Median Nerve Palsy in Pediatric Supracondylar Humerus Fractures Recovers Faster With Open Than Closed Reduction.

BACKGROUND: Management of supracondylar humerus fractures (SCHF) with coexisting median nerve injury is controversial. Although many nerve injuries improve with the reduction and stabilization of the fracture, the speed and completeness of recovery are unclear. This study investigates median nerve recovery time using the serial examination. METHODS: A prospectively maintained database of SCHF-related nerve injuries referred to a tertiary hand therapy unit between 2017 and 2021 was interrogated. Factors related to the injury (vascularity, Gartland grade, open vs. closed fracture) and treatment (fixation modality, adequacy, timing of reduction, vascular and nerve intervention, and secondary procedures) were assessed.Primary outcomes were the motor recovery of Medical Research Council (MRC) grade 4 or 5 in flexor pollicis longus or flexor digitorum profundus (index) and detection of the 2.83 Semmes Weinstein monofilament.A retrospective clinical note review of all SCHF presenting during the same period was also conducted. RESULTS: Of 1096 SCHF, 74 (7%) had an associated median nerve palsy. Twenty-one patients [mean age 7 years (SD 1.6)] with SCHF-related median nerve injuries underwent serial examination. Nineteen (90%) were modified Gartland III or IV, and 10 (48%) were pulseless on presentation. The mean follow-up was 324 days.The mean motor recovery time was 120 days (SD 71). Four (27%) and 2 (13%) patients had not achieved MRC grade 4 by 6 months and 2 years, respectively. Only 50% attained MRC grade 5 at 2 years.When compared with closed reduction, those who underwent open reduction recovered motor function 80 days faster (mean 71 vs. 151 d, P =0.03) and sensory function 110 days faster (52 vs. 162, P =0.02). Fewer patients recovered after closed reduction (8 of 10) than open (5 of 5).Modified Gartland grade, vascular status, adequacy of reduction, and secondary surgery were not associated with recovery time. CONCLUSIONS: Median nerve recovery seems to occur slower than previously thought, is often incomplete, and is affected by treatment decisions (open vs. closed reduction). Retrospective reporting methods may overestimate median nerve recovery. LEVEL OF EVIDENCE: Level III-therapeutic.

Pathway analysis of microarray data from corpora cavernosal tissue of patients with a prostatectomy or Peyronie disease in comparison with a cavernous nerve-injured rat model of erectile dysfunction.

INTRODUCTION: Patients with a prostatectomy are at high risk of developing erectile dysfunction (ED) that is refractory to phosphodiesterase type 5 inhibitors. The cavernous nerve (CN) is frequently damaged during prostatectomy, causing loss of innervation to the penis. This initiates corpora cavernosal remodeling (apoptosis and fibrosis) and results in ED. AIM: To aid in the development of novel ED therapies, the current aim was to obtain a global understanding of how signaling mechanisms alter in the corpora cavernosa with loss of CN innervation that results in ED. METHODS: Microarray and pathway analysis were performed on the corpora cavernosal tissue of patients with a prostatectomy (n = 3) or Peyronie disease (control, n = 3). Results were compared with an analysis of a Sprague-Dawley rat CN injury model (n = 10). RNA was extracted by TRIzol, DNase treated, and purified by a Qiagen Mini Kit. Microarray was performed with the Human Gene 2.0 ST Array and the RU34 rat array. Differentially expressed genes were identified through several analytic tools (ShinyGO, Ingenuity, WebGestalt) and databases (GO, Reactome). A 2-fold change was used as the threshold for differential expression. OUTCOMES: Pathways that were altered (up- or downregulated) in response to CN injury in the prostatectomy patients and a rat CN injury model were determined. RESULTS: Microarray identified 197 differentially expressed protein-coding genes in the corpora cavernosa from the prostatectomy cohort, with 100 genes upregulated and 97 genes downregulated. Altered signaling pathways that were identified that affect tissue morphology included the following: neurologic disease, cell death and survival, tissue and cellular development, skeletal and muscle development and disorders, connective tissue development and function, tissue morphology, embryonic development, growth and proliferation, cell-to-cell signaling, and cell function and maintenance. These human pathways have high similarity to those observed in the CN-injured rat ED model. CLINICAL IMPLICATIONS: Significant penile remodeling continues in patients long after the acute surgical injury to the CN takes place, offering the opportunity for clinical intervention to reverse penile remodeling and improve erectile function. STRENGTHS AND LIMITATIONS: Understanding how signaling pathways change in response to CN injury and how these changes translate to altered morphology of the corpora cavernosa and ensuing ED is critical to identify strategic targets for therapy development. CONCLUSION: Altered signaling in pathways that regulate tissue homeostasis, morphogenesis, and development was identified in penes of patients with a prostatectomy, and competitive forces of apoptosis and proliferation/regeneration were found to compete to establish dominance after CN injury. How these pathways interact to regulate penis tissue homeostasis is a complex process that requires further investigation.

Machine-Learning Analysis of Serum Proteomics in Neuropathic Pain after Nerve Injury in Breast Cancer Surgery Points at Chemokine Signaling via SIRT2 Regulation.

BACKGROUND: Persistent postsurgical neuropathic pain (PPSNP) can occur after intraoperative damage to somatosensory nerves, with a prevalence of 29-57% in breast cancer surgery. Proteomics is an active research field in neuropathic pain and the first results support its utility for establishing diagnoses or finding therapy strategies. METHODS: 57 women (30 non-PPSNP/27 PPSNP) who had experienced a surgeon-verified intercostobrachial nerve injury during breast cancer surgery, were examined for patterns in 74 serum proteomic markers that allowed discrimination between subgroups with or without PPSNP. Serum samples were obtained both before and after surgery. RESULTS: Unsupervised data analyses, including principal component analysis and self-organizing maps of artificial neurons, revealed patterns that supported a data structure consistent with pain-related subgroup (non-PPSPN vs. PPSNP) separation. Subsequent supervised machine learning-based analyses revealed 19 proteins (CD244, SIRT2, CCL28, CXCL9, CCL20, CCL3, IL.10RA, MCP.1, TRAIL, CCL25, IL10, uPA, CCL4, DNER, STAMPB, CCL23, CST5, CCL11, FGF.23) that were informative for subgroup separation. In cross-validated training and testing of six different machine-learned algorithms, subgroup assignment was significantly better than chance, whereas this was not possible when training the algorithms with randomly permuted data or with the protein markers not selected. In particular, sirtuin 2 emerged as a key protein, presenting both before and after breast cancer treatments in the PPSNP compared with the non-PPSNP subgroup. CONCLUSIONS: The identified proteins play important roles in immune processes such as cell migration, chemotaxis, and cytokine-signaling. They also have considerable overlap with currently known targets of approved or investigational drugs. Taken together, several lines of unsupervised and supervised analyses pointed to structures in serum proteomics data, obtained before and after breast cancer surgery, that relate to neuroinflammatory processes associated with the development of neuropathic pain after an intraoperative nerve lesion.

Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated. AIMS: To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP. METHODS: Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-ß1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN. OUTCOMES: Effects of LIES on EF, erectile tissue remodeling and CN structure. RESULTS: EF was decreased (P < .05) 7 days after BCNI and increased (P < .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P < .05) after BCNI and normalized by LIES. Protein expressions of TGF-ß1, IL-6, and CRP were increased in the penis (P < .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P < .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P < .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P < .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P < .05) after BCNI and decreased (P < .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups. CLINICAL TRANSLATION: LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery. STRENGTHS & LIMITATIONS: This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required. CONCLUSION: This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686-696.

Glass Fragment Injury to the Craniocervical Junction with Interatlantooccipital Penetration to the Subarachnoid Space: Not-To-Be-Missed Important Aspects of Craniocervical Trauma Even in the Middle of the COVID-19 Pandemic: Case Report and Review of Literature.

BACKGROUND: Nonmissile penetrating injuries to the craniocervical junction caused by a glass fragment are rare, and a standard management strategy has not been established. CASE DESCRIPTION: A 75-year-old Japanese man was brought into our emergency department after receiving a left retroauricular stab wound by broken glass fragments. After spinal immobilization, a computed tomography (CT) scan revealed glass fragments penetrating at the right craniocervical junction to the interatlantooccipital subarachnoid space. CT angiography showed that both vertebral arteries were not injured. Magnetic resonance imaging demonstrated that the glass fragments did not penetrate the cervical cord or medulla oblongata. These glass fragments were removed via a midline incision from the external occipital protuberance to the C7 and with laminectomy without suboccipital craniectomy. Five of the glass fragments were found and removed in total. The dural defect was patched with a free fascia autograft. His postoperative course was uneventful. Postoperative CT angiography showed that both vertebral arteries were intact and the glass fragments had been removed completely. CONCLUSIONS: CT graphical diagnosis is useful for the management of penetrating craniocervical junction trauma, and it should be considered in the evaluation of patients who have suffered craniocervical penetrating injury even in the absence of major wounds or bleeding. Spinal immobilization of patients with craniocervical penetrating injuries is crucial to avoid not only secondary neurologic damage but also secondary critical vascular damage. Incomplete or inadequate assessment of craniocervical stab wounds results in unexpected hazards that are preventable.

Selected pathobiological features and principles of pharmacological pain management.

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury-either peripheral or central-may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling. Therefore, optimal pain management for patients with chronic neuropathic pain requires a multimodal approach that comprises pharmacological and psychological interventions. Non-opioid analgesics (e.g., paracetamol, aspirin, or other non-steroidal anti-inflammatory drugs) are first-line agents used in the treatment of mild-to-moderate acute pain, while opioids of increasing potency are indicated for the treatment of persistent, moderate-to-severe inflammatory pain. N-methyl D-aspartate receptor antagonists, antidepressants, anticonvulsants, or a combination of these should be considered for the treatment of chronic neuropathic pain. This review discusses the various neural signals that mediate acute and chronic pain, as well as the general principles of pain management.

Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model.

INTRODUCTION: The human placenta provides a bountiful and noncontroversial source of stem cells which have the potential for regeneration of injured tissue. These cells may restore erectile function after neurovascular tissue injury such as that seen in radical pelvic surgeries and pelvic trauma. AIM: To determine the effect of human placenta-derived stem cells on erectile function recovery and histological changes at various time points in a cavernous nerve injury rat model and to study the fate of injected stem cells throughout the regenerative process. METHODS: Human placental stem cells (PSCs) were dual labeled with monomeric Katushka far red fluorescent protein (mKATE)-renLUC using a lentivirus vector. A pelvic neurovascular injury-induced erectile dysfunction model was established in male, athymic rats by crushing the cavernous nerves and ligating the internal pudendal neurovascular bundles, bilaterally. At the time of defect creation, nonlabeled PSCs were injected into the corpus cavernosum at a concentration of 2.5 × 106 cells/0.2 mL. The phosphate-buffered saline-treated group served as the negative control group, and age-matched rats (age-matched controls) were used as the control group. Erectile function, histomorphological analyses, and Western blot were assessed at 1, 6, and 12 weeks after model creation. The distribution of implanted, dual-labeled PSCs was monitored using an in vivo imaging system (IVIS). Implanted cells were further tracked by detection of mKATE fluorescence in histological sections. MAIN OUTCOME MEASURE: The main outcome measure includes intracavernous pressure/mean arterial pressure ratio, neural, endothelial, smooth muscle cell regeneration, mKATE fluorescence, and IVIS imaging. RESULTS: The ratio of intracavernous pressure to mean arterial pressure significantly increased in PSC-injected rats compared with phosphate-buffered saline controls (P < 0.05) at the 6- and 12-week time points, reaching 72% and 68% of the age-matched control group, respectively. Immunofluorescence staining and Western blot analysis showed significant increases in markers of neurons (84.3%), endothelial cells (70.2%), and smooth muscle cells (70.3%) by 6 weeks in treatment groups compared with negative controls. These results were maintained through 12 weeks. IVIS analysis showed luminescence of implanted PSCs in the injected corpora immediately after injection and migration of cells to the sites of injury, including the incision site and periprostatic vasculature by day 1. mKATE fluorescence data revealed the presence of PSCs in the penile corpora and major pelvic ganglion at 1 and 3 days postoperatively. At 7 days, immunofluorescence of penile PSCs had disappeared and was diminished in the major pelvic ganglion. CLINICAL IMPLICATIONS: Placenta-derived stem cells may represent a future "off-the-shelf" treatment to mitigate against development of erectile dysfunction after radical prostatectomy or other forms of pelvic injury. STRENGTH & LIMITATIONS: Single dose injection of PSCs after injury resulted in maximal functional recovery and tissue regeneration at 6 weeks, and the results were maintained through 12 weeks. Strategies to optimize adult stem cell therapy might achieve more effective outcomes for human clinical trials. CONCLUSION: Human PSC therapy effectively restores the erectile tissue and function in this animal model. Thus, PSC therapy may provide an attractive modality to lessen the incidence of erectile dysfunction after pelvic neurovascular injury. Further improvement in tissue regeneration and functional recovery may be possible using multiple injections or systemic introduction of stem cells. Gu X, Thakker PU, Matz EL, et al. Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model. J Sex Med 2020;17:400-411.

Pressure Injuries Treated With Anodal and Cathodal High-voltage Electrical Stimulation: the Effect on Blood Serum Concentration of Cytokines and Growth Factors in Patients With Neurological Injuries. A Randomized Clinical Study.

It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans. PURPOSE: The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1ß, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-ß1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression. METHODS: This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 µs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1ß, IL-10, TGF-ß1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05. RESULTS: Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1ß concentrations correlated positively with the decrease of PI size (P <.05). CONCLUSION: Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1ß concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.

Microcirculatory Changes in Experimental Models of Stroke and CNS-Injury Induced Immunodepression.

Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression.

Cannabinoids for the treatment of spasticity.

This review summarizes studies that examined the effectiveness of cannabinoids in treating spasticity, with a focus on understanding the relevance of the existing evidence to paediatric populations. MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched to identify studies that examined the use of cannabinoids in spasticity. We identified 32 studies in adult and paediatric populations. Results were summarized by condition, with adult and paediatric studies considered separately. There is evidence from randomized controlled clinical trials that cannabinoids are more effective than placebo in reducing symptoms of spasticity in adults with multiple sclerosis. Most positive effects were based on patient-rated rather than clinician-rated measures, were modest in size, and should be considered in the context of the narrow therapeutic index of cannabinoids for spasticity and adverse effects. There were comparatively few, and no large studies, of spasticity in conditions other than multiple sclerosis. Few studies have been conducted in paediatric populations. Paediatric studies of spasticity provide low quality evidence and are inadequate to inform clinical practice. Cannabinoids have modest efficacy in reducing muscle spasticity in adults with multiple sclerosis. There is limited evidence of efficacy for cannabinoid use in other conditions, particularly in paediatric populations. Studies in paediatric populations have been of low quality and are insufficient to inform clinical practice.

CANNABINOIDES PARA EL TRATAMIENTO DE LA ESPASTICIDAD: Esta revisión resume los estudios que examinaron la efectividad de los cannabinoides en el tratamiento de la espasticidad, con un enfoque en la comprensión de la relevancia de la evidencia existente para las poblaciones pediátricas. Se realizaron búsquedas en Medline, Embase, PsycINFO y la Biblioteca Cochrane para identificar estudios que examinaron el uso de cannabinoides en la espasticidad. Se identificaron 32 estudios en poblaciones adultas y pediátricas. Los resultados se resumieron por condición, con estudios en adultos y pediátricos considerados por separado. Existe evidencia de ensayos clínicos controlados aleatorios de que los cannabinoides son más efectivos que el placebo para reducir los síntomas de la espasticidad en adultos con esclerosis múltiple. La mayoría de los efectos positivos se basaron en las medidas clasificadas por el paciente en lugar de las clasificadas por el médico, fueron de tamaño modesto y deben considerarse en el contexto del estrecho índice terapéutico de los cannabinoides para la espasticidad y los efectos adversos. Hubo comparativamente pocos, y no hay estudios grandes, de espasticidad en afecciones distintas a la esclerosis múltiple. Se han realizado pocos estudios en poblaciones pediátricas. Los estudios pediátricos de espasticidad proporcionan evidencia de baja calidad y son inadecuados para informar la práctica clínica.

CANABINÓIDES PARA O TRATAMENTO DA ESPASTICIDADE: Esta revisão sintetiza estudos que examinaram a efetividade de canabinóides no tratamento da espasticidade, com foco na compreensão da relevância da evidência existente para populações pediátricas. Medline, Embase, PsycINFO, e Cochrane Library foram pesquisados para identificar estudos que examinaram o uso de canabinóides na espasticidade. Identificamos 32 estudos em populações adultas e pediátricas. Os resultados foram sintetizados por condição com estudos em adultos e pediátricos considerados separadamente. Há evidência de ensaios clínicos randomizados controlados de que os canabinóides são mais efetivos do que placebos na redução de sintomas de espasticidade em adultos com esclerose múltipla. A maioria dos efeitos positivos foram baseados em medidas fornecidas por pacientes e não por clínicos, eram de tamanho modesto, e devem ser considerados no contexto do estreito índice terapêutico dos canabinóides para espasticidade e efeitos adversos. Houve comparativamente menos, e nenhum grande estudo, da espasticidade em condições diferentes da esclerose múltipla. Poucos estudos foram conduzidos em populações pediátricas. Estudos pediátricos da espasticidade fornecem baixa evidência de qualidade e são inadequados para informar a prática clínica.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

BACKGROUND: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. AIM: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. METHODS: Male rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. OUTCOMES: Intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. RESULTS: Following RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. CLINICAL TRANSLATION: RT-induced ED may result from damage to the ganglia controlling erections. STRENGTHS & LIMITATIONS: This study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. CONCLUSION: This is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined. Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27-41.

Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury.

BACKGROUND: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion. AIM: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique. METHODS: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI. OUTCOMES: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis. RESULTS: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals. CLINICAL IMPLICATIONS: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion. STRENGTH & LIMITATIONS: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials. CONCLUSION: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26.

Unión cráneo-cervical - anatomía normal y correlación con imágenes / Cranio Cervical Junction - Anatomy and Imaging Correlation

La solicitud de estudios de imagen en pacientes con trauma cervical es muy frecuente en la práctica diaria. Esa patología es causa relativamente frecuente de discapacidad en pacientes jóvenes junto con el trauma encéfalo craneano. En un porcentaje no despreciable de los casos, las lesiones traumáticas comprometen la unión cráneo- cervical y en esos pacientes, la morbi-mortalidad es más significativa. La transición entre el cráneo y el raquis se basa en un conjunto de estructuras óseas relacionadas por articulaciones muy móviles y estabilizadas por un grupo de ligamentos y músculos que le brindan al mismo tiempo gran solidez. Para una correcta interpretación de los estudios de imagen de uso corriente en la clínica, es fundamental un sólido conocimiento anatómico de la unión cráneo-cervical y sus componentes. Es el objetivo de esta revisión, sistematizar la anatomía de la unión cráneo-cervical con especial énfasis en sus ligamentos, analizar la fisiología de sus movimientos y el concepto de estabilidad para luego realizar una correlación con tomografía computada multi-detector y resonancia magnética.

The request of imaging techniques in patients with cervical spine trauma is very common in clinical practice. Cervical trauma is a relatively common cause of disability in young patients. In a significant percentage of cases traumatic injuries compromise the cranio-cervical junction with more important morbidity and mortality in this group of patients. The transition between the skull and the spine is based on a set of bony structures, high mobility joints, and stabilization mechanism formed by a group of ligaments and muscles. A solid anatomical knowledge of the cranio-cervical junction and its components is essential for a correct interpretation of current high resolution imaging studies. The goal of this review is highlight the anatomy of the cranio-cervical junction with special emphasis on the ligaments, analyze the biomechanics of their movements and the concept of stability. At last but not leastwe will establish a correlation with multidetector computed tomography and high-resolutionmagnetic resonance imaging.

Novel Concept Enabling an Old Idea: A Flexible Electrode Array to Treat Neurogenic Erectile Dysfunction.

INTRODUCTION: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement. AIM: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively. METHODS: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system. MAIN OUTCOME MEASURE: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array. RESULTS: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01). CLINICAL IMPLICATIONS: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury. STRENGTH & LIMITATIONS: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice. CONCLUSION: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569.

Traumatic fractures resulting from collisions in children and adolescents: A retrospective observational study.

To investigate the incidence and pattern of child and adolescent (≤18 years old) traumatic fractures (TFs) as a result of collisions.We retrospectively reviewed 270 child and adolescent patients (228 males and 42 females aged 12.8 ±â€Š5.1 years old) with TFs as a result of collisions admitted to our university-affiliated hospitals from 2001 to 2010. The incidence and patterns were summarized with respect to different age groups, sex, etiology, and whether the patient presented with nerve injury.The most common etiologies were struck by object (105, 38.9%) and wounded by person (74, 27.4%). The most common fracture sites were upper limb fractures (126, 46.7%) and craniofacial fractures (82, 30.4%). A total of 65 (24.1%) patients suffered a nerve injury. The frequency of early and late complications/associated injuries was 35.6% (n = 96) and 8.5% (n = 23), respectively. The mean age (P = .001) and frequency of wounded by person (P = .038) was significantly larger in male than in female patients. The frequency of earthquake injury (P < .001) and lower limb fractures (P = .002) was significantly larger in females than in male patients. The frequency of upper limb fracture was significantly higher in the wounded by machine group (83.3%) than in the other groups (all P < .05). The frequency of lower limb fractures was significantly higher in the earthquake injury group (64.7%) than in the other groups (all P < .05). The frequency of craniofacial fracture was significantly higher in the wounded by person group (54.1%) than in the other groups (all P < .05). The emergency admission rate (P = .047), frequency of wounded by person (P < .001), craniofacial fracture (P < .001), and early complications/associated injuries (P < .001) were significantly larger in patients with nerve injury than in other patients.Struck by object and upper limb fractures were the most common etiology and site, respectively. Wounded by person and craniofacial fractures were risk factors for nerve injury. Therefore, we should pay more attention to patients wounded by person, presenting with craniofacial fracture, to find whether there is nerve injury.

Occipital Condyle Fracture Extending to the Inferior Part of the Clivus.

Although rarely reported in the literature, serious occipital and condylar fractures have been diagnosed more often with the widespread use of computed cranial tomography in traumas. In this paper, a 16-year-old female with a left occipital fracture extending from the left occipital condyle anterior of the hypoglossal canal to the inferior part of the clivus is presented. The fracture which had caused a neurological deficit was cured with conservative treatment. For delayed hypoglossal nerve paralysis due to swelling within the canal, methylprednisolone was started, and a complete cure was attained in about 10 days. Traumatic damage of bony structures of the condyle and clivus at the junction of many vital nerves, vessels, and ligaments may lead to traumatic deficit and death.

Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction.

BACKGROUND: Whether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown. AIM: To investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI). METHODS: MSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. OUTCOMES: Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed. RESULTS: MSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs. CLINICAL TRANSLATION: Combined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models. STRENGTHS AND LIMITATIONS: The study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition. CONCLUSION: Combined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs. Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284-295.

Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury.

BACKGROUND: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases. AIM: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI). METHODS: Rats underwent BCNI or a sham operation and were treated with vehicle or ß-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry. OUTCOMES: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content. RESULTS: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. ß-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content. CLINICAL TRANSLATION: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction. STRENGTHS AND LIMITATIONS: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation. CONCLUSION: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313.

Tartamudez neurógena: revisión de la bibliografía / Neurogenic stuttering: a review of the literature

Introducción. La tartamudez neurógena es un trastorno del ritmo de habla de origen neurológico en el cual el paciente sabe perfectamente lo que quiere decir, pero es incapaz de articularlo a causa de la prolongación, el cese o la repetición involuntaria de un sonido. Objetivo. Reunir nuevos datos referentes a la epidemiología, la fisiopatología, el diagnóstico, la evaluación y el tratamiento de la tartamudez neurógena. Desarrollo. Se llevó a cabo una revisión de todos los artículos publicados en PubMed y Scopus entre enero de 2000 y septiembre de 2016. Se examinaron 33 publicaciones. La tartamudez neurógena es una entidad poco frecuente cuya incidencia epidemiológica no se ha definido completamente. Aparece en el marco de diversas enfermedades neurológicas y ligada a distintos lugares del sistema nervioso. A pesar de los avances recientes en el conocimiento del mecanismo subyacente, aún no ha sido posible determinar un único mecanismo fisiopatológico de este trastorno. El diagnóstico diferencial es complejo y requiere un buen conocimiento de otros trastornos del lenguaje. El tratamiento se basa actualmente en terapias logopédicas específicas. Conclusión. La tartamudez neurógena es un trastorno complejo que no se conoce con detalle. Nuevos estudios ayudarían a esclarecer los mecanismos fisiopatológicos que se ocultan tras ella y abrirían la puerta a nuevos métodos terapéuticos (AU)

Introduction. Neurogenic stuttering is a disorder of neurologic origin in the rhythm of speech during which the patient knows exactly what he wants to say but is unable to because of an involuntary prolongation, cessation or repetition of a sound. Aim. To assemble new insights regarding the epidemiology, pathophysiology, diagnosis, evaluation and treatment of neurogenic stuttering. Development. A review of all PubMed and Scopus published articles between January 2000 and September 2016 was performed. Thirty-three publications were analyzed. Neurogenic stuttering is a rare entity whose epidemiological incidence is yet not fully established. It is correlated with several neurological diseases and with several possible localizations within the nervous system. Notwithstanding the recent advances in the understanding of the underlying mechanism, it is not yet possible to establish a single pathophysiological mechanism of neurogenic stuttering. The differential diagnosis is complex and requires the detailed knowledge of other language disorders. The treatment is currently based on specific speech language therapy strategies. Conclusion. Neurogenic stuttering is a complex disorder which is not fully understood. Additional studies might help to better explain the underlying pathophysiological mechanism and to open doors to novel therapeutic methods (AU)