Biological differences between adult and perinatal human mesenchymal stromal cells and their impact on the manufacturing processes.

The biological properties of human mesenchymal stromal cells (hMSCs) have been explored in over a thousand clinical trials in the last decade. Although hMSCs can be isolated from multiple sources, the degree of biological similarity between cell populations from these sources remains to be determined. A comparative study was performed investigating the growth kinetics and functionality of hMSCs isolated from adipose tissue (AT), bone marrow (BM) and umbilical cord tissue (UCT) expanded in monolayer over five passages. Adult hMSCs (AT, BM) had a slower proliferation ability than the UCT-hMSCs, with no apparent differences in their glucose consumption profile. BM-hMSCs produced higher concentrations of endogenous vascular endothelial growth factor (VEGF) compared to AT- and UCT-hMSCs. This study also revealed that UCT-hMSCs were more efficiently transduced by a lentiviral vector carrying a VEGF gene than their adult counterparts. Following cellular immunophenotypic characterization, no differences across the sources were found in the expression levels of the typical markers used to identify hMSCs. This work established a systematic approach for cell source selection depending on the hMSC's intended clinical application.

Generating suspension-adapted human mesenchymal stromal cells (S-hMSCs) for the scalable manufacture of extracellular vesicles.

BACKGROUD: Human mesenchymal stromal cells (hMSCs) are a naturally adherent cell type and one of the most studied cellular agents used in cell therapy over the last 20 years. Their mechanism of action has been primarily associated with paracrine signaling, which has contributed to an increase in the number of studies focused on hMSC-related extracellular vesicles (EVs). METHODS: In this study, we demonstrate for the first time that human telomerase reverse transcriptase (hTERT) immortalized hMSCs can be adapted to suspension culture, eliminating the need for microcarriers or other matrixes to support cell growth. RESULTS: This novel cell line, named suspension hMSCs (S-hMSCs), has a doubling time of approximately 55 hours, with a growth rate of 0.423/d. Regarding its immunophenotype characteristics, S-hMSCs retained close to 90% of CD73 and CD105 expression levels, with the CD90 receptor being downregulated during the adherent to suspension adaptation process. An RNA sequencing analysis showed an upregulation of the transcripts coding for CD44, CD46 and CD47 compared to the expression levels in AT-hMSCs and hTERT-hMSCs. The cell line herein established was able to generate EVs using a chemically defined medium formulation with these nanoparticles averaging 150 nm in size and displaying the markers CD63, CD81, and TSG101, while not expressing the negative marker calnexin. CONCLUSION: This body of evidence, combined with the visual confirmation of EV presence using transmission electron microscopy, demonstrates the EV-producing capabilities of the novel S-hMSCs. This cell line provides a platform for process development, drug discovery and translational studies in the EV field.

Scalable manufacturing of gene-modified human mesenchymal stromal cells with microcarriers in spinner flasks.

Due to their immunomodulatory properties and in vitro differentiation ability, human mesenchymal stromal cells (hMSCs) have been investigated in more than 1000 clinical trials over the last decade. Multiple studies that have explored the development of gene-modified hMSC-based products are now reaching early stages of clinical trial programmes. From an engineering perspective, the challenge lies in developing manufacturing methods capable of producing sufficient doses of ex vivo gene-modified hMSCs for clinical applications. This work demonstrates, for the first time, a scalable manufacturing process using a microcarrier-bioreactor system for the expansion of gene-modified hMSCs. Upon isolation, umbilical cord tissue mesenchymal stromal cells (UCT-hMSCs) were transduced using a lentiviral vector (LV) with green fluorescent protein (GFP) or vascular endothelial growth factor (VEGF) transgenes. The cells were then seeded in 100 mL spinner flasks using Spherecol microcarriers and expanded for seven days. After six days in culture, both non-transduced and transduced cell populations attained comparable maximum cell concentrations (≈1.8 × 105 cell/mL). Analysis of the culture supernatant identified that glucose was fully depleted after day five across the cell populations. Lactate concentrations observed throughout the culture reached a maximum of 7.5 mM on day seven. Immunophenotype analysis revealed that the transduction followed by an expansion step was not responsible for the downregulation of the cell surface receptors used to identify hMSCs. The levels of CD73, CD90, and CD105 expressing cells were above 90% for the non-transduced and transduced cells. In addition, the expression of negative markers (CD11b, CD19, CD34, CD45, and HLA-DR) was also shown to be below 5%, which is aligned with the criteria established for hMSCs by the International Society for Cell and Gene Therapy (ISCT). This work provides a foundation for the scalable manufacturing of gene-modified hMSCs which will overcome a significant translational and commercial bottleneck. KEY POINTS: • hMSCs were successfully transduced by lentiviral vectors carrying two different transgenes: GFP and VEGF • Transduced hMSCs were successfully expanded on microcarriers using spinner flasks during a period of 7 days • The genetic modification step did not cause any detrimental impact on the hMSC immunophenotype characteristics.

Understanding the impact of bioactive coating materials for human mesenchymal stromal cells and implications for manufacturing.

Bioactive materials interact with cells and modulate their characteristics which enable the generation of cell-based products with desired specifications. However, their evaluation and impact are often overlooked when establishing a cell therapy manufacturing process. In this study, we investigated the role of different surfaces for tissue culture including, untreated polystyrene surface, uncoated Cyclic Olefin Polymer (COP) and COP coated with collagen and recombinant fibronectin. It was observed that human mesenchymal stromal cells (hMSCs) expanded on COP-coated plates with different bioactive materials resulted in improved cell growth kinetics compared to traditional polystyrene plates and non-coated COP plates. The doubling time obtained was 2.78 and 3.02 days for hMSC seeded in COP plates coated with collagen type I and recombinant fibronectin respectively, and 4.64 days for cells plated in standard polystyrene treated plates. Metabolite analysis reinforced the findings of the growth kinetic studies, specifically that cells cultured on COP plates coated with collagen I and fibronectin exhibited improved growth as evidenced by a higher lactate production rate (9.38 × 105 and 9.67 × 105 pmol/cell/day, respectively) compared to cells from the polystyrene group (5.86 × 105 pmol/cell/day). This study demonstrated that COP is an effective alternative to polystyrene-treated plates when coated with bioactive materials such as collagen and fibronectin, however COP-treated plates without additional coatings were found not to be sufficient to support cell growth. These findings demonstrate the key role biomaterials play in the cell manufacturing process and the importance of optimising this selection.

Recommendations of good practice to prevent aspiration pneumonia in older adults at risk of oropharyngeal dysphagia living in nursing homes: A modified e-Delphi study protocol.

BACKGROUND: Aspiration pneumonia (AP) is a subset of pneumonia caused by the aspiration of food and fluids to the lungs and is highly prevalent in the older population. Oropharyngeal dysphagia (OD) is one of the risk factors for AP and it is also associated with malnutrition, dehydration and poor functional outcomes. As pneumonia is the second most common infection in nursing homes (NHs) and OD represents a major concern to NH staff, good practices for the prevention of AP in older adults at risk of OD are needed. PURPOSE: The aim of this modified e-Delphi study is to build consensus among a panel of experts regarding a set of recommendations for NH staff on good practices to prevent AP in older adults at risk of OD living in NHs. The objective of this paper is to establish the methodology inherent to the Delphi study. METHODS: An online modified Delphi study will be developed in three rounds. Criteria for the Delphi panel participants include holding a master's or doctoral degree in OD or speech and language therapy; or having 10 or more years of experience in OD; or having at least one scientific publication related to OD. A previously described modified Delphi methodology will be used to achieve consensus (75% agreement). An additional round will be performed to collect the experts' perspectives regarding the priority for application of each recommendation previously validated. DISCUSSION: This protocol aimed to describe the methodology of a future Delphi study on the prevention of AP, seeking to fulfil the gap in the literature regarding this topic. The modified Delphi technique is a widely used method for collecting experts' opinion in health sciences, but the absence of standardised guidelines allows some heterogeneity between studies with the same aim. WHAT THIS PAPER ADDS: What is already known on the subject Aspiration pneumonia (AP) is related to three main risk factors: impaired safety of swallow, impaired nutritional status and poor oral health. It is known that being dependent for feeding is one of the main risk factors for AP and around 50% of nursing home (NH) residents need feeding assistance. Thus, it is important to promote specialised intervention and care by the NH staff for preventing AP. What this paper adds to existing knowledge It is hypothesised that increasing the knowledge of NH staff regarding the best practices for preventing AP in older adults at risk of oropharyngeal dysphagia (OD) will improve outcomes such as quality of life, incidence of AP and mortality. What are the potential or actual clinical implications of this work? The recommendations resulting from this study will address a current gap in healthcare practice of NH staff regarding older adults at increased risk for OD and, consequently, for AP.

Anti-Algics in the Therapeutic Response of Breast and Urological Cancers.

The effect of anti-algics on tumor progression and the overall survival of patients is controversial and remains unclear. Herein, we disclose the in vitro effects of the local anesthetics lidocaine, ropivacaine, and levobupivacaine on breast (MCF7), prostate (PC3, LNCaP), and bladder (TCCSUP, HT1376) cancer cell lines, both as monotherapy and in combination with standard-of-care therapeutics. Assays for cell proliferation, viability, death profile, and migration were performed. Additionally, we explored the clinical outcomes of opioid use through a cross-sectional study involving 200 metastatic prostate cancer patients. The main clinical data collected included the type of opioid therapy administered, dosage, treatment duration, disease progression, and overall survival. Results obtained demonstrate that treatment with local anesthetics has a promising selective anti-tumor effect on these types of cancer, with higher effects when associated with docetaxel. This points out the use of local anesthetics as an added value in the treatment of prostate carcinoma patients. Alternatively, chronic opioid use was correlated with reduced overall survival (p < 0.05) and progression-free survival (p < 0.05) at each treatment line in the observational study. While these results provide valuable insights, larger prospective studies are imperative to comprehensively evaluate the clinical impact of opioid analgesics in prostate cancer patients.

Factors Predicting Pressure Injury Incidence in Older Adults Following Elective Total Hip Arthroplasty: A Longitudinal Study.

OBJECTIVE: To identify the factors associated with pressure injury (PI) development in older adult patients who underwent elective total hip arthroplasty (THA). METHODS: A nonexperimental longitudinal prospective study was conducted with a sample of 40 patients undergoing elective THA. Patients were evaluated for PI at hospital admission, 24 hours postsurgery, at discharge, and 1 month after surgery. RESULTS: The incidence of PIs (category 1 or category 2) in this study was 7.9% 24 hours after surgery and 24.3% at discharge. The most common PI location was the sacrum/coccyx or the ischial tuberosity. This study found significant relationships between PIs and female sex (odds ratio [OR], 8.75), body fat mass percentage (OR, 1.15), and the motor score from a Functional Independence Measure scale (OR, 0.89). Finally, the following variables were also associated with PIs (P < .1): skeletal muscle mass (OR, 0.82), lower limb with osteoarthritis weight (OR, 0.61), lower limb without osteoarthritis weight (OR, 0.62), and geriatric depression scale (OR, 1.12). CONCLUSIONS: This work identifies those patients at higher risk of PI, enabling targeted prevention and treatment in the population of patients undergoing elective THA. The findings of this study are in line with extant literature and suggest that women with a higher percentage of body fat and less mobility had a higher risk of PI.

Nursing workload assessment in an intensive care unit: A 5-year retrospective analysis.

AIMS: To study the correlation between the workload of intensive care nursing teams and the sociodemographic, anthropometric and clinical characteristics of patients in critical condition in a Portuguese Intensive Care Unit (ICU) during a 5-year period. BACKGROUND: Currently, indices of nursing workload quantification are one of the resources used for planning and evaluating ICUs. Evidence shows that there are several factors related to critical patients and their hospitalisation which potentially influence the nursing workload. DESIGN: Retrospective cohort analysis of a health record database from adult patients admitted to a Portuguese ICU between 1 January 2015-31 December 2019. METHODS: Simplified Therapeutic Intervention Scoring System (TISS-28) scores of 730 adult patients. Three TISS-28 assessments were considered: first assessment, last assessment and average. The STROBE guidelines were used in reporting this study. RESULTS: The TISS-28 has an average of 34.2 ± 6.9 points at admission, which is considered a high nursing workload. A somewhat lower result was found for the discharge and average assessments. It shows that basic activities accounted for the highest percentage of time spent (38.0%), followed by the cardiovascular support category (26.5%). The TISS-28 shows consistent results throughout the study period, despite a small trend reduction in the last 2 years. CONCLUSIONS: Lower workloads were found for age ≤44 years and with a shorter length of stay. Higher workload was more probable in patients classified in Cullen Class IV (OR = 2.5) and with a normal to higher weight percentile (OR = 1.9 and 1.5, respectively). RELEVANCE TO CLINICAL PRACTICE: Knowledge of the factors influencing the nursing workload facilitates the implementation of rules to improve performance in nursing interventions, based on the redefinition of care priorities, increased productivity, human resources management and reduction of additional costs to the organisation, related to possible adverse events, among others.

First Population-Based Screening of Abdominal Aortic Aneurysm in Portugal.

BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) repairs in Portugal is one of the lowest mentioned in the literature. This phenomenon can be justified either by a low prevalence of the disease or by its low detection rate. To date, the prevalence of the pathology is unknown. The objective of the study was to estimate the prevalence of AAA and its associated risk factors, in men aged ≥65 years and to evaluate the population's disease awareness. METHODS: All males aged ≥65 years registered in a Portuguese primary health care unit were invited to participate. The abdominal aorta was measured by ultrasound (inner to inner method). Concomitant risk factors and patient's AAA awareness were also assessed. An aortic diameter >30 mm was considered aneurysmatic. RESULTS: Nine hundred thirty-three patients were invited for the screening. Of these, 715 participated in the study (participation rate of 76.6%). The AAA prevalence in this sample was 2.1%. Eighty-five percent of the evaluated patients had never heard of the disease before. The mean age of the assessed population was 72.3 years; Multiple logistic regression analysis showed a positive association between AAA and history of smoking (odds ratio [OR] 8.8, P = 0.037) and history of dyslipidemia (OR 9.6, P = 0.035). A negative association was found between diabetes and AAA (OR 0.33, P = 0.045). CONCLUSIONS: The found prevalence shows that a significant number of potentially fatal AAAs remains to be diagnosed in Portugal. These results highlight the need for an effective program of AAA detection in Portugal. The lack of awareness in the Portuguese population for this pathology should also prompt reflexion.

Validity and reliability of the Intelligibility in Context Scale: European Portuguese version.

The purpose of the study was to evaluate the validity, reliability, sensitivity and specificity of the European-Portuguese version of the Intelligibility in Context Scale (ICS-EP). Seventy-six children (age: M = 60.6, SD = 8.1 months), 25 having a parent or teacher concern about how they talked and 51 with no concern, were assessed with the phonetic-phonological test (TFF-ALPE) to calculate the following severity measures: percentage of phonemes correct (PPC), percentage of consonants correct (PCC), and percentage of vowels correct (PVC). Parents also filled out a questionnaire about their child's development (e.g. concern about how the child talks). The ICS was then completed by parents to estimate their children's intelligibility with different communicative partners. The results showed that item-level scores were different according to communicative partners. The mean ICS score for the whole sample was 4.5 (SD = 0.6), showing that children were "usually" to "always" intelligible. The ICS had excellent internal consistency (α = 0.96). Children with parental concern about their speech presented significantly lower mean scores (M = 3.91, SD = 0.59) than children without parental concerns (M = 4.78, SD = 0.36). There was a positive correlation between the ICS scores and PPC (r = .655), PCC (r = .654), and PVC (r = .588). A simple linear model was also obtained between the ICS mean score and the severity measures analyzed. High values were obtained for sensitivity (0.80) and specificity (0.84), using a cut-off point of 4.36. We conclude that the ICS-EP has good psychometric properties, suggesting it to be a valid tool for estimating children's intelligibility when talking with different communicative partners. Therefore, this version of the ICS can be used as a screening measure for children's speech intelligibility.

Pain, pain intensity and pain disability in high school students are differently associated with physical activity, screening hours and sleep.

BACKGROUND: Studies exploring the association between physical activity, screen time and sleep and pain usually focus on a limited number of painful body sites. Nevertheless, pain at different body sites is likely to be of different nature. Therefore, this study aims to explore and compare the association between time spent in self-reported physical activity, in screen based activities and sleeping and i) pain presence in the last 7-days for 9 different body sites; ii) pain intensity at 9 different body sites and iii) global disability. METHODS: Nine hundred sixty nine students completed a questionnaire on pain, time spent in moderate and vigorous physical activity, screen based time watching TV/DVD, playing, using mobile phones and computers and sleeping hours. Univariate and multivariate associations between pain presence, pain intensity and disability and physical activity, screen based time and sleeping hours were investigated. RESULTS: Pain presence: sleeping remained in the multivariable model for the neck, mid back, wrists, knees and ankles/feet (OR 1.17 to 2.11); moderate physical activity remained in the multivariate model for the neck, shoulders, wrists, hips and ankles/feet (OR 1.06 to 1.08); vigorous physical activity remained in the multivariate model for mid back, knees and ankles/feet (OR 1.05 to 1.09) and screen time remained in the multivariate model for the low back (OR = 2.34. Pain intensity: screen time and moderate physical activity remained in the multivariable model for pain intensity at the neck, mid back, low back, shoulder, knees and ankles/feet (Rp2 0.02 to 0.04) and at the wrists (Rp2 = 0.04), respectively. Disability showed no association with sleeping, screen time or physical activity. CONCLUSIONS: This study suggests both similarities and differences in the patterns of association between time spent in physical activity, sleeping and in screen based activities and pain presence at 8 different body sites. In addition, they also suggest that the factors associated with the presence of pain, pain intensity and pain associated disability are different.

Portuguese Older Adults Presenting at the Emergency Department: Predictive Validity of the Identification of Seniors at Risk (ISAR) Tool.

Following an emergency department (ED) visit, older adults are more likely to experience poorer outcomes than younger adults. It is crucial to identify older patients using a validated tool. One of the most studied tools is the Identification of Seniors at Risk (ISAR), which is used to identify older adults at risk of adverse outcomes after ED admission. The purpose of the current study was to examine the sensitivity, specificity, and interrater reliability of the Portuguese version of the ISAR when considering early (30 days) and late (180 days) outcomes. Four hundred two older adults presenting in EDs from January 2013 to August 2014 were prospectively enrolled and surveyed. The ISAR threshold (cutoff =2) presented a better compromise between sensitivity (81.8% to 88.7%) and specificity (14.7% to 28.1%) when compared to cutoffs =1 or =3, respectively. Interrater reliability results were very good (0.81 to 0.94). Overall, the Portuguese ISAR appears worthwhile for screening older adults at risk in EDs. [Journal of Gerontological Nursing, xx(x), xx-xx.].

Portuguese nurses' knowledge of and attitudes toward hospitalized older adults.

Portugal is impacted by the rapid growth of the aging population, which has significant implications for its health care system. However, nurses have received little education focusing on the unique and complex care needs of older adults. This gap in the nurses' education has an enormous impact in their knowledge and attitudes and affects the quality of nursing care provided to older adults. A cross-sectional study was conducted among 1068 Portuguese nurses in five hospitals (northern and central region) with the following purposes: (i) explore the knowledge and attitudes of nurses about four common geriatric syndromes (pressure ulcer, incontinence, restraint use and sleep disturbance) in Portuguese hospitals; and (ii) evaluate the influence of demographic, professional and nurses' perception about hospital educational support, geriatric knowledge, and burden of caring for older adults upon geriatric nursing knowledge and attitudes. The mean knowledge and attitudes scores were 0.41 ± 0.15 and 0.40 ± 0.21, respectively (the maximum score was 1). Knowledge of nurses in Portuguese hospitals about the four geriatric syndromes (pressure ulcers, sleep disturbance, urinary incontinence and restraint use) was found inadequate. The nurses' attitudes towards caring for hospitalized older adults were generally negative. Nurses who work in academic hospitals demonstrated significantly more knowledge than nurses in hospital centers. The attitudes of nurses were significantly associated with the hospital and unit type, region, hospital educational support, staff knowledge, and perceived burden of caring for older adults. The study findings support the need for improving nurses' knowledge and attitudes towards hospitalized older adults and implementing evidence-based guidelines in their practice.

Quasi-perfusion studies for intensified lentiviral vector production using a continuous stable producer cell line.

Quasi-perfusion culture was employed to intensify lentiviral vector (LV) manufacturing using a continuous stable producer cell line in an 8-day process. Initial studies aimed to identify a scalable seeding density, with 3, 4, and 5 × 104 cells cm-2 providing similar specific productivities of infectious LV. Seeding at 3 × 104 cells cm-2 was selected, and the quasi-perfusion was modulated to minimize inhibitory metabolite accumulation and vector exposure at 37°C. Similar specific productivities of infectious LV and physical LV were achieved at 1, 2, and 3 vessel volumes per day (VVD), with 1 VVD selected to minimize downstream processing volumes. The optimized process was scaled 50-fold to 1,264 cm2 flasks, achieving similar LV titers. However, scaling up beyond this to a 6,320 cm2 multilayer flask reduced titers, possibly from suboptimal gas exchange. Across three independent processes in 25 cm2 to 6,320 cm2 flasks, reproducibility was high with a coefficient of variation of 7.7% ± 2.9% and 11.9% ± 3.0% for infectious and physical LV titers, respectively. The optimized flask process was successfully transferred to the iCELLis Nano (Cytiva) fixed-bed bioreactor, with quasi-perfusion at 1 VVD yielding 1.62 × 108 TU.

Continuous manufacturing of lentiviral vectors using a stable producer cell line in a fixed-bed bioreactor.

Continuous manufacturing of lentiviral vectors (LVs) using stable producer cell lines could extend production periods, improve batch-to-batch reproducibility, and eliminate costly plasmid DNA and transfection reagents. A continuous process was established by expanding cells constitutively expressing third-generation LVs in the iCELLis Nano fixed-bed bioreactor. Fixed-bed bioreactors provide scalable expansion of adherent cells and enable a straightforward transition from traditional surface-based culture vessels. At 0.5 vessel volume per day (VVD), the short half-life of LVs resulted in a low total infectious titer at 1.36 × 104 TU cm-2. Higher perfusion rates increased titers, peaking at 7.87 × 104 TU cm-2 at 1.5 VVD. The supernatant at 0.5 VVD had a physical-to-infectious particle ratio of 659, whereas this was 166 ± 15 at 1, 1.5, and 2 VVD. Reducing the pH from 7.20 to 6.85 at 1.5 VVD improved the total infectious yield to 9.10 × 104 TU cm-2. Three independent runs at 1.5 VVD and a culture pH of 6.85 showed low batch-to-batch variability, with a coefficient of variation of 6.4% and 10.0% for total infectious and physical LV yield, respectively. This study demonstrated the manufacture of high-quality LV supernatant using a stable producer cell line that does not require induction.

A Case Report and an Overview of the Differential Diagnosis of Pigmented Lesions of the Conjunctiva: Just a Freckle or Something to Heckle?

A 42-year-old darkly pigmented woman presented at our emergency department with complaints of pruritus, foreign body sensation, and blurry vision. Besides findings compatible with mild dry eye disease, anterior segment examination revealed dark pigmented, ill-defined areas of the conjunctiva surrounding the temporal limbus and temporal bulbar conjunctiva in the left eye and involving the superior and inferior tarsal conjunctiva in both eyes. The patient reported no recent changes in these lesions. A diagnosis of complexion-associated melanosis in the palpebral conjunctiva of both eyes and primary acquired melanosis in the bulbar conjunctiva of the left eye was assumed, and the patient was placed under regular follow-up. Preservative-free tears were also recommended for her dry eye condition. Conjunctival pigmented lesions are a common finding during ophthalmologic evaluations. They pose a significant diagnostic challenge due to the wide array of differential diagnoses and the concern of misdiagnosing melanoma. A comprehensive clinical history and multidisciplinary evaluation are crucial in managing these cases.

Clinical outcomes and prognostic factors in Acanthamoeba keratitis.

PURPOSE: To report clinical findings and prognostic factors for visual and morphological outcomes in patients with Acanthamoeba keratitis (AK). METHODS: Single-center, retrospective, longitudinal study of 51 cases of AK diagnosed by real-time polymerase chain reaction (RT-PCR) between March 2010 and October 2022. The primary outcome was the final best corrected visual acuity (BCVA). Poor visual outcome was defined as a final BCVA ≥ 1 logMAR unit, while good visual outcome was defined as a final BCVA < 1 logMAR unit. Eyes from these two groups were compared, regarding demographic and initial clinical variables, anti-Acanthamoeba treatment used, and complications of the disease. Early diagnosis was defined as ≤ 14 days from symptom onset to diagnostic confirmation and initiation of Acanthamoeba medical treatment. Multivariable logistic regression was used to determine predictors of poor visual outcome. RESULTS: A total of 51 eyes from 46 patients diagnosed with AK, all contact lens (CL) wearers, were included in this study. Average follow-up was 39.0 ± 30.2 [total range 14-120] months. Thirty-one eyes (60.8 %) presented good visual outcome, with a lower baseline age (30.5 ± 9.0 vs. 42.3 ± 15.8; p = 0.020), better initial BCVA (0.8 ± 0.7 logMAR units vs. 1.3 ± 0.9 logMAR units; p = 0.047), higher rate of early diagnosis (45.2 % vs. 5.6 %; p = 0.004), and higher rate of therapeutic epithelial debridement (64.5 % vs. 10 %; p < 0.001). 20 eyes (39.2 %) presented poor visual outcome, with 12 eyes undergoing evisceration/enucleation (23.5 %). These 20 eyes presented a higher rate of complications (90 % vs. 61.3 %; p = 0.031). In multivariable analysis, early diagnosis of AK (OR 19.78; 95 % CI 2.07-189.11; p = 0.010) and therapeutic epithelial debridement (OR 19.02; 95 % CI 3.27-110.57; p = 0.001) were associated with a good visual outcome. CONCLUSIONS: In the present study, poor visual outcome was present in 39 % of affected eyes. Early AK diagnosis (≤14 days from symptom onset) and therapeutic epithelial debridement were associated with good final visual outcome.

A Comprehensive Analysis of Age and Gender Effects in European Portuguese Oral Vowels.

The knowledge about the age effects in speech acoustics is still disperse and incomplete. This study extends the analyses of the effects of age and gender on acoustics of European Portuguese (EP) oral vowels, in order to complement initial studies with limited sets of acoustic parameters, and to further investigate unclear or inconsistent results. A database of EP vowels produced by a group of 113 adults, aged between 35 and 97, was used. Duration, fundamental frequency (f0), formant frequencies (F1 to F3), and a selection of vowel space metrics (F1 and F2 range ratios, vowel articulation index [VAI] and formant centralization ratio [FCR]) were analyzed. To avoid the arguable division into age groups, the analyses considered age as a continuous variable. The most relevant age-related results included: vowel duration increase in both genders; a general tendency to formant frequencies decrease for females; changes that were consistent with vowel centralization for males, confirmed by the vowel space acoustic indexes; and no evidence of F3 decrease with age, in both genders. This study has contributed to knowledge on aging speech, providing new information for an additional language. The results corroborated that acoustic characteristics of speech change with age and present different patterns between genders.

Systematic review and meta-analysis of cell therapy for COVID-19: global clinical trial landscape, published safety/efficacy outcomes, cell product manufacturing and clinical delivery.

During the pandemic of severe respiratory distress syndrome coronavirus 2 (SARS-CoV2), many novel therapeutic modalities to treat Coronavirus 2019 induced disease (COVID-19) were explored. This study summarizes 195 clinical trials of advanced cell therapies targeting COVID-19 that were registered over the two years between January 2020 to December 2021. In addition, this work also analyzed the cell manufacturing and clinical delivery experience of 26 trials that published their outcomes by July 2022. Our demographic analysis found the highest number of cell therapy trials for COVID-19 was in United States, China, and Iran (N=53, 43, and 19, respectively), with the highest number per capita in Israel, Spain, Iran, Australia, and Sweden (N=0.641, 0.232, 0,223, 0.194, and 0.192 trials per million inhabitants). The leading cell types were multipotent mesenchymal stromal/stem cells (MSCs), natural killer (NK) cells, and mononuclear cells (MNCs), accounting for 72%, 9%, and 6% of the studies, respectively. There were 24 published clinical trials that reported on infusions of MSCs. A pooled analysis of these MSC studies found that MSCs provide a relative risk reduction for all-cause COVID-19 mortality of RR=0.63 (95% CI 0.46 to 0.85). This result corroborates previously published smaller meta-analyses, which suggested that MSC therapy demonstrated a clinical benefit for COVID-19 patients. The sources of the MSCs used in these studies and their manufacturing and clinical delivery methods were remarkably heterogeneous, with some predominance of perinatal tissue-derived products. Our results highlight the important role that cell therapy products may play as an adjunct therapy in the management of COVID-19 and its related complications, as well as the importance of controlling key manufacturing parameters to ensure comparability between studies. Thus, we support ongoing calls for a global registry of clinical studies with MSC products that could better link cell product manufacturing and delivery methods to clinical outcomes. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the near future, preventing pathology through vaccination still remains the best protection to date. We conducted a systematic review and meta-analysis of advanced cell therapy clinical trials as potential novel treatment for COVID-19 (resulting from SARS-CoV-2 coronavirus infection), including analysis of the global clinical trial landscape, published safety/efficacy outcomes (RR/OR), and details on cell product manufacturing and clinical delivery. This study had a 2-year observation interval from start of January 2020 to end of December 2021, including a follow-up period until end of July to identify published outcomes, which covers the most vivid period of clinical trial activity, and is also the longest observation period studied until today. In total, we identified 195 registered advanced cell therapy studies for COVID-19, employing 204 individual cell products. Leading registered trial activity was attributed to the USA, China, and Iran. Through the end of July 2022, 26 clinical trials were published, with 24 out of 26 articles employing intravenous infusions (IV) of mesenchymal stromal/stem cell (MSC) products. Most of the published trials were attributed to China and Iran. The cumulative results from the 24 published studies employing infusions of MSCs indicated an improved survival (RR=0.63 with 95% Confidence Interval 0.46 to 0.85). Our study is the most comprehensive systematic review and meta-analysis on cell therapy trials for COVID-19 conducted to date, clearly identifying the USA, China, and Iran as leading advanced cell therapy trial countries for COVID-19, with further strong contributions from Israel, Spain, Australia and Sweden. Although advanced cell therapies may provide an important adjunct treatment for patients affected by COVID-19 in the future, preventing pathology through vaccination remains the best protection.

Impact of Wound Dressing Changes on Nursing Workload in an Intensive Care Unit.

The objective of this study is to understand how the type of wound dressing changes (routine or frequent) in patients admitted to intensive care units influences nurses' workload. This study used a database of retrospective and analytical observational study from one Portuguese intensive care unit. The sample included 728 adult patients admitted between 2015 and 2019. The nursing workload was assessed by the TISS-28 scale, both at admission and at discharge. The linear regression results show that patients with frequent dressing changes are associated with a higher nursing workload, both at admission (Coef. 1.65; 95% CI [0.53; 2.77]) and discharge (Coef. 1.27; 95% CI [0.32; 2.22]). In addition, age influences the nursing workload; older people are associated with a higher nursing workload (at admission Coef. 0.07; 95% CI [0.04; 0.10]; at discharge Coef. 0.08; 95% CI [0.05; 0.10]). Additionally, an increase in nursing workload at admission would significantly increase the nursing workload at discharge (Coef. 0.27; 95% CI [0.21; 0.33]). The relative stability of the nursing workload over the studied years is also another important finding (the influence of studied years is non-significant). In conclusion, patients with frequent dressing changes presented higher TISS-28 scores when compared with patients with an exchange of routine dressings, which leads to a higher nursing workload.