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Obesity as a Predictor for Pulmonary Embolism and Performance of the Age-Adjusted D-Dimer Strategy in Obese Patients with Suspected Pulmonary Embolism.
INTRODUCTION
Obesity is a risk factor for venous thromboembolism, but studies evaluating its association with pulmonary embolism (PE) in patients with suspected PE are lacking.
OBJECTIVES
To evaluate whether body mass index (BMI) and obesity (i.e., BMI ≥30 kg/m2) are associated with confirmed PE in patients with suspected PE and to assess the efficiency and safety of the age-adjusted D-dimer strategy in obese patients.
METHODS
We conducted a secondary analysis of a multinational, prospective study, in which patients with suspected PE were managed according to the age-adjusted D-dimer strategy and followed for 3 months. Outcomes were objectively confirmed PE at initial presentation, and efficiency and failure rate of the diagnostic strategy. Associations between BMI and obesity, and PE were examined using a log-binomial model that was adjusted for clinical probability and hypoxia.
RESULTS
We included 1,593 patients (median age: 59 years; 56% women; 22% obese). BMI and obesity were not associated with confirmed PE. The use of the age-adjusted instead of the conventional D-dimer cut-off increased the proportion of obese patients in whom PE was considered ruled out without imaging from 28 to 38%. The 3-month failure rate in obese patients who were left untreated based on a negative age-adjusted D-dimer cut-off test was 0.0% (95% confidence interval: 0.0-2.9%).
CONCLUSION
BMI on a continuous linear scale and obesity were not predictors of confirmed PE among patients presenting with a clinical suspicion of PE. The age-adjusted D-dimer strategy appeared safe in ruling out PE in obese patients with suspected PE
Exploring preferences of older adults for dental services: A pilot multi-national discrete choice experiment.
OBJECTIVES
To pilot an exploration of older adults' future preferences using discrete choice experiments to understand who should provide dental examinations and treatment, where these services should be provided, and participants' willingness to pay and willingness to travel.
BACKGROUND
The proportion of older adults in the general population is increasing and is recognised as a pressing public health challenge.
MATERIALS AND METHODS
Older people aged 65 years and over were recruited into this study from the UK, Switzerland and Greece. Drawing on earlier stakeholder engagement, a set of choice experiments are developed to explore the future preferences of older people for dental examinations and dental treatment, as they anticipated losing their independence. These were presented to the participants using a range of platforms, because of the COVID pandemic. Data were analysed in STATA using a random-effects logit model.
RESULTS
Two hundred and forty-six participants (median age 70 years) completed the pilot study. There was a strong preference across all countries for a dentist to undertake a dental examination (Greece: β = 0.944, Switzerland: β = 0.260, UK β = 0.791), rather than a medical doctor (Greece: β = -0.556, Switzerland: β = -0.4690, UK: β = -0.468). Participants in Switzerland and the UK preferred these examinations to be undertaken in a dental practice (Switzerland: β = 0.220, UK: β = 0.580) while participants in Greece preferred the dental examination to be undertaken in their homes (β = 1.172). Greek participants preferred dental treatment to be undertaken by a specialist (β = 0.365) in their home (β = 0.862), while participants from the UK and Switzerland preferred to avoid any dental treatment at home (Switzerland: β = -0.387; UK: β = -0.444). Willingness to pay analyses highlighted that participants in Switzerland and the UK were willing to pay more to ensure the continuity of future service provision at a family dental practice (Switzerland: β = 0.454, UK: β = 0.695).
CONCLUSION
Discrete choice experiments are valuable for exploring older people's preferences for dental service provision in different countries. Future larger studies should be conducted to further explore the potential of this approach, given the pressing need to design services that are fit for purpose for older people. Continuity of dental service provision is considered as important by most older people, as they anticipate losing their dependence
Pulmonary vein isolation durability and lesion regression in patients with recurrent arrhythmia after pulsed-field ablation.
BACKGROUND
A novel multipolar pulsed-field ablation (PFA) catheter has recently been introduced for pulmonary vein isolation (PVI). Pre-market data showed high rates for PVI-durability during mandatory remapping studies.
OBJECTIVE
To present post-market data in patients with recurrent arrhythmias.
METHODS
Consecutive patients undergoing a redo procedure after an index PFA PVI using a bipolar-biphasic PFA system were included. 3-D electro-anatomical maps (3D-EAM) on redo procedure were compared to the 3D-EAM acquired after ablation during the index procedure. PVI durability was assessed on a per-vein and per-patient level and the sites of reconnections were identified. Furthermore, lesion extent around veins with durable isolation was compared to study lesion regression.
RESULTS
Of 341 patients treated with a PFA PVI, 29 (8.5%) underwent a left atrial redo ablation due to arrhythmia recurrence. At the end of the index procedure, 110/112 veins (98%, four common ostia) were isolated. On redo procedures performed a median of 6 months after the first ablation, 3D-EAM identified 69/110 (63%) PVs with durable isolation. In 6 (21%) patients, all PVs were durably isolated. Reconnections were more often found on the right-sided veins and on the anterior aspects of the upper veins. Only minor lesion regression was observed between the index and redo procedure (a median of 3 mm (0 - 9.5) on the posterior wall).
CONCLUSION
In patients with arrhythmia recurrence after PFA PVI using a first-generation PFA device, durable isolation was observed in 63% of the veins and 21% of the patients showed durable isolation of all previously isolated veins
Ischemic Stroke in Cancer: Mechanisms, Biomarkers, and Implications for Treatment.
Ischemic stroke is an important cause of morbidity and mortality in cancer patients. The underlying mechanisms linking cancer and stroke are not completely understood. Long-standing and more recent evidence suggests that cancer-associated prothrombotic states, along with treatment-related vascular toxicity, such as with chemotherapy and immunotherapy, contribute to an increased risk of ischemic stroke in cancer patients. Novel biomarkers, including coagulation, platelet and endothelial markers, cell-free DNA, and extracellular vesicles are being investigated for their potential to improve risk stratification and patient selection for clinical trials and to help guide personalized antithrombotic strategies. Treatment of cancer-related stroke poses unique challenges, including the need to balance the risk of recurrent stroke and other thromboembolic events with that of bleeding associated with antithrombotic therapy. In addition, how and when to restart cancer treatment after stroke remains unclear. In this review, we summarize current knowledge on the mechanisms underlying ischemic stroke in cancer, propose an etiological classification system unique to cancer-related stroke to help guide patient characterization, provide an overview of promising biomarkers and their clinical utility, and discuss the current state of evidence-based management strategies for cancer-related stroke. Ultimately, a personalized approach to stroke prevention and treatment is required in cancer patients, considering both the underlying cancer biology and the individual patient's risk profile
Nassif Nassar: Secularity as a Victory for Justice (2009). Translated and introduced by Michael Frey
Oral Presentation: Injectable cell encapsulated hyaluronic acid microgels for nucleus pulposus regeneration
INTRODUCTION
Low back pain (LBP) is a widespread health problem affecting a considerable proportion of adults worldwide, with estimates suggesting that as many as 80% may experience it1 . One of the leading causes of LBP is intervertebral disc (IVD) degeneration. Mesenchymal stromal cells (MSCs) offer promising potential to regenerate IVD in the initial stages of degeneration2 . The conventional method for stem cell delivery is typically done through direct injection into the target tissue or site. Nevertheless, there is an ongoing debate regarding the survival of transplanted cells in cell suspensions within the challenging environment of degenerated IVD, which could negatively impact the effectiveness of cell therapy3 . Utilizing microgels as carriers for delivering cells shows promise in addressing this challenge. Microgels replicate the three-dimensional natural environment of cells, facilitate efficient substance transfer, and can be administered through injection4 . Due to its biocompatibility, biodegradability, non-immunogenic, non-toxic, and noninflammatory properties, hyaluronic acid has been used as a biomaterial for clinical products for over three decades5 . Herein, injectable microgels based on hyaluronic acid (HA) were developed for MSCs delivery to the IVD.
METHODS
Tyramine-grafted HA (HA-Tyr) was prepared using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and n-hydroxysulfosuccinimide (NHS) chemistry6 . HA-Tyr solutions with different concentrations (1.5, 2, and 2.5 % w/v) were extruded and microdroplets were generated using a flicking-based vibrating nozzle system. The droplets were directly collected in a H2 O 2 solution and formed microgels. The gelation time and crosslinking conditions were optimized to produce spherical microgels at a high production rate. These cell-encapsulated microgels were utilized for discogenic induction.
RESULTS
With this novel approach, uniform microgels could be fabricated with narrow distribution and spherical shape. Light microscopy images showed that the HA-Tyr microgels have spherical shape morphology within a size range of 505 ± 47µm (Figures 1A). This was also verified by scanning electron microscopy (SEM) as shown in Figure 1B. The resulting HA-Tyr microgels are injectable through needles with conventional gauges (21 G) and disperse rapidly in aqueous media after injection (Figure 1C). Live/dead staining confirmed that the concentration for the crosslinker did not damage the encapsulated cells, as there was abundant green staining, indicating live cells. Also, cell-encapsulated microgels showed an even distribution of cells within the microgels (Figure 1D).
DISCUSSION
This study demonstrates that HA-Tyr-based microgels serve as a reliable system for delivering cells to degenerated IVD by injecting cell-encapsulated microgels. In addition, the current encapsulation procedure can be adjusted to meet the needs of different applications. For instance, it can serve as a dynamic bioreactor system for cultivating MSCs and producing cell-based therapies such as growth factors. Additionally, it can create in-vitro platforms for drug screening and disease modeling or act as bioinks for bottom-up tissue engineering in bioprinting.
REFERENCES
1. McKee, Christina, et al. "Mesenchymal stem cells transplanted with self-assembling scaffolds differentiated to regenerate nucleus pulposus in an ex vivo model of degenerative disc disease." Applied Materials Today 18 (2020): 100474.
2. Friedmann, Andrea, et al. "Intervertebral disc regeneration injection of a cell-loaded collagen hydrogel in a sheep model." International Journal of Molecular Sciences 22.8 (2021): 4248.
3. Xu, Haibin, et al. "Growth differentiation factor-5–gelatin methacryloyl injectable microspheres laden with adipose-derived stem cells for repair of disc degeneration." Biofabrication 13.1 (2020): 015010.
4. Panebianco, Christopher J., et al. "Genipin-crosslinked fibrin seeded with oxidized alginate microbeads as a novel composite biomaterial strategy for intervertebral disc cell therapy." Biomaterials 287 (2022): 121641.
5. Russo, Fabrizio, et al. "A hyaluronan and platelet-rich plasma hydrogel for mesenchymal stem cell delivery in the intervertebral disc: an organ culture study." International journal of molecular sciences 22.6 (2021): 2963.
6. Jooybar, Elaheh, et al. "An injectable platelet lysate-hyaluronic acid hydrogel supports cellular activities and induces chondrogenesis of encapsulated mesenchymal stem cells." Acta biomaterialia 83 (2019): 233-244.
Acknowledgements
This research was supported by the Council for Development of Stem Cell Sciences and Technologies (#57940), Iran National Science Foundation (# 99002288) and a Swiss National Science Bridge Discovery Project # 40B2-0_211510/
Rezension von ‘Köniz. Im Spannungsfeld zwischen Stadt und Land‘, von Christina Haas, Hannah Wälti und Anne-Catherine Schröter, Bern 2022
Hier rezensiert der Autor das von Christina Haas, Hannah Wälti und Anne-Catherine Schröter herausgegebene Buch ‘Köniz. Im Spannungsfeld zwischen Stadt und Land‘, das in Bern 2022 erschienen ist
Primary stability and osseointegration comparing a novel tapered design tissue-level implant with a parallel design tissue-level implant. An experimental in vivo study.
OBJECTIVES
The aim of the present study was to compare a novel tapered, double-threaded self-tapping tissue-Level design implant (TLC) to a well-established parallel walled tissue-level (TL) implant in terms of primary and secondary stability over time.
MATERIALS AND METHODS
Test TLC (n = 10/per timepoint) and control TL (n = 10/per timepoint) implants were placed in the mandible of minipigs and left for submerged healing for 3, 6, and 12 weeks. Maximum insertion torque and implant stability quotient (ISQ) were measured for each implant at placement. Osseointegration and cortical bone maintenance were histologically evaluated by measuring total bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC).
RESULTS
A significantly higher maximum insertion torque was measured for the test implant TLC compared to the control TL implant (57.83 ± 24.73 Ncm and 22.62 ± 23.16 Ncm, respectively; p < .001). The mean ISQ values were comparable between the two implant types (75.00 ± 6.70 for TL compared to 75.40 ± 3.20 for TLC, p = .988). BIC was comparable between both implant types at each of the evaluated time points. The fBIC was found to be significantly more coronal at 12 weeks for the TLC implant compared to the TL implant (0.31 ± 0.83 mm for TLC compared to -0.22 ± 0.85 for TL, p = .027).
CONCLUSION
The novel tapered tissue level design implant showed improved primary stability and an overall improved crestal bone height maintenance compared to the parallel walled design at 12 weeks