To examine the safety and effectiveness of extracorporeal shockwave therapy (ESWT) for reducing pain and improving functionality in people with knee osteoarthritis (KOA).
The Cochrane Library, ...PubMed, CINAHL, Physiotherapy Evidence Database (PEDro) and Google Scholar were systematically searched for randomized trials published up to September 30th of 2019. The main outcome measures to evaluate the treatment effect were pain, as reported on a visual analogue scale (VAS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the range of motion (ROM) and walking tests. A quantitative analysis was conducted using the inverse variance method and the random effects model.
Fourteen studies were included (n = 782 participants and 877 knees). Moderate quality of evidence showed that ESWT causes a decrease on the pain VAS mean difference (MD) = 1.7 cm; confidence interval (CI) 95%: 1.1–2.3 and WOMAC (MD = 13.9 points; CI 95%: 6.9–20.8). The effect of ESWT using medium energetic density was greater than with low or high density in the WOMAC (Chi2 = 9.8, p = 0.002) and bordered statistical significance on the VAS (Chi2 = 3.8, p = 0.05). Very low quality of evidence showed that ESWT causes moderate improvement in the knee ROM (MD = 17.5°; CI 95%: 9.4–25.5) and walking test standardized mean difference (SMD) = 0.58; CI 95%: 0.35–0.81.
ESWT is an effective treatment for improving pain and functionality in patients with KOA in the short term with few minor side effects. Further clinical trials should include longer follow-up periods and be designed to lower the risk of bias.
•Extracorporeal shock wave therapy is a non-invasive and safe therapy for the treatment of knee osteoarthritis.•Extracorporeal shock wave therapy decreases pain and improves function in patients with knee osteoarthritis.•Doses of medium energetic density obtained better results than low or high density in WOMAC and VAS scales.
ABSTRACT
Background
There is scarce evidence on the fourth dose of severe acute respiratory syndrome coronavirus 2 vaccines in chronic kidney disease (CKD) patients. We evaluated the humoral response ...and effectivity of the fourth dose in the CKD spectrum: non-dialysis CKD (ND-CKD), haemodialysis (HD), peritoneal dialysis (PD) and kidney transplant (KT) recipients.
Methods
This is a prespecified analysis of the prospective, observational, multicentric SENCOVAC study. In patients with CKD who had received a complete initial vaccination and one or two boosters and had anti-Spike antibody determinations 6 and 12 months after the initial vaccination, we analysed factors associated with persistent negative humoral response and higher anti-Spike antibody titres as well as the efficacy of vaccination on coronavirus disease 2019 (COVID-19) severity.
Results
Of 2186 patients (18% KT, 8% PD, 69% HD and 5% ND-CKD), 30% had received a fourth dose. The fourth dose increased anti-Spike antibody titres in HD (P = .001) and ND-CKD (P = .014) patients and seroconverted 72% of previously negative patients. Higher anti-Spike antibody titres at 12 months were independently associated with repeated exposure to antigen (fourth dose, previous breakthrough infections), previous anti-Spike antibody titres and not being a KT recipient. Breakthrough COVID-19 was registered in 137 (6%) patients, 5% of whom required admission. Admitted patients had prior titres <620 UI/ml and median values were lower (P = .020) than in non-admitted patients.
Conclusions
A fourth vaccine dose increased anti-Spike antibody titres or seroconverted many CKD patients, but those with the highest need for a vaccine booster (i.e. those with lower pre-booster antibody titres or KT recipients) derived the least benefit in terms of antibody titres. Admission for breakthrough COVID-19 was associated with low anti-Spike antibody titres.
Graphical Abstract
Graphical Abstract
Background & Aims:
We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin.
...Methods:
Patients (n = 159; 94 men; age, 41.7 ± 11.1 years) with chronic hepatitis C (genotype 1, n = 113; non-1 genotype, n = 46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated.
Results:
A sustained virological response was associated with lower age, insulin resistance index, body mass index, and γ-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (
P = .0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49–8.3;
P = .001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08–3.06;
P = .012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01–1.84;
P = .029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%–43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%–75.1%) genotype 1 patients without insulin resistance (
P = .007; odds ratio, 3.12, 95% confidence interval, 1.42–6.89).
Conclusions:
Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.
There is a paucity of knowledge on the long-term outcome in patients diagnosed with COVID-19. We describe a cohort of patients with a constellation of symptoms occurring four weeks after diagnosis ...causing different degrees of reduced functional capacity. Although different hypothesis have been proposed to explain this condition like persistent immune activation or immunological dysfunction, to date, no physiopathological mechanism has been identified. Consequently, there are no therapeutic options besides symptomatic treatment and rehabilitation.
We evaluated patients with symptoms that persisted for at least 4 weeks after COVID-19. Epidemiological and clinical data were collected. Blood tests, including inflammatory markers, were conducted, and imaging studies made if deemed necessary. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcription polymerase chain reaction (RT-PCR) in plasma, stool, and urine were performed. Patients were offered antiviral treatment (compassionate use).
We evaluated 29 patients who reported fatigue, muscle pain, dyspnea, inappropriate tachycardia, and low-grade fever. Median number of days from COVID-19 to positive RT-PCR in extra-respiratory samples was 55 (39-67). Previous COVID-19 was mild in 55% of the cases. Thirteen patients (45%) had positive plasma RT-PCR results and 51% were positive in at least one RT-PCR sample (plasma, urine, or stool). Functional status was severely reduced in 48% of the subjects. Eighteen patients (62%) received antiviral treatment. Improvement was seen in most patients (p = 0.000) and patients in the treatment group achieved better outcomes with significant differences (p = 0.01).
In a cohort of COVID-19 patients with persistent symptoms, 45% of them have detectable plasma SARS-CoV-2 RNA. Our results indicate possible systemic viral persistence in these patients, who may benefit of antiviral treatment strategies.
The purpose of this study was to detect coronavirus disease 2019 (COVID-19) cases with persistent positive reverse transcription-PCR (RT-PCR) results for severe acute respiratory syndrome coronavirus ...2 (SARS-CoV-2), for which viable virus can be inferred due to the presence of subgenomic (SG) viral RNA, which is expressed only in replicating viruses. RNA remnants purified from diagnostic nasopharyngeal specimens were used as the templates for RT-PCR-specific detection of SG E gene RNA. As controls, we also detected viral genomic RNA for the E gene and/or a human housekeeping gene (RNase P). We assessed the samples of 60 RT-PCR-positive cases with prolonged viral SARS-CoV-2 shedding (24 to 101 days) since the first diagnostic RT-PCR. SG viral RNA was detected in 12/60 (20%) of the persistent cases, 28 to 79 days after the onset of symptoms. The age range of the cases with prolonged viral shedding and the presence of SG RNA was quite wide (40 to 100 years), and the cases were equally distributed between males (42%) and females (58%). No case was HIV positive, although seven were immunosuppressed. According to the severities of the COVID-19 episodes, they were mild (40%), intermediate (20%), and severe (40%). In a percentage of persistent SARS-CoV-2 PCR-positive cases, the presence of actively replicating virus may be inferred, far beyond diagnosis. We should not assume a universal lack of infectiousness for COVID-19 cases with prolonged viral shedding.
Summary
Anti‐cluster of differentiation 20 (CD20) monoclonal antibodies (mAbs) have shown promise in follicular lymphoma (FL) as post‐induction therapy, by enhancing antibody‐dependent cellular ...cytotoxicity (ADCC). However, cytotoxic cells are reduced after this treatment. We hypothesised that ex vivo expanded lymphokine‐activated killer (LAK) cells administered to FL‐remission patients are safe and improve anti‐CD20 efficacy. This open, prospective, phase II, single‐arm study assessed safety and efficacy of ex vivo expanded LAK cells in 20 FL‐remission patients following rituximab maintenance. Mononuclear cells were obtained in odd rituximab cycles and stimulated with interleukin 2 (IL‐2) for 8 weeks, after which >5 × 108 LAK cells were injected. Patients were followed‐up for 5 years. At the end of maintenance, peripheral blood cells phenotype had not changed markedly. Natural killer, LAK and ADCC activities of mononuclear cells increased significantly after recombinant human IL‐2 (rhIL‐2) stimulation in all cycles. Rituximab significantly enhanced cytotoxic activity. No patients discontinued treatment. There were no treatment‐related serious adverse events. Three patients had progressed by the end of follow‐up. After a median (interquartile range) follow‐up of 59.4 (43.8–70.9) months, 85% of patients remained progression free. No deaths occurred. Quality‐of‐life improved throughout the study. Post‐induction LAK cells with rituximab seem safe in the long term. Larger studies are warranted to confirm efficacy.
The principal role of wine yeast is to transform efficiently the grape-berries’ sugars to ethanol, carbon dioxide, and other metabolites, without the production of off-flavors. Wine yeast strains are ...able to ferment musts, while other commercial or laboratory strains fail to do so. The genetic differences that characterize wine yeast strains in contrast to the biological ageing of the veil-forming yeasts in Sherry wines are poorly understood. Saccharomyces cerevisiae strains frequently exhibit rather specific phenotypic features needed for adaptation to a special environment, like fortified wines with ethanol up to 15% (v/v), known as Sherry wines. Factors that affect the correct development of the veil of flor during ageing are also reviewed, along with the related aspects of wine composition, biofilm formation processes, and yeast autolysis. This review highlights the importance of yeast ecology and yeast metabolic reactions in determining Sherry wine quality and the wealth of untapped indigenous microorganisms co-existing with the veil-forming yeast strains. It covers the complexity of the veil forming wine yeasts’ genetic features, and the genetic techniques often used in strain selection and monitoring during fermentation or biological ageing. Finally, the outlook for new insights to protect and to maintain the microbiota of the Sherry wines will be discussed.
Since the COVID-19 outbreak, specific mRNA-based anti-SARS-CoV-2 vaccines have been developed and distributed worldwide. Because this is the first time that mRNA vaccines have been used, there are ...several questions regarding their capacity to confer immunity and the durability of the specific anti-SARS-CoV-2 response. Therefore, the objective of this study was to recruit a large cohort of healthcare workers from the Gregorio Marañón Hospital vaccinated with the mRNA-1273 or BNT126b2 vaccines and to follow-up on IgG anti-RBD levels at 8 months post-vaccination.
We recruited 4,970 volunteers and measured IgG anti-RBD antibodies on days 30 and 240 post-vaccination.
We observed that both vaccines induced high levels of antibodies on day 30, while a drastic wane was observed on day 240, where mRNA-1273 vaccinated induced higher levels than BNT162b2. Stratifying by vaccine type, age, gender, and comorbidities, we identified that older mRNA-1273-vaccinated volunteers had higher antibody levels than the younger volunteers, contrary to what was observed in the BNT162b2-vaccinated volunteers.
In conclusion, we observed that mRNA-1273 has a higher capacity to induce a humoral response than BNT162b2 and that age is a factor in the specific response.
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