Ultrasound Probe Pressure Affects Aortic Wall Stiffness: A Patient-Specific Computational Study in Abdominal Aortic Aneurysms.

PURPOSE: Ultrasound imaging is key in the management of patients with an abdominal aortic aneurysm (AAA). It was recently shown that the cyclic diameter variations between diastole and systole, which can be quantified with US imaging, increase significantly with the strength of the applied probe pressure on the patient's abdomen. The goal of this study is to investigate this effect more thoroughly. METHODS: With finite-element modeling, pulsatile blood pressure and probe pressure are simulated in three patient-specific geometries. Two distinct models for the aortic wall were simulated: a nonlinear hyperelastic and a linear elastic model. In addition, varying stiffness was considered for the surrounding tissues. The effect of light, moderate, and firm probe pressure was quantified on the stresses and strains in the aortic wall, and on two in vivo stiffness measures. In addition, the Elasticity Loss Index was proposed to quantify the change in stiffness due to probe pressure. RESULTS: Firm probe pressure decreased the measured aortic stiffness, and material stiffness was affected only when the wall was modeled as nonlinear, suggesting a shift in the stress-strain curve. In addition, stiffer surrounding tissues and a more elongated aneurysm sac decreased the responsiveness to the probe pressure. CONCLUSION: The effect of probe pressure on the AAA wall stiffness was clarified. In particular, the AAA wall nonlinear behavior was found to be of primary importance in determining the probe pressure response. Thus, further work will intend to make use of this novel finding in a clinical context.

Prenatal cell-free DNA testing of women with pregnancy-associated cancer: a retrospective cross-sectional study.

Background: Incidentally, the non-invasive prenatal test (NIPT) shows chromosomal aberrations suspicious of a maternal malignancy, especially after genome-wide testing. The aim of this study is to determine how many cases of cancer in pregnancy are diagnosed or missed with NIPT and whether in retrospect subtle changes in NIPT results could have detected cancer. Methods: We identified Dutch patients diagnosed in 2017-2021 with pregnancy-associated cancer from the International Network on Cancer, Infertility and Pregnancy (INCIP) Registry, who underwent NIPT in the Dutch NIPT implementation study (TRIDENT-2). We retrospectively assessed how many of these women showed a malignancy suspicious-NIPT, their tumour types and -stages, and the time interval between NIPT and cancer diagnosis. Findings: Of 143 women with pregnancy-associated cancer, we included 65 patients that underwent an NIPT. Fifty-four women had a solid tumour and 11 a haematological malignancy. Sixteen (24.6%) NIPTs were malignancy suspicious (15 genome-wide, one targeted). All 10 haematological cancer patients with genome-wide NIPT had a malignancy suspicious-NIPT, irrespective of the disease stage. Only five patients with a solid tumour had a genome-wide malignancy suspicious-NIPT (4/5 advanced cancer stage III or IV). The mean time between date of NIPT and cancer diagnosis was significantly shorter after a malignancy suspicious-NIPT compared to a non-suspicious-NIPT, respectively 49.9 days (± SD 31.8) and 100.7 days (± SD 74.9), p = 0.001. Interpretation: All genome-wide NIPT in women with pregnancy-associated haematological malignancies were malignancy suspicious. Women with a solid tumour showed a malignancy suspicious-NIPT in only a minority of cases, mainly the advanced stages. Funding: None.

Transcutaneous vagus nerve stimulation: a bibliometric study on current research hotspots and status.

Background: Transcutaneous Vagal Nerve Stimulation (tVNS) has been used as a promising noninvasive neuromodulation technique for the treatment of various systems.The aim of this study was to analyze the research hotspots and future directions of tVNS in the 21st century by using bibliometric methods. Methods: The study object was the literature related to tVNS from the Web of Science database from 2000 to May 2024. In order to measure and analyze the number of literature issuance, institutions, authors, countries, keywords, co-citations, and journals of publication, we used VOSviewer, Citespace, Bibliometrix R-package, and Scimago Graphica software. A narrative review of the current research content of tVNS was conducted to gain a better understanding of the current state of the field. Results: A total of 569 papers were included in the study. The results show that from 2000 to 2024, the number of publications shows an increasing trend year by year, involving a total of 326 research institutions. The United States, China, and Germany are the major research centers. The study identified 399 keywords, which roughly formed 11 natural clusters, revealing that the current hotspots of related research are mainly reflected in 3 areas: intervention efficacy on nervous system diseases, mechanism of action of tVNS, and stimulation mode of tVNS. The top 10 most cited references focus on research into the mechanism of action of tVNS. Conclusion: The efficacy and safety of tVNS have been confirmed in previous studies, but a standardized tVNS treatment protocol has not yet been developed, and most clinical studies have small sample sizes and lack multicenter and multidisciplinary collaboration. Currently, tVNS is used in the treatment of neurological diseases, psychiatric diseases, cardiovascular diseases, and some autoimmune diseases. It is expected that future research in this field will continue to focus on the application of tVNS in central nervous system diseases and the exploration of related mechanisms, and at the same time, with the rise of non-invasive neuromodulation technology, the application of tVNS in other diseases also has great potential for development.

A cavalpulmonary assist device utilising impedance pumping enhanced by peristaltic effect.

BACKGROUND: Fontan procedure, the standard surgical palliation to treat children with single ventricular defects, causes systemic complications over years due to lack of pumping at cavopulmonary junction. A device developed specifically for cavopulmonary support is thus considered, while current commercial ventricular assist devices (VAD) induce high shear rates to blood, and have issues with paediatric suitability. AIM: To demonstrate the feasibility of a small, valveless, non-invasive to blood and pulsatile rotary pump, which integrates impedance and peristaltic effects. METHODS: A prototype pump was designed and fabricated in-house without any effort to optimise its specification. It was then tested in vitro, in terms of effect of pumping frequency, background pressure differences and pump size on output performance. RESULTS: Net flow rate (NFR) and maximum pressure head delivery are both reasonably linearly dependent on pumping frequency within normal physiological range. Positive linearity is also observed between NFR and the extent of asymmetric pumping. The device regulates NFR in favourable pressure head difference and overcomes significant adverse pressure head difference. Additionally, performance is shown to be insensitive to device size. CONCLUSIONS: The feasibility of the novel rotary pump integrating impedance and peristaltic effects is demonstrated to perform in normal physiological conditions without any optimisation effort. It provides promising results for possible future paediatric cavopulmonary support and warrants further investigation of miniaturisation and possible haemolysis.

Effects of Non-Invasive Brain Stimulation for Degenerative Cerebellar Ataxia: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to assess the effectiveness of non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES), as a neurological intervention for degenerative cerebellar ataxia (DCA) based on preregistration (PROSPERO: CRD42023379192). OBJECTIVE: We aimed to explore clinical outcomes and examine the parameters associated with NIBS efficacy in DCA patients. METHODS: The PubMed, Cochrane Library, CHINAL, and PEDro databases were searched for relevant randomized controlled trials (RCTs). Data extraction, quality assessment, and heterogeneity analyses were conducted; the Grading, Recommendations, Assessment, Development, and Evaluation was used to assess the quality of evidence and a meta-analysis was performed. RESULTS: Seventeen RCTs that included 661 patients on the scale for assessment and rating of ataxia (SARA) and 606 patients on the International Cooperative Ataxia Rating Scale (ICARS) were included. These RCTs showed a serious risk of bias (RoB) and low certainty of evidence for both outcomes. NIBS significantly reduced SARA (MD = -2.49, [95% confidence interval: -3.34, -1.64]) and ICARS (-5.27 [-7.06, -3.47]); the subgroup analysis showed significant effects: rTMS and tES reduced both outcomes. However, there were no significant differences in the effects of rTMS and tES. Additional subgroup analysis indicated the impact of rTMS frequency and the total number of tES sessions on ataxia. CONCLUSION: Non-invasive brain stimulation may reduce ataxia in DCA patients, but the estimated effect size may change in future studies because the RoB was serious and the certainty of evidence was low, and the heterogeneity was high. To establish evidence for selecting NIBS methods and parameters, continued high-quality RCTs are required.

Modulation of electroencephalogram brain activity dynamics by 10 Hz parietal repetitive transcranial magnetic stimulation: Implications for recovery of the minimally conscious state.

BACKGROUND AND OBJECTIVES: Despite the fact that the parietal cortex is associated with consciousness, the underlying mechanisms of parietal repetitive transcranial magnetic stimulation (rTMS) have not yet been specifically investigated. The present study aims to examine the effects of parietal rTMS on patients with disorders of consciousness (DoC) and identify a novel potential target. METHODS: Twenty minimally conscious state (MCS) patients were stochastically assigned to a real or sham rTMS group in a controlled trial. The real rTMS group was administered over the parietal cortex, with a frequency of 10 Hz and a rest motor threshold of 90 %. The sham rTMS group was identical to the real rTMS group without magnetic stimulation over the cortex. Pre- and post-treatment resting-state electrophysiological (EEG) data and coma recovery scale-revised (CRS-R) score were gathered. Microstate analyses were calculated to evaluate the brain activity dynamics. RESULTS: The real rTMS treatment improved the CRS-R scores. There were notable alterations in the mean microstate duration (MMD) of microstate B in the real rTMS group. The sham rTMS group did not exhibit such changes in CRS-R score or EEG results, which were not statistically significant. Furthermore, the MMD and RTC of microstate E were found to be negatively correlated with baseline CRS-R scores. CONCLUSION: Parietal rTMS can induce behavioral improvement and brain activity dynamics in patients with MCS. EEG microstates can be used as a valuable method to study neurophysiological mechanisms behind MCS. And the parietal cortex represents an alternative for rTMS therapy protocols.

Characteristics and predictors of outcome in children with severe acute bronchiolitis: A 10-yearexperience.

BACKGROUND: Severe acute bronchiolitis (SAB) can be life-threatening for infants and may be responsible for the congestion of intensive care units (ICU) during epidemics. We aimed to study the clinical and paraclinical characteristics of patients with SAB requiring a transfer to the ICU in order to examine their outcomes and to identify the predictors of a stay of ≥7 days and/or death. METHODS: This was a cross-sectional retrospective study including infants aged ≤12 months transferred to the ICU for their first episode of SAB between 1 January 2010 and 31 December 2019. RESULTS: We collected data on 380 patients with a median age of 1.75 months. They had a history of prematurity (20.53 %), low birth weight (18.68 %), parental atopy (12.89 %), and comorbidity (7.37 %, mainly congenital heart disease [5 %]). The leading cause of transfer was hypoxemia and increased oxygen requirements (49.73 %). The patients required mechanical ventilation (MV) in 63.42 % of the cases and noninvasive ventilation (NIV) in 67.63 %. NIV has supplanted MV over the years. Its use has increased from 40.4 % in 2010 to 96 % in 2019 compared with 83.84 % and 42 % for MV. A total of 14 (3.68 %) patients died. The independent predictors of a stay of ≥7 days and/or death were young age ≤2 months (p = 0.002), failure to thrive (p = 0.006), apnea (p = 0.045), dehydration (p = 0.018), the presence of biological inflammatory reaction (p = 0.002), isolation of respiratory syncytial virus (p < 0.001), and bacterial coinfection (p = 0.013).NIV was a protective factor (p < 0.001). A severity score ranging from 0 to 17 was established with an optimal cut-off value of 5 points. CONCLUSION: Specific caution is needed in patients with these severity predictors. The generalization ofNIV in general pediatrics departments would improve SAB management and reduce transfers to the ICU.

Coupled pulsatile vascular and paravascular fluid dynamics in the human brain.

BACKGROUND: Cardiac pulsation propels blood through the cerebrovascular network to maintain cerebral homeostasis. The cerebrovascular network is uniquely surrounded by paravascular cerebrospinal fluid (pCSF), which plays a crucial role in waste removal, and its flow is suspected to be driven by arterial pulsations. Despite its importance, the relationship between vascular and paravascular fluid dynamics throughout the cardiac cycle remains poorly understood in humans. METHODS: In this study, we developed a non-invasive neuroimaging approach to investigate the coupling between pulsatile vascular and pCSF dynamics within the subarachnoid space of the human brain. Resting-state functional MRI (fMRI) and dynamic diffusion-weighted imaging (dynDWI) were retrospectively cardiac-aligned to represent cerebral hemodynamics and pCSF motion, respectively. We measured the time between peaks (∆TTP) in d d ϕ f M R I and dynDWI waveforms and measured their coupling by calculating the waveforms correlation after peak alignment (correlation at aligned peaks). We compared the ∆TTP and correlation at aligned peaks between younger [mean age: 27.9 (3.3) years, n = 9] and older adults [mean age: 70.5 (6.6) years, n = 20], and assessed their reproducibility within subjects and across different imaging protocols. RESULTS: Hemodynamic changes consistently precede pCSF motion. ∆TTP was significantly shorter in younger adults compared to older adults (-0.015 vs. -0.069, p < 0.05). The correlation at aligned peaks were high and did not differ between younger and older adults (0.833 vs. 0.776, p = 0.153). The ∆TTP and correlation at aligned peaks were robust across fMRI protocols (∆TTP: -0.15 vs. -0.053, p = 0.239; correlation at aligned peaks: 0.813 vs. 0.812, p = 0.985) and demonstrated good to excellent within-subject reproducibility (∆TTP: intraclass correlation coefficient = 0.36; correlation at aligned peaks: intraclass correlation coefficient = 0.89). CONCLUSION: This study proposes a non-invasive technique to evaluate vascular and paravascular fluid dynamics. Our findings reveal a consistent and robust cardiac pulsation-driven coupling between cerebral hemodynamics and pCSF dynamics in both younger and older adults.

Combination of Waist Circumference and Circulating Levels of IGFBP-2 as a Simple Screening Tool for Early Detection of Metabolic Dysfunction-Associated Steatotic Liver Disease.

Optimal non-invasive biomarkers for metabolic dysfunction-associated steatotic liver disease (MASLD) remain elusive, especially in the detection of early stages. This study tested in an asymptomatic cohort of 171 men (49.2 ± 8.6 years) and 131 women (51.8 ± 8.5 years) whether waist circumference (WC) and circulating levels of insulin-like growth factor-binding protein 2 (IGFBP-2) could identify individuals with liver fat >5% as assessed by magnetic resonance spectroscopy. Participants with high WC (> 85 or 90 cm for women and men, respectively) and low IGFBP-2 (< 260 or 230 ng/mL for women and men, respectively) were characterized by a higher risk of having MASLD (46.3%, p < 0.0001). Among the 68 individuals with MASLD, 73.5% fell into the subgroup with high WC and low IGFBP-2 concentrations (p < 0.0001). When combined, these markers reached a sensitivity of 73.5% and specificity of 75.2% for MASLD. Thus, WC and plasma IGFBP-2 levels might be useful as a novel, simple, and non-invasive index to support existing tools in the identification of individuals at risk of early-stage MASLD.

Noninvasive Technologies for the Diagnosis of Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

Early cutaneous squamous cell carcinoma (cSCC) diagnosis is essential to initiate adequate targeted treatment. Noninvasive diagnostic technologies could overcome the need of multiple biopsies and reduce tumor recurrence. To assess performance of noninvasive technologies for cSCC diagnostics, 947 relevant records were identified through a systematic literature search. Among the 15 selected studies within this systematic review, 7 were included in the meta-analysis, comprising of 1144 patients, 224 cSCC lesions, and 1729 clinical diagnoses. Overall, the sensitivity values are 92% (95% confidence interval [CI] = 86.6-96.4%) for high-frequency ultrasound, 75% (95% CI = 65.7-86.2%) for optical coherence tomography, and 63% (95% CI = 51.3-69.1%) for reflectance confocal microscopy. The overall specificity values are 88% (95% CI = 82.7-92.5%), 95% (95% CI = 92.7-97.3%), and 96% (95% CI = 94.8-97.4%), respectively. Physician's expertise is key for high diagnostic performance of investigated devices. This can be justified by the provision of additional tissue information, which requires physician interpretation, despite insufficient standardized diagnostic criteria. Furthermore, few deep learning studies were identified. Thus, integration of deep learning into the investigated devices is a potential investigating field in cSCC diagnosis.

Biomarkers in Kidney Transplantation.

Currently in the United States, there are more than 250,000 patients with a functioning kidney allograft and over 100,000 waitlisted patients awaiting kidney transplant, with a burgeoning number added to the kidney transplant wait list every year. Although early post-transplant care is delivered at the transplant center, the increasing number of kidney transplant recipients requires general nephrologists to actively participate in the long-term care of these patients. Serum creatinine and proteinuria are imperfect traditional biomarkers of allograft dysfunction and lag behind subclinical allograft injury. This manuscript reviews the various clinically available biomarkers in the field of kidney transplantation for a general nephrologist with a focus on the utility of donor-derived cell-free DNA, as a marker of early allograft injury. Blood gene expression profiling, initially studied in the context of early identification of subclinical rejection, awaits validation in larger multicentric trials. Urinary cellular messenger ribonucleic acid and chemokine CXCL10 hold promising potential for early diagnosis of both subclinical and acute rejection. Torque tenovirus, a ubiquitous DNA virus is emerging as a biomarker of immunosuppression exposure as peripheral blood torque tenovirus copy numbers might mirror the intensity of host immunosuppression. Although high-quality evidence is still being generated, evidence and recommendations are provided to aid the general nephrologist in implementation of novel biomarkers in their clinical practice.

Comparison of facial skin ageing in healthy Asian and Caucasian females quantified by in vivo line-field confocal optical coherence tomography 3D imaging.

BACKGROUND: Quantitative biomarkers of facial skin aging were investigated in 109 healthy Asian female volunteers, aged 20 to 70 years. MATERIALS AND METHODS: In vivo 3D Line-field Confocal Optical Coherence Tomography (LC-OCT) imaging, enhanced by Artificial Intelligence (AI)-based quantification algorithms, was utilized to compute various metrics, including stratum corneum thickness (SC), viable epidermal (VE) thickness, and Dermal-Epidermal Junction (DEJ) undulation along with cellular metrics for the temple, cheekbone, and mandible. RESULTS: Comparison with data from a cohort of healthy Caucasian volunteers revealed similarities in the variations of stratum corneum and viable epidermis layers, as well as cellular shape and size with age in both ethnic groups. However, specific findings emerged, such as larger, more heterogeneous nuclei in both layers, demonstrated by an increase in nuclei volume and their standard deviation, and increased network atypia, all showing significant age-related variations. Caucasian females exhibited a flatter and more homogeneous epidermis, evidenced by a decreased standard deviation of the number of layers, and a less dense cellular network with fewer cells per layer, indicated by a decrease in cell surface density. CONCLUSION: Ethnicity-wise comparisons highlighted distinct biological features specific to each population. Asian individuals showed significantly higher DEJ undulation, higher compactness, and lower cell network atypia compared to their Caucasian counterparts across age groups. Differences in stratum corneum and viable epidermal thickness on the cheekbone were also significant. LC-OCT 3D imaging provides valuable insights into the aging process in different populations and underscores inherent biological differences between Caucasian and Asian female volunteers.

Swallowing during provision of helmet ventilation: Review and provisional multidisciplinary guidance.

Use of noninvasive ventilation provided by a helmet increased globally during and after the COVID-19 pandemic. This approach may reduce need for intubation and its associated clinical complications in critically ill patients. Use of helmet interface minimizes virus aerosolization while enabling verbal communication, oral feeding and coughing/expectoration of secretions during its administration. Although improved oral hydration is a recognized benefit of helmet NIV, relatively little is known about the safety and efficiency of swallowing during helmet NIV. Risk of aspiration is a key consideration given the fragile pulmonary status of critically ill patients requiring respiratory support, and therefore the decision to initiate oral intake is best made based on multidisciplinary input. We reviewed the current published evidence on NIV and its effects on upper airway physiology and swallowing function. We then presented a case example demonstrating preservation of swallowing performance with helmet NIV. Last, we offer provisional multidisciplinary guidance for clinical practice, and provide directions for future research.

Non-invasive wool hormone assessment of Australian merino rams (Ovis aries): a pilot investigation of cortisol and testosterone.

Introduction: Non-invasive hormone assessment is growing in interest as producers and livestock researchers seek new methods to assess animal welfare. Non-invasive wool assessment offers long-term, historic reflections of hormone concentration at the scale of weeks and months - and are not limited by sampling stress - thus making wool an appropriate tissue for long-term hormone analysis. This pilot study quantified cortisol and testosterone concentrations of ram fleece and determined if there is a significant difference between segments of the sample staple, and whether there is a correlation between hormones. Cortisol is a glucocorticoid produced within the adrenal glands and secreted in anticipation of or in response to a stressor. Testosterone is an androgen mainly synthesised within the testes of males and responsible for several critical functions including regulation of muscle growth, libido and spermatogenesis. Methods: In our study, 70 topknot wool samples were collected from rams on a commercial stud property in Dirranbandi, Queensland, Australia. Of these animals, 12 samples were selected at random to undergo cortisol and testosterone quantification. In the laboratory, a single, intact staple was isolated from the total sample, divided into 10 mm segments and prepared for their respective (cortisol or testosterone) immunoassays. Results: No significant difference (p > 0.05) was found between wool segments for either cortisol or testosterone, however, statistical differences (p < 0.05) were found between individuals for both hormones. A strong positive correlation (R2 = 0.9173, p < 0.05) was found between wool cortisol and testosterone concentrations. Discussion: In summary, this study reveals the major future possibilities for non-invasive wool hormone assessment in merino rams.

The efficacy and safety of continuous theta burst stimulation for auditory hallucinations: a systematic review and meta-analysis of randomized controlled trials.

Objective: Auditory hallucinations are the most frequently occurring psychotic symptom in schizophrenia. Continuous theta burst stimulation (cTBS) has been used as an adjuvant treatment for auditory hallucinations. This meta-analysis focused on randomized controlled clinical trials (RCTs) to assess the efficacy of adjuvant cTBS on auditory hallucinations in schizophrenia. Methods: We performed a comprehensive search of four international databases from their inception to January 14, 2024, to identify relevant RCTs that assessed the effects of adjuvant cTBS on auditory hallucinations. The key words included "auditory hallucinations", "continuous theta burst stimulation" and "transcranial magnetic stimulation". Inclusion criteria included patients with auditory hallucinations in schizophrenia or schizoaffective disorder. The Revised Cochrane risk-of-bias tool for randomized trials (RoB1) were used to evaluate the risk of bias and the Review Manager Software Version 5.4 was employed to pool the data. Results: A total of 4 RCTs involving 151 patients with auditory hallucinations were included in the analysis. The Cochrane risk of bias of these studies presented "low risk" in all items. Preliminary analysis showed no significant advantage of adjuvant cTBS over sham stimulation in reducing hallucinations [4 RCTs, n = 151; SMD: -0.45 (95%CI: -1.01, 0.12), P = 0.13; I2 = 61%]. Subgroup analysis revealed that patients treated with adjuvant cTBS for more than 10 stimulation sessions and total number of pulses more than 6000 [3 RCTs, n = 87; SMD: -4.43 (95%CI: -8.22, -0.63), P = 0.02; I2 = 47%] had a statistically significant improvement in hallucination symptoms. Moreover, the rates of adverse events and discontinuation did not show any significant difference between the cTBS and sham group. Conclusions: Although preliminary analysis did not revealed a significant advantage of adjuvant cTBS over sham stimulation, subgroup analysis showed that specific parameters of cTBS appear to be effective in the treatment of auditory hallucinations in schizophrenia. Further large-scale studies are needed to determine the standard protocol of cTBS for treating auditory hallucinations. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024534045.

Noninvasive Therapies: A Forthcoming Approach to Parkinson's Treatment.

In this review, we have discussed the invasive and non-invasive treatment options for Parkinson's Disease (PD) following their safety, specificity, and reliability. Initially, this study has highlighted the invasive treatment options and the side effects they possess. A deep understanding of L-Dopa treatment, as oral or infusion, and the use of dopamine agonists has indicated that there is a need to acquire an alternative treatment for PD. The combined therapy with L-Dopa has been proven to affect PD, but with some limitations, such as mild to chronic side effects, with particular requirements of age and health of the patient and a large amount of expenditure. In the discussion of noninvasive methods to treat PD, we have found that this approach is comparatively slow and requires repetitive sessions, but is safe, effective, and reliable at any stage of PD. Electroconvulsive therapy has revealed its effectiveness in various neurological diseases, including PD. Transcranial current stimulation (direct or alternative) has already been shown to have an alleviative response to PD symptoms. Transcranial magnetic stimulations and other strategies of using the magnetic field for potential treatment options for PD need to be explored further imminently.

The use of saliva and blood progesterone to profile the menstrual cycles of youth professional football players.

Background: Understanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected "in situ", with relative ease, necessary in applied sport environments. Objective: The aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method. Methodology: Twenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast. Results: According to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = <0.001, 95% CI 0.72-0.86). The association between serum and saliva progesterone was weaker in the oligomenorrheic group (r = 0.47, p = <0.001, 95% CI 0.27-0.64) and was not present in the anovulatory or amenorrhoeic groups. Conclusions: Salivary measurements of progesterone are well correlated with capillary blood when taken during eumenorrheic menstrual cycles and presents a viable, non-invasive method of establishing characteristic progesterone fluctuations in applied sport settings. The strength of the association appears to be concentration dependent. A luteal phase saliva progesterone (P4) >50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.

New diagnostic and nonsurgical local treatment modalities for early stage lung cancer.

This paper highlights developments in diagnostic and nonsurgical local treatment modalities that have changed the management of early-stage lung cancer. These innovations aim to enhance diagnostic accuracy, minimize invasiveness, and improve patient outcomes. Liquid biopsies are emerging as promising tools for non-invasive diagnosis and monitoring, enabling earlier intervention without being standardized yet as well as not yet anchored in the guidelines. Endobronchial navigation has emerged as an innovative tool. By combining electromagnetic or GPS-like technology with 3D imaging and a steerable catheter, it enables accurate biopsy of small, peripheral lesions that were once challenging to sample, with a very low pneumothorax rate. Regarding nonsurgical treatments, stereotactic body radiotherapy (SBRT) continues to shine as a non-invasive local treatment modality for early-stage lung cancer and is the guideline-recommended standard-of-care for inoperable patients and patients refusing the risk of surgical resection. The low toxicity and excellent local control has made it an attractive alternative to surgery even in fitter patients. Percutaneous ablative techniques utilising energies such as microwave or pulse-field electroporation are options for patients who are not candidates for surgery or SBRT. Bronchoscopic ablation delivers the same energies but with a very lower pneumothorax rate and it is therefore also open to patients with multiple and bilateral lesions.