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.

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.

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.

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.

Alta hospitalar de clientes com lesão neurológica incapacitante: impreteríveis encaminhamentos para reabilitação / Hospital discharge of patients with disabling neurological injury: necessary referrals to rehabilitation

Resumo Trata-se de pesquisa de abordagem qualitativa realizada no segundo semestre de 2014, mediante entrevistas com 12 médicos e 13 enfermeiros gestores atuantes em Hospital de grande porte, referência na área de urgência e emergência para a Zona da Mata Mineira. Buscou identificar os critérios utilizados por médicos e enfermeiros para o preparo da alta de pessoas com lesão neurológica incapacitante e indicação para acesso a programa de reabilitação física. Para o tratamento dos dados, utilizou-se a técnica de Análise de Conteúdo, modalidade temática. Os resultados mostram que os gestores hospitalares ainda encontram dificuldades para proceder ao encaminhamento adequado dessas pessoas para serviços especializados de reabilitação, o que compromete a autonomia e independência para o autocuidado. Conclui-se que os gestores além de envolver cuidadores e familiares no preparo da alta de pessoas com lesão neurológica que resulta em incapacidades para o autocuidado, deveriam avaliar as condições de acessibilidade em seus domicílios e fazer encaminhamentos adequados para serviços de reabilitação disponíveis na comunidade, a despeito da pouca divulgação acerca dos fluxos da Rede de Cuidados da Pessoa com Deficiência.

Abstract The present qualitative study was conducted in the second semester of 2014 via interviews with 12 doctors and 13 nurses working as managers at a large hospital that serves as a reference center for urgent and emergent care in the Zona da Mata region of Minas Gerais State, Brazil. The study sought to identify the criteria that doctors and nurses use to discharge individuals with disabling neurological injury with instructions related to accessing physical rehabilitation programs. Thematic content analysis was used to examine data. The results show that the participating hospital managers still have difficulties providing adequate referrals to specialized rehabilitation services and that their patients’ autonomy and independence for self-care are impaired as a result. We concluded that in addition to involving relatives and other caregivers in the discharge of patients with a neurological injury that impairs their self-care abilities, managers should assess the accessibility of the patient’s home and make adequate referrals to rehabilitation services in the community in light of the poor dispersal of information about what is available within the Care for People with Disability Network.

Barefoot Plantar Pressure Indicates Progressive Neurological Damage in Patients with Human T-Cell Lymphotropic Virus Type 1 Infection.

BACKGROUND: The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals. METHODOLOGY: We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient's clinical history and examinations of the patient's reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed. MAIN FINDINGS: The prevalence of neurological disturbances-altered reflexes and skin tactile sensitivity and increased risk of falling-was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects. CONCLUSIONS: The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection.

Nanoparticle Improved Stem Cell Therapy for Erectile Dysfunction in a Rat Model of Cavernous Nerve Injury.

PURPOSE: Recently intracavernous injection of stem cells has garnered great interest as a potential treatment of erectile dysfunction. However, most stem cells are washed out immediately after intracavernous injection. The goal of this study was to investigate using NanoShuttle™ magnetic nanoparticles to maintain stem cells in the corpus cavernosum after intracavernous injection, thereby improving stem cell therapy of erectile dysfunction in an animal model. MATERIALS AND METHODS: Adipose derived stem cells were magnetized with NanoShuttle magnetic nanoparticles to create Nano-adipose derived stem cells. A total of 24 rats underwent bilateral cavernous nerve crush and were randomly assigned to 3 groups, including adipose derived stem cells, Nano-adipose derived stem cells and Nano-adipose derived stem cells plus magnet. Cells were tracked at days 1, 3, 5 and 9 after intracavernous injection. Another 40 rats with bilateral cavernous nerve crush were randomly assigned to 4 groups, including bilateral cavernous nerve crush, bilateral cavernous nerve crush plus adipose derived stem cell intracavernous injection, bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection and bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection plus magnet. Functional testing and histological analysis were performed 4 weeks after intracavernous injection. RESULTS: In the in vitro study 1) NanoShuttle magnetic nanoparticles were successfully bound to adipose derived stem cells and 2) Nano-adipose derived stem cells migrated toward the magnet. In the in vivo study 1) cell tracking showed that Nano-adipose derived stem cells were successfully retained in the corpus cavernosum using the magnet for up to 3 days while most adipose derived stem cells were washed out in other groups by day 1 after intracavernous injection, and 2) intracavernous pressure/mean arterial pressure, and αSMA (α-smooth muscle actin) and PECAM-1 (platelet endothelial cell adhesion molecule 1) expression in the Nano-adipose derived stem cell group was significantly higher than in the other groups. CONCLUSIONS: Magnetization of adipose derived stem cells with NanoShuttle magnetic nanoparticles kept adipose derived stem cells in the corpus cavernosum and improved adipose derived stem cell therapy of erectile dysfunction in an animal model.

Classificação AO e conceito de Dennis na indicação cirúrgica dos traumatismos raquidianos e raquimedulares. Todas as situações são contempladas? / Spinal trauma and spinal cord injury: The AO classification. The Denis concept. The surgical indication. Are all situations addressed?

Os autores discutem a aplicação da classificação AO e do conceito de Denis na qualificação dos traumatismos raquimedular e raquidiano, com ênfase nas indicações de cirurgia da coluna vertebral, expondo um quadro prático para tomada de decisão, que engloba todas as situações. Citam que embora tais classificações, as mais usadas na atualidade, sejam úteis para alicerçar o raciocínio clínico e cirúrgico dos casos de traumatismo raquimedular (TRM) e traumatismo raquidiano (TR), independente da forma de classificação empregada, ou mesmo que surjam outras classificações para os mesmos propósitos, duas questões serão sempre as mais importantes a serem respondidas pelos médicos assistentes na tomada de decisão: Há déficit neurológico? Há instabilidade da coluna vertebral?

The authors discuss the application of the AO classification and the concept of Denis, in qualifying of spinal cord injury, with emphasis on indications of spine surgery, exposing a practical framework for decision making, which includes all situations. Although these ratings, the most used are useful to support the clinical reasoning and surgical cases, two questions must always be answered by attending physicians for making decisions: Is there neurological deficit? Is there instability of the spine?

Randomized clinical trial comparing self-gripping mesh with suture fixation of lightweight polypropylene mesh in open inguinal hernia repair.

BACKGROUND: Postoperative pain is an important adverse event following inguinal hernia repair. The aim of this trial was to compare postoperative pain within the first 3 months and 1 year after surgery in patients undergoing open mesh inguinal hernia repair using either a self-gripping lightweight polyester mesh or a polypropylene lightweight mesh fixed with sutures. METHODS: Adult men undergoing Lichtenstein repair for primary inguinal hernia were randomized to ProGrip™ self-gripping mesh or standard sutured lightweight polypropylene mesh. RESULTS: In total 557 men were included in the final analysis (self-gripping mesh 270, sutured mesh 287). Early postoperative pain scores were lower with self-gripping mesh than with sutured lightweight mesh: mean visual analogue pain score relative to baseline +1·3 and +8·6 respectively at discharge (P = 0·033), and mean surgical pain scale score relative to baseline +4·2 and +9·7 respectively on day 7 (P = 0·027). There was no significant difference in mid-term (1 month) and long-term (3 months and 1 year) pain scores between the groups. Surgery was significantly quicker with self-gripping mesh (mean difference 7·6 min; P < 0·001). There were no significant differences in reported mesh handling, analgesic consumption, other wound complications, patient satisfaction or hernia recurrence between the groups. CONCLUSION: Self-gripping mesh for open inguinal hernia repair was well tolerated and reduced early postoperative pain (within the first week), without increasing the risk of early recurrence. It did not reduce chronic pain. REGISTRATION NUMBER: NCT00827944 (http://www.clinicaltrials.gov).

Valproic acid prevents penile fibrosis and erectile dysfunction in cavernous nerve-injured rats.

INTRODUCTION: Bilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases. AIMS: This study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI-induced ED and penile fibrosis. METHODS: Five groups of rats (8-10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor-ß1 (TGF-ß1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α-SMA) antibodies. MAIN OUTCOME MEASURES: We measured ICP; HDAC3, HDAC4, fibronectin, and TGF-ß1 protein expression; penile fibrosis; penile α-SMA content. RESULTS: There was a voltage-dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF-ß1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α-SMA between all groups. Furthermore, VPA-treated BCNI rats had improved erectile responses to CNS (P < 0.05). CONCLUSION: HDAC-induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post-radical prostatectomy.