Effect of Cyclin-Dependent Kinase 4/6 Inhibitors on Circulating Cells in Patients with Metastatic Breast Cancer.

The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) with endocrine therapy (ET) is the standard-of-care for estrogen receptor (ER)-positive, HER2-negative (ER+/HER2- advanced/metastatic breast cancer (mBC). However, the impact of CDK4/6i on circulating immune cells and circulating tumor cells (CTCs) in patients receiving CDK4/6i and ET (CDK4/6i+ET) remains poorly understood. This was a prospective cohort study including 44 patients with ER+/HER2- mBC treated with CDK4/6i+ET in either first or second line. Peripheral blood samples were collected before (baseline) and 3 months (t2) after therapy. Immune cell's subsets were quantified by flow cytometry, and microfluidic-captured CTCs were counted and classified according to the expression of cytokeratin and/or vimentin. Patients were categorized according to response as responders (progression-free survival [PFS] ≥ 6.0 months; 79.1%) and non-responders (PFS < 6.0 months; 20.9%). CDK4/6i+ET resulted in significant changes in the hematological parameters, including decreased hemoglobin levels and increased mean corpuscular volume, as well as reductions in neutrophil, eosinophil, and basophil counts. Specific immune cell subsets, such as early-stage myeloid-derived suppressor cells, central memory CD4+ T cells, and Vδ2+ T cells expressing NKG2D, decreased 3 months after CDK4/6i+ET. Additionally, correlations between the presence of CTCs and immune cell populations were observed, highlighting the interplay between immune dysfunction and tumor dissemination. This study provides insights into the immunomodulatory effects of CDK4/6i+ET, underscoring the importance of considering immune dynamics in the management of ER+/HER2- mBC.

Photodynamic inactivation of E. coli with cationic imidazolyl-porphyrin photosensitizers and their synergic combination with antimicrobial cinnamaldehyde.

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.

Electromyographic analysis of the three subdivisions of the gluteus medius during Wall Press Exercise and Figure-of-Four Position.

BACKGROUND: Gluteus medius (GM) is a segmented muscle involving three muscular subdivisions. Rehabilitation exercises has been suggested to strengthen specific subdivisions. OBJECTIVE: This study aimed to evaluate muscular activation of the anterior, middle, and posterior subdivisions of the GM during two different exercises. METHODS: A total of 28 healthy active subjects participated in this study. Muscle activity using surface electromyography was recorded for the three GM subdivisions during figure-of-four position (FFP) and wall press (WP). Non-parametric Kruskal-Wallis test was used to detect differences between GM subdivisions on each exercise and the Mann-Whitney U test was used to compare muscular activation across exercises. RESULTS: There were statistically significant differences (P< 0.001) in all GM subdivision during FFP and WP exercises. Both exercises showed greater activation of the posterior subdivision than the middle and anterior subdivisions, with the WP causing highest activation of the posterior subdivision. CONCLUSION: In line with the WP exercise, the FFP produces sufficient activity to provide potential strength gains on the posterior subdivision and could be a viable option to include in the early stages of the rehabilitation process. Clinicians may use this information to make more informed decisions about exercise selection for strengthening specific GM subdivision.

Screening a Targeted Panel of Genes by Next-Generation Sequencing Improves Risk Stratification in Real World Patients with Acute Myeloid Leukemia.

Although mutation profiling of defined genes is recommended for classification of acute myeloid leukemia (AML) patients, screening of targeted gene panels using next-generation sequencing (NGS) is not always routinely used as standard of care. The objective of this study was to prospectively assess whether extended molecular monitoring using NGS adds clinical value for risk assessment in real-world AML patients. We analyzed a cohort of 268 newly diagnosed AML patients. We compared the prognostic stratification of our study population according to the European LeukemiaNet recommendations, before and after the incorporation of the extended mutational profile information obtained by NGS. Without access to NGS data, 63 patients (23%) failed to be stratified into risk groups. After NGS data, only 27 patients (10%) failed risk stratification. Another 33 patients were re-classified as adverse-risk patients once the NGS data was incorporated. In total, access to NGS data refined risk assessment for 62 patients (23%). We further compared clinical outcomes with prognostic stratification, and observed unexpected outcomes associated with FLT3 mutations. In conclusion, this study demonstrates the prognostic utility of screening AML patients for multiple gene mutations by NGS and underscores the need for further studies to refine the current risk classification criteria.

Lifestyle-Integrated Functional Exercise for People With Dementia: A Pilot Study.

The objective of this study was to explore the feasibility and preliminary effectiveness of the Lifestyle-Integrated Functional Exercise for People with Dementia (LiFE4D) on health-related physical fitness, cognitive function, physical activity, and respiratory and upper limb functions. A randomized controlled pilot study was conducted (control group: usual care; experimental group: usual care and LiFE4D). The feasibility of LiFE4D was determined considering recruitment, protocol acceptability, adherence, and safety. Measures of health-related physical fitness, cognitive function, physical activity, and respiratory and upper limb functions were assessed at the baseline and 3 months. Twelve participants (8 [66.7%] female, 82 [72.2-84] years) were included, six per group. Recruitment was challenging. LiFE4D was acceptable with excellent adherence and no major adverse events. Cardiorespiratory endurance (effect size = 1.64, 95% confidence interval [CI; 0.33, 2.95]) and balance (effect size = 1.46, 95% CI [0.19, 2.73]) improved after LiFE4D. LiFE4D seems to be feasible and safe, and it shows potential to significantly improve the health-related physical fitness of people with dementia.

The MOVE.TE Falls Prevention and Management Program: lessons learnt in the Portuguese context.

MOVE.TE is a non-profit participatory physiotherapy platform that aims at translating knowledge in the field of physiotherapy and developing freely available evidence-based physiotherapy programmes targeting the primary care services of the Portuguese National Health service. A group of volunteer academics and clinicians collaborated at different stages and time points to create the first ever falls prevention and management programme and guidance for Physiotherapy in primary care, in Portugal. This report describes this seven-step process. In spite of many challenges, this project constitutes an example of advocacy in physiotherapy for the promotion of better healthcare for older adults.

[Effects of mild intensity physical activity on the physical condition of older adults: A systematic review]. / Efectos de la actividad física de intensidad suave sobre las condiciones físicas de los adultos mayores: revisión sistemática.

Physical activity can improve function in people over 65. The aim of the study was to evaluate the efficacy of mild intensity exercise interventions on the functional health and quality of life of this population. A systematic review was conducted using WOS (n=20), Scopus (n=235), PubMed (n=15), and PEDro (n=20) databases. Eight studies met the inclusion criteria. Six hundred and nineteen subjects with an age range of 60-103 years were evaluated. Interventions included endurance, aerobic, and vibration exercises. Those who used pedometers, telephone calls and follow-up controls showed positive effects in increasing physical activity. Five studies evaluated strength and showed that increasing strength also improved balance and walking speed. The results indicate that applying mild intensity physical activity interventions is a way of ensuring improved functional health and quality of life in older people.

Home-Based Physical Activity Programs for People With Dementia: Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Physical activity has the potential to improve health outcomes in people with dementia, namely when living at home. However, the knowledge about home-based physical activity for this population is scarce. Thus, we aim to identify and synthesize the effects of home-based physical activity for people with dementia. RESEARCH DESIGN AND METHODS: A systematic review was conducted. Quality of studies was assessed using the Delphi List. Effect sizes (ES) were calculated with MetaXL 2.0. A meta-analysis was conducted for the Mini-Mental Status Examination (MMSE), Neuropsychiatric Inventory (NPI), Cornell Scale for Depression in Dementia, Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS-ADL), Functional Reach test, Timed Up and Go (TUG) test, Short Physical Performance Battery, Dementia Quality of Life, NPI Caregivers subscale and Zarit Burden Interview (ZBI). RESULTS: Sixteen randomized controlled trials were included. Most were of high quality and published after 2015. A large heterogeneity of interventions was found. Meta-analysis showed significant results in MMSE (ES = 0.71, 95% CI 0.43, 0.99), NPI (ES = -0.37, 95% CI -0.57, -0.17), ADCS-ADL (ES = 0.80, 95% CI 0.53, 1.07), Functional Reach test (ES = 2.24, 95% CI 1.80, 2.68), TUG test (ES = -2.40, 95% CI -2.84, -1.96), NPI Caregivers subscale (ES = -0.63, 95% CI -0.94, -0.32), and ZBI (ES = -0.45, 95% CI -0.77, -0.13). Few minor adverse events and high adherence to intervention were found. DISCUSSION AND IMPLICATIONS: Home-based physical activity seems safe and effective in delaying cognitive function decline and improving changes in behavioral and psychological symptoms of dementia, activities of daily living, health-related physical fitness, and carer's burden in people with dementia living at home.

Cerebral Venous Air Embolism: A Rare Phenomenon.

Cerebral venous air embolism (CVAE) is an extremely rare phenomenon. Most reports of cerebral air embolism focus on the arterial territory, and consequently CVAE has remained poorly understood, especially regarding its pathophysiology and treatment. The authors describe an elderly male patient who was admitted through the Emergency Department with subacute confusion. A brain computed tomography (CT) showed multiple cerebral venous gas emboli. No potential causes were found apart from previous peripheral vein cannulation and intravenous medication administration. The patient received supportive treatment, with complete radiological resolution of the gas emboli, while maintaining his previous confusional state. The aim of this report is to highlight a rare and understudied entity, and discuss its causes, proposed pathophysiology and appropriate management. LEARNING POINTS: Cerebral venous air embolism (CVAE) is a very rare phenomenon, assumed to result from retrograde progression of air bubbles introduced into the venous circulation through central venous catheter manipulation or, less often, peripheral vein cannulation, although its precise pathophysiology remains to be completely understood.CVAE's clinical presentation can be varied, often mimicking acute stroke, and diagnosis can easily be established through a conventional brain-CT scan.Treatment must be initiated promptly by placing the patient in the Trendelenburg position and providing high concentration oxygen, intravascular volume expansion and other supportive measures as needed; hyperbaric oxygen therapy may be considered for selected patients.

Systemic mastocytosis - a diagnostic challenge.

Mastocytosis refers to a group of disorders characterized by the infiltration of clonally derived mast cells to the skin or extracutaneous tissues resulting in a heterogeneous clinical picture. It is a rare hematologic disorder in all its forms. The exact incidence is unknown; it affects patients of any age and males and females equally. Its molecular pathogenesis is incompletely understood. The clinical features of mastocytosis result from both chronic and episodic mast cell mediator release, signs and symptoms arising from diffuse or focal tissue infiltration, and, occasionally, the presence of an associated non-mast cell clonal hematologic disease. The histopathologic analysis is essential for definitive diagnosis but there is no curative treatment. The authors report a clinical case of a 72-year-old woman with no history of allergies, with bicytopenia, weight loss, and diffuse axial osteolytic lesions. This is a rare clinical case of aggressive systemic mastocytosis for which palliative treatment can improve survival and quality of life. A brief review of the literature about this pathology is also included.

Systemic mastocytosis - a diagnostic challenge

Mastocytosis refers to a group of disorders characterized by the infiltration of clonally derived mast cells to the skin or extracutaneous tissues resulting in a heterogeneous clinical picture. It is a rare hematologic disorder in all its forms. The exact incidence is unknown; it affects patients of any age and males and females equally. Its molecular pathogenesis is incompletely understood. The clinical features of mastocytosis result from both chronic and episodic mast cell mediator release, signs and symptoms arising from diffuse or focal tissue infiltration, and, occasionally, the presence of an associated non-mast cell clonal hematologic disease. The histopathologic analysis is essential for definitive diagnosis but there is no curative treatment. The authors report a clinical case of a 72-year-old woman with no history of allergies, with bicytopenia, weight loss, and diffuse axial osteolytic lesions. This is a rare clinical case of aggressive systemic mastocytosis for which palliative treatment can improve survival and quality of life. A brief review of the literature about this pathology is also included.

A construção de uma estratégia didática para a utilização das cartilhas "Os caminhos da esquistossomose" em escolas públicas de ensino fundamental, no município de Barra Mansa/RJ / The construction of a teaching strategy for the use of booklets

A esquistossomose está entre as parasitoses de maior importância no Brasil devido à alta morbidade e mortalidade em algumas regiões. Em função disso, o estudo, inserido no campo da Educação em Saúde, teve como objetivo principal construir uma estratégia didática para a utilização das cartilhas da série “Os Caminhos da Esquistossomose”, desenvolvidas por um grupo de pesquisadores do Instituto René Rachou (Fiocruz/MG), para a utilização, por mediação docente, em escolas públicas de Ensino Fundamental, visando a inserção e exploração de materiais educativos no processo de ensino e aprendizagem no espaço escolar pelos docentes. A pesquisa foi realizada com alunos do 9º ano do Ensino Fundamental em duas escolas públicas do município de Barra Mansa. Foi realizada uma pesquisa descritiva, com abordagem qualitativa, tendo como instrumentos de coleta de dados, entrevistas (individuais e grupo focal), questionários, e formulários para a observação. Os resultados obtidos indicaram que a utilização da estratégia desenvolvida, facilitou o ensino e a aprendizagem sobre a esquistossomose, além de possibilitar a disseminação do conhecimento nesse campo.

Early Diagnosis of Invasive Aspergillosis in Neutropenic Patients. Comparison between Serum Galactomannan and Polymerase Chain Reaction.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in profoundly neutropenic patients, so early diagnosis is mandatory. AIM: Consecutive patients with hematological malignancies undergoing intensive chemotherapy were screened for IA with two different methods which were compared. METHODS: From October 2000 to August 2003 we tested 1311 serum samples from 172 consecutive patients with a polymerase chain reaction assay and between April 2005 and April 2008 we tested 806 serum samples from 169 consecutive patients with a Galactomannan (GM) test. Bronchoalveolar (BAL) samples were obtained whenever the patient's condition allowed and tested with either method. RESULTS: The serum PCR assay had a sensitivity of 75.0% and a specificity of 91.9% and the serum GM assay had a sensitivity of 87.5% and a specificity of 93.1%, (P > 0.05). The presence of two or more consecutive positive serum samples was predictive of IA for both assays. BAL GM/PCR was positive in some patients without serum positivity and in patients with 2 or more positive serum GM/PCR. CONCLUSIONS: No significant differences between the 2 serum tests were found. The GM assay has the advantage of being standardized among several laboratories and is incorporated in the criteria established by the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycosis Study Group (EORTC/MSG), however is much more expensive. BAL GM and PCR sampling aids in IA diagnosis but needs further validation studies to differentiate between colonization and true infection in cases where serum GM or PCR are negative.

Polymerase chain reaction screening for fungemia and/or invasive fungal infections in patients with hematologic malignancies.

INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS: PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI.