San Miguel D Tucuman, Argentina

PBM as Strategy to CABG Anemic Patients Bypass Graft (CABG)

Anemia increases the risk of postoperative complications and mortality in patients undergoing coronary artery bypass grafting (CABG). In addition, the use of blood transfusions during cardiac surgery is associated with adverse effects and unfavorable outcomes. To reduce the need for transfusions and improve post-operative results, erythropoietin is used as part of Patient Blood Management (PBM). In anemic patients undergoing CABG, the use of Erythropoietin (EPO) can eliminate the need for blood components during and after surgery, as well as reduce adverse events and inflammation. The objectives of the proposed study are to reduce or eliminate the number of transfusions in the intraoperative and postoperative context by means of a Patient Blood Management (PBM) anemia treatment protocol for anemic patients who will undergo Coronary Artery Bypass Graft Surgery (CABG). The proposed study is a prospective, non-controlled interventional study to be carried out with anemic patients awaiting CABG surgery at Hospital São Paulo. There will be three groups of 40 participants each: Control Group (CG) of non-anemic individuals preoperatively; Non- PBM Group (NPBMG) of anemic individuals preoperatively and treated with blood components according to need; PBM Group (GPBM) of anemic individuals preoperatively and treated with EPO. The following parameters will be compared: length of postoperative hospital stay; mortality; postoperative cardiovascular events: clinical stroke, perioperative infarction, surgical reoperation due to bleeding; non- cardiovascular events: surgical site-associated infection and acute renal dysfunction; time in postoperative intensive care; time on mechanical ventilation; need for vasoactive drug use; inflammatory process and intra- and postoperative cardiac cell death. Confounding factors such as demographic and clinical parameters will be included in the analysis. It is expected that the GPBM will obtain the best results in relation to the GNPBM, similar to or better than the CG.

The Effect of Erythropoietin on Alveolar Fluid Clearance in Patients With Acute Respiratory Distress Syndrome

This study was designed as a double-blind, randomized controlled trial. Neither the subject nor the investigator knew the allocation of treatment drugs. Subjects signed the informed consent form, completed all screening assessments, and were randomized in the order of screening eligibility after screening eligibility. The investigator or designee generated the corresponding case number and drug number using a simple randomization method. Information about the subject's trial product allocation was placed in an emergency envelope and retained by the investigator for use in an emergency. Randomised subjects who withdraw from the clinical trial for any reason, regardless of whether they have taken the trial medication, will retain their case number and medication number and will not be allowed to re-enter the trial. The investigator participating in this trial is a clinician with appropriate experience, who can make treatment decision based on the clinical response and laboratory test results of the subject. The specific process of the study is as follows: 1. The subjects of this study were patients with ARDS admitted to ICU. 2. After signing the informed consent form, complete medical history collection, vital signs and detailed physical examination will be performed. Patients meeting the inclusion criteria but not meeting the exclusion criteria will be randomized into the study. 3. Patients with ARDS who met the inclusion criteria were connected to PiCCO, randomly assigned to the following two groups, and monitored continuously for 3 days. Group A: Erythropoietin, 40000 IU, single intravenous injection. Group B: 0.9%NaCl group, with the same volume as group A, single intravenous injection. 4. The baseline values of extravascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) were monitored by PiCCO after recording the general conditions of the subjects included in the study before intervention. After EPO or 0.9% NaCl intervention, EVLWI and PVPI at 0, 6, 12, 24, 48 and 72h after EPO or normal saline administration, and blood gas analysis, CRP, PCT, blood routine, inflammatory factors (TNF-a,IL-6,IL-8,IL-1β), endothelial cell injury marker (s-ICAM-1), alveolar epithelial cell injury marker (sRAGE,SP-D) and other laboratory indicators and clinical indicators such as peak airway pressure, mean airway pressure and positive end-expiratory pressure (PEEP) at 0, 1, 2 and 3 days after administration were recorded. The hospital survival rate and 28-day survival rate were compared between the experimental group and the control group.

Erythropoietin for Neonatal Encephalopathy in LMIC (EMBRACE Trial)

The burden of neonatal encephalopathy is far higher in low and middle-income countries. Recently, the Hypothermia for Encephalopathy in Low and Middle-Income Countries Trial (HELIX) study concluded cooling therapy did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries. In fact, the results found that cooling therapy significantly increased death alone. This warrants exploration of the efficacy of other treatment adjuncts for these settings. One medication with potential for monotherapy is Erythropoietin. Erythropoietin is an erythropoiesis stimulating cytokine used for the treatment of anaemia. It is a Food and Drug Administration (FDA) approved drug that is widely used for treatment of anaemia including premature babies and has extensive safety profile in newborn babies. Erythropoietin is also produced by neurons and glia in the hippocampus, internal capsule, cortex, and midbrain in response to hypoxia. More recently, erythropoietin has been reported as having anti-apoptotic, anti-inflammatory and anti-oxidative effects, making it a prime neuroprotective candidate. It also reduces free iron accumulation which occurs due to hypoxic ischemia by inducing erythropoiesis, which promotes neurogenesis. Extensive preclinical small and large animal models have demonstrated neuroprotective and neuro reparative effects of Erythropoietin when used as monotherapy. A number of small randomised controlled trials have been reported from low and middle-income countries. A systematic review and meta-analysis of Erythropoietin monotherapy in babies with neonatal encephalopathy in LMIC showed pooled data including a total of 348 babies from 5 clinical trials in LMIC suggest 40% relative risk reduction (Risk Ratio 0.62 (95% Confidence Intervals (CI) 0.40 to 0.98) in death or disability at 18 months with Erythropoietin, compared with placebo. None of these clinical trials have reported any serious adverse events of Erythropoietin monotherapy. Erythropoietin dose used in these trials varied from 300U/kg to 2500U/kg, single dose to a maximum of two weeks of duration starting within 24 hours after birth. The largest of these trials, reported from China have used a low dose (500U/kg) on alternate days for two weeks. This trial recruited 153 babies with moderate or severe encephalopathy and reported that Erythropoietin significantly reduced death or disability at 18 months. More recently, another randomised controlled trial of Erythropoietin involving 62 normothermic babies with moderate or severe neonatal encephalopathy has been reported from Government Medical College, Aurangabad in India. The investigators used an Erythropoietin dose of 500 U/kg alternate days for 10 days starting within 24 hours. Neonatal mortality was significantly lower (39%; 12/31) in the Erythropoietin group compared with the placebo group (71%; 22/31) (p=0.01). No adverse events were reported in the Erythropoietin group. The EMBRACE trial is a phase III, multi-country, double-blinded, placebo-controlled randomised controlled trial of Erythropoietin versus sham injection (placebo) in babies with neonatal encephalopathy in low and middle-income countries. All clinical and study team except for the nurse administering the trial drug will be masked to the intervention. The investigators plan to randomise 504 babies in this trial. The dosing regimen will be IV/Sub cutaneous Erythropoietin 500unit/kg within 6 hours of birth and then daily until 8 days. In total, there will be 9 doses. Body temperature of all babies will be monitored 4 hourly for the first three days after birth and normothermia (36.0-37.5°C) will be maintained as a part of the usual care at these hospitals with an algorithm to prevent/treat hyperthermia. Magnetic resonance biomarkers including spectroscopy and diffusion tensor imaging will be acquired between 1 to 2 weeks of age in all recruited babies. The MR scanners and sequences at each site will be harmonised prior to recruitment. The trial will have an 18 month recruitment period, a 18 month follow-up period, and 5 months for data analysis and write up. A pilot study (external pilot) of 50 babies will be done prior to the start of the EMBRACE trial (Jan 2023 to April 2023) but these patients will not be included in the main trial. Minor updates to the trial protocol may be made after the completion of the pilot trial.

Evaluation of Erythropoietin on Alveolar Ridge Preservation

II. Aim of the study: To assess the efficiency of Erythropoietin in alveolar ridge preservation. 1. Objectives: Primary objective: Dimensional changes of the ridge clinically and radiographically. Secondary objective: 1. Postoperative pain. 2. Postoperative wound healing. 3. Histomorphometric analysis of the bone regeneration patterns of the extraction sockets. III. Materials and Methods 1. Study design and patient selection: It is a randomized controlled clinical trial. Patients will be selected from the outpatient clinic of the Department of Oral Medicine and Periodontology-Ain Shams University and the British University of Egypt. All patients will sign an informed consent about the details of the surgery according to the Ethical Committee Ain Shams University. 2. Sample size: The sample size was estimated based on assuming confidence level= 95% and study power= 80%. Pandya et al. [29] reported that the Collagen percentage was 2.1%±0.6% in EPO treated sockets while it was 1%±0.6% in non-treated sockets, the average Standard deviation was 0.6%n. The minimum sample size was calculated to be 5 extraction sockets per group. This was increased to 7 sockets to make up for lost to follow-up cases. The total sample size = number of groups × number per group= 3×7= 21 sockets. The sample size was collected by G power 3.0.10. 3. Eligibility criteria: Inclusion criteria: 1. Age range (18-40). 2. Hopeless teeth indicated for extraction such as root fractures, caries, internal root resorption, external root resorption, endodontic failures. 3. Systemically free patients using Cornell Medical Index-Health Questionnaire [36]. 4. Patients diagnosed with intact surrounding alveolar bone (socket type I) [37]. 5. Maxillary anterior teeth and/or premolars indicated for extraction. 6. Enough zone of keratinized tissue (≥2 mm). Exclusion criteria: 1. Smokers 2. Occlusal trauma at the site of the graft 3. Pregnancy and lactation 4. Bad compliance with the plaque control instructions following initial therapy. 4. Interventions: Pre-surgical phase: Patients will be initially examined. All patients will receive oral hygiene instructions using roll technique with a soft-bristled toothbrush and interdental floss, and phase I therapy using an ultrasonic device if necessary. At baseline, intraoral periapical radiographs, clinical periodontal measurements including plaque Index [38] , bleeding on probing (BOP) [38], probing depth (PD) [38], and clinical attachment level (CAL) [38] will be recorded at teeth adjacent to the extraction socket area using a UNC periodontal probe [38]. Impressions will be taken using Alginate impression material before the extraction day. Diagnostic casts will be made for the fabrication of a customized stent to standardize the measurements of marginal crestal bone levels at baseline and 4 months post-extraction [39]. Surgical preparation of Extraction socket: 1. After anesthetizing the surgical field with local anesthesia (4% Articaine , 1: 100 000 epinephrine), An atraumatic extraction procedure will be performed by cutting the periodontal ligaments gently to preserve the buccal plate of bone using periotome and forceps. 2. The socket will be irrigated with saline and curetted from any granulation tissue following extraction then the buccal and lingual plate of bone will be checked for absence of any fenestration or dehiscence using UNC periodontal probe. 3. Computer-generated randomization will be used to randomly divide the sockets into three groups. Group I: Extraction sockets filled with CS/ β-GP/gelatin hydrogels loaded EPO until the crestal level. Group II: extraction sockets filled with CS/ β-GP/gelatin hydrogels alone until the crestal level. Group III: Natural healing socket (control group). 4. In the three groups, the flaps will be sutured with criss-cross horizontal mattress technique with polypropylene 5-0 . Implant placement Surgery Patients will return for a follow-up examination at 4 months and implant placement. 1. After anesthetizing the surgical field with local anesthesia (4% Articaine, 1: 100 000 epinephrine), a papillary sparing will be incised using Bard-Parker scalpel carrying blade number 15C; a crestal flap will be elevated by Molt number 5 mucoperiosteal elevator. 2. The first drill will be a trephine bur to collect a core bone biopsy; the collected bone will be preserved in a diluted formaldehyde solution to fix the sample to perform the histomorphometry. 3. Sequential twist drills will be used until the final drill following the implant manufacturer instructions. 4. In the three groups, the flaps will be sutured with criss-cross horizontal mattress technique suture type using 5-0 polypropylene sutures. Postoperative care instruction and medication of both surgeries: - Patients will be instructed to rinse twice daily with a 0.12% chlorhexidine gluconate solution for 2 weeks, and the sutures will be removed after 2 weeks later. - Analgesic and antibiotic drugs were prescribed after the surgical procedure. Ibobrufen (400 mg.) will be prescribed upon patient's need with a maximum dose 2400mg per day for pain relief [40]. Amoxicillin (500 mg.) every 12 hours for 7 days or clindamycin (300 mg.) every 8 hours for 5 days, for patients having a penicillin allergy, three times per day, for infection control [41]. 5. Assessment: A) Clinical assessment: 1. Dimensional changes width changes will be measured using bone caliper at baseline immediately following tooth extraction and 4 months postoperatively [42]. 2. Postoperative Pain level Pain score will be reported by the patient directly through Visual Analogue Scale score (between 0 and 10. 0: no pain, 1: minimal pain, 5: moderate pain, 10: severe pain) VAS will be recorded at day 14 post-extraction [43]. Post-operative pain was assessed indirectly by mean consumption of analgesics for 7 days postoperatively, will be recorded in milligrams[44]. 3. Postoperative wound healing Wound healing will be recorded the 1st and 2 weeks postoperatively through Landry Wound Healing Index (LWHI) [45] which evaluates the extraction site based on tissue color, response to touch, the marginality of the incision line, and extent of the area. The rating is from 1 = very poor to 5 = excellent. B) Radiographic assessment: Dimensional changes will be measured using Cone Beam computed Tomography (CBCT) at baseline immediately following tooth extraction and 4 months postoperatively [42]. C) Histomorphometric assessment: Histological and histomorphometric assessment of bone regeneration patterns of core biopsy harvested at the re-entry surgery for implant placement 4 months post extraction using H&E stains to evaluate bone trabeculae and Modified Masson Trichrome to evaluate bone maturity[46].

Effect of the Combined Programme on Perioperative Anaemia（CPPA）

Study of Erythropoietin in Newborns and Children

The Effect of Combined Iron Protocols on Perioperative Allogeneic Transfusion

1. Hypothesis:The combined protocol of preoperative sucrose iron, human erythropoietin, and vitamin C will demonstrate superiority in reducing perioperative allogeneic red blood cell (RBC) transfusion volume compared to standard care in patients with iron deficiency anemia undergoing major cardiac surgery with cardiopulmonary bypass. 2. Interventions 2.1.Experimental group: Patients in the experimental group will receive a combination therapy consisting of intravenous sucrose iron (200 mg), subcutaneous recombinant human erythropoietin (150 IU/kg), and intravenous vitamin C (2 g), administered once daily for three consecutive days within the week prior to surgery. 2.2.Control group: Routine perioperative management based on clinical judgment, including observation, monitoring, and standard nursing practices. 3. Primary endpoint: Total volume of allogeneic RBC transfusion (units) from surgery initiation to postoperative day 5. 4. Stratification in randomization: Stratification factors include types of surgery, preoperative baseline hemoglobin level. 5. Follow-up time important points include: baseline upon hospital admission, the morning of surgery, postoperative day 1, postoperative day 5, at discharge, 30 ± 7 days after surgery, and 90 ± 7 days after surgery. 6. All perioperative transfusion decisions will follow standardized restrictive transfusion thresholds. When the patient's hemoglobin concentration falls below the threshold of 70 g/L during surgery or ICU monitoring, or below 70-80 g/L in the general ward, and/or when signs of anemia or hemodynamic instability are present-including shock, severe arrhythmias, respiratory distress, heart rate >120 beats/min, systolic blood pressure (SBP) <80 mmHg, mean arterial pressure (MAP) <55-60 mmHg, or a reduction in SBP or MAP exceeding 25% from baseline-these findings may indicate significant hypovolemia and warrant consideration of transfusion intervention.

NAION Treatment With Oral Prednisolone and Erythropoietin Injection

Perioperative Blood Conservation: Role of Combined Iron Supplementation Protocols in Reducing Allogeneic Transfusion

1. Hypothesis:The combined protocol of preoperative sucrose iron, human erythropoietin, and vitamin C will demonstrate superiority in reducing perioperative allogeneic red blood cell (RBC) transfusion volume compared to standard care in patients with iron deficiency anemia undergoing major cardiac surgery with cardiopulmonary bypass. 2. Interventions 2.1.Experimental group: Patients in the experimental group will receive a combination therapy consisting of intravenous sucrose iron (200 mg), subcutaneous recombinant human erythropoietin (150 IU/kg), and intravenous vitamin C (2 g), administered once daily for three consecutive days within the week prior to surgery. All perioperative transfusion decisions will follow standardized restrictive transfusion thresholds. 2.2.Control group: Routine perioperative management based on clinical judgment, including observation, monitoring, and standard nursing practices. 3. Primary endpoint: Total volume of allogeneic RBC transfusion (units) from surgery initiation to postoperative day 5. 4. Stratification in randomization: Stratification factors include types of surgery, preoperative baseline hemoglobin level. 5. Outcome assessors will be blinded to group allocation to reduce assessment bias. 6. Follow-up time points include: baseline upon hospital admission, the morning of surgery, postoperative day 1, postoperative day 5, at discharge, 30 ± 7 days after surgery, and 90 ± 7 days after surgery. 7. When the patient's hemoglobin concentration falls below the threshold of 70 g/L during surgery or ICU monitoring, or below 70-80 g/L in the general ward, and/or when signs of anemia or hemodynamic instability are present-including shock, severe arrhythmias, respiratory distress, heart rate >120 beats/min, systolic blood pressure (SBP) <80 mmHg, mean arterial pressure (MAP) <55-60 mmHg, or a reduction in SBP or MAP exceeding 25% from baseline-these findings may indicate significant hypovolemia and warrant consideration of transfusion intervention.

Prospective Evaluation of Diagnosis and Treatment of Patients With Autoimmune Cytopenias Including Autoimmune Hemolytic Anemia, Immune Thrombocytopenia, and Chronic Idiopathic/Autoimmune Neutropenia

This observational study will characterize the diagnostic and therapeutic management of autoimmune cytopenias including autoimmune hemolytic anemia, immune thrombocytopenia, and chronic idiopathic/autoimmune neutropenia to evaluate predictors of outcome. Additionally, a subgroup of patients with myelodysplastic syndromes (diagnosed according to current WHO 5th edition 2022) will be included to evaluate the presence of autoimmune activation, and red cell metabolism.