Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis (ATLAS-PPX).

Fitusiran, a subcutaneous (SC) investigational siRNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This Phase 3, open-label study (NCT03549871) evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥ 12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent (BPA)/clotting factor concentrate (CFC) prophylaxis. Participants continued their prior BPA/CFC prophylaxis for 6 months before switching to once-monthly 80 mg fitusiran prophylaxis for 7 months (onset and efficacy periods). Primary endpoint was annualized bleeding rate (ABR) in the BPA/CFC prophylaxis and fitusiran efficacy period. Secondary endpoints included spontaneous ABR (AsBR) and joint ABR (AjBR). Safety and tolerability were assessed. Of 80 enrolled participants, 65 (inhibitor/non-inhibitor, n = 19/46) were eligible for ABR analyses. Observed median (IQR) ABRs were 6.5 (2.2, 19.6)/4.4 (2.2, 8.7) with BPA/CFC prophylaxis versus 0.0 (0.0, 0.0)/0.0 (0.0, 2.7) in the corresponding fitusiran efficacy period. Estimated mean ABRs were substantially reduced with fitusiran by 79.7% (P = 0.0021) and 46.4% (P = 0.0598) versus BPA/CFC prophylaxis, respectively. Forty-one participants (63.1%) experienced zero treated bleeds with fitusiran versus 11 (16.9%) with BPAs/CFCs. Median AsBR and AjBR were both 2.2 with BPA/CFC prophylaxis and 0.0 in the fitusiran efficacy period. Two participants (3.0%) experienced suspected or confirmed thromboembolic events with fitusiran. Once-monthly fitusiran prophylaxis significantly reduced bleeding events versus BPA/CFC prophylaxis in PwHA/B, with or without inhibitors and reported adverse events were generally consistent with previously identified risks of fitusiran.

Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context.

Background: Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge. Objectives: To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction. Design: Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region. Methods: Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up. Results: A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients' expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product's summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. Conclusion: The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.

Implementing gene therapy for hemophilia in the Nordic context Why was this study done? • Despite improvements in hemophilia care, challenges remain including treatment burden and impaired quality of life. • Gene therapy may overcome these challenges. • The introduction of gene therapy presents a challenge in many ways. What did the researchers do? • We, as representatives from six Hemophilia Comprehensive Care Centers in the Nordic region, sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri- and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, plus follow-up. What did the researchers find? • We developed a gene therapy transit map and identified key stakeholders. • The approach to prepare the vector will differ between the Nordic centers, but the pharmacy unit will be a key stakeholder. We therefore developed a pharmacy checklist for the implementation of gene therapy. • For the future, Advanced Therapy Medicinal Product centers will be implemented. • Patients' expectations, commitments and concerns need to be addressed repeatedly. • Education of patients and the expanded health care professionals team will be the key to successful and optimal clinical management. • Eligibility testing according to the product's summary of product characteristics and close follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. • Access to both chromogenic and one-stage factor activity assay results from a specialized coagulation laboratory with a short turn-around time is important. What do the findings mean? • The approach to delivering gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation will be applicable to all. • The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.

Inspection and maintenance of industrial infrastructure with autonomous underwater robots.

Underwater infrastructure, such as pipelines, requires regular inspection and maintenance including cleaning, welding of defects and valve-turning or hot-stabbing. At the moment, these tasks are mostly performed by divers and Remotely Operated Vehicles (ROVs) but the use of intervention Autonomous Underwater Vehicles (intervention-AUVs) can greatly reduce operation time, risk, and cost. However, autonomous underwater manipulation has not yet reached a high technological readiness and is an intensively researched topic. This review identifies key requirements based on necessary inspection and maintenance methods, linking them to the current technology and deriving major challenges which need to be addressed in development. These include the handling of tools, where a separation between handheld and mounted tools is detected in already employed underwater intervention vehicles such as the Sabertooth by Saab Seaeye or the Aquanaut by Nauticus robotics, two vehicles capable of semi-autonomous intervention. The main challenge identified concerns high level autonomy, i.e., the process of decision-making. This process includes detecting the correct point of interest, maximizing the workspace of the manipulator, planning the manipulation considering required forces, and monitoring the progress to allow for corrections and high quality results. In order to overcome these issues, reliable close range sensing and precise end point navigation is needed. By identifying these persisting challenges, the paper provides inspiration for further development directions in the field of autonomous underwater intervention.

Gene Therapy with Etranacogene Dezaparvovec for Hemophilia B.

BACKGROUND: Moderate-to-severe hemophilia B is treated with lifelong, continuous coagulation factor IX replacement to prevent bleeding. Gene therapy for hemophilia B aims to establish sustained factor IX activity, thereby protecting against bleeding without burdensome factor IX replacement. METHODS: In this open-label, phase 3 study, after a lead-in period (≥6 months) of factor IX prophylaxis, we administered one infusion of adeno-associated virus 5 (AAV5) vector expressing the Padua factor IX variant (etranacogene dezaparvovec; 2×1013 genome copies per kilogram of body weight) to 54 men with hemophilia B (factor IX activity ≤2% of the normal value) regardless of preexisting AAV5 neutralizing antibodies. The primary end point was the annualized bleeding rate, evaluated in a noninferiority analysis comparing the rate during months 7 through 18 after etranacogene dezaparvovec treatment with the rate during the lead-in period. Noninferiority of etranacogene dezaparvovec was defined as an upper limit of the two-sided 95% Wald confidence interval of the annualized bleeding rate ratio that was less than the noninferiority margin of 1.8. Superiority, additional efficacy measures, and safety were also assessed. RESULTS: The annualized bleeding rate decreased from 4.19 (95% confidence interval [CI], 3.22 to 5.45) during the lead-in period to 1.51 (95% CI, 0.81 to 2.82) during months 7 through 18 after treatment, for a rate ratio of 0.36 (95% Wald CI, 0.20 to 0.64; P<0.001), demonstrating noninferiority and superiority of etranacogene dezaparvovec as compared with factor IX prophylaxis. Factor IX activity had increased from baseline by a least-squares mean of 36.2 percentage points (95% CI, 31.4 to 41.0) at 6 months and 34.3 percentage points (95% CI, 29.5 to 39.1) at 18 months after treatment, and usage of factor IX concentrate decreased by a mean of 248,825 IU per year per participant in the post-treatment period (P<0.001 for all three comparisons). Benefits and safety were observed in participants with predose AAV5 neutralizing antibody titers of less than 700. No treatment-related serious adverse events occurred. CONCLUSIONS: Etranacogene dezaparvovec gene therapy was superior to prophylactic factor IX with respect to the annualized bleeding rate, and it had a favorable safety profile. (Funded by uniQure and CSL Behring; HOPE-B ClinicalTrials.gov number, NCT03569891.).

Prostatic artery embolization in men with severe hemophilia a: a case report of two patients.

BACKGROUND: This is the first case report describing the peri- and postoperative hemostasis plans in two men with severe hemophilia A (HA) who underwent prostatic artery embolization (PAE) for symptomatic benign prostatic hyperplasia (BPH). CASE PRESENTATION: Two patients with severe HA and lower urinary tract symptoms (LUTS) not responding to medical therapy underwent PAE at our institution. In both patients, intermittent administration of decreasing doses of extended half-life recombinant factor VIII (EHL rFVIII) concentrate from 30 min before to 7 days after the PAE resulted in good hemostatic control. In addition to EHL rFVIII, tranexamic acid was administered in the same timeframe to augment the action of EHL rFVIII and to account for possible mucosal bleeding from the urinary tract. Both patients reported a minor localized hematoma at the femoral puncture site in the right groin, that resolved spontaneously. No other bleeding complications were observed. CONCLUSIONS: The procoagulant effects of the chosen dosing of EHL rFVIII showed sufficient to perform a technically successful embolization. At 6 months follow-up, both patients had significant reduction in self-reported urinary symptoms and were content with the outcome.

A national Danish proof of concept on feasibility and safety of home -based intensive chemotherapy in patients with acute myeloid leukemia.

Technological advances have made it possible to offer home-based chemotherapy to patients without health care professionals being present. Prior studies on effects of home-based treatment lack inclusion of patients with hematologic malignancies. We present data from a multicenter single-arm feasibility and safety study of home-based intensive chemotherapy in patients with newly diagnosed acute myeloid leukemia and their quality of life and psychological wellbeing. This national study included patients from six sites in Denmark who received intensive chemotherapy on programmed CADD Solis infusion pumps through a central venous catheter and were also managed as outpatients during treatment-induced pancytopenia. Data are presented from 104 patients, receiving 272 treatments with 1.096 (mean 4.57, SD 3.0) home infusion days out of 1.644 treatment days (67 %). Sixty-two of 168 (36.9 %) reinduction and consolidation treatment cycles ensuing pancytopenia phases were solely handled in the outpatient clinic. Patients reported high satisfaction with home-based treatment, which had a positive influence on their ability to be involved in their treatment and be socially and physically active. No unexpected events occurred during the intervention. Overall, patients improved in all quality of life outcomes over time. Home-based intensive chemotherapy treatment was feasible and safe in this population. ClinicalTrials.gov identifier: NCT04904211.

[SARS-CoV-2 vaccine-induced immune thrombosis and thrombocytopenia].

Vaccine-induced immune thrombosis and thrombocytopenia (VITT) is a new syndrome, which has emerged after introduction of the adenovirus vector-based COVID-19 vaccines ChAdOx1 nCoV-19 og Ad26.COV2-SVITT is characterised by venous thrombosis at unusual, and often multiple localisations, especially including cerebral venous sinus thrombosis. Besides, bleeding manifestations often occur. Biochemically, VITT is characterised by thrombocytopaenia and elevated fibrin d-dimer. VITT is a rapidly progressing and potentially life-threatening syndrome where rapid diagnosis and treatment are essential as argued in this review.

A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2.

Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual. A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism. Although causality has not been established, our case emphasizes the importance of clinical awareness. Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.

Increments in DNA-thioguanine level during thiopurine-enhanced maintenance therapy of acute lymphoblastic leukemia.

Maintenance therapy containing methotrexate and 6-mercapto - purine is essential to cure acute lymphoblastic leukemia (ALL). Cytotoxicity is elicited by incorporation of thioguanine nucleotides into DNA (DNA-TG), and higher leukocyte DNA-TG is associated with increased relapse-free survival. As 6-thioguanine provides 6- fold higher cytosolic levels of thioguanine nucleotides than does 6- mercapto purine, we added low-dose 6-thioguanine to methotrexate/6- mercapto purine maintenance therapy to explore if this combination results in significantly higher DNA-TG. The target population of the "Thiopurine Enhanced ALL Maintenance therapy" (TEAM) study was 30 patients with non-high-risk ALL, aged 1-45 years on methotrexate/6-mercaptopurine maintenance therapy receiving no other systemic chemotherapy. Incremental doses of 6-thioguanine were added to methotrexate/6-mercaptopurine maintenance therapy (starting 6-thioguanine dose: 2.5 mg/m2/day, maximum: 12.5 mg/m2/day). The primary endpoint was DNA-TG increments. Thirty-four patients were included, and 30 patients completed maintenance therapy according to the TEAM strategy. Of these 30 patients, 26 (87%) tolerated 10.0-12.5 mg/m2/day as the maximum 6-thioguanine dose. TEAM resulted in significantly higher DNA-TG levels compared to those in both TEAM patients before their inclusion in TEAM (on average 251 fmol/mg DNA higher [95% confidence interval: 160-341; P<0.0001]), and with historical patients receiving standard methotrexate/6-mercapto - purine maintenance therapy (on average 272 fmol/mg DNA higher [95% confidence interval: 147-398; P<0.0001]). TEAM did not increase myelotoxicity or hepatotoxicity. In conclusion, TEAM is an innovative and feasible approach to improve maintenance therapy and results in higher DNA-TG levels without inducing additional toxicity. It may therefore be an effective strategy to reduce the risk of ALL relapse through increased DNA-TG. This will be tested in a randomized ALLTogether-1 substudy.

[Work-up of thrombophilia].

The number of thrombophilia investigations has been steadily increasing over the past decade. However, it is debatable to what extent treatment of thromboembolic events is further qualified by thrombophilia investigations. Based of the most recent literature as well as international and national expert opinions, this review provides a status on the frequency and severity of inherited and acquired thrombophilia, discusses indication for thrombophilia assessment, states the analyses to be included in the test panel, and the clinical implications that presence of thrombophilia may have.

Histiocytic Sarcoma: Challenging Course, Dismal Outcome.

Histiocytic sarcoma (HS) is a rare hematopoietic neoplasm derived from non-Langerhans histiocytic cells of the monocyte/macrophage system. With an incidence of 0.17/million individuals and a slight male preference, HS presents with a wide age distribution. Most commonly, it occurs as a primary malignancy. In approximately 25% of the cases a presumed transdifferentiation of a preexisting hematolymphoid disorder can be demonstrated. The clinical presentation varies from a localized solitary mass to severe disseminated disease often with extranodal involvement including skin, soft tissue, the gastrointestinal tract and the hematopoietic system. Systemic symptoms in terms of weight loss, fever and night sweats often occur. The diagnostic work-up of HS is extremely challenging due to the rarity of the disease as well as a wide differential diagnosis in terms of a histologic overlap with diverse mimics. No standardized treatment for HS exists and especially in a disseminated disease the clinical course is overly aggressive with a dismal outcome. The median overall survival from the time of diagnosis is approximately six months. We report a 43-year-old previously healthy Caucasian male admitted to our hospitals with abdominal pain and a feeling of fatigue. We demonstrate both the challenges of a correct diagnosis and an effective treatment as well as the aggressive nature of histiocytic sarcoma.

Introduction of a Comprehensive Diagnostic and Interdisciplinary Management Approach in Haematological Patients with Mucormycosis: A Pre and Post-Intervention Analysis.

Mucormycosis is a life threatening infection in patients with haematological disease. We introduced a Mucorales-PCR and an aggressive, multidisciplinary management approach for mucormycosis during 2016-2017 and evaluated patient outcomes in 13 patients diagnosed and treated in 2012-2019. Management principle: repeated surgical debridement until biopsies from the resection margins were clean as defined by negative Blankophor microscopy, Mucorales-PCR (both reported within 24 h), and cultures. Cultured isolates underwent EUCAST E.Def 9.3.1 susceptibility testing. Antifungal therapy (AFT) (mono/combination) combined with topical AFT (when possible) was given according to the minimal inhibitory concentration (MIC), severity of the infection, and for azoles, specifically, it was guided by therapeutic drug monitoring. The outcome was evaluated by case record review. All patients underwent surgery guided by diagnostic biopsies from tissue and resection margins (195 samples in total). Comparing 2012-2015 and 2016-2019, the median number of patients of surgical debridements was 3 and 2.5 and of diagnostic samples: microscopy/culture/PCR was 3/3/6 and 10.5/10/10.5, respectively. The sensitivity of microscopy (76%) and Mucorales-PCR (70%) were similar and microscopy was superior to that of culture (53%; p = 0.039). Initial systemic AFT was liposomal amphotericin B (n = 12) or posaconazole (n = 1) given as monotherapy (n = 4) or in combination with isavuconazole/posaconazole (n = 3/6) and terbinafine (n = 3). Nine patients received topical amphotericin B. All received isavuconazole or posaconazole consolidation therapy (n = 13). Mucormycosis related six month mortality was 3/5 in 2012-2015 and 0/7 patients in 2016-2019 (one patient was lost for follow-up). Implementation of combination therapy (systemic+topical AFT/combination systemic AFT) and aggressive surgical debridement guided by optimised diagnostic tests may improve the outcome of mucormycosis in haematologic patients.

[Venous thromboembolism in patients with COVID-19].

The importance of venous thromboembolism (VTE) as a major complication in patients with severe corona virus disease 2019 (COVID-19) is becoming increasingly evident. In this review, we describe the proposed pathophysiology of the prothrombotic coagulation changes observed in patients with COVID-19. Further, based on a review of the currently available evidence on VTE prevalence in patients with COVID-19, we present and discuss the recommendations from the Danish Society of Thrombosis and Haemostasis on the use of thromboprophylaxis in patients with COVID-19.

Ruminococcus gnavus bacteraemia in a patient with multiple haematological malignancies.

We present a case of Ruminococcus gnavus sepsis in a woman suffering from multiple myeloma and myelodysplastic syndrome. R. gnavus , a Gram-positive coccus and a gut commensal, has been described in nine cases of infection in the literature, with most infections having occurred in patients with either gastrointestinal symptoms or prosthesis infections. In this case, R gnavus was identified by mass spectrometry, and showed susceptibility to penicillin, meropenem, tetracycline, metronidazole and clindamycin. The patient was successfully treated initially with intravenous piperacillin/tazobactam and metronidazole, and then switched to oral penicillin and metronidazole. The cause of infection is hypothesized to have been a shift in the gut microbiota towards an excess growth of R. gnavus caused by immunosuppression, and bacterial translocation across a vulnerable mucosal barrier due to prednisolone treatment and severe thrombocytopenia.

Systematic patient involvement for homebased outpatient administration of complex chemotherapy in acute leukemia and lymphoma.

Based on experience with comprehensive patient involvement, we present data from implementation of portable, programmable infusion pumps (PPP) for home-based chemotherapy administration in patients with acute leukaemia and in lymphoma patients receiving (carmustine, etoposide, cytarabine, melphalan) BEAM regimen. Data from 84 patients, receiving 177 cycles of PPP administered chemotherapy, showed convincing safety with minor equipment errors encountered and with high patient satisfaction. In-hospital days could be reduced with 52% out of a total of 1197 treatment days. Homebased PPP has several advantages from a patient perspective and furthermore frees up in-hospital beds for patients in need of them.

Transfusion transmission of hepatitis A virus with fecal shedding in a previously hepatitis A vaccinated recipient.

We describe a rare case of hepatitis A virus (HAV) replication in feces despite presence of hepatitis A antibodies in an acute myeloid leukemia (AML) patient after transfusion with HAV contaminated platelets. The patient has been vaccinated against HAV years before the AML diagnosis. Transient infection and reshedding should thus be considered in antibody-positive hematological patients. Transfusion associated HAV transmission is rare, and little evidence exists on the clinical consequences and possible effect of treatment with immunoglobulin. Further reporting on fecal shedding despite antibodies are needed, as HAV antibody levels are used as course of action for post-exposure prophylaxis and infection control.

Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B.

Gene therapy for hemophilia B aims to ameliorate bleeding risk and provide endogenous factor IX (FIX) activity/synthesis through a single treatment, eliminating the requirement for FIX concentrate. AMT-060 combines an adeno-associated virus-5 (AAV5) vector with a liver-specific promoter driving expression of a codon-optimized wild-type human FIX gene. This multinational, open-label study included 10 adults with hemophilia B (FIX ≤2% of normal) and severe-bleeding phenotype. No participants tested positive for AAV5-neutralizing antibodies using a green-fluorescent protein-based assay, and all 10 were enrolled. A single dose of 5 × 1012 or 2 × 1013 genome copies of AMT-060/kilogram was administered to 5 participants each. In the low-dose cohort, mean endogenous FIX activity increased to 4.4 IU/dL. Annualized FIX use was reduced by 81%, and mean annualized spontaneous bleeding rate (ASBR) decreased from 9.8% to 4.6% (53%). In the higher-dose cohort, mean FIX activity increased to 6.9 IU/dL. Annualized FIX use decreased by 73%, and mean ASBR declined from 3.0 to 0.9 (70%). There was no reduction in traumatic bleeds. FIX activity was stable in both cohorts, and 8 of 9 participants receiving FIX at study entry stopped prophylaxis. Limited, asymptomatic, and transient alanine aminotransferase elevations in the low-dose (n = 1) and higher-dose (n = 2) cohorts were treated with prednisolone. No decrease in FIX activity or capsid-specific T-cell responses were detected during transaminase elevations. A single infusion of AMT-060 had a positive safety profile and resulted in stable and clinically important increases in FIX activity, a marked reduction in spontaneous bleeds and FIX concentrate use, without detectable cellular immune responses against capsids. This trial was registered at www.clinicaltrials.gov as #NCT02396342; EudraCT #2013-005579-42.

Application of whole-exome sequencing to direct the specific functional testing and diagnosis of rare inherited bleeding disorders in patients from the Öresund Region, Scandinavia.

Rare inherited bleeding disorders (IBD) are a common cause of bleeding tendency. To ensure a correct diagnosis, specialized laboratory analyses are necessary. This study reports the results of an upfront diagnostic strategy using targeted whole exome sequencing. In total, 156 patients with a significant bleeding assessment tool score participated in the study, of which a third had thrombocytopenia. Eighty-seven genes specifically associated with genetic predisposition to bleeding were analysed by whole exome sequencing. Variants were classified according to the five-tier scheme. We identified 353 germline variants. Eight patients (5%) harboured a known pathogenic variant. Of the 345 previously unknown variants, computational analyses predicted 99 to be significant. Further filtration according to the Mendelian inheritance pattern, resulted in 59 variants being predicted to be clinically significant. Moreover, 34% (20/59) were assigned as novel class 4 or 5 variants upon targeted functional testing. A class 4 or 5 variant was identified in 30% of patients with thrombocytopenia (14/47) versus 11% of patients with a normal platelet count (12/109) (P < 0·01). An IBD diagnosis has a major clinical impact. The genetic investigations detailed here extricated our patients from a diagnostic conundrum, thus demonstrating that continuous optimization of the diagnostic work-up of IBD is of great benefit.

Integration of fiber-optic sensor arrays into a multi-modal tactile sensor processing system for robotic end-effectors.

With the increasing complexity of robotic missions and the development towards long-term autonomous systems, the need for multi-modal sensing of the environment increases. Until now, the use of tactile sensor systems has been mostly based on sensing one modality of forces in the robotic end-effector. The use of a multi-modal tactile sensory system is motivated, which combines static and dynamic force sensor arrays together with an absolute force measurement system. This publication is focused on the development of a compact sensor interface for a fiber-optic sensor array, as optic measurement principles tend to have a bulky interface. Mechanical, electrical and software approaches are combined to realize an integrated structure that provides decentralized data pre-processing of the tactile measurements. Local behaviors are implemented using this setup to show the effectiveness of this approach.