Effects of Blood Flow Restriction Training in Patients before and after Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-Analysis.

(1) Objective: To examine the effects of blood flow restriction (BFR) training on muscle strength, cross-sectional area and knee-related function in patients selected for anterior cruciate ligament reconstruction (ACLR). (2) Methods: A literature search was conducted in PubMed, PEDro, Cochrane Library, Web of Science, SCOPUS, and ProQuest databases until 20 May 2024. Controlled clinical trials comparing the effects of BFR training with unrestricted training in patients before or after ACLR were selected. The GRADE approach was used to assess the degree of certainty for each meta-analysis. (3) Results: Ten studies were included (n = 287 participants). Standardized mean differences in favor of BFR training applied postoperatively were observed in knee extensor (SMD = 0.79; 95% CI = 0.06 to 1.52; I2: 68%) and flexor isokinetic strength (SMD = 0.53; 95% CI = 0.04 to 1.01; I2: 0%), and quadriceps cross-sectional area (SMD = 0.76; 95% CI = 0.27 to 1.26; I2: 0%). No changes were found in knee extensor isometric strength and knee-related function. The degree of certainty according to the GRADE was very low. (4) Conclusions: Very low degree of certainty suggests that BFR training provides additional benefits to unrestricted training on isokinetic strength and quadriceps cross-sectional area in patients undergoing ACLR.

Tobramycin Systemic Absorption in Lung Transplant Recipients Treated With Inhaled Tobramycin: A Cohort Study.

Inhaled tobramycin treatment has been associated with nephrotoxicity in some case reports, but limited data are available about serum levels and its possible systemic absorption in lung transplant recipients (LTR). We conducted a single-center, observational and retrospective study of all adult (>18 years old) LTR treated with inhaled tobramycin for at least 3 days between June 2019 and February 2022. Trough serum levels were collected and >2 µg/mL was considered a high drug level. The primary outcome assessed the presence of detectable trough levels, while the secondary outcome focused on the occurrence of acute kidney injury (AKI) in individuals with detectable trough levels. Thirty-four patients, with a median age of 60 years, were enrolled. The primary indications for treatment were donor bronchial aspirate bacterial isolation (18 patients) and tracheobronchitis (15 patients). In total, 28 patients (82%) exhibited detectable serum levels, with 9 (26%) presenting high levels (>2 µg/mL). Furthermore, 9 patients (26%) developed acute kidney injury during the treatment course. Median trough tobramycin levels were significantly elevated in invasively mechanically ventilated patients compared to non-ventilated individuals (2.5 µg/mL vs. 0.48 µg/mL) (p < 0.001). Inhaled tobramycin administration in LTRs, particularly in those requiring invasive mechanical ventilation, may result in substantial systemic absorption.

Is adding dry needling to a standard care protocol beneficial in patients with chronic neck pain? A randomized placebo-controlled trial.

PURPOSE: To evaluate the short-term effects of adding a dry needling therapy to a standard care protocol based on education, exercise and electrotherapy, compared to a sham procedure and to a standard care protocol in isolation in patients with chronic neck pain. MATERIAL AND METHODS: A randomized placebo-controlled trial was performed. The participants in the dry needling group received a standard care protocol based on patient education, therapeutic exercise and electrotherapy, as well as two sessions of dry needling in the upper trapezius, levator scapulae, and/or sternocleidomastoid muscles. The participants in the sham dry needling group received the same standard care protocol and two sessions of sham dry needling. The participants in the control group received the same standard care protocol. The outcomes measured were pain intensity, pressure pain threshold, neck disability, range of movement, activation of deep cervical flexor muscles, kinesiophobia, pain catastrophizing, anxiety, and depression. RESULTS: No significant group by time interactions were found for any of the outcome variables except for lower cervical spine range of movement (F = 3.79; p = 0.030). CONCLUSION: The addition of two sessions of dry needling in the superficial neck muscles to a standard protocol did not yield superior results compared to either the standard care alone or the standard care plus sham dry needling in patients with chronic neck pain in any outcome except for cervical range of movement.

Curricular and pedagogical approaches for physical activity prescription training: a mixed-methods study of the "Exercise is Medicine" workshops in Colombia.

BACKGROUND: The physical activity (PA) prescription workshop for physicians, through the global health initiative "Exercise is Medicine" (EIM), has trained more than 4000 health care professionals (HCPs) in Latin America. It has shown to be effective in increasing PA prescription knowledge and awareness among HCPs. The purpose of this paper is to evaluate the curricular and pedagogical approach used by EIM Colombia at the PA prescription workshops implemented between 2014 and 2015. METHODS: A mixed methods study, with a sequential explanatory design was implemented among a convenience sample of HCPs attending twenty-six PA prescription workshops. HCPs health status, PA personal habits, and medical practices were collected using a questionnaire at baseline among 795 participants (pre-test measurement), and subsequently quantitatively analyzed. A workshop satisfaction survey was administered after the completion of the workshop among 602 HCPs. The curricular and pedagogical approach of the workshop, the designers' and students' contextual factors, and perceptions about the workshop were measured using qualitative methods (analysis of the procedures manual, two workshop observations, three semi-structured interviews, and one focus group including 8 HCPs). RESULTS: The workshop is student-centered and guided by an expert with an academic and clinical background. Learning was achieved with theoretical and practical components using authentic performance and collaborative learning. An active teaching and learning approach was used with strategies such as interactive lectures, hands-on elements, and role-playing (patient-counselor). The workshop emphasized an individual approach when prescribing PA integrating in clinical practice not only health benefits but also patient´s beliefs, motivations, needs, and barriers. CONCLUSIONS: Evidence-based practices and authentic performance were the most salient pedagogical elements used by EIM Colombia at the PA prescription workshop. A knowledge assessment that includes the practical aspect is suggested for future workshops. The curricular and pedagogical approach of the PA prescription workshop implemented in Colombia is well received by the medical community and a useful continuing medical education intervention with a potential contribution to current, and future health promotion needs.

Sumoylation in astrocytes induces changes in the proteome of the derived small extracellular vesicles which change protein synthesis and dendrite morphology in target neurons.

Emerging evidence highlights the relevance of the protein post-translational modification by SUMO (Small Ubiquitin-like Modifier) in the central nervous system for modulating cognition and plasticity in health and disease. In these processes, astrocyte-to-neuron crosstalk mediated by extracellular vesicles (EVs) plays a yet poorly understood role. Small EVs (sEVs), including microvesicles and exosomes, contain a molecular cargo of lipids, proteins, and nucleic acids that define their biological effect on target cells. Here, we investigated whether SUMOylation globally impacts the sEV protein cargo. For this, sEVs were isolated from primary cultures of astrocytes by ultracentrifugation or using a commercial sEV isolation kit. SUMO levels were regulated: 1) via plasmids that over-express SUMO, or 2) via experimental conditions that increase SUMOylation, i.e., by using the stress hormone corticosterone, or 3) via the SUMOylation inhibitor 2-D08 (2',3',4'-trihydroxy-flavone, 2-(2,3,4-Trihydroxyphenyl)-4H-1-Benzopyran-4-one). Corticosterone and 2-D08 had opposing effects on the number of sEVs and on their protein cargo. Proteomic analysis showed that increased SUMOylation in corticosterone-treated or plasmid-transfected astrocytes increased the presence of proteins related to cell division, transcription, and protein translation in the derived sEVs. When sEVs derived from corticosterone-treated astrocytes were transferred to neurons to assess their impact on protein synthesis using the fluorescence non-canonical amino acid tagging assay (FUNCAT), we detected an increase in protein synthesis, while sEVs from 2-D08-treated astrocytes had no effect. Our results show that SUMO conjugation plays an important role in the modulation of the proteome of astrocyte-derived sEVs with a potential functional impact on neurons.

Effectiveness of aquatic training based on aerobic and strengthening exercises in patients with fibromyalgia: systematic review with meta-analysis.

BACKGROUND AND PURPOSE: fibromyalgia is a chronic condition causing widespread pain, fatigue, limited physical function, and reduced quality of life. Aquatic training is recommended as a first-line non-pharmacological treatment. This study aims to evaluate the effectiveness of aquatic training based on aerobic and strengthening exercises in improving symptoms in women with fibromyalgia. MATERIAL AND METHODS: a systematic review with meta-analysis was conducted by searching the PubMed, Scopus, Cochrane Library and Web of Science databases. Randomized clinical trials that compared aquatic therapy with either a control group or a land-based exercise group were included. Study quality was assessed using the PEDro scale, the risk of bias was evaluated using the Cochrane Risk of Bias Tool, and the certainty of the evidence was assessed the GRADE guidelines. RESULTS: six randomized clinical trials comprising 9 publications showed that aquatic therapy had statistically significant benefits compared to no intervention, including pain, fatigue, fibromyalgia impact, depression, physical function, and mental health in the short term. In the medium term, improvements were observed in fibromyalgia impact, physical function, and mental health. However, aquatic therapy was not found to be superior to land-based exercise. CONCLUSION: low to very low certainty of evidence suggested that aquatic training may reduce pain, fibromyalgia impact, fatigue and depression and improve physical function and mental health in patients with fibromyalgia. Further studies should investigate the medium and long-term effects of aquatic training using larger sample sizes.

Isavuconazole use and TDM in real-world pediatric practice.

Isavuconazole (ISA) is approved for treating invasive aspergillosis and mucormycosis in adults, but its use in children remains off-label. We report on the use of ISA in real-world pediatric practice with 15 patients receiving ISA for treatment of invasive fungal infections. Therapeutic drug monitoring (TDM) was performed in all patients, with 52/111 (46.8%) Ctrough determinations out of range, thus supporting the need for TDM in children, especially those receiving extracorporeal membrane oxygenation (ECMO).

Multicentre cross-sectional study assessing content validity of the International Classification of Functioning, disability and health core set for post-acute musculoskeletal conditions in primary care physiotherapy services.

OBJECTIVE: To assess content validity of the comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for post-acute musculoskeletal conditions in primary care physiotherapy services. DESIGN: Multicentre cross-sectional study. SUBJECTS: Patients with musculoskeletal disorders referred to primary care physiotherapy services. METHODS: Structured interviews were conducted using categories from the ICF Core Set, and their relevance was assessed using a visual analogue scale. An ICF category had to represent a problem for at least 5% of the sample in order to be validated. RESULTS: The study sample comprised 274 patients. All categories in the ICF Core Set were confirmed. Body functions related to pain and movement were the most commonly impaired, with ICF categories "b280 Sensation of pain" and "b710 Mobility of joint functions" having the highest prevalence (87.2% and 84.7%, respectively). Activity limitations and participation restrictions were concentrated in chapters "d4 Mobility" (63.5% for "d430 Lifting and carrying objects") and "d2 General tasks and demands" (59.5% for "d240 Handling stress and other psychological demands"). The most relevant environmental factors were "e225 Climate" (55.8%) and "e580 Health services, systems and policies" (39.4%). CONCLUSION: The ICF Core Set for post-acute musculoskeletal conditions shows appropriate content validity for primary care physiotherapy services.

Validation of the International Classification of Functioning, Disability, and Health (ICF) core set for post-acute musculoskeletal conditions in a primary care physiotherapy setting from the perspective of patients using focus groups.

PURPOSE: To validate the comprehensive ICF core set for post-acute musculoskeletal conditions from the perspective of patients in a primary care physiotherapy setting. MATERIALS AND METHODS: A qualitative study was conducted with patients suffering from musculoskeletal problems. A phenomenological approach based on focus groups was used to identify the most relevant aspects related to physical therapy care in their condition. The data were analyzed using a meaning condensation procedure, identifying relevant themes and concepts. The identified concepts were linked to the ICF and compared to the ICF core set for post-acute musculoskeletal conditions. RESULTS: Forty-three patients were included in eight focus groups. A total of 1281 relevant concepts were extracted and related to 156 ICF second-level entities. Entities in the ICF core set for post-acute musculoskeletal conditions were 95.7% confirmed. Eighty-nine additional second-level ICF entities were identified. CONCLUSIONS: Entities in the ICF core set for post-acute musculoskeletal conditions are relevant to patients seen in primary care physical therapy units. However, there are areas of functioning related to community health care not covered by this ICF-based tool.IMPLICATIONS OF REHABILITATIONAn ICF-based framework is feasible for the assessment of musculoskeletal conditions.Post-acute musculoskeletal ICF core set was confirmed in patient focus groups.Additional ICF categories emerged for a primary care physical therapy setting.Community features of functioning could be addressed by a tailored ICF core set.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study.

PURPOSE: The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. METHODS: We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. RESULTS: Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p=0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p=0.04), respiratory failure (59.3% vs 42.8%, p=0.001), ICU admission (17.8% vs 7%, p=0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p=0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06-6.73). CONCLUSIONS: Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection.

The effectiveness of non-surgical interventions in athletes with groin pain: a systematic review and meta-analysis.

BACKGROUND: Groin pain is a common pathology among athletes, presenting pain and a reduced range of motion (ROM) as clinical characteristics. Passive physical therapy (PPT) and exercise therapy (ET) interventions are chosen firstly before surgery. The aim of this systematic review and meta-analysis was: (i) to qualitative review the effects of each non-surgical intervention; (ii) to quantitative compare the effects of PPTs plus ET intervention to ET in isolation in pain intensity, and hip ROM in athletes with groin pain. METHODS: A systematic review and meta-analysis was conducted. Pubmed, PEDro, Web of science, Scopus and Cochrane library were searched. Randomized controlled trials comparing PPT plus ET to ET interventions were included. The methodological quality and risk of bias of the included studies, were assessed with the PEDro scale and the Cochrane risk-of-bias tool. To assess the certainty of evidence the GRADEpro GDT was used. Meta-analyses were conducted using RevMan 5.4 using mean difference analysis to assess the variables pain intensity and hip ROM. RESULTS: A total of 175 studies was identified from the consulted databases. Five studies were included for systematic- review, from which three studies were meta-analyzed. The methodological quality of the included studies ranged from poor to high. ET compared to PPT plus ET provided statistically significant improvements in pain intensity in the short-term (MD = 2.45; 95% CI 1.11, 3.79; I2 :65%). No statistically significant differences between interventions were obtained for hip ROM in the short-term. CONCLUSIONS: The qualitative review showed that PPTs plus ET and ET seem to have positive effects on pain intensity and hip ROM. The quantitative analysis found very low certainty of evidence proposing a positive effect in pain intensity for ET interventions based on hip muscles stretching, compared to PPT combined with ET, in the short-term.

Effects of exercise therapy on diabetic neuropathy: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the effects of exercise therapy on neuropathic symptoms, signs, psychosocial aspects, and physical function in people with diabetic neuropathy (DN). METHODS: A search in PubMed, Web of Science, Physiotherapy Evidence (PEDro), and Cochrane databases was performed from inception to Invalid Date NaN, . Randomized clinical trials (RCTs) were selected in patients with DN comparing exercise therapy with a control group. The studies' methodological quality was assessed with the PEDro scale. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess the overall quality. RESULTS: Eleven RCTs (n = 517 participants) were included. Nine studies showed high methodological quality. Mean (MD) and standardized mean differences (SMD) were observed in favor of exercise therapy for symptoms (MD = -1.05; confidence interval 95% = -1.90 to -0.20), signs (SMD = -0.66; confidence interval 95%= -1 to -0.32), and physical function (SMD = -0.45; confidence interval 95% = -0.66 to -0.24). No changes were found in psychosocial aspects (SMD = -0.37; confidence interval 95% = -0.92 to 0.18). The overall quality of evidence was very low. CONCLUSION: The quality of evidence suggesting that exercise therapy provides short-term benefits in neuropathic symptoms, signs, and physical function in patients with DN is very low. Furthermore, there were no effects found on psychosocial aspects.

Researcher's Perspective on Musculoskeletal Conditions in Primary Care Physiotherapy Units through the International Classification of Functioning, Disability, and Health (ICF): A Scoping Review.

(1) Background: Musculoskeletal disorders are the second cause of disability in the world. The International Classification of Functioning Disability and Health (ICF) is a tool for systematically describing functioning. Outcome measures for musculoskeletal disorders and functioning concepts embedded in them have not been described under the ICF paradigm. The objective of this scoping review was to identify ICF categories representing the researcher's perspective and to compare them with the ICF core set for post-acute musculoskeletal conditions. (2) Methods: This review was conducted as follows: (a) literature search using MEDLINE/PubMed, CINAHL, Web of Science, and Scopus databases; (b) study selection applying inclusion criteria (PICOS): musculoskeletal conditions in primary care, application of physiotherapy as a treatment, outcome measures related to functioning, and experimental or observational studies conducted in Western countries during the last 10 years; (c) extraction of relevant concepts; (d) linkage to the ICF; (e) frequency analysis; and (f) comparison with the ICF core set. (3) Results: From 540 studies identified, a total of 51 were included, and 108 outcome measures were extracted. In the ICF linking process, 147 ICF categories were identified. Analysis of data showed that 84.2% of the categories in the ICF core set for post-acute musculoskeletal conditions can be covered by the outcome measures analyzed. Sixty-eight relevant additional ICF categories were identified. (4) Conclusion: Outcome measures analyzed partially represent the ICF core set taken as a reference. The identification of additional categories calls into question the applicability of this core set in primary care physiotherapy units.

Dot Immunobinding Assay for the Rapid Serodetection of Scedosporium/Lomentospora in Cystic Fibrosis Patients.

The detection of Scedosporium/Lomentospora is still based on non-standardized low-sensitivity culture procedures. This fact is particularly worrying in patients with cystic fibrosis (CF), where these fungi are the second most common filamentous fungi isolated, because a poor and delayed diagnosis can worsen the prognosis of the disease. To contribute to the discovery of new diagnostic strategies, a rapid serological dot immunobinding assay (DIA) that allows the detection of serum IgG against Scedosporium/Lomentospora in less than 15 min was developed. A crude protein extract from the conidia and hyphae of Scedosporium boydii was employed as a fungal antigen. The DIA was evaluated using 303 CF serum samples (162 patients) grouped according to the detection of Scedosporium/Lomentospora in the respiratory sample by culture, obtaining a sensitivity and specificity of 90.48% and 79.30%, respectively; positive and negative predictive values of 54.81% and 96.77%, and an efficiency of 81.72%. The clinical factors associated with the results were also studied using a univariate and a multivariate analysis, which showed that Scedosporium/Lomentospora positive sputum, elevated anti-Aspergillus serum IgG and chronic Pseudomonas aeruginosa infection were significantly associated with a positive result in DIA, while Staphylococcus aureus positive sputum showed a negative association. In conclusion, the test developed can offer a complementary, rapid, simple and sensitive method to contribute to the diagnosis of Scedosporium/Lomentospora in patients with CF.

A survey to describe common practices on antifungal monitoring among Spanish clinicians.

INTRODUCTION: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. METHODS: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. RESULTS: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. CONCLUSIONS: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.

Lack of ApoE inhibits ADan amyloidosis in a mouse model of familial Danish dementia.

The Apolipoprotein E-ε4 allele (APOE-ε4) is the strongest genetic risk factor for late onset Alzheimer disease (AD). ApoE plays a critical role in amyloid-ß (Aß) accumulation in AD, and genetic deletion of the murine ApoE gene in mouse models results in a decrease or inhibition of Aß deposition. The association between the presence of ApoE and amyloid in amyloidoses suggests a more general role for ApoE in the fibrillogenesis process. However, whether decreasing levels of ApoE would attenuate amyloid pathology in different amyloidoses has not been directly addressed. Familial Danish dementia (FDD) is an autosomal dominant neurodegenerative disease characterized by the presence of widespread parenchymal and vascular Danish amyloid (ADan) deposition and neurofibrillary tangles. A transgenic mouse model for FDD (Tg-FDD) is characterized by parenchymal and vascular ADan deposition. To determine the effect of decreasing ApoE levels on ADan accumulation in vivo, we generated a mouse model by crossing Tg-FDD mice with ApoE KO mice (Tg-FDD+/-/ApoE-/-). Lack of ApoE results in inhibition of ADan deposition up to 18 months of age. Additionally, our results from a genetic screen of Tg-FDD+/-/ApoE-/- mice emphasize the significant role for ApoE in neurodegeneration in FDD via glial-mediated mechanisms. Taken together, our findings suggest that the interaction between ApoE and ADan plays a key role in FDD pathogenesis, in addition to the known role for ApoE in amyloid plaque formation in AD.