Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial
The journal of sexual medicine. 2021
BACKGROUND Animal studies postulate that platelet-rich plasma (PRP) injections improve key elements of the pathophysiologic mechanisms leading to erectile dysfunction (ED). AIM: To conduct the first double-blind, randomized, placebo-controlled trial assessing the efficacy and safety of PRP injections in patients with mild and moderate ED. METHODS Sixty sexually active patients with mild and moderate ED were randomly assigned to two sessions, with a one-month difference, of 10 mL PRP (n = 30) or placebo (n = 30) intracavernosal injections. An FDA-approved separation system was used. Patients were evaluated at 1, 3 and 6 months after completion of the treatment protocol. A per-protocol analysis was applied. All participants withheld any ED treatment during the trial. OUTCOMES The achievement of minimal clinically important difference (MCID) in the International Index of Erectile Function - Erectile Domain (IIEF-EF) from baseline to 6 months after final treatment. Erectile function at all time points, as well as safety of PRP injections, were also evaluated. RESULTS At 6 months, a MCID was achieved by 20/29 (69%) patients in the PRP group compared to 7/26 (27%) in the placebo group. The risk difference between the two groups was 42% (95%CI: 18-66), P < 0.001 and the baseline-adjusted mean between-group-difference in the IIEF-EF score was 3.9 points (95%CI: 1.8-5.9). Similarly, a statistically significant difference of both the number of participants attaining a MCID and the IIEF-EF score was also observed at the 1- and 3-month evaluation between the two groups. Accordingly, patients receiving PRP were more satisfied with the treatment. No adverse events were observed during the study period. CLINICAL IMPLICATIONS Intracavernosal PRP injection therapy used as outlined in this trial appears to be a safe and effective short-term treatment for the management of mild to moderate ED. STRENGTHS & LIMITATIONS We conducted the first clinical trial exploring the role of PRP in the management of ED. Conversely, our findings lack external validity due to single-center design. Furthermore, our results cannot be extrapolated to other PRP separation systems. CONCLUSIONS PRP intracavernosal injections may be a promising addition to the urologist's armamentarium for the management of ED. Still, further high-quality studies are warranted to corroborate our findings. Evangelos P, Mykoniatis I, Pyrgidis N, et al. Platelet-Rich Plasma (PRP) Improves Erectile Function: A Double-Blind, Randomized, Placebo-Controlled Clinical Trial. J Sex Med 2021;XX:XXX-XXX.
Tranexamic acid to reduce head injury death in people with traumatic brain injury: the CRASH-3 international RCT
Health technology assessment (Winchester, England). 2021;25(26):1-76
BACKGROUND Tranexamic acid safely reduces mortality in traumatic extracranial bleeding. Intracranial bleeding is common after traumatic brain injury and can cause brain herniation and death. We assessed the effects of tranexamic acid in traumatic brain injury patients. OBJECTIVE To assess the effects of tranexamic acid on death, disability and vascular occlusive events in traumatic brain injury patients. We also assessed cost-effectiveness. DESIGN Randomised trial and economic evaluation. Patients were assigned by selecting a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients, caregivers and those assessing outcomes were masked to allocation. All analyses were by intention to treat. We assessed the cost-effectiveness of tranexamic acid versus no treatment from a UK NHS perspective using the trial results and a Markov model. SETTING 175 hospitals in 29 countries. PARTICIPANTS Adults with traumatic brain injury within 3 hours of injury with a Glasgow Coma Scale score of ≤ 12 or any intracranial bleeding on computerised tomography scan, and no major extracranial bleeding, were eligible. INTERVENTION Tranexamic acid (loading dose 1 g over 10 minutes then infusion of 1 g over 8 hours) or matching placebo. MAIN OUTCOME MEASURES Head injury death in hospital within 28 days of injury in patients treated within 3 hours of injury. Secondary outcomes were early head injury deaths, all-cause and cause-specific mortality, disability, vascular occlusive events, seizures, complications and adverse events. RESULTS Among patients treated within 3 hours of injury (n = 9127), the risk of head injury death was 18.5% in the tranexamic acid group versus 19.8% in the placebo group (855/4613 vs. 892/4514; risk ratio 0.94, 95% confidence interval 0.86 to 1.02). In a prespecified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the tranexamic acid group versus 14.0% in the placebo group (485/3880 vs. 525/3757; risk ratio 0.89, 95% confidence interval 0.80 to 1.00). There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury (166/2846 vs. 207/2769; risk ratio 0.78, 95% confidence interval 0.64 to 0.95), but in those with severe head injury (689/1739 vs. 685/1710; risk ratio 0.99, 95% confidence interval 0.91 to 1.07) there was no apparent reduction (p-value for heterogeneity = 0.030). Early treatment was more effective in mild and moderate head injury (p = 0.005), but there was no obvious impact of time to treatment in cases of severe head injury (p = 0.73). The risk of disability, vascular occlusive events and seizures was similar in both groups. Tranexamic acid is highly cost-effective for mild and moderate traumatic brain injury (base case of £4288 per quality-adjusted life-year gained). CONCLUSION Early tranexamic acid treatment reduces head injury deaths. Treatment is cost-effective for patients with mild or moderate traumatic brain injury, or those with both pupils reactive. FUTURE WORK Further trials should examine early tranexamic acid treatment in mild head injury. Research on alternative routes of administration is needed. LIMITATIONS Time to treatment may have been underestimated. TRIAL REGISTRATION Current Controlled Trials ISRCTN15088122, ClinicalTrials.gov NCT01402882, EudraCT 2011-003669-14, Pan African Clinical Trial Registry PACTR20121000441277. FUNDING The project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 26. See the NIHR Journals Library website for further project information. In addition, funding was provided by JP Moulton Charitable Trust, Joint Global Health Trials (Medical Research Council, Department for International Development and the Wellcome Trust). This project was funded by the NIHR Global Health Trials programme.
Adults with traumatic brain injury enrolled in the CRASH-3 trial (n=9127).
Tranexamic acid (TXA), (n= 4613).
Matching placebo (n= 4514).
The risk of head injury death was 18.5% in the TXA group versus 19.8% in the placebo group. In a pre-specified analysis excluding patients with a Glasgow Coma Scale score of 3 or bilateral unreactive pupils at baseline, the results were 12.5% in the TXA group versus 14.0% in the placebo group. There was a reduction in the risk of head injury death with tranexamic acid in those with mild to moderate head injury, but in those with severe head injury there was no apparent reduction. Early treatment was more effective in mild and moderate head injury, but there was no obvious impact of time to treatment in cases of severe head injury. The risk of disability, vascular occlusive events and seizures was similar in both groups.
Desmopressin effects on bleeding during functional endoscopic sinus surgery on patients with chronic rhinosinusitis
American journal of otolaryngology. 2021;42(5):103024
OBJECTIVE In this study we aimed to determine whether Desmopressin (DDAVP) can alter bleeding and improves surgeon visual field and decrease operation time or lessen use of anesthesiology medication in a clinical trial study. METHOD This study is a randomized clinical trial using the permuted block randomization method. 44 patients were enrolled in study and divided into two equal intervention-control groups. The intervention group received maximum dose of 0/2 micrograms per kg of DDAVP. In the control group, 30 min before the surgery, 100 ml of normal saline will be injected. RESULTS The amount of bleeding was 517/17 cc in control group during surgery while it was 387/72 cc in group receiving DDAVP which is significantly lower. The satisfaction of surgeon regarding suitable visual field was 6/45 in control group while it was 3/77 in DDAVP receivers which is lower. CONCLUSION It seems that intravenous DDAVP can reduce bleeding during surgery and offer an enhanced vision for surgeon during surgery but it has no potential efficacy on reduction of period of surgery and need for anesthesiology medication like remifentanil and isoflurane.
Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial
The Lancet. Haematology. 2021
BACKGROUND For decades, patients with sickle cell disease have had only a limited number of therapies available. In 2019, voxelotor (1500 mg), an oral once-daily sickle haemoglobin polymerisation inhibitor, was approved in the USA for the treatment of sickle cell disease in patients aged 12 years and older on the basis of HOPE trial data. To further describe the applicability of voxelotor as a treatment for this chronic illness, we report the long-term efficacy and safety of this drug at 72 weeks of treatment; the conclusion of the placebo-controlled HOPE trial. METHODS HOPE is an international, randomised, double-blind, placebo-controlled, phase 3 trial done at 60 clinical sites in Canada, Egypt, France, Italy, Jamaica, Kenya, Lebanon, Netherlands, Oman, Turkey, the USA, and the UK. Patients (aged 12-65 years) with confirmed sickle cell disease, a haemoglobin concentration of 5·5-10·5 g/dL at enrolment, and who had between one and ten vaso-occlusive crisis events in the previous 12 months were enrolled. Patients receiving regularly scheduled transfusion therapy, who had received a transfusion in the previous 60 days, or who had been admitted to hospital for a vaso-occlusive crisis in the previous 14 days were excluded. Patients were randomly assigned (1:1:1) to receive either once-daily oral voxelotor 1500 mg, voxelotor 900 mg, or placebo for 72 weeks. Randomisation was done centrally by use of an interactive web response system, stratified by baseline hydroxyurea use (yes vs no), age group (adolescents [12 to <18 years] vs adults [18 to 65 years]), and geographic region (North America vs Europe vs other). The primary endpoint (already reported) was the proportion of patients who achieved a haemoglobin response at week 24. In this final analysis, we report prespecified long-term efficacy assessments by intention to treat, including changes in haemoglobin concentrations from baseline to week 72, changes in the concentration of haemolysis markers (absolute and percentage reticulocytes, indirect bilirubin concentrations, and lactate dehydrogenase concentrations) from baseline to week 72, the annualised incidence of vaso-occlusive crises, and patient functioning, as assessed with the Clinical Global Impression of Change (CGI-C) scale. Safety was assessed in patients who received at least one dose of treatment (modified intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT03036813. FINDINGS Between Dec 5, 2016, and May 3, 2018, 449 patients were screened, of whom 274 were randomly assigned to the voxelotor 1500 mg group (n=90), the voxelotor 900 mg group (n=92), or the placebo group (n=92). At week 72, the adjusted mean change in haemoglobin concentration from baseline was 1·0 g/dL (95% CI 0·7 to -1·3) in the voxelotor 1500 mg group, 0·5 g/dL (0·3 to -0·8) in the voxelotor 900 mg group, and 0·0 g/dL (-0·3 to 0·3) in the placebo group, with a significant difference observed between the voxelotor 1500 mg group and the placebo group (p<0·0001), and between the voxelotor 900 mg group and the placebo group (p=0·014). Significant improvements in markers of haemolysis, as assessed by the difference in adjusted mean percentage change from baseline at week 72 versus placebo, were observed in the voxelotor 1500 mg group in indirect bilirubin concentrations (-26·6% [95% CI -40·2 to -12·9]) and percentage of reticulocytes (-18·6% [-33·9 to -3·3]). The proportion of patients in the voxelotor 1500 mg group who were rated as "moderately improved" or "very much improved" at week 72 with the CGI-C was significantly greater than in the placebo group (39 [74%] of 53 vs 24 [47%] of 51; p=0·0057). Serious adverse events unrelated to sickle cell disease were reported in 25 (28%) of 88 patients in the voxelotor 1500 mg group, 20 (22%) of 92 patients in the voxelotor 900 mg group, and 23 (25%) of 91 patients in the placebo group. Grade 3 or 4 adverse events were infrequent (ie, occurred in <10% of patients); anaemia occurred in five or more patients (two [2%] patients in the voxelotor 1500 mg group, seven [8%] patients in the voxelotor 900 mg group, and three [3%] patients in the placebo group). Of all 274 patients, six (2%) deaths occurred during the study (two deaths in each treatment group), all of which were judged as unrelated to treatment. INTERPRETATION Voxelotor 1500 mg resulted in rapid and durable improvements in haemoglobin concentrations maintained over 72 weeks and has potential to address the substantial morbidity associated with haemolytic anaemia in sickle cell disease. FUNDING Global Blood Therapeutics.
The effect of platelet-rich fibrin (PRF) on wound healing, adhesion, and hemostasis after endoscopic sinus surgery in patients with nasal polyposis
American journal of otolaryngology. 2021;42(5):103010
PURPOSE Chronic rhinosinusitis (CRS) is one of the most common chronic diseases seen worldwide. Endoscopic sinus surgery (ESS) has become a widely accepted procedure for medically refractory chronic rhinosinusitis and nasal polyps. Prevention of revision surgery often depends on good wound healing and less adhesion formation. In recent years, the effects of platelet-rich fibrin (PRF) on tissue healing have been addressed in many surgical branches, especially for dental implant surgery and plastic surgery. METHODS This prospective study was conducted with 50 patients who underwent endoscopic sinus surgery for the diagnosis of nasal polyposis. While the middle meatus in one nasal cavity was filled with PRF and supported with Nasopore, only Nasopore was used in the other nasal cavity middle meatus. The patients were followed up clinically at weeks 1, 2, 3, 4, 8, and 12 postoperatively. The assessor determined the presence of adhesion, crusting, bleeding, frontal ostium stenosis, granulation, and infection, and if present, the grades of these complications were scored according to a questionnaire. RESULTS In our study, adhesion, infection, bleeding, granulation, and frontal ostium stenosis were less common in the PRF group, and a statistically significant difference was found between the groups. CONCLUSION In our study, better results were obtained in terms of adhesion, infection, bleeding, granulation, and frontal ostium stenosis after ESS as a result of the effects of PRF on wound healing. The application of PRF is an inexpensive and easy procedure. PRF can be a good alternative to other types of tampons after ESS.
Assessment of the perioperative effect of vasopressin in patients undergoing laparoscopic myomectomy: A double-blind randomised study
Indian journal of anaesthesia. 2021;65(2):139-145
BACKGROUND AND AIMS Myomectomy is associated with perioperative bleeding. The aim of the study is to evaluate the effect of intramyometrial vasopressin on blood loss and the associated cardiovascular complications during myomectomy. METHODS The study included 194 patients classified into two groups- 1) Vasopressin group: the vasopressin was diluted as 0.1 unit/ml and 15 ml was injected by the surgeon in the plane between the myometrium and the myoma. 2) Control group: The patients received an equal amount of normal saline. The monitored parameters included the amount of blood loss, required blood transfusion, heart rate, mean arterial blood pressure, the incidence of hypertension, hypotension, bradycardia, tachycardia, electrocardiogram (ECG) changes and the blood troponin I level. RESULTS The heart rate decreased significantly in both groups, but the decrease was lower with vasopressin than the control group through the time points T3 to T5 (P < 0.05) The mean arterial blood pressure increased significantly in both groups, but the increase was higher with vasopressin than the control group through T3 to T5 (P < 0.05). The amount of blood loss decreased significantly with vasopressin than the control groups (P = 0.001). The number of transfused packed red blood cells was lower with vasopressin than the control group (P = 0.001). The incidence of hypertension, bradycardia and atrial extrasystole was higher with vasopressin than the control group (P = 0.005, P = 0.012, P = 0.033, respectively). CONCLUSION Intramyometrial vasopressin decreases blood loss and blood transfusion, but it is associated with cardiovascular complications that may be serious as reported in other studies. Therefore, anaesthesiologists and gynaecologists must follow the precautions to avoid and minimise the incidence of complications with intramyometrial vasopressin.
Prothrombin complex concentrates and andexanet for management of direct factor Xa inhibitor related bleeding: a meta-analysis
European review for medical and pharmacological sciences. 2021;25(6):2637-2653
There are potential concerns related to bleeding caused by oral anticoagulants, especially in the elderly. Andexanet alfa has been authorized for use to reverse the effects of oral anticoagulants. Off-label use of four factor prothrombin complex concentrate (4F-PCC) for the reversal of oral factor Xa inhibitors is common. However, not much is known about their efficacy and safety profile. The intent of this meta-analysis was to evaluate the efficacy and safety of 4F-PCC and andexanet alfa for management of major bleeding due to oral factor Xa inhibitors. Comprehensive searches were done systematically through PubMed, Scopus and Google scholar databases. Studies that were retrospective record based or adopted prospective cohort approach and reported either of the three main outcomes, i.e., achieved hemostasis rate or rate of thrombotic events or mortality rate were included in the meta-analysis. Statistical analyses were done using STATA version 13.0. A total of 22 studies were included in the meta-analysis. All the studies had a single arm with no control/comparator group. The pooled rate of good to excellent hemostatic control upon use of andexanet was 80% (95% CI; 72% to 88%) and for 4F-PCC, it was 76% (95% CI; 70% to 83%). A comparatively higher pooled rate of thrombotic complications upon use of andexanet [13% (95% CI; 5% to 20%) was noted, compared to use of aPCC/4F-PCC [4% (95% CI; 3% to 5%). The pooled all-cause mortality rate within 30 days of administration was 24% (95% CI; 12% to 35%) with andexanet use and 19% (95% CI; 14% to 25%) for aPCC/4F-PCC. The findings suggest that use of both andexanet and aPCC/4F-PCC achieves a good hemostasis but there is an associated risk of thrombotic events and mortality. Future studies should have a control group to better establish evidence on efficacy and safety of these agents.
Neonatal Uterine Bleedings: An Ignored Sign but a Possible Cause of Early-Onset Endometriosis - A Systematic Review
Biomedicine hub. 2021;6(1):6-16
OBJECTIVE Based on the hypothesis that neonatal uterine bleedings (NUB), occurring mostly in the first week after birth, could represent a pathogenetic mechanism for early-onset endometriosis, this systematic review (SR) was undertaken to evaluate the prevalence and screening strategies used to assess and quantify NUB. DESIGN Both a SR and a sample literature search in PubMed and Embase were conducted to gather information on NUB prevalence and screening techniques. This was performed by an information specialist. Only full-text articles regarding the assessment of NUB in neonates in the first 2 weeks after birth were included. No limit on language or publication data was used. MATERIALS AND METHODS The SR was registered in PROSPERO (CRD42019138121). Data was first assessed for eligibility on title and abstract by 2 blinded review authors. Any disagreements were discussed with a third reviewer if necessary. Subsequently, full-text articles were read and assessed for quality using the Cochrane Collaboration Handbook. RESULTS Out of 1,988 articles in the systematic search, 10 relevant articles were selected, of which 8 were identified through the systematic search and 2 were found through other sources. The sample search of 4,445 articles did not bring up relevant articles. Results were not comparable due to the heterogeneity of screening techniques, although data showed consensus. The prevalence of visible bleeding ranged from 3.3 to 53.8% and the prevalence of occult bleeding from 25.4 to 96.7%. The occurrence was the highest between the 3rd and 7th day postpartum (PP) and the bleeding lasted for 3-4 days on average. Various screening techniques for detecting NUB were found in the literature, including the use of hemoglobin detection devices (such as Hemastix) in the vaginal vestibulum, comparison of diapers with stains of known volume, colposcopy, and ultrasonography. CONCLUSION The reported prevalence of NUB varies considerably, with a consistent occurrence between the 3rd and the 7th day PP. Literature to assess NUB is dated. The techniques are poorly described and heterogeneous. Future research should focus on prospective cohort studies in order to attempt to correlate NUB cases to (early-onset) endometriosis.
Treatment for bleeding oesophageal varices in people with decompensated liver cirrhosis: a network meta-analysis
The Cochrane database of systematic reviews. 2021;4:Cd013155
BACKGROUND Approximately 40% to 95% of people with liver cirrhosis have oesophageal varices. About 15% to 20% of oesophageal varices bleed within about one to three years after diagnosis. Several different treatments are available, including, among others, endoscopic sclerotherapy, variceal band ligation, somatostatin analogues, vasopressin analogues, and balloon tamponade. However, there is uncertainty surrounding the individual and relative benefits and harms of these treatments. OBJECTIVES To compare the benefits and harms of different initial treatments for variceal bleeding from oesophageal varices in adults with decompensated liver cirrhosis, through a network meta-analysis; and to generate rankings of the different treatments for acute bleeding oesophageal varices, according to their benefits and harms. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, Science Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform, and trials registers until 17 December 2019, to identify randomised clinical trials (RCTs) in people with cirrhosis and acute bleeding from oesophageal varices. SELECTION CRITERIA We included only RCTs (irrespective of language, blinding, or status) in adults with cirrhosis and acutely bleeding oesophageal varices. We excluded RCTs in which participants had bleeding only from gastric varices, those who failed previous treatment (refractory bleeding), those in whom initial haemostasis was achieved before inclusion into the trial, and those who had previously undergone liver transplantation. DATA COLLECTION AND ANALYSIS We performed a network meta-analysis with OpenBUGS software, using Bayesian methods, and calculated the differences in treatments using odds ratios (OR) and rate ratios with 95% credible intervals (CrI) based on an available-case analysis, according to National Institute of Health and Care Excellence Decision Support Unit guidance. We performed also the direct comparisons from RCTs using the same codes and the same technical details. MAIN RESULTS We included a total of 52 RCTs (4580 participants) in the review. Forty-eight trials (4042 participants) were included in one or more comparisons in the review. The trials that provided the information included people with cirrhosis due to varied aetiologies and those with and without a previous history of bleeding. We included outcomes assessed up to six weeks. All trials were at high risk of bias. A total of 19 interventions were compared in the trials (sclerotherapy, somatostatin analogues, vasopressin analogues, sclerotherapy plus somatostatin analogues, variceal band ligation, balloon tamponade, somatostatin analogues plus variceal band ligation, nitrates plus vasopressin analogues, no active intervention, sclerotherapy plus variceal band ligation, balloon tamponade plus sclerotherapy, balloon tamponade plus somatostatin analogues, balloon tamponade plus vasopressin analogues, variceal band ligation plus vasopressin analogues, balloon tamponade plus nitrates plus vasopressin analogues, balloon tamponade plus variceal band ligation, portocaval shunt, sclerotherapy plus transjugular intrahepatic portosystemic shunt (TIPS), and sclerotherapy plus vasopressin analogues). We have reported the effect estimates for the primary and secondary outcomes when there was evidence of differences between the interventions against the reference treatment of sclerotherapy, but reported the other results of the primary and secondary outcomes versus the reference treatment of sclerotherapy without the effect estimates when there was no evidence of differences in order to provide a concise summary of the results. Overall, 15.8% of the trial participants who received the reference treatment of sclerotherapy (chosen because this was the commonest treatment compared in the trials) died during the follow-up periods, which ranged from three days to six weeks. Based on moderate-certainty evidence, somatostatin analogues alone had higher mortality than sclerotherapy (OR 1.57, 95% CrI 1.04 to 2.41; network estimate; direct comparison: 4 trials; 353 participants) and vasopressin analogues alone had higher mortality than sclerotherapy (OR 1.70, 95% CrI 1.13 to 2.62; network estimate; direct comparison: 2 trials; 438 participants). None of the trials reported health-related quality of life. Based on low-certainty evidence, a higher proportion of people receiving balloon tamponade plus sclerotherapy had more serious adverse events than those receiving only sclerotherapy (OR 4.23, 95% CrI 1.22 to 17.80; direct estimate; 1 RCT; 60 participants). Based on moderate-certainty evidence, people receiving vasopressin analogues alone and those receiving variceal band ligation had fewer adverse events than those receiving only sclerotherapy (rate ratio 0.59, 95% CrI 0.35 to 0.96; network estimate; direct comparison: 1 RCT; 219 participants; and rate ratio 0.40, 95% CrI 0.21 to 0.74; network estimate; direct comparison: 1 RCT; 77 participants; respectively). Based on low-certainty evidence, the proportion of people who developed symptomatic rebleed was smaller in people who received sclerotherapy plus somatostatin analogues than those receiving only sclerotherapy (OR 0.21, 95% CrI 0.03 to 0.94; direct estimate; 1 RCT; 105 participants). The evidence suggests considerable uncertainty about the effect of the interventions in the remaining comparisons where sclerotherapy was the control intervention. AUTHORS' CONCLUSIONS Based on moderate-certainty evidence, somatostatin analogues alone and vasopressin analogues alone (with supportive therapy) probably result in increased mortality, compared to endoscopic sclerotherapy. Based on moderate-certainty evidence, vasopressin analogues alone and band ligation alone probably result in fewer adverse events compared to endoscopic sclerotherapy. Based on low-certainty evidence, balloon tamponade plus sclerotherapy may result in large increases in serious adverse events compared to sclerotherapy. Based on low-certainty evidence, sclerotherapy plus somatostatin analogues may result in large decreases in symptomatic rebleed compared to sclerotherapy. In the remaining comparisons, the evidence indicates considerable uncertainty about the effects of the interventions, compared to sclerotherapy.
Intravenous iron supplementation after liver surgery: Impact on anemia, iron, and hepcidin levels-a randomized controlled trial
BACKGROUND Anemia is a recognized risk factor for perioperative related morbidity and mortality and is frequently reported in liver surgeries with an estimated incidence of 32%. We aim to assess the impact of intravenous iron administration in the immediate postoperative period on anemia and iron status as well as to determine the kinetics of hepcidin after liver surgery. METHODS The HepciFer trial, a randomized controlled trial, included 50 patients undergoing liver surgery. In accordance with the randomization process, patients received either ferric carboxymaltose (15 mg/kg, maximum 1 g) or placebo 4 hours after surgery. RESULTS The mean hemoglobin level, 7 days after surgery, did not differ significantly between the intervention and control group (11.1 ± 1.8 g/dL and 10.4 ± 1.6 g/dL, respectively) with a mean difference of +0.7 g/dL ([95% confidence interval, -0.3 to +1.7], P = .173). Within patients receiving intravenous iron supplementation, none presented biological signs of functional iron deficiency. Hepcidin levels remained significantly higher during the observation period in the intervention group. Inflammatory biomarkers, red blood cells transfusion rate and hospital duration of stay were similar between groups. CONCLUSION Intravenous ferric carboxymaltose administration did not result in a significant increase of hemoglobin levels 7 days after surgery. However, this study suggests that intravenous iron supplementation in the immediate postoperative settings prevents functional iron deficiency. Intravenous iron supplementation overcame the hepcidin-mediated blockade of iron absorption and should be considered as the preferred route of administration in the postoperative period.