Abstract

BACKGROUND Striae gravidarum (SG) is a connective tissue disorder seen commonly in primigravidas. It is associated with impairment in the quality of life. OBJECTIVE To determine the efficacy of ablative fractional carbon dioxide (CO2) laser combined with autologous platelet-rich plasma (PRP) versus ablative fractional CO2 laser and placebo in the treatment of SG. STUDY DESIGN Randomized, double-blinded, placebo-controlled trial METHODOLOGY The study was conducted in 16 patients with SG. The assigned treatment area (abdomen) was divided into two sides and was randomly assigned to the PRP side and the control side. All patients received ablative fractional CO2 laser. Immediately after each laser procedure, the PRP side received autologous PRP, while the control side received plain normal saline solution (pNSS) as a placebo. The study was done for three sessions, at intervals of 4 weeks. An independent assessor used the photographs taken at weeks 6, 10, 14 and 16 to assess the clinical improvement. The patient satisfaction was reported at the same intervals. A quartile grading scale was used to measure both the clinical improvement and patient satisfaction. Data were analyzed using the Jonckheere-Terpstra test. Histopathology was done before treatment, and at the end of the study period. RESULTS The combination of ablative fractional CO2 laser and autologous PRP had better clinical improvement and patients' satisfaction compared to ablative fractional CO2 laser and placebo. However, both outcome measures were not statistically significant. CONCLUSION Ablative fractional CO2 laser combined with autologous PRP appears to be an effective treatment in SG.

Abstract

BACKGROUND AND OBJECTIVE Osteonecrosis of the femoral head (ONFH) is a devastating disease, and there is some evidence that extracorporeal shock wave therapy (ESWT) and intra-articular platelet-rich plasma (PRP) injection might alleviate pain and improve joint function in individuals with ONFH. The objective of this study was to compare the effectiveness and safety of PRP and ESWT in symptomatic ONFH patients. METHODS A total of 60 patients aged 40-79 with unilateral ONFH at Association Research Circulation Osseous (ARCO) stages I, II, and III were randomly assigned to the PRP (N=30) or the ESWT group (N=30). Four treatment sessions were provided in both groups. Assessments were performed at baseline, and 1-, 3-, 6-, and 12-month. Primary outcomes were measured by the visual analogue scale (VAS), and pressure pain thresholds (PPTs). Secondary outcomes were assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Harris Hip Score (HHS), and magnetic resonance imaging (MRI). The linear mixed-model analysis was used to evaluate the differences between groups and within groups and the "group by time" interaction effects. RESULTS There were significant differences between groups in terms of changes over time for VAS, PPTs, WOMAC, and HHS since 3-month and maintained up to 12-month (P<0.05, except for PPTs at 12-month). The simple main effects showed that the patients in PRP group had greater improvements in VAS (mean difference = -0.82, 95% CI [-1.39, -0.25], P=0.005), WOMAC (mean difference = -4.19, 95% CI [-7.00, -1.37], P=0.004), and HHS (mean difference = 5.28, 95% CI [1.94, 8.62], P=0.002). No related adverse events were reported. CONCLUSION This study supported the effectiveness and safety of both the PRP injection and ESWT in treating ONFH patients. For symptomatic patients with ONFH, intra-articular PRP injection appeared superior to ESWT in pain relief and functional improvement.

Abstract

BACKGROUND Subchondral bony structure damage plays an essential role in the pathogenesis of osteoarthritis (OA) knee. An intra-articular injection cannot reach the damaged subchondral bony structure and treat its pathologies effectively. The objective of the study was to compare the clinical effects of single intra-articular injection with or without intra-osseous injections of PRP in the treatment of osteoarthritis (OA) knee. METHODS This was a single-blind, parallel-group, randomized clinical trial. Fifty patients, with OA knee (K&L grade III), with ages between 50 and 65 years, were randomly allocated into 'intra-osseous, intra-articular PRP' ('IO+IA-PRP') (n = 25) or 'intra-articular PRP' group ('IA-PRP') (n = 25). Patients in the 'IO+IA-PRP' group received 18 ml PRP injection, and the 'IA-PRP' group received 8 ml PRP injection. Intra-osseous injections were given at the tibial plateau (5 ml) and femoral condyle (5 ml), along with intra-articular knee injection (8 ml), under fluoroscopic guidance. Outcomes were measured using VAS-pain, the knee injury and osteoarthritis outcome score (KOOS), and the treatment satisfaction scale. All patients (n = 50) were followed up till six months. RESULTS The mean age was 57.12(4.27) years and 57.00(4.96) years in the 'IO+IA-PRP' and 'IA-PRP' groups. Both groups showed significant improvement in pain relief (VAS pain) and KOOS parameters: pain, symptoms, ADL function, sport and recreation function, and quality of life. Compared to the 'IA-PRP' group, the 'IO+IA-PRP' group showed a greater reduction of VAS pain at six months. However, no significant difference was obtained in VAS pain-relief between these two groups (p = 0.422) at six months. Similarly, at 6 months, in inter-group comparison, except 'sport and recreation function' (p < 0.05), no significant differences were obtained in mean-scores of KOOS parameters: pain (p = 0.514); symptom (p = 0.148), ADL-function (p = 0.991), QoL-(p = 0.376). Patients in the 'IO+IA-PRP' group complained of significant 'injection-associated' adverse events and consumed a greater number of Acetaphenomen. CONCLUSIONS Both groups showed significant improvement following the intervention. Intra-osseous PRP injections did not provide any additional benefit over intra-articular PRP injection until six months regarding pain relief and functional improvement.

Abstract

BACKGROUND Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77-1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66-1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14-4·29); for patients who were antibody negative, the OR was 0·51 (0·29-0·90; p(interaction)=0·001). INTERPRETATION When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING US National Institutes of Health.

Abstract

BACKGROUND The efficacy of recombinant human erythropoietin (rHuEPO) in sparing red blood cell (RBC) transfusions in children with hemolytic uremic syndrome related to Shiga toxin-producing Escherichia coli (STEC-HUS) is uncertain. METHODS We conducted a pilot randomized controlled open trial between December 2018 and January 2021. Children were randomized to the intervention (subcutaneous rHuEPO 50 U/kg three times weekly until discharge + RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability) or to the control arm (RBC transfusion if hemoglobin ≤ 7 g/dL and/or hemodynamic instability). Primary outcome was the number of RBC transfusions received during hospitalization. Secondary outcomes were to explore whether baseline EPO levels were adequate to the degree of anemia, to correlate selected acute phase parameters with the number of RBC transfusions, and to assess possible adverse events. RESULTS Twelve patients per arm were included; they were comparable at recruitment and throughout the disease course. Median number of RBC transfusions was similar between groups (1.5, p = 0.76). Most patients had baseline EPO levels adequate to the degree of anemia, which did not correlate with the number of transfusions (r = 0.19, p = 0.44). Conversely, baseline (r = 0.73, p = 0.032) and maximum lactic dehydrogenase levels (r = 0.78, p = 0.003), creatinine peak (r = 0.71, p = 0.03) and dialysis duration (r = 0.7, p = 0.04) correlated significantly with RBC requirements. No side effects were recorded. CONCLUSION In children with STEC-HUS, the administration of rHuEPO did not reduce the number of RBC transfusions. Larger studies addressing higher doses and similar severity of kidney failure at rHuEPO initiation (e.g. at start of dialysis) are warranted. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03776851. A higher resolution version of the Graphical abstract is available as Supplementary information.

Abstract

BACKGROUND High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) μg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL gov (identifier: NCT02718079).

Abstract

BACKGROUND Interventions for chronic discogenic spine pain are currently insufficient in lowering individual patient suffering and global disease burden. A 2016 study of platelet rich plasma (PRP) for chronic discogenic pain previously demonstrated clinically significant response among active group patients compared with controls. OBJECTIVES To replicate the previous research to move this intervention forward as a viable option for patient care. STUDY DESIGN A double-blind, randomized, placebo-controlled study. SETTING Multicenter private practices. METHODS Twenty-six (12 men, 14 women) human patients, ages 25 to 71 with a diagnosis of chronic lumbar discogenic pain, were randomly assigned to active (PRP) or control (saline) groups in a ratio of 2 active to 1 control. Baseline and follow-up Oswestry Disability Index and Numeric Pain Rating Scale questionnaires were obtained to track patient outcomes at 8 weeks postoperatively. RESULTS Within group assessment showed clinically significant improvement in 17% of PRP patients and clinically significant decline in 5% (1 patient) of the active group. Clinically significant improvement was seen in 13% of placebo group patients and no placebo patients had clinically significant decline secondary to the procedure. LIMITATIONS Possible explanations may include a range of factors including differences in patient demographics, outcome-measure sensitivity, or misalignment of statistical analyses. CONCLUSIONS These findings are markedly different than the highly promising results of the 2016 PRP study. This study posits necessary caution for researchers who wish to administer PRP for therapeutic benefit and may ultimately point to necessary redirection of interventional research for discogenic pain populations.

Abstract

BACKGROUND Concerns regarding cardiovascular safety with current treatments for anemia in patients with dialysis-dependent (DD)-CKD have encouraged the development of alternatives. Roxadustat, an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates erythropoiesis by increasing endogenous erythropoietin and iron availability. METHODS In this open-label phase 3 study, patients with DD-CKD and anemia were randomized 1:1 to oral roxadustat three times weekly or parenteral epoetin alfa per local clinic practice. Initial roxadustat dose depended on erythropoiesis-stimulating agent dose at screening for patients already on them and was weight-based for those not on them. The primary efficacy end point was mean hemoglobin change from baseline averaged over weeks 28‒52 for roxadustat versus epoetin alfa, regardless of rescue therapy use, tested for noninferiority (margin, -0.75 g/dl). Adverse events (AEs) were assessed. RESULTS Among 2133 patients randomized (n=1068 roxadustat, n=1065 epoetin alfa), mean age was 54.0 years, and 89.1% and 10.8% were on hemodialysis and peritoneal dialysis, respectively. Mean (95% confidence interval) hemoglobin change from baseline was 0.77 (0.69 to 0.85) g/dl with roxadustat and 0.68 (0.60 to 0.76) g/dl with epoetin alfa, demonstrating noninferiority (least squares mean difference [95% CI], 0.09 [0.01 to 0.18]; P<0.001). The proportion of patients experiencing ≥1 AE and ≥1 serious AE was 85.0% and 57.6% with roxadustat and 84.5% and 57.5% with epoetin alfa, respectively. CONCLUSIONS Roxadustat effectively increased hemoglobin in patients with DD-CKD, with an AE profile comparable to epoetin alfa. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Safety and Efficacy Study of Roxadustat to Treat Anemia in Patients With Chronic Kidney Disease, on Dialysis. CLINICALTRIALS gov Identifier: NCT02174731.

Abstract

BACKGROUND Platelet-rich plasma (PRP) is gaining large interest in clinical practice as a minimally invasive injective treatment for knee osteoarthritis (OA). Different preparation methods are available, and the presence of leukocytes, deemed detrimental in some preclinical studies, is one of the most debated aspects regarding PRP efficacy. PURPOSE To compare the safety and effectiveness of leukocyte-rich PRP (LR-PRP) and leukocyte-poor PRP (LP-PRP) for the treatment of knee OA. STUDY DESIGN Randomized controlled trial; Level of evidence, 1. METHODS A total of 192 patients with symptomatic knee OA (Kellgren-Lawrence grade 1-3) were randomly allocated to 3 weekly injections of LR-PRP or LP-PRP. LP-PRP was obtained with a filter for leukodepletion. LR-PRP and LP-PRP were divided into aliquots of 5 mL, with a mean platelet concentration of 1146.8 × 10(9)/L and 1074.9 × 10(9)/L and a mean leukocyte concentration of 7991.4 × 10(6)/L and 0.1 × 10(6)/L, respectively. Patients were evaluated at baseline and thereafter at 2, 6, and 12 months for the primary outcome, the International Knee Documentation Committee (IKDC) subjective score; and for secondary outcomes, the Knee injury and Osteoarthritis Outcome Score (KOOS) subscales, EuroQol-visual analog scale (EQ-VAS), and Tegner score. RESULTS No differences between groups were observed in terms of absolute values or improvement of the clinical scores across all follow-up intervals. The mean IKDC subjective score at baseline and 12 months improved from 45.6 to 60.7 in the LR-PRP group as compared with 46.8 to 62.9 in the LP-PRP group (P = .626). No severe adverse events were described in either group, although 15 mild adverse events (knee pain or swelling) were reported: 12.2% for LR-PRP and 4.7% for LP-PRP (P = .101). No statistically significant difference was also found between LR-PRP and LP-PRP in terms of failures (7.8% vs 3.5%, P = .331). CONCLUSION This double-blind randomized trial showed that 3 intra-articular LR-PRP or LP-PRP injections produced similar clinical improvement in the 12 months of follow-up in patients with symptomatic knee OA. Both treatment groups reported a low number of adverse events, without intergroup differences. The presence of leukocytes did not significantly affect the clinical results of PRP injections. REGISTRATION NCT02923700 (ClinicalTrials.gov identifier).

Abstract

BACKGROUND Treatment with erythropoietin is well established for anemia in chronic kidney disease patients but not well studied in acute kidney injury. METHODS This is a multicenter, randomized, pragmatic controlled clinical trial. It included 134 hospitalized patients with anemia defined as hemoglobin < 11 g/dL and acute kidney injury defined as an increase of serum creatinine of ≥ 0.3 mg/dL within 48 h or 1.5 times baseline. One arm received recombinant human erythropoietin 4000 UI subcutaneously every other day (intervention; n = 67) and the second received standard of care (control; n = 67) during the hospitalization until discharge or death. The primary outcome was the need for transfusion; secondary outcomes were death, renal recovery, need for dialysis. RESULTS There was no statistically significant difference in transfusion need (RR = 1.05, 95%CI 0.65,1.68; p = 0.855), in renal recovery full or partial (RR = 0.96, 95%CI 0.81,1.15; p = 0.671), in need for dialysis (RR = 11.00, 95%CI 0.62, 195.08; p = 0.102) or in death (RR = 1.43, 95%CI 0.58,3.53; p = 0.440) between the erythropoietin and the control group. CONCLUSIONS Erythropoietin treatment had no impact on transfusions, renal recovery or mortality in acute kidney injury patients with anemia. The trial was registered on ClinicalTrials.gov (NCT03401710, 17/01/2018).