Amanda Reed-Maldonado

Low-intensity Extracorporeal Shock Wave Treatment Improves Erectile Function: A Systematic Review and Meta-analysis

CONTEXT As a novel therapeutic method for erectile dysfunction (ED), low-intensity extracorporeal shock wave treatment (LI-ESWT) has been applied recently in the clinical setting. We feel that a summary of the current literature and a systematic review to evaluate the therapeutic efficacy of LI-ESWT for ED would be helpful for physicians who are interested in using this modality to treat patients with ED. OBJECTIVE A systematic review of the evidence regarding LI-ESWT for patients with ED was undertaken with a meta-analysis to identify the efficacy of the treatment modality. EVIDENCE ACQUISITION A comprehensive search of the PubMed and Embase databases to November 2015 was performed. Studies reporting on patients with ED treated with LI-ESWT were included. The International Index of Erectile Function (IIEF) and the Erection Hardness Score (EHS) were the most commonly used tools to evaluate the therapeutic efficacy of LI-ESWT. EVIDENCE SYNTHESIS There were 14 studies including 833 patients from 2005 to 2015. Seven studies were randomized controlled trials (RCTs); however, in these studies, the setup parameters of LI-ESWT and the protocols of treatment were variable. The meta-analysis revealed that LI-ESWT could significantly improve IIEF (mean difference: 2.00; 95% confidence interval [CI], 0.99-3.00; p<0.0001) and EHS (risk difference: 0.16; 95% CI, 0.04-0.29; p=0.01). Therapeutic efficacy could last at least 3 mo. The patients with mild-moderate ED had better therapeutic efficacy after treatment than patients with more severe ED or comorbidities. Energy flux density, number of shock waves per treatment, and duration of LI-ESWT treatment were closely related to clinical outcome, especially regarding IIEF improvement. CONCLUSIONS The number of studies of LI-ESWT for ED have increased dramatically in recent years. Most of these studies presented encouraging results, regardless of variation in LI-ESWT setup parameters or treatment protocols. These studies suggest that LI-ESWT could significantly improve the IIEF and EHS of ED patients. The publication of robust evidence from additional RCTs and longer-term follow-up would provide more confidence regarding use of LI-ESWT for ED patients. PATIENT SUMMARY We reviewed 14 studies of men who received low-intensity extracorporeal shock wave treatment (LI-ESWT) for erectile dysfunction (ED). There was evidence that these men experienced improvements in their ED following LI-ESWT.

Low-Intensity Extracorporeal Shock Wave Therapy Enhances Brain-Derived Neurotrophic Factor Expression through PERK/ATF4 Signaling Pathway

Low-intensity extracorporeal shock wave therapy (Li-ESWT) is used in the treatment of erectile dysfunction, but its mechanisms are not well understood. Previously, we found that Li-ESWT increased the expression of brain-derived neurotrophic factor (BDNF). Here we assessed the underlying signaling pathways in Schwann cells in vitro and in penis tissue in vivo after nerve injury. The result indicated that BDNF were significantly increased by the Li-ESWT after nerve injury, as well as the expression of BDNF in Schwann cells (SCs, RT4-D6P2T) in vitro. Li-ESWT activated the protein kinase RNA-like endoplasmic reticulum (ER) kinase (PERK) pathway by increasing the phosphorylation levels of PERK and eukaryotic initiation factor 2a (eIF2α), and enhanced activating transcription factor 4 (ATF4) in an energy-dependent manner. In addition, GSK2656157—an inhibitor of PERK—effectively inhibited the effect of Li-ESWT on the phosphorylation of PERK, eIF2α, and the expression of ATF4. Furthermore, silencing ATF4 dramatically attenuated the effect of Li-ESWT on the expression of BDNF, but had no effect on hypoxia-inducible factor (HIF)1α or glial cell-derived neurotrophic factor (GDNF) in Schwann cells. In conclusion, our findings shed new light on the underlying mechanisms by which Li-ESWT may stimulate the expression of BDNF through activation of PERK/ATF4 signaling pathway. This information may help to refine the use of Li-ESWT to further improve its clinical efficacy.

The Current Status of Stem-Cell Therapy in Erectile Dysfunction: A Review

Stem cells are undifferentiated cells that are capable of renewal and repair of tissue due to their capacity for division and differentiation. The purpose of this review is to describe recent advances in the use of stem cell (SC) therapy for male erectile dysfunction (ED). We performed a MEDLINE database search of all relevant articles regarding the use of SCs for ED. We present a concise summary of the scientific principles behind the usage of SC for ED. We discuss the different types of SCs, delivery methods, current pre-clinical literature, and published clinical trials. Four clinical trials employing SC for ED have been published. These articles are summarized in this review. All four report improvements in ED after SC therapy. SC therapy remains under investigation for the treatment of ED. It is reassuring that clinical trials thus far have reported positive effects on erectile function and few adverse events. Safety and methodical concerns about SC acquisition, preparation and delivery remain and require continued investigation prior to wide-spread application of these methods.

Effects and Mechanisms of Low-Intensity Pulsed Ultrasound for Chronic Prostatitis and Chronic Pelvic Pain Syndrome

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is one of the most common urologic diseases, and no curative treatments have been identified. Low-intensity pulsed ultrasound (LIPUS) has been successfully used in promoting tissue healing, inhibiting inflammation and pain, differentiating stem cells, and stimulating nerve regeneration/muscle regeneration, as well as enhancing angiogenesis. Very recently, LIPUS has been proven an effective approach for CP/CPPS. This review summarizes the possible mechanisms responsible for the therapeutic effect of LIPUS for CP/CPPS. To search publications relevant to the topics of this review, the search engine for life sciences of Entrez was used. We reviewed the available evidence from 1954 through 2015 concerning LIPUS for CP/CPPS. According to the literature, both transrectal and transperineal approaches of LIPUS are effective for CP/CPPS.

Low-intensity extracorporeal shock wave therapy promotes myogenesis through PERK/ATF4 pathway

Stress urinary incontinence (SUI) is a significant health problem for women. Treatments employing muscle derived stem cells (MDSCs) may be a promising approach to this prevalent, bothersome condition, but these treatments are invasive and require collection of cells from one site for injection into another. It is also unknown whether or not these cells establish themselves and function as muscle cells in the target tissues. Alternatively, low‐intensity extracorporeal shock wave therapy (Li‐ESWT) is non‐invasive and has shown positive outcomes in the treatment of multiple musculoskeletal disorders, but the biological effects responsible for clinical success are not yet well understood. The aim of this study is to explore the possibility of employing Li‐ESWT for activation of MDSCs in situ and to further elucidate the underlying biological effects and mechanisms of action in urethral muscle.

Advances in the understanding of priapism

Priapism, a persistent penile erection lasting longer than 4 hours and unrelated to sexual activity, is one of the most common emergencies treated by urologists. Priapism can be categorized as ischemic, recurrent ischemic (stuttering), and non-ischemic. Advances in understanding the pathophysiology of various types of priapism have led to targeted management strategies. This review aims to provide an up-to-date picture of the pathophysiology and management of priapism. A search of Medline and PubMed for relevant publications using the term “priapism” was performed. In addition to the “classical” articles, emphasis was placed on publications from January 2013 to September 2016 to evaluate the most recent literature available. Though advances in both basic and clinical research continue and effective treatment options are available, methods for the prevention of priapism continue to be elusive.

Transgenic animal model for studying the mechanism of obesity-associated stress urinary incontinence

To study and compare the function and structure of the urethral sphincter in female Zucker lean (ZL) and Zucker fatty (ZF) rats and to assess the viability of ZF fats as a model for female obesity‐associated stress urinary incontinence (SUI).

Impaired contractility of the circular striated urethral sphincter muscle may contribute to stress urinary incontinence in femal zucker fatty rats

Obesity has been an independent risk factor for female stress urinary incontinence (SUI), the mechanism of this association remains unknown. The aim of this study is to validate the hypothesis that urethral dysfunction is a possible contributor to SUI in obese women.

Learning Penile Anatomy to Improve Function

2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 Learning the Penile Anatomy to Improve Function 62 63 ONE of the most famous edicts from all scientific spongiosum pressurizes and constricts the urethral 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 fields, especially the fields of architecture, engineering and biology, is that form follows function. The principle is that the shape of an object should be based on its intended purpose. In no other organ is this as true as in the human penis. The penis is a complex and dynamic organ with dramatically contrasting functions. In a flaccid state the penis serves as a conduit for urine flow. In its erect state it serves as a biological battering ram for the purposes of copulation and fertilization. The organ operates largely independently. As described by Leonardo da Vinci, “The penis does not obey the order of its master, who tries to erect or shrink it at will. Instead, the penis erects freely while its master is asleep. The penis must be said to have its own mind.” The penis is subjected to greater cyclical shifts in pressure than any other organ in the body. In its flaccid state the corpora cavernosa of the penis have a resting pressure of 0 to 5 mm Hg. With erection this pressure rises to around 100 mm Hg. With contraction of the bulbocavernosus muscle the intracavernous pressure rises to approximately 145 to 220 mm Hg. This tremendous pressure is then increased even further with axial loading during the act of intercourse. The form of the penis is expertly engineered to withstand these tremendous shifts in pressure. The skeleton of the penis, which is composed of collagen and elastin fibers, the outer longitudinal layer and the inner circular layers of the tunica albuginea, the midline intercorporeal septum and intracorporeal struts, and the latticework of the corporeal scaffold, is designed to contain and support penile erection. When the penis returns to its flaccid state, the structure recovers its form effortlessly. The hemodynamics of the corpus spongiosum and the glans are different from those of the corpora cavernosa. During erection the pressure in the corpus spongiosum and glans is only a third to half that in the corpora cavernosa. This is because the thin tunica of the spongiosum ensures minimal venous occlusion. This moderate increase of pressure and volume of the spaces in the corpus

Comparison of Topical Hemostatic Agents in a Swine Model of Extremity Arterial Hemorrhage: BloodSTOP iX Battle Matrix vs. QuikClot Combat Gauze

BloodSTOP iX Battle Matrix (BM) and QuikClot Combat Gauze (CG) have both been used to treat traumatic bleeding. The purpose of this study was to examine the efficacy and initial safety of both products in a swine extremity arterial hemorrhage model, which mimics combat injury. Swine (37.13 ± 0.56 kg, NBM = 11, NCG = 9) were anesthetized and splenectomized. We then isolated the femoral arteries and performed a 6 mm arteriotomy. After 45 s of free bleeding, either BM or CG was applied. Fluid resuscitation was provided to maintain a mean arterial pressure of 65 mmHg. Animals were observed for three hours or until death. Fluoroscopic angiography and wound stability challenge tests were performed on survivors. Tissue samples were collected for histologic examination. Stable hemostasis was achieved in 11/11 BM and 5/9 CG subjects, with recovery of mean arterial pressure and animal survival for three hours (p < 0.05, Odds Ratio (OR) = 18.82 (0.85–415.3)). Time to stable hemostasis was shorter for the BM-treated group (4.8 ± 2.5 min vs. 58 ± 20.1 min; Median = 2, Interquartile Range (IQR) = 0 min vs. Median = 60, IQR = 120 min; p < 0.05) and experienced longer total stable hemostasis (175.2 ± 2.5 min vs. 92.4 ± 29.9 min; Median = 178, IQR = 0 min vs. Median = 120, IQR = 178 min; p < 0.05). Post-treatment blood loss was lower with BM (9.5 ± 2.4 mL/kg, Median = 10.52, IQR = 13.63 mL/kg) compared to CG (29.9 ± 9.9 mL/kg, Median = 29.38, IQR = 62.44 mL/kg) (p = 0.2875). Standard BM products weighed less compared to CG (6.9 ± 0.03 g vs. 20.2 ± 0.4 g) (p < 0.05) and absorbed less blood (3.4 ± 0.8 g vs. 41.9 ± 12.3 g) (p < 0.05). Fluoroscopic angiography showed recanalization in 5/11 (BM) and 0/5 (CG) surviving animals (p = 0.07, OR = 9.3 (0.41–208.8)). The wound stability challenge test resulted in wound re-bleeding in 1/11 (BM) and 5/5 (CG) surviving animals (p < 0.05, OR = 0.013 (0.00045–0.375)). Histologic evidence indicated no wound site, distal limb or major organ damage in either group. BM is more effective and portable in treating arterial hemorrhage compared to CG. There was no histologic evidence of further damage in either group.