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Frontiers in Immunology 2024Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of...
Despite advances in surgical and therapeutic approaches, high-grade serous ovarian carcinoma (HGSOC) prognosis remains poor. Surgery is an indispensable component of therapeutic protocols, as removal of all visible tumor lesions (cytoreduction) profoundly improves the overall survival. Enhanced predictive tools for assessing cytoreduction are essential to optimize therapeutic precision. Patients' immune status broadly reflects the tumor cell biological behavior and the patient responses to disease and treatment. Serum cytokine profiling is a sensitive measure of immune adaption and deviation, yet its integration into treatment paradigms is underexplored. This study is part of the IMPACT trial (NCT03378297) and aimed to characterize immune responses before and during primary treatment for HGSOC to identify biomarkers for treatment selection and prognosis. Longitudinal serum samples from 22 patients were collected from diagnosis until response evaluation. Patients underwent primary cytoreductive surgery or neoadjuvant chemotherapy (NACT) based on laparoscopy scoring. Twenty-seven serum cytokines analyzed by Bio-Plex 200, revealed two immune phenotypes at diagnosis: Immune High with marked higher serum cytokine levels than Immune Low. The immune phenotypes reflected the laparoscopy scoring and allocation to surgical treatment. The five Immune High patients undergoing primary cytoreductive surgery exhibited immune mobilization and extended progression-free survival, compared to the Immune Low patients undergoing the same treatment. Both laparoscopy and cytoreductive surgery induced substantial and transient changes in serum cytokines, with upregulation of the inflammatory cytokine IL-6 and downregulation of the multifunctional cytokines IP-10, Eotaxin, IL-4, and IL-7. Over the study period, cytokine levels uniformly decreased in all patients, leading to the elimination of the initial immune phenotypes regardless of treatment choice. This study reveals distinct pre-treatment immune phenotypes in HGSOC patients that might be informative for treatment stratification and prognosis. This potential novel biomarker holds promise as a foundation for improved assessment of treatment responses in patients with HGSOC. ClinicalTrials.gov Identifier: NCT03378297.
Topics: Humans; Female; Ovarian Neoplasms; Cystadenocarcinoma, Serous; Cytokines; Middle Aged; Aged; Neoadjuvant Therapy; Phenotype; Cytoreduction Surgical Procedures; Biomarkers, Tumor; Neoplasm Grading; Prognosis; Treatment Outcome; Adult
PubMed: 38947323
DOI: 10.3389/fimmu.2024.1394497 -
International Journal of Emergency... Jun 2024Cardiopulmonary resuscitation is a crucial skill for emergency medical services. As high-risk-low-frequency events pose an immense mental load to providers, concepts of...
BACKGROUND
Cardiopulmonary resuscitation is a crucial skill for emergency medical services. As high-risk-low-frequency events pose an immense mental load to providers, concepts of crew resource management, non-technical skills and the science of human errors are intended to prepare healthcare providers for high-pressure situations. However, medical errors occur, and organizations and institutions face the challenge of providing a blame-free error culture to achieve continuous improvement by avoiding similar errors in the future. In this case, we report a critical medical error during an anaphylaxis-associated cardiac arrest, its handling and the unexpected yet favourable outcome for the patient.
CASE PRESENTATION
During an out-of-hospital cardiac arrest due to chemotherapy-induced anaphylaxis, a patient received a 10-fold dose of epinephrine due to shortcomings in communication and standardization via a central venous port catheter. The patient converted from a non-shockable rhythm into a pulseless ventricular tachycardia and subsequently into ventricular fibrillation. The patient was cardioverted and defibrillated and had a return of spontaneous circulation with profound hypotension only 6 min after the administration of 10 mg epinephrine. The patient survived without any residues or neurological impairment.
CONCLUSIONS
This case demonstrates the potential deleterious effects of shortcomings in communication and deviation from standard protocols, especially in emergencies. Here, precise instructions, closed-loop communication and unambiguous labelling of syringes would probably have avoided the epinephrine overdose central to this case. Interestingly, this serious error may have saved the patient's life, as it led to the development of a shockable rhythm. Furthermore, as the patient was still in profound hypotension after administering 10 mg of epinephrine, this high dose might have counteracted the severe vasoplegic state in anaphylaxis-associated cardiac arrest. Lastly, as the patient was receiving care for advanced malignancy, the likelihood of termination of resuscitation in the initial non-shockable cardiac arrest was significant and possibly averted by the medication error.
PubMed: 38943049
DOI: 10.1186/s12245-024-00663-9 -
BMC Cancer Jun 2024Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes... (Randomized Controlled Trial)
Randomized Controlled Trial
Process evaluation protocol plan for a home-based physical activity intervention versus educational intervention for persistent taxane-induced peripheral neuropathy (B-HAPI study): a randomized controlled trial.
BACKGROUND
Evaluation publications typically summarize the results of studies to demonstrate the effectiveness of an intervention, but little is shared concerning any changes implemented during the study. We present a process evaluation protocol of a home-based gait, balance, and resistance exercise intervention to ameliorate persistent taxane-induced neuropathy study according to 7 key elements of process evaluation.
METHODS
The process evaluation is conducted parallel to the longitudinal, randomized control clinical trial examining the effects of the home-based gait, balance, and resistance exercise program for women with persistent peripheral neuropathy following treatment with taxanes for breast cancer (IRB approval: Pro00040035). The flowcharts clarify how the intervention should be implemented in comparable settings, fidelity procedures help to ensure the participants are comfortable and identify their individual needs, and the process evaluation allows for the individual attention tailoring and focus of the research to avoid protocol deviation.
CONCLUSIONS
The publication of the evaluation protocol plan adds transparency to the findings of clinical trials and favors process replication in future studies. The process evaluation enables the team to systematically register information and procedures applied during recruitment and factors that impact the implementation of the intervention, thereby allowing proactive approaches to prevent deviations from the protocol. When tracking an intervention continuously, positive or negative intervention effects are revealed early on in the study, giving valuable insight into inconsistent results. Furthermore, a process evaluation adds a participant-centered element to the research protocols, which allows a patient-centered approach to be applied to data collection.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04621721, November 9, 2020, registered prospectively.
PROTOCOL VERSION
April 27, 2020, v2.
Topics: Humans; Peripheral Nervous System Diseases; Female; Breast Neoplasms; Taxoids; Exercise Therapy; Patient Education as Topic; Exercise; Bridged-Ring Compounds; Longitudinal Studies; Research Design; Randomized Controlled Trials as Topic
PubMed: 38937667
DOI: 10.1186/s12885-024-12444-x -
Frontiers in Robotics and AI 2024We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has...
We recently introduced a frameless, navigated, robot-driven laser tool for depth electrode implantation as an alternative to frame-based procedures. This method has only been used in cadaver and non-recovery studies. This is the first study to test the robot-driven laser tool in an recovery animal study. A preoperative computed tomography (CT) scan was conducted to plan trajectories in sheep specimens. Burr hole craniotomies were performed using a frameless, navigated, robot-driven laser tool. Depth electrodes were implanted after cut-through detection was confirmed. The electrodes were cut at the skin level postoperatively. Postoperative imaging was performed to verify accuracy. Histopathological analysis was performed on the bone, dura, and cortex samples. Fourteen depth electrodes were implanted in two sheep specimens. Anesthetic protocols did not show any intraoperative irregularities. One sheep was euthanized on the same day of the procedure while the other sheep remained alive for 1 week without neurological deficits. Postoperative MRI and CT showed no intracerebral bleeding, infarction, or unintended damage. The average bone thickness was 6.2 mm (range 4.1-8.0 mm). The angulation of the planned trajectories varied from 65.5° to 87.4°. The deviation of the entry point performed by the frameless laser beam ranged from 0.27 mm to 2.24 mm. The histopathological analysis did not reveal any damage associated with the laser beam. The novel robot-driven laser craniotomy tool showed promising results in this first recovery study. These findings indicate that laser craniotomies can be performed safely and that cut-through detection is reliable.
PubMed: 38933084
DOI: 10.3389/frobt.2024.1355409 -
Journal of Clinical Medicine Jun 2024Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate... (Review)
Review
Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These issues can lead to functional impairments, including difficulties in chewing, swallowing, and speech. The fibula flap is widely used for mandibular reconstruction due to its long bone segment and robust vascular supply, though it may not always provide adequate bone height for optimal dental rehabilitation. This systematic review aims to determine if the double-barreled fibula flap (DBFF) configuration is a viable alternative for mandibular reconstruction and to evaluate the outcomes of dental implants placed in this type of flap. This study adhered to the Cochrane Collaboration criteria and PRISMA guidelines and was registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols Database (INPLASY2023120026). We included clinical studies published in English, Spanish, or French that focused on adult patients undergoing segmental mandibulectomy followed by DBFF reconstruction and dental rehabilitation. Data sources included Medline/PubMed, the Cochrane Library, EMBASE, Scopus, and manual searches. Two reviewers independently screened and selected studies, with discrepancies resolved by a third reviewer. Data extraction captured variables such as publication year, patient demographics, number of implants, follow-up duration, flap survival, implant failure, and aesthetic outcomes. The risk of bias was assessed using the JBI appraisal tool, and the certainty of evidence was evaluated using the GRADE approach. A total of 17 clinical studies were included, evaluating 245 patients and 402 dental implants. The average patient age was 43.7 years, with a mean follow-up period of 34.3 months. Flap survival was high, with a 98.3% success rate and only four flap losses. The implant failure rate was low at 1.74%. Esthetic outcomes were varied, with only three studies using standardized protocols for evaluation. The overall certainty of evidence for flap survival was moderate, low for implant failure, and very low for aesthetics due to the subjective nature of assessments and variability in reporting. The primary limitations of the evidence included in this review are the observational design of the studies, leading to an inherent risk of bias, inconsistency in reporting methods, and imprecision in outcome measures. Additionally, the subjective nature of aesthetic evaluations and the variability in assessment tools further limit the reliability of the findings. The DBFF technique demonstrates excellent outcomes for mandibular reconstruction, with high flap survival and low implant failure rates, making it a viable option for dental rehabilitation. However, the evidence for aesthetic outcomes is less certain, highlighting the need for more rigorous and standardized research. This review supports the DBFF as a good alternative for mandibular reconstruction with successful dental implant integration, although further studies are needed to enhance the reliability of aesthetic evaluations.
PubMed: 38930078
DOI: 10.3390/jcm13123547 -
Animals : An Open Access Journal From... Jun 2024Estimating a dog's patellar position involves various methods, which categorize it as norma, alta (high), or baja (low). However, they require various calculations. We...
Estimating a dog's patellar position involves various methods, which categorize it as norma, alta (high), or baja (low). However, they require various calculations. We aimed to evaluate the clinical applicability of a new method, the tibial plateau-patella angle (TPPA). This could aid in planning patella luxation surgery, estimating the patella position after TPLO and various osteotomies. We conducted a two-step study: first, on 15 stifles without pathologies from nine canine cadavers, and second, using 100 patient X-rays from the archive. Three stifle angle positions (45 ± 5°, 90 ± 5°, and 135 ± 5°) and three weight groups (S, M, and L) were evaluated in the first part of this study. Based on these results, the second part of this study was conducted using 100 pathology-free radiographs at the optimal stifle angle (90 ± 5°) from the archive. All radiographs were measured by three observers with varying levels of experience. Our results indicate that the stifle angle significantly impacted the TPPA, whereby lower values were detected with higher stifle angles, which remained consistent within the weight groups. High inter- and intra-observer agreement was achieved. The physiological TPPA values ranged from 26.7° to 48.8°, remaining consistent within the various weight groups. Observer 3 in Group S exhibited a 20% (insignificant) deviation, possibly due to challenges in determining the caudal point of the tibial plateau. In contrast with humans, TPPA values in dogs are negatively correlated with stifle angles, independent of weight. Our reliable and reproducible protocol suggests the potential benefits of training on small-breed dogs stifles.
PubMed: 38929417
DOI: 10.3390/ani14121798 -
Methods and Protocols Jun 2024Primary healthcare facilities lack routine diagnostic screening due to resource limitations and dependence on syndromic management, resulting in an unprecedented...
Evaluation of the Sexually Transmitted Infections Programme among Key and Priority Populations in Primary Healthcare Facilities to Inform a Targeted Response: A Protocol Paper.
Primary healthcare facilities lack routine diagnostic screening due to resource limitations and dependence on syndromic management, resulting in an unprecedented prevalence and incidence of sexually transmitted infections (STIs), particularly among key and priority populations. Specific focuses are essential to strengthen current STI control measures. Therefore, this article describes the protocol for evaluating STI programme among key and priority populations in selected primary healthcare facilities in South Africa. We will employ an exploratory, descriptive research design to assess the STI programme in terms of its facility operations, functions, scope, gaps, delivery services, STI surveillance methods, and indicators in the selected primary healthcare facilities. A purposive sample of 15-20 STI programme stakeholders will be selected from five primary healthcare facilities in Limpopo Province, South Africa. The programme evaluation will use the World Health Organization assessment checklist tool, a globally recognised and validated instrument comprising open- and closed-ended questions to assess the STI programme. This tool, known for its credibility and reliability, ensures the study's validity. Quantitative data will be captured on STATA software (College Station, TX, USA) version 18 for descriptive analysis and presented as the mean and standard deviation for continuous variables, proportions and percentages for categorical variables. A ≤ 0.05 will demonstrate a statistically significant level. Thematic content analysis will be conducted for the qualitative data using Atlas. ti software (Technical University, Berlin, Germany) version 23.1. The study's results will inform new approaches to strengthen STI coverage, service delivery, and linkage to care.
PubMed: 38921826
DOI: 10.3390/mps7030047 -
Epidemiological Characterization and Genetic Variation of the SARS-CoV-2 Delta Variant in Palestine.Pathogens (Basel, Switzerland) Jun 2024The emergence of new SARS-CoV-2 variants in Palestine highlights the need for continuous genetic surveillance and accurate screening strategies. This case series study...
The emergence of new SARS-CoV-2 variants in Palestine highlights the need for continuous genetic surveillance and accurate screening strategies. This case series study aimed to investigate the geographic distribution and genetic variation of the SARS-CoV-2 Delta Variant in Palestine in August 2021. Samples were collected at random in August 2021 ( = 571) from eight districts in the West Bank, Palestine. All samples were confirmed as positive for COVID-19 by RT-PCR. The samples passed the quality control test and were successfully sequenced using the ARTIC protocol. The Delta Variant was revealed to have four dominant lineages: B.1.617 (19%), AY.122 (18%), AY.106 (17%), and AY.121 (13%). The study revealed eight significant purely spatial clusters ( < 0.005) distributed in the northern and southern parts of Palestine. Phylogenetic analysis of SARS-CoV-2 genomes ( = 552) showed no geographically specific clades. The haplotype network revealed three haplogroups without any geographic distribution. Chronologically, the Delta Variant peak in Palestine was shortly preceded by the one in the neighboring Israeli community and shortly followed by the peak in Jordan. In addition, the study revealed an extremely intense transmission network of the Delta Variant circulating between the Palestinian districts as hubs (SHR ≈ 0.5), with Al-Khalil, the district with the highest prevalence of COVID-19, witnessing the highest frequency of transitions. Genetic diversity analysis indicated closely related haplogroups, as haplotype diversity (Hd) is high but has low nucleotide diversity (π). However, nucleotide diversity (π) in Palestine is still higher than the global figures. Neutrality tests were significantly ( < 0.05) low, including Tajima's D, Fu-Li's F, and Fu-Li's D, suggesting one or more of the following: population expansion, selective sweep, and natural negative selection. Wright's F-statistic (Fst) showed genetic differentiation (Fst > 0.25) with low to medium gene flow (Nm). Recombination events were minimal between clusters (R) and between adjacent sites (R). The study confirms the utility of the whole genome sequence as a surveillance system to track the emergence of new SARS-CoV-2 variants for any possible geographical association and the use of genetic variation analysis and haplotype networking to delineate any minimal change or slight deviation in the viral genome from a reference strain.
PubMed: 38921818
DOI: 10.3390/pathogens13060521 -
Cells Jun 2024Dopaminergic neurons are the predominant brain cells affected in Parkinson's disease. With the limited availability of live human brain dopaminergic neurons to study... (Comparative Study)
Comparative Study
Dopaminergic neurons are the predominant brain cells affected in Parkinson's disease. With the limited availability of live human brain dopaminergic neurons to study pathological mechanisms of Parkinson's disease, dopaminergic neurons have been generated from human-skin-cell-derived induced pluripotent stem cells. Originally, induced pluripotent stem-cell-derived dopaminergic neurons were generated using small molecules. These neurons took more than two months to mature. However, the transcription-factor-mediated differentiation of induced pluripotent stem cells has revealed quicker and cheaper methods to generate dopaminergic neurons. In this study, we compared and contrasted three protocols to generate induced pluripotent stem-cell-derived dopaminergic neurons using transcription-factor-mediated directed differentiation. We deviated from the established protocols using lentivirus transduction to stably integrate different transcription factors into the AAVS1 safe harbour locus of induced pluripotent stem cells. We used different media compositions to generate more than 90% of neurons in the culture, out of which more than 85% of the neurons were dopaminergic neurons within three weeks. Therefore, from our comparative study, we reveal that a combination of transcription factors along with small molecule treatment may be required to generate a pure population of human dopaminergic neurons.
Topics: Humans; Dopaminergic Neurons; Induced Pluripotent Stem Cells; Cell Differentiation; Transcription Factors; Lentivirus
PubMed: 38920646
DOI: 10.3390/cells13121016 -
Entropy (Basel, Switzerland) Jun 2024Quantum private comparison (QPC) enables two users to securely conduct private comparisons in a network characterized by mutual distrust while guaranteeing the...
Quantum private comparison (QPC) enables two users to securely conduct private comparisons in a network characterized by mutual distrust while guaranteeing the confidentiality of their private inputs. Most previous QPC protocols were primarily used to determine the equality of private information between two users, which constrained their scalability. In this paper, we propose a QPC protocol that leverages the entanglement correlation between particles in a four-particle cluster state. This protocol can compare the information of two groups of users within one protocol execution, with each group consisting of two users. A semi-honest third party (TP), who will not deviate from the protocol execution or conspire with any participant, is involved in assisting users to achieve private comparisons. Users encode their inputs into specific angles of rotational operations performed on the received quantum sequence, which is then sent back to TP. Security analysis shows that both external attacks and insider threats are ineffective at stealing private data. Finally, we compare our protocol with some previously proposed QPC protocols.
PubMed: 38920521
DOI: 10.3390/e26060512