Exercise variables and pain threshold reporting for strength training protocols in people with haemophilia: a systematic review of clinical trials

Introduction: Although strength exercise is often prescribed for people with haemophilia (PWH), it remains unknown how exercise variables and pain thresholds are used to prescribe strength training in PWH. Aim: To analyse how strength exercise variables and pain thresholds have been used to prescribe strength training in PWH. Methods: A systematic search was conducted in PubMed, Embase, Web of Science, CENTRAL and CINAHL databases from inception to 7 September 2022. Studies whose intervention included strengthening training in adults with haemophilia were included. Two independent reviewers were involved in study selection, data extraction and risk of bias assessment. Results: Eighteen studies were included. The least reported variables among the studies were: prophylactic factor coverage (11.1%), pain threshold/tolerability (5.6%), intensity (50%), total or partial range of motion (27.8%), time under tension (27.8%), attentional focus modality (0%), therapist experience in haemophilia (33.3%) and adherence assessment (50%). In contrast, weekly frequency (94.4%), duration (weeks) (100%), number of sets/repetitions (88.9%), repetitions to failure/not to failure (77.8%), types of contraction (77.8%), rest duration (55.6%), progression (55.6%), supervision (77.8%), exercise equipment (72.2%) and adverse event record (77.8%) had a higher percentage of reported (>50% of studies). Conclusion: Future research on strength training for PWH should improve information on pain threshold and other important variables such as prophylactic factor coverage, intensity, range of motion, time under tension, attentional focus modality, therapist experience in haemophilia and adherence assessment. This could improve clinical practice and comparison of different protocols

The impact of Charlson comorbidity index on the functional capacity of COVID-19 survivors: a prospective cohort study with one-year follow-up

Objective: To determine the association between the Charlson comorbidity index (CCI) score after discharge with 6-min walk test (6MWT) 1 year after discharge in a cohort of COVID-19 survivors. Methods: In this prospective study, data were collected from a consecutive sample of patients hospitalized for COVID-19. The CCI score was calculated from the comorbidity data. The main outcome was the distance walked in the 6MWT at 1 year after discharge. Associations between CCI and meters covered in the 6MWT were assessed through crude and adjusted linear regressions. The model was adjusted for possible confounding factors (sex, days of hospitalization, and basal physical capacity through sit-to-stand test one month after discharge). Results: A total of 41 patients were included (mean age 58.8 +/- 12.7 years, 20/21 men/women). A significant association was observed between CCI and 6MWT (meters): (i) crude model: beta = -18.7, 95% CI = -34.7 to -2.6, p < 0.05; (ii) model adjusted for propensity score including sex, days of hospitalization, and sit-to-stand: beta = -23.0, 95% CI = -39.1 to -6.8, p < 0.05. Conclusions: A higher CCI score after discharge indicates worse performance on the 6MWT at 1-year follow-up in COVID-19 survivors. The CCI score could also be used as a screening tool to make important clinical decisions

Risk of cancer in family members of patients with lynch-like syndrome

Lynch syndrome (LS) is a common cause of hereditary colorectal cancer (CRC). Some CRC patients develop mismatch repair deficiency without germline pathogenic mutation, known as Lynch-like syndrome (LLS). We compared the risk of CRC in first-degree relatives (FDRs) in LLS and LS patients. LLS was diagnosed when tumors showed immunohistochemical loss of MSH2, MSH6, and PMS2; or loss of MLH1 with BRAF wild type; and/or no MLH1 methylation and absence of pathogenic mutation in these genes. CRC and other LS-related neoplasms were followed in patients diagnosed with LS and LLS and among their FDRs. Standardized incidence ratios (SIRs) were calculated for CRC and other neoplasms associated with LS among FDRs of LS and LLS patients. In total, 205 LS (1205 FDRs) and 131 LLS families (698 FDRs) had complete pedigrees. FDRs of patients with LLS had a high incidence of CRC (SIR, 2.08; 95% confidence interval (CI), 1.56-2.71), which was significantly lower than that in FDRs of patients with LS (SIR, 4.25; 95% CI, 3.67-4.90; p < 0.001). The risk of developing other neoplasms associated with LS also increased among FDR of LLS patients (SIR, 2.04; 95% CI, 1.44-2.80) but was lower than that among FDR of patients with LS (SIR, 5.01, 95% CI, 4.26-5.84; p < 0.001). FDRs with LLS have an increased risk of developing CRC as well as LS-related neoplasms, although this risk is lower than that of families with LS. Thus, their management should take into account this increased risk

Translocated LPS Might Cause Endotoxin Tolerance in Circulating Monocytes of Cystic Fibrosis Patients

Cystic Fibrosis (CF) is an inherited pleiotropic disease that results from abnormalities in the gene codes of a chloride channel. The lungs of CF patients are chronically infected by several pathogens but bacteraemia have rarely been reported in this pathology. Besides that, circulating monocytes in CF patients exhibit a patent Endotoxin Tolerance (ET) state since they show a significant reduction of the inflammatory response to bacterial stimulus. Despite a previous description of this phenomenon, the direct cause of ET in CF patients remains unknown. In this study we have researched the possible role of microbial/endotoxin translocation from a localized infection to the bloodstream as a potential cause of ET induction in CF patients. Plasma analysis of fourteen CF patients revealed high levels of LPS compared to healthy volunteers and patients who suffer from Chronic Obstructive Pulmonary Disease. Experiments in vitro showed that endotoxin concentrations found in plasma of CF patients were enough to induce an ET phenotype in monocytes from healthy controls. In agreement with clinical data, we failed to detect bacterial DNA in CF plasma. Our results suggest that soluble endotoxin present in bloodstream of CF patients causes endotoxin tolerance in their circulating monocytes

Transketolase-Like 1 Expression Is Modulated during Colorectal Cancer Progression and Metastasis Formation

Background Transketolase-like 1 (TKTL1) induces glucose degradation through anaerobic pathways, even in presence of oxygen, favoring the malignant aerobic glycolytic phenotype characteristic of tumor cells. As TKTL1 appears to be a valid biomarker for cancer prognosis, the aim of the current study was to correlate its expression with tumor stage, probability of tumor recurrence and survival, in a series of colorectal cancer patients. Methodolody/Principal Findings Tumor tissues from 63 patients diagnosed with colorectal cancer at different stages of progression were analyzed for TKTL1 by immunohistochemistry. Staining was quantified by computational image analysis, and correlations between enzyme expression, local growth, lymph-node involvement and metastasis were assessed. The highest values for TKTL1 expression were detected in the group of stage III tumors, which showed significant differences from the other groups (Kruskal-Wallis test, P = 0.000008). Deeper analyses of T, N and M classifications revealed a weak correlation between local tumor growth and enzyme expression (Mann-Whitney test, P = 0.029), a significant association of the enzyme expression with lymph-node involvement (Mann-Whitney test, P = 0.0014) and a significant decrease in TKTL1 expression associated with metastasis (Mann-Whitney test, P = 0.0004). Conclusions/Significance To our knowledge, few studies have explored the association between variations in TKTL1 expression in the primary tumor and metastasis formation. Here we report downregulation of enzyme expression when metastasis appears, and a correlation between enzyme expression and regional lymph-node involvement in colon cancer. This finding may improve our understanding of metastasis and lead to new and more efficient therapies against cancer

Mamitis clínica en el vacuno lechero español: incidencia y costes

Clinical mastitis in Spanish dairy herds has been studied. Since April 2005 up to December 2006, in 25 Spanish herds 1,054 cases registered were available. Aims were to determine mastitis incidence and factors of risk, to analyze whether yield production has been affected, and to quantify mastitis costs along 2006. The 25% lactations were infected at least once with average recurrence of 1.64. Descriptive analysis showed that 29% of cases occurred within the first month after calving. Primiparous showed higher mastitis frequency at early and late lactation while in multiparous cases number was progressively decreasing since the first month. Multiparous were statistically more liable to mastitis than primiparous. Mastitis did not show effect on yield production. Mastitis costs included treatment products and discarded milk. Individual daily production at each case onset was estimated by using monthly official milking records. An average mastitis case cost was 73.93 Euros, cheaper in primiparous than in multiparous because of lower milk production. Average discarded milk represented 74% of total cost per case. Mastitis costs were 117 Euros per infected cow and lactation. Then, annual economic losses due to mastitis were 3,190 Euros per average herd, showing the concern of producers on selecting resistant animals as well as the importance of the implementation of systematic recording for clinical mastitis in Spanish dairy farms.Se ha estudiado la mamitis clínica en 25 explotaciones utilizando 1.054 casos registrados desde abril de 2005 a diciembre de 2006. Los objetivos del trabajo fueron determinar la incidencia, analizar si la producción se vio afectada y calcular los costes generados en el año 2006. El 25% de las lactaciones presentaron algún episodio de mamitis, siendo la recurrencia media de 1,64. El 29% de los primeros casos se diagnosticaron en el primer mes tras el parto. Las primíparas fueron más susceptibles al principio y al final de la lactación, mientras que las multíparas presentaron menos casos según avanzaba la lactación. Sólo resultaron estadísticamente significativos el rebaño y el número de lactación, siendo las vacas con más de un parto más propensas a la mamitis. La producción de leche no se vio afectada. Los costes de mamitis incluyeron los correspondientes a medicamentos y a la leche retirada no comercializada. La producción individual diaria en el momento de la infección fue estimada utilizando el control lechero mensual oficial. El coste medio de mamitis fue de 73,93 Euros, siendo más caro en las multíparas debido a una mayor producción. El coste medio por media de leche retirada representó el 74% del coste por caso. El coste por vaca infectada fue de 117 Euros por lactación, lo que supone unas pérdidas económicas anuales por rebaño medio de 3.190 Euros, justificando la preocupación de los productores por seleccionar animales resistentes y la necesidad de sistematizar la recogida de mamitis clínicas en las explotaciones lechera españolas