Objective:
Aim of this trial was to compare efficacy of activated platelet-rich plasma against hyaluronic acid as intra-articular injections to people with osteoarthritis of the knee.
Design:
Phase-2 ...randomized controlled trial, with blind patients and outcome assessors.
Setting:
Outpatient rehabilitation service; years 2011–2013.
Subjects:
Patients with knee osteoarthritis grades 2–3 at magnetic resonance imaging (MRI) were included after consent and randomized. Target sample size was 25 patients per group.
Interventions:
Patients received three activated platelet-rich plasma (intervention group) or hyaluronic acid (controls) intra-articular injections at 4-week intervals.
Main measures:
Main outcome measure was proportion of patients with >1 grade improvement at six months from last injection, as assessed by a radiologist blind to study group. Patients were evaluated over time clinically and with functional scales (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Lysholm, Tegner, American Knee Society Score (AKSS), Lequesne, visual analogue scale (VAS) for pain).
Results:
Overall, 30 patients were randomized to intervention and 28 to control group. For primary outcome, 28 patients (29 knees) in the intervention and 22 (25 knees) in the control group were available. Patients with at least 1 grade improvement at repeat MRI were 14 (48.3%) in the intervention and 2 (8%) in the control group (P < 0.003). Improvement in symptoms and functional scales was consistently higher in the intervention group. No side-effects were observed in either group.
Conclusion:
Activated platelet-rich plasma reduces articular damage as evident at MRI, as soon as six months after treatment; it reduces pain and improves patient’s function and overall quality of life.
Patients with inherited thrombocytopenias often require platelet transfusions to raise their platelet count before surgery or other invasive procedures; moreover, subjects with clinically significant ...spontaneous bleeding may benefit from an enduring improvement of thrombocytopenia. The hypothesis that thrombopoietin-mimetics can increase platelet count in inherited thrombocytopenias is appealing, but evidence is scarce. We conducted a prospective, phase II clinical trial to investigate the efficacy of the oral thrombopoietin-mimetic eltrombopag in different forms of inherited thrombocytopenia. We enrolled 24 patients affected by
-related disease,
-related thrombocytopenia, X-linked thrombocytopenia/ Wiskott-Aldrich syndrome, monoallelic Bernard-Soulier syndrome, or
-related thrombocytopenia. The average pre-treatment platelet count was 40.4 ×10
/L. Patients received a 3- to 6-week course of eltrombopag in a dose-escalated manner. Of 23 patients evaluable for response, 11 (47.8%) achieved a major response (platelet count >100 ×10
/L), ten (43.5%) had a minor response (platelet count at least twice the baseline value), and two patients (8.7%) did not respond. The average increase of platelet count compared to baseline was 64.5 ×10
/L (
<0.001). Four patients with clinically significant spontaneous bleeding entered a program of long-term eltrombopag administration (16 additional weeks): all of them obtained remission of mucosal hemorrhages, with the remission persisting throughout the treatment period. Treatment was globally well tolerated: five patients reported mild adverse events and one patient a moderate adverse event. In conclusion, eltrombopag was safe and effective in increasing platelet count and reducing bleeding symptoms in different forms of inherited thrombocytopenia. Despite these encouraging results, caution is recommended when using thrombopoietinmimetics in inherited thrombocytopenias predisposing to leukemia. ClinicalTrials.gov identifier: NCT02422394.
Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients ...are not conclusive.
The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity.
In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 h since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (<30 - ≥20 ng/mL), moderately deficient (<20 - ≥10 ng/mL), severely deficient (<10 ng/mL).
The prevalence of 25(OH)vitamin D insufficiency, moderate deficiency and severe deficiency was 13.2%, 22.5% and 54.3%, respectively.
25(OH)Vitamin D deficiency (<20 ng/mL) was not associated with COVID-19 clinical features and outcomes. Unexpectedly, after adjusting for major confounders, a significant positive association between increasing 25(OH)vitamin D levels and in-hospital mortality (on a continuous logarithmic scale, odds ratio = 1.73 95% CI, 1.11 to 2.69; P = .016) was observed.
Very low 25(OH)vitamin D levels were highly prevalent and suggestive of deficiency among our hospitalized severe COVID-19 patients, but low 25(OH)vitamin D levels were not associated with outcome variables. Whether 25(OH)vitamin D adequacy may influence clinical outcomes in COVID-19 and the unexpected correlation between higher 25(OH)vitamin D levels and mortality require further investigations by large intervention trials.
In spite of improvements of average benefit from adjuvant/neoadjuvant treatments, there are still individual patients with early breast cancer at high risk of relapse. We explored the association ...with outcome of robust gene cluster-based metagenes linked to proliferation, ER-related genes, and immune response to identify those high-risk patients.
A total of 3,847 publicly available gene-expression profiles were analyzed (untreated, N = 826; tamoxifen-treated, N = 685; chemotherapy-treated, N = 1,150). Genes poorly performing in formalin-fixed samples were removed. Outcomes of interest were pathologic-complete response (pCR) and distant metastasis-free survival (DMFS). In ER(+)HER2(-), the proliferation and ER-related metagenes were combined to define three risk groups. In HER2(+) and ER(-)HER2(-) risk groups were defined by tertiles of an immune-related metagene.
The high-proliferation/low-ER group of ER(+)HER2(-) breast cancer had significantly higher pCR rate OR, 5.01 (1.76-17.99), P = 0.005, but poorer outcome HR = 3.73 (1.63-8.51), P = 0.0018 than the low-proliferation/high-ER. A similar association with outcome applied to patients with residual disease (RD) after neoadjuvant chemotherapy (P = 0.01). In ER(-)HER2(-) and HER2(+) breast cancer, immune metagene in the high tertile was linked to higher pCR 33.7% vs. 11.6% in high and low tertile, respectively; OR, 3.87 (1.79-8.95); P = 0.0009. In ER(-)HER2(-), after adjuvant/neoadjuvant chemotherapy, 5-year DMFS was 85.4% for high-tertile immune metagene, and 43.9% for low tertile. The outcome association was similar in patients with RD (P = 0.0055). In HER2(+) breast cancer treated with chemotherapy the association with risk of relapse was not significant.
We developed metagene-based predictors able to define low and high risk of relapse after adjuvant/neoadjuvant therapy. High-risk patients so defined should be preferably considered for trials with investigational agents.
Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this ...setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period. This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed. Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
COVID-19 outbreak deeply impacted on mental health, with high rate of psychological distress in healthcare professionals, patients and general population. Current literature on trauma showed no ...increase in ICU admissions for deliberate self-inflicted injuries in the first weeks after the beginning of COVID-19.
We tested the hypothesis that self-inflicted injuries/harms of any method requiring ICU admission increased in the year following COVID-19 outbreak.
Retrospective cohort single-center study comparing admissions to ICU the year before and the year after the pandemic start. All patients admitted to polyvalent ICUs-Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy from February 21st, 2019 to February 21st, 2020 (pre-COVID) and from February 22nd, 2020 to February 22nd, 2021 (post-COVID) were enrolled.
We enrolled 1038 pre-COVID and 854 post-COVID patients. In post-COVID, the incidence of self-inflicted injuries was 32/854 (3.8% 2.5-5.1), higher than in pre-COVID (23/1038, 2.2%-p = 0.0014-relative increase 72.7%). The increase was more relevant when excluding COVID-19 patients (suicide attempts 32/697 (4.6% 3.0-6.2)-relative increase 109.1%; p < 0.0001). Both in pre-COVID and post-COVID, the most frequent harm mean was poisoning 15 (65.2%) vs. 25 (78.1%), p = 0.182 and the analysed population was younger than general ICU population (p = 0.0015 and < 0.0001, respectively). The distribution of admissions for self-inflicted injuries was homogeneous in pre-COVID along the year. In post-COVID, no admissions were registered during the lockdown; an increase was observed in summer with pandemic curve at minimal levels.
An increase in ICU admissions for self-inflicted injuries/harms was observed in the year following COVID-19 outbreak.
Microarray technology applied to microRNA (miRNA) profiling is a promising tool in many research fields; nevertheless, independent studies characterizing the same pathology have often reported poorly ...overlapping results. miRNA analysis methods have only recently been systematically compared but only in few cases using clinical samples.
We investigated the inter-platform reproducibility of four miRNA microarray platforms (Agilent, Exiqon, Illumina, and Miltenyi), comparing nine paired tumor/normal colon tissues. The most concordant and selected discordant miRNAs were further studied by quantitative RT-PCR. Globally, a poor overlap among differentially expressed miRNAs identified by each platform was found. Nevertheless, for eight miRNAs high agreement in differential expression among the four platforms and comparability to qRT-PCR was observed. Furthermore, most of the miRNA sets identified by each platform are coherently enriched in data from the other platforms and the great majority of colon cancer associated miRNA sets derived from the literature were validated in our data, independently from the platform. Computational integration of miRNA and gene expression profiles suggested that anti-correlated predicted target genes of differentially expressed miRNAs are commonly enriched in cancer-related pathways and in genes involved in glycolysis and nutrient transport.
Technical and analytical challenges in measuring miRNAs still remain and further research is required in order to increase consistency between different microarray-based methodologies. However, a better inter-platform agreement was found by looking at miRNA sets instead of single miRNAs and through a miRNAs - gene expression integration approach.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hyperimmune plasma from Covid-19 convalescent is a potential treatment for severe Covid-19. We conducted a multicenter one arm proof of concept interventional study. Patients with Covid-19 disease ...with moderate-to-severe Acute Respiratory Distress Syndrome, elevated C-reactive Protein and need for mechanical ventilation and/or CPAP were enrolled. One to three 250-300 ml unit of hyperimmune plasma (neutralizing antibodies titer ≥1:160) were administered. Primary outcome was 7-days hospital mortality. Secondary outcomes were PaO2/FiO2, laboratory and radiologic changes, as well as weaning from mechanical ventilation and safety. The study observed 46 patients from March, 25 to April, 21 2020. Patients were aged 63, 61% male, of them, 30 were on CPAP and 7 intubated. PaO2/FiO2 was 128 (SD 47). Bilateral infiltrates on chest X-ray was present in 36 patients (84%). Symptoms and ARDS duration were 14 (SD 7) and 6 days (SD 3). Three patients (6.5%) died within 7 days as compared to an expected 15% from the National Statistics and 30% from a small concurrent cohort of 23 patients. The upper one-sided 90%CI was 13.9%, allowing to reject the null hypothesis of a 15% mortality. PaO2/FiO2 increased by 112 units (95%CI 82 to142) in survivors, the chest radiogram severity decreased in 23% (95%CI 5% to 42%); CRP, Ferritin and LDH decreased by 60, 36 and 20% respectively. Weaning from CPAP was obtained in 26/30 patients and 3/7 were extubated. Five serious adverse events occurred in 4 patients (2 likely, 2 possible treatment related). In conclusion, Hyperimmune plasma in Covid-19 shows promising benefits, to be confirmed in a randomized controlled trial. This proof of concept study could open to future developments including hyperimmune plasma banking, development of standardized pharmaceutical products and monoclonal antibodies.
Background:
Nutritional support, including nutritional counseling and oral nutritional supplements (ONSs), has been recommended at the earliest opportunity in head and neck (H&N) cancer patients. The ...limited available evidence on the efficacy of immunonutrition during chemoradiotherapy (CT-RT) in H&N cancer patients is positive with regard to some secondary endpoints, but is still scanty, particularly with regard to toxicity and treatment tolerance. We hypothesize that early systematic provision of ONSs with a high-protein–high-calorie mixture containing immunonutrients (Impact) compared to standard high-calorie–high-protein nutritional blends, in addition to nutritional counseling, may be beneficial to patients with H&N cancer during CT-RT. Hence, we designed the present study to evaluate the efficacy, in terms of treatment tolerance, toxicity and response, body weight, body composition, protein-calorie intake, quality of life (QoL), fatigue, muscle strength and immunological profile of the early systematic provision of ONSs enriched in immunonutrients compared to isonitrogenous standard blends, in H&N cancer patients undergoing CT-RT.
Methods:
This is a pragmatic, bicentric, randomized (1:1), parallel-group, open label, controlled, pilot clinical trial.
Discussion:
Many efforts are still to be taken to improve the efficacy of nutritional support in oncology. Immunonutrition represents a promising approach also in H&N cancer patients, but the evidence on its efficacy in improving clinical outcomes during CT-RT is still inconclusive. The present pilot study, which guarantees the early provision of nutritional assessment and support to all the enrolled patients in accordance with the recent guidelines and recommendations, could represent one of the first proofs of the clinical effectiveness of early oral immunonutrition in cancer patients undergoing CT-RT and could stimulate further large randomized trials, potentially resulting in the improvement of supportive care quality.
Trial registration:
This study is registered on ClinicalTrials.gov Identifier: NCT04611113.
Genome-wide gene expression analyses of tumors are a powerful tool to identify gene signatures associated with biologically and clinically relevant characteristics and for several tumor types are ...under clinical validation by prospective trials. However, handling and processing of clinical specimens may significantly affect the molecular data obtained from their analysis. We studied the effects of tissue handling time on gene expression in human normal and tumor colon tissues undergoing routine surgical procedures.
RNA extracted from specimens of 15 patients at four time points (for a total of 180 samples) after surgery was analyzed for gene expression on high-density oligonucleotide microarrays. A mixed-effects model was used to identify probes with different expression means across the four different time points. The p-values of the model were adjusted with the Bonferroni method.
Thirty-two probe sets associated with tissue handling time in the tumor specimens, and thirty-one in the normal tissues, were identified. Most genes exhibited moderate changes in expression over the time points analyzed; however four of them were oncogenes, and two confirmed the effect of tissue handling by independent validation.
Our results suggest that a critical time point for tissue handling in colon seems to be 60 minutes at room temperature. Although the number of time-dependent genes we identified was low, the three genes that already showed changes at this time point in tumor samples were all oncogenes, hence recommending standardization of tissue-handling protocols and effort to reduce the time from specimen removal to snap freezing accounting for warm ischemia in this tumor type.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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