The Role of TLR-2 in Lethal COVID-19 Disease Involving Medullary and Resident Lung Megakaryocyte Up-Regulation in the Microthrombosis Mechanism.

Patients with COVID-19 have coagulation and platelet disorders, with platelet alterations and thrombocytopenia representing negative prognostic parameters associated with severe forms of the disease and increased lethality. METHODS: The aim of this study was to study the expression of platelet glycoprotein IIIa (CD61), playing a critical role in platelet aggregation, together with TRL-2 as a marker of innate immune activation. RESULTS: A total of 25 patients were investigated, with the majority (24/25, 96%) having co-morbidities and dying from a fatal form of SARS-CoV-2(+) infection (COVID-19+), with 13 men and 12 females ranging in age from 45 to 80 years. When compared to a control group of SARS-CoV-2 (-) negative lungs (COVID-19-), TLR-2 expression was up-regulated in a subset of patients with deadly COVID-19 fatal lung illness. The proportion of Spike-1 (+) patients found by PCR and ISH correlates to the proportion of Spike-S1-positive cases as detected by digital pathology examination. Furthermore, CD61 expression was considerably higher in the lungs of deceased patients. In conclusion, we demonstrate that innate immune prolonged hyperactivation is related to platelet/megakaryocyte over-expression in the lung. CONCLUSIONS: Microthrombosis in deadly COVID-19+ lung disease is associated with an increase in the number of CD61+ platelets and megakaryocytes in the pulmonary interstitium, as well as their functional activation; this phenomenon is associated with increased expression of innate immunity TLR2+ cells, which binds the SARS-CoV-2 E protein, and significantly with the persistence of the Spike-S1 viral sequence.

The Impact of Antimicrobial Resistance in Cystic Fibrosis.

The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.

Attitudes Toward the Adoption of Remote Patient Monitoring and Artificial Intelligence in Parkinson's Disease Management: Perspectives of Patients and Neurologists.

OBJECTIVE: Early detection of Parkinson's Disease (PD) progression remains a challenge. As remote patient monitoring solutions (RMS) and artificial intelligence (AI) technologies emerge as potential aids for PD management, there's a gap in understanding how end users view these technologies. This research explores patient and neurologist perspectives on AI-assisted RMS. METHODS: Qualitative interviews and focus-groups were conducted with 27 persons with PD (PwPD) and six neurologists from Finland and Italy. The discussions covered traditional disease progression detection and the prospects of integrating AI and RMS. Sessions were recorded, transcribed, and underwent thematic analysis. RESULTS: The study involved five individual interviews (four Italian participants and one Finnish) and six focus-groups (four Finnish and two Italian) with PwPD. Additionally, six neurologists (three from each country) were interviewed. Both cohorts voiced frustration with current monitoring methods due to their limited real-time detection capabilities. However, there was enthusiasm for AI-assisted RMS, contingent upon its value addition, user-friendliness, and preservation of the doctor-patient bond. While some PwPD had privacy and trust concerns, the anticipated advantages in symptom regulation seemed to outweigh these apprehensions. DISCUSSION: The study reveals a willingness among PwPD and neurologists to integrate RMS and AI into PD management. Widespread adoption requires these technologies to provide tangible clinical benefits, remain user-friendly, and uphold trust within the physician-patient relationship. CONCLUSION: This study offers insights into the potential drivers and barriers for adopting AI-assisted RMS in PD care. Recognizing these factors is pivotal for the successful integration of these digital health tools in PD management.

Tumor Inflammatory Microenvironment of the Thyroid Cancer: Relationship between Regulatory T-Cell Imbalance, and p-NFΚB (p65) Expression-A Preliminary Study.

BACKGROUND: Inflammatory microenvironment is an essential component of all tumors, including thyroid cancer. Autoimmune thyroid diseases are often associated with thyroid cancer. CD25, expressed in Treg cells and B cells, has been found to be associated with autoimmune thyroid diseases and the NFkB pathway is critical to tumor formation, regulating immune-related genes, and pro-inflammatory cytokine. METHODS: Protein expression of CD25 and NFkB and its phosphorylated form was analyzed by immunohistochemistry in 80 patients with thyroid cancer (10 cases of cancers with Hashimoto's thyroiditis and 70 cases without). RESULTS: CD25 was mainly detected in the nucleus of the inflammatory cells such as in the thyrocytes and neoplastic cells. Protein staining was detected in the T-lymphocytes of the outermost zone of the lymphoid follicles. Moreover, in all cancer alterations, there were a higher level of p-NFkB than in the surrounding tissues. Again, p-NFkB staining was evident in neoplastic cells but not evident in inflammatory cells. CONCLUSIONS: Strong inflammatory infiltrate in the tumor microenvironment is correlated with an invasive phenotype. CD25 and p-NFkB levels were statistically significantly overexpressed in cancer cells.

The Role of Toll-like Receptor-4 in Macrophage Imbalance in Lethal COVID-19 Lung Disease, and Its Correlation with Galectin-3.

To the current data, there have been 6,955,141 COVID-19-related deaths worldwide, reported to WHO. Toll-like receptors (TLRs) implicated in bacterial and virus sensing could be a crosstalk between activation of persistent innate-immune inflammation, and macrophage's sub-population alterations, implicated in cytokine storm, macrophage over-activation syndrome, unresolved Acute Respiratory Disease Syndrome (ARDS), and death. The aim of this study is to demonstrate the association between Toll-like-receptor-4 (TLR-4)-induced inflammation and macrophage imbalance in the lung inflammatory infiltrate of lethal COVID-19 disease. Twenty-five cases of autopsy lung tissues were studied by digital pathology-based immunohistochemistry to evaluate expression levels of TLR-4 (CD 284), pan-macrophage marker CD68 (clone KP1), sub-population marker related to alveolar macrophage Galectin-3 (GAL-3) (clone 9C4), and myeloid derived CD163 (clone MRQ-26), respectively. SARS-CoV-2 viral persistence has been evaluated by in situ hybridation (ISH) method. This study showed TLR-4 up-regulation in a subgroup of patients, increased macrophage infiltration in both Spike-1(+) and Spike-1(-) lungs (p < 0.0001), and a macrophage shift with important down-regulation of GAL-3(+) alveolar macrophages associated with Spike-1 persistence (p < 0.05), in favor of CD163(+) myeloid derived monocyte-macrophages. Data show that TLR-4 expression induces a persistent activation of the inflammation, with inefficient resolution, and pathological macrophage shift, thus explaining one of the mechanisms of lethal COVID-19.

Intraoperative lung ultrasound improves subcentimetric pulmonary nodule localization during VATS: Results of a retrospective analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) resection of deep-seated lung nodules smaller than 1 cm is extremely challenging. Several methods have been proposed to overcome this limitation but with not neglectable complications. Intraoperative lung ultrasound (ILU) is the latest minimally invasive proposed technique. The aim of the current study was to analyze the accuracy and efficacy of ILU associated with VATS to visualize solitary and deep-seated pulmonary nodules smaller than 1 cm. METHODS: Patients with subcentimetric solitary and deep-seated pulmonary nodules were included in this retrospective study from November 2020 to December 2022. Patients who received VATS aided with ILU were considered as group A and patients who received conventional VATS as group B (control group). The rate of nodule identification and the time for localization with VATS alone and with VATS aided with ILU in each group were analyzed. RESULTS: A total of 43 patients received VATS aided with ILU (group A) and 31 patients received conventional VATS (group B). Mean operative time was lower in group A (p < 0.05). In group A all the nodules were correctly identified, while in group B in one case the localization failed. The time to identify the lesion was lower in group A (7.1 ± 2.2 vs. 13.8 ± 4.6; p < 0.05). During hospitalization three patients (6.5%; p < 0.05) in group B presented air leaks that were conservatively managed. CONCLUSION: Intracavitary VATS-US is a reliable, feasible, real-time and effective method of localization of parenchymal lung nodules during selected wedge resection procedures.

On care infrastructures and health practices: How people in health promotion programmes try to change their everyday life.

This paper contributes to challenging common behavioural or cognitive explanations for health and wellbeing outcomes, focussing on social practices through which people, with the help of other subjects, try to improve their health conditions. To renew the debate about health promotion, my work is placed at the intersection between the sociology of health and illness and science and technology studies, adopting the concepts of care infrastructures and health practices that are introduced in the next section. With this goal, my paper draws on a qualitative study concerning a Workplace Health Promotion programme aimed at reducing the risks of Type-2 diabetes and cardiovascular diseases among sedentary workers. The findings illustrate how a care infrastructure in the field of health promotion is designed, put to work, repaired and 'put aside' in relation to two health practices ('doing physical activity' and 'following the Mediterranean diet'). Drawing on the presented case, I show how the change in daily habits in the fields of nutrition and physical activity is a collective effort involving different spheres of life, connecting human and non-human elements and bringing out affective intensities among them.

The co-production of a workplace health promotion program: expected benefits, contested boundaries.

Workplace health promotion (WHP) are often depicted as an opportunity for pursuing a better and broader well-being condition under the assumption that working environments affect the physical, mental, and social well-being of individuals who spend large proportion of waking hours at work. While most empirical studies provided medical evidence to the effectiveness of WHP programs, scholars question the instrumental purposes of these programs founded on the belief that "healthy workers are better workers". Little is known, for instance, about the design of WHP programs and their acceptance by workers. Our study addresses this gap, analyzing the co-production of a WHP program in an Italian research institute promoted by the healthcare authority, the local government and the national center for prevention and security in the workplaces. To this aim, we adopt the notion of boundary object investigate how different stakeholders reclaim to take part and being involved in this process, re-shaping their goals and their boundaries and why a WHP program or parts of it may be rejected or re-negotiated by its recipients. Our analysis reveals how each stakeholder contributes to re-shape the WHP program which emerges as the modular product of the composition of each matter of concern. Most notably, the strong rooting in a clinical perspective and the original focus on only workers at risk is gradually flanked by initiatives to involve all employees. Moreover, workers draw a line as for the legitimacy of employers' intervention in the personal sphere of health promotion, embracing interventions addressing diet and physical activity while rejecting measures targeting smoking and alcohol consumption.

On digital intimacy: redefining provider-patient relationships in remote monitoring.

Remote monitoring has often been thought to lead to a highly structured and standardised care process. Several studies have stressed that patient-provider communication could be hindered if mediated by technologies, leading to an impoverished relationship. We argue that while remote monitoring leads to a redefinition of the patient-provider relationship, it could also offer the opportunity to develop a more intimate acquaintance not possible via only routine visits. The study is part of a clinical trial aimed at assessing the acceptability of a remote monitoring platform for type 1 diabetes. Drawing on practice-based studies, we focused our analysis on the practice of text message exchange between patients and providers. The 396 conversations were coded with a template analysis, leading to the identification of two main categories: 'knowing the patient' and 'knowing about the patient'. The analysis reveals that the practice of messaging led to the development of a 'digital intimacy', a relationship characterised by a thorough familiarity made possible by electronic devices that extends to face-to-face encounters. Drawing on our case, we argue that remote monitoring can foster greater intimacy between patients and providers, which is made possible by the overall increase in the quantity and quality of communication between patients and providers.

'Homemade': Building, mending, and coordinating a care network.

In recent decades, longer life expectancy, the consequent greater number of patients with often concurrent diseases, and the need of healthcare institutions to reduce the costs of services, have engendered changes in all European healthcare systems. On one side, healthcare systems increasingly rely on the self-management skills of patients, who undertake a growing amount of 'sickness work' from which they are relieved only in the case of severe illness. On the other, the inability of public healthcare systems to satisfy the increased demand for care has led to the growth of private healthcare organizations as well as cooperatives of health professionals who offer their services privately. The care of citizens, therefore, is increasingly distributed across networks of actors with very different objectives, logics of action and professional backgrounds (public and private healthcare organizations, community medical services, voluntary organizations). Despite the attention devoted by social studies of medicine to the work done by citizens in supporting the work of clinicians and nurses, the work performed in connection to the management of care networks have been only marginally investigated. Drawing on a qualitative research carried out in the Province of Trento (Italy) and focused on the different ways in which elderly people with chronic conditions manage their conditions outside the healthcare and welfare institutions, in this paper we are interested in deepening the understanding of the invisible work citizens perform in connection to the management of care services and professionals. That is, the work needed in order to activate, mend and coordinate complex networks of care.

Text Messaging and Type 1 Diabetes Management: Qualitative Study Exploring Interactions Among Patients and Health Care Professionals.

BACKGROUND: The diffusion of information and communication technologies (ICTs) in type 1 diabetes (T1D) management has generated a debate on the ways in which ICTs can support the patient-provider relationship. Several studies have focused on text messages. Most of the literature proposes quantitative analysis of the impact of text messaging on the clinical conditions of patients and/or their satisfaction with the technology, while the qualitative studies have focused mainly on patients' perceptions about strengths and weaknesses of this technology. OBJECTIVE: In contrast to past studies, we adopted a qualitative approach for the in-depth examination of patient-health care professionals' interactions in text messaging. METHODS: The study focused on the use of the Trento Cartella Clinica del Cittadino Diabetes System (TreC-DS), a digital platform with a built-in messaging system, in two diabetes centers, integrating message analysis with interviews with patients and health care professionals. Each center focused on a specific patient profile: the first one focused on pregnant women with T1D and the second one focused on adult patients with poorly controlled diabetes. RESULTS: The main results of the study were as follows: (1) Health care professionals and patients perceived the messaging system as useful for sharing information (ie, pregnant women for prescriptions and adults with poorly controlled diabetes for advice); (2) The content and communication styles of the two centers differed: in the case of pregnant women, interactions via text messaging were markedly prescriptive, while in the case of adult patients with poorly controlled diabetes, they were conceived as open dialogues; and (3) Conversations were initiated mainly by professionals; in the cases considered, it was mainly the diabetes center that decided whether a messaging conversation was needed. CONCLUSIONS: The results show how the features of interactions of text messaging changed based on the patient profiles in two different centers. In addition, in both diabetes centers that were involved, the system seems to have laid a foundation for a closer relationship between patients and health care professionals.

Managing complex therapies outside hospitals. An analysis of GPs practices of how to support medication at home.

Support systems for the management of prescriptions are commonplace in hospitals, whilst they are rarely found in general practice. This exploratory study draws on a qualitative survey conducted with focus groups to investigate the information needs of General Practitioners (GPs) in regard to the therapeutic management of complex patients, the purpose being to identify possible areas of application. The question addressed is whether the systems existing in hospitals can be usefully adapted and used by GPs or if a different approach needs to be adopted to design other tools. The analysis shows that the information needs of GPs relative to medication management are significantly different from those of their hospital colleagues because the former are not directly responsible for the administration but instead operate within a care network on which they cannot exercise direct control. This study suggests that support systems for therapy management should be designed on the assumption that it derives from cooperative work by a heterogeneous network of actors, and therefore with functionalities intended to satisfy the coordination needs of all the actors involved in the process.

[Splenic abscesses: 6 cases in 15 years]. / Gli ascessi splenici: 6 casi in 15 anni.

Splenic abscesses are a rare type of disease, owing to the quite exceptional primary forms, but the prevalence of the disease is rising as a result of the increase in the population at risk. The authors report on their experience based on 6 observations of such cases over a period of 15 years. The diagnosis was obtained by ultrasonography in all 6 cases. Only one case was successfully treated by percutaneous drainage, the other 5 all requiring splenectomy. Only one patient, suffering from Chédiak-Higashi disease, died of bronchopneumonia 6 months postoperatively. Nowadays the disease is diagnosed earlier than it was in the past owing to the increasingly widespread use and refinement of diagnostic methods, but even today identification of splenic abscess may still be late due to the presence of predisposing diseases which mask the clinical picture, and also because, since the condition is so rare, one very often fails to think of it in the early stages. An analysis of the recent literature indicates that percutaneous drainage is a reliable technique which presents a high therapeutic success rate and low cost compared to surgery. Though we believe that the ongoing progress in the fields of ultrasonography and CT-guided intervention may allow us to treat increasing numbers of patients with splenic abscesses in future, we feel, also in the light of our own experience, that splenectomy still remains the reference treatment, in that ideal conditions for successful percutaneous drainage do not often present themselves.