Low Dose Intravenous Ascorbic Acid for Erythropoietin-Hyporesponsive Anemia in Diabetic Hemodialysis Patients with Iron Overload

Background.?Recent report demonstrates that inadequate iron mobilization and defective iron utilization may cause recombinant erythropoieitin (rEPO) hyporesponsiveness in hemodialysis (HD) patients with iron overload. The effect of intravenous ascorbic acid (IVAA) in HD patients selected on the basis of iron overload and EPO resistance also has been proven. However, it is uncertain whether IVAA still works in diabetic ESRD patients with hyperferritinemia. Therefore, the aim of this study focusing on diabetic ESRD patients was to analyze the potential effect of low dose IVAA on improvement of anemia and erythropoiesis-related parameters when compared with control period. Patients and Method.?This study consisted of 22 chronic hemodialysis patients with type II diabetes in a single dialysis unit. In studies of this type, all eligible patients are followed up, but the primary comparison is still between different sequentially treatment including control period and post-IVAA period in same patients. IVAA patients received ascorbic acid, 100 mg each administered intravenously three times per week for eight weeks of treatment and four months of post-treatment follow-up. Results.?The demographic characteristics of 22 diabetic uremic patients show that mean age is 63.6 ± 10.2 years old. The ratio of sex (M/F) = 10/12. Mean duration of HD is 46.7 ± 33.2 months. As for the urea kinetic study between these two periods including KT/V, nPCR, and URR, there is no significantly different. As for anemia-related parameters, Hb and Hct increased significantly in post-IVAA period after 3 months compared with control period, while MCV did not increase significantly. Serum ferritin significantly decreased at study completion. The same situation is for iron. As for TS, it significantly increased at one month and further markedly increased at subsequent three months. Conclusion.?This study has demonstrated that short-term low dose IVAA therapy can facilitate iron release from reticuloendothelial system but also increase iron utilization in diabetic hemodialysis patients with iron overload. Therefore, IVAA is a potential adjuvant therapy to treat erythropoeitin-hyporesponsive anemia in iron-overloaded patients.     

低剂量糖皮质激素对重度马兜铃酸肾病患者病情进展的作用

目的：观察低剂量糖皮质激素对重度慢性马兜铃酸肾病患者病情进展的影响。方法：选择北京协和医院肾内科重度慢性马兜铃酸肾病患者37例,根据治疗方案分为两组：激素治疗组（非透析治疗＋低剂量糖皮质激素治疗,23例）和对照组（单纯非透析治疗,14例）,两组患者一般资料及血生化指标差异无统计学意义。分别观察患者初始、3月、6月、9月、12月的血肌酐水平及其变化程度,及随诊过程中血压、血红蛋白、血生化指标的变化,同时观察治疗的不良反应。结果：对照组患者随诊过程中血肌酐逐渐升高,6月、9月、12月的血肌酐值较基础水平差异有统计学意义（P〈0.05）;而激素治疗组血肌酐水平在随诊3～6月持续下降,较基础水平差异有统计学意义（P〈0.05）,9月、12月略有回升,但和治疗前相比差异无统计学意义（P〉0.05）。对照组患者在随诊至1年时,绝大多数肾功能恶化明显,而激素治疗组则绝大多数维持稳定或好转。两组患者在随诊过程中绝大多数无明显不适主诉,血生化指标、血压、血红蛋白等基本维持稳定。该治疗方法安全性较好,多数患者可耐受。结论：低剂量糖皮质激素可延缓重度慢性马兜铃酸肾病患者肾功能的进展。     

Correction of Hemodialysis Anemia is Associated with Significant Increase in Serum Concentration of IGF-I in Patients Treated with Erythropoietin: A Randomized Controlled Study

Background: The effect of erythropoietin (EPO) therapy on the serum level of IGF-I among hemodialysis patients is debated. The aim of this study is to study the effect of EPO on the erythropoiesis and the change of serum level of IGF-I among adequately hemodialyzed patients. Patients and methods: Forty patients (25 males and 15 females) who had an adequate level of both hemodialysis and nutrition were randomly allocated into two equal groups. Besides parenteral iron, the first group of patients received a conventional EPO dose regimen of 2000 U subcutaneously (SC) thrice weekly, the second group of patients remained on parenteral iron and ranked as a control group. The patients were subjected to thorough laboratory investigations. IGF-I concentration was measured before and at the end of the study. Results. Both groups were comparable in their demographic, laboratory, dialysis level, and nutritional status. There was no statistical differences in hemoglobin, hematocrit %, iron store indices and serum level of IGF-I at the study entry. We found a significant rise of both hemoglobin and hematocrit as well as IGF-I serum level in the EPO group at the end of the study in comparison to their values at the starting points in comparison to the control group (P< 0.001). Conclusion: Erythropoietin therapy enhances erythropoiesis and modulates the serum concentration of IGF-I.     

Serum Biomarkers of Iron Stores Are Associated with Increased Risk of All-Cause Mortality and Cardiovascular Events in Nondialysis CKD Patients,with or without Anemia

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Treatment of Iron Deficiency Anemia in Orthopedic Surgery with Intravenous Iron: Efficacy and Limits: A Prospective Study

Background: Preoperative anemia is frequent in patients undergoing orthopedic surgery. The purpose of this study was to assess the preoperative increase of hemoglobin in iron deficiency anemia patients treated with intravenous iron.

Methods: After obtaining written informed consent, 20 patients with iron deficiency anemia received 900 mg intravenous iron sucrose over 10 days starting 4 weeks before surgery. Changes of hemoglobin and iron status were measured over 4 weeks and at discharge. In the last 11 patients, endogenous erythropoietin was also measured. Data were analyzed using the Friedman test followed by pairwise Wilcoxon signed rank tests with Bonferroni correction.

Results: Hemoglobin increased significantly (P < 0.0001) after intravenous iron treatment. Overall, the mean maximum increase was 1.0 +/- 0.6 g/dl (range, 0.2-2.2 g/dl). Ferritin increased from 78 +/- 70 to 428 +/- 191 [mu]g/l (P = 0.0001), ferritin index decreased from 2.7 +/- 2.4 to 1.5 +/- 1.0 (P = 0.0001), and soluble transferrin receptor decreased from 4.1 +/- 2.3 mg/l to 3.7 +/- 2.3 mg/l (P = 0.049), whereas transferrin saturation (20.5 +/- 9.0 to 22.9 +/- 9.0%) and serum iron (13.3 +/- 4.6 to 13.1 +/- 4.5 [mu]m) did not change significantly after intravenous iron treatment. Endogenous erythropoietin decreased from 261 +/- 130 pg/ml to 190 +/- 49 pg/ml 2 weeks after intravenous iron treatment (P = 0.050, not significant after Bonferroni correction). No adverse events related to intravenous iron were observed. The maximum increase of hemoglobin was observed 2 weeks after the start of intravenous iron treatment, indicating that administration of intravenous iron 2-3 weeks before surgery may be optimal.     

Preliminary Screening Results of Fabry Disease in Kidney Transplantation Patients: A Single-Center Study

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by the deficiency of alfa-galactosidase A (AGALA) and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of female patients. FD is underdiagnosed or even misdiagnosed in patients undergoing kidney transplantation. We initiated a selective screening study for FD among kidney transplant patients in our center. In this study, 1095 male and female patients were included. Dried blood samples on Guthrie papers were used to analyze galactosidase A enzyme for male patients. Genetic analyses were performed in all female and male patients with low enzyme activity. In total, 648 female and 447 male patients with functioning grafts were evaluated. Among 1095 patients, 5 male patients had AGALA activity below threshold and 3 female patients had galactosidase alpha gene DNA variations. One male patient had a disease-causing mutation. The other 4 patients had polymorphisms causing low enzyme activity. All the 3 female patients had mutations that were associated with FD according to Human Gene Mutation Database (ID: CM025441). In contrast, these mutations were reported as unknown clinical significance in Clinvar (rs149391489). The patients with clinical findings suggesting FD were planned to be analyzed for Lyso Gb3. In our selective screening study, 8 variations were found among 1095 kidney transplantation patients, which needs further investigation to determine causes of FD. Clinical findings, physical examination, and family history are also necessary to evaluate the genetic changes as a mutation in this selected population.     

Oral Zinc as a Novel Adjuvant and Sparing Therapy for Systemic Isotretinoin in Acne Vulgaris: A Preliminary Comparative Study

BackgroundSystemic isotretinoin is the most effective treatment for acne vulgaris (AV). However, numerous side effects are associated with isotretinoin. Oral zinc has a better safety profile and has been used to treat AV with variable results. ObjectiveWe sought to evaluate the safety and efficacy of combining oral zinc to low-dose systemic isotretinoin in AV patients.MethodsSixty AV patients were divided into two groups. Group A received oral zinc sulfate plus low-dose isotretinoin and Group B received the standard isotretinoin dosage. At each visit acne severity, photos, side effects, and patient-reported satisfaction were recorded.ResultsIn the two groups, no significant difference in reduction of lesion count and Global Acne Grading System scores. The frequency of treatment-related side effects was (20%) in Group A and (76.7%) in Group B. Furthermore, there was no difference regarding the relapse rates between both groups (p>0.05). Finally, the patients’ satisfaction rates did not differ between the two groups.ConclusionOral zinc plus low-dose isotretinoin resulted in satisfactory improvement in AV patients with fewer side effects. Further studies are recommended to compare the efficacy of other zinc preparations if combined with systemic isotretinoin at different concentrations.     

Effects of Perioperative Oral Amantadine on Postoperative Pain and Morphine Consumption in Patients after Radical Prostatectomy: Results of a Preliminary Study

Background: Amantadine is known to be a noncompetitive N-methyl-d-aspartate receptor antagonist and may be useful in preventing postoperative central sensitization, acute opioid tolerance, and opioid-induced hyperalgesia, thereby decreasing pain and analgesic requirements. The aim of this pilot study was to evaluate the effects of perioperative oral amantadine on postoperative pain and analgesic consumption.

Methods: Twenty-four patients scheduled to undergo radical prostatectomy were given oral amantadine before and after surgery in a randomized, double-blind, placebo-controlled manner. After surgery, patients received intravenous patient-controlled analgesia with morphine for 48 h. Wound pain intensity, sensitivity to mechanical pressure around the surgical wound, and incidence of bladder spasm pain were assessed. Blood samples were drawn for analysis of amantadine, morphine, and the morphine metabolites. Adverse effects and patient satisfaction were assessed.

Results: The cumulative morphine consumption was significantly lower in the amantadine group at all time points (except at 48 h), amounting to a 32% reduction over the 48-h period. Forty-eight hours after surgery, visual analog pain scores to pressure applied near the wound were significantly lower in the amantadine group than in the placebo group. In addition, the number of patients reporting bladder spasm pain was significantly lower in the amantadine group. Plasma concentration of morphine-3-glucuronide was significantly lower at the end of surgery in the amantadine group. Pharmacokinetic analyses showed that the plasma clearance of morphine at 22-24 h after surgery was also significantly lower in the amantadine group.     

In-office Painless Aminolevulinic Acid Photodynamic Therapy: A Proof of Concept Study and Clinical Experience in More Than 100 Patients

Objective: To evaluate the efficacy, safety, and pain of in-office “painless” aminolevulinic acid photodynamic therapy aimed at decreasing treatment-associated pain in patients undergoing removal of actinic keratoses. Design: Prospective split-face study comparing short aminolevulinic acid incubation times of 15 minutes followed by extended exposure (60 minutes) of continuous blue light versus conventional aminolevulinic acid photodynamic therapy. Prospective assessment of pain in patients undergoing in-office “painless” aminolevulinic acid photodynamic therapy. Setting: Clinical practice office. Participants: Three patients with actinic keratoses participated in the split-face study and 101 in the pain assessment study. Measurements: Evaluations in the split-face study included removal of actinic keratoses, skin temperature, and pain measured on a 10-point visual analog scale. Pain was assessed using the visual analog scale in the pain assessment study. Results: In the split-face study, in-office “painless” aminolevulinic acid photodynamic therapy resulted in a 52-percent reduction in lesions versus 44 percent for conventional aminolevulinic acid photodynamic therapy. Maximum pain scores of in-office “painless” aminolevulinic acid photodynamic therapy were all 0 at each time point, and the average score for conventional aminolevulinic acid photodynamic therapy was 7. Baseline skin temperatures increased from a baseline of 29 to 32°C to 34 to 35°C by minute 10 of blue light activation on both sides of the face. Results from the pain assessment study indicated no or minimal (scores 0-2) pain in nearly all patients who received in-office “painless” aminolevulinic acid photodynamic therapy as monotherapy or in combination with 5-fluoruacil or imiquimod used as pretreatments. Conclusions: In-office “painless” aminolevulinic acid photodynamic therapy appears to be effective for removing actinic keratoses and is associated with little or no pain in nearly all patients. This procedure should be evaluated in large-scale controlled trials.Actinic keratoses (AKs) are part of the spectrum between photodamaged skin and invasive squamous cell carcinoma (SCC).1-5 They are a major health care concern because of their increasing prevalence worldwide,6-10 economic impact,9-11 and decreased quality of life of affected individuals.10,12 Results from observational studies have indicated that AKs evolve into primary invasive SCC or in situ SCC at a rate ranging between 1/1,000 lesions per year13 to 0.60 percent at one year and 2.57 percent at four years.14 It is recommended that all AKs be treated because it is not currently possible to predict which will evolve into invasive SCC.15-17A variety of therapeutic modalities are used to treat AKs.1,18-20 Focally destructive therapies, such as cryotherapy,21 electrodessication and curettage,22 and shave excision23 are most often used to treat individual AKs. Large areas of actinically damaged skin require “field therapies” such as 5-fluoruacil (5-FU),24-26 imiquimod,26-30 diclofenac gel,31-33 ingenol mebutate,34,36 aminolevulinic acid photodynamic therapy (ALA PDT)35,37 and methyl-aminolevulinic acid PDT (MAL PDT),38,39 chemical peels,40 dermabrasion,41-43 and laser resurfacing.44,45PDT produces reactive oxygen species that result in tissue destruction46 and it destroys AKs because of the preferential accumulation of the photosensitizing molecule, protoporphyrin IX (PpIX) within AKs following topical application of pro-drugs ALA47 and MAL.48 PDT is safe and effective for treatment of large surface skin areas, provides good adherence because it is performed under supervision in a clinic setting, has minimal post-treatment downtime versus other AK field therapies, and produces good-to-excellent cosmetic outcomes with minimal potential for scarring.49,50 PDT also has several drawbacks, most notably pain during the first few minutes of light activation phase.51-53 Nearly two-thirds of patients undergoing ALA PDT report this pain as “moderate-severe” following 1, 2, or 3-hour ALA incubations.54 Pain with PDT has been related to cellular destruction and inflammation and possibly a direct effect of PDT on nerve fibers55-57; it has now become clear that PDT-related pain is associated with PpIX tissue accumulation based on fluorescence and the fluence rate of the activating light source.58 Topical anesthetics,55 cooling devices,59-61 nerve blockade,61,62 and treatment interruption63 have limited efficacy in managing PDT-related pain, which can lead to reluctance of patients to undergo future PDT treatments.A novel approach to minimizing discomfort during PDT, daylight-mediated PDT, uses a brief (30-minute) incubation period followed by 1.5 to 2.5 hours of daylight exposure.64-66 The shortened incubation period is designed to minimize PpIX build-up in the targeted tissue prior to daylight PpIX activation, and photobleaching prevents further buildup of PpIX and minimizes patient discomfort.67,68 Limitations to daylight-mediated PDT include dependence on favorable weather conditions and patient adherence to the treatment protocol outside the clinic.65Based on the efficacy and improved tolerability of daylight-mediated PDT, an in-office painless (IOP) ALA PDT protocol was developed. It involves applying ALA topically to actinically damaged skin, incubating without occlusion for 15 minutes, and then 60 minutes of continuous blue light activation. This report summarizes results from a split-face comparison of IOP ALA PDT and a standard short (75 minute) ALA incubation protocol followed by the standard 1,000 seconds of blue light activation carried out in three patients, and assessment of pain associated with this treatment in 101 patients undergoing 121 treatments over a two-year time period. In the latter study, IOP ALA PDT was employed as either a full-face monotherapy or in combination with one week of prior treatment with 5% and 0.5% 5-FU and 3.75% and 5% imiquimod.     

Outcomes and Quality of Life after Platelet-rich Plasma Therapy in Patients with Recalcitrant Hindfoot and Ankle Diseases: A Preliminary Report of 12 Patients

The present study aimed to determine the outcomes and quality of life after platelet-rich plasma therapy in patients with chronic recalcitrant diseases of the hindfoot and ankle and to identify the crucial clinical variables. The records of 12 adult patients with diseases of the hindfoot and ankle were included in the present study. These patients had been treated with platelet-rich plasma from September 2010 to April 2011 after 3 to 6 months or more of conservative treatment had been unsuccessful. They had attended the follow-up visits, were consecutively enrolled, and retrospectively studied. A total of 3 mL of autologous platelet-rich plasma was injected under fluoroscopic or ultrasound guidance into the affected areas. All patients had been evaluated using visual analog scale foot and ankle scoring before treatment and at set intervals after treatment. According to their scores at the final follow-up visit (mean 16 months), the patients were allocated to the satisfactory (score ≥ 80; n = 8) and unsatisfactory (score < 80; n = 4) groups. The health-related quality of life was assessed using the Medical Outcomes Study short-form, 36-item survey at the final follow-up visit, because the study was retrospective, and the information was not available before treatment. The mean visual analog score at the final follow-up visit (79.71 ± 17.81) was significantly greater than the mean pretreatment score (57.89 ± 20.77; p = .002). Four patients (33%) had unsatisfactory results. The mean short-form, 36-item score for the satisfactory group (85.23 ± 11.30) was significantly greater than that (57.33 ± 12.91) of the unsatisfactory group (p = .003). No definitive factors influencing the outcome of this treatment were found. The substantial number of patients with an unsatisfactory outcome indicates that platelet-rich plasma injection might be an option but might not be a mainstay of nonoperative treatment of problematic conditions of the hindfoot and ankle. The actual benefit of this treatment, including the factors influencing its outcome, are still inconclusive.     

Effects of Middle Ear Packing with Collagen Polyvinylpyrrolidone and Hyaluronic Acid in Guinea Pigs

ABSTRACT

Objective: The aim of this study was to evaluate otoscopic and microscopic changes produced on the healthy mucosa of the middle ear (ME) and tympanic membrane (TM) of guinea pigs after packing with a collagen polyvinylpyrrolidone (CPVP) sponge soaked in hyaluronic acid (HA). Material and methods: In 24 guinea pigs, myringotomy on the right side was created and the ME was packed as follows: Group I (n = 6): Absorbable gelatin sponge (AGS) soaked in saline solution; Group II (n = 6): AGS sponge soaked in HA, Group III (n = 6): CPVP sponge soaked in saline solution, Group IV (n = 6): CPVP sponge soaked in HA. Four weeks after miringotomy, the ME and TM integrity and residual packing material were evaluated otoscopically. Histologically, we evaluated inflammatory changes on the ME mucosa. Results: All animals in Groups I and II showed residual packing material (p < .001 ANOVA, TUKEY). Histologically, more inflammation was observed in Groups I, II, and III than in Group IV (p < .001 ANOVA, TUKEY). Group IV showed greater fibroblastic reaction (p < .02, ANOVA, TUKEY) versus other groups. Conclusion: The CPVP sponge soaked in HA used as ME packing material is biocompatible and nontoxic, because it produces minimal inflammatory changes on the healthy mucosa of the ME and TM of guinea pigs. However, more research with injured mucosa is needed to validate its usefulness in otosurgery.     

Combination of Intravenous and Intra‐Articular Application of Tranexamic Acid and Epsilon‐Aminocaproic Acid in Primary Total Knee Arthroplasty: A Prospective Randomized Controlled Trial

ObjectiveThere were limited randomized controlled trials (RCTs) of epsilon‐aminocaproic acid (EACA) versus tranexamic acid (TXA) in total knee arthroplasty (TKA). The aim of the study was to compare the efficacy and safety of TXA and EACA in the combination of intravenous (IV) and intra‐articular (IA) administration on reducing blood loss in patients following primary TKA.MethodsFrom January 2020 to January 2021, a total of 181 patients undergoing a primary unilateral TKA were enrolled in this prospective randomized controlled trial. Patients in the TXA group (n = 90) received 20 mg/kg of intravenous TXA preoperatively, 1 g of intra‐articular TXA intraoperatively, and three doses of 20 mg/kg intravenous TXA at 0, 3, 6 h postoperatively. Patients in the EACA group (n = 91) received 120 mg/kg of intravenous EACA preoperatively, 2 g of intra‐articular EACA intraoperatively, and three doses of 40 mg/kg intravenous EACA at 0, 3, 6 h postoperatively. The primary outcomes were total blood loss (TBL), transfusion rates and drop of hemoglobin (HB) level. The secondary outcomes included postoperative hospital stays and postoperative complications. The chi‐square tests and Fisher''s exact tests were utilized to compare categorical variables, while the independent‐samples t‐tests and Mann–Whitney tests were used to compare continuous variables.ResultsThe patients who received TXA averaged less TBL than the patients who received EACA (831.83 ml vs 1065.49 ml, P = 0.015), and HB drop in TXA group was generally less than that of EACA group on postoperative day 1 and 3 (20.84 ± 9.48 g/L vs 24.99 ± 9.40 g/L, P = 0.004; 31.28 ± 11.19 vs 35.46 ± 12.26 g/L, P = 0.047). The length of postoperative stays in EACA group was 3.66 ± 0.81 day, which is longer than 2.62 ± 0.68 day in TXA group (P < 0.001). No transfusions were required in either group. The risk of nausea and vomiting in TXA group was significantly higher than that in EACA group (11/90 vs 0/91, P < 0.01).ConclusionAlthough the TBL and HB drop were slightly greater in EACA group, these results were not clinically important, given that no transfusions were required. EACA could be an alternative to TXA, especially for patients with severe nausea and vomiting after using TXA postoperatively. Further studies are needed to adjust dosage of EACA to make better comparison of the two drugs.     

青少年特发性脊柱侧凸矫形术后多次口服与静脉应用氨甲环酸对于降低术后失血量及输血率的回顾性研究

目的 评估术后多次应用氨甲环酸能否有效降低青少年特发性脊柱侧凸（adolescent idiopathic scoliosis,AIS）病人术后的失血量以及输血率,以及口服和静脉给药是否具有等效性。方法 回顾性分析2018年1月至2021年1月于我院行矫形手术的AIS病人的临床资料,筛选出术中采取同一给药方案给予氨甲环酸的病人：切皮前静脉滴注50 mg/kg氨甲环酸并以10 mg/kg/h持续滴注至手术结束。根据不同的术后给药方案将其分为口服组（于术后4、10、16 h口服1 g氨甲环酸）,静脉组（于术后6、12、18 h静滴0.5 g氨甲环酸）以及对照组（术后不给予氨甲环酸）。共有214例病人符合纳入标准。为提高组间可比性,本研究按口服组人数配平每组样本量,最终每组各纳入50例病人。记录并比较三组病人的术后失血量、输血率、引流量、凝血指标以及并发症等。结果 口服组、静脉组的术后失血量［（961.2±311.2） mL、（974.5±392.1） mL］和输血率（12%、14%）均显著低于对照组［（1 451.2±408.1） mL、36%］,差异有统计学意义（P＜0.05）。此外,口服组、静脉组的术后引流量、最大血红蛋白丢失值显著低于对照组,血红蛋白最低值显著高于对照组,差异有统计学意义（P＜0.05）,但口服组和静脉组间比较,差异无统计学意义（P＞0.05）。三组病人术前、术后第1~3天的凝血指标比较,差异均无统计学意义（P＞0.05）,且所有病人均未发生静脉血栓、肝肾功能异常等药物相关并发症。结论 术后多次给予氨甲环酸可以有效降低矫形术后失血量及输血率,口服给药与静脉给药具有等效性。