regeneration, implantation of decellularised IVD tissues has been explored to halt and/or revert the degenerative cascade and the associated LBP symptoms. Over the last few years, several researchers have focused on the optimisation of IVD decellularisation methods, combining physical, chemical and enzymatic treatments, in order to successfully develop a cell-free matrix. Recellularisation of IVD-based scaffolds with different cell types has been attempted and numerous methods have been explored to address proper IVD regeneration. Herein, the advances in IVD decellularisation methods, sterilisation procedures, repopulation and biocompatibility tests are reviewed. Additionally, the importance of the donor profile for therapeutic success is also addressed. Finally, the perspectives and major hurdles for clinical use of the decellularised ECM-based biomaterials for IVD are discussed. The studies reviewed support the notion that tissue-engineering-based strategies resorting to decellularised IVD may represent a major advancement in the treatment of disc degeneration and consequent LBP.

IL-1ß-pre-conditioned mesenchymal stem/stromal cells' secretome modulates the inflammatory response and aggrecan deposition in intervertebral disc.

Mesenchymal stem/stromal cells (MSCs) have been increasingly used in clinical trials for low-back pain (LBP) and intervertebral disc (IVD) degeneration with promising results. Their action mechanisms are not fully understood, but they reduce IVD pro-inflammatory markers in a pro-inflammatory/degenerative IVD microenvironment. In this study the therapeutic potential of the MSC secretome, as an alternative cell-free approach for treating degenerated IVDs, was examined. Human bone marrow-derived MSC secretome (MSCsec) was collected after 48 h of preconditioning in IL-1ß (10 ng/mL) and low oxygen (6 % O2), mimicking the degenerative IVD. IL-1ß-pre-conditioning of MSCs increased secretion of pro-inflammatory markers hIL-6, hIL-8, hMCP-1, etc. The therapeutic effect of MSCsec was tested in a pro-inflammatory/degenerative IVD ex vivo model. MSCsec down-regulated IVD gene expression of pro-inflammatory cytokines (bIL-6, bIL-8) and matrix degrading enzyme bMMP1, while bMMP3 and bTIMP2 were up-regulated, at 48 h. After 14 d, MSCsec-treated IVDs revealed increased aggrecan deposition, although no differences in other ECM components were observed. Protein analysis of the MSCsec-treated IVD supernatant revealed a significant increase of CXCL1, MCP-1, MIP-3α, IL-6, IL-8 and GRO α/ß/γ (related to TNF, NOD-like receptor and neutrophil chemotaxis signalling), and a decrease of IFN-γ, IL-10, IL-4, IL-5 and TNF-α (associated with T-cell receptor signalling). MSCsec-treated IVD supernatants did not promote angiogenesis and neurogenesis in vitro. Overall, MSCsec can be a safe therapeutic approach, presenting a strong immunomodulatory role in degenerated IVD while potentiating aggrecan deposition, which can open new perspectives on the use of MSCsec as a cell-based/ cell-free therapeutic approach to LBP.

Oral administration of Hsp65-producing Lactococcus lactis attenuates allergic asthma in a murine model.

AIMS: Allergic asthma is a chronic inflammatory lung disease characterized by a Th2-type immune response pattern. The development of nonspecific immunotherapy is one of the primary goals for the control of this disease. METHODS AND RESULTS: In this study, we evaluated the therapeutic effects of Lactococcus lactis-producing mycobacterial heat shock protein 65 (LLHsp65) in an ovalbumin (OVA)-induced allergic asthma model. OVA-challenged BALB/c mice were orally administrated with LLHsp65 for 10 consecutive days. The results demonstrate that LLhsp65 attenuates critical features of allergic inflammation, like airway hyperresponsiveness and mucus production. Likewise, the treatment decreases the pulmonary eosinophilia and the serum level of OVA-specific IgE. In addition to deviating immune responses towards Th1-cytokine profile, increase regulatory T cells, and cytokine levels, such as IL-6 and IL-10. CONCLUSIONS: Our results reveal that the mucosal immunotherapy of LLHsp65 significantly reduces the overall burden of airway allergic inflammation, suggesting a promising therapeutic strategy for allergic asthma treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This research reveals new perspectives on nonspecific immunotherapy based on the delivery of recombinant proteins by lactic acid bacteria to treat of allergic disorders.

Learning complex texture discrimination.

Higher-order spatial correlations contribute strongly to visual structure and salience, and are common in the natural environment. One method for studying this structure has been through the use of highly controlled texture patterns whose obvious structure is defined entirely by third- and higher-order correlations. Here we examine the effects that longer-term training has on discrimination of 17 such texture types. Training took place in 14 sessions over 42 days. Discrimination performance increased at different rates for different textures. The time required to complete a visit reduced by 25.4% (p=0.0004). Factor analysis was applied to data from the learning and experienced phases of the experiment. This indicated that the gain in speed was accompanied by an increase in the number of mechanisms contributing to discrimination. Learning was not affected by sleep quality but was affected by extreme tiredness (p<0.01). The improved discrimination and speed were retained for 2.5 months. Overall, the effects were consistent with perceptual learning. The observed learning is likely related to the adaptation of innate mechanisms that underlie our ability to identify nonredundant, visually salient structure in natural images. It may involve cortical V2 and appears to involve increased strength, speed, and breadth of connections within our internal representation of this complex perceptual space.

Molecular Profile of Sensitization to Dermatophagoides pteronyssinus Dust Mite in Portugal.

BACKGROUND AND OBJECTIVES: To analyze component-resolved diagnosis of sensitization to Dermatophagoides pteronyssinus (Der p) in patients with respiratory allergy and the association between diagnostic findings and clinical severity in different geographical areas. METHODS: The study population comprised 217 patients (mean age, 25.85 [12.7] years; 51.16% female) selected from 13 centers in Portugal (5 from the North, n=65). All had allergic rhinitis with or without asthma and positive skin prick test results to at least 1 dust mite. Specific IgE (sIgE) to Der p, Dermatophagoides farinae, Lepidoglyphus destructor, Der p 1, Der p 2, Der p 10, and Der p 23 was determined using ImmunoCAP. The Mann-Whitney test was applied for the following comparisons: rhinitis vs rhinitis and asthma; mild vs moderate-to-severe rhinitis; North vs South. RESULTS: The prevalence of sensitization was 98.2% for Der p, and 72.4%, 89.4%, 9.7%, and 77% for Der p 1, Der p 2, Der p 10, and Der p 23, respectively. The corresponding median sIgE levels were 8.56, 17.7, 0.01, and 3.95 kUA/L. sIgE to all allergens was higher in patients with moderate-to-severe rhinitis and rhinitis with asthma (nonsignficant). Concentrations of sIgE to Der p 2 were significantly higher in the South than in the North (P=.0496). CONCLUSION: The most common sensitization in Portugal was to Der p. The highest prevalence and median sIgE level were observed for Der p 2. All sIgE values for molecular components were higher in more symptomatic patients (nonsignificant). Concentrations of sIgE to Der p 2 were higher in the South, probably because of the warmer temperature and/or the larger sample size.

Risk factors for developmental defects of enamel in children from southeastern Brazil.

INTRODUCTION: Developmental Defects of Enamel (DDEs) comprise qualitative and/or quantitative changes to the enamel during amelogenesis. The aetiology of DDE remains inconclusive. AIM: To determine the association of pre, peri, and postnatal factors with the presence of DDE. DESIGN: Cross-sectional study with 353 children (8 to 11 years-old) in a Brazilian town. METHODS: One calibrated dentist assessed DDE using the Developmental Defects of Enamel Index and a questionnaire collected medical and sociodemographic data. MAIN OUTCOMES: Children with at least one type of DDE were categorized into the DDE group. Subtypes of DDE were also recorded. RESULTS: 63.1% of children had at least one type of DDE. Diffuse opacity was present in 36.7%, demarcated opacity in 14.8%, and hypoplasia in 5.83% of the children. In multivariate analysis, demarcated opacities and hypoplasia were associated with birth weight ⟨ 2500g (OR = 4.82; 95% CI 1.23-1.95). CONCLUSION: Low birth weight predicted DDE.

What do asthmatic patients think about telemedicine visits?

Summary: Introduction. Due to the Coronavirus disease 2019 (COVID-19) outbreak and the national emergency state, virtual visits were implemented as an alternative to in-person visits. With this study we aimed to establish asthma patients' general satisfaction with the quality of health care provided by virtual visits (phone or video calls). Materials and methods. A questionnaire (9 questions) was published on the Facebook page of the Portuguese Association of Asthmatics. It was available online for general self-reported asthmatic patients to answer during one month, starting on 11st May 2020. The survey only allowed one answer per registered user. Results. Fifty-five responses were obtained. Patients were satisfied with communication with providers (> 88%); nevertheless, one-half evaluated the virtual visit as inferior when compared to in-person visits. About one third attributed a classification of 6 or less (0-10 scale, 0 being the worst and 10 the best consultation possible), but still most of the patients would either recommend it or use this kind of medical visits in the future, even outside the actual pandemic context. Patients also referred some important limitations, as lack of physical examination and the fact that the medical visit was more impersonal. Only 27% had technical issues accessing virtual visits. Positive aspects were also named, such as virtual visits being practical and avoiding the need to move to the hospital. Discussion and conclusions. Our survey revealed that small changes could further increase patients' satisfaction, adherence and confidence in telemedicine. Although presenting some limitations, virtual visits seem to be generally well accepted by asthmatic patients and it might be a good alternative for in-person visits, at leastin such difficult times when social distancing is recommended.

Secondary sphincter repair for anal incontinence following obstetric sphincter injury: functional outcome and quality of life at 18 years of follow-up.

AIM: Secondary sphincter repair has been the conventional management of anal incontinence (AI) when a structural defect in the sphincter is recognized. However, disappointing long-term results have contributed to a tendency towards an increasing use of alternative treatment methods. This study aimed to assess the long-term functional outcomes following a secondary sphincter repair in women with AI after obstetric sphincter injury. METHOD: This is a questionnaire study of women who underwent a secondary sphincter repair in Denmark between January 1990 and December 2005. Patients were identified through the Danish National Patient Registry. Functional outcomes were assessed by a self-administered questionnaire in 2010 and 2018. Primary outcomes were Wexner and St. Mark's scores. Impact on quality of life was assessed using the Fecal Incontinence Quality of Life Scale. RESULTS: Functional outcome was assessed in 370 women in 2010 and 255 women in 2018. At 18.3 [interquartile range (IQR 15.0-22.0)] years of follow-up, the mean ± SD Wexner score was 8.8 ± 4.8 and the mean St. Mark's score was 11.7 ± 5.0. Flatus incontinence was the most frequent symptom, reported by 97%. Incontinence for liquid and solid stools was reported by 75% and 54%, respectively. There were no significant changes in incontinence frequencies over time. Women with a Wexner score of ≥ 9 had a significantly lower quality of life score in all domains than did women with a Wexner score of < 9 (P < 0.001). CONCLUSION: At long-term follow-up, few patients are fully continent following a secondary sphincter repair. However, it appears that the functional results remain stable at very long-term follow-up.

Role of Recombinant Parvalbumin Gad c 1 in the Diagnosis and Prognosis of Fish Allergy.

BACKGROUND AND OBJECTIVES: The prevalence of fish allergy has increased in recent years. The parvalbumin Gad c 1 is a major cod allergen that is used as a follow-up marker in patients with fish allergy. Objectives: To determine the clinical and laboratory characteristics of a population of patients with fish allergy. To analyze the role of the specific IgE (sIgE) of recombinant Gad c 1 (rGad c 1) and skin prick tests (SPTs) in confirming the acquisition of tolerance to fish. METHODS: We performed a retrospective study of patients with fish allergy from July 1, 2005 to December 31, 2016. The population was characterized according to demographic data, species of fish associated with allergic reactions, and symptoms. The SPT wheal diameter and sIgE for fish and rGad c 1 were evaluated before acquisition of tolerance (T0) and afterwards (T1). RESULTS: The study population comprised 81 patients (68% male). Most reactions were triggered by hake (51%), mackerel (30%), and cod (26%). The most frequent manifestations were urticaria/angioedema (72%), gastrointestinal symptoms (35%), and eczema (33%); 42% of patients experienced anaphylaxis. At T0, the average sIgE values were as follows: cod, 32.2 kUA/L; sardine, 18.4 kUA/L; hake, 17.5 kUA/L; salmon, 13.9 kUA/L; tuna, 4.5 kUA/L; and rGad c 1, 22.9 kUA/L. In patients who acquired tolerance to at least 1 fish species (n=60; 74%), the mean value of rGad c 1 at T1 (5.1 kUA/L) was significantly lower than at T0 (16.8 kUA/L) (P=.001). Significant values were also recorded for the average diameter of the SPT wheal and the evaluations at T0 and T1 for hake (9.42 mm/3.79 mm) and salmon (7.8 mm/2.8 mm) (P=.002 and P=.026, respectively). CONCLUSION: The decrease in sIgE to rGad c 1 and the mean wheal diameter of SPT for hake and salmon can be used as markers of prognosis in the acquisition of tolerance by fish-allergic patients.

Impact of loop diuretics on critically ill patients with a positive fluid balance.

The impact of the use of loop diuretics to prevent cumulative fluid balance in non-oliguric patients is uncertain. This is a retrospective study to estimate the association of time-averaging loop diuretic exposure in a large population of non-cardiac, critically ill patients with a positive fluid balance (> 5% of body weight). The exposure was loop diuretic and the main outcomes were 28-day mortality, severe acute kidney injury and successful mechanical ventilation weaning. Time-fixed and daily time-varying variables were evaluated with a marginal structural Cox model, adjusting bias for time-varying exposure and the presence of time-dependent confounders. A total of 14,896 patients were included. Patients receiving loop diuretics had better survival (unadjusted hazard ratio 0.56, 95%CI 0.39-0.81 and baseline variables adjusted hazard ratio 0.53, 95%CI 0.45-0.62); after full adjusting, loop diuretics had no association with 28-day mortality (full adjusted hazard ratio 1.07, 95%CI 0.74-1.54) or with reducing severe acute kidney injury occurrence during intensive care unit stay - hazard ratio 1.05 (95%CI 0.78-1.42). However, we identified an association with prolonged mechanical ventilation (hazard ratio 1.59, 95%CI 1.35-1.89). The main results were consistent in the sub-group analysis for sepsis, oliguria and the study period (2002-2007 vs. 2008-2012). Also, equivalent doses of up to 80 mg per day of furosemide had no significant association with mortality. After adjusting for time-varying variables, the time average of loop diuretic exposure in non-cardiac, critically ill patients has no association with overall mortality or severe acute kidney injury; however, prolonged mechanical ventilation is a concern.

Early secondary repair of obstetric anal sphincter injury: postoperative complications, long-term functional outcomes, and impact on quality of life.

BACKGROUND: An early secondary repair of the anal sphincter may be necessary if primary repair of obstetric anal sphincter injury (OASIS) is complicated by wound rupture or severe infection. The objective of this study was to assess the long-term functional outcomes, morbidity, and impact on quality of life (QoL) following an early secondary repair of OASIS. METHODS: This retrospective cohort study was conducted at Aarhus University Hospital, Denmark. All women having a secondary repair of the anal sphincter within 21 days of delivery from February 1991 to February 2017 were included (n = 51). Complications were assessed by reviewing medical records. The patient-reported outcomes were assessed in 2018 by questionnaires. Primary outcome was Wexner score and St. Mark's score. Impact on QoL was assessed using the Fecal Incontinence Quality of Life Scale (FIQLS). RESULTS: After a median follow-up time of 6.7 years (IQR 3.3-16.6), 34 women completed the questionnaire. The mean (SD) Wexner score was 5.2 ± 4.7 and the mean (SD) St. Mark's score was 6.8 ± 5.7. Women with a Wexner score ≥ 9 had a significantly lower QoL score in all domains of the FIQLS compared to women with a Wexner score < 9 (p < 0.001). Postoperative complications were experienced by 37%. Ten women developed a fistula of which nine required surgical treatment. CONCLUSIONS: An early secondary repair of the anal sphincter can be performed within 21 days of delivery with functional long-term outcomes comparable to those following a late sphincter repair. However, there is an imminent risk of complications, mainly fistulas, which should be taken into consideration when choosing the ideal timing of the repair.

Evolution of Api m10 Specific IgE and IgG4 After One Year of Bee Venom Immunotherapy.

Summary: Background. Bee-venom (BV) anaphylaxis can be life-threatening, requiring treatment with BV immunotherapy (bVIT). Different molecular profiles may be associated with different outcomes after bVIT. Methods. In 19 patients with BV anaphylaxis, sensitized both to Api m1 and Api m10, we evaluated sIgE and sIgG4 Api m1 and Api m10 levels before and after 1 year bVIT.Results.7 patients (37%) had higher baseline Api m10 than Api m1 sIgE levels (Api m10 predominant). bVIT reduced sIgE to both components but sIgG4 levels were increased only for Api m1. 5 patients (2 in the Api m10 predominant group) were re-stung without anaphylaxis. Conclusions. Although there was no increase in Api m10 sIgG4 levels after 1 year bVIT, we did not observe relevant differences in other outcomes between patients with predominant Api m1 or Api m10 sensitization.

Subcutaneous immunotherapy with aeroallergens Evaluation of adherence in real life.

Summary: Introduction. Adherence in allergen immunotherapy is crucial for its efficacy. At least 3 years of treatment are recommended for achieving a long-term modifying effect. Objectives. To assess patient's adherence and to identify determinant factors for allergen subcutaneous immunotherapy (SCIT) suspension in patients with respiratory allergy. Methods. Retrospective analysis of the medical record of patients submitted to SCIT between January 2013 and December 2016 in our Department. Results. 323 patients were included: 52% female; mean age 30±13 years; average treatment time 19±13 months. 52 patients (16%) stopped SCIT: 54% female; mean age 30±9 years; average treatment time 12±6 months; 67% dropped the treatment during the 1st year, 27% in the 2nd and 6% during the 3rd year of treatment. Adherence rate determined was 77%. The most frequent reasons for withdrawal were due to economic reasons (47.9%), followed by patients' perception of no clinical improvement (23%) and change to sublingual immunotherapy (11.6%). Conclusion. Adherence rate in our study was 77%. Economic reasons were the main cause of abandonment in the first year, while the perception of non improvement was the main reason for abandonment in subsequent years. Adequate information on SCIT prescribing and rigorous monitoring of patients during the treatment can improve adherence.

Dynamical aspects of supercooled TIP3P-water in the grooves of DNA.

We investigate by molecular dynamics simulations the mobility of the water located at the DNA minor and major grooves. We employ the TIP3P water model, and our system is analyzed for a range of temperatures 190-300 K. For high temperatures, the water at the grooves shows an Arrhenius behavior similar to that observed in the bulk water. At lower temperatures, a departure from the bulk behavior is observed. This slowing down in the dynamics is compared with the dynamics of the hydrogen of the DNA at the grooves and with the autocorrelation functions of the water hydrogen bonds. Our results indicate that the hydrogen bonds of the water at the minor grooves are highly correlated, which suggests that this is the mechanism for the slow dynamics at this high confinement.