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What is new in flexor tendon pulleys and the gaps between them in triphalangeal fingers of the hand?
No full text20.500.12530/87858The flexor tendon pulleys in the fingers of the hand are fibrous structures of variable size, shape, and thickness that cover the synovial sheath of these tendons. Despite their clinical relevance, their arrangement and configuration in each of the triphalangeal fingers have been little studied and with small sample sizes. 192 triphalangeal fingers belonging to 48 fresh body donors' hands were dissected. Multivariate analysis was carried out. Twenty-five cases (52%) were left hands, and 26 of the 48 hands belonged to female donors (54.2%). The results were analyzed by fingers for each of the 5 annular pulleys, the 3 cruciform pulleys and the gaps between them. In addition, the most and least frequent configurations of the pulleys in each of the fingers were studied, observing that the classic pattern with all the pulleys appeared only in 3 fingers (1.56%), while the most frequent pattern was A1-A2-C1-A3-A4, which was seen in 35 fingers (18.22%). CONCLUSIONS: The flexor pulleys in the triphalangeal fingers of the hand have shown enormous variability in arrangement and shape, and also rarely appear all in the same finger. This peculiar anatomical arrangement can help the different professionals who perform their clinical work in this region
Tetanus-diphtheria vaccine can prime SARS-CoV-2 cross-reactive T cells.
No full textVaccines containing tetanus-diphtheria antigens have been postulated to induce cross-reactive immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which could protect against coronavirus disease (COVID-19). In this work, we investigated the capacity of Tetanus-diphtheria (Td) vaccine to prime existing T cell immunity to SARS-CoV-2. To that end, we first collected known SARS-CoV-2 specific CD8+ T cell epitopes targeted during the course of SARS-CoV-2 infection in humans and identified as potentially cross-reactive with Td vaccine those sharing similarity with tetanus-diphtheria vaccine antigens, as judged by Levenshtein edit distances (≤ 20% edits per epitope sequence). As a result, we selected 25 potentially cross-reactive SARS-CoV-2 specific CD8+ T cell epitopes with high population coverage that were assembled into a synthetic peptide pool (TDX pool). Using peripheral blood mononuclear cells, we first determined by intracellular IFNγ staining assays existing CD8+ T cell recall responses to the TDX pool and to other peptide pools, including overlapping peptide pools covering SARS-CoV-2 Spike protein and Nucleocapsid phosphoprotein (NP). In the studied subjects, CD8+ T cell recall responses to Spike and TDX peptide pools were dominant and comparable, while recall responses to NP peptide pool were less frequent and weaker. Subsequently, we studied responses to the same peptides using antigen-inexperienced naive T cells primed/stimulated in vitro with Td vaccine. Priming stimulations were carried out by co-culturing naive T cells with autologous irradiated peripheral mononuclear cells in the presence of Td vaccine, IL-2, IL-7 and IL-15. Interestingly, naive CD8+ T cells stimulated/primed with Td vaccine responded strongly and specifically to the TDX pool, not to other SARS-CoV-2 peptide pools. Finally, we show that Td-immunization of C57BL/6J mice elicited T cells cross-reactive with the TDX pool. Collectively, our findings support that tetanus-diphtheria vaccines can prime SARS-CoV-2 cross-reactive T cells and likely contribute to shape the T cell responses to the virus
The cardiomyopathy of cystic fibrosis: a modern form of Keshan disease.
No full text20.500.12530/87912We conducted a study to determine the prevalence of structural heart disease in patients with CF, the characteristics of a cardiomyopathy not previously described in this population, and its possible relationship with nutritional deficiencies in CF. We studied 3 CMP CF patients referred for heart-lung transplantation and a prospective series of 120 adult CF patients. All patients underwent a clinical examination, blood tests including levels of vitamins and trace elements, and echocardiography with evaluation of myocardial strain. Cardiac magnetic resonance imaging (CMR) was performed in patients with CMP and in a control group. Histopathological study was performed on hearts obtained in transplant or necropsy. We found a prevalence of 10% (CI 4.6%-15.4%) of left ventricular (LV) dysfunction in the prospective cohort. Myocardial strain parameters were already altered in CF patients with otherwise normal hearts. Histopathological examination of 4 hearts from CF CMP patients showed a unique histological pattern of multifocal myocardial fibrosis similar to Keshan disease. Four of the five CF CMP patients undergoing CMR showed late gadolinium uptake, with a characteristic patchy pattern in 3 cases (p 10% of adults with CF showed significant cardiac involvement, with histological and imaging features resembling Keshan disease. Selenium deficiency was associated with the presence and severity of LV dysfunction in these patients
Long-term multidisciplinary follow-up programs in pediatric cardiac arrest survivors.
No full text20.500.12530/87858Long-term outcome studies after pediatric cardiac arrest (CA) are few. They require a CA registry and dedicated outcome teams. Learning about the long-term outcomes is very important for developing prognostication guidelines, improving post-cardiac care, counseling caregivers about the future of their child, and creating opportunities for therapeutic intervention studies to improve outcomes. Few PICUs worldwide provide a multidisciplinary follow-up program as routine practice at an outpatient clinic with standardized measurements, using validated instruments including neuropsychological assessments by psychologists. The primary goal of such a follow-up program should be to provide excellent care to children and their caregivers, thereby resulting in a high attendance. Pediatric psychologists, neurologists and pediatricians/pediatric intensivists should ideally be involved to screen for delayed development and psychosocial problems and offer appropriate care at the same time. Preferably, outcomes should consist of evaluation of morbidity (physical and neuropsychological), functional health and Health Related Quality Of Life (QoL) of the patient and their caregivers
Impact of COVID-19 infection on genitourinary cancer management. SOGUG-COVID-19: A spanish, multicenter, observational study.
No full text20.500.12530/87854The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain. SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals. Data were collected from patients' medical records in a short period of time, coinciding with the first waves of COVID-19, when the mortality was also higher in the general population. From November 2020 to April 2021, 408 patients were enrolled in the study. The median age was 70 years, and 357 patients (87.5%) were male. Most frequent Cancer Origin was: prostate (40.7%), urothelial (31.4%) and kidney (22.1%). Most patients (71.3%) were diagnosed at the metastatic stage, and 33.3% had poorly differentiated histology. Anticancer treatment during the infection was reported in 58.3% of patients, and 21.3% had received immunotherapy prior to or concurrent with the infection. The most frequent COVID-19 symptoms were pyrexia (49.0%), cough (38.2%) and dyspnea (31.9%). Median age was higher for patients with pneumonia (p Patients with genitourinary cancers seem exceptionally vulnerable to COVID-19 regardless of tumor type or anticancer therapy. Age and tumor stage were the only identified risk factors for severe COVID-19
A complex of cadherin 17 with desmocollin 1 and p120-catenin regulates colorectal cancer migration and invasion according to the cell phenotype.
No full textCadherin-17 (CDH17), a marker of differentiation in intestinal cells, binds and activates α2β1 integrin to promote cell adhesion and proliferation in colorectal cancer (CRC) metastasis. Furthermore, CDH17 associates with p120- and β-catenin in a manner yet to be fully elucidated. In this report, we explored the molecular mediators involved in this association, their contribution to CRC dissemination and potential therapeutic implications. Proteomic and confocal analyses were employed to identify and validate CDH17 interactors. Functional characterization involved the study of proliferation, migration, and invasion in cell lines representative of various phenotypes. Immunohistochemistry was conducted on CRC tissue microarrays (TMA). In vivo animal experiments were carried out for metastatic studies. We found that desmocollin-1 (DSC1), a desmosomal cadherin, interacts with CDH17 via its extracellular domain. DSC1 depletion led to increased or decreased invasion in CRC cells displaying epithelial or mesenchymal phenotype, respectively, in a process mediated by the association with p120-catenin. Down-regulation of DSC1 resulted in an increased expression of p120-catenin isoform 1 in epithelial cells or a shift in cellular location in mesenchymal cells. Opposite results were observed after forced expression of CDH17. DSC1 is highly expressed in budding cells at the leading edge of the tumor and associates with poor prognosis in the stem-like, mesenchymal CRC subtypes, while correlates with a more favorable prognosis in the less-aggressive subtypes. In vivo experiments demonstrated that DSC1 silencing reduced tumor growth, liver homing, and metastasis in CRC mesenchymal cells. Furthermore, a synthetic peptide derived from CDH17, containing the NLV motif, effectively inhibited invasion and liver homing in vivo, opening up new possibilities for the development of novel therapies focused on desmosomal cadherins. These findings shed light on the multifaceted roles of CDH17, DSC1, and p120-catenin in CRC metastasis, offering insights into potential therapeutic interventions for targeting desmosomal cadherins in poorly-differentiated carcinomas
Demographic Trends in Liver Transplant Survivors After 3 Decades of Program Implementation: The Impact of Cohort and Period Effects on Life Expectancy.
No full text20.500.12530/87858Demographic analyses may reveal current patterns of change in the outcomes of rapidly developing medical procedures because they incorporate the period perspective. We analyzed the changes in size, age structure, and hospitalizations in the population of liver transplantation (LT) survivors in our center during the last 30 y (n = 1114 patients) and generated projections, including life expectancy (LE), considering cohort and period effects. Life tables were used to project the complete LE (overall 1990-2020 experience), the cohort LE (according to the decade of surgery: 1990-2000, 2000-2010, and 2010-2020), and the period LE (current 2015-2020 experience). The population of LT recipients in follow-up continued to experience progressive growth and aging since 1990 (492 patients [41.9% >65 y] in 2020), and the magnitude of these phenomena may double in the next 30 y. However, the number of admissions and days of admission has been decreasing. The complete LE at LT was 12.4 y, whereas the period LE was 15.8 y. The cohort LE (limited to 10 y) was 5.3, 6.3, and 7.3 y for the 1990-2000, 2000-2010, and 2010-2020 cohorts, respectively. The target population of our medical care after LT is growing and aging. The prevalence of both of these phenomena is expected to increase in the coming years and is associated with a current improvement in LE. However, the hospitalization burden associated with LT survivors is declining. The period effect should be considered for generating up-to-date information on these current trends, which are crucial when designing health policies for LT survivors
Genome-Wide Association Screens for Anterior Cruciate Ligament Tears.
No full text20.500.12530/87909The etiopathogenesis of ACL rupture is not clarified. The aim of this study is to identify genomic regions and genetic variants relevant to anterior cruciate ligament injury susceptibility that could be involved in non-contact anterior cruciate ligament ruptures. A systematic review of the literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines with a PRISMA checklist and algorithm. A search of PubMed, MEDLINE, CINAHL, Cochrane, EMBASE, and Google Scholar databases was conducted using combinations of the terms "anterior cruciate ligament", "ACL", "rupture", "genetics", "single nucleotide polymorphisms", and "SNP" since the inception of the databases until 2021. Twenty-three studies were included. A total of 7724 patients were analyzed. In total, 3477 patients had ACL ruptures and 4247 patients were controls. Genetic variants in genes encoding for collagens, elastin, fibrillin, matrix metalloproteinases, proteoglycans, angiogenesis-associated signaling cascade proteins, growth differentiation factors, tissue inhibitors of metalloproteases, interleukins, and fibrinogen were analyzed. Findings regarding the association between genes encoding for collagen (COL3A1, COL1A1, and COL12A1), aggrecan (ACAN), decorin (DCN), matrix metalloproteinase (MMP3), interleukin 6 (IL-6), vascular endothelial growth factor A (VEGFA), biglycan (BGN), fibrinogen (FGB), and ACL injuries were found to be inconclusive. Additional evidence is required in order to establish substantial conclusions regarding the association between genetic variants and ACL rupture
Patient-reported outcome measures for systemic lupus erythematosus: an expert Delphi consensus to guide implementation in routine care.
No full textSystemic lupus erythematosus (SLE) may result in great impact on patients' quality of life, social relationships, and work productivity. The use of patient-reported outcome measures (PROMs) in routine care could help capture disease burden to guide SLE management and optimize disease control. We aimed to explore the current situation, appropriateness, and feasibility of PROMs to monitor patients with SLE in routine care, from healthcare professionals' and patients' perspectives. A scientific committee developed a Delphi questionnaire, based on a focus group with patients and a literature review, including 22 statements concerning: 1) Use of PROMs in routine care (n = 2); 2) PROMs in SLE management (n = 13); 3) Multidisciplinary management of patients with SLE (n = 4), and 4) Aspects on patient empowerment (n = 3). Statements included in Sects. 2-4 were assessed from three perspectives: current use, appropriateness, and feasibility (with currently available resources). For each statement, panellists specified their level of agreement using a 7-point Likert scale. A consensus was reached when ≥ 70% of the panellists agreed (6,7) or disagreed (1,2) on each statement. Fifty-nine healthcare professionals and 16 patients with SLE participated in the Delphi-rounds. A consensus was reached on the value of PROMs to improve SLE management (83%) and the key role of healthcare professionals (77%) and the need for a digital tool connected to the electronic medical record (85%) to promote and facilitate PROMs collection. PROMs most frequently used in clinical practice are pain (56%), patient's global assessment (44%) and fatigue (39%), all on visual analogue scales. Panellists agreed on the need to implement multidisciplinary consultation (79%), unify complementary tests (88%), incorporate pharmacists into the healthcare team (70%), and develop home medication dispensing and informed telepharmacy programmes (72%) to improve quality of care in patients with SLE. According to panellists, patient associations (82%) and nurses (80%) are critical to educate and train patients on PROMs to enhance patient empowerment. Although pain, fatigue, and global assessment were identified as the most feasible, PROMs are not widely used in routine care in Spain. The present Delphi consensus can provide a road map for their implementation being key for SLE management
Cardiovascular and Cerebrovascular Morbidity in Patients with Urolithiasis: An Epidemiological Approach Based on Hospitalization Burden Data from 1997 to 2021.
No full text20.500.12530/87908Background: Patients with kidney stones (KSFs) are known to have a heightened risk of coronary heart disease (CHD) or stroke. The objective of the present study was to describe the natural history of these complications through the longitudinal analysis of the hospitalizations due to kidney stones in Spain from 1997 to 2021. Methods: A retrospective longitudinal observational study was developed based on nationwide hospitalization data (minimum basic data base). Three different analyses were carried out. In the first step, the prevalence of coronary or cerebrovascular events in kidney stone hospitalizations was compared with the hospitalization burden of CHD or strokes related to the general population. In the second step, a survival analysis of the kidney stones-hospitalized patients using the Kaplan-Meier method was conducted. In the third step, a Cox regression was used to assess the influence of the classical comorbidities in the development of the lithiasic patients-cardiovascular disease. Results: Kidney stone-hospitalized patients exhibit a significantly higher risk of CHD (OR = 14.8 CI95%: 14.7-14.9) and stroke (OR = 6.7 CI95%: 6.6-6.8) compared to the general population across in all age groups, although they had less cardiovascular risk factors. A total of 9352 KSFs (1.5%) developed a coronary event within an average time of 78.8 months. A total of 2120 KSFs (0.33%) suffered a stroke in an average time of 71.1 months. Diabetes, hypertension, hyperlipidemia, and being overweight were identified as risk factors for developing CHD and stroke using a univariate and multivariate analysis. Conclusions: Our study confirms previous studies in which kidney stones must be considered as a risk factor for developing CHD or cerebrovascular disease. Preventive strategies should target patients with kidney stones and classical risk cardiovascular factors to mitigate modifiable conditions associated with cardiovascular diseases