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Study Question: What is the vaginal polymorphonuclear (PMN) spermicidal mechanism to reduce the excess of sperm?Summary Answer: We show that PMNs are very efficient at killing sperm by a trogocytosis-dependent spermicidal activity independent of neutrophil extracellular traps (NETs).What Is Known Already: Trogocytosis has been described as an active membrane exchange between immune cells with a regulatory purpose. Recently, trogocytosis has been reported as a mechanism which PMNs use to kill tumour cells or Trichomonas vaginalis.Study Design, Size, Duration: We used in vivo murine models and human ex vivo sperm and PMNs to investigate the early PMN-sperm response.Participants/materials, Setting, Methods: We set up a live/dead sperm detection system in the presence of PMNs to investigate in vivo and ex vivo PMN-spermicidal activity by confocal microscopy, flow cytometry and computer-assisted sperm analysis (SCA).Main Results and the Role Of Chance: We revealed that PMNs are highly efficient at killing sperm by way of a NETs-independent, contact-dependent and serine proteases-dependent engulfment mechanism. PMNs 'bite' sperm and quickly reduce sperm motility (within 5 min) and viability (within 20 min) after contact.Large Scale Data: N/A.Limitations, Reasons For Caution: This study was conducted using murine models and healthy human blood PMNs; whether it is relevant to human vaginal PMNs or to cases of infertility is unknown.Wider Implications Of the Findings: Vaginal PMNs attack and immobilize excess sperm in the vagina by trogocytosis because sperm are exogenous and may carry pathogens. Furthermore, this mechanism of sperm regulation has low mucosal impact and avoids an exacerbated inflammatory response that could lead to mucosal damage or infertility.Study Funding/competing Interest(s): This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants, PI16/00050, and PI19/00078, co-financed by ERDF (FEDER) Funds from the European Commission, 'A way of making Europe' and IiSGM intramural grant II-PI-MRC-2017. M.R. holds a Miguel Servet II contract (CPII14/00009). M.C.L. holds IiSGM intramural contract. There are no competing interests. [ABSTRACT FROM AUTHOR]

The Accreditation Subcommittee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published in 1996. Haemopoietic stem cell transplantation today includes grafting with allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia. An updated report with revised tables and operating definitions is presented here.Bone Marrow Transplantation (2006) 37, 439–449. doi:10.1038/sj.bmt.1705265; published online 30 January 2006 [ABSTRACT FROM AUTHOR]

Introduction: Breast cancer (BC) is the most common malignant tumor in women. Between 20 % and 30 % of patients develop metastases from BC, 50 % of them in the liver. The mean survival rate reported in patients with liver metastases from BC (LMBC) ranges from 3 to 29 months. The role of surgery in LMBC is not clearly defined. The objective of the present study was to determine the long-term survival and disease-free survival of patients undergoing surgery for LMBC and to identify the patients who most likely benefit from surgery., Material and Methods: This retrospective multicenter cohort study included all consecutive patients undergoing LMBC surgery at the participating European centers from January 1, 2010, to December 31, 2015. The ClinicalTrials.gov ID is NCT04817813., Results: A hundred women (mean age 52.6 years) undergoing LMBC surgery were included. Five-year disease-free survival was 29 %, and 5-year overall survival was 60 %. Median survival after BC surgery was 12.4 years, and after LMBC surgery, 7 years. Patients with ECOG 1, ASA score I-II, metachronous LMBC, positive hormone receptors, and who had received neoadjuvant and adjuvant hormone treatment obtained the best overall and disease-free survival results., Conclusions: In cases of correct patient selection and as part of a comprehensive onco-surgical strategy, surgery for LMBC improves overall long-term survival. In our series, certain factors were linked to better disease-free and overall survival; consideration of these factors could improve the selection of the best candidates for LMBC surgery., Gov Id: NCT04817813., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Severe combined immunodeficiencies (SCIDs) correspond to the most severe form of primary immunodeficiency. The extreme severity of the clinical presentation in SCID has legitimately led physicians to consider these conditions as medical emergencies. Hundreds of patients worldwide have undergone allogeneic haematopoietic stem cell transplantation (HCST) in the last 40 years. The complete absence of the T cell compartment in SCID prompted the development (starting in the early 1980s) of haploidentical, parental HSCT for the many patients who do not have a human leucocyte antigen (HLA)-identical sibling. Despite the undeniable progress made in this field over recent years, the long-lasting immunodeficiency that follows partially HLA-incompatible transplantation is still responsible for a mortality rate of 30% at one year post-transplantation. New approaches for reconstituting T cell compartments more rapidly are under intense preclinical development and are discussed herein., (© 2012 Blackwell Publishing Ltd.)

Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Aim of the Study: This paper provides significant ethnobotanical information on pharmaceutical plant uses in Northern Navarra from an area known both for its high biological diversity and its cultural significance, suggesting the survival of uses lost elsewhere. Collect, analyze and evaluate the ethnobotanical knowledge about medicinal plants in Northern Navarra (Iberian Peninsula) with 4243 km(2) and 71,069 inhabitants., Material and Methods: We performed semi-structured interviews with 253 informants (mean age 69; 61% women, 39% men) in 120 locations, identified the plant reported and analyzed the results, comparing them with those from other territories., Results: The informants reported data on 174 medicinal plants belonging to 63 botanical families. This work is focused on human medicinal plant uses, which represent 98% of the pharmaceutical uses (1725 use reports). The species with the highest number of cites are Chamaemelum nobile, Sambucus nigra and Verbena officinalis, with a long tradition of use in The Mountain (Navarra). All different plant parts are used; aerial part is exploited more frequently than other plant parts. Most of the listed remedies use a single ingredient, typically soaked in water. Usually, the administration is primarily oral followed by topical applications., Conclusions: The main ailments treated are digestive troubles, wounds and dermatological problems, and respiratory affections. Informants reported 24 new or scarcely cited uses for 23 medicinal plants. For 35% of the species (8) we have not found bibliographical references in the scientific literature and 48% (11) have only one to three references., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Hematopoietic stem cell transplantation remains the only treatment for most patients with severe combined immunodeficiencies (SCIDs) or other primary immunodeficiencies (non-SCID PIDs)., Objective: To analyze the long-term outcome of patients with SCID and non-SCID PID from European centers treated between 1968 and 2005., Methods: The product-limit method estimated cumulative survival; the log-rank test compared survival between groups. A Cox proportional-hazard model evaluated the impact of independent predictors on patient survival., Results: In patients with SCID, survival with genoidentical donors (n = 25) from 2000 to 2005 was 90%. Survival using a mismatched relative (n = 96) has improved (66%), similar to that using an unrelated donor (n = 46; 69%; P = .005). Transplantation after year 1995, a younger age, B(+) phenotype, genoidentical and phenoidentical donors, absence of respiratory impairment, or viral infection before transplantation were associated with better prognosis on multivariate analysis. For non-SCID PID, in contrast with patients with SCID, we confirm that, in the 2000 to 2005 period, using an unrelated donor (n = 124) gave a 3-year survival rate similar to a genoidentical donor (n = 73), 79% for both. Survival was 76% in phenoidentical transplants (n = 23) and worse in mismatched related donor transplants (n = 47; 46%; P = .016)., Conclusion: This is the largest cohort study of such patients with the longest follow-up. Specific issues arise for different patient groups. Patients with B-SCID have worse survival than other patients with SCID, despite improvements in each group. For non-SCID PID, survival is worse than SCID, although more conditions are now treated. Individual disease categories now need to be analyzed so that disease-specific prognosis may be better understood and the best treatments planned., (Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

Wiskott-Aldrich syndrome (WAS) is a rare X-linked immunodeficiency with microthrombocytopenia, eczema, recurrent infections, autoimmune disorders, and malignancies that are life-threatening in the majority of patients. In this long-term, retrospective, multicenter study, we analyzed events that occurred in 96 WAS patients who received transplants between 1979 and 2001 who survived at least 2 years following hematopoietic stem-cell transplantation (HSCT). Events included chronic graft-versus-host disease (cGVHD), autoimmunity, infections, and sequelae of before or after HSCT complications. Three patients (3%) died 2.1 to 21 years following HSCT. Overall 7-year event-free survival rate was 75%. It was lower in recipients of mismatched related donors, also in relation with an older age at HSCT and disease severity. The most striking finding was the observation of cGVHD-independent autoimmunity in 20% of patients strongly associated with a mixed/split chimerism status (P < .001), suggesting that residual-host lymphocytes can mediate autoimmune disease despite the coexistence of donor lymphocytes. Infectious complications (6%) related to splenectomy were also significant and may warrant a more restrictive approach to performing splenectomy in WAS patients. Overall, this study provides the basis for a prospective, standardized, and more in-depth detailed analysis of chimerism and events in long-term follow-up of WAS patients who receive transplants to design better-adapted therapeutic strategies.

Hurler's syndrome (HS), the most severe form of mucopolysaccharidosis type-I, causes progressive deterioration of the central nervous system and death in childhood. Allogeneic stem cell transplantation (SCT) before the age of 2 years halts disease progression. Graft failure limits the success of SCT. We analyzed data on HS patients transplanted in Europe to identify the risk factors for graft failure. We compared outcomes in 146 HS patients transplanted with various conditioning regimens and grafts. Patients were transplanted between 1994 and 2004 and registered to the European Blood and Marrow Transplantation database. Risk factor analysis was performed using logistic regression. 'Survival' and 'alive and engrafted'-rate after first SCT was 85 and 56%, respectively. In multivariable analysis, T-cell depletion (odds ratio (OR) 0.18; 95% confidence interval (CI) 0.04-0.71; P=0.02) and reduced-intensity conditioning (OR 0.08; 95% CI 0.02-0.39; P=0.002) were the risk factors for graft failure. Busulfan targeting protected against graft failure (OR 5.76; 95% CI 1.20-27.54; P=0.028). No difference was noted between cell sources used (bone marrow, peripheral blood stem cells or cord blood (CB)); however, significantly more patients who received CB transplants had full-donor chimerism (OR 9.31; 95% CI 1.06-82.03; P=0.044). These outcomes may impact the safety/efficacy of SCT for 'inborn-errors of metabolism' at large. CB increased the likelihood of sustained engraftment associated with normal enzyme levels and could therefore be considered as a preferential cell source in SCT for 'inborn errors of metabolism'.

CD40 ligand (CD40L) deficiency causes recurrent sinopulmonary infection, Pneumocystis carinii pneumonia, and Cryptosporidium parvum infection. Approximately 40% to 50% of patients survive to the third decade: long-term survival is unclear. Hematopoietic stem cell transplantation (HSCT) is curative. We present a retrospective analysis of 38 European patients undergoing HSCT for CD40L deficiency in 8 European countries between 1993 and 2002. Donor stem cell source included 14 HLA-identical siblings, 22 unrelated donors, and 2 phenotypically matched parental stem cells (12 T-cell depleted). Of the patients, 34 engrafted and 26 (68%) survived; 3 had autologous reconstitution, 22 (58%) were cured, and 1 engrafted but has poor T-cell immune reconstitution. There were 18 evaluated patients who responded to vaccination. Of the patients, 12 (32%) died from infection-related complications, with severe cryptosporidiosis in 6. Grades 2 to 4 graft-versus-host disease (GvHD) associated with infection occurred in 6 of 12 fatal cases. HSCT cured 58% of patients, 72% of those without hepatic disease. Early T-cell function following whole marrow HSCT may limit cryptosporidial disease, but survival was similar after T-cell-depleted HSCT. Preexisting lung damage was the most important adverse risk factor. Further studies will determine optimal timing and type of HSCT.

Background: Transplantation of allogeneic haemopoietic stem cells can cure several primary immunodeficiencies. This European report focuses on the long-term results of such procedures done between 1968 and December, 1999, for primary immunodeficiencies., Methods: The report includes data from 37 centres in 18 countries, which participated in a European registry for stem-cell transplantation in severe combined immuno deficiencies (SCID) and in other immunodeficiency disorders (non-SCID). 1082 transplants in 919 patients were studied (566 in 475 SCID patients, 512 in 444 non-SCID patients; four procedures excluded owing to insufficient data). Minimum follow-up of 6 months was required., Findings: In SCID, 3-year survival with sustained engraftment was significantly better after HLA-identical than after mismatched transplantation (77% vs 54%; p=0.002) and survival improved over time. In HLA-mismatched stem-cell transplantation, B(-) SCID had poorer prognosis than B(+) SCID. However, improvement with time occurred in both SCID phenotypes. In non-SCID, 3-year survival after genotypically HLA-matched, phenotypically HLA-matched, HLA-mismatched related, and unrelated-donor transplantation was 71%, 42%, 42%, and 59%, respectively (p=0.0006). Acute graft versus host disease predicted poor prognosis whatever the donor origin except in related HLA-identical transplantation in SCID., Interpretation: The improvement in survival over time indicates more effective prevention and treatment of disease-related and procedure-related complications--eg, infections and graft versus host disease. An important factor is better prevention of graft versus host disease in the HLA-non-identical setting by use of more efficient methods of T-cell depletion. For non-SCID, stem-cell transplantation can provide a cure, and grafts from unrelated donors are almost as beneficial as those from genetically HLA-identical relatives.

We have performed a retrospective analysis of the development of T- and B-cell functions after HLA-nonidentical T-cell-depleted bone marrow transplantation (BMT) performed in 193 patients with severe combined immunodeficiency (SCID) at 18 European centers between December 1982 and December 31, 1993. One hundred sixteen of 193 patients were alive with evidence of engraftment 6 months after BMT. Development of T-cell function occurred earlier than B-cell function and was achieved more frequently up to the time of last follow-up. The median time to achieve normal T-cell function was 8.7 months, whereas the median time to achieve normal B-cell function was 14.9 months. Twenty-four patients died later than 6 months post-BMT, mainly due to chronic graft-versus-host disease (cGVHD) and/or viral infection. Absence of T-cell reconstitution 6 months after BMT, unlike absence of B-cell reconstitution, was associated with a poor outcome. Two additional factors were associated with a poor outcome: presence of cGVHD 6 months after BMT and B- SCID versus B+ SCID. However, two of these three factors remained as significant prognostic factors in a multivariate analysis: the absence of T-cell function and the presence of cGVHD 6 months after BMT. Analysis of the factors influencing the development of immune reconstitution showed that T- and B-cell functions occurred earlier and more frequently in B+ SCID versus B- SCID patients. Acute GVHD was associated with a slower development of T-cell function at 6 months, and cGVHD had a negative influence on the development of T-cell function afterwards, but neither acute nor chronic GVHD was found to influence the development of B-cell function. Once engraftment occurred, whether patients had or had not received Busulfan in the conditioning regimen did not influence the kinetics and quality of T-cell function development. In a multivariate study, two factors were found to influence the T-cell function 6 months after BMT: type of SCID and acute GVHD. The results of this retrospective analysis should lead to new protocols adapted to SCID disease, considering that disease-related as well as BMT-related parameters influence the development of immune function and thereby long-term outcome after HLA-nonidentical T-cell-depleted BMT.

Objective: For children with life-threatening inborn errors of metabolism without a matched related bone marrow donor, transplantation from an HLA genetically nonidentical donor is the only therapeutic option. To reduce the high risk of graft rejection in this setting without increasing the conditioning regimen, a protocol based on the infusion of an antiadhesion antibody directed against the CD11a (leukocyte function-associated antigen 1 [LFA-1]) molecule was performed by the European Bone Marrow Transplantation-European Society for Immunodeficiency group with promising results. To optimize engraftment, and thereby survival, further, the additional blockade of a second important leukocyte adhesion and signalization pathway mediated by the CD2 and LFA-3 interaction was attempted in a multicenter protocol conducted by the European Bone Marrow Transplantation-European Society for Immunodeficiency group. Results of this study (ie, engraftment and survival) were compared with a historical control group that received the anti-LFA-1 antibody alone. Factors that may have affected engraftment and survival were also considered in this study., Methods: Forty-four children with inborn errors, including inherited immunodeficiencies (excluding severe combined immunodeficiencies), Chédiak-Higashi syndrome, familial hemophagocytic lymphohistiocytosis, and malignant osteopetrosis, received bone marrow from HLA-nonidentical related donors or from HLA-identical unrelated donors at 13 European centers between August 1990 and June 1993. Bone marrow was depleted of T cells by use of either erythrocyte (E) rosetting or monoclonal antibodies (MoAbs) to prevent graft-versus-host disease. The conditioning regimen consisted of busulfan and cyclophosphamide for all patients plus etoposide for patients with osteopetrosis, familial hemophagocytic lymphohistiocytosis, and Chédiak-Higashi syndrome. Infusions of MoAbs specific for the CD11a and the CD2 molecules were started 4 and 3 days, respectively, before and continued through the first 10 and 11 days, respectively, after bone marrow transplantation (a total of 14 injections)., Results: The overall sustained engraftment rate was 69.8%, with full chimerism in 80.6% of patients and no late graft rejection with the use of two MoAbs versus 65.7% and 58.1%, respectively, in the control group, in which only one MoAb was infused. The overall actuarial survival rate with a functional graft was 40.9%, with a mean follow-up of 39.3 months with two MoAbs versus 37.8% with one. The engraftment rate was significantly influenced by the T-cell depletion method, with better results for recipients of E rosette- depleted marrow (78.6% vs 20% for Campath 1-M plus complement-depleted marrows). Graft-versus-host disease and the kinetics of immune reconstitution were similar in both groups., Conclusions: The overall engraftment rate and overall survival rate with engraftment in patients treated with anti-LFA-1 and anti-CD2 were similar to those in patients treated with anti-LFA-1 antibody alone. However, although the number of patients is too small to draw definitive conclusions, results from the combined use of the two MoAbs indicates a trend toward better engraftment and survival after infusion of E rosette-depleted marrow. Further improvement in survival would demand additional strategies to hasten immunologic recovery.

Bone marrow (BM) transplantations performed between 1977 and 1991 at 13 European centers in 149 patients with 11 different primary immunodeficiency (ID) diseases (excluding severe combined immunodeficiency) were analyzed retrospectively. Overall survival among recipients of HLA genetically identical BM (n = 56) was 66%. Since October 1985, the date of a previous survey, a significant improvement in survival has been achieved in most ID diseases (overall survival, 81.5% v 51.7%; P < .01), primarily because of a decrease in the frequency of infectious complications. In long-term survivors, disease correction is excellent, with minimal sequelae in most patients. In 22 patients who received closely matched BM (ie, from phenotypically identical related donors, matched unrelated donors, or one HLA-ag-mismatched related donors), the survival rate (45.5%) was not significantly better than among 71 recipients of BM with 2 or 3 mismatched HLA antigens (38%). In the latter group, favorable outcome was associated with younger age, with transplantation since October 1985 (47% v 25%; P < .0001), and with a diagnosis of leukocyte adhesion deficiency. The improvement in outcome was mainly because of a higher engraftment rate and a decrease in the frequency of infections, although Epstein-Barr virus-induced B-lymphocyte proliferative disorders occurred in 16 patients (mainly those with Wiskott-Aldrich syndrome), 10 of whom died. The improvement in engraftment corresponded to the introduction of treatment in vivo with anti-LFA-1 antibody to prevent rejection of T-cell-depleted grafts (74% engraftment and 45% survival in 38 treated patients versus 37.5% and 21%, respectively, in 24 untreated patients.