Paravertebral Ganglioneuroma in Pediatric Age: A Case Report.

Ganglioneuromas (GNs) are rare benign tumors common in the pediatric population. Although mostly asymptomatic, some can cause symptoms, particularly neurological ones. Here, we report a case of a two-year-old male child, who presented changes in gait, an alarming sign, during a child health surveillance appointment. On physical examination, the child presented a "duck" gait pattern, axial and appendicular hypotonia, proximal weakness of the pelvic girdle, and a positive Gowers sign. The child was referred to a pediatric neurology appointment where he underwent neuraxial magnetic resonance imaging, identifying a large and expansive formation in the dorsolumbar transition suggestive of neuroblastoma, considering the age group. However, a computed tomography-guided biopsy revealed it to be a paravertebral GN. Tumor resection was performed, leaving some paravertebral tumor residue. After one year of motor rehabilitation, the child had a normal neurological examination. The child is currently five years old and is undergoing annual clinical and imaging surveillance. This case allows us to reflect on the importance of encouraging children and young people to attend recommended surveillance appointments and reminds us that the rarest situations can occur.

Pulse generators for enhanced magnetomotive ultrasound: Toward a cost-effective imaging for tissue characterization.

Magnetomotive ultrasound (MMUS) stands out as a promising and effective ultrasound-based method for detecting magnetic nanoparticles (MNPs) within tissues. This innovative technique relies on the precise estimation of micrometric displacements induced by the interaction of an external magnetic field with MNPs. Pulsed MMUS has emerged as a strategic alternative to address limitations associated with harmonic excitation, such as heat generation in amplifiers and coils, frequency-dependent tissue mechanical responses, and prolonged magnetic field rise times. Despite the growing interest in MMUS, the devices conventionally employed to excite the coil are not specifically tailored to generate intense magnetic fields while minimizing interference with the transient behavior of induced displacements. To bridge this gap, our work introduces the design and fabrication of two pulse generators: one based on a capacitor-discharge circuit and the other on a resonant-inverter circuit. We evaluated the performance of these pulse generators by considering parameters such as the magnetic field generated, rise and fall times, and their ability to supply sustained current for varied pulse widths across different pulse repetition frequencies. Furthermore, we carried out a practical MMUS implementation using tissue-mimicking phantoms, demonstrating the capability of both devices to achieve magnetic fields of up to 1 T and average displacements of 25 µm within the phantom. In addition, we estimated the shear wave velocity, effective shear modulus, and their temperature-dependent variations. Our findings highlight the versatility and efficacy of the proposed pulse generators and emphasize their potential as low-cost platforms for theranostic applications, enabling the assessment of targeted entities within biological tissues.

BAMLET administration via drinking water inhibits intestinal tumor development and promotes long-term health.

Though new targeted therapies for colorectal cancer, which progresses from local intestinal tumors to metastatic disease, are being developed, tumor specificity remains an important problem, and side effects a major concern. Here, we show that the protein-fatty acid complex BAMLET (bovine alpha-lactalbumin made lethal to tumor cells) can act as a peroral treatment for colorectal cancer. ApcMin/+ mice, which carry mutations relevant to hereditary and sporadic human colorectal cancer, that received BAMLET in the drinking water showed long-term protection against tumor development and decreased expression of tumor growth-, migration-, metastasis- and angiogenesis-related genes. BAMLET treatment via drinking water inhibited the Wnt/ß-catenin and PD-1 signaling pathways and prolonged survival without evidence of toxicity. Systemic disease in the lungs, livers, spleens, and kidneys, which accompanied tumor progression, was inhibited by BAMLET treatment. The metabolic response to BAMLET included carbohydrate and lipid metabolism, which were inhibited in tumor prone ApcMin/+ mice and weakly regulated in C57BL/6 mice, suggesting potential health benefits of peroral BAMLET administration in addition to the potent antitumor effects. Together, these findings suggest that BAMLET administration in the drinking water maintains antitumor pressure by removing emergent cancer cells and reprogramming gene expression in intestinal and extra-intestinal tissues.

Craniofacial syndromes and class III phenotype: common genotype fingerprints? A scoping review and meta-analysis.

Skeletal Class III (SCIII) is among the most challenging craniofacial dysmorphologies to treat. There is, however, a knowledge gap regarding which syndromes share this clinical phenotype. The aims of this study were to: (i) identify the syndromes affected by the SCIII phenotype; (ii) clarify the involvement of maxillary and/or mandibular structures; (iii) explore shared genetic/molecular mechanisms. A two-step strategy was designed: [Step#1] OMIM, MHDD, HPO, GeneReviews and MedGen databases were explored; [Step#2]: Syndromic conditions indexed in [Step#1] were explored in Medline, Pubmed, Scopus, Cochrane Library, WOS and OpenGrey. Eligibility criteria were defined. Individual studies were assessed for risk of bias using the New Ottawa Scale. For quantitative analysis, a meta-analysis was conducted. This scoping review is a hypothesis-generating research. Twenty-two studies met the eligibility criteria. Eight syndromes affected by the SCIII were targeted: Apert syndrome, Crouzon syndrome, achondroplasia, X-linked hypohidrotic ectodermal dysplasia (XLED), tricho-dento-osseous syndrome, cleidocranial dysplasia, Klinefelter and Down syndromes. Despite heterogeneity between studies [p < 0.05], overall effects showed that midface components were affected in Apert and Down Syndromes, lower face in Klinefelter Syndrome and midface and lower face components in XLED. Our review provides new evidence on the craniofacial characteristics of genetically confirmed syndromes exhibiting the SCIII phenotype. Four major regulatory pathways might have a modulatory effect on this phenotype. IMPACT: What does this review add to the existing literature? To date, there is no literature exploring which particular syndromes exhibit mandibular prognathism as a common trait. Through this research, it was possibly to identify the particular syndromes that share the skeletal Class III phenotype (mandibular prognathism) as a common trait highlighting the common genetic and molecular pathways between different syndromes acknowledging their impact in craniofacial development.

Measuring the value of solidarity: The abem financial assistance program for out-of-pocket payments on pharmacy medicines in Portugal.

OBJECTIVE: Out-of-pocket payments for prescribed medicines are still comparatively high in Portugal. The abem program was launched in Portugal in May 2016 to aid vulnerable groups by completely covering out-of-pocket costs of prescribed medicines in community pharmacies. This study assesses the impact of the program on poverty and catastrophic health expenditures. METHODS: A longitudinal study was carried out with the analysis of several program databases (from the beginning of the program in May 2016 to September 2018) covering the cohorts of beneficiaries, daily data on medicines dispensed, social referencing entities, and solidarity pharmacies. The study provides estimates of standard poverty measures (intensity and severity) as well as the incidence of catastrophic health expenditures. RESULTS: More than 6000 beneficiaries were supported (56.8% female, 34.7% aged 65 or over), encompassing 127,510 medicines (mainly nervous system and cardiovascular system) with an average 26.9% co-payment (payments totalling €1.5 million). The program achieved substantial reductions in poverty (3.4% in intensity, 5.6% in severity), and eliminated cases with catastrophic health expenditures in medicines that would have affected 7.5% of the beneficiaries. CONCLUSIONS: Findings confirm a continuous increase in the number of beneficiaries, enabling access to medicines especially for the vulnerable elderly, and a sizable impact on eliminating out-of-pocket payments for medicines in the target population.

Mitigating skin tone bias in linear array in vivo photoacoustic imaging with short-lag spatial coherence beamforming.

Photoacoustic (PA) imaging has the potential to deliver non-invasive diagnostic information. However, skin tone differences bias PA target visualization, as the elevated optical absorption of melanated skin decreases optical fluence within the imaging plane and increases the presence of acoustic clutter. This paper demonstrates that short-lag spatial coherence (SLSC) beamforming mitigates this bias. PA data from the forearm of 18 volunteers were acquired with 750-, 810-, and 870-nm wavelengths. Skin tones ranging from light to dark were objectively quantified using the individual typology angle (ITA°). The signal-to-noise ratio (SNR) of the radial artery (RA) and surrounding clutter were measured. Clutter was minimal (e.g., -16 dB relative to the RA) with lighter skin tones and increased to -8 dB with darker tones, which compromised RA visualization in conventional PA images. SLSC beamforming achieved a median SNR improvement of 3.8 dB, resulting in better RA visualization for all skin tones.

Does participation in the European Trauma Course lead to new behaviours and organisational change? A Portuguese experience.

BACKGROUND: Medical educational courses can be successful from an immediate feedback perspective but not lead to new behaviour or organisational changes in the workplace. The aim of this study was to assess the self-perceived impact of the European Trauma Course (ETC) on Reanima trainees' behaviour and organisational change. METHODS: A 40-item questionnaire based on Holton's evaluation model was used to evaluate the candidate's perceptions. The results were analysed with descriptive and inferential statistical analysis using nonparametric tests with α = 0.05. RESULTS: Out of 295 participants, 126 responded to the survey. Of these, 94% affirmed that the ETC modified their approach to trauma patients, and 71.4% described a change in their behaviour. Postcourse responders changed their behaviour in their initial approach to trauma care in the nontechnical skills of communication, prioritisation and teamwork. Being an ETC instructor strongly influenced the acquisition of new material, and this group was able to implement changes in attitudes. Individuals with no previous trauma course experience identified lack of self-efficacy as a significant obstacle to introducing new work-based learning. In contrast, responders with ATLS training noted a lack of ETC colleagues as the main impediment for moving from conceptualisation to experimentation in the workplace. CONCLUSIONS: Participation in the ETC led to behavioural changes in the workplace. However, the ability to influence others and bring about wider organisational changes was more difficult to achieve. Major factors were the status of the person, their experience and self-efficacy. National organisational impact was obtained, which went far beyond our aspirations in acknowledging change in individual daily practice. Future research studies will include the effect of implementing the ETC methodology on the outcome of trauma patients.

Expert perspectives on strategic factors for the management and prevention of heart failure in Portugal.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) has significant morbidity and mortality, and its prevalence will continue to increase in the future. This unfavorable evolution requires reflection as well as recommendations and decisions based on expert critical and strategic appraisal. METHODS: In the Acceleration on Heart Failure Empowerment and Awareness - the Portuguese Challenge (ATHENA-PT) study, a range of strategic factors that represent the strengths, weaknesses, threats, and opportunities (SWOT) of HF in Portugal were established. These factors were assessed quantitatively by experts, to create a final SWOT matrix for the management and prevention of HF in Portugal and to outline recommendations. RESULTS: For HF management, the panel emphasized the following strategic recommendations: (i) reimbursement of natriuretic peptides testing in primary healthcare; (ii) reimbursement of Doppler assessment in echocardiographic studies and promotion of detailed information in reports; (iii) intervention to improve the prognosis of patients with HF with preserved ejection fraction; (iv) ensuring effective healthcare transition between hospital and ambulatory units, using checklists/protocols; and (v) reinforcement and commitment to the training of primary health physicians and to the cardiac rehabilitation of patients. For the prevention of HF, the following recommendations/proposals were proposed: (i) campaigns to raise awareness of cardiovascular disease risk factors; (ii) promotion of physical exercise and healthy eating; and (iii) avoidance of therapeutic inertia in the management of risk factors. CONCLUSIONS: The acknowledgment of various strategic factors and their prioritization by experts made it possible to create and reinforce a range of new strategic recommendations for the management and prevention of HF.

Hybrid Nanoparticles of Citrate-Coated Manganese Ferrite and Gold Nanorods in Magneto-Optical Imaging and Thermal Therapy.

The development of nanomaterials has drawn considerable attention in nanomedicine to advance cancer diagnosis and treatment over the last decades. Gold nanorods (GNRs) and magnetic nanoparticles (MNPs) have been known as commonly used nanostructures in biomedical applications due to their attractive optical properties and superparamagnetic (SP) behaviors, respectively. In this study, we proposed a simple combination of plasmonic and SP properties into hybrid NPs of citrate-coated manganese ferrite (Ci-MnFe2O4) and cetyltrimethylammonium bromide-coated GNRs (CTAB-GNRs). In this regard, two different samples were prepared: the first was composed of Ci-MnFe2O4 (0.4 wt%), and the second contained hybrid NPs of Ci-MnFe2O4 (0.4 wt%) and CTAB-GNRs (0.04 wt%). Characterization measurements such as UV-Visible spectroscopy and transmission electron microscopy (TEM) revealed electrostatic interactions caused by the opposing surface charges of hybrid NPs, which resulted in the formation of small nanoclusters. The performance of the two samples was investigated using magneto-motive ultrasound imaging (MMUS). The sample containing Ci-MnFe2O4_CTAB-GNRs demonstrated a displacement nearly two-fold greater than just using Ci-MnFe2O4; therefore, enhancing MMUS image contrast. Furthermore, the preliminary potential of these hybrid NPs was also examined in magnetic hyperthermia (MH) and photoacoustic imaging (PAI) modalities. Lastly, these hybrid NPs demonstrated high stability and an absence of aggregation in water and phosphate buffer solution (PBS) medium. Thus, Ci-MnFe2O4_CTAB-GNRs hybrid NPs can be considered as a potential contrast agent in MMUS and PAI and a heat generator in MH.

General health check-ups: To check or not to check? A question of choosing wisely.

In high-income countries, regular general health check-ups are part of the fabric of the health care systems. The hidden concept of general health check-ups, promoted for more than a century, is to identify diseases at a stage at which early intervention can be effective. However, there has been little evidence to support the benefits of such checkups. Choosing wisely (CW) campaigns may represent a tremendous opportunity to eventually shift patients and physicians away from the non-evidence based yet firmly entrenched practice of the general health check-up. As campaign leaders and members of the CW working group of the European Federation of Internal Medicine, we want to join the discussion by giving our perspective based on the best available evidence.

Histology-Agnostic Drugs: A Paradigm Shift-A Narrative Review.

Cancer diagnosis and therapeutics have been traditionally based on pathologic classification at the organ of origin. The availability of an unprecedented amount of clinical and biologic data provides a unique window of opportunity for the development of new drugs. What was once treated as a homogeneous disease with a one-size-fits-all approach was shown to be a rather heterogeneous condition, with multiple targetable mutations that can vary during the course of the disease. Clinical trial designs have had to adapt to the exponential growth of targetable mechanisms and new agents, with ensuing challenges that are closer to those experienced with rare diseases and orphan medicines. To face these problems, precision/enrichment and other novel trial designs have been developed, and the concept of histology-agnostic targeted therapeutic agents has emerged. Patients are selected for a specific agent based on specific genomic or molecular alterations, with the same compound used to potentially treat a multiplicity of cancers, granted that the actionable driver alteration is present. There are currently approved drugs for such indications, but this approach has raised issues on multiple levels. This review aims to address the challenges of this new concept and provide insights into possible solutions and frameworks on how to tackle them.

Atherosclerosis in the primary health care setting: A real-word data study.

INTRODUCTION AND OBJECTIVES: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. METHODS: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. RESULTS: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). CONCLUSIONS: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.

Relationship between lymphedema after breast cancer treatment and biophysical characteristics of the affected tissue.

The treatment of breast cancer is often complicated by lymphedema of the upper limbs. Standard lymphedema evaluation methodologies are not able to measure tissue fibrosis. The ultrasound aspects related to tissue microstructures of lymphedema are neglected in clinical evaluations. The objective of this study was to identify and measure the degree of impairment, topography, and biophysical alterations of subcutaneous lymphedema tissue secondary to the treatment of breast cancer by ultrasonography. Forty-two women at a mean age of 58 (±9.7) years, with unilateral lymphedema due to breast cancer treatment, were evaluated. The upper limbs were divided into affected (affected by lymphedema) and control (contralateral limb). Each limb was subdivided into seven areas, defined by perimetry, evaluated in pairs. The biophysical characteristics thickness, entropy, and echogenicity were evaluated by ultrasonography. The results showed a significant difference in the echogenicity and thickness variables between the affected and unaffected upper limb, in all the extent of the upper limb, while entropy showed no significant difference. The findings indicate that the data presented were consistent both in identifying and measuring the degree of impairment and biophysical changes in the subcutaneous tissue of lymphedema secondary to the treatment of breast cancer.

Broadening risk factor or disease definition as a driver for overdiagnosis: A narrative review.

Medical overuse-defined as the provision of health services for which potential harms exceed potential benefits-constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension-using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease).

Lost in transition: a systematic review of the association between unemployment and mental health.

BACKGROUND: Unemployment can involve financial strain and major psychosocial challenges. Integration of the existing evidence is needed to better characterize the association between unemployment and mental health, independently of macroeconomic contexts. AIMS: Main objectives of this study: (a) review, integrate, and summarize evidence about the association between unemployment and anxiety disorders, mood disorders, and suicidal behaviour, and (b) identify variables affecting this association. METHOD: Systematic review of literature following PRISMA guidelines. PubMed, Web of Science, SciELO, RCAAP, and Cochrane Library databases were searched. Quantitative empirical studies on the association between unemployment and mental illness of community-based samples were included. The quality of the evidence provided in the studies was assessed following pre-defined methodological criteria. RESULTS: Overall, 294 articles were considered eligible. In total, 55.7% of the studies were conducted in Europe; 91.4% supported a positive association between increased unemployment rates and anxiety, mood disorders, or suicidal behavior. Men and young adults were most severely affected by unemployment. Education and social support were found to buffer the negative outcomes of job loss. CONCLUSIONS: Unemployment was inversely associated with mental health irrespectively of the economic context; unemployed individuals were more vulnerable to commit suicide and suffer from anxiety and mood disorders.

Pharmacy interventions on COVID-19 in Europe: Mapping current practices and a scoping review.

BACKGROUND: The COVID-19 pandemic has put community pharmacists at the frontline of prevention, preparedness, response, and recovery efforts. Pharmacies had to reorganize and implement several different interventions and measures within a very short time frame. OBJECTIVES: 1) To map the current reported practice and trends and to review the literature on pharmacy-based interventions on COVID-19 provided in Europe; 2) To identify knowledge gaps and future avenues for pharmacy research, policy, and practice in response to public health emergencies. METHODS: We used a mixed methods approach combining country mapping of current practices of pharmacy interventions on COVID-19 reported by pharmacy associations in Europe with a scoping review of published literature. RESULTS: We mapped current practices on 31 pharmacy interventions on COVID-19 in 32 countries in Europe. Almost all preventive measures to reduce health risks have been provided in most countries. Other frequent interventions reflected preparedness for stockpiling, increased demand for services and products, and important patient care interventions exceeding dispensing role. Expanded powers granted to pharmacies and legislation passed in view of COVID-19 enabled services that improve access to medicines and relevant products, patient screening and referral including point-of-care antigen testing, support to vulnerable patients, and COVID-19 vaccination. We identified 9 studies conducted in pharmacies in 7 countries in Europe. Most studies are cross-sectional and/or descriptive. Pharmacy associations played an important supporting role by developing and updating guidance and emergency plans to assist community pharmacists. CONCLUSIONS: A wide array of pharmacy interventions on COVID-19 was implemented in several countries within a very short time frame. Research on pharmacy interventions on COVID-19 is still in its infancy but confirmed the wide array of interventions provided and expanded powers granted to pharmacies. These findings may provide a significant impact to improve pharmacy research, policy, and practice in response to future public health emergencies in Europe and globally.