The Scope and Impact of Viral Infections in Common Variable Immunodeficiency (CVID) and CVID-like Disorders: A Literature Review.

Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency disorder characterised by impaired antibody production, leading to recurrent infections and an increased susceptibility to viral pathogens. This literature review aims to provide a comprehensive overview of CVID's relationship with viral infections, encompassing disease pathogenesis, key presenting features, specific monogenic susceptibilities, the impact of COVID-19, and existing treatment options. The pathogenesis of CVID involves complex immunological dysregulation, including defects in B cell development, antibody class switching, and plasma cell differentiation. These abnormalities contribute to an impaired humoral immune response against viral agents, predisposing individuals with CVID to a broad range of viral infections. Genetic factors play a prominent role in CVID, and monogenic drivers of CVID-like disease are increasingly identified through advanced genomic studies. Some monogenic causes of the CVID-like phenotype appear to cause specific viral susceptibilities, and these are explored in the review. The emergence of the COVID-19 pandemic highlighted CVID patients' heightened predisposition to severe outcomes with viral infections. This review explores the clinical manifestations, outcomes, and potential therapeutic approaches for COVID-19 in CVID patients. It assesses the efficacy of prophylactic measures for COVID-19, including vaccination and immunoglobulin replacement therapy, as well as trialled therapies.

Consensus recommendations on fasting during Ramadan for patients with kidney disease: review of available evidence and a call for action (RaK Initiative).

Ramadan fasting (RF) involves abstaining from food and drink during daylight hours; it is obligatory for all healthy Muslims from the age of puberty. Although sick individuals are exempt from fasting, many will fast anyway. This article explores the impact of RF on individuals with kidney diseases through a comprehensive review of existing literature and consensus recommendations. This study was conducted by a multidisciplinary panel of experts.The recommendations aim to provide a structured approach to assess and manage fasting during Ramadan for patients with kidney diseases, empowering both healthcare providers and patients to make informed decisions while considering their unique circumstances.

Self-reported preferences and barriers to continued professional development in primary care physicians: a cross-sectional web-based survey in Qatar.

INTRODUCTION: High quality and effective primary healthcare is a national priority in Qatar. Continuing professional development (CPD) for physicians is a cornerstone of this objective, yet little is known about physicians' preferences or barriers to CPD participation. METHOD: A needs assessment was conducted using a cross-sectional web-based survey of primary care physicians registered with the Department of Healthcare Practitioners (DHP) between March and June 2017. RESULTS: Two-hundred-and-eighty-one complete surveys were submitted representing physicians in both public (N = 129) and private sectors (N = 152). Physicians completed medical degrees and postgraduate training across multiple countries, and most had been practicing in Qatar for 5 years or less. 'Activities during working hours', 'cost' and 'work commitments' were the most common barriers. There was little consensus regarding the optimal timing of CPD activities, although public sector physicians were more likely to indicate weekend activities as a barrier to participation (30% vs. 9%). Over 90% of participants preferred traditional lectures, workshops, case-based sessions, small group and online self-paced learning as formats for CPD delivery, however alternative modes of delivery were also deemed acceptable (> 80% agreement). CONCLUSION: Understanding primary care physicians' barriers and preferences is an essential component of a larger necessitated needs assessment of CPD in primary care practitioners in Qatar. Further research is warranted to understand the underlying beliefs driving physicians' choices and the apparent variation between those working in the public and private sectors. CPD developers should consider approaches to mitigate perceived barriers and understand preferences to maximize the quality of participation.

Lung Ultrasound Reduces Chest X-rays in Postoperative Care after Thoracic Surgery: Is There a Role for Artificial Intelligence?-Systematic Review.

BACKGROUND: Chest X-ray (CXR) remains the standard imaging modality in postoperative care after non-cardiac thoracic surgery. Lung ultrasound (LUS) showed promising results in CXR reduction. The aim of this review was to identify areas where the evaluation of LUS videos by artificial intelligence could improve the implementation of LUS in thoracic surgery. METHODS: A literature review of the replacement of the CXR by LUS after thoracic surgery and the evaluation of LUS videos by artificial intelligence after thoracic surgery was conducted in Medline. RESULTS: Here, eight out of 10 reviewed studies evaluating LUS in CXR reduction showed that LUS can reduce CXR without a negative impact on patient outcome after thoracic surgery. No studies on the evaluation of LUS signs by artificial intelligence after thoracic surgery were found. CONCLUSION: LUS can reduce CXR after thoracic surgery. We presume that artificial intelligence could help increase the LUS accuracy, objectify the LUS findings, shorten the learning curve, and decrease the number of inconclusive results. To confirm this assumption, clinical trials are necessary. This research is funded by the Slovak Research and Development Agency, grant number APVV 20-0232.

3D Bioprinting tissue analogs: Current development and translational implications.

Three-dimensional (3D) bioprinting is a promising and rapidly evolving technology in the field of additive manufacturing. It enables the fabrication of living cellular constructs with complex architectures that are suitable for various biomedical applications, such as tissue engineering, disease modeling, drug screening, and precision regenerative medicine. The ultimate goal of bioprinting is to produce stable, anatomically-shaped, human-scale functional organs or tissue substitutes that can be implanted. Although various bioprinting techniques have emerged to develop customized tissue-engineering substitutes over the past decade, several challenges remain in fabricating volumetric tissue constructs with complex shapes and sizes and translating the printed products into clinical practice. Thus, it is crucial to develop a successful strategy for translating research outputs into clinical practice to address the current organ and tissue crises and improve patients' quality of life. This review article discusses the challenges of the existing bioprinting processes in preparing clinically relevant tissue substitutes. It further reviews various strategies and technical feasibility to overcome the challenges that limit the fabrication of volumetric biological constructs and their translational implications. Additionally, the article highlights exciting technological advances in the 3D bioprinting of anatomically shaped tissue substitutes and suggests future research and development directions. This review aims to provide readers with insight into the state-of-the-art 3D bioprinting techniques as powerful tools in engineering functional tissues and organs.

Coaxial Placement of Balloon-Expandable and Self-Expanding Stents: Impact on Crush Resistance and Luminal Recovery in a Benchtop Model.

During endovascular interventions, coaxial deployment of stents may be required to preserve luminal gain. This study characterized in vitro the effect on crush resistance and postcompression recovery when 316L stainless steel balloon-expandable (BE) and laser-cut nitinol self-expanding (SE) venous stents were deployed coaxially. Various stent configurations were parallel-plate compressed from a fully expanded state to 50% diameter reduction (Criterion, Model 42; MTS, Eden Prairie, Minnesota) in a 37 °C ± 1 water bath. Coaxial deployments of SE stent inside BE stent and BE stent inside SE stent demonstrated higher crush resistances compared with each stent individually or their mathematical summation (analysis of variance P < .0001; pairwise comparison P < .01). The configuration of SE stent inside BE stent showed higher postcompression luminal recovery at 48.7% compared with that of BE stent inside SE stent at 27.5% (P = .0001). Coaxial deployment of SE stent inside BE stent may improve crush resistance and luminal recovery after compression in the appropriate clinical context.

219Three-dimensional printing as a cutting-edge, versatile and personalizable vascular stent manufacturing procedure: Toward tailor-made medical devices.

Vascular stents (VS) have revolutionized the treatment of cardiovascular diseases, as evidenced by the fact that the implantation of VS in coronary artery disease (CAD) patients has become a routine, easily approachable surgical intervention for the treatment of stenosed blood vessels. Despite the evolution of VS throughout the years, more efficient approaches are still required to address the medical and scientific challenges, especially when it comes to peripheral artery disease (PAD). In this regard, three-dimensional (3D) printing is envisaged as a promising alternative to upgrade VS by optimizing the shape, dimensions and stent backbone (crucial for optimal mechanical properties), making them customizable for each patient and each stenosed lesion. Moreover, the combination of 3D printing with other methods could also upgrade the final device. This review focuses on the most recent studies using 3D printing techniques to produce VS, both by itself and in combination with other techniques. The final aim is to provide an overview of the possibilities and limitations of 3D printing in the manufacturing of VS. Furthermore, the current situation of CAD and PAD pathologies is also addressed, thus highlighting the main weaknesses of the already existing VS and identifying research gaps, possible market niches and future directions.

Usability and acceptance of crowd-based early warning of harmful algal blooms.

Crowdsensing has become an alternative solution to physical sensors and apparatuses. Utilizing citizen science communities is undoubtedly a much cheaper solution. However, similar to other participatory-based applications, the willingness of community members to be actively involved is paramount to the success of implementation. This research investigated factors that affect the continual use intention of a crowd-based early warning system (CBEWS) to mitigate harmful algal blooms (HABs). This study applied the partial least square-structural equation modeling (PLS-SEM) using an augmented technology acceptance model (TAM). In addition to the native TAM variables, such as perceived ease of use and usefulness as well as attitude, other factors, including awareness, social influence, and reward, were also studied. Furthermore, the usability factor was examined, specifically using the System Usability Scale (SUS) score as a determinant. Results showed that usability positively affected the perceived ease of use. Moreover, perceived usefulness and awareness influenced users' attitudes toward using CBEWS. Meanwhile, the reward had no significant effects on continual use intention.

High-'n'-dry? A comparison of cannabis and alcohol use in drivers presenting to hospital after a vehicular collision.

DESIGN: This was a prospective observational study. BACKGROUND AND AIMS: The characteristics of cannabis-involved motor vehicle collisions are poorly understood. This study of injured drivers identifies demographic and collision characteristics associated with high tetrahydrocannabinol (THC) concentrations. SETTING: The study was conducted in 15 Canadian trauma centres between January 2018 and December 2021. CASES: The cases (n = 6956) comprised injured drivers who required blood testing as part of routine trauma care. MEASUREMENTS: We quantified whole blood THC and blood alcohol concentration (BAC) and recorded driver sex, age and postal code, time of crash, crash type and injury severity. We defined three driver groups: high THC (THC ≥ 5 ng/ml and BAC = 0), high alcohol (BAC ≥ 0.08% and THC = 0) and THC/BAC-negative (THC = 0 = BAC). We used logistic regression techniques to identify factors associated with group membership. FINDINGS: Most injured drivers (70.2%) were THC/BAC-negative; 1274 (18.3%) had THC > 0, including 186 (2.7%) in the high THC group; 1161 (16.7%) had BAC > 0, including 606 (8.7%) in the high BAC group. Males and drivers aged less than 45 years had higher adjusted odds of being in the high THC group (versus the THC/BAC-negative group). Importantly, 4.6% of drivers aged less than 19 years had THC ≥ 5 ng/ml, and drivers aged less than 19 years had higher unadjusted odds of being in the high THC group than drivers aged 45-54 years. Males, drivers aged 19-44 years, rural drivers, seriously injured drivers and drivers injured in single-vehicle, night-time or weekend collisions had higher adjusted odds ratios (aORs) for being in the high alcohol group (versus THC/BAC-negative). Drivers aged less than 35 or more than 65 years and drivers involved in multi-vehicle, daytime or weekday collisions had higher adjusted odds for being in the high THC group (versus the high BAC group). CONCLUSIONS: In Canada, risk factors for cannabis-related motor vehicle collisions appear to differ from those for alcohol-related motor vehicle collisions. The collision factors associated with alcohol (single-vehicle, night-time, weekend, rural, serious injury) are not associated with cannabis-related collisions. Demographic factors (young drivers, male drivers) are associated with both alcohol and cannabis-related collisions, but are more strongly associated with cannabis-related collisions.

An update on VEXAS syndrome.

INTRODUCTION: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a recently described, late-onset, acquired autoinflammatory disorder caused by mutations in the UBA1 gene. The various clinical manifestations of VEXAS broadly divided into inflammatory or haematological. VEXAS defines a new disease category - the hematoinflammatory disorders triggered by somatic mutations restricted to blood but causing systemic inflammation with multi-organ involvement and associated with aberrant bone marrow status. VEXAS causes significant morbidity and reduced life expectancy, but the optimum standard of care remains undefined. AREAS COVERED: This review describes the discovery of VEXAS, relevant genetic causes and immunopathology of the disease. A detailed account of its various clinical manifestations and disease mimics is provided. Current treatment and management options are discussed. EXPERT OPINION: New rare variants in UBA1 and VEXAS-like UBA1 negative cases are reported. Consensus diagnostic criteria might be required to define VEXAS and its related disorders. Investigation of sporadic, VEXAS-like cases will require the application of deep sequencing using DNA obtained from various cellular or tissue locations. Prospective studies are needed to define the optimal supportive and treatment options for patients with varying disease severity and prognosis. VEXAS-specific hematopoietic stem cell transplant selection criteria also require development.

The added value of the nurse practitioner: An evolutionary concept analysis.

AIM: Nurse practitioners' added value is often mentioned in publications, but there is no consensus on what value is being added, what value is being added to, and in comparison with what can be considered to be an added value. A concept analysis was conducted to clarify the attributes, antecedents and meaning and better understand the Nurse practitioners' added value. DESIGN: Rodgers' evolutionary concept analysis. METHODS: We selected 16 studies from CINAHL, PubMed, Embase and Medline to conduct a thematic analysis, considering the date, location and discipline of publications. RESULTS: Nurse practitioners' added value include: skills and competencies, activities performed, positive outcomes, and positive role perceptions, and antecedents and consequences were also identified. Nurse practitioners' added value is context-dependent and is often understood by comparing it to a context prior to implementation or other professional roles.

Access to cardiac PET/CT by sarcoidosis patients and cost-effectiveness analysis of cardiac PET/MR compared to the standard of care.

IMPORTANCE: Cardiac sarcoidosis is associated with a high mortality rate. Given multiple barriers to obtaining cardiac PET imaging, we suspect individuals with access to this imaging modality are not representative of the Sarcoid patient population, which in the United States are predominantly Black females. OBJECTIVE: To evaluate the demographics of patients with cardiac PET access and the cost-effectiveness of cardiac PET/MR imaging relative to standard of care. DESIGN: This is a retrospective, observational study. The demographic information of patients with suspected cardiac sarcoidosis and cardiac PET/CT imaging within a national registry of sarcoidosis were reviewed (n = 4561). An individual-level, continuous, time-state transition model was used for the evaluation of long-term cost-effectiveness for the combined cardiac PET/MR compared to standard of care cardiac MR followed by cardiac PET/CT. RESULTS: Patients who underwent cardiac PET in the national registry had 88.35% higher odds of being male (p < 0.001) and 43.82% higher odds of being White (p = 0.003) than their counterparts who did not have cardiac PET imaging. Combined cardiac PET/MR had overall lower total lifetime costs ($8761 vs $10,777) and overall improved expected quality of life-years compared to the standard of care (0.77 vs 0.69). CONCLUSION AND RELEVANCE: The findings suggest that patients with access to cardiac PET/CT are not representative of the patient population most likely to have cardiac sarcoidosis in this limited study evaluation. Universal insurance coverage should be considered for Cardiac PET imaging as same day cardiac PET and MR imaging has potential long-term cost and quality of life benefit.

Decellularized Extracellular Matrix-Based Bioinks for Tendon Regeneration in Three-Dimensional Bioprinting.

In the last few years, attempts to improve the regeneration of damaged tendons have been rising due to the growing demand. However, current treatments to restore the original performance of the tissue focus on the usage of grafts; although, actual grafts are deficient because they often cannot provide enough support for tissue regeneration, leading to additional complications. The beneficial effect of combining 3D bioprinting and dECM as a novel bioink biomaterial has recently been described. Tendon dECMs have been obtained by using either chemical, biological, or/and physical treatments. Although decellularization protocols are not yet standardized, recently, different protocols have been published. New therapeutic approaches embrace the use of dECM in bioinks for 3D bioprinting, as it has shown promising results in mimicking the composition and the structure of the tissue. However, major obstacles include the poor structural integrity and slow gelation properties of dECM bioinks. Moreover, printing parameters such as speed and temperature have to be optimized for each dECM bioink. Here, we show that dECM bioink for 3D bioprinting provides a promising approach for tendon regeneration for future clinical applications.

Improving Diagnosis and Clinical Management of Acquired Systemic Autoinflammatory Diseases.

Systemic autoinflammatory diseases (SAID) are conditions caused by dysregulation or disturbance of the innate immune system, with neutrophils and macrophages the main effector cells. Although there are now more than 40 distinct, genetically defined SAIDs, the genetic/molecular diagnosis remains unknown for a significant proportion of patients with the disease onset in adulthood. This review focuses on new developments related to acquired/late onset SAID, including phenocopies of monogenic disorders, Schnitzler's syndrome, Adult onset Still's disease, VEXAS syndrome, and autoinflammatory complications associated with myelodysplastic syndrome.

Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience.

Background: Individuals with primary and secondary immunodeficiency (PID/SID) were shown to be at risk of poor outcomes during the early stages of the SARS-CoV-2 pandemic. SARS-CoV-2 vaccines demonstrate reduced immunogenicity in these patients. Objectives: To understand whether the risk of severe COVID-19 in individuals with PID or SID has changed following the deployment of vaccination and therapeutics in the context of the emergence of novel viral variants of concern. Methods: The outcomes of two cohorts of patients with PID and SID were compared: the first, infected between March and July 2020, prior to vaccination and treatments, the second after these intervention became available between January 2021 and April 2022. Results: 22.7% of immunodeficient patients have been infected at least once with SARS-CoV-2 since the start of the pandemic, compared to over 70% of the general population. Immunodeficient patients were typically infected later in the pandemic when the B.1.1.529 (Omicron) variant was dominant. This delay was associated with receipt of more vaccine doses and higher pre-infection seroprevalence. Compared to March-July 2020, hospitalization rates (53.3% vs 17.9%, p<0.0001) and mortality (Infection fatality rate 20.0% vs 3.4%, p=0.0003) have significantly reduced for patients with PID but remain elevated compared to the general population. The presence of a serological response to vaccination was associated with a reduced duration of viral detection by PCR in the nasopharynx. Early outpatient treatment with antivirals or monoclonal antibodies reduced hospitalization during the Omicron wave. Conclusions: Most individuals with immunodeficiency in the United Kingdom remain SARS-CoV-2 infection naïve. Vaccination, widespread availability of outpatient treatments and, possibly, the emergence of the B.1.1.529 variant have led to significant improvements in morbidity and mortality followings SARS-CoV-2 infection since the start of the pandemic. However, individuals with PID and SID remain at significantly increased risk of poor outcomes compared to the general population; mitigation, vaccination and treatment strategies must be optimized to minimize the ongoing burden of the pandemic in these vulnerable cohorts.