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Background. With the latest COVID-19 deaths reported to WHO now exceeding 3.3 million, COVID-19 has developed into a milestone of our medical generation, causing disruption in communities and hospital services. With complications raging from respiratory failure to inflammatory complication and even thrombotic events, we wanted to establish if lymphopenia is a predictive marker of disease severity in patients infected with SARS-CoV-2. Material and methods. 152 patients were included from 4 different departments of Colentina Clinical Hospital in this retrospective observational study beginning with July 2020 to March 2021. All of these patients were confirmed with COVID-19 by real-time reverse transcriptase polymerase chain reaction test for nasal and pharyngeal swab samples. As including criteria we have set the patients hospitalized confirmed with COVID-19, with at least 10 days of hospitalization. The data in demographic, basic clinical and laboratory characteristics and particular evolution was obtained from electronical medical records from each department involved in the study, by maintaining personal data confidentially. We set up criteria for lymphopenia as absolute lymphocyte count below 1.5 x 1000/µl, based on the laboratory reference values. The study group was divided into several groups: male and female, ICU (Intensive Care Unit) and non-ICU, deceased and released, lymphopenia at day 1 (day of admission to hospital) , lymphopenia at day 10 (10 days after hospital admission). Results. The age of the patients ranged from 17 to 92, with the median age of 57.62. Enrolled were 73 (47.4%) female patients and 79 (52.6%) male patients, with an ICU admission rate of 35.71% (55 patients), and a mortality rate of 21.43% (33 patients). Patients who have a severe form of COVID-19 and are admitted to the ICU for mechanical ventilation did not recover and died (p < 0.001). Male patients may have higher risk of requiring admission in ICU (p value = 0.357) and higher risk of death (p value = 0.241). Even in our small group of 152 patients, the elderly patients suffered a more severe form of the disease, which was reflected on the number of admission days (p = 0.07). In our specific population, based on the statistics, if we take the number of lymphocytes on the day of admission as the dependent factor, we can safely say that there is a statistically significant correlation between lymphopenia at day 1 and the ICU admission (p < 0.001) or death (p = 0.014). The number of lymphocytes following 10 days of admission is another prognostic marker as we can see from the results of statistic tests: there is a statistically significant correlation between lymphopenia at day 10 and the ICU admission (p < 0.001) or death (p < 0.001). Age is another predictive factor regarding the number of lymphocytes following 10 days of admission (r = -0.078 and p = 0.356). Conclusion. Lymphopenia is an easy-to-determine, efficient and reliable biomarker to establish the disease evolution in patients with COVID-19.

Background. Stem cell transplantation is an important therapeutic approach for patients with malignant hemopathies, whether we refer to autologous or allogeneic stem cell transplantation. Aims and methods. We present the characteristics of a group of 54 patients diagnosed with malignant haemopathy in the Department of Hematology of the Colentina Clinical Hospital, between 2004 and 2018, and who have benefited from stem cell transplantation both in the country and abroad. The data analyzed were: diagnosis of the disease, type of response to induction therapy, type and timing of transplantation, transplant in first remission or relapse, if there were patients who benefited from a second transplant, post-transplant survival, as well as demographics. The statistical analysis was performed using the system MedCalc Statistical Software Version 18.11.3. Results and conclusions. Survival analysis was applied separately for autotransplant patients and those who benefited from allotransplant (Kaplan Meier survival analyses). Significant differences were observed due to transplantation type and due to relapse after transplant, in our lot of patients. Post-transplant recurrence was an unfavorable prognostic factor for both autologous and allogeneic transplanted patients. Update. A new challenge: The COVID-19 pandemic threat. The SARS-CoV-2 infection is a threat for immunocompromised patients. From a group of 9 patients hospitalized in 2020 for COVID-19 in the Department of Hematology of the Colentina Clinical Hospital, and who have benefited in the past from stem cell transplantation (2 patients) or organ transplant (1 patient – lung, 3 patients – liver, 3 patients – kidney) in Romania, 4 of them have required hospitalization in the Intensive Care Unit (ICU) (authors's observational data). New data are needed to elucidate the prognostic factors to establish the outcome of transplant patients such as for all cancer patients or immunocompromised patients in the current COVID pandemic 19 era and the impact on public health.

Background: Fibrocystic changes are associated with an increased risk of breast cancer. Genetic alterations have been found in fibrocystic changes with or without epithelial changes, suggesting that critical oncogenic events are occurring at an early stage.Methods: We investigated a unique collective of 17 breast cancer patients who, prior to the diagnosis of invasive breast cancer, underwent open surgical biopsy showing fibrocystic changes of the breast. The time span between biopsy for fibrocystic changes and invasive carcinoma ranged from 1 to 11 years (average 5.3 years). Ten (58.8%) of the patients had an ipsilateral invasive carcinoma, and 7 (41.2%) of the patients developed an invasive carcinoma of the contralateral breast. Massive parallel sequencing targeting genes frequently mutated in breast cancer was performed on the fibrocystic breast tissue as well as the ensuing cancer tissue.Results: In 9 cases, somatic mutations were found in the tumor tissue, the most prevalent being PIK3CA mutations (n = 4), followed by TP53 mutations (n = 2). None of these mutations were present in the previously removed mastopathy tissue. In one of the cases, an ERBB3 E928G mutation was present in the mastopathy as well as in the tumor tissue, with the variant allele frequency in the mastopathy being

Abstract Background Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. Methods In this study, 382 infants born at 24+0–27+6 weeks’ gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks’ postmenstrual age. The secondary outcomes are BPD at 36 weeks’ postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). Discussion This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0–27+6 weeks’ gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks’ postmenstrual age of life. Trial registration ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Abstract Background Postpartum depression constitutes a significant public health issue, with prevalence rates ranging between 8 and 19% in high-income nations. Nevertheless, numerous barriers, including time constraints, societal stigmatization, and feelings of shame, contribute to the limited utilization of healthcare services during the postpartum period. Digital interventions offer an opportunity to enhance care for women experiencing postpartum depressive symptoms. Methods We will conduct a two-arm randomized controlled trial to assess the effectiveness of a smartphone-based intervention in comparison to a treatment-as-usual control group in Germany. Our aim is to randomize 556 participants in a 1:1 ratio. Participants in the intervention group will be provided access to a preventive smartphone-based intervention called “Smart-e-Moms,” which incorporates therapeutic support and comprises 10 concise modules rooted in cognitive-behavioral therapy. For the intervention group, evaluations will take place at baseline (t0), prior to sessions 4 and 8 (intermediate assessments), and upon completing the intervention 6 weeks after baseline (t1). The control group’s assessments will be at baseline (t0) and 6 weeks after baseline. Follow-up assessments are scheduled at 12 and 24 weeks from baseline to examine the short-term stability of any observed effects. We anticipate that participants in the intervention group will exhibit improvements in their postpartum depressive symptoms (as measured with the Edinburgh Postnatal Depression Scale). Additionally, we will analyze secondary outcomes, including maternal bonding, stress levels, self-efficacy, satisfaction with the intervention, and healthcare utilization. Discussion If Smart-e-Moms proves to be effective, it has the potential to play a significant role in postpartum depression care within German-speaking regions. Ideally, this intervention could not only benefit maternal well-being but also improve the prospects for healthy child development. Trial registration German clinical trials registry DRKS00032324. Registered on January 26, 2024.

Introduction: Infantile-onset Pompe disease (IOPD) is due to mutations in the GAA gene leading to profound deficiency of the lysosomal enzyme α-1,4-glucosidase. The disease is characterized by severe hypotonia, hypertrophic cardiomyopathy, macroglossia, and liver enlargement with onset in the first months of life. In the late-onset form (LOPD), muscle signs predominate with a clinical picture resembling muscle dystrophies. Enzyme replacement therapy with alglucosidase alfa (rhGAA) has been available since 2006 and patients treated with the enzyme show improved outcomes. Nevertheless, there is evidence that some patients have a suboptimal response or, after an initial improvement, reach a plateau with stabilization of the clinical picture. Thus, a new enzyme formulation, avalglucosidase alfa (neoGAA), with a higher degree of mannosylation, was developed. Methods: We conducted a multicenter survey that collected data on four patients with IOPD, aged 6 to 16 years, who were switched to neoGAA thanks to a compassionate use program, after being treated for an average of 11.5 years with rhGAA. Follow-up data, including biochemical parameters and clinical features, were analyzed to determine clinical outcomes and the safety profile after a mean of 9 months. Results: Patients with IOPD who were treated with neoGAA showed a positive change in biomarker levels. Moreover, the clinical picture revealed improved motor performance and cardiac parameters in patients who previously responded poorly. Conclusion: This study highlights the improved efficacy of neoGAA, as a next generation enzyme replacement therapy, in 4 Italian patients with IOPD. Several clinical parameters showed a positive response to the new formulation suggesting that, if used at diagnosis, neoGAA may result in better outcomes for patients with IOPD.

Introduction: Robust immunoassays for quantification of Alzheimer's disease (AD)-specific biomarkers are required for routine diagnostics. We report analytical performance characteristics of four new chemiluminescence immunoassays (ChLIA, EUROIMMUN) running on closed, fully automated random-access instruments for quantification of Aβ1-40, Aβ1-42, tTau, and pTau(181) in human cerebrospinal fluid (CSF). Methods: ChLIAs were validated according to the guidelines of the Clinical and Laboratory Standards Institute (CLSI). Optimal cut-offs for biomarkers and biomarker ratios were determined using samples from 219 AD patients and 220 patients with AD-related symptoms. For performance comparison, biomarker concentrations were measured in 110 diagnostic leftover samples using the ChLIAs and established Lumipulse G assays (Fujirebio). Results: All ChLIAs met CLSI criteria. Overall agreement between assays was 89.0%–97.3 % with highly correlating results (Pearson's correlation coefficients: 0.82–0.99). Passing-Bablok regression analysis revealed systematic differences. Discussion: EUROIMMUN ChLIAs showed good analytical performances and represent new valuable tools for diagnostics of AD.

Objetivo: Avaliar a evolução das prevalências de baixo peso e excesso de peso entre gestantes adolescentes e adultas nas diferentes regiões brasileiras acompanhadas pelo Sistema de Vigilância Alimentar e Nutricional (SISVAN) entre os anos de 2010 e 2019. Método: Estudo ecológico incluindo todas as gestantes atendidas na Atenção Primária à Saúde, em todas as regiões (Norte, Nordeste, Centro-Oeste, Sudeste e Sul) do Brasil. As tendências das prevalências de baixo peso e excesso de peso entre as gestantes adultas e adolescentes entre 2010 e 2019 foram analisadas por modelos de regressão por pontos de inflexão (joinpoint regression analysis). Resultados: As prevalências de baixo peso em gestantes adolescentes diminuíram ao longo dos anos no Brasil (p = 0,040), porém menos na região Centro-Oeste (p = 0,164). Já o baixo peso em gestantes adultas diminuiu no Brasil (p < 0,001) e em todas as macrorregiões ao longo dos anos. A prevalência de sobrepeso e obesidade aumentou entre as gestantes adolescentes e adultas no Brasil (p < 0,001) e em todas as macrorregiões. Conclusão: As gestantes brasileiras atendidas na Atenção Primária são acometidas por uma dupla carga de desvios nutricionais, que aumentam o risco de desfechos desfavoráveis para a mãe e o bebê.

Abstract Background Mental health issues are common among patients with chronic physical conditions, affecting approximately one in five patients. Poor mental health is associated with worse disease outcomes and increased mortality. Problem-solving therapy (PST) may be a suitable treatment for targeting poor mental health in these patients. This study protocol describes a randomised controlled trial of the Healthy Mind intervention, a general practice-based intervention offering PST to patients with type 2 diabetes and/or ischaemic heart disease and poor mental well-being. Methods A stepped-wedge cluster-randomised controlled trial with 1-year follow-up will be conducted in Danish general practice. At the annual chronic care consultation, patients with type 2 diabetes and/or chronic ischaemic heart disease will be screened for poor mental well-being. Patients in the control group will be offered usual care while patients in the intervention group will be offered treatment with PST provided by general practitioners (GPs) or general practice staff, such as nurses, who will undergo a 2-day PST course before transitioning from the control to the intervention group. The primary outcome is change in depressive symptoms after 6 and 12 months. Secondary outcomes include change in mental well-being, anxiety, and diabetes distress (patients with type 2 diabetes) after 6 and 12 months as well as change in total cholesterol levels, low-density lipoprotein (LDL) levels, and blood glucose levels (patients with diabetes) after 12 months. Process outcomes include measures of implementation and mechanisms of impact. We aim to include a total of 188 patients, corresponding to approximately 14 average-sized general practices. Discussion The Healthy Mind trial investigates the impact of PST treatment for patients with chronic disease and poor mental well-being in general practice. This will be the first randomised controlled trial determining the effect of PST treatment for patients with chronic diseases in general practice. The results of this study will provide relevant insights to aid GPs, and general practice staff manage patients with poor mental well-being. Trial registration ClinicalTrials.gov NCT05611112. Registered on October 28, 2022.

Abstract Chronic, non-healing wounds represent a significant challenge for healthcare systems worldwide, often requiring significant human and financial resources. Chronic wounds arise from the complex interplay of underlying comorbidities, such as diabetes or vascular diseases, lifestyle factors, and genetic risk profiles which may predispose extremities to local ischemia. Injuries are further exacerbated by bacterial colonization and the formation of biofilms. Infection, consequently, perpetuates a chronic inflammatory microenvironment, preventing the progression and completion of normal wound healing. The current standard of care (SOC) for chronic wounds involves surgical debridement along with localized wound irrigation, which requires inpatient care under general anesthesia. This could be followed by, if necessary, defect coverage via a reconstructive ladder utilizing wound debridement along with skin graft, local, or free flap techniques once the wound conditions are stabilized and adequate blood supply is restored. To promote physiological wound healing, a variety of approaches have been subjected to translational research. Beyond conventional wound healing drugs and devices that currently supplement treatments, cellular and immunotherapies have emerged as promising therapeutics that can behave as tailored therapies with cell- or molecule-specific wound healing properties. However, in contrast to the clinical omnipresence of chronic wound healing disorders, there remains a shortage of studies condensing the current body of evidence on cellular therapies and immunotherapies for chronic wounds. This review provides a comprehensive exploration of current therapies, experimental approaches, and translational studies, offering insights into their efficacy and limitations. Ultimately, we hope this line of research may serve as an evidence-based foundation to guide further experimental and translational approaches and optimize patient care long-term.

Introduction: Lung cancer (LC) is a disease with a great impact worldwide in the number of deaths and health costs. The high incidence and mortality of this disease associated with late diagnosis and the improved prognosis with early detection determine that it is a pathology that can benefit from early detection. Low radiation dose tomography (LDCT) demonstrated a method that can be performed periodically to a group of people at high risk of developing CP and thus reduce mortality from this disease. However, this benefit is such when it is developed under an organized program with multidisciplinary participation specialized in lung cancer. Methods: It is proposed to determine basic guidelines for the development of early detection of lung cancer in Latin America so that it can be carried out uniformly, with the lowest risk and the maximum expected benefit. The main publications referring to this topic were analyzed, considering the diversity of care and access in Latin America. Result: Minimum requirements are developed for the implementation of a program. Discussion: The number of programs in the region is small and depends more on individual efforts than on general health policies. We consider that these guidelines can serve as support for the development of more programs in the region and in a more homogeneous way.

Abstract Background Vision is an important and defining element of laparoscopy and significantly affects the outcome of surgery in terms of time, error, and precision. Several new imaging systems have become available for laparoscopic surgery, including three-dimensional (3D) high-definition (HD) and two-dimensional (2D) ultra-high-resolution (4K) monitors. 3D HD systems offer a number of potential benefits to surgeons and patients over traditional 2D systems, including reduced operating time, blood loss, and hospital stay. However, the performance of 3D systems against the new, ultra-high definition 4K systems is barely known and highly controversial. There is a paucity of studies comparing them in clinical settings. The aim of this study is to compare 2D 4K and 3D HD perspectives in gastric bypass surgery. Methods Forty-eight patients with an indication for gastric bypass will be randomized to receive laparoscopic gastric bypass surgery using either 2D 4K or 3D HD systems. The operations will be performed by a well-coordinated team of three senior surgeons. The primary outcome is operative time. Secondary outcomes include intraoperative complications, blood loss, operator workload as assessed by the validated Surg-TLX questionnaire, and postoperative complications according to the Clavien-Dindo classification. An interim analysis is planned after enrollment of 12 participants for each group. Discussion This prospective, randomized trial is designed to test the hypothesis that the use of a 3D HD system will result in a significant improvement in operative time compared to a 2D 4K system in bariatric surgery. The objective is to provide clinical evidence for new laparoscopic imaging systems and to evaluate potential benefits. Trial registration This trial is registered at clinicaltrials.gov under the identifier NCT05895058. Registered 30 May 2023. BASEC2023-D0014 [Registry ID Swissethics, approved 3 May 2023]. SNCTP000005489 [SNCTP study register, last updated 13 July 2023].

AbstractBackground Task shifting from general practitioners (GPs) to other health professionals could solve the increased workload, but an overview of the evidence is lacking for out-of-hours primary care (OOH-PC).Objectives To evaluate the content and quality of task shifting from GPs to other health professionals in clinic consultations and home visits in OOH-PC.Methods Four database literature searches were performed on 13 December 2021, and updated in August 2023. We included articles that studied content (patient characteristics, reason for encounter) and/or quality (patient satisfaction, safety, efficiency) of task shifting in face-to-face contacts at OOH-PC. Two authors independently screened articles for inclusion and assessed the methodological quality of included articles using the JBI critical appraisal checklist. Data was extracted and results were synthesised in a narrative summary.Results The search identified 1,829 articles, resulting in the final inclusion of seven articles conducted in the UK or the Netherlands. Studies compared GPs with other health professionals (mainly nurses). These other health professionals saw patients with less urgent health problems, younger patients, and patients with less complex health problems than GPs. Most studies concluded that other health professionals provided safe and vastly efficient care corresponding to the level of GPs but findings about productivity were inconclusive.Conclusion The level of safety and efficiency of care provided by other health professionals in OOH-PC seems like that of GPs, although they mainly see patients presenting with less urgent and less complex health problems.

Summary: Background: Mucositis is a common and highly impactful side effect of conventional and emerging cancer therapy and thus the subject of intense investigation. Although common practice, mucositis assessment is heterogeneously adopted and poorly guided, impacting evidence synthesis and translation. The Multinational Association of Supportive Care in Cancer (MASCC) Mucositis Study Group (MSG) therefore aimed to establish expert recommendations for how existing mucositis assessment tools should be used, in clinical care and trials contexts, to improve the consistency of mucositis assessment. Methods: This study was conducted over two stages (January 2022–July 2023). The first phase involved a survey to MASCC-MSG members (January 2022–May 2022), capturing current practices, challenges and preferences. These then informed the second phase, in which a set of initial recommendations were prepared and refined using the Delphi method (February 2023–May 2023). Consensus was defined as agreement on a parameter by >80% of respondents. Findings: Seventy-two MASCC-MSG members completed the first phase of the study (37 females, 34 males, mainly oral care specialists). High variability was noted in the use of mucositis assessment tools, with a high reliance on clinician assessment compared to patient reported outcome measures (PROMs, 47% vs 3%, 37% used a combination). The World Health Organization (WHO) and Common Terminology Criteria for Adverse Events (CTCAE) scales were most commonly used to assess mucositis across multiple settings. Initial recommendations were reviewed by experienced MSG members and following two rounds of Delphi survey consensus was achieved in 91 of 100 recommendations. For example, in patients receiving chemotherapy, the recommended tool for clinician assessment in clinical practice is WHO for oral mucositis (89.5% consensus), and WHO or CTCAE for gastrointestinal mucositis (85.7% consensus). The recommended PROM in clinical trials is OMD/WQ for oral mucositis (93.3% consensus), and PRO-CTCAE for gastrointestinal mucositis (83.3% consensus). Interpretation: These new recommendations provide much needed guidance on mucositis assessment and may be applied in both clinical practice and research to streamline comparison and synthesis of global data sets, thus accelerating translation of new knowledge into clinical practice. Funding: No funding was received.

Resumen: Objetivo: Analizar las líneas de acción propuestas por los proyectos de promoción de la salud participantes en el proyecto de investigación EvaluAGPS, y su relación con las puntuaciones obtenidas con EvalGuía, una herramienta para evaluar la participación comunitaria basada en la evidencia. Diseño: Estudio multicéntrico cuali-cuantitativo. Emplazamiento: Proyectos de atención primaria o de red intersectorial de atención primaria y municipalidades de 5 comunidades autónomas en España. Participantes: Personas que trabajan en 10 proyectos de promoción de la salud, seleccionados con muestreo intencional según criterios de inclusión (proyectos con un mínimo de participación comunitaria centrados en la salud comunitaria). Método: Se recogieron los datos mediante cuestionarios (herramienta EvalGuía) y talleres participativos. Los datos cuantitativos se analizaron con estadística descriptiva, los datos cualitativos se analizaron utilizando el análisis de matriz. Resultados: Tras pasar la herramienta EvalGuía, las puntuaciones más bajas estaban en la evaluación de resultados, conocimiento de leyes relacionadas con participación comunitaria, diversidad en el grupo motor, medidas de conciliación, recursos financieros y devolución de resultados. Las líneas de acción planteadas eran heterogéneas y no siempre coinciden con las priorizadas. Las líneas priorizadas giraban en torno a la organización del proyecto y a la comunicación. Conclusiones: La herramienta EvalGuía puede ser útil para diseñar planes de acción en proyectos de promoción de la salud. La implementación de medidas en 12 meses para aumentar la diversidad del grupo motor, incorporar medidas de conciliación o mejorar la evaluación es difícil. Se requiere más tiempo para implementar este tipo de medidas. Abstract: Objective: To analyse the lines of action identified in the health promotion projects participating in the EvaluA GPS research, and their relationship with the scores assigned in EvalGuia, a tool for evaluating evidence-based community participation. Design: Qualitative-quantitative multicentre study. Setting: Primary care or intersectoral network of primary care and municipalities in five autonomous communities in Spain. Participants: Participants of 10 health promotion projects, selected with convenience sampling, following inclusion criteria (projects with a minimum of community engagement and centred on community health). Method: Data were collected through questionnaires (EvalGuía tool) and participatory workshops. Quantitative data were analysed with descriptive statistics, qualitative data were analysed using matrix analysis. Results: After implementing the EvalGuide tool, the lowest scores were assigned in outcome evaluation, knowledge of policies related to community participation, diversity in the core working group, inclusivity policies, financial resources and diffusion of results. The lines of action proposed were heterogeneous and did not always match with those prioritised as lower score. The prioritised lines revolved around project organisation and communication. Conclusions: The EvalGuide tool can be helpful to design action plans in Health Promotion projects. The implementation of measures in 12 months to increase the diversity of the core working group, to incorporate work–life balance measures or to improve evaluation is difficult. More time is needed to implement such measures.

Abstract Background Genomic sequencing in congenital heart disease (CHD) patients often discovers novel genetic variants, which are classified as variants of uncertain significance (VUS). Functional analysis of each VUS is required in specialised laboratories, to determine whether the VUS is disease causative or not, leading to lengthy diagnostic delays. We investigated stem cell cardiac disease modelling and transcriptomics for the purpose of genetic variant classification using a GATA4 (p.Arg283Cys) VUS in a patient with CHD. Methods We performed high efficiency CRISPR gene editing with homology directed repair in induced pluripotent stem cells (iPSCs), followed by rapid clonal selection with amplicon sequencing. Genetic variant and healthy matched control cells were compared using cardiomyocyte disease modelling and transcriptomics. Results Genetic variant and healthy cardiomyocytes similarly expressed Troponin T (cTNNT), and GATA4. Transcriptomics analysis of cardiomyocyte differentiation identified changes consistent with the patient’s clinical human phenotype ontology terms. Further, transcriptomics revealed changes in calcium signalling, and cardiomyocyte adrenergic signalling in the variant cells. Functional testing demonstrated, altered action potentials in GATA4 genetic variant cardiomyocytes were consistent with patient cardiac abnormalities. Conclusions This work provides in vivo functional studies supportive of a damaging effect on the gene or gene product. Furthermore, we demonstrate the utility of iPSCs, CRISPR gene editing and cardiac disease modelling for genetic variant interpretation. The method can readily be applied to other genetic variants in GATA4 or other genes in cardiac disease, providing a centralised assessment pathway for patient genetic variant interpretation.

Cognitive impairment is a core feature of schizophrenia spectrum disorders (SSD). Violent and aggressive behavior represents a complex issue in psychiatry, and people with SSD have been shown to be at risk of being both victims and perpetrators of violence. In this review, the complex relationship between cognitive impairment and violent behavior is explored, also considering the usefulness of treating cognitive impairment to improve violence-related outcomes. Several studies report that cognitive impairment is linked to violent behavior, but significant differences between domains and conflicting results are also present, leaving the identification of specific cognitive profiles predicting violent behavior in SSD as an important aim for future research. Evidence regarding the effectiveness of treating cognitive impairment to improve violent behavior, while heterogeneous, provides more consistent results: cognition-targeting interventions appear to provide significant benefits also in the prevention of aggression in people living with SSD, and preliminary evidence shows cognition-focused interventions targeting violent behavior improve both cognition- and violence-related outcomes. Implementing these interventions in clinical practice could be of great usefulness, particularly in forensic contexts. Physical exercise, which improves cognitive performance and psychosocial functioning in SSD, appears to reduce violent behavior in healthy individuals, but requires further studies in clinical samples.

Anemia affects humans throughout life, and is linked to higher morbidity and mortality. Unclear is whether hemoglobin values are equivalent between women and men. This study evaluates the association of preoperative hemoglobin levels with in-hospital mortality and estimates thresholds for survival equity between men and women. All adult patients undergoing surgery between 2010 and 2019 from 14 German hospitals were included in the study. Thresholds for survival equity were determined with generalized additive models. In total, 842,130 patients with a median in-hospital follow-up time of 7 days were analyzed. During follow-up 20,370 deaths occurred. Preoperative hemoglobin stratified in-hospital mortality (log-rank test p

Abstract Background Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs. Methods In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO. Discussion The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention. Trial registration EudraCT 2021–003177-58. Registered on 22 December 2021. https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58 .

Purpose. To describe the acoustic characteristics of a classroom, voice quality, fatigue, and vocal load of university professors. Methods. Exploratory, observational, longitudinal, and descriptive study with a single group of participants, including vocal monitoring data over two weeks. Acoustic characterization of the classroom, perceptual-auditory evaluation, and acoustic analysis of voice samples were conducted before and after classes. Vocal dosimetry was performed during classes, and the Vocal Fatigue Index (VFI) was assessed at the beginning of each week. Descriptive analysis of the findings was conducted, and randomization test was performed to verify the internal reliability of the judge. Results. All participants reported speaking loudly in the classroom, with the majority reporting vocal changes in the past six months, and only one participant reported a current vocal change. The classroom had acoustical measures and estimations that deviated from established standards. The professors used high vocal intensities during classes. After the classes, an increase in the absolute values of the aggregated data for CAPE-V, jitter, and fundamental frequency was found, varying within the range of normality. Furthermore, there was an observed increase in both post-lesson intensity and VFI when comparing the two-week period. Conclusions. Vocal intensities and VFI were possibly impacted by the acoustics of the classroom. The increase in average VFI between the weeks may be attributed to a cumulative fatigue sensation. Further research with a larger number of participants and in acoustically conditioned classrooms is suggested in order to evaluate collective intervention proposals aimed at reducing the vocal load on teachers.

Summary: Background: Patients with chronic lymphocytic leukemia (CLL) have a higher risk of developing other malignancies (OMs) compared to the general population. However, the impact of CLL-related risk factors and CLL-directed treatment is still unclear and represents the focus of this work. Methods: We conducted a retrospective international multicenter study to assess the incidence of OMs and detect potential risk factors in 19,705 patients with CLL, small lymphocytic lymphoma, or high-count CLL-like monoclonal B-cell lymphocytosis, diagnosed between 2000 and 2016. Data collection took place between October 2020 and March 2022. Findings: In 129,254 years of follow-up after CLL diagnosis, 3513 OMs were diagnosed (27.2 OMs/1000 person-years). The most common hematological OMs were Richter transformation, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Non-melanoma skin (NMSC) and prostate cancers were the most common solid tumors (STs).The only predictor for MDS and AML development was treatment with fludarabine and cyclophosphamide with/without rituximab (FC ± R) (OR = 3.7; 95% CI = 2.79–4.91; p

Anna Viola,1 Maria Giulia Demarzo,1,2 Alfredo Abbruzzese,1,3 Marco Muscianisi,1 Michele Francesco Chiappetta,1,3 Giuseppe Costantino,1 Omar Ksissa,1,3 Angela Alibrandi,4 Walter Fries1 1Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy; 2Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l’Oncologia, Gastroenterology Unit, University of Genoa, Genoa, Italy; 3Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy; 4Department of Economics; Unit of Statistical and Mathematical Sciences, University of Messina, Messina, ItalyCorrespondence: Anna Viola, Clinical Unit of Gastroenterology and Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, Via Consolare Valeria 1, Messina, 9815, Italy, Tel +39 3338377928, Email aviola@unime.itPurpose: New therapeutic approaches for ulcerative colitis (UC) are now available, but there is still no robust evidence for predictors of poor outcomes. We aimed to evaluate the factors associated with a chronic active UC disease course.Patients and Methods: Data of all UC outpatients followed for at least 3 years after diagnosis between 2005 and 2018 were retrospectively collected. The primary aim was to identify risk factors for chronic active disease 3 years after diagnosis. Moreover, the following variables were investigated: proximal disease extension or disease regression, proctocolectomy, early use of biologics (BIO) or immunomodulators (IMM), hospitalization, colorectal cancer, and adherence. We defined adherence as both, taking the prescribed therapy and constancy in scheduled follow-up visits.Results: A total of 345 UC patients followed for a median period of 82 months were included. Patients with extensive colitis at diagnosis had a higher rate of chronic active disease 3 years after diagnosis (p< 0.012) together with a higher rate of surgery (p< 0.001) at maximum follow-up. Patients with pancolitis showed significant disease regression over time (51%) without differences in treatment. The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26– 0.95). Adherent patients developed chronic active disease (p< 0.025) less frequently but did receive more frequent IMM (p< 0.045) or BIO (p< 0.009) therapy.Conclusion: Patients diagnosed with pancolitis were more likely to have chronic active disease and to undergo colectomy. The only predictor for developing chronically active UC regardless of disease extension was the lack of adherence to therapy within the first 3 years after diagnosis, underlining the importance of tight control of UC patients and the need to timely identify potential risk factors for non-adherence.Keywords: outcome, adherence, surgery, hospitalization, disease course

Sotos syndrome is an autosomal dominant condition characterized by overgrowth with advanced bone age, macrodolicocephaly, motor developmental delays and learning difficulties, and characteristic facial features caused by heterozygous pathogenetic variants in the NSD1 gene located on chromosome 5q35. The prevalence of heart defects (HDs) in individuals with Sotos syndrome is estimated to be around 15–40%. Septal defects and patent ductus arteriosus are the most commonly diagnosed malformations, but complex defects have also been reported. The aim of our study was to analyze the prevalence of HD, the anatomic types, and the genetic characteristics of 45 patients with Sotos syndrome carrying pathogenetic variants of NSD1 or a 5q35 deletion encompassing NSD1, who were followed at Bambino Gesù Children’s Hospital in Rome. Thirty-nine of the forty-five patients (86.7%) had a mutation in NSD1, while six of the forty-five (13.3%) had a deletion. Most of the patients (62.2%, 28/45) were male, with a mean age of 14 ± 7 years (range 0.2–37 years). A total of 27/45 (60.0%) of the patients had heart defects, isolated or combined with other defects, including septal defects (12 patients), aortic anomalies (9 patients), mitral valve and/or tricuspid valve dysplasia/insufficiency (1 patient), patent ductus arteriosus (3 patients), left ventricular non-compaction/hypertrabeculated left ventricle (LV) (4 patients), aortic coarctation (1 patient), aortopulmonary window (1 patient), and pulmonary valve anomalies (3 patients). The prevalences of HD in the two subgroups (deletion versus intragenic mutation) were similar (66.7% (4/6) in the deletion group versus 58.91% (23/39) in the intragenic variant group). Our results showed a higher prevalence of HD in patients with Sotos syndrome in comparison to that described in the literature, with similar distributions of patients with mutated and deleted genes. An accurate and detailed echocardiogram should be performed in patients with Sotos syndrome at diagnosis, and a specific cardiological follow-up program is needed.

Abstract Background There is level 1 evidence for cerebral thrombectomy with thrombolysis in acute large vessel occlusion. Many hospitals are now contemplating setting up this life-saving service. For the hospital, however, the first treatment is associated with an initial high cost to cover the procedure. Whilst the health economic benefit of treating stroke is documented, this is the only study to date performing matched-pair, patient-level costing to determine treatment cost within the first hospital episode and up to 90 days post-event. Methods We conducted a retrospective coarsened exact matched-pair analysis of 50 acute stroke patients eligible for thrombectomy. Results Thrombectomy resulted in significantly more good outcomes (mRS 0–2) compared to matched controls (56% vs 8%, p = 0.001). More patients in the thrombectomy group could be discharged home (60% vs 28%), fewer were discharged to nursing homes (4% vs 16%), residential homes (0% vs 12%) or rehabilitation centres (8% vs 20%). Thrombectomy patients had fewer serious adverse events (n = 30 vs 86) and were, on average, discharged 36 days earlier. They required significantly fewer physiotherapy sessions (18.72 vs 46.49, p = 0.0009) resulting in a median reduction in total rehabilitation cost of £4982 (p = 0.0002) per patient. The total cost of additional investigations was £227 lower (p = 0.0369). Overall, the median cost without thrombectomy was £39,664 per case vs £22,444, resulting in median savings of £17,221 (p = 0.0489). Conclusions Mechanical thrombectomy improved patient outcome, reduced length of hospitalisation and, even without procedural reimbursement, significantly reduced cost to the thrombectomy providing hospital.

Abstract Background In Germany, general practices are usually contacted first by patients with health complaints, including symptoms characteristic of SARS-CoV-2. Within general practices, medical assistants (MAs) are the first contact person for patients and perform various tasks in close physical patient contact. Working conditions of MAs have been characterized as challenging, e.g., due to low salaries, a high workload, time pressure and frequent interruptions. The potential changes of working conditions and job-related challenges experienced by MAs due to the SARS-CoV-2 pandemic have not been fully explored. We aimed to address this knowledge gap among MAs working in general practices in Germany. Methods Semi-structured telephone interviews were conducted between March and April 2021 with 24 MAs. Medical assistants of legal age, who worked in general practices in Germany, and who were continuously employed and without change of employer in 2020 were eligible for participation. Interview recordings were transcribed verbatim and content-analyzed using MAXQDA, using deductive and inductive coding. Results The SARS-CoV-2 pandemic posed great challenges for MAs, including a dramatic increase in workload, changes in occupational tasks, increased hygiene measures, rearrangements of work organization, childcare issues, and structural and personnel challenges within their practice. Participants described both improved but also worsened collaboration with their employers and colleagues due to the pandemic. Many MAs complained about issues regarding SARS-CoV-2-related billing processes and an increase in unpleasant patient behavior, including disregard of practice rules or frequent verbal insults. Many also did not feel adequately appreciated by politics, media, or society for their efforts during the pandemic. Positive changes were perceived to be the expansion of digital communication channels and a growing social cohesiveness of practice teams. Conclusions Our study suggests that the SARS-CoV-2 pandemic posed great challenges for MAs. The pandemic seems to have worsened MAs’ working conditions, which had been described as challenging already prior to the pandemic. In order to improve job satisfaction and to prevent loss of healthcare personnel, measures must be taken to improve working conditions of MAs in general practices.

Abstract Purpose A qualitative study was carried out to explore obese adolescents' understanding of physical activity, perceptions of the ideal body type and to identify facilitators of and barriers to physical activity. Methods Twenty‐two adolescents 12–18 years of age and 14 of their parents were recruited from an obesity intervention programme in Brooklyn, New York, from June to November 2017. Data were collected using focus groups and individual semi‐structured interviews, followed by interpretative phenomenological analysis of the transcripts. Results The adolescents wanted to ‘lose some weight’, but not to be ‘thin’ or ‘look hungry’. Most females desired a ‘slim‐thick’ figure, which was ‘a flat stomach with big thighs, and curvy’. Fun and support from parents, peers and programme staff facilitated achieving their physical activity goals. Barriers included low self‐efficacy, inactive families, fear of neighbourhood gangs and crime and perceptions that the parks were small and overcrowded, with limited physical activity options for adolescents. Conclusion These findings highlight the need to consider local norms concerning body image when designing obesity interventions. To effectively reduce childhood obesity in New York City, policy should prioritize the promotion of public safety, improvement of neighbourhood parks and increase options for physical activity. Patient or Public Contribution The voices and narratives of patients and their families informed this study.

Hemophilia patients have a deficiency in or dysfunction of clotting factors, which can lead to a bleeding tendency. However, paradoxically, some hemophilia patients may also be at an increased risk of developing thrombotic events such as deep vein thrombosis or pulmonary embolism. The pathophysiology of thrombosis in hemophilia patients is not fully understood, but it is thought to involve a complex interplay of various factors, including the severity of the hemophilia, the presence of other risk factors such as obesity, smoking, or the use of hormonal therapies, and the presence of certain genetic mutations that increase the risk of thrombosis. In addition, it has been suggested that the use of clotting factor replacement therapy, which is a standard treatment for hemophilia, may also contribute to the development of thrombosis in some cases.

Abstract Background Non-invasive measurement of somatosensory-evoked potentials (SEP) in a large animal model is important to translational cognitive research. We sought to develop a methodology for neurophysiological recording via a transcranial electroencephalography (EEG) cap under an effective sedative regimen with dexmedetomidine, midazolam, and butorphanol that will produce sedation instead of anesthesia while not compromising data quality. Results Pigs received intramuscular dexmedetomidine, midazolam, and butorphanol for SEP assessment with peroneal nerve stimulation. Semi-quantitative sedation assessment was performed after the animal was sufficiently sedated and 30 min later, during the transcranial SEP recording. SEP data were analyzed with commercial software. Binary qualitative analysis of the recording was categorized by an experienced neurophysiologist. All four animals had adequate surface SEP recordings. Animals received 43 [21–47] mcg/kg of dexmedetomidine, 0.3 [0.2–0.3] mg/kg of midazolam, and 0.3 [0.3–0.3] mg/kg of butorphanol IM. All treatments resulted in moderate to deep sedation (Baseline median sedation score 11.5 [11–12]; median score at 30 min: 11.5 [10.5–12]). Heart rate (median [range]) (55 [49–71] beats per minute), respiratory rate (24 [21–30] breaths per minute), and hemoglobin oxygen saturation (99 [98–100]%) and body temperature (37.7 [37.4–37.9] °C) remained within clinically acceptable ranges. There were no undesirable recovery incidents. Conclusions In this pilot study, we demonstrate the feasibility of SEP recording via a transcranial EEG cap under an effective sedative regimen in pigs. Our approach will expand the use of a large animal model in neurotranslational research.

Many ocular complications are described in the literature after dental injections. Facial nerve palsy is a rare complication. We report a case of a 60-year-old woman in the American Society of Anesthesiologists (ASA) I classification under orthodontic treatment with aligners that required an inferior alveolar block for endodontic treatment. Optocaine with epinephrine 1:200,000 and a disposable needle 25 G × 36 mm mounted on a dental syringe were used, and the effect of the anesthesia arose after 10 min. Facial nerve palsy on the side of the injection arose after 1 h and 40 min from the injection, and the patient was immediately visited by an ophthalmologist who reported the examination reported in the present case report. The authors report this unusual case with a subsequent onset and short duration of facial nerve palsy and discuss possible anesthetic solution pathways.

Background and Objectives: Despite the vast heterogeneity in the genetic defects causing hemophilia A (HA), large intron inversions represent a major cause of disease, accounting for almost half of the cases of severe HA worldwide. We investigated the intron 22 and intron 1 inversion status in a cohort of Romanian unrelated patients with severe HA. Moreover, we evaluated the role of these inversions as relative risk factors in inhibitor occurrence. Materials and Methods: Inverse shifting—a polymerase chain reaction method was used to detect the presence of intron 22 and intron 1 inversions in 156 Romanian patients with HA. Results: Intron inversion 22 was found in 41.7% of the patients, while intron 1 inversion was detected in 3.2% of the patients. Overall, large intron inversions represented the molecular defect in 44.9% of the studied patients. Our findings are in accord with previously published reports from Eastern Europe countries and with other international studies. The risk of inhibitor development was higher in patients with inversion 1 compared to the patients with HA without any inversion detected. Conclusions: The current study demonstrates the major causative role of large intron inversions in severe HA in Romanian patients. Moreover, our study confirms the contribution of intron 1 inversion in inhibitor development.

The novel amphiphilic polyacrylate grafted with cholesterol moieties, PAAbCH, previously synthesized, was deeply characterized and investigated in the lab and on a pre-industrial scale. Solid-state NMR analysis confirmed the polymer structure, and several water-based pharmaceutical and cosmetic products were developed. In particular, stable oil/water emulsions with vegetable oils, squalene, and ceramides were prepared, as well as hydrophilic medicated films loaded with diclofenac, providing a prolonged drug release. PAAbCH also formed polyelectrolyte hydrogel complexes with chitosan, both at the macro- and nano-scale. The results demonstrate that this polymer has promising potential as an innovative excipient, acting as a solubility enhancer, viscosity enhancer, and emulsifying agent with an easy scale-up transfer process.

La escisión mesorrectal transanal (TaTME: transanal total mesorectal escision) es la última de una larga lista de desarrollos técnicos y tecnológicos para el tratamiento del cáncer de recto medio y bajo. Incluso para los cirujanos colorrectales experimentados, lograr una escisión mesorrectal total (emt) de calidad en cirugía oncológica no siempre es sencillo, por la dificultad de obtener un adecuado acceso a la pelvis. Los estudios realizados han mostrado resultados comparables al abordaje laparoscópico, con tasas elevadas de escisiones mesorrectales completas y bajo porcentaje de margen circunferencial radial (CRM: circumferential radial margin) y distal positivos, con un adecuado número de ganglios resecados. Como toda técnica nueva, su implementación puede traer consecuencias no intencionales. La complejidad del abordaje, la dificultad en la identificación de nuevos repères y planos anatómicos, ha llevado a complicaciones graves como la lesión uretral o la siembra tumoral pelviana. Por ello, la comunidad quirúrgica ha retrasado la implementación masiva de la técnica y desarrollado estrategias de enseñanza y monitorización de este procedimiento para su realización en centros de alto volumen. El objetivo de esta publicación es presentar el primer caso de TaTME en un centro docente universitario y difundir en nuestra comunidad científica el fundamento de la técnica, sus indicaciones, describir los principales pasos técnicos, complicaciones, resultados oncológicos y funcionales.

Cervical cancer is the second most common gynecologic malignancy in Asia and is the leading cause of death in women in developing countries. The cervical cancer stage will significantly affect the prognosis and management. Based on the International Federation of Gynecology and Obstetrics (FIGO) 2018 classification of cervical cancer, magnetic resonance imaging (MRI) has a crucial role in determining cervical cancer staging. This study aimed to evaluate the role of T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) sequences in assessing cervical carcinoma, with the pathological diagnosis being taken as the standard for cervical cancer diagnosis. This study was conducted on seven patients diagnosed with cervical cancer from pathological examination in January 2020 to March 2021 in the Department of Radiology Dr. Hasan Sadikin General Hospital Bandung. We detect the presence of locoregional lesions and extensions of cervical carcinoma using MRI with T2WI and DWI sequences in patients who have previously been diagnosed histopathologically. This study involved seven cervical cancer patients. Pelvic MRI with T2WI and DWI sequences was performed. The imaging results in these patients show that one patient has stage IB1 cervical cancer, four patients have stage IIB, one patient has stage IIIA, and one has stage IIIC1 cervical cancer. This study concluded that T2WI and DWI sequences in MRI are essential and sufficient for diagnosing cervical cancer.

Abstract Intestinal diverticulosis is a chronic disorder that might present with acute symptoms, due to colonic perforation. Pneumoperitoneum and air bubbles spreading in different anatomical locations can be seen. These complications need careful consideration and, when appropriate, surgery, for an otherwise chronic condition that can be successfully treated through conservative measures.

Objetivo general: Descripción del trabajo realizado en la Policlínica Especializada en Conductas Autolesivas (PECA) de la Clínica de Psiquiatría Infantil. Presentación de un posible modelo de prevención del segundo o posteriores intentos de autoeliminación(IAE). Objetivos específicos: Analizar características epidemiológicas y psicopatológicas individuales y familiares de los adolescentes que realizaron un intento de autoeliminación durante el período evaluado. Analizar la utilidad de implementación de un dispositivo que posibilite la prevención de la recidiva del IAE. Explorar estrategias que aseguren la continuidad del tratamiento. Método: Estudio descriptivo, transversal de una muestra de niños y adolescentes de edades entre 6 y 15 años que consultaron por comportamientos suicidas en un periodo de 9 meses (n=102 pacientes), en los años 2012-2013. Se realizaron entrevistas clínicas semiestructuradas, se aplicó la CBCL (Child Behavior Check List) y Cuestionario complementario. Resultados: El 78.8% de la muestra son del sexo femenino y el 75% tienen entre 12-14 años. Primer IAE 68%, segundo o más IAE 16%. Escolarizados 63,6%. Media de PT (Problemas Totales) 66,4. El 42,3% de los padres refieren que sus hijos son víctima de violencia. Del n 102, 90 continúan su tratamiento. Frecuencia de reingresos 12%. Un suicidio. Conclusiones: El desarrollo de un modelo de prevención del segundo o posteriores intentos de autoeliminación durante un periodo de 9 meses, evidencia la importancia de un seguimiento de proximidad. Las alteraciones emocionales y conductuales objetivadas en una población joven se favorecen por los bajos niveles de escolaridad y la violencia intrafamiliar.

Classifying spinal tumors can be challenging due to nonspecific clinical and radiological qualities, and a precise biopsy is crucial for an accurate diagnosis and treatment planning. This study aimed to enhance the accuracy and efficiency of spinal biopsies integrating Cone Beam Computed Tomography (CBCT) and magnetic resonance imaging (MRI) modalities using an O-arm CT navigation system. Eighteen patients with different spinal lesions underwent 18 biopsies following the Stealth Station navigation system Spine 8 protocol. Preoperative MRI scans were merged with intraoperative CT navigation systems for continuous monitoring during the biopsy process. The combined imaging technique accurately identified the diseased lesion type in all biopsies, demonstrating 100% sensitivity and specificity. In conclusion, combining MRI and CT imaging modalities significantly improved spinal biopsy accuracy and efficiency, differentiating between pathological entities. However, large-scale studies are desired to validate these findings and investigate potential benefits in different clinical scenarios. Although this method requires general anesthesia, its potential profits in avoiding misdiagnosed lesions and decreasing the need for further invasive procedures make it a promising approach for improving spinal biopsy accuracy and efficiency.

Background and Objectives: Colitis with Clostridium difficile is an important health problem that occurs with an intensity that varies between mild and severe. Surgical interventions are required only in fulminant forms. There is little evidence regarding the best surgical intervention in these cases. Materials and Methods: Patients with C. difficile infection were identified from the two surgery clinics from the ‘Saint Spiridon’ Emergency Hospital Iași, Romania. Data regarding the presentation, indication for surgery, antibiotic therapy, type of toxins, and post-operative outcomes were collected over a 3-year period. Results: From a total of 12,432 patients admitted for emergency or elective surgery, 140 (1.12%) were diagnosed with C. difficile infection. The mortality rate was 14% (20 cases). Non-survivors had higher rates of lower-limb amputations, bowel resections, hepatectomy, and splenectomy. Additional surgery was necessary in 2.8% of cases because of the complications of C. difficile colitis. In three cases, terminal colostomy was performed and as well as one case with subtotal colectomy with ileostomy. All patients who required the second surgery died within the 30-day mortality period. Conclusions: In our prospective study, the incidence was increased both in cases of patients with interventions on the colon and in those requiring limb amputations. Surgical interventions are rarely required in patients with C. difficile colitis.

Background and Objectives: Triage systems help provide the right care at the right time for patients presenting to emergency departments (EDs). Triage systems are generally used to subdivide patients into three to five categories according to the system used, and their performance must be carefully monitored to ensure the best care for patients. Materials and Methods: We examined ED accesses in the context of 4-level (4LT) and 5-level triage systems (5LT), implemented from 1 January 2014 to 31 December 2020. This study assessed the effects of a 5LT on wait times and under-triage (UT) and over-triage (OT). We also examined how 5LT and 4LT systems reflected actual patient acuity by correlating triage codes with severity codes at discharge. Other outcomes included the impact of crowding indices and 5LT system function during the COVID-19 pandemic in the study populations. Results: We evaluated 423,257 ED presentations. Visits to the ED by more fragile and seriously ill individuals increased, with a progressive increase in crowding. The length of stay (LOS), exit block, boarding, and processing times increased, reflecting a net raise in throughput and output factors, with a consequent lengthening of wait times. The decreased UT trend was observed after implementing the 5LT system. Conversely, a slight rise in OT was reported, although this did not affect the medium-high-intensity care area. Conclusions: Introducing a 5LT improved ED performance and patient care.

According to the literature, interproximal enamel reduction (IER) has become a consolidated technique used in orthodontic treatments to gain space in particular situations such as dental crowding, non-extractive therapies, tooth-size discrepancies, and prevention of dental relapse. There are different methods to realize stripping, and enamel surfaces resulting after this procedure can be analyzed with SEM. The aim of this study was to analyze how different devices of IER leave the surface of the teeth. One hundred and sixty freshly extracted, intact human lower incisors were included in the study, fixed in a plaster support, and then processed with four different techniques of enamel reduction and finishing. Then, they were divided randomly into eight groups (A1–A2, B1–B2, C1–C2, D, and E), each containing twenty teeth. The A, B, and C groups were divided into two subgroups and then all the teeth were observed at SEM. Each digital image acquired by SEM showed that there were streaks on the surfaces, due to the cutter used. The results of this study showed that only group C2 (tungsten carbide bur followed by twelve steps of medium–fine–ultrafine 3M Soft Lex disks) has a few line, which is very similar to group E (untreated group), while the other groups have a lot of lines and show a rougher final surface.

Background and Objectives: Palliative care is an interdisciplinary medical specialty focused on improving the quality of life of critically ill patients, including those with frailty, during their illness. Materials and Methods: We conducted an extensive literature review on Pubmed focusing on palliative care in neuro-oncology patients admitted to intensive care units (ICUs). Results: We identified 967 articles and, after excluding 952 articles in accordance with the PRISMA flow chart, we included a total of 15 articles in the final selection. The potential role of palliative care in neuro-oncology appears necessary to ensure comprehensive end-of-life patient care. However, this seems underestimated and poorly applied, especially in the context of intensive care units. Medical personnel also face ethical dilemmas, considering not only the pathology but also the socio-spiritual context of the patient. In addition, caregivers’ understanding of prognosis and realistic goals is critical for optimal end-of-life management. Conclusions: The provision of palliative care to neuro-oncological patients admitted to ICU is a complex challenge supported by fragmented evidence. Additional research on palliative care and communication about end-of-life care in the neuro-oncology and neuro-ICU setting is needed.

Abstract Background Multipotent mesenchymal stromal/stem cell (MSC) therapy is under investigation in promising (pre-)clinical trials for wound healing, which is crucial for survival; however, the optimal cell dosage remains unknown. The aim was to investigate the efficacy of different low-to-high MSC dosages incorporated in a biodegradable collagen-based dermal regeneration template (DRT) Integra®. Methods We conducted a porcine study (N = 8 Yorkshire pigs) and seeded between 200 and 2,000,000 cells/cm2 of umbilical cord mesenchymal stromal/stem cells on the DRT and grafted it onto full-thickness burn excised wounds. On day 28, comparisons were made between the different low-to-high cell dose groups, the acellular control, a burn wound, and healthy skin. Result We found that the low dose range between 200 and 40,000 cells/cm2 regenerates the full-thickness burn excised wounds most efficaciously, followed by the middle dose range of 200,000–400,000 cells/cm2 and a high dose of 2,000,000 cells/cm2. The low dose of 40,000 cells/cm2 accelerated reepithelialization, reduced scarring, regenerated epidermal thickness superiorly, enhanced neovascularization, reduced fibrosis, and reduced type 1 and type 2 macrophages compared to other cell dosages and the acellular control. Conclusion This regenerative cell therapy study using MSCs shows efficacy toward a low dose, which changes the paradigm that more cells lead to better wound healing outcome.

Summary: Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation.

Aims of the studyTo analyze the prevalence of self-reported anxiety and depression in a monocentric cohort of patients with Systemic Lupus Erythematosus (SLE); to study the main determinants and the impact on quality of life (QoL).MethodsA cross-sectional observational study including adult outpatients with SLE. Demographic and clinical data were analyzed: indices of disease activity (SELENA-SLEDAI); damage (SLICC-DI); comorbidities and concomitant therapies. The definitions for remission (DORIS) and “Lupus Low Disease Activity State” (LLDAS) were applied. At enrollment, each patient completed the following questionnaires: SF-36, FACIT-Fatigue, Lupus Impact Tracker (LIT), Systemic Lupus Activity Questionnaire (SLAQ), and the Hospital Anxiety and Depression Scale (HADS) in order to self-assess anxiety and depression symptoms. The Student t-test and Chi2 tests were conducted for univariate analysis. The Spearman test was used for linear correlation between continuous data. Multivariate analysis was performed by multiple linear and logistic regression.ResultsOne hundred fifty-four consecutive patients with SLE were enrolled, the majority female and Caucasian with a mean age = 43.3 ± 13.7 years. 79.9% were in LLDAS or remission. 36.4% had a SDI > 1. 13.7% of patients had concomitant fibromyalgia. 37.4% had symptoms indicating anxiety and 25% of depression according to the HADS questionnaire. In the multivariate analysis, patients with active disease were significantly more anxious and depressed (p < 0.01) compared to patients in LLDAS or remission. Fibromyalgia and older age were independently associated with anxiety and depression, respectively (p < 0.05). Active skin involvement was significantly linked to depression (p < 0.05). Higher scores on the HADS questionnaire (higher levels of anxiety and depression) were found to be significantly linked to patients’ perception of higher disease activity and worse quality of life, irrespective of disease activity, age and fibromyalgia.ConclusionSymptoms of anxiety and depression are frequent in SLE patients, including outpatients with mild/moderate disease. Such symptoms have a significant negative impact on QoL and perception of disease activity, regardless of other factors. Moreover, disease activity, advanced age and fibromyalgia appear to be significantly linked to mood disorders. Assessing symptoms of the anxious-depressive spectrum in patients with SLE could lead to improvement in patients’ perception of health status and quality of life.

Abstract Background Depressive disorders often remain undiagnosed or are treated inadequately. Online-based programs may reduce the present treatment gap for depressive disorders and reduce disease-related costs. This study aimed to examine the potential of the internet intervention “deprexis” to reduce the total costs of statutory health insurance. Changes in depression severity, health-related quality of life and impairment in functioning were also examined. Method A total of 3805 participants with, at minimum, mild depressive symptoms were randomized to either a 12-week online intervention (deprexis) or a control condition. The primary outcome measure was statutory health insurance costs, estimated using health insurers’ administrative data. Secondary outcomes were: depression severity, health-related quality of life, and impairment in functioning; assessed on patient’s self-report at baseline, post-treatment, and three-months’ and nine-months’ follow-up. Results In both groups, total costs of statutory health insurance decreased during the study period, but changes from baseline differed significantly. In the intervention group total costs decreased by 32% from 3139€ per year at baseline to 2119€ in the study year (vs. a mean reduction in total costs of 13% in the control group). In comparison to the control group, the intervention group also showed a significantly greater reduction in depression severity, and impairment in functioning and a significantly greater increase in health-related quality of life. Conclusion The study underlines the potential of innovative internet intervention programs in treating depressive disorders. The results suggest that the use of deprexis over a period of 12 weeks leads to a significant improvement in symptoms with a simultaneous reduction in the costs of statutory health insurance.

Background and Objectives: Discussion is open about the relationship between diabetes (DM) and hearing loss (HL). There is a lot of evidence in the literature suggesting a causal link between these conditions, beyond being considered simple comorbidities. The difficulty in identifying populations free from confounding factors makes it difficult to reach definitive conclusions on the pathophysiological mechanisms at play. Nonetheless, there is numerous evidence that demonstrates how the population affected by DM is more affected by sensorineural HL (SNHL) and exhibit a higher prevalence of idiopathic sudden sensorineural HL (ISSNHL). Materials and Methods: Articles reporting potentially relevant information were reviewed, and the most significant results are discussed in this article. Starting from the possible mechanisms relating to auditory impairment in the diabetic condition, this article summarizes the studies on auditory evaluation in subjects with DM1 and DM2 and addresses the relationship between DM and ISSNHL. Results: DM is considered a risk factor for SNHL, although some studies have reported no relationship when the associations were adjusted for age, gender, and hypertension. Macro and microvascular insults that cause decreased blood flow, oxygen exchange, and ion transport are major complications of hypertension and DM and can have a direct effect on the sensory and support cells of the cochlea. Conclusions: Given the difficulty of carrying out studies on populations without confounding factors, new laboratory studies are strongly required to clarify which specific physiopathological mechanisms underlie the diabetic damage caused to the hearing organs and how pharmacological management may contribute to counteracting the pathophysiological effects of the diabetic condition on the auditory system.

Aortic aneurysms represent a very common pathology that can affect any segment of the aorta. These types of aneurysms can be localized on the thoracic segment or on the abdominal portion, with the latter being more frequent. Though there are similarities between thoracic and abdominal aortic aneurysms, these pathologies are distinct entities. In this article, we undertook a review regarding the different mechanisms that can lead to the development of aortic aneurysm, and we tried to identify the different manners of treatment. For a long time, aortic wall aneurysms may evolve in an asymptomatic manner, but this progressive dilatation of the aneurysm can lead to a potentially fatal complication consisting in aortic rupture. Because there are limited therapies that may delay or prevent the development of acute aortic syndromes, surgical management remains the most common manner of treatment. Even though, surgical management has improved much in the last years, thus becoming less invasive and sophisticated, the morbi-mortality linked to these therapies remains increased. The identification of the cellular and molecular networks triggering the formation of aneurysm would permit the discovery of modern therapeutic targets. Molecular and cellular mechanisms are gaining a bigger importance in the complex pathogenesis of aortic aneurysms. Future studies must be developed to compare the findings seen in human tissue and animal models of aortic aneurysm, so that clinically relevant conclusions about the aortic aneurysm formation and the pharmacological possibility of pathogenic pathways blockage can be drawn.

Abstract Besides violence, the risk of under nutrition and infection, migrant children with noncommunicable chronic diseases face serious challenges in the management of their conditions. Management of diabetic ketoacidosis in a severely malnourished patient includes careful hydration, therapeutic feeding, and monitoring.

Introducción: la equinococosis quística músculo-esque­lética es poco frecuente, pudiendo determinar retrasos diagnósticos y errores terapéuticos. Reporte de caso: presentamos el caso de un paciente con un quiste hidático primario único a nivel de la región femoral posterior derecha, infectado. Discusión: se realizó una revisión en las bases de datos PubMed y LILACS sobre el diagnóstico y manejo terapéutico de los quistes hidáticos músculo-esqueléticos primarios. Conclusiones: la equinococosis quística músculo-esquelética debe ser tenida en cuenta dentro de los diagnósticos diferenciales de tumoraciones de partes blandas en pacientes provenientes de zonas endémicas. La tomografía computada y/o resonancia magnética cumplen un rol diagnóstico y de planificación terapéutica. El tratamiento es quirúrgico, a medida del paciente y del quiste, en función de su topografía, tamaño y fundamentalmente relaciones vasculo nerviosas y musculares. Otros factores a tener en cuenta son las futuras secuelas funcionales y resultados estéticos.