Isolation of two triterpenoids from Phlomis purpurea, one of them with anti-oomycete activity against Phytophthora cinnamomi, and insights into its biosynthetic pathway.

Phytophthora cinnamomi is an important plant pathogen responsible for dieback diseases in plant genera including Quercus, Fagus, Castanea, Eucalyptus, and Pinus, among others, all over the world. P. cinnamomi infection exerts tremendous ecological and economic losses. Several strategies have been developed to combat this pathogenic oomycete, including the search for novel anti-oomycete compounds. In this work, a Mediterranean vascular plant, Phlomis purpurea, has been screened for secondary bioactivity against this pathogen. The genus Phlomis includes a group of herbaceous plants and shrubs described as producers of many different bioactive compounds, including several triterpenoids. Triterpenoids are well-known molecules synthesized by plants and microorganisms with potent antioxidant, antitumoral, and antimicrobial activities. We have isolated by HPLC-DAD and characterized by HPLC-MS and NMR two nortriterpenoid compounds (phlomispentaol A and phlomispurtetraolone) from the root extracts of P. purpurea. One of them (phlomispentaol A) is active against the plant pathogenic oomycete P. cinnamomi (based on in vitro inhibition bioassays). Based on their chemical structure and their relationship to other plant triterpenoids, oleanolic acid is proposed to be the common precursor for these molecules. The anti-oomycete activity shown by phlomispentaol A represents a promising alternative to counteract the worldwide-scale damage caused to forest ecosystems by this pathogen.

Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission.

Pre-transplant measurable residual disease (MRD) predicts relapse and outcome of allogeneic haematopoietic cell transplantation (allo-HCT). The impact of MRD on the outcomes of post-transplant cyclophosphamide (PTCy)-based allo-HCT from a matched unrelated donor (UD) is unknown. This study assessed the impact of MRD in acute myeloid leukaemia (AML) in the first complete remission (CR1). A total of 272 patients (MRD negative [MRD-], n = 165; MRD positive [MRD+], n = 107) with a median follow-up of 19 (range: 16-24) months were studied. The incidence of grades II-IV and grades III-IV acute GVHD at day 180 was 25.2% and 25% (p = 0.99), and 10.6% and 6.8% (p = 0.29), respectively, and 2-year chronic GVHD was 35% and 30.4% (p = 0.96) in MRD+ and MRD- cohorts, respectively. In multivariate analysis, MRD+ status was associated with a higher incidence of relapse (RI) (hazard ratio [HR] = 2.56, 95% CI: 1.39-4.72), lower leukaemia-free survival (LFS) (HR = 2.04, 95% CI: 1.23-3.39), overall survival (OS) (HR = 1.83, 95% CI: 1.04-3.25) and GVHD-free, relapse-free survival (GRFS) (HR = 1.69, 95% CI: 1.10-2.58). MRD status did not have a significant impact on non-relapse mortality (NRM), or acute or chronic GVHD risk. Among patients with AML undergoing UD allo-HCT with PTCy, pre-transplant MRD+ status predicted a higher relapse rate, lower LFS, OS and GRFS.

EZH2 mutations at diagnosis in follicular lymphoma: a promising biomarker to guide frontline treatment.

EZH2 is mutated in nearly 25% of follicular lymphoma (FL) cases. Little is known about how EZH2 affects patients' response to therapy. In this context, the aim of this study was to retrospectively analyze the frequency of mutations in EZH2 at diagnosis in tissue and ctDNA in patients with FL and to assess the patients' outcomes after receiving immunochemotherapy, depending on the EZH2 mutation status. Among the 154 patients included in the study, 27% had mutated EZH2 (46% with high-grade and 26% with low-grade FL). Of the mutated tissue samples, the mutation in ctDNA was identified in 44% of cases. EZH2 mutation in ctDNA was not identified in any patient unmutated in the tissue.Unmutated patients who received R-CHOP had significantly more relapses than patients who received R-Bendamustine (16/49 vs. 2/23, p = 0.040). Furthermore, our results show that patients with mutated EZH2 treated with R-CHOP vs. those treated with R-Bendamustine present a lower incidence of relapse (10% vs. 42% p = 0.09 at 4 years), a higher PFS (92% vs. 40% p = 0.039 at 4 years), and higher OS (100% vs. 78% p = 0.039 at 4 years). Based on these data, RCHOP could be a more suitable regimen for mutated patients, and R-bendamustine for unmutated patients. These findings could mean the first-time identification of a useful biomarker to guide upfront therapy in FL.

Prevalence, characteristics, and impact of Adverse Events in 34 Madrid hospitals. The ESHMAD study.

INTRODUCTION: Adverse Events (AE) are one of the main problems in healthcare. Therefore, many policies have been developed worldwide to mitigate their impact. The Patient Safety Incident Study in Hospitals in the Community of Madrid (ESHMAD) measures the results of them in the region. METHODS: Cross-sectional study, conducted in May 2019, in hospitalised patients in 34 public hospitals using the Harvard Medical Practice Study methodology. A logistic regression model was carried out to study the association of the variables with the presence of AE, calibrated and adjusted by patient. RESULTS: A total of 9,975 patients were included, estimating a prevalence of AE of 11.9%. A higher risk of AE was observed in patients with surgical procedures (OR[CI95%]: 2.15[1.79 to 2.57], vs. absence), in Intensive Care Units (OR[CI95%]: 1.60[1.17 to 2.17], vs. Medical), and in hospitals of medium complexity (OR[CI95%]: 1.45[1.12 to 1.87], vs. low complexity). A 62.6% of AE increased the length of the stay or it was the cause of admission, and 46.9% of AE were considered preventable. In 11.5% of patients with AE, they had contributed to their death. CONCLUSIONS: The prevalence of AE remains similar to the previously estimated in studies developed with the same methodology. AE keep leading to longer hospital stays, contributing to patient's death, showing that it is necessary to put focus on patient safety again. A detailed analysis of these events has enabled the detection of specific areas for improvement according to the type of care, centre, and patient.

The association of graft-versus-leukemia effect and graft-versus host disease in haploidentical transplantation with post-transplant cyclophosphamide for AML.

The association of graft-versus-host disease (GVHD) and graft-versus-leukemia effect after stem-cell transplantation (SCT) is well established but with limited data in the setting of haploidentical SCT (haploSCT) with post-transplant cyclophosphamide (PTCy). We used a series of landmark analyses to investigate this association in 805 AML patients following haploSCT. On day +100, 707 patients were alive and leukemia-free, 500 had no prior acute GVHD, 137 had acute GVHD grade II and 70 had grade III-IV. Subsequent relapse rates were 20.3%, 23.2% and 15.0%, respectively (P = 0.52). Subsequent non-relapse mortality (NRM) was 8.6%, 17.8% and 38.6%, respectively (P < 0.0001). Leukemia-free survival (LFS) was 71.0%, 59.0% and 46.3%, respectively (P < 0.0001). Multivariate analysis showed that acute GVHD grade II and grade III-IV were not associated with relapse (HR 1.21, P = 0.37 and HR 1.03, P = 0.94), but were associated with increased NRM (HR 2.09, P = 0.005 and HR 6.41, P < 0.0001) and lower LFS (HR 1.47, P = 0.02 and HR 2.59, P = < 0.0001). Chronic GVHD was not associated with subsequent relapse. Extensive chronic GVHD was associated with higher NRM (HR 6.72, P < 0.0001) and inferior LFS (HR 3.29, P = < 0.0001). GVHD of any type or grade is not associated with lower relapse after haploSCT with PTCy. Severe forms are associated with higher NRM and lower survival.

A strategic reflection for the management and implementation of CAR-T therapy in Spain: an expert consensus paper.

CAR-T cell therapy represents a therapeutic revolution in the prognosis and treatment of patients with certain types of hematological cancer. However, they also pose new challenges in the healthcare, regulatory and financial fields. The aim of the RET-A project was to undertake a strategic reflection on the management of CAR-T therapies within the Spanish National Health System, to agree on recommendations that will help to better deal with the new context introduced by these cell therapies in the present and in the future. This think tank involved 40 key agents and opinion leaders. The experts identified three great challenges for implementing advanced therapies in Spain: therapeutic individualisation, with a multidisciplinary approach; acceleration of access times, by minimizing bureaucracy; and increase in the number of centers qualified to manage the CAR-T therapies in the NHS. The experts agreed on the ideal criteria for designating those qualified centers. They also agreed on a comprehensive CAR-T care pathway with the timings and roles which would ideally be involved in each part of the process.

Chronic stress indicated by hair cortisol concentration in anaesthesiologists and its relationship to work experience and emotional intelligence: A cross-sectional biomarker and survey study.

BACKGROUND: Anaesthesia is a stressful medical specialty. The reaction to stress is constituted by behavioural, psychological and physiological components. Chronic physiological stress can have negative consequences for health. OBJECTIVES: First, we hypothesised that chronic physiological stress is higher for both beginning and late-career consultant anaesthesiologists. Second, we hypothesised that individuals high in emotional intelligence endure lower physiological stress. DESIGN: Cross-sectional biomarker and survey study. SETTING: Participants were recruited during the May 2019 annual meeting of the Dutch Anaesthesia Society. PARTICIPANTS: Of the 1348 colleagues who attended the meeting, 184 (70 male/114 female) participated in the study. Of the study participants, 123 (67%) were consultant anaesthesiologists (52 male/71 female) and 61 (33%) were resident anaesthesiologists (18 male/43 female). Exclusion criteria were endocrine disorders and not having enough hair. Also, experience of a recent major life event led to exclusion from analysis of our hypotheses. MAIN OUTCOME MEASURES: Chronic physiological stress was measured by hair cortisol concentration. Emotional intelligence was assessed using a validated Dutch version of the Trait Emotional Intelligence Questionnaire. As secondary measures, psychological sources of stress were assessed using validated Dutch versions of the home-work interference (SWING) and the effort-reward imbalance questionnaires. RESULTS: In support of Hypothesis 1, hair cortisol concentration was highest among early and late-career consultant anaesthesiologists (quadratic effect: b = 45.5, SE = 16.1, t = 2.8, P = 0.006, R2 = 0.14). This nonlinear pattern was not mirrored by self-reported sources of psychological stress. Our results did not support Hypothesis 2; we found no evidence for a relationship between emotional intelligence and physiological stress. CONCLUSION: In the early and later phases of an anaesthesiologist's career, physiological chronic stress is higher than in the middle of the career. However, this physiological response could not be explained from known sources of psychological stress. We discuss these findings against the background of key differences between physiological and psychological stress.

Postoperative pain reduction by pre-emptive N-acetylcysteine: an exploratory randomized controlled clinical trial.

BACKGROUND: A new potential target for multimodal pain management is the group-II metabotropic glutamate receptor subtypes, which can be activated by N-acetylcysteine. We investigated whether pre-emptive administration of N-acetylcysteine leads to a reduction in postoperative pain after laparoscopic inguinal hernia repair. METHODS: Sixty American Society of Anesthesiologists I-II patients scheduled for elective inguinal hernia repair were randomized to receive either N-acetylcysteine (150 mg/kg) or placebo intravenously 1 hour before surgery. The primary outcome was the visual analogue score during movement in the morning (approximately 24 hours) after surgery. Among secondary outcomes were postoperative opioid consumption and safety of intravenous N-acetylcysteine. RESULTS: In total, 23 patients were analyzed per group. Pain scores were similar at all timepoints with a 24 hours median score of 34 (IQR of 19.0 to 42.5) in the N-acetylcysteine group and a median score of 26 (16.0 to 50.0) in the placebo group. The percentage of patients using opioids after surgery was 22% versus 39% day 1 (p=0.63); 9% versus 26% day 2 (p=0.14); 9% versus 17% day 3 (p=0.35) in the N-acetylcysteine group compared with placebo group. Side effects resembling anaphylactoid reactions in response to the administration of N-acetylcysteine were present in more than half of the patients. CONCLUSIONS: Without finding important differences between N-acetylcysteine and placebo group in pain scores postoperatively, but with a high percentage of bothersome side effects for the N-acetylcysteine group, we would not recommend the use of pre-emptive intravenous N-acetylcysteine to reduce postoperative pain in laparoscopic inguinal hernia repair patients based on this study. TRIAL REGISTRATION NUMBER: NCT03354572.

Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT.

BACKGROUND: There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). METHODS: We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. RESULTS: Median age of patients was 38 years (range 18-76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II-IV and III-IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. CONCLUSIONS: Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

The Study on Safety in Hospitals in the Region of Madrid (ESHMAD) design: Screening and analysis of incidents and adverse events.

BACKGROUND: A Study related to Safety in Hospitals in the Region of Madrid (ESHMAD) was carried out in order to determine the prevalence, magnitude and characteristics of adverse events in public hospitals. This work aims to define a useful methodology for the multicenter study of adverse events in the Region of Madrid, to set out the preliminary results of the hospital enrollment and to establish a model of a strategy of training of trainers for its implementation. METHODS: ESHMAD was a multicenter, double phase study for the estimation of adverse events and incidents prevalence across the Region of Madrid. First phase comprehended a 1-day cross-sectional prevalence study, in which it was collected, through a screening guide, information about admission, patient characteristics, intrinsic and extrinsic risk factors, and the possibility of an adverse event or incident had happened during the hospitalization. Second phase was a retrospective nested cohort study, in which it was used a Modular Review Form for reviewing the positive screenings of the first phase, identifying in each possible adverse event or incident the classification of the patient safety event, clinical onset, root, and associated causes and factors, impact, and preventability. A pilot study was performed in an Internal Medicine Unit of a tertiary hospital. RESULTS: 34 public hospitals participated, belonging to 6 healthcare categories and with more than 10,000 hospitalisations aggregate capacity. 72 coordinators were enrolled in the strategy of training of trainers, which was performed through five on-site training workshops. In the pilot study, 45.2% patients were identified with at least one positive event of the screening. Of them, 48.1% (25 positive events) were identified as truly AE, with a result of 0.29 EA per analyzed patient. CONCLUSIONS: The ESHMAD protocol allows to estimate the prevalence of adverse events, and the strategy of training of trainers facilitated the spread of the research methodology among the participants.

Outcome of T-cell-replete haploidentical stem cell transplantation improves with time in adults with acute lymphoblastic leukemia: A study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation.

BACKGROUND: The use of haploidentical hematopoietic cell transplantation (haplo-HCT) with posttransplantation cyclophosphamide prophylaxis is gaining traction in patients with acute lymphoblastic leukemia (ALL). METHODS: The Acute Leukemia Working Party/European Society for Blood and Marrow Transplantation registry was used to evaluate the outcomes of adult patients with ALL who underwent haplo-HCT during 2011 through 2015 and compared them with the outcomes of those who underwent transplantation during 2016 through 2018. RESULTS: The analysis consisted of 195 patients, including 79 who underwent transplantation during 2011 through 2015 and 116 who underwent transplantation during 2016 through 2018. Overall, the 2-year leukemia-free survival and relapse incidence rates were 56.5% and 21%, respectively. The 100-day incidence of grade 2 through 4 acute graft-vs-host disease (GVHD) was 34.5%. The rates of nonrelapse mortality (NRM) and overall survival (OS) were 22.5% and 64.7%, respectively. Patients who underwent transplantation during 2016 through 2018 experienced improved rates of leukemia-free survival (64.9% vs 47.3%; P = .019) and OS (75.5% vs 53.5%; P = .006). Patients who underwent transplantation during 2016 through 2018 developed more grade 2 through 4 acute GVHD (42% vs 26.4%; P = .047). The incidence of relapse, GVHD-free/relapse-free survival, grade 3 and 4 acute GVHD, chronic GVHD, and extensive chronic GVHD did not differ significantly between groups. In multivariate analysis, more recently transplanted patients had a significantly reduced risk of NRM (hazard ratio, 0.44; 95% CI, 0.22-0.89; P = .022) and improved OS (hazard ratio, 0.47; 95% CI, 0.26-0.86; P = .014). A comparable analysis of patients who had acute myeloid leukemia during the same timeframes did not reveal any statistically significant differences in any outcomes. CONCLUSIONS: The outcome of adult patients with ALL who receive posttransplant cyclophosphamide has improved over time, with an impressive 2-year OS of 75% and, most recently, an NRM rate of only 17%.

Preoperative diagnosis of intraductal papillary neoplasm of the bile duct with endoscopic ultrasound.

Intraductal papillary mucinous neoplasm of the bile duct is a rare tumour only recently classified as a distinct pathological entity. These neoplasms, rarely encountered in clinical practice in the UK, are now considered to be important precursors for the development of cholangiocarcinoma. We present a histologically confirmed case of intraductal papillary neoplasm of the bile duct in a male patient and discuss the main radiographic manifestations of this rare condition across multiple imaging modalities, with an emphasis on the imaging features of endoscopic ultrasonography and its role in establishing the diagnosis.

Peri-operative swelling of fingers: A prospective observational study.

BACKGROUND: In most Dutch hospitals, because of putative peri-operative swelling of the fingers, patients must remove rings before entering the operating theatre. If this proves impossible, destructive methods for removal may be required. For some patients, this might be too radical, as the risk of wearing rings may not be in proportion to the economic and emotional damage to the patient. OBJECTIVE: The objective of this study was to determine whether peri-operative swelling of fingers occurs in elective surgery patients. DESIGN: A prospective observational study. SETTING: University Medical Centre. PATIENTS: Five groups of patients: major cardiothoracic surgery, major noncardiothoracic surgery, nonmajor surgery with a minimum of one overnight stay, nonmajor surgery without overnight stay and surgery under intrathecal anaesthesia. MAIN OUTCOME MEASURE: Finger swelling, as measured by the circumference of the first phalanx of the middle and ring fingers of both hands, pre-operatively and at 3, 24 and 48 h postsurgery, using a roller tape with one winding and 20-g weights in a custom-made frame. RESULTS: One hundred and forty-eight patients were enrolled. Peri-operative swelling reached statistical significance in all groups and was most prominent in major cardiothoracic and noncardiothoracic surgery (maximum increases in circumference were 10.6 and 7.3%, respectively). In all groups, maximal swelling was observed 24 h postsurgery. CONCLUSION: Peri-operative swelling of fingers is a common phenomenon, which is related to the extent of the surgical procedure. TRIAL REGISTRATION: Netherlands Trial Register NL8066.

A new standardised nomenclature in ophthalmology: Criteria and quantitative evaluation indicators of medical procedures. / Nuevo nomenclátor estandarizado en oftalmología: Criterios e indicadores cuantitativos de baremación de actos médicos.

PURPOSE: To create a new list of medical procedures in ophthalmology based on the International Classification of Diseases ICD-9-CM. To establish the general principles that define criteria, quantitative indicators, and scales. To develop the algorithms needed to calculate fees for medical procedures. METHODS: The out-of-date processes were removed from the list, and new techniques were added, descriptors were modified, procedures with similar descriptions were grouped together, and others were relocated to other group according to surgical complexity conditions. The criteria to calculate the medical fees were defined: training and complexity (U), proficient responsibility (R), and health value (V), with their respective quantitative indicators: period of training necessary to master a technique, frequency of complications that worsen the preoperative situation, and days of incapacity for work due to the process. The Relative Value Unit (RVU) was defined as the score sum of R, V and U. The final fee per medical procedure was calculated as the product of the RVU by its unit cost and by the weighting coefficient (WC). RESULTS: A new catalogue was prepared with 161 medical procedures, grouped into consultations, diagnostic procedures (DX.PR), therapeutic procedures (TX.PR), and surgical interventions, increasing in complexity from group 0 to group 8. The following characters were described for each one of the procedures: OMC and ICD-9-MC code, descriptor term, group, proposed modification: no changes or minimums in the descriptors, grouping of acts by similar definitions, change of origin group, new procedures, and procedures removed. The indicators for assessment were also scored: U between 1-4 points, and R and V between 0-3 points. Using their sum, the number of RVUs per medical procedure (between 1 and 10) was calculated which, together with the unit cost of the RVU and the WC (between 0.05 and 1), will determine the final rate. CONCLUSIONS: The new standardised ophthalmological nomenclature updates and improves the old classification, adapting the procedures to the descriptors included in the ICD-9-CM, and incorporating all the new techniques. Additionally, the declaration of the general principles allows defining new criteria, quantitative indicators, rating scales, and algorithms to calculate fees for medical procedures.

Post-transplant cyclophosphamide after matched sibling, unrelated and haploidentical donor transplants in patients with acute myeloid leukemia: a comparative study of the ALWP EBMT.

BACKGROUND: The use of post-transplant cyclophosphamide (PTCy) is highly effective in preventing graft-versus-host disease (GVHD) in the haploidentical (Haplo) transplant setting and is being increasingly used in matched sibling (MSD) and matched unrelated (MUD) transplants. There is no information on the impact of donor types using homogeneous prophylaxis with PTCy. METHODS: We retrospectively compared outcomes of adult patients with acute myeloid leukemia (AML) in first complete remission (CR1) who received a first allogeneic stem cell transplantation (SCT) with PTCy as GVHD prophylaxis from MSD (n = 215), MUD (n = 235), and Haplo (n = 789) donors registered in the EBMT database between 2010 and 2017. RESULTS: The median follow-up was 2 years. Haplo-SCT carried a significantly increased risk of acute grade II-IV GVHD (HR 1.6; 95% CI 1.1-2.4) and NRM (HR 2.6; 95% CI 1.5-4.5) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9) that translated to no differences in LFS (HR 1.1; 95% CI 0.8-1.4) or GVHD/relapse-free survival (HR 1; 95% CI 0.8-1.3). Interestingly, the use of peripheral blood was associated with an increased risk of acute (HR 1.9; 95% CI 1.4-2.6) and chronic GVHD (HR 1.7; 95% CI 1.2-2.4) but a lower risk of relapse (HR 0.7; 95% CI 0.5-0.9). CONCLUSIONS: The use of PTCy in patients with AML in CR1 receiving SCT from MSD, MUD, and Haplo is safe and effective. Haplo-SCT had increased risk of acute GVHD and NRM and lower relapse incidence but no significant difference in survival.

Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for T Cell Acute Lymphoblastic Leukemia: A Report from the European Society for Blood and Marrow Transplantation Acute Leukemia Working Party.

Allogeneic hematopoietic cell transplantation (HCT) is recommended in high-risk patients with T cell acute lymphoblastic leukemia (T-ALL). For patients without an HLA-identical donor, haploidentical (haplo-) HCT is becoming the leading source of stem cell donation. However, data are scarce on predictive factors for outcome in that setting. We identified 122 adults (20% female; median age, 31 years; range, 18 to 68 years) with T-ALL who underwent haplo-HCT with post-transplantation cyclophosphamide (ptCy) between 2010 and 2017. The median duration of follow-up of living patients was 23 months. The 2-year incidences of relapse and nonrelapse mortality were 45% and 21%, respectively. The 2-year leukemia-free survival (LFS), overall survival (OS), and graft-versus-host disease, relapse-free survival (GRFS) were 34%, 42%, and 27%, respectively. The 2-year LFS and OS were highly influenced by disease status at transplantation, being 49% and 55%, respectively, for patients in first complete remission (CR1); 34% and 50%, respectively, for those in second CR (CR2); and 8% and 12%, respectively, for patients with active disease. On multivariate analysis, only disease status was found to affect LFS and OS. Transplantation in CR2 negatively affected LFS, whereas active disease at the time of haplo-HCT negatively affected LFS and OS. In conclusion, haplo-HCT with ptCy produced encouraging results in this challenging disease, particularly when performed in patients in CR. Despite the limitation of the small sample size, our results were not affected by the type of conditioning, calling into question the need for total body irradiation-based myeloablative conditioning in that setting.

Azo dyes decolorization under high alkalinity and salinity conditions by Halomonas sp. in batch and packed bed reactor.

Biodecolorization and biodegradation of azo dyes are a challenge due to their recalcitrance and the characteristics of textile effluents. This study presents the use of Halomonas sp. in the decolorization of azo dyes Reactive Black 5 (RB5), Remazol Brilliant Violet 5R (RV5), and Reactive Orange 16 (RO16) under high alkalinity and salinity conditions. Firstly, the effect of air supply, pH, salinity and dye concentration was evaluated. Halomonas sp. was able to remove above 84% of all dyes in a wide range of pH (6-11) and salt concentrations (2-10%). The decolorization efficiency of RB5, RV5, and RO16 was found to be ≥ 90% after 24, 13 and 3 h, respectively, at 50 mg L-1 of dyes. The process was monitored by HPLC-DAD, finding a reduction of dyes along the time. Further, Halomonas sp. was immobilized in volcanic rocks and used in a packed bed reactor for 72 days, achieving a removal rate of 3.48, 5.73, and 8.52 mg L-1 h-1, for RB5, RV5 and RO16, respectively, at 11.8 h. The study has confirmed the potential of Halomonas sp. to decolorize azo dyes under high salinity and alkalinity conditions and opened a scope for future research in the treatment of textile effluents.

Sacral nerve stimulation for constipation: long-term outcomes.

BACKGROUND: There has been some controversy regarding the efficacy of sacral nerve stimulation (SNS) for the treatment of chronic constipation, due to less positive outcomes and concerns about cost-effectiveness in the long term. The aim of the present study was to evaluate the long-term outcomes of SNS in patients with chronic constipation. METHODS: A retrospective study was conducted on patients who had SNS for chronic constipation in 2008-2017 at our institution. Clinical factors, profile of constipation, physiology studies, and patient satisfaction with SNS therapy were investigated during a follow-up period up to 10 years after the implantation. RESULTS: Twenty-nine patients [86% female, median age 49 years (range 17-86)] were tested for SNS, and 24 received implants after a positive test phase [median 47 days (range 21-56 days)]. There were 27 bilateral and 2 unilateral implants, in S3 or S4 depending on best response. Mean follow-up was 59 months. Efficacy was considered as a score > 5 (on a scale of 1-10) in general symptom improvement. Nine (37.9%) implanted patients had a satisfaction score > 5. In 6 cases (25%), patient satisfaction was higher than 9. Due to the small sample size, there were no statistically significant variables considered as predictors of response. CONCLUSIONS: Our results agree with current studies which describe around a 30% response of SNS for refractory constipation. However, there is a small group of patients highly satisfied with SNS therapy. More studies are needed to better understand this profile and optimize outcomes.