Effect of Donated Premature Milk in the Prevention of Bronchopulmonary Dysplasia.

INTRODUCTION: Breastfeeding is one of the strategies that has been shown to be effective in preventing severe forms of bronchopulmonary dysplasia (BPD). When mother's own milk (MOM) is not available, pasteurized donor milk (DM) is the best alternative. However, the evidence is inconclusive on the difference in the incidence of bronchopulmonary dysplasia (BPD) between patients fed MOM and those fed with DM. As standard DM is usually mature pooled milk donated by mothers who have delivered their babies at term, the potential benefits of preterm milk may be lost. MATERIALS AND METHODS: An observational, retrospective, single-center study was conducted in the neonatology department of a high-complexity hospital. The study included newborns <32 weeks of gestational age born between January 2020 and December 2022. When supplemental milk was needed, non-pooled preterm pasteurized donor milk (PDM) matched for gestational age and moment of lactation was used in this study, classifying preterm infants in two groups: mainly MOM (>50% of the milk) or mainly PDM (>50% of the milk). Two groups were established: those who received >50% MOM and those who received >50% PDM. They were also classified according to the diagnosis of DBP: one group included no BPD or grade 1 BPD (noBPD/1), while the other included grade 2 or 3 BPD (BPD 2-3). The objectives of this study were, firstly, to evaluate the incidence of BPD 2-3 among patients who predominantly received PDM versus MOM. Secondly, to analyze differences in the type of human milk received and its nutritional components, as well as to study the growth in patients with or without BPD. RESULTS: One hundred ninety-nine patients were included in the study. A comparison of noBPD/1 versus BPD 2-3 groups between those receiving mainly MOM versus PDM showed no significant differences (19% vs. 20%, p 0.95). PDM colostrum in BPD 2-3 compared to noBPD/1 was higher in protein content (2.24 g/100 mL (SD 0.37) vs. 2.02 g/100 mL (SD 0.29) p < 0.01), although the statistical significance decreased after adjustment for gestational age and birth weight z-score (OR 3.53 (0.86-14.51)). No differences were found in the macronutrients in the mature milk of patients feeding more than 50% PDM in both study groups. Growth of BPD 2-3 showed a greater decrease in the difference in z-scores for height at birth and at discharge compared to noBPD/1 (-1.64 vs. -0.43, p 0.03). CONCLUSIONS: The use of mainly MOM or PDM demonstrates a similar incidence of noBPD/1 or BPD 2-3. Non-pooled and matched by gestational age and time of lactation preterm donor milk can probably be an alternative when mother's own milk is not available, with a similar protective effect in the prevention of severe BPD.

Monitorización del grado de satisfacción tras intervención nutricional en pacientes con cáncer / Monitoring satisfaction level after nutritional intervention in cancer patients

Introducción: La identificación temprana de la angustiapsicosocial y el impacto de la caquexia permiten intervencio-nes oportunas para mejorar los síntomas.Los PREM (Patient-Reported Experience Measures) aportanvalor a pacientes y organizaciones sanitarias. El poder real delos mismos se encuentra en la posibilidad de cruzarlos con da-tos clínicos. Esto permite identificar puntos críticos y áreas demejora de la calidad asistencial de los procesos. La intervención nutricional en pacientes seleccionadosbrinda un beneficio significativo para algunos aspectos comoel funcionamiento emocional, la disnea, la pérdida de apetitoy el estado de salud global.Por ello, se propone evaluar el grado de satisfacción de lospacientes en los que se ha realizado una intervención nutri-cional durante el tratamiento oncológico activo.Metodología: Estudio retrospectivo, exploratorio, delgrado de satisfacción, en referencia a la intervención nutricio-nal, en pacientes tratados por cáncer en el Hospital de Día deOncología del hospital Universitario Doctor Peset de Valencia,entre enero de 2022 y enero de 2023. Resultados: Se incluyeron un total de 93 pacientes. Seelaboró un cuestionario de 15 preguntas que se ofreció a los50 últimos pacientes incluidos. Respondieron de forma volun-taria y anónima 28 (56%). En el 95% de los casos la inter-vención nutricional se valoró de forma satisfactoria.Conclusiones: La identificación temprana de la desnutri-ción y la intervención oportuna tienen un impacto favorableen el grado de satisfacción del paciente.(AU)

Introduction: Early identification of psychosocial distressand the impact of cachexia allows for timely interventions toimprove symptoms. Patient-Reported Experience Measures(PREMs) add value to patients and healthcare organizations.Their true power lies in the ability to cross-reference themwith clinical data. This enables the identification of criticalpoints and areas for improving the quality of care processes.Nutritional intervention in selected cancer patients providessignificant benefits for aspects such as emotional functioning,dyspnea, loss of appetite, and overall health status. Therefore, we propose to evaluate the satisfaction level ofpatients who have undergone nutritional intervention duringactive oncological treatment. Methodology: Retrospective exploratory study of satisfac-tion levels regarding nutritional intervention in cancer patientstreated at the Oncology Day Hospital of the UniversityHospital Doctor Peset in Valencia, between January 2022 andJanuary 2023.Results: A total of 93 patients were included. A question-naire consisting of 15 questions was developed and offered tothe last 50 included patients. Twenty-eight (56%) respondedvoluntarily and anonymously. In 95% of cases, nutritional in-tervention was evaluated satisfactorily.Conclusions: Early identification of malnutrition andtimely intervention have a favorable impact on patient satis-faction levels.(AU)

T-cell immune profile in blood of systemic mastocytosis: Association with disease features.

BACKGROUND: Systemic mastocytosis (SM) is a heterogeneous disease characterized by an expansion of KIT-mutated mast cells (MC). KIT-mutated MC display activated features and release MC mediators that might act on the tumour microenvironment and other immune cells. Here, we investigated the distribution of lymphocyte subsets in blood of patients with distinct subtypes of SM and determined its association with other disease features. METHODS: We studied the distribution of TCD4+ and TCD4- cytotoxic cells and their subsets, as well as total NK- and B cells, in blood of 115 SM patients-38 bone marrow mastocytosis (BMM), 67 indolent SM (ISM), 10 aggressive SM (ASM)- and 83 age-matched healthy donors (HD), using spectral flow cytometry and the EuroFlow Immunomonitoring panel, and correlated it with multilineage KITD816V , the alpha-tryptasemia genotype (HαT) and the clinical manifestations of the disease. RESULTS: SM patients showed decreased counts (vs. HD) of TCD4- cytotoxic cells, NK cells and several functional subsets of TCD4+ cells (total Th1, Th2-effector memory, Th22-terminal effector and Th1-like Tregs), together with increased T-follicular-helper and Th1/Th17-like Treg counts, associated with different immune profiles per diagnostic subtype of SM, in multilineal versus MC-restricted KITD816V and in cases with a HαT+ versus HαT- genotype. Unique immune profiles were found among BMM and ISM patients with MC-restricted KITD816V who displayed HαT, anaphylaxis, hymenoptera venom allergy, bone disease, pruritus, flushing and GI symptoms. CONCLUSION: Our results reveal altered T- and NK-cell immune profiles in blood of SM, which vary per disease subtype, the pattern of involvement of haematopoiesis by KITD816V , the HαT genotype and specific clinical manifestations of the disease.

Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.

Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.

Development of a Rapid Adeno-Associated Virus (AAV) Identity Testing Platform through Comprehensive Intact Mass Analysis of Full-Length AAV Capsid Proteins.

Adeno-associated viruses (AAVs) are commonly used as vectors for the delivery of gene therapy targets. Characterization of AAV capsid proteins (VPs) and their post-translational modifications (PTMs) have become a critical attribute monitored to evaluate product quality. Liquid chromatography-mass spectrometry (LC-MS) analysis of intact AAV VPs provides both quick and reliable serotype identification as well as proteoform information on each VP. Incorporating these analytical strategies into rapid good manufacturing practice (GMP)-compliant workflows containing robust, but simplified, data processing methods is necessary to ensure effective product quality control (QC) during production. Here, we present a GMP-compliant LC-MS workflow for the rapid identification and in-depth characterization of AAVs. Hydrophilic interaction liquid chromatography (HILIC) MS with difluoroacetic acid as a mobile phase modifier is utilized to achieve the intact separation and identification of AAV VPs and their potential proteoforms. Peptide mapping is performed to confirm PTMs identified during intact VP analysis and for in-depth PTM characterization. The intact separations platform is then incorporated into a data processing workflow developed using GMP-compliant software capable of rapid AAV serotype identification and, if desired, specific serotype PTM monitoring and characterization. Such a platform provides product QC capabilities that are easily accessible in a regulatory setting.

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.

Multi-Attribute Method (MAM) Analytical Workflow for Biotherapeutic Protein Characterization from Process Development to QC.

The multi-attribute method (MAM) has emerged significantly in recent years to support biotherapeutic protein characterization from process development to the QC environment. MAM is a liquid chromatography mass spectrometry (LC-MS) based peptide mapping approach, which combines the benefits from liquid chromatography coupled to high resolution accurate mass mass spectrometry (LC-HRAM MS), enabling direct assessment of protein sequence and product quality attributes with site specificity. These product quality attributes may impact efficacy, safety, stability, and process robustness. MAM is intended to replace conventional analytical approaches as it offers a more streamlined strategy for parallel monitoring of multiple attributes in a single analysis with high sensitivity and confidence, and ultimately supports more robust Quality by Design (QbD) approaches and faster decision cycles for biotherapeutic development. MAM consists of three main stages. The first stage is sample digestion, which typically entails proteolytic digestion of the protein. The second stage is reversed-phase chromatographic separation of the generated peptides and detection by HRAM MS in two phases. During MAM Phase I (discovery phase), data-dependent acquisition (DDA) MS/MS is performed to enable confident identification of peaks and development of a peptide workbook. During MAM Phase II (monitoring phase), full MS acquisition is only carried out for the monitoring of predefined product quality attributes (PQAs). The third stage is data processing, which entails analysis and reporting for each of the two phases including evaluation of sequence coverage, assessment of PQAs and peptide workbook creation during phase I, and targeted monitoring of predefined product attributes and new peak detection (NPD) during phase II. The latter is a comparative analysis that uses a base peak alignment algorithm to determine any non-monitored differences between the LC-MS chromatograms of a test sample and a reference standard. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: In-solution sample digestion Alternate Protocol: Automated sample digestion Basic Protocol 2: Reversed-phase chromatographic separation and detection by HRAM-MS (RPLC-HRAM MS) Basic Protocol 3: Data processing and reporting.

MALAT1 expression is associated with aggressive behavior in indolent B-cell neoplasms.

MALAT1 long non-coding RNA has oncogenic roles but has been poorly studied in indolent B-cell neoplasms. Here, MALAT1 expression was analyzed using RNA-seq, microarrays or qRT-PCR in primary samples from clinico-biological subtypes of chronic lymphocytic leukemia (CLL, n = 266), paired Richter transformation (RT, n = 6) and follicular lymphoma (FL, n = 61). In peripheral blood (PB) CLL samples, high MALAT1 expression was associated with a significantly shorter time to treatment independently from other known prognostic factors. Coding genes expressed in association with MALAT1 in CLL were predominantly related to oncogenic pathways stimulated in the lymph node (LN) microenvironment. In RT paired samples, MALAT1 levels were lower, concordant with their acquired increased independency of external signals. Moreover, MALAT1 levels in paired PB/LN CLLs were similar, suggesting that the prognostic value of MALAT1 expression in PB is mirroring expression differences already present in LN. Similarly, high MALAT1 expression in FL predicted for a shorter progression-free survival, in association with expression pathways promoting FL pathogenesis. In summary, MALAT1 expression is related to pathophysiology and more aggressive clinical behavior of indolent B-cell neoplasms. Particularly in CLL, its levels could be a surrogate marker of the microenvironment stimulation and may contribute to refine the clinical management of these patients.

Análisis de factores de riesgo de vaciamiento gástrico lento tras la duodenopancreatectomía cefálica / Study of risk factors for delayed gastric emptying after partial pancreatoduodenectomy

Introducción: El vaciamiento gástrico lento (VGL) es una de las complicaciones más frecuentes tras la duodenopancreatectomía cefálica. El objetivo del actual estudio es analizar los factores de riesgo de su aparición. Métodos: Análisis de factores de riesgo de VGL sobre una base de datos prospectiva de 390 pacientes intervenidos entre 2013 y 2021. Se realizó un estudio retrospectivo comparativo entre pacientes con y sin VGL y posteriormente un estudio de factores de riesgo de VGL mediante modelos de regresión logística univariante y multivariante. Resultados: La incidencia de VGL en el global de la serie fue del 28%. Un 63% de los pacientes presentaron alguna complicación y la mortalidad postoperatoria fue del 3,1%. Se evidenció que la edad mediana (73 años vs. 68 años, p<0,001) y la creatinina preoperatorias (75 vs. 68.5, p<0,001) eran superiores en el grupo VGL. El estudio de factores de riesgo evidenció que la edad superior a 60 años (p=0,002) y la fístula pancreática (p<0,001) eran factores de riesgo de VGL. Conclusiones: La presencia de fístula pancreática se confirma como factores de riesgo de VGL tras la duodenopancreatectomía. Además, se demuestra que la edad superior a 60 años es un factor de riesgo de VGL. (AU)

Introduction: Delayed gastric emptying is one of the most frequent complications after pancreatoduodenectomy. Methods: We performed an analysis of risk factors for delayed gastric emptying on a prospective database of 390 patients operated on between 2013 and 2021. A comparative retrospective study was carried out between patients with and without delayed gastric emptying and subsequently a study of risk factors for delayed gastric emptying using univariate and multivariate logistic regression models. Results: The incidence of delayed gastric emptying in the overall series was 28%. The morbidity of the group was 63% and postoperative mortality was 3.1%. Focusing in delayed gastric emptying, it was shown that the median age (73 years vs. 68 years, p<0.001) and preoperative creatinine (75 vs. 65.5, p<0.001) were higher in the group with this complication. The study of risk factors showed that age over 60 years (p=0.002) and pancreatic fistula (p<0.001) were risk factors for delayed gastric emptying. Conclusions: The presence of pancreatic fistula is confirmed as risk factor for slow gastric emptying after pancreaticoduodenectomy. In addition, age over 60 years is shown to be a risk factor for slow gastric emptying. (AU)

Needle arthroscopy of the elbow through an anterior transbrachial portal.

Background: Current innovation in needle arthroscopy is improving the safety of anterior portals around the elbow. This study evaluated the proximity to the radial nerve, median nerve, and brachial artery on cadaveric specimens of an anterior portal used for elbow arthroscopy. Methods: Ten fresh-frozen adult cadaveric extremities were used. After marking the cutaneous references, the NanoScope cannula was introduced just lateral to the biceps tendon, through the brachialis muscle and the anterior capsule. Elbow arthroscopy was performed. Dissection was then carefully performed on all specimens with the NanoScope cannula in place. The shortest distance from the cannula to the median nerve, radial nerve, and brachial artery was measured with a handheld sliding digital caliper. Results: The cannula was an average of 12.92 mm away from the radial nerve, 22.27 mm from the median nerve, and 16.8 mm from the brachial artery. Needle arthroscopy performed through this portal allows complete visualization of the anterior compartment of the elbow, as well as direct visualization of the posterolateral compartment. Conclusion: Needle arthroscopy of the elbow through an anterior transbrachialis portal is safe for the main neurovascular structures. In addition, this technique allows complete visualization of the anterior and posterolateral compartments of the elbow through the humerus-radius-ulna space.

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.

Multi-Attribute Method (MAM): An Emerging Analytical Workflow for Biopharmaceutical Characterization, Batch Release and cGMP Purity Testing at the Peptide and Intact Protein Level.

The rapid growth of biotherapeutic industry, with more and more complex molecules entering the market, forces the need for advanced analytical platforms that can quickly and accurately identify and quantify product quality attributes. Mass spectrometry has the potential to provide more detailed information about the quality attributes of complex products, and MS methods are more sensitive than UV methods for detection of impurities. The multi-attribute method (MAM), a liquid chromatography-mass spectrometry based analytical approach is an emerging platform which supports biotherapeutic characterization and cGMP testing. The main advantage lies in the ability to monitor multiple quality attributes in a single assay, both at the peptide and the intact level, facilitating streamlined biopharmaceutical production, from research and development to the QC environment. This review highlights the current landscape of the MAM approach with special attention given to increased analytical throughput, general requirements for QC in terms of instrumentation and software, regulatory requirements, and industry acceptance of the MAM platform.

Exploring proteoforms of the IgG2 monoclonal antibody panitumumab using microchip capillary electrophoresis-mass spectrometry.

The IgG2 type monoclonal antibody panitumumab is an anti-epidermal growth factor receptor (EGFR) drug used for the treatment of EGFR-expressing, chemotherapy resistant, metastatic colorectal carcinoma. In this study, panitumumab drug product was first analysed using size exclusion chromatography coupled to mass spectrometry for rapid identity testing. The experimental data led to the identification of two panitumumab isoforms with several prominent forms remaining unidentified, despite apparently low sample complexity. Microchip capillary electrophoresis-mass spectrometry (CE-MS) was subsequently utilised for a more detailed characterization. It was observed that panitumumab is subject to partial N-terminal pyroglutamate formation. Incomplete conversion is uncharacteristic for N-terminally exposed glutamines and in case of panitumumab gives rise to forms which show successive mass offsets of 17 Da, respectively. If not separated before mass spectrometric analysis, e.g. by capillary electrophoresis, such near isobaric species coalesce into single MS peaks, which subsequently hampers or prevents their assignment. With a total of 42 panitumumab isoforms assigned by CE-MS, these observations highlight a potential pitfall of commonly applied rapid identity testing workflows and demonstrate that even low complexity biopharmaceuticals can require separation strategies which offer high separation selectivity for species close in mass.

Multi-attribute method (MAM) to assess analytical comparability of adalimumab biosimilars.

Adalimumab drug product (Humira ®), the first fully human monoclonal antibody (mAb) approved by FDA in 2002, led the top ten list of best-selling mAbs in 2018 and has been the most profitable drug in the world. With the expiration of patent protection in Europe in 2018 and in United States by 2023, the landscape is changing as up to 10 adalimumab biosimilars are expected to enter the market in the US. Biosimilars offer the potential to lower costs on health care systems and increase patient accessibility. The analytical similarity of seven different adalimumab biosimilars was accomplished in the present study using the multi-attribute method (MAM), a LC-MS based peptide mapping technique that allows for primary sequence assessment and evaluation of multiple quality attributes including deamidation, oxidation, succinimide formation, N- and C- terminal composition and detailed N-glycosylation analysis. In the first step, characterization of the most relevant post-translational modifications of a reference product was attained during the discovery phase of MAM. During the second step, as part of the MAM targeted monitoring phase, adalimumab batch-to batch variability was evaluated to define statistical intervals for the establishment of similarity ranges. The third step describes biosimilarity evaluation of predefined quality attributes and new peak detection for the assessment of any new or modified peak compared to the reference product. This study highlights a new perspective of the MAM approach and its underlying power for biotherapeutic comparability exercises in addition to analytical characterization. MAM offers a streamlined comparability assessment workflow based on high-confidence quality attribute analysis using high-resolution accurate mass mass spectrometry (HRAM MS) and the capability to detect any new or modified peak compared to the reference product.

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.

Cation exchange chromatography on a monodisperse 3 µm particle enables extensive analytical similarity assessment of biosimilars.

Biosimilarity assessment requires extensive characterization and comparability exercises to investigate product quality attributes of an originator product and its potential biosimilar(s) and to highlight any differences between them. Performing a thorough comparison allows a shortened approval path, which also eliminates lengthy and expensive clinical trials, ensuring comparable product quality and efficacy but at lower drug prices. The wide variety of analytical methods available for biosimilar assessment ranges from biological to analytical assays, each providing orthogonal information to fully characterize biosimilar candidates. Intact native mass spectrometry (MS) has been shown to be an excellent tool for detection and monitoring of important quality attributes such as N-glycosylation, deamidation, sequence truncation and higher order structures. When combined with efficient upfront separation methods, simplification of the proteoform heterogeneity and associated complexity prior to MS analysis can be achieved. Native mass spectrometry can provide robust and accurate results within short analysis times and requires minimal sample preparation. In this study we report the use of a monodisperse strong cation exchange chromatography phase hyphenated with Orbitrap mass spectrometry (SCX-MS) to compare the best-selling biopharmaceutical product Humira® with 7 commercially approved biosimilar products. SCX-MS analysis allowed for the identification of previously described as well as so far unreported proteoforms and their relative quantitation across all samples, revealing differences in N-glycosylation and lysine truncation, as well as unique features for some products such as sialylation and N-terminal clipping. SCX-MS analysis, powered by a highly efficient separation column, enabled deep and efficient analytical comparison of biosimilar products.

The relationship between patient empowerment and related constructs, affective symptoms and quality of life in patients with type 2 diabetes: a systematic review and meta-analysis.

Introduction: The aim of this systematic review is to assess the relationship between patient empowerment and other empowerment-related constructs, and affective symptoms and quality of life in patients with type 2 diabetes. Methods: A systematic review of the literature was conducted, according to the PRISMA guidelines. Studies addressing adult patients with type 2 diabetes and reporting the association between empowerment-related constructs and subjective measures of anxiety, depression and distress, as well as self-reported quality of life were included. The following electronic databases were consulted from inception to July 2022: Medline, Embase, PsycINFO, and Cochrane Library. The methodological quality of the included studies was analyzed using validated tools adapted to each study design. Meta-analyses of correlations were performed using an inverse variance restricted maximum likelihood random-effects. Results: The initial search yielded 2463 references and seventy-one studies were finally included. We found a weak-to-moderate inverse association between patient empowerment-related constructs and both anxiety (r = -0.22) and depression (r = -0.29). Moreover, empowerment-related constructs were moderately negatively correlated with distress (r = -0.31) and moderately positively correlated with general quality of life (r = 0.32). Small associations between empowerment-related constructs and both mental (r = 0.23) and physical quality of life (r = 0.13) were also reported. Discussion: This evidence is mostly from cross-sectional studies. High-quality prospective studies are needed not only to better understand the role of patient empowerment but to assess causal associations. The results of the study highlight the importance of patient empowerment and other empowerment-related constructs such as self-efficacy or perceived control in diabetes care. Thus, they should be considered in the design, development and implementation of effective interventions and policies aimed at improving psychosocial outcomes in patients with type 2 diabetes. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020192429, identifier CRD42020192429.

Ultrasonography-guided Intervention in the Achilles Tendon and Plantar Fascia.

Tendinopathy is very common in the foot and ankle. Achilles tendinopathy is a painful overuse injury that often occurs in athletes, especially those who participate in running and jumping sports. Plantar fasciitis is the most frequent cause of plantar pain in the adult heel. Initial treatment of these conditions is conservative. However, in some cases symptoms only improve slowly, and many cases are intractable. When conservative management fails, ultrasonography guided injections are indicated. We discuss the main interventions performed in the foot and ankle for Achilles tendinopathy, retrocalcaneal bursitis, and plantar fasciitis. We describe the different agents that can be used and the various ultrasonography-guided procedures that offer technical and practical information to improve daily clinical practice.