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We present a patient with an aortic aneurysm and the epidemiology, etiology, screening, symptoms and therapeutic options of abdominal aortic aneurysms are discussed. A widening of the abdominal aorta >3 cm is termed aortic aneurysm. As patients with aortic aneurysm are mostly oligosymptomatic until rupture occurs and an estimated 30'000 patients annually die from ruptured aortic aneurysm in the US a screening of the population at greatest risk (smokers, familial predisposition) is recommended. Screening is best done by ultrasound. Noninvasive therapy is limited to antiplatelet therapy and optimal adjustment of risk factors. For definitive treatment endovascular aortic repair (EVAR) is considered an established alternative to open surgery with lower 30 daysmortality but higher reintervention rate. [ABSTRACT FROM AUTHOR]

Travel-related venous thromboembolism( VTE) is probably less frequent than previously suspected and becomes relevant when a flight lasts eight hours or more. Usually, general measures such as avoiding constrictive clothing or dehydration and doing gymnastics and walking around in the cabin are sufficient for preventing VTE. Compression stockings can be recommended when risk factors for VTE are present. Low molecular weight heparins in prophylactic dosage should be considered after previous VTE. [ABSTRACT FROM AUTHOR]

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The article discusses a case study of a 24-year-old Caucasian woman with a history of painful lesions on the fingertips and subungual haemorrhages. The diagnosis of secondary antiphospholipid syndrome (APS) was made after the patient underwent several diagnostic procedures such as capillary microscopy of the nail and dilute Russell viper venom time (DRVVT) screening and confirmation test. The researchers based their diagnosis on a systemic lupus erythematosus (SLE) predisposition.

Immune thrombotic thrombocytopenic purpura (iTTP) is a rare and potentially life-threatening disorder. Treatment advances have lowered morbidity rates, but past acute events can still cause long-term consequences, reducing health-related quality of life (HRQoL) and determining cognitive impairment, anxiety, and depression. We aimed to investigate these aspects and the role of caplacizumab and rituximab: 39 patients were evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), the FACIT-Fatigue, the Hospital Anxiety and Depression Scale, and the Functional Assessment in Cancer Therapy-Cognitive Function questionnaires. The median age at study inclusion was 50 years (IQR 38-60), and the median follow-up from diagnosis was 97 months (IQR 14-182); 82% of patients were female, and 36% had one or more recurrences. Caplacizumab was administered in 16 patients (41%), as well as rituximab. ITTP patients reported lower physical and mental HRQoL scores than the general population. No differences in physical or mental domains were observed between patients treated or not with caplacizumab, while those who received rituximab reported lower scores in mental health. Neurological impairment at diagnosis correlated with worse fatigue. The majority of patients (72%) reported anxiety or depression (82%). ITTP had a significant impact on the long-term cognitive function, fatigue, depression, and anxiety levels of patients, with a negative effect on their HRQoL. Our findings underscore the need to pay special attention to patients' long-term physical and mental health, regardless of the medical treatments received., (© 2024. The Author(s).)

Objectives: We aimed to investigate the association between financial toxicity (FT) and the health-related quality of life profile of long-term survivors of acute promyelocytic leukaemia (APL) treated within a universal healthcare system., Methods: We evaluated FT using the financial difficulties item of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). We also compared the prevalence of clinically important problems and symptoms between the survivors of APL with or without FT, using evidence-based thresholds for the EORTC QLQ-C30. A multivariable logistic regression analysis was performed to explore potential risk factors associated with FT., Results: Overall, 352 long-term survivors of APL, with a median age of 53.9 years and a median time since diagnosis of 12.2 years, were analysed. Of these, 71 (20.2%) reported having FT. The prevalence of clinically important problems and symptoms was generally higher across most EORTC QLQ-C30 scales for those survivors who reported FT. The three largest differences between patients with and without FT were observed for emotional functioning (+35.4 percentage points), dyspnoea (+33.1 percentage points) and physical functioning (+27.0 percentage points). The presence of FT was independently associated with having comorbidities and not receiving a salary/pension., Conclusions: These findings suggest that even many years after being diagnosed, one-fifth of long-term survivors of APL experience FT. Interventions to assist with employment may be critical to minimise the risk of FT in the most vulnerable survivors., Competing Interests: Competing interests: AV: research funding from Jazz Pharmaceuticals; consultancy for Amgen, Servier, AstraZeneca, Pfizer, Kyte-Gilead, Abbvie, Janssen, Astellas, Astex, Otzuka, Stemline Menarini, BMS, Glycostem, Novartis and Delbert; all outside the submitted work. MV: Honoraria from Amgen, Incyte, Novartis, Dephaforum Srl, Abbvie and Astrazeneca; advisory board for Amgen; all outside the submitted work. FE: consultancy or advisory role for AbbVie, Incyte, Syros, Novartis and JAZZ Pharmaceuticals; all outside the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Somatic hypermutation status of the IGHV gene is essential for treating patients with chronic lymphocytic leukemia/small lymphocytic lymphoma. Unlike the conventional low-throughput method, assessment of somatic hypermutation by next-generation sequencing (NGS) has potential for uniformity and scalability. However, it lacks standardization or guidelines for routine clinical use. We critically assessed the performance of an amplicon-based NGS assay across 458 samples. Using a validation cohort (35 samples), the comparison of two platforms (Ion Torrent versus Illumina) and two primer sets [leader versus framework region 1 (FR1)] in their ability to identify clonotypic IGHV rearrangement(s) revealed 97% concordance. The mutation rates were identical by both platforms when using the same primer set (FR1), whereas a slight overestimation bias (+0.326%) was found when comparing FR1 with leader primers. However, for nearly all patients this did not affect the stratification into mutated or unmutated categories, suggesting that use of FR1 may provide comparable results if leader sequencing is not available and allowing for a simpler NGS laboratory workflow. In routine clinical practice (423 samples), the productive rearrangement was successfully detected by either primer set (leader, 97.7%; FR1, 94.7%), and a combination of both in problematic cases reduced the failure rate to 1.2%. Higher sensitivity of the NGS-based analysis also detected a higher frequency of double IGHV rearrangements (19.1%) compared with traditional approaches., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective. Muscle activation patterns in the muscle-to-force null space, i.e. patterns that do not generate task-relevant forces, may provide an opportunity for motor augmentation by allowing to control additional end-effectors simultaneously to natural limbs. Here we tested the feasibility of muscular null space control for augmentation by assessing simultaneous control of natural and extra degrees of freedom. Approach. We instructed eight participants to control translation and rotation of a virtual 3D end-effector by simultaneous generation of isometric force at the hand and null space activity extracted in real-time from the electromyographic signals recorded from 15 shoulder and arm muscles. First, we identified the null space components that each participant could control more naturally by voluntary co-contraction. Then, participants performed several blocks of a reaching and holding task. They displaced an ellipsoidal cursor to reach one of nine targets by generating force, and simultaneously rotated the cursor to match the target orientation by activating null space components. We developed an information-theoretic metric, an index of difficulty defined as the sum of a spatial and a temporal term, to assess individual null space control ability for both reaching and holding. Main results. On average, participants could reach the targets in most trials already in the first block (72%) and they improved with practice (maximum 93%) but holding performance remained lower (maximum 43%). As there was a high inter-individual variability in performance, we performed a simulation with different spatial and temporal task conditions to estimate those for which each individual participants would have performed best. Significance. Muscular null space control is feasible and may be used to control additional virtual or robotics end-effectors. However, decoding of motor commands must be optimized according to individual null space control ability., (© 2022 IOP Publishing Ltd.)

This work presents a novel technique to control multi-functional hand for robot-assisted laparoscopic surgery. We tested the technique using the MUSHA multi-functional hand, a robot-aided minimally invasive surgery tool with more degrees of freedom than the standard commercial end-effector of the da Vinci robot. Extra degrees of freedom require the development of a proper control strategy to guarantee high performance and avoid an increasing complexity of control consoles. However, developing reliable control algorithms while reducing the control side's mechanical complexity is still an open challenge. In the proposed solution, we present a control strategy that projects the human hand motions into the robot actuation space. The human hand motions are tracked by a LeapMotion camera and mapped into the actuation space of the virtualized end-effector. The effectiveness of the proposed method was evaluated in a twofold manner. Firstly, we verified the Lyapunov stability of the algorithm, then an user study with 10 subjects assessed the intuitiveness and usability of the system., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ficuciello, Villani, Lisini Baldi and Prattichizzo.)

It is likely that when using an artificially augmented hand with six fingers, the natural five plus a robotic one, corticospinal motor synergies controlling grasping actions might be different. However, no direct neurophysiological evidence for this reasonable assumption is available yet. We used transcranial magnetic stimulation of the primary motor cortex to directly address this issue during motor imagery of objects' grasping actions performed with or without the Soft Sixth Finger (SSF). The SSF is a wearable robotic additional thumb patented for helping patients with hand paresis and inherent loss of thumb opposition abilities. To this aim, we capitalized from the solid notion that neural circuits and mechanisms underlying motor imagery overlap those of physiological voluntary actions. After a few minutes of training, healthy humans wearing the SSF rapidly reshaped the pattern of corticospinal outputs towards forearm and hand muscles governing imagined grasping actions of different objects, suggesting the possibility that the extra finger might rapidly be encoded into the user's body schema, which is integral part of the frontal-parietal grasping network. Such neural signatures might explain how the motor system of human beings is open to very quickly welcoming emerging augmentative bioartificial corticospinal grasping strategies. Such an ability might represent the functional substrate of a final common pathway the brain might count on towards new interactions with the surrounding objects within the peripersonal space. Findings provide a neurophysiological framework for implementing augmentative robotic tools in humans and for the exploitation of the SSF in conceptually new rehabilitation settings., (© 2021. The Author(s).)

Circulating cell-free DNA from blood plasma of cancer patients can be used to non-invasively interrogate somatic tumor alterations. Here we develop MSK-ACCESS (Memorial Sloan Kettering - Analysis of Circulating cfDNA to Examine Somatic Status), an NGS assay for detection of very low frequency somatic alterations in 129 genes. Analytical validation demonstrated 92% sensitivity in de-novo mutation calling down to 0.5% allele frequency and 99% for a priori mutation profiling. To evaluate the performance of MSK-ACCESS, we report results from 681 prospective blood samples that underwent clinical analysis to guide patient management. Somatic alterations are detected in 73% of the samples, 56% of which have clinically actionable alterations. The utilization of matched normal sequencing allows retention of somatic alterations while removing over 10,000 germline and clonal hematopoiesis variants. Our experience illustrates the importance of analyzing matched normal samples when interpreting cfDNA results and highlights the importance of cfDNA as a genomic profiling source for cancer patients.

Objective:  In patients with cancer-associated venous thromboembolism (VTE), the risk of recurrence is similar after incidental and symptomatic events. It is unknown whether the same applies to incidental VTE not associated with cancer., Methods and Results:  We compared baseline characteristics, anticoagulation therapy, all-cause mortality, and VTE recurrence rates at 90 days between patients with incidental ( n  = 131; 52% without cancer) and symptomatic ( n  = 1,931) VTE included in the SWIss Venous ThromboEmbolism Registry (SWIVTER). After incidental VTE, 114 (87%) patients received anticoagulation therapy for at least 3 months. The mortality rate was 9.2% after incidental and 8.4% after symptomatic VTE for hazard ratio (HR) 1.10 (95% confidence interval [CI] 0.49-2.50). After adjustment for competing risk of death, recurrence rate was 3.1 versus 2.8%, respectively, for sub-HR 1.07 (95% CI 0.39-2.93). These results were consistent among cancer (mortality: 15.9% vs. 12.6%; HR 1.32, 95% CI 0.67-2.59; recurrence: 4.8% vs. 4.7%; HR 1.02, 95% CI 0.30-3.42) and noncancer patients (mortality: 2.9% vs. 2.1%; HR 1.37, 95% CI 0.33-5.73; recurrence: 1.5% vs. 2.3%; HR 0.63, 95% CI 0.09-4.58). Patients with incidental VTE who received anticoagulation therapy for at least 3 months had lower mortality (4% vs. 41%) and recurrence rate (1% vs. 18%) compared with those who did not., Conclusion:  In SWIVTER, more than half of incidental VTE events occurred in noncancer patients who often received anticoagulation therapy. Among noncancer patients, early mortality and recurrence rates were similar after incidental versus symptomatic VTE. Our findings suggest that anticoagulation therapy for incidental VTE may be beneficial regardless of the presence of cancer., Competing Interests: D.S. is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland. S.B. reports personal fees from BTG Pharmaceuticals and Leo Pharma, personal fees and nonfinancial support from Bayer HealthCare, and nonfinancial support from Daiichi-Sankyo, outside the submitted work. J.H.B. reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation, grants and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Daiichi-Sankyo, outside the submitted work. R.P.E. reports personal fees from Bayer, Daiichi-Sankyo, and Sanofi-Aventis, outside the submitted work. W.K. reports personal fees and nonfinancial support from Bayer, Pfizer, Shire/Takeda, Roche, Daiichi-Sankyo, and Novo Nordisk, outside the submitted work. M.H. reports personal fees from Sanofi-Aventis, Daiichi-Sankyo, and Bayer, outside the submitted work. N.K. reports personal fees from Bayer, Boston Scientific, Optimed, Bard, and BTG, outside the submitted work., (Thieme. All rights reserved.)

Background and Objective: In a proof-of-concept study, we aimed to verify whether the wearable haptic anklets, a device that delivers personalized suprathreshold alternating exteroceptive stimulation at the anklets on demand, may improve the quality of walking, including the freezing of gate (FOG), in idiopathic Parkinson's disease (PD) patients. The clinical relevance of the presented device as a walking pacemaker to compensate the disturbed locomotion through the generation of a more physiological internal walking rhythm should be verified in a dedicated clinical trial., Methods: We tested 15 patients diagnosed as idiopathic PD, during their regular treatment regimen. Patients were evaluated during walking with the device switched on and off, personalized at their most comfortable cadence. Stride velocity, variance, and length, as well as FOG episode duration during walking or turning of 180°, were quantified by an optical high-performance motion capture VICON system., Results: The alternating, rhythmic, sensory stimulation significantly improved either walking velocity or reduced inter-stride variance. Effects were more variable on stride length. The significant reduction of FOG episodes' duration correlated with clinical severity of scales rating gate and balance. No safety problems occurred., Conclusions: The WEARHAP-PD device, whose Technology Readiness Level (TRL) is 6, significantly improved some walking abilities (walking velocity and stride variance) and reduced the duration of FOG episodes in idiopathic PD patients. Unlike the traditional auditory and visual explicit cues that require the user's allocation of attention for correct functioning, the interaction of the patients with the surrounding environment was preserved, due to the likely implicit processing of haptic stimuli.

Renal impairment (RI) has increased substantially over the last decades. In the absence of data from confirmatory research, real-life data on anticoagulation treatment and clinical outcomes of venous thromboembolism (VTE) in patients with RI are needed. In the SWIss Venous ThromboEmbolism Registry (SWIVTER), 2,062 consecutive patients with objectively confirmed VTE were enrolled. In the present analysis, we compared characteristics, initial and maintenance anticoagulation, and adjusted 90-day clinical outcomes of those with (defined as estimated creatinine clearance < 30 mL/min) and without severe RI. Overall, 240 (12%) patients had severe RI; they were older, and more frequently had chronic and acute comorbidities. VTE severity was similar between patients with and without severe RI. Initial anticoagulation in patients with severe RI was more often performed with unfractionated heparin (44 vs. 24%), and less often with low-molecular-weight heparin (LMWH) (52 vs. 61%) and direct oral anticoagulants (DOACs; 4 vs. 12%). Maintenance anticoagulation in patients with severe RI was more frequently managed with vitamin K antagonists (70 vs. 60%) and less frequently with DOAC (12 vs. 21%). Severe RI was associated with increased risk of 90-day mortality (9.2 vs. 4.2%, hazard ratio [HR]: 2.27, 95% confidence interval [CI]: 1.41-3.65), but with similar risk of recurrent VTE (3.3 vs. 2.8%, HR: 1.19, 95% CI: 0.57-2.52) and major bleeding (2.1 vs. 2.0%, HR: 1.05, 95% CI: 0.41-2.68). In patients with severe RI, the use of LMWH versus any other treatment was associated with reduced mortality (HR: 0.37; 95% CI: 0.14-0.94; p  = 0.036) and similar rate of major bleeding (HR: 0.59, 95% CI: 0.17-2.00; p  = 0.39). Acute or chronic comorbidities rather than VTE severity or recurrence may explain increased early mortality in patients with severe RI. The higher rate of VTE recurrence, specifically fatal events, than major bleeding reinforces the need for effective anticoagulation in VTE patients with severe RI., Competing Interests: D.S. is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland. J.H.B. reports grants from the Swiss National Science Foundation and the Swiss Heart Foundation, grants and personal fees from Boehringer Ingelheim, Pfizer, Bayer, and Daiichi Sankyo, outside the submitted work. R.P.E. reports personal fees from Bayer and Sanofi-Aventis, outside the submitted work. W.K. reports personal fees and nonfinancial support from Bayer, Pfizer, Shire/Takeda, Roche, Daiichi Sankyo, and Novo Nordisk, outside the submitted work. M.H. reports personal fees from Sanofi-Aventis, Daiichi Sankyo, and Bayer, outside the submitted work., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Immunoglobulin heavy chain (IGH) clonality testing by next-generation sequencing (NGS) offers unique advantages over current low-throughput methods in the assessment of B-cell lineage neoplasms. Clinical use remains limited because assays are not standardized and validation/implementation guidelines are not yet developed. Herein, we describe our clinical validation and implementation of NGS IGH clonality testing and summarize our experience based on extensive routine use. NGS-based clonality testing targeting IGH FR1, FR2, FR3, and the conserved leader sequence upstream of FR1 was validated using commercially available kits. Data were analyzed by commercial and in-house-developed bioinformatics pipelines. Performance characteristics were evaluated directly comparing with capillary electrophoresis (CE) assays (BIOMED-2 primers). Assays were monitored after implementation (>1.5 years), concurrently testing by CE methods. A total of 1189 clinical samples were studied (94 validation, 1095 postimplementation). NGS showed superior performance compared with CE assays. For initial assessment, clonality detection rate was >97% for all malignancy types. Concordance with CE was 96%; discordances were related to higher sensitivity/resolution of NGS and improved detection in cases with high somatic hypermutation. Routine NGS clonality assessment is feasible and superior to existing assays, enabling accurate and specific index clone assessment and future tracking of all rearrangements in a patient sample. Successful implementation requires new standardization, validation, and implementation processes, which should be performed as a multicenter and multidisciplinary collaboration., (Copyright © 2019 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interest: Dr. Spirk is an employee of Sanofi-Aventis (Suisse) SA, Vernier, Switzerland.