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Conventional cardiotocography (CTG) has been used extensively to monitor the fetal condition during labour. However, conventional non-invasive monitoring is limited by the difficulty of obtaining an adequate signal quality, particularly in the case of obese parturients. Furthermore, the rate of operative deliveries keeps rising despite the ability for conventional intrapartum monitoring. Electrophysiological monitoring is an alternative technique that has been developed over the past decades to improve signal quality. This non-invasive, transabdominal and wireless alternative measures fetal heart rate by fetal electrocardiography (NI-fECG), and uterine activity by electrohysterography (EHG). Both NI-fECG and EHG have been proven to be more accurate and reliable than conventional non-invasive methods and are less affected by maternal Body Mass Index. Nevertheless, it is still unknown whether electrophysiological intrapartum monitoring leads to better obstetric and neonatal outcomes. This study aims to investigate whether electrophysiological monitoring during labour affects the number of operative interventions compared with conventional monitoring during labour.
This is a single-centre cohort intervention random sampling study which will be performed in a tertiary obstetric care centre. In total, 3471 term pregnant women with a singleton fetus in cephalic position and indication for continuous fetal monitoring during labour will be included. Eligible women will be prospectively included in the cohort for conventional monitoring. From these women, 90.9% of women will be randomly sampled and will be offered electrophysiological monitoring. A historical cohort of an additional 2100 women who received conventional monitoring will be added to the conventional group. This historical cohort was collected between April 2019 and February 2023. The primary outcome will be the number of operative interventions during labour. Secondary outcome measures include maternal and neonatal outcomes, patient and healthcare professional perspectives and costs.
This study received approval from the Medical Ethics Committee of Máxima Medical Centre (W22.071) on 1 November 2023. All participants will provide informed consent prior to data collection. Results of the study will be disseminated in peer-reviewed scientific journals and conference presentations.
This study aimed to compare the 3-year recurrence rates of diabetic foot ulcers (DFU) and the rate of endovascular reintervention for chronic limb-threatening ischaemia (CLTI) to recurrence rates of advanced-stage cancers. We systematically collected original data reporting 3-year DFU recurrence from studies published through 2024 and calculated a pooled mean. These findings were compared to recurrence rates for advanced breast, prostate, colorectal, and lung cancers using contemporary sources from the National Cancer Institute and American Cancer Society. CLTI reintervention data were drawn from the BEST-CLI trial. The pooled 3-year DFU recurrence rate was 58%, while the CLTI reintervention rate was 50%—comparable to cancer recurrence rates: breast (25%–40%), prostate (30%–40%), colorectal (30%–50%), and lung (60%–80%). Despite these comparable risks, DFU and CLTI remain underrecognized in terms of their recurrent burden on individuals, families, and health systems. The data presented here underscore the need to reframe healed DFU and post-intervention CLTI not as an endpoint but as a remission—a state requiring structured surveillance and proactive management, much like in oncology. Developing interdisciplinary survivorship care plans for individuals with DFU and CLTI, modelled on those used in cancer care, may improve communication, enhance secondary prevention, and foster more ulcer-free, hospital-free, and activity-rich days.
Over the past decades, interest in second breast-conserving therapy (BCT) has increased due to, among others, advances in radiotherapy techniques. Preoperative partial breast irradiation (PBI) is an experimental treatment for patients with low-risk primary breast cancer. This approach can downstage the tumour and may possibly reduce toxicity and improve cosmetic outcomes compared with postoperative radiotherapy. This study aims to evaluate the feasibility of single-dose preoperative PBI and second breast-conserving surgery (BCS) for patients with an ipsilateral recurrent breast event (IRBE) after previous BCT.
The REPEAT trial is a multicentre, prospective, single-arm trial investigating ablative single-dose preoperative PBI in patients with an IRBE. Eligible patients are ≥50 years, have a unifocal non-lobular invasive breast cancer ≤2 cm, Bloom-Richardson grade 1 or 2, oestrogen receptor-positive, human epidermal growth factor receptor 2-negative and clinically negative axillary lymph nodes. The study plans to enrol 25 patients. Radiotherapy planning will involve the use of CT and MRI in the treatment position. Single-dose PBI of 20 Gy to the tumour and 15 Gy to the surrounding 2 cm of breast tissue will be delivered using a conventional or MR-guided linear accelerator. Tumour response will be monitored preoperatively using MRI and liquid biopsies to identify biomarkers for evaluating radiosensitivity. BCS will be performed 3 (±one) weeks post PBI. The primary endpoint is the incidence of grade 2 or higher treatment-associated acute toxicity within 90 days. Secondary endpoints include the evaluation of acute (grade 1) and late toxicity, radiologic and pathologic response, mastectomy rate, patient-reported outcomes, cosmetic outcome, local, regional and distant recurrence rates, survival outcome and biomarkers in liquid biopsies and tumour tissue. Patients will be followed up to 5 years after PBI.
Ethical approval from the Medical Research Ethics Committee of the Amsterdam UMC has been obtained (NL85983.018.24). The results will be disseminated via peer-reviewed academic journal and presentation at conferences. In addition, summaries will be shared with the participating patients.
The trial was registered prospectively on October 11th 2024 at clinicaltrials.gov (NCT06640881).
Guidelines for symptomatic knee osteoarthritis (OA) dictate the initiation of conservative treatment (physical therapy, analgesics and intra-articular injections with corticosteroids) as a first line defence. When conservative treatment fails, the golden standard is invasive joint replacement surgery, but for a substantial group of patients who do not respond to the current conservative treatment, this is not (yet) indicated. The RADIOPHENOL study investigates if denervation of knee sensory (genicular) nerves can serve the gap between conservative and invasive treatment for younger patients and for patients who cannot undergo joint replacement surgery due to comorbid health conditions.
The RADIOPHENOL study is a multicentre unblinded randomised controlled trial with three parallel arms (1:1:1). In total, 192 patients with knee OA Kellgren-Lawrence grades 2–4 but not eligible for joint replacement according to the orthopaedic surgeon due to young age, old age and/or comorbidity or technical reasons are eligible and will be randomised to three groups of 64 patients. Group A: traditional radiofrequency ablation, group B: chemical neurolysis with phenol, group C: conservative medical management. Primary outcome is the Oxford Knee Score at 6 months. Secondary outcomes include Western Ontario and McMaster Universities Osteoarthritis Index, knee pain by numeric rating scale, physical functionality, health-related quality of life, mental health, change in medication use, predictive value of a diagnostic block, procedure time, patient discomfort score during the intervention and adverse events.
The protocol (V.2.0, 15 May 2023), was approved by the Ethics Committee of Amsterdam UMC (NL83410.018.22 – METC2022.0890) on 31 July 2023. We aim to publish our results in international peer-reviewed journals.
ClinicalTrials.gov NCT06094660, including the WHO Trial Registration data set items. Registered on 20 October 2023, first patient enrolled on 27 November 2023.
by Mahmoud A. A. Ibrahim, Doaa G. M. Mahmoud, Alaa H. M. Abdelrahman, Khlood A. A. Abdeljawaad, Gamal A. H. Mekhemer, Tamer Shoeib, Mohamed A. El-Tayeb, Peter A. Sidhom, Paul W. Paré, Mohamed-Elamir F. Hegazy
Mycobacterium tuberculosis is a lethal human pathogen, with the key flavoenzyme for catalyzing bacterial cell-wall biosynthesis, decaprenylphosphoryl-D-ribose oxidase (DprE1), considered an Achilles heal for tuberculosis (TB) progression. Inhibition of DprE1 blocks cell wall biosynthesis and is a highly promising antitubercular target. Macozinone (PBTZ169, a benzothiazinone (BTZ) derivative) is an irreversible DprE1 inhibitor that has attracted considerable attention because it exhibits an additive activity when combined with other anti-TB drugs. Herein, 754 BTZ analogs were assembled in a virtual library and evaluated against the DprE1 target using a covalent docking approach. After validation of the employed covalent docking approach, BTZ analogs were screened. Analogs with a docking score less than –9.0 kcal/mol were advanced for molecular dynamics (MD) simulations, followed by binding energy evaluations utilizing the MM-GBSA approach. Three BTZ analogs–namely, PubChem-155-924-621, PubChem-127-032-794, and PubChem-155-923-972– exhibited higher binding affinities against DprE1 compared to PBTZ169 with ΔGbinding values of –77.2, –74.3, and –65.4 kcal/mol, versus –49.8 kcal/mol, respectively. Structural and energetical analyses were performed for the identified analogs against DprE1 throughout the 100 ns MD simulations, and the results demonstrated the great stability of the identified BTZ analogs. Physicochemical and ADMET characteristics indicated the oral bioavailability of the identified BTZ analogs. The obtained in-silico results provide promising anti-TB inhibitors that are worth being subjected to in-vitro and in-vivo investigations.
by Mahmoud A. A. Ibrahim, Maggie N. S. Hanna, Al-shimaa S. M. Rady, Peter A. Sidhom, Shaban R. M. Sayed, Mohamed A. El-Tayeb, Ahmed M. Awad, Hatem Tallima, Tamer Shoeib
The study of the interactions between biomolecules and nanostructures is quite fascinating. Herein, the adsorption propensity of beryllium oxide (Be12O12) nanocarrier toward nucleobases (NBs) was investigated. In terms of DFT calculations, the adsorption tendency of Be12O12 toward NBs, including cytosine (NB-C), guanine (NB-G), adenine (NB-A), thymine (NB-T), and uracil (NB-U), was unveiled through various configurations. Geometrical, electronic, and energetic features for Be12O12, NBs, and their associated complexes were thoroughly evaluated at M06-2X/6-311+G** level of theory. The potent adsorption process within NBs∙∙∙Be12O12 complexes was noticed through favorable interaction (Eint) and adsorption (Eads) energies with values up to –53.04 and –38.30 kcal/mol, respectively. Generally, a significant adsorption process was observed for all studied complexes, and the favorability followed the order: NB-C∙∙∙ > NB-G∙∙∙ > NB-A∙∙∙ > NB-T∙∙∙ > NB-U∙∙∙Be12O12 complexes. Out of all studied complexes, the most potent adsorption was found for NB-C∙∙∙Be12O12 complex within configuration A (Eint = –53.04 kcal/mol). In terms of energy decomposition, SAPT analysis revealed electrostatic (Eelst) forces to be dominant within the studied adsorption process with values up to –99.88 kcal/mol. Analyzing QTAIM and NCI, attractive intermolecular interactions within the studied complexes were affirmed. From negative values of thermodynamic parameters, the nature of the considered adsorption process was revealed to be spontaneous and exothermic. Regarding density of state, IR, and Raman analyses, the occurrence of the adsorption process within NBs∙∙∙Be12O12 complexes was confirmed. Noticeable short recovery time values were observed for all studied complexes, confirming the occurrence of the desorption process. The findings provided fundamental insights into the potential application of Be12O12 nanocarrier in drug and gene delivery processes.
Diabetic foot ulcers (DFUs) pose a significant clinical challenge, often leading to amputations and hospitalisation. This study aimed to investigate the characteristics and outcomes of DFUs treated with surgical debridement and standardised wound care. This descriptive cross-sectional study focused on diabetic patients with appropriate vascular conditions, as determined by an Ankle Brachial Index >0.9. Based on their infection status, participants were admitted to Poursina Hospital in Rasht, Iran, and subjected to initial supportive measures, antibiotic therapy and surgical debridement. The study incorporated primary treatment with wet bandages, silver spray and fibrinolysin ointment. Statistical analysis employed SPSS 22 software. Most patients were male (54.7%) and under 60 years old (50.7%). Overweight status was prevalent in 69.3% of diabetic ulcer patients, amongst whom 48% underwent wrist debridement. The 64% and 36% of the cases had grade III and grade II Texas index. Moreover, 96% of patients exhibited signs of infection and were classified as Stage Texas B. Reoperation was necessary for 34.7% of patients. The mean hospital stay was 8.5 ± 7.55 days, and the average recovery time was 15.2 ± 15.19 days. Out of 75 patients, 10 were unable to return to limb function due to disability. In this study, around one-third of patients required secondary repair with grafts and flaps. A small number of them were unable to recover because of underlying disability, and the mean recovery time in other cases was 24 days. Future studies should follow up with patients for longer periods to assess long-term therapeutic outcomes and quality of life.
Objetivo principal: identificar qué actividades guían el trabajo de la enfermera en una unidad de cuidados intensivos para adultos. Metodología: revisión integradora, realizada sobre la base de Literatura Latinoamericana y del Caribe en Ciencias de la Salud y Sistema de Análisis y Recu-peración de Literatura Médica en línea, entre enero y febrero de 2019. La búsqueda resultó en 15 producciones, que fueron analizadas a través del análisis de contenido temático. Resultados principales: a partir del análisis de los estudios, surgió la siguiente categoría temática: “Actividades que guían el trabajo de la enfermera en una unidad de cuidados intensivos para adultos”, destacando: observación y vigilancia constantes, manejo de instrumentos tecnológicos e interpretación de información de estos dispositivos, desempeño y comunicación entre un equipo multidisciplinario, realizando una evaluación y plan de atención al paciente. Conclusión principal: aunque algunas actividades pueden caracterizarse como técnicas, también existen aquellas que involucran la subjetividad de las enfermeras, dirigidas a una atención más individualizada y guiadas por el ejercicio de la autonomía.
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