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Advance Higher Education has recently generated a transformed UK Athena Swan charter. One of their new strategies to identify improvement areas in the member institutions' culture is through the Athena Swan Culture Survey. This research aims to establish an easy and fast methodology to analyse the results of this survey and assess its validity and reliability. After ethical approval, the complete Athena Swan Culture Survey with six constructs, 28 items and a 5-point Likert scale was populated within the Department of Engineering of the Manchester Metropolitan University. The responses were statistically analysed through descriptive statistic to evaluate the degree of compliance, indifference and room for improvement, bivariant (Correlations, Two-Factor Analysis of Variance) and multivariant statistic (Confirmatory and Exploratory Factor Analysis, Internal Consistency and Structural Equation Model) to validate and appraise the reliability of the survey. The study showed that after a recodification of the "Bullying" construct, all the constructs were valid and had excellent or good reliability with Cronbach's alpha coefficients between 0.916 and 0.856 except the Work-Life balance construct. Chi-squared test and two-factor ANOVA indicated that the responses were not influenced by the gender or ethnicity. The study proves that reliable results can be obtained with a small sample as long as it is statistically representative, and the items present high communalities. Guidelines to calculate the degree of compliance and to faithfully identify improvement areas of the applicants were presented. Finally, suggestions for future research areas and improvements on the Athena Swan Culture Survey were proposed.

To describe and compare the characteristics of necrotizing fasciitis (NF) in patients with and without haematological malignancy. All adult patients diagnosed with NF and treated at our hospital were included (January 2010–March 2019). Diagnosis was based on intraoperative findings or consistent clinical/radiological characteristics, and patients were classified as group A (with haematological malignancy) or group B (without haematological malignancy). Student’s t (quantitative), Fisher’s exact (qualitative), and Kaplan-Meyer tests were used for the statistical analysis. The study included 29 patients: 8 in group A and 21 in group B. All haematological patients had severe neutropenia (0.2 [0.02–0.5] ×109 cells/L; p 6 did not predict mortality in either group. In our study, NF in patients with haematological malignancies was mainly due to Gram-negative bacilli, associated to high and early mortality rates. In our experience, the LRINEC scale was not useful for predicting mortality.

Although SARS-CoV-2 vaccines immunogenicity in patients with cancer has been investigated, whether they can significantly improve the severity of COVID-19 in this specific population is undefined.Capitalizing on OnCovid (NCT04393974) registry data we reported COVID-19 mortality and proxies of COVID-19 morbidity, including post-COVID-19 outcomes, according to the vaccination status of the included patients.2090 eligible patients diagnosed with COVID-19 between 02/2020 and 11/2021 were included, of whom 1930 (92.3%) unvaccinated, 91 (4.4%) fully vaccinated and 69 (3.3%) partially vaccinated. With the exception of a higher prevalence of patients from the UK (p = 0.0003) and receiving systemic anticancer therapy at COVID-19 diagnosis (p = 0.0082) among fully vaccinated patients, no demographics/oncological features were associated with vaccination status. The 14-days case fatality rate (CFR) (5.5% vs 20.7%, p = 0.0004) and the 28-days CFR (13.2% vs 27.4%, p = 0.0028) demonstrated a significant improvement for fully vaccinated patients in comparison with unvaccinated patients. The receipt of prior full vaccination was also associated with reduced symptomatic COVID-19 (79.1% vs 88.5%, p = 0.0070), need of COVID-19 oriented therapy (34.9% vs 63.2%, p 0.0001), complications from COVID-19 (28.6% vs 39.4%, p = 0.0379), hospitalizations due to COVID-19 (42.2% vs 52.5%, p = 0.0007) and oxygen therapy requirement (35.7% vs 52%, p = 0.0036). Following Inverse Probability Treatment Weighting (IPTW) procedure no statistically significant difference according to the vaccination status was confirmed; however, all COVID-19 related outcomes were concordantly in favour of full vaccination. Among the 1228 (58.8%) patients who underwent a formal reassessment at participating centres after COVID-19 resolution, fully vaccinated patients experienced less sequelae than unvaccinated patients (6.7% vs 17.2%, p = 0.0320).This analysis provides initial evidence in support of the beneficial effect of SARS-CoV-2 vaccines against morbidity and mortality from COVID-19 in patients with cancer.

The omicron (B.1.1.529) variant of SARS-CoV-2 is highly transmissible and escapes vaccine-induced immunity. We aimed to describe outcomes due to COVID-19 during the omicron outbreak compared with the prevaccination period and alpha (B.1.1.7) and delta (B.1.617.2) waves in patients with cancer in Europe.In this retrospective analysis of the multicentre OnCovid Registry study, we recruited patients aged 18 years or older with laboratory-confirmed diagnosis of SARS-CoV-2, who had a history of solid or haematological malignancy that was either active or in remission. Patient were recruited from 37 oncology centres from UK, Italy, Spain, France, Belgium, and Germany. Participants were followed up from COVID-19 diagnosis until death or loss to follow-up, while being treated as per standard of care. For this analysis, we excluded data from centres that did not actively enter new data after March 1, 2021 (in France, Germany, and Belgium). We compared measures of COVID-19 morbidity, which were complications from COVID-19, hospitalisation due to COVID-19, and requirement of supplemental oxygen and COVID-19-specific therapies, and COVID-19 mortality across three time periods designated as the prevaccination (Feb 27 to Nov 30, 2020), alpha-delta (Dec 1, 2020, to Dec 14, 2021), and omicron (Dec 15, 2021, to Jan 31, 2022) phases. We assessed all-cause case-fatality rates at 14 days and 28 days after diagnosis of COVID-19 overall and in unvaccinated and fully vaccinated patients and in those who received a booster dose, after adjusting for country of origin, sex, age, comorbidities, tumour type, stage, and status, and receipt of systemic anti-cancer therapy. This study is registered with ClinicalTrials.gov, NCT04393974, and is ongoing.As of Feb 4, 2022 (database lock), the registry included 3820 patients who had been diagnosed with COVID-19 between Feb 27, 2020, and Jan 31, 2022. 3473 patients were eligible for inclusion (1640 [47·4%] were women and 1822 [52·6%] were men, with a median age of 68 years [IQR 57-77]). 2033 (58·5%) of 3473 were diagnosed during the prevaccination phase, 1075 (31·0%) during the alpha-delta phase, and 365 (10·5%) during the omicron phase. Among patients diagnosed during the omicron phase, 113 (33·3%) of 339 were fully vaccinated and 165 (48·7%) were boosted, whereas among those diagnosed during the alpha-delta phase, 152 (16·6%) of 915 were fully vaccinated and 21 (2·3%) were boosted. Compared with patients diagnosed during the prevaccination period, those who were diagnosed during the omicron phase had lower case-fatality rates at 14 days (adjusted odds ratio [OR] 0·32 [95% CI 0·19-0·61) and 28 days (0·34 [0·16-0·79]), complications due to COVID-19 (0·26 [0·17-0·46]), and hospitalisation due to COVID-19 (0·17 [0·09-0·32]), and had less requirements for COVID-19-specific therapy (0·22 [0·15-0·34]) and oxygen therapy (0·24 [0·14-0·43]) than did those diagnosed during the alpha-delta phase. Unvaccinated patients diagnosed during the omicron phase had similar crude case-fatality rates at 14 days (ten [25%] of 40 patients vs 114 [17%] of 656) and at 28 days (11 [27%] of 40 vs 184 [28%] of 656) and similar rates of hospitalisation due to COVID-19 (18 [43%] of 42 vs 266 [41%] of 652) and complications from COVID-19 (13 [31%] of 42 vs 237 [36%] of 659) as those diagnosed during the alpha-delta phase.Despite time-dependent improvements in outcomes reported in the omicron phase compared with the earlier phases of the pandemic, patients with cancer remain highly susceptible to SARS-CoV-2 if they are not vaccinated against SARS-CoV-2. Our findings support universal vaccination of patients with cancer as a protective measure against morbidity and mortality from COVID-19.National Institute for Health and Care Research Imperial Biomedical Research Centre and the Cancer Treatment and Research Trust.

Recent studies have shown a suboptimal humoral response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) messenger RNA (mRNA) vaccines in patients diagnosed with hematologic malignancies; however, data about cellular immunogenicity are scarce. The aim of this study was to evaluate both the humoral and cellular immunogenicity 1 month after the second dose of the mRNA-1273 vaccine. Antibody titers were measured by using the Elecsys and LIAISON anti–SARS-CoV-2 S assays, and T-cell response was assessed by using interferon-γ release immunoassay technology. Overall, 76.3% (184 of 241) of patients developed humoral immunity, and the cellular response rate was 79% (184 of 233). Hypogammaglobulinemia, lymphopenia, active hematologic treatment, and anti-CD20 therapy during the previous 6 months were associated with an inferior humoral response. Conversely, age >65 years, active disease, lymphopenia, and immunosuppressive treatment of graft-versus-host disease (GVHD) were associated with an impaired cellular response. A significant dissociation between the humoral and cellular responses was observed in patients treated with anti-CD20 therapy (the humoral response was 17.5%, whereas the cellular response was 71.1%). In these patients, B-cell aplasia was confirmed while T-cell counts were preserved. In contrast, humoral response was observed in 77.3% of patients undergoing immunosuppressive treatment of GVHD, whereas only 52.4% had a cellular response. The cellular and humoral responses to the SARS-CoV-2 mRNA-1273 vaccine in patients with hematologic malignancies are highly influenced by the presence of treatments such as anti-CD20 therapy and immunosuppressive agents. This observation has implications for the further management of these patients., The authors also thank the Cellex Foundation for providing research facilities and equipment and the CERCA Programme/Generalitat de Catalunya for institutional support.

IMPORTANCE Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020;12.5% (95% Cl, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021(all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%) vs 427 of 1008 [42.4%); P = .001), and have advanced tumors (708 of 1626 [46.4%) vs 536 of 1008 [56.1%]: P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%) vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%) vs 418 of 1008 [42.1%); P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%) vs 501of 1008 [49.7%); P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p

The success of allogeneic stem cell transplant is hampered by the development of acute and chronic graft-versus-host disease (GvHD) which has direct impact on treatment-related mortality and morbidity. As a result, T cell depletion through positive selection of CD34+ cells has emerged as a promising strategy to reduce acute and chronic GvHD in these patients. In this review, we summarize the main characteristics of allogeneic stem cell transplant with CD34+ cell selection including risks of graft failure, GvHD, infection, organ toxicity, and long-term survival. Moreover, we highlight future strategies to improve the results of this platform and to consolidate its use in clinical practice.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy resulting in increased definitive cure rates or extended disease-free survival in various malignant and nonmalignant hematologic diseases. However, because of the high risk of severe complications of this therapy, up to 50% of patients may require being admitted to the intensive care unit (ICU) to manage life-threatening conditions. We aimed to evaluate the in-hospital mortality of allo-HSCT recipients admitted to the ICU and to identify those variables associated with in-hospital mortality. A 10-year (January 2010 to December 2019), single-center, retrospective study was conducted in Vall d´Hebron University Hospital, Barcelona. We included all consecutive allo-HSCT patients who required admission to the ICU. Baseline and disease-related characteristics were registered. Severity scores and the need for organ support were also assessed on days 1, 3, and 5 of ICU admission. In-hospital mortality–associated independent variables were identified using the Cox proportional hazards regression model. Three hundred twenty-three patients underwent allo-HSCT during the study period, of whom 82 (25%) were admitted to the ICU; 53 (65%) male, with a median age of 51 (38-59) years. Most patients received allo-HSCT for the treatment of lymphoma (20 patients [24%]) or acute leukemia (44 patients [54%]). The median Acute Physiology And Chronic Health Evaluation II score was 23 (17-28), and the median Sequential Organ Failure Assessment (SOFA) score on admission was 9 (7-11). Forty-nine (60%) patients died in the ICU, and 11 (13%) died in the hospital after being discharged from the ICU. Disease-related characteristics were not associated with mortality. Yet, SOFA score on day 1 (hazard ratio [HR]: 1.11 [95% confidence interval {CI}: 1.04-1.02]; P = .002), the need for vasopressors on day 3 (HR: 2.35 [95% CI: 1.27-4.36]; P = .007), and a nondecreasing SOFA score on day 5 (HR: 2.13 [95% CI: 1.03-4.39]; P = .04), were independently associated with in-hospital mortality. Mortality in allo-HSCT patients who require ICU admission remains high. In the present study, SOFA score, the need for vasopressors on day 3, and a nondecreasing SOFA score on day 5 predicted in-hospital mortality.

Objective To compare the efficacy and safety of CD34+ selected ex vivo T-cell depletion (TCD) vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy-Sir-MMF) as graft-vs-host disease (GVHD) prophylaxis. Methods We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). Results Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < .001) in TCD and PTCy-Sir-MMF, respectively. The 2-year non-relapse mortality, relapse, disease-free and overall survival were 25% vs 8% (P = .01), 20% vs 16% (P = .2), 55% vs 76% (P = .004), 57% vs 83% (P = .004) for TCD and PTCy-Sir-MMF, respectively. Cumulative incidence of cytomegalovirus and Epstein-Barr infection requiring therapy was 76% vs 40% (P < .001) and 32% vs 0% (P < .001) in TCD and PTCy-Sir-MMF, respectively. PTCy-Sir-MMF platform showed faster T-cell reconstitution. Conclusions PTCy-Sir-MMF provides better survival outcomes but is associated with higher risk of cGVHD compared to TCD.

Patients receiving an allogeneic hematopoietic cell transplantation (allo-HCT) after the use of PD-1 inhibitors seem to be at a higher risk of developing acute graft-versus-host disease (aGHVD) through etiopathogenetic mechanisms not fully elucidated. Herein, we investigated the effect of nivolumab administered prior to allo-HCT on the following early T-cell reconstitution and its modulation by the GVHD prophylaxis (tacrolimus/sirolimus vs. posttransplant cyclophosphamide [PTCY]). In all nivolumab-exposed patients we detected circulating nivolumab in plasma for up to 56 days after allo-HCT. This residual nivolumab was able to bind and block PD-1 on T-cells at day 21 after allo-HCT, inducing a T cell activation that was differentially modulated depending on the GVHD prophylactic regimen. Among patients receiving tacrolimus/sirolimus, nivolumab-exposed patients had a higher incidence of severe aGVHD and a more effector T-cell profile compared with anti-PD-1-naive patients. Conversely, patients receiving PTCY-based prophylaxis showed a similar risk of aGVHD and T-cell profile irrespective of the previous nivolumab exposure. In conclusion, nivolumab persists in plasma after transplantation, binds to allogeneic T cells and generates an increased T-cell activation. This T-cell activation status can be mitigated with the use of PTCY, thus reducing the risk of aGVHD.

In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%,p = .01), along with shorter overall survival (51.8% vs 77.8%,p < .01) at 2 years than patients treated with BF. There were no significant differences in the cumulative incidence of grade II-IV acute GVHD or moderate-severe chronic GVHD or relapse between both groups. These results suggest that TBF does not seem to improve the traditional RIC BF regimen, at least when associated with SIR-TAC prophylaxis.

Chordoma is a rare, slow-growing tumour arising from remnants of the notochord. It is most often located in the base of the skull and the sacrococcygeal region, being located in the cervical region in only 6% of cases. A rare case is presented of a left para-spinal chordoma, of which less than 10 cases have been reported in literature. It was located at C2-C4 level in a young male with no personal history of interest. Radiographic findings suggested that this was a slow-growing tumour, of cystic dominance, which eroded the bone structures and encompassed the left vertebral artery. Surgical excision was performed, and in the analysis of the surgical piece, cell proliferation was observed, with a stromal myxoid-chondroid appearance, epithelioid and physaliphorous (PAS+) cells, all of them compatible with chordoma.

This study aims to understand and estimate the forces while the anterior cruciate ligament (ACL) is subjected to loading during stair negotiation. 9 healthy subjects were recruited and asked to negotiate stairs while their motion was captured. An OpenSim model was developed to estimate the ACL length from kinematic data. The forces were estimated using a force/displacement relationship. The peak ACL force was 0.416±0.089 N/BW and was recorded at full extension of the knee while the participants were descending stairs. The forces experienced by the right and left ACL of women were highly significant compared to ACL forces in men and the ACL forces in old people were significantly higher than in younger people. These forces will be used as boundary conditions in a novel finite element model (FEM) to estimate tensile and shear stress levels in the ACL to gain design information to create a tissue engineered ACL implant. The CIRP-Biomanufacturing conference promotes the exchange of knowledge on biodesign and biofabrication in order to develop novel medical devices for improving quality of life. This work is relevant to the conference since it contributes to a better understanding of the mechanical behavior of ACL throughout its range of motion and it is the starting point for the design and manufacture of new ACL implants.

In clinical practice, patients with myelodysplastic syndromes (MDS) are usually classified in low or high-risk groups to take therapeutic decisions, conservative for low-risk, whereas active for high-risk. Nevertheless, in the Revised International Prognostic Scoring System (IPSS-R) is not well stated which patients are low or high-risk. This study was aimed to ascertain in 364 MDS patients which IPSS-R threshold better dichotomized in low vs. high-risk. The best dichotomization was obtained with an IPSS-R cut-point of 3. Accordingly, 68% patients were classified as low-risk (median OS, 61.3 months) and 32% as high-risk MDS (median OS, 13.9 months) (p < .001). Interestingly, the intermediate IPSS-R risk patients presented an OS more related to the high IPSS-R than to the low IPSS-R risk group. In conclusion, an IPSS-R cut-point of 3 led to a meaningful stratification in low and high-risk that can be helpful for the clinical management of MDS patients.

Chordoma is a rare, slow-growing tumour arising from remnants of the notochord. It is most often located in the base of the skull and the sacrococcygeal region, being located in the cervical region in only 6% of cases. A rare case is presented of a left para-spinal chordoma, of which less than 10 cases have been reported in literature. It was located at C2-C4 level in a young male with no personal history of interest. Radiographic findings suggested that this was a slow-growing tumour, of cystic dominance, which eroded the bone structures and encompassed the left vertebral artery. Surgical excision was performed, and in the analysis of the surgical piece, cell proliferation was observed, with a stromal myxoid-chondroid appearance, epithelioid and physaliphorous (PAS+) cells, all of them compatible with chordoma.

Introduction Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for severe and persistent thrombocytopenia after allo-SCT. Patients and methods We performed a retrospective multicenter study including patients from centers of GETH with prolonged isolated thrombocytopenia (PT) or secondary failure of platelet recovery (SFPR) after allo-SCT. PT was defined as the engraftment of all peripheral blood cell lines but with platelet count ≤20000/µL for 7 consecutive days or requirement of transfusion for more than 60 days after allo-SCT. SFPR was defined as a decline of platelet counts to ≤20000/µL for 7 consecutive days or requirement of transfusion after achievement platelets ≥50000/µL without transfusion for 7 days post-SCT. The primary endpoint was platelet recovery to ≥50000/µL. Results Eighty-six patients with thrombocytopenia after allo-SCT were included. The characteristic of the patients, are summarized in table 1. Sixteen (19%) of the patients had PT and 71 (82%) SFPR. TPO-RA was started at a median time of 127 days (27-1177) after allo-SCT (41% Romiplostim / 59% Eltrombopag). Median initial and maximum administered doses were 50 mg/daily (25-150) and 75 (25-150) for Eltrombopag and 1 µg/kg (1-7) and 5 (1-10) for Romiplostin, respectively. Eighteen patients (21%) were previously treated with cell infusion (67% mesenchymal cells and 33% CD34+ boost). Median platelet count before TPO-RA onset was 14000/µL (1000-57000). Platelet recovery to ≥50000/µL was 60% and the response was achieved at a median time of 56 days (2-247). Responses were similar considering all potential causes of thrombocytopenia evaluated. 81% of the patients had decrease number of megakaryocytes prior to treatment showing a worse response to therapy: median time to ≥20000/µL platelets 43 days versus 28 days (p=0.011), with also a lower rate of platelet recovery to ≥50000/µL (62% versus 85% if normal megakaryocytes). In patients treated with Eltrombopag, 27% had neutropenia 1000/µL after therapy. The median treatment duration was 62 days (7-700) and 62% discontinued TPO-Ra maintaining response. Grade 3-4 adverse events (hepatic and asthenia) were observed in only 2% of the cases. At last follow up with a median of 10 months (1-59), 72% of the patients maintained the response and 61 (71%) were alive. Death rate was significantly lower in responder-patients to TPO-RAs, 15% versus 53% in non-responders (p Conclusion To our knowledge this is the biggest series analyzing the use of TPO-Ra after allo-SCT. Our results support the efficacy and safety in this new setting with responses around 60% and a low number of side effects. Additional studies to identify predictors of response are needed. Disclosures No relevant conflicts of interest to declare.

Allo-HCT has been shown to be feasible in patients previously exposed to anti-PD-1 monoclonal antibodies, albeit their use has been associated with a more frequent and more severe acute GVHD. Our aim was to study the effect of pre-transplant exposure to the anti-PD1 nivolumab on early immune response after allo-HCT and how this response becomes modulated by the use of PTCY. Twelve patients diagnosed with lymphoproliferative neoplasms who underwent an allo-HCT from HLA matched related or unrelated donors were analyzed. Considering pre-HCT exposure to nivolumab and type of GVHD prophylaxis, patients were classified into 4 groups: previous nivolumab and GVHD prophylaxis with PTCY (Nivo-PTCY, n=3), previous nivolumab and standard GVHD prophylaxis with tacrolimus and sirolimous (Nivo-TacSiro, n=3), no previous nivolumab and GVHD prophylaxis with PTCY (Control-PTCY, n=3) and no previous nivolumab and standard GVHD prophylaxis (Control-TacSiro, n=3). Patients exposed to nivolumab received a median of 8.5 (range 4-16) doses at 3mg/Kg, being the median time from the last dose of nivolumab to allo-HCT of 84 (range, 34-154) days. With a median of 29 (range 23-37) days, all 3 patients in the Nivo-TacSiro group experienced fatal grade 3-4 acute GVHD. No other grade 3-4 GVHD was observed in the other patients and only 2 (1 in each control group) had grade 2 acute GVHD. All 12 patients were in full-donor chimera on day +21. Concentration of nivolumab in plasma was measured on Day 0 (allo-HCT), +7, +14, +21, +28 and +56 by ELISA. Early immune response on day +21 was assessed by flow cytometry analyzing changes in the T-cell repertoire, variations on the expression of PD-1 and other inhibitory receptors (TIM-3 and LAG-3), and modifications in the myeloid compartment. Residual nivolumab was detected as late as 56 days after allo-HCT in the plasma from all 6 patients exposed to the drug (Figure 1A). In addition PD-1 expression on CD4+ and CD8+ T cells on day +21 was found to be lower in these patients compared to control groups, pointing out that residual nivolumab was able to block PD-1 on donor-derived T-cells after allo-HCT (Figure 1B). We then analyzed the effect of pre-transplant nivolumab on early (day +21) immune response after allo-HCT by comparing groups of patients with the same GVHD prophylaxis. Hence, patients in the Nivo-TacSiro subgroup presented a lower CD4+/CD8+ ratio, lower counts of naïve CD8+ T cells (Figure 1C), higher percentage of IFN-γ-producing CD4+ and CD8+ T cells, lower expression of TIM-3 on CD4+ an CD8+ T cells as well as promotion of Th1 differentiation after allo-HCT than Control-TacSiro patients. Also, these patients had a higher proportion of classical monocytes and higher expression of the activation marker CD86 than patients not exposed to anti-PD1 (Figure 1D). All this immune activation was in line with the clinical scenario of severe GVHD observed later on in the 3 patients of the Nivo-TacSiro subgroup. Conversely, patients in the Nivo-PTYC subgroup had similar proportions of T-cell subpopulations (especially in the CD8 compartment), Th1 differentiation, and monocyte profile at day +21 than patients in the Control-PTYC subgroup, indicating that previous nivolumab exposure has little influence on the effect of PTCY. Finally, a direct comparison of the two GVHD prophylaxis schemes used in the 6 patients previously exposed to nivolumab revealed that Nivo-PTCY patients had a higher CD4+/CD8+ ratio, higher proportion of CD4+ and CD8+ effector memory T-cells (Figure 1C), lower percentage of IFN-γ-producing T cells, as well as an attenuated Th1 response and a lower proportion of classical monocytes (Figure 1D) after allo-HCT compared with Nivo-TacSiro patients. In conclusion, pre-transplant nivolumab is detectable in plasma of patients within 2 months following allo-HCT and it seems to be responsible for an altered early T-cell and monocyte activation status in patients receiving standard GVHD prophylaxis. PTCY seems capable of inducing a more tolerant profile of immune cells in patients previously exposed to nivolumab. Therefore, the use of PTCY as GVHD prophylaxis in patients previously exposed to immune checkpoint inhibitors warrants further investigation. Disclosures Iacoboni: Roche: Honoraria; Celgene: Other: Travel funding.

This study of Addisonia excentrica (Tiberi, 1855) is the first on the population dynamics of any cocculiniform limpet. We conducted 2 years of monthly sampling by trawling off the coast of Malaga province, Spain (Western Mediterranean), at 47 –311 m. We sampled 482 egg cases of the lesser spotted dogfish (Scyliorhinus canicula), in which A. excentrica lives and feeds, which yielded 987 specimens of A. excentrica. Of capsules containing A. excentrica, 70.3% were collected between 50 and 100 m depth, where the mean percentage of occupied capsules (incidence) was 32.8%; the greatest incidence was found between 100 and 150 m (42.1%). The maximum depth of living A. excentrica was 222 m. In samples collected at 50–100 m recently settled individuals (,2 mm) predominated throughout the year. Larvae and apohermaphroditic specimens with mature oocytes (.7.2 mm) were scarce, but they were also present almost all year round, suggesting continuous reproduction. A positive correlation between the relative age of the egg case and the mean length of limpets was found. The long embryonic development of dogfish and the slow decay of egg cases provides enough time for larvae or young individuals to mature within a single egg case. Once mature, the limpets leave the capsule and spawn on the nearby bottom. Continuous reproduction and aggregated egg laying areas of the dogfish may improve the chances of larvae finding the egg cases during what is presumably a short larval life, and facilitate emigration of juveniles or large specimens to neighbouring capsules. Addisonia enodis Simone, 1996 is considered to be a junior synonym of A. excentrica. The larval shell of A. excentrica is described; it is very similar in shape and sculpture to the larval shell of Lepetella species, but larger. Newly settled specimens start to discard the protoconch at a size smaller than 0.4 mm.

Nauplii, copepodids and adults of a new mesoparasitic genus and species of Chitonophilidae, Lepetellicola brescianii, are described from the pallial cavity of a deepwater cocculiniform limpet, Lepetella sierrai, collected in the Bay of Biscay and Gulf of Cadiz. Re-examination of the type material of the recently established Nucellicolidae revealed several important observational errors in the original description, such as the oversight of the rootlet system in the adult female and misinterpretations of the tagmosis and antennulary segmentation in the late copepodid. Lamb et al.’s (1996) criteria used to justify the familial distinctiveness of the Nucellicolidae are all invalid. The family is relegated to a junior synonym of the Chitonophilidae on the basis of overwhelming support provided by copepodid and adult morphology. The impact of heterochrony on the body plan of adults and developmental stages is discussed. Phylogenetic analysis supports a basal dichotomy dividing the Chitonophilidae into a mesoparasitic clade, utilizing exclusively polyplacophoran hosts, and a sisterclade grouping genera associated with chitons, prosobranch gastropods and cocculiniform limpets. The presence of maxillipeds and postmaxillipedal apodemes in the adult males of the latter clade is considered as apomorphic rather than plesiomorphic, being the result of incomplete moulting and correlated with the ventral position of the genital apertures. Nucellicola is identified as the sistergroup of the only other endoparasitic genus, Tesonesma, found in the body cavity of chitons. The inferred relationships indicate that host switching has occurred twice in the evolution of the Chitonophilidae. Examination of the antennulary segmentation and setation patterns of copepodids in Lepetellicola and Nucellicola unequivocally refutes both the current placement of the Chitonophilidae in the Poecilostomatoida and its alternative assignment to the Siphonostomatoida. Exclusion from the Poecilostomatoida is reinforced by the absence of a coxo-basis in the antenna. The family is placed with the cyclopoids, providing further evidence for the crown-group status of the Poecilostomatoida within the currently paraphyletic Cyclopoida. A critical review of the published reports of brooding in cocculiniform limpets demonstrated that there is, as yet, no tangible evidence for this phenomenon in either the Lepetelloidea or Cocculinoidea. © 2002 The Linnean Society of London, Biological Journal of the Linnean Society, 2002, 75, 187–217.

A 37-year-old woman with a history of undergoing bariatric urgery and a tummy tuck was diagnosed at age 32 as HLA 27 positive and with ankylosing spondylitis and stage IV bilatral sacroiliitis according to the modified New York criteria. She urrently showed no signs of arthritis or enthesitis. She was iniially treated with Etanercept® and Abdalimumab®, but presented ymptoms of peripheral polyneuropathy that were probably secndary to the use of these drugs and which had to be replaced y Abatacept®, with a compassionate care indication in this ase. In March 2010, with the patient undergoing follow-up by the heumatology department, she began with episodes of acute back ain radiating to the ribs, of a mechanical nature and which intenified during the last week appearing even at rest. She had no eurological deficits or any other symptoms. On physical examiation the patient had a modified Schober test of 12.5 cm, a Bath nkylosing Spondylitis Functional Index Index (BASFI) of 1 and a ath Ankylosing Spondylitis Disease Activity Index (BASDAI) of 2.8. one densitometry showed femoral osteopenia (T-score −2.2, Zcore −2.9) but there was no lumbar osteopenia or osteoporosis T-score 0.2, Z-score −0.8). She had not received prior glucocortioid treatment or had other risk factors for osteoporosis.

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