Abstract

BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.

Abstract

BACKGROUND Kawasaki disease (KD) is often complicated by coronary artery lesion (CAL), including dilatation or aneurysms. Intravenous immunoglobulin (IVIG) is used with aspirin to prevent CAL in KD. OBJECTIVE Given that the primary treatment for other vasculitis is the use of corticosteroids, this study has been performed to evaluate the effect of intravenous methylprednisolone pulse (IVMP) therapy in preventing CAL in KD. METHOD A randomized, single-blind clinical trial was conducted on 40 KD patients aged six months to five years. Patients were randomized into two groups according to the main treatment plan in addition to aspirin: case group (IVMP for three consecutive days and then oral prednisolone for three days) and control group (intravenous immunoglobulin 2 g/kg). Echocardiography was performed for all children at least three times, during the acute phase, two weeks, and two months later. RESULTS Data analysis at the end of the study was done on 40 patients (20 patients in each group). There were no significant differences in age and sex distribution, mean fever, and acute phase duration, as well as baseline echocardiography in the two groups. The frequency of CAL was 20% in the case group and 45% in the control group, after two weeks (p<0.05), but there was no significant difference between two groups in types of coronary artery lesion after two weeks and the frequency and severity of CAL after two months. CONCLUSION IVMP as initial line therapy effectively control systemic and vascular inflammation and decrease coronary artery damage in KD.

Abstract

PURPOSE The benefit of adjuvant medications, such as platelet-rich plasma (PRP) and hyaluronic acid (HA), following arthrocentesis remains controversial. The purpose of this study was to evaluate the efficacy of PRP and HA injection following arthrocentesis in subjects with symptomatic temporomandibular joint osteoarthritis (TMJ-OA). METHODS AND MATERIALS The authors implemented a prospective randomized single-blinded pilot clinical study. Healthy adults diagnosed with TMJ-OA who were treated with nonsurgical treatments initially, but failed to respond, participated in this study. Subjects were randomly allocated to HA, PRP, or combined HA+PRP groups following arthrocentesis. The primary outcome variable was the change in pain at 1 and 6 months postoperatively, using the Visual Analogue Scale (VAS). The secondary outcome variables were the changes in maximum mouth opening (MMO), lateral and protrusive mandibular movements, and pathologic TMJ sounds at 1 and 6 months postoperatively. Descriptive and bivariate statistics were computed. The significance level was set at P value < .05, using SPSS 19. RESULTS A total of 30 consecutive patients (15 males and 15 females) with a mean age of 29.63 ± 8.34 years were followed for 6 months in this study. The mean reduction in pain at 6 months was 4.1 ± 0.9, 4.1 ± 1.1, and 5.1 ± 1.0 for HA, PRP, and HA/PRP, respectively (P < .05). In all 3 treatment groups, mean VAS parameters had significantly reduced after treatment and these postoperative values were significantly lower in the PRP+HA group (P < .001). The mean increase of MMO after 6 months was 8.0 ± 2.8, 8.0 ± 3.0, and 10.1 ± 3.3 for HA, PRP, and HA/PRP, respectively (P < .05). MMO, lateral, and protrusive mandibular movements significantly improved after treatment in all 3 groups (P < .001). TMJ noises were significantly reduced in all treatment groups (P < .001), but the PRP+HA group exhibited a greater reduction. CONCLUSION Combined HA and PRP injection following arthrocentesis is more effective than HA or PRP alone in the management of TMJ-OA.

Abstract

OBJECTIVES The use of autologous platelet concentrates has shown growing evidence as a promising therapy. We conducted a split-mouth study to evaluate the effectiveness of injectable platelet-rich fibrin (PRF) compared to triamcinolone acetonide (TA) in the treatment of oral lichen planus (OLP). MATERIALS AND METHODS This split-mouth randomized trial included twelve patients with symptomatic, bilateral OLP lesions. The participants were randomly allocated to receive a 1-mL intralesional PRF injection on one side of the buccal mucosa and a 0.5-mL TA injection on the counterpart side. The application was performed once a week for 4 weeks. The outcomes were measured using a visual analog scale score, REU score, and lesion areas. RESULTS Both injectable TA and PRF were effective in the management of oral lichen planus. After four weeks of treatment, there was an average reduction in the VAS score (68.5% i-PRF, 91% TA) and an average reduction in the REU score (74% i-PRF, 91% TA). There were no statistically significant differences between the two treatment methods (P > 0.05). CONCLUSIONS Intralesional injection with TA showed more effectiveness than i-PRF in the management of OPL lesions. Although, i-PRF cannot be considered a first-line treatment option, it showed promising alternative therapy choice with no side effects.

Abstract

BACKGROUND Erythropoietin is a glycoprotein that mainly regulates erythropoiesis. In patients with chronic renal failure with anemia, darbepoetin alfa can stimulate erythropoiesis, correct anemia, and maintain hemoglobin levels. This study was designed to demonstrate the efficacy and safety of darbepoetin alfa injections as being not inferior to epoetin alfa injections (Recombinant Human Erythropoietin injection, rHuEPO) when maintaining hemoglobin (Hb) levels within the target range (10.0-12.0 g/dL) for the treatment of renal anemia. METHODS Ninety-five patients were enrolled in this study from April 15, 2013 to April 10, 2014 at 25 sites. In this study, patients (n = 95) aged 18-70 years were randomized into a once per week intravenous darbepoetin alfa group (n = 56) and a twice or three times per week intravenous epoetin alfa group (n = 39) for 28 weeks, who had anemia with hemoglobin levels between 6 g/dL and 10 g/dL due to chronic kidney disease (CKD) and were undergoing hemodialysis or hemofiltration with ESA-naive (erythropoiesis stimulating agent-naive). The primary efficacy profile was the mean Hb level (the non-inferiority margin was -1.0 g/dL, week 21-28); the secondary efficacy profiles were the Hb increase rate (week 0-4), the target Hb achievement cumulative rate and time, the change trends of the Hb levels, and the target Hb maintenance ratio. Adverse events (AEs) were observed and compared, and the efficacy and safety were analyzed between the two treatment groups. Additionally, the frequencies of dose adjustments between the darbepoetin alfa and epoetin alfa groups were compared during the treatment period. SAS® software version 9.2 was used to perform all statistical analyses. Descriptive statistics were used for all efficacy, safety, and demographic variable analyses, including for the primary efficacy indicators. RESULTS The mean Hb level was 11.3 g/dL in the darbepoetin alfa group and 10.7 g/dL in the epoetin alfa group, respectively; the difference of the lower limits of the 95% confidence intervals (CI) between the two groups was 0.1 g/dL (>-1.0 g/dL), and non-inferiority was proven; the Hb levels started to increase in the first four weeks at a similar increase rate; no obvious differences were observed between the groups in the target Hb achievement cumulative rates, and the Hb levels as well as the target Hb level maintenance rate changed over time. The incidence of AEs was 62.5% in the darbepoetin alfa group and 76.9% in the epoetin alfa group. All the adverse events observed in the study were those commonly associated with hemodialysis. CONCLUSION Darbepoetin alfa intravenously once per week can effectively increase Hb levels and maintain the target Hb levels well, which makes it not inferior to epoetin alfa intravenously twice or three times per week. Darbepoetin alfa shows an efficacy and safety comparable to epoetin alfa for the treatment of renal anemia.

Abstract

BACKGROUND Time to treatment matters in traumatic haemorrhage but the optimal prehospital use of blood in major trauma remains uncertain. We investigated whether use of packed red blood cells (PRBC) and lyophilised plasma (LyoPlas) was superior to use of 0·9% sodium chloride for improving tissue perfusion and reducing mortality in trauma-related haemorrhagic shock. METHODS Resuscitation with pre-hospital blood products (RePHILL) is a multicentre, allocation concealed, open-label, parallel group, randomised, controlled, phase 3 trial done in four civilian prehospital critical care services in the UK. Adults (age ≥16 years) with trauma-related haemorrhagic shock and hypotension (defined as systolic blood pressure <90 mm Hg or absence of palpable radial pulse) were assessed for eligibility by prehospital critial care teams. Eligible participants were randomly assigned to receive either up to two units each of PRBC and LyoPlas or up to 1 L of 0·9% sodium chloride administered through the intravenous or intraosseous route. Sealed treatment packs which were identical in external appearance, containing PRBC-LyoPlas or 0·9% sodium chloride were prepared by blood banks and issued to participating sites according to a randomisation schedule prepared by the co-ordinating centre (1:1 ratio, stratified by site). The primary outcome was a composite of episode mortality or impaired lactate clearance, or both, measured in the intention-to-treat population. This study is completed and registered with ISRCTN.com, ISRCTN62326938. FINDINGS From Nov 29, 2016 to Jan 2, 2021, prehospital critical care teams randomly assigned 432 participants to PRBC-LyoPlas (n=209) or to 0·9% sodium chloride (n=223). Trial recruitment was stopped before it achieved the intended sample size of 490 participants due to disruption caused by the COVID-19 pandemic. The median follow-up was 9 days (IQR 1 to 34) for participants in the PRBC-LyoPlas group and 7 days (0 to 31) for people in the 0·9% sodium chloride group. Participants were mostly white (62%) and male (82%), had a median age of 38 years (IQR 26 to 58), and were mostly involved in a road traffic collision (62%) with severe injuries (median injury severity score 36, IQR 25 to 50). Before randomisation, participants had received on average 430 mL crystalloid fluids and tranexamic acid (90%). The composite primary outcome occurred in 128 (64%) of 199 participants randomly assigned to PRBC-LyoPlas and 136 (65%) of 210 randomly assigned to 0·9% sodium chloride (adjusted risk difference -0·025% [95% CI -9·0 to 9·0], p=0·996). The rates of transfusion-related complications in the first 24 h after ED arrival were similar across treatment groups (PRBC-LyoPlas 11 [7%] of 148 compared with 0·9% sodium chloride nine [7%] of 137, adjusted relative risk 1·05 [95% CI 0·46-2·42]). Serious adverse events included acute respiratory distress syndrome in nine (6%) of 142 patients in the PRBC-LyoPlas group and three (2%) of 130 in 0·9% sodium chloride group, and two other unexpected serious adverse events, one in the PRBC-LyoPlas (cerebral infarct) and one in the 0·9% sodium chloride group (abnormal liver function test). There were no treatment-related deaths. INTERPRETATION The trial did not show that prehospital PRBC-LyoPlas resuscitation was superior to 0·9% sodium chloride for adult patients with trauma related haemorrhagic shock. Further research is required to identify the characteristics of patients who might benefit from prehospital transfusion and to identify the optimal outcomes for transfusion trials in major trauma. The decision to commit to routine prehospital transfusion will require careful consideration by all stakeholders. FUNDING National Institute for Health Research Efficacy and Mechanism Evaluation.

Abstract

PURPOSE Peptic ulcer is a multifactorial and complex disease and affects a wide range of people worldwide. We provided a novel therapeutic approach for peptic ulcer and observed its effect. METHODS Peptic ulcer patients were enrolled from 2016 to 2017 in Chongqing and randomly assigned to two groups: a control group that used only rabeprazole and a platelet-rich plasma (PRP) group that received a combination therapy of autologous PRP (aPRP) and rabeprazole. The therapeutic effect was assessed via the ulcer size and symptom score. RESULTS A total of 27 patients were included (12 patients in the control group and 15 patients in the PRP group) in this study. Our results showed that all participants have healed in 30 days, and there was no significant difference in healing time between the PRP group and the control group in different independent variables. However, regression analysis revealed that the healing time was 6.99 days shorter in the PRP group than that in the control group, and patients with higher symptom scores in the initial examination need more time to heal during treatment. Endoscopic results showed that the repaired ulcer in the PRP group was more similar to the normal gastric mucosa tissue than that the control group. CONCLUSION This study showed an encouraging preliminary result that aPRP has a positive result in patients with peptic ulcer and seems to be a better choice for refractory peptic ulcer treatment. Although further follow-up studies are needed to determine the duration of efficacy of aPRP, the approach will be helpful in improving the clinical treatment of peptic ulcer.

Abstract

BACKGROUND Preoperative anemia affects perioperative outcomes and often causes fatigue and psychological disorders. Therefore, anemia should be treated before a patient undergoes surgery. Ninjin'yoeito (NYT), a Japanese Kampo medicine composed of ginseng and Japanese angelica root with the other 10 herbs, is administered for anemia, fatigue and anxiety; however, there are a few reports that have prospectively examined the effects of NYT before surgery for gynecological diseases. Hence, we tended to investigate its efficacy and safety. METHODS In this open-label randomized trial, women with gynecological diseases accompanied by preoperative anemia (defined as < 11.0 g/dL Hemoglobin [Hb]) were randomly assigned (1:1) into the iron supplementation and NYT groups. Patients of the iron supplementation group and the NYT group received 100 mg/day iron supplementation with and without NYT (7.5 g/day) for at least 10 days before surgery. The primary endpoint was improvement in Hb levels before and after treatment, and Cancer Fatigue Scale (CFS) and Visual Analogue Scale for Anxiety (VAS-A) scores between groups. Statistical analyses were performed with Wilcoxon signed rank test, Wilcoxon rank sum test, and Fisher's exact test as appropriate. RESULTS Forty patients were enrolled of whom 30 patients were finally analyzed after allocating 15 to each group. There was no difference in the characteristics between both groups. Hb significantly increased in both groups (iron supplementation group, 9.9 ± 0.8 g/dL vs. 11.9 ± 1.6 g/dL; NYT group, 9.8 ± 1.0 g/dL vs. 12.0 ± 1.0 g/dL); the difference in the elevations in Hb between both groups was statistically insignificant (P = 0.72). Contrarily, CFS (17.9 ± 10.2 vs. 8.1 ± 5.2) and VAS-A (56 mm (50-70) vs. 23 mm (6-48)) scores were significantly decreased only in the NYT group and these changes were greater in the NYT group (∆CFS, P = 0.015; ∆VAS-A, P = 0.014). Liver dysfunction occurred in one patient of the NYT group. CONCLUSIONS For treating preoperative anemia in women with gynecological conditions, NYT administration along with iron supplementation safely and efficiently improved the preoperative fatigue and anxiety in addition to the recovery from anemia. TRIAL REGISTRATION jRCT1051190012 (28/April/2019, retrospectively registered).

Abstract

Evidence of effectiveness of prophylactic use of tranexamic acid (TXA) in thrombocytopenia is lacking. To determine whether TXA safely reduces bleeding incidence in patients undergoing treatment for hematologic malignancies, a randomized double blind clinical trial was conducted June 2016 through June 2020. Of 3120 screened adults 356 patients were eligible and enrolled, and 337 patients (mean age, 53.9; 141 (41.8%) women), randomized to 1,300mg TXA orally or 1,000mg TXA intravenously (n=168) versus placebo (n=169) thrice daily for maximum 30 days. 330 patients were activated when their platelet counts fell below 30,000/µl; 279 (83%) had complete outcome ascertainment. WHO grade 2 or higher bleeding was observed in the 30 days following activation in 50.3% (73/145) and 54.2% (78/144) of patients in the TXA and placebo groups, adjusted odds ratio: 0.83 (95%CI:0.50,1.34; p=0.44). There was no statistically significant difference in mean number of platelet transfusions (0.1;95%CI:-1.9,2.0), mean days alive without grade 2 or higher bleeding (0.8;95%CI:-0.4,2.0), thrombotic events (6/163 (3.7%) TXA, 9/163 (5.5%) placebo), or deaths due to serious bleeding. Most common adverse events were: diarrhea [(116/164 (70.7%) TXA and 114/163 (69.9%) placebo)]; febrile neutropenia [111/164 (67.7%) TXA, 105/163 (64.4%) placebo]; fatigue [106/164 (64.6%) TXA, 109/163 (66.9%) placebo]; and nausea [104/164 (63.4%) TXA, 97/163 (59.5%) placebo]. Among patients with hematologic malignancy undergoing chemotherapy or hematopoietic stem cell transplantation, prophylactic treatment with tranexamic acid compared with placebo did not significantly reduce the risk of WHO grade 2 or higher bleeding. Trial Registration: Clinicaltrials.gov Identifier: NCT02578901.

Abstract

OBJECTIVES Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion-related pro-inflammatory cytokine production. This may be because of alterations in recipient immune responses. METHODS This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro-inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks' gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. RESULTS By the third transfusion, infants receiving unwashed blood had an increase in IL-17A (P = 0.04) and TNF (P = 0.007), whereas infants receiving washed blood had reductions in IL-17A (P = 0.013), TNF (P = 0.048), IL-6 (P = 0.001), IL-8 (P = 0.037), IL-12 (P = 0.001) and IFN-γ (P = 0.001). The magnitude of the post-transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL-12 (P = 0.001), IL-17A (P = 0.01) and TNF (P = 0.03), with the difference between the groups reaching significance by the third transfusion (P < 0.001 for each cytokine). CONCLUSION The pro-inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.