A Mixture of Topical Forms of Polydeoxyribonucleotide, Vitamin C, and Niacinamide Attenuated Skin Pigmentation and Increased Skin Elasticity by Modulating Nuclear Factor Erythroid 2-like 2.

It is well-known that increased oxidative stress caused by ultraviolet B (UV-B) radiation induces melanogenesis and activates metalloproteinases (MMPs), which degrade collagen and elastin fibers, leading to decreased skin elasticity. Various antioxidant agents, such as vitamin C and niacinamide, have been evaluated for use as treatments for photoaging or skin pigmentation. In this study, we evaluated the ability of a topical liquid formula of polydeoxyribonucleotide (PDRN), vitamin C, and niacinamide (PVN) delivered via a microneedling therapy system (MTS) to attenuate photoaging and pigmentation by increasing nuclear factor erythroid 2-like 2 (NRF2)/heme oxygenase-1 (HO-1) and decreasing MMP expression in a UV-B-radiated animal model. The effects of the PVN were compared with those of individual PDRN and hydroquinone (HQ) compounds. The expression of NRF2/HO-1 significantly increased in response to HQ, PDRN, and PVN in UV-B-radiated animal skin. The activity of nicotinamide adenine dinucleotide phosphate hydrogen oxidase decreased in response to HQ, PDRN, and PVN, and the superoxide dismutase activity increased. The expression of tumor protein p53 and microphthalmia-associated transcription factor and tyrosinase activity decreased in response to HQ, PDRN, and PVN, and this decrease was accompanied by decreased melanin content in the skin. The expression of nuclear factor kappa-light-chain enhancer of activated B cells and MMP2/3/9 decreased in response to HQ, PDRN, and PVN in UV-B-radiated skin. However, the expression of collagen type I α1 chain and the amount of collagen fibers that were evaluated by Masson's trichrome staining increased in response to HQ, PDRN, and PVN. The contents of elastin fibers, fibrillin 1/2 and fibulin 5 increased in response to HQ, PDRN, and PVN. In conclusion, PVN delivered via MTS led to decreased melanogenesis and destruction of collagen and elastin fibers by MMPs, and, thus, PVN decreased skin pigmentation and increased skin elasticity.

The Prophylaxis of Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome With Defibrotide After Hematopoietic Stem Cell Transplantation in Children: Single Center Experience.

Hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most severe and life-threatening complications after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is approved for adult and pediatric patients with VOD/SOS with renal or pulmonary dysfunction after HSCT in the United States, and for severe VOD/SOS post-HSCT in patients above 1 month of age in the European Union. Several studies have examined whether DF prophylaxis can reduce the incidence of VOD/SOS in high-risk patients. A total of 334 pediatric allogeneic HSCT were included in this study. All patients received DF at the dose of 25 mg/kg/d, from the first day of the conditioning regimen to the 30th day after transplantation for VOD/SOS prophylaxis. Seventeen patients (5.08%) developed VOD/SOS; 4 of these had moderate, while 13 had mild VOD/SOS. None of the patients were developed severe or very severe VOD/SOS. In conclusion, we showed that prophylactic intervention with DF lowered the incidence of VOD/SOS in high-risk pediatric patients.

Defibrotide in hematopoietic stem cell transplantation: A multicenter survey study of the Spanish Hematopoietic Stem Cell Transplantation Group (GETH).

BACKGROUND: Defibrotide is approved in European Union for the treatment of severe sinusoidal obstruction syndrome (SOS) after HSCT. However, it has also been used for SOS prophylaxis, moderate SOS and in other complications such as transplant-associated thrombotic microangiopathy (TAM). The objective of this study was to evaluate current uses, effectiveness and safety of defibrotide in patients with HSCT. METHODS: This multicenter, retrospective study included patients treated with defibrotide for any indication at 28 HSCT centers of the Grupo Español de Trasplante Hematopoyetico (GETH) including the pediatric subgroup Grupo Español de Trasplante de Medula en Niños (GETMON). RESULTS: Three hundred and eighty eight patients treated with defibrotide between January 2011 and December 2018 were included. 253 patients were children, and 135 patients were adults. In total, 332 transplants were allogeneic, and the remainder were autologous. Main indications for defibrotide use were severe/very severe SOS in 173 patients, SOS prophylaxis in 135 patients, moderate SOS in 41 patients, TAM in six patients and suspected SOS in 33 patients. Overall survival (OS) at day +100 in the SOS prophylaxis group was 89% (95% CI, 87%-91%). In the group of patients with moderate and severe/very severe SOS, the OS at day +100 was 80% (95% CI, 74%-86%) and 62% (95% CI, 59%-65%), respectively (P = .0015). With a longer follow-up, median of 2 years (4 months-7 years), OS was 63% (95% CI, 59%-67%) in the SOS prophylaxis patients. OS for patients with moderate and severe/very severe SOS groups was 53% (95% CI, 47%-61%) and 26% (95% CI, 22%-30%), respectively (P = .006). 191 patients died, and SOS was the main cause of death in 23 patients (12%). CONCLUSIONS: Defibrotide has an acceptable safety profile with an improved response in severe/very severe SOS compared with historical controls, mainly in pediatric patients. Use of defibrotide for prophylaxis may improve prognosis of patients at high risk of complications due to endothelial damage such as those who receive a second transplant. SOS has an important impact on the HSCT long-term survival, as can be concluded from our study.

NLRP3 Inflammasome: A New Pharmacological Target for Reducing Testicular Damage Associated with Varicocele.

Many bioactive natural compounds are being increasingly used for therapeutics and nutraceutical applications to counteract male infertility, particularly varicocele. The roles of selenium and Polydeoxyribonucleotide (PDRN) were investigated in an experimental model of varicocele, with particular regard to the role of NLRP3 inflammasome. Male rats underwent sham operation and were daily administered with vehicle, seleno-L-methionine (Se), PDRN, and with the association Se-PDRN. Another group of rats were operated for varicocele. After twenty-eight days, sham and varicocele rats were sacrificed and both testes were weighted and analyzed. All the other rats were challenged for one month with the same compounds. In varicocele animals, lower testosterone levels, testes weight, NLRP3 inflammasome, IL-1ß and caspase-1 increased gene expression were demonstrated. TUNEL assay showed an increased number of apoptotic cells. Structural and ultrastructural damage to testes was also shown. PDRN alone significantly improved all considered parameters more than Se. The Se-PDRN association significantly improved all morphological parameters, significantly increased testosterone levels, and reduced NLRP3 inflammasome, caspase-1 and IL-1ß expression and TUNEL-positive cell numbers. Our results suggest that NLRP3 inflammasome can be considered an interesting target in varicocele and that Se-PDRN may be a new medical approach in support to surgery.

Polydeoxyribonucleotide Exerts Protective Effect Against CCl4-Induced Acute Liver Injury Through Inactivation of NF-κB/MAPK Signaling Pathway in Mice.

Acute liver injury (ALI) causes life-threatening clinical problem, and its underlying etiology includes inflammation and apoptosis. An adenosine A2A receptor agonist, polydeoxyribonucleotide (PDRN), exhibits anti-inflammatory and anti-apoptotic effects by inhibiting the secretion of pro-inflammatory cytokines. In the current study, the protective effect of PDRN against carbon tetrachloride (CCl4)-induced ALI was investigated using mice. For the induction of ALI, mice received intraperitoneal injection of CCl4 twice over seven days. Mice from the PDRN-treated groups received an intraperitoneal injection of 200 µL saline containing PDRN (8 mg/kg), once a day for seven days, starting on day 1 after the first CCl4 injection. In order to confirm that the action of PDRN occurs through the adenosine A2A receptor, 8 mg/kg 3,7-dimethyl-1-propargylxanthine (DMPX), an adenosine A2A receptor antagonist, was treated with PDRN. Administration of CCl4 impaired liver tissue and increased the liver index and histopathologic score. The expression of pro-inflammatory cytokines was increased, and apoptosis was induced by the administration of CCl4. Administration of CCl4 activated nuclear factor-kappa B (NF-κB) and facilitated phosphorylation of signaling factors in mitogen-activated protein kinase (MAPK). In contrast, PDRN treatment suppressed the secretion of pro-inflammatory cytokines and inhibited apoptosis. PDRN treatment inactivated NF-κB and suppressed phosphorylation of signaling factors in MAPK. As a result, liver index and histopathologic score were reduced by PDRN treatment. When PDRN was treated with DMPX, the anti-inflammatory and anti-apoptotic effect of PDRN disappeared. Therefore, PDRN can be used as an effective therapeutic agent for acute liver damage.

Polydeoxyribonucleotide-delivering therapeutic hydrogel for diabetic wound healing.

Patients with diabetes experience delayed wound healing because of the uncontrolled glucose level in their bloodstream, which leads to impaired function of white blood cells, poor circulation, decreased production and repair of new blood vessels. Treatment using polydeoxyribonucleotide (PDRN), which is a DNA extracted from the sperm cells of salmon, has been introduced to accelerate the healing process of diabetic wounds. To accelerate the wound-healing process, sustained delivery of PDRN is critical. In this study, taking advantage of the non-invasive gelation property of alginate, PDRN was loaded inside the hydrogel (Alg-PDRN). The release behavior of PDRN was altered by controlling the crosslinking density of the Alg hydrogel. The amount of PDRN was the greatest inside the hydrogel with the highest crosslinking density because of the decreased diffusion. However, there was an optimal degree of crosslinking for the effective release of PDRN. In vitro studies using human dermal fibroblasts and diabetes mellitus fibroblasts and an in ovo chorioallantoic membrane assay confirmed that the Alg-PDRN hydrogel effectively induced cell proliferation and expression of angiogenic growth factors and promoted new blood vessel formation. Its effectiveness for accelerated diabetic wound healing was also confirmed in an in-vivo animal experiment using a diabetic mouse model.

Full recovery of near complete tear of anterior cruciate ligament without surgery: a case report.

INTRODUCTION: The anterior cruciate ligament (ACL) is the region where spraining or tearing is most prevalent when the knee is injured. Complete ACL ruptures have a much less favorable outcome without surgical intervention. Polydeoxyribonucleotide (PDRN) is a relatively safe substance widely used for regenerative therapy. PATIENT CONCERNS: A 43-year-old female patient visited our clinic with Rt. knee pain after slipping, which she rated as 7/10 on a numeric rating scale. DIAGNOSIS: She was diagnosed as having a near complete tear of the ACL at the femoral attachment, partial tear of the lateral collateral ligament. INTERVENTIONS: Ultrasound-guided PDRN injections were carried out 5 times at intervals of about 2 weeks. OUTCOMES: At 3-month follow-up, the patient demonstrated an improvement in knee symptoms (numeric rating scale 0) and ROM without any complications. Even after 2 years and 5 months since the diagnosis, she has been doing her daily life well without any pain. CONCLUSION: This is the first report of successful PDRN injection for near complete tear of ACL and partial tear of lateral collateral ligament without surgery.

Venoocclusive Disease With Both Hepatic and Pulmonary Involvement.

Pulmonary venoocclusive disease (PVOD) is a rare form of pulmonary vascular disease with pulmonary hypertension characterized by preferential involvement of the pulmonary venous system. Hepatic venoocclusive disease (HVOD), also known as sinusoidal obstruction syndrome, is a condition that occurs in 13% to 15% of patients after hematopoietic stem cell transplantation (HSCT). Although hepatic and pulmonary venoocclusive diseases may share some pathologic features as well as some etiologies such as HSCT, these two disorders have never been described together in a single adult patient. We report the case of a patient who received HSCT and developed HVOD and PVOD within 9 months. Despite their differences, PVOD and HVOD share common risk factors and associated conditions, suggesting that in the context of HSCT, the two diseases share common pathophysiological mechanisms. Optimal treatment for HSCT-related PVOD remains to be determined.

Synergic regenerative effects of polydeoxyribonucleotide and microcurrent on full-thickness rotator cuff healing in a rabbit model.

BACKGROUND: Rotator cuff tendon tears (RCTTs) are common adult injuries. We hypothesized that a local injection of polydeoxyribonucleotide (PDRN) and microcurrent therapy (MIC) would be more effective in regenerating a tendon tear than PDRN administration alone. OBJECTIVES: To evaluate the effect of PDRN combined with MIC on the regeneration of RCTTs in a rabbit subscapularis tendon chronic RCTT model. METHODS: Rabbits (n=24) were allocated to 3 groups at 6 weeks after full-thickness RCTT (FTRCTT): 0.2mL normal saline (G1-SAL); 0.2mL PDRN with Sham MIC (G2-PDRN+Sham MIC); and 0.2mL PDRN with MIC (G3-PDRN+MIC). All treatments were performed under ultrasound guidance. PDRN was injected weekly for 4 weeks and sham MIC or MIC was applied daily for 4 weeks after the first PDRN injection. RESULTS: In the G3-PDRN+MIC group, the mean (SD) subscapularis tendon tear size was continuously reduced from 1 week post-treatment to 4 weeks and was significantly decreased as compared with the other 2 groups [6.0 (1.5) vs. G1: 11.5 (1.8) and G2: 9.1 (1.6) mm2; G3 vs. G1, P<0.001; G3 vs. G2, P=0.018]. The gross morphologic mean tendon tear size was significantly smaller in the G3-PDRN+MIC group than G1-SAL and G2-PDRN+ Sham MIC groups [8.8 (3.5) vs. 15.9 (2.3) and 12.4 (1.6) mm2; G3 vs. G1, P<0.001; G3 vs. G2, P=0.03]. Mean values for regenerated collagen type 1 fibers, angiogenesis, and walking parameters were all greater for the G3-PDRN+MIC group than the other 2 groups based on histological examination and motion analysis [collagen type 1, G3: 1.60 (0.80) vs. G1: 0.45 (0.60), G2: 1.10 (0.74), G3 vs. G1, P<0.001; G3 vs. G2, P=0.002] [angiogenesis, G3: 2.44 (0.73) vs. G1: 0.80 (0.82) and G2: 2.06 (0.81), G3 vs. G1, P<0.001; G3 vs. G2, P=0.006] [walking distance, G3: 6391.4 (196.9) vs. G1: 4852.8 (137.3) and G2: 5514.4 (257.3) cm; G3 vs. G1, P<0.001; G3 vs. G2, P<0.001]. CONCLUSIONS: On gross morphologic, histological, and motion analysis, combined PDRN with MIC therapy was more effective than PDRN alone treating a rabbit model of chronic traumatic FTRCTT.

The efficacy and safety of polydeoxyribonucleotide for the treatment of knee osteoarthritis: Systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The purpose of this study was to use meta-analysis techniques to evaluate the efficacy and safety of polydeoxyribonucleotide (PDRN) injections for knee osteoarthritis (OA) treatment. METHODS: Multiple comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched in November 2018 for studies that compared the effectiveness and safety of intra-articular PDRN injection for the knee joint with hyaluronic acid (HA) injection. Two reviewers independently determined study inclusion and they extracted data using a standardized data extraction form. The predefined primary outcome was Visual Analogue Scale. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS), and adverse events. RESULTS: Five randomized controlled trials were included in the meta-analysis. After 1 and 2 months, patients in the PDRN group showed significantly better improvement in pain than the HA group (P = .04 and P = .02, respectively). There was no significant difference in pain after 4 months. The pooled analysis showed that no significant differences were seen in function (KOOS and KSS) scores between the PDRN and HA groups (all P > .05) at all time points. There was no significant difference in adverse events between 2 groups (relative risks = 2.15, 95% confidential interval: 0.17-26.67, P = .55). CONCLUSION: The intra-articular use of PDRN was similar in function to HA, and the pain-relief effect was superior to HA for 2 months post-injection. Therefore, it could be a favorable alternative to HA to treat persistent pain associated with knee OA while avoiding side effects.Level of evidence I.

Acute Graft-vs.-Host Disease-Associated Endothelial Activation in vitro Is Prevented by Defibrotide.

Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed in vitro studies using endothelial cell (EC) lines. We found that DF significantly and dose-dependently suppressed EC proliferation and notably reduced their ability to form vascular tubes in Matrigel. To explore whether DF administered prophylactically or therapeutically has a significant effect on aGVHD endothelial dysfunction, ECs were exposed to media containing sera from patients with aGVHD (n = 22) in the absence or presence of DF and from patients that did not develop aGVHD (n = 13). ECs upregulated adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), the adherence junction protein VE-cadherin, von Willebrand factor (VWF), and Akt phosphorylation in response to aGVHD sera. These responses were suppressed upon treatment with DF. In summary, DF inhibits vascular angiogenesis and endothelial activation induced by sera from aGVHD patients. Our results support the view that DF has notable positive effects on endothelial biology during aGVHD.

Polydeoxyribonucleotide injection in the treatment of patients with carpal tunnel syndrome: Retrospective preliminary study.

BACKGROUND: Corticosteroid injection is beneficial in treating carpal tunnel syndrome (CTS) due to its anti-inflammatory effects. However, its side effects limit widespread usage. Recently, several studies have found that polydeoxyribonucleotide offers anti-inflammatory capabilities with fewer side effects, making it an ideal alternative. Nevertheless, there has been no study on its effectiveness in patients with CTS. Therefore, we evaluate the effectiveness of polydeoxyribonucleotide in patients with CTS. Based on the criteria, 30 patients with CTS who received two-consecutive polydeoxyribonucleotide injections (with a week interval) were initially included. METHOD: Patients with CTS were investigated retrospectively. To evaluate the effectiveness of polydeoxyribonucleotide in patients with CTS, numeric rating scale (NRS), cross-sectional area (CSA) of the median nerve, and severity and functional status scores of CTS based on the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) were assessed. RESULTS: There was a significant improvement in the NRS, CSA, and functional and severity scores of BCTQ after two-consecutive polydeoxyribonucleotide injections (P < .05). CONCLUSION: In conclusion, although more research is needed to evaluate the effectiveness of polydeoxyribonucleotide in patients with CTS, the findings here suggest that polydeoxyribonucleotide may be a viable alternative to corticosteroids in patients with CTS.

Ultrasound-guided peri-brachial plexus polydeoxyribonucleotide injection for a patient with postherpetic brachial plexopathy: A case report.

RATIONALE: Although most complications of herpes zoster (HZ) are associated with the spread of varicella-zoster virus from the initially involved sensory ganglion, motor nerve impairment, such as limb weakness, is a rare but severe complication that is difficult to treat. PATIENT CONCERN: A 73-year-old female presented with sudden left upper limb pain and weakness after HZ. DIAGNOSIS: Brachial plexopathy following HZ (postherpetic brachial plexopathy). INTERVENTION: Despite alleviation of the vesicles with antiviral treatments, the left upper limb weakness and neuropathic pain did not improve. After obtaining patient's consent, ultrasound-guided polydeoxyribonucleotide (PDRN) injection was performed around the left brachial plexus. OUTCOMES: The patient showed marked improvement in left arm pain from numerical rating scale (NRS) 9 to 4, 1 day after PDRN injection. Subsequently, the pain improved to NRS 3, and motor weakness improved to Medical Research Council grade 2 to 4. LESSONS: PDRN can be considered a viable substitute for corticosteroid injection in treatment of motor weakness and neuropathic pain after HZ.

[Medical prevention and treatment of radiation-induced urological and nephrological complications]. / Prévention médicale et traitement des complications urologiques et néphrologiques secondaires à la radiothérapie.

Abdominal and pelvic irradiations play a major place in the management of patients with cancer and present a risk of acute and late side effects. Radiation-induced lesions can affect kidney or urological structures. These side effects can have an impact in the quality of life of patients. The aim of this article is to describe the physiopathology, the symptomatology, and the principles of management of radiation-induced nephropathy, uretheritis, cystitis, and urethritis.

Clinical effects of recombinant thrombomodulin and defibrotide on sinusoidal obstruction syndrome after allogeneic hematopoietic stem cell transplantation.

Sinusoidal obstruction syndrome (SOS) is a lethal complication after hematopoietic stem cell transplantation (HSCT). Defibrotide (DF) is the only drug internationally recommended for SOS treatment in Western countries. Recombinant human soluble thrombomodulin (rhTM), which is promising for the treatment of patients with disseminated intravascular coagulation, is also reported to be potentially effective for SOS. To clarify the safety and efficacy of DF and rhTM, we conducted a retrospective survey of these agents in Japan. Data from 65 patients who underwent allogeneic HSCT and received DF (n = 24) or rhTM (n = 41) for SOS treatment were collected. The complete response rates for SOS on day 100 were 50% and 54% in the DF and rhTM groups, respectively. The 100-day overall survival rates were 50% in the DF group, and 48% in the rhTM group. Several severe hemorrhagic adverse events were observed in one patient in the DF group and five patients in the rhTM group. The main causes of death were SOS-related death, and no patient died of direct adverse events of DF or rhTM. Our results suggest that rhTM, as well as DF, can be effective as a novel treatment option for SOS.

Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease after Autologous or Allogeneic Hematopoietic Stem Cell Transplantation in Children: a retrospective study of the Italian Hematology-Oncology Association-Hematopoietic Stem Cell Transplantation Group.

Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy by applying the new European Society for Blood and Marrow Transplantation (EBMT) criteria and to analyze the risk factors underlying this complication. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. Among 5072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD, and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range, 1 to 104). Sixty-nine patients (67%) were treated with defibrotide for a median time of 16 days (range, 4 to 104). In multivariable analysis age < 2 years, use of busulfan during the conditioning regimen, female gender, and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival at 1 year was worse in patients with SOS/VOD (P = .0033), and this difference disappeared 5 years after HSCT. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P < .001). Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Nonrelapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood.

The effect of polydeoxyribonucleotide on the treatment of radiating leg pain due to cystic mass lesion in inner aspect of right sciatic foramen: A CARE compliant case report.

RATIONALE: Radiating leg pain usually originates from the lumbar spine and occasionally from peripheral lesions. Here we report a case involving a patient with radiating pain in the right leg who exhibited 2 suspicious lesions, including 1 spinal lesion and 1 extraspinal cystic mass lesion, on magnetic resonance imaging. Polydeoxyribonucleotide sodium (PDRN) was recently noted as such a substitute. PDRN has anti-inflammatory effects, as it lowers the expression of inflammatory cytokines including interleukin-6 and tumor necrosis factor-alpha. PATIENT CONCERNS: A 51-year-old man (weight, 93 kg; height, 168 cm) working as a bus driver presented at the pain clinic with continuous right buttock pain, radiating leg pain and a tingling sensation involving the calf and dorsum of the foot, since 1 week. DIAGNOSES: He was definitively diagnosed using differential blocks, which revealed the cyst to be the actual cause of the pain. INTERVENTIONS: Surgical resection was not feasible because of the position of the cyst; therefore, corticosteroid injection under ultrasonographic guidance was attempted. However, this provided short-term relief. Subsequently, a solution containing PDRN was injected around the piriformis muscle and repeated 3 more times at intervals of 2 weeks. OUTCOMES: After PDRN injection, we conducted two follow-up monitoring every two months for 2 months. Last follow-up, the patient no longer complained of pain. this resulted in relatively long-term relief from pain. LESSONS: The findings from this case suggest that PDRN is an effective alternative for steroids in patients with radiating leg pain, although its efficacy and safety needs to be evaluated in further large-scale studies.

Economic Burden of Veno-occlusive Disease in Patients With B-cell Acute Lymphoblastic Leukemia in the United States.

PURPOSE: The goal of this study was to evaluate the incidence, inpatient mortality, and economic burden of hepatic veno-occlusive disease (VOD) in adults with B-cell acute lymphoblastic leukemia (ALL) in the United States. METHODS: Using MarketScan Commercial Claims and Encounters Database and Medicare Supplemental and Coordination of Benefits Database, data for patients with B-cell ALL from April 1, 2009, to October 31, 2016, were extracted by using diagnosis codes. VOD was identified based on clinical criteria and expert opinions. Patients with VOD were followed up from diagnosis of VOD until the earliest occurrence of inpatient death, end of continuous enrollment, end of study period, or for a maximum of 100days. The incidence of VOD and VOD-associated inpatient mortality were calculated. VOD-related health care costs based on paid adjudicated claims were calculated. FINDINGS: Of the 2571 adults with B-cell ALL, the overall incidence of VOD was low at 3.4% (88 of 2571). Of these patients with VOD, 52% (46 of 88) experienced multiorgan failure and were identified as having severe VOD. VOD was only identified in patients having undergone hematopoietic stem cell transplantation (5.4% [88 of 1624]). The inpatient mortality rate of those with any VOD over the 100-day postindex period was 26.1%, and the inpatient mortality was even higher for patients with severe VOD (37.0%). Total mean (SD) medical costs per patient during the 100 days' post-VOD diagnosis were $55,975 ($160,335); mean (SD) costs per patient were ∼4-fold higher for severe ($86,953 [$206,906]) versus nonsevere ($22,047 [$72,847]) VOD. IMPLICATIONS: Clinical criteria were used to identify VOD events and thus VOD might be underdiagnosed. The mortality of VOD also might be underestimated because only inpatient deaths are captured in the data. The incidence and mortality of VOD could also be underestimated because we focused on adult patients who might receive reduced-intensity treatment. The economic burden of VOD may be underestimated because the Healthcare Common Procedure Coding System code specific for defibrotide was not available, and thus the cost for defibrotide might not be included. Finally, as the study population consisted of patients with commercial or Medicare supplemental insurance, results may not be generalizable to all patients with VOD in the United States. Although VOD occurred infrequently in adults with B-cell ALL, it was associated with high inpatient mortality and substantial costs. Patients with severe VOD were associated with highest mortality and highest costs. Given the clinical and economic burden associated with VOD, it is important that patients at high risk for VOD be identified and treated to minimize this risk.

Neuroprotective Effects of Polydeoxyribonucleotide in a Murine Model of Cadmium Toxicity.

Cadmium (Cd) is a harmful heavy metal, which causes severe brain damage and neurotoxic effects. Polydeoxyribonucleotide (PDRN) stimulates adenosine A2A receptor, thus contrasting several deleterious mechanisms in course of tissue damages. We aimed to investigate the possible neuroprotective effect of PDRN in a murine model of Cd-induced brain toxicity. Male C57 BL/6J mice were treated as follows: vehicle (0.9% NaCl, 1 ml/kg/day), PDRN (8 mg/kg/day), CdCl2 (2 mg/kg/day), and CdCl2 + PDRN. Animals were tested with the Morris water maze test to assess spatial memory and learning. After 14 days of treatment, brains were processed to evaluate the presence of edema in the cerebral tissue, the expression of mammalian target of rapamycin kinase (mTOR) and brain-derived neurotrophic factor (BDNF), and the morphological behavior of the hippocampal structures. After CdCl2 administration, the escape latency was high, protein expression of BDNF was significantly decreased if compared to controls, mTOR levels were higher than normal controls, and brain edema and neuronal damages were evident. The coadministration of CdCl2 and PDRN significantly diminished the escape latency, increased BDNF levels, and decreased protein expression of mTOR. Furthermore, brain edema was reduced and the structural organization and the number of neurons, particularly in the CA1 and CA3 hippocampal areas, were improved. In conclusion, a functional, biochemical, and morphological protective effect of PDRN against Cd induced toxicity was demonstrated in mouse brain.