Pain characteristics in Italian people with spinal cord injury: a multicentre study.

STUDY DESIGN: Multicentre cross-sectional study. OBJECTIVE: The objective of this study is to evaluate prevalence, location and characteristics of pain in hospital inpatients people with spinal cord injury (SCI). SETTING: Ten Italian rehabilitation centres specialized in spinal injury care, where inpatients are admitted both after the acute lesion and for late complications (time since injury, median [IQR]: 0.8 [0.2-8.2] years). METHODS: All the persons were submitted to AIS scale assessment [1] and modified Ashworth scale [2]; personal data and anamnesis were recorded; any pain within 1 week was investigated and the International Spinal Cord Injury Pain Basic Data Set (ISCIPBDS) Italian version [3] was administered by physicians expert in type of pain definition. RESULTS: Of 385 included persons, 275 (72%) suffered pain, with the score value median [IQR]: 6 [4-8]. The worst pain of the person was nociceptive in 52% and neuropathic in 48% of the cases; 46% of nociceptive pain was located in the neck-shoulder region, whereas 67% of neuropathic pain was located in the sublesional part of the body. In 48% of the whole population, spasticity was observed but only 74% of them had pain. Being old and female are associated with high pain development, OR (95% CI): 1.24 (1.01-1.04) and 1.83 (1.05-3.20), respectively. CONCLUSIONS: A high prevalence of pain is confirmed in persons with SCI, with both nociceptive and neuropathic pain characteristics. Only old age and female sex resulted as variables highly associated with pain.

Bladder management during pregnancy in women with spinal-cord injury: an observational, multicenter study.

INTRODUCTION AND HYPOTHESIS: Pregnancy in women with spinal-cord injury (SCI) poses a clinical challenge. We hypothesized that changes in the management of neurogenic bladder during pregnancy are commonly required and should receive more attention. METHODS: Data were collected by retrospective analysis of medical records and via cross-sectional survey of 52 women with SCI, representing 67 pregnancies, at ten Italian neurourological clinics. All participants provided informed consent. RESULTS: Between 1976 and 2013, 39 participants had one child, 11 had two children, and two had three children. Mean age at the time of SCI was 18 years and at the time of first pregnancy was 30 years. Delivery occurred from weeks 32 to 40 in 98% of first and second pregnancies, and 94% of neonates were healthy. Oxybutynin was used by four women during five pregnancies, which resulted in delivery of healthy babies. Intermittent catheterization was used before 54% of first pregnancies and 39% of second pregnancies. Bladder management was altered during 45% of these pregnancies, and the most common changes were increased use or frequency of intermittent catheterization or use of an indwelling catheter. Urinary tract infections occurred in 48% of pregnancies, and an irregular course was reported in 13% of pregnancies mainly related to tetraplegia and urological complications. CONCLUSIONS: Pregnancy in women with SCI generally has good outcomes and limited risks but frequently necessitates changes in the management of neurogenic bladder. High levels of awareness and focused monitoring of bladder issues are recommended.

Brush border myosin Ia has tumor suppressor activity in the intestine.

The loss of the epithelial architecture and cell polarity/differentiation is known to be important during the tumorigenic process. Here we demonstrate that the brush border protein Myosin Ia (MYO1A) is important for polarization and differentiation of colon cancer cells and is frequently inactivated in colorectal tumors by genetic and epigenetic mechanisms. MYO1A frame-shift mutations were observed in 32% (37 of 116) of the colorectal tumors with microsatellite instability analyzed, and evidence of promoter methylation was observed in a significant proportion of colon cancer cell lines and primary colorectal tumors. The loss of polarization/differentiation resulting from MYO1A inactivation is associated with higher tumor growth in soft agar and in a xenograft model. In addition, the progression of genetically and carcinogen-initiated intestinal tumors was significantly accelerated in Myo1a knockout mice compared with Myo1a wild-type animals. Moreover, MYO1A tumor expression was found to be an independent prognostic factor for colorectal cancer patients. Patients with low MYO1A tumor protein levels had significantly shorter disease-free and overall survival compared with patients with high tumoral MYO1A (logrank test P = 0.004 and P = 0.009, respectively). The median time-to-disease recurrence in patients with low MYO1A was 1 y, compared with >9 y in the group of patients with high MYO1A. These results identify MYO1A as a unique tumor-suppressor gene in colorectal cancer and demonstrate that the loss of structural brush border proteins involved in cell polarity are important for tumor development.

The Female Sexual Function Index (FSFI): linguistic validation of the Italian version.

INTRODUCTION: Although several new measurements for female sexual dysfunction (FSD) have recently been developed, the Female Sexual Function Index (FSFI) remains the gold standard for screening and one of the most widely used questionnaires. The Italian translation of the FSFI has been used in several studies conducted in Italy, but a linguistic validation of the Italian version does not exist. AIM: The aim of this study was to perform a linguistic validation of the Italian version of the FSFI. METHODS: A multicenter cross-sectional study conducted in 14 urological and gynecological clinics, uniformly distributed over Italian territory. We performed all steps necessary to determine the reliability and the test-retest reliability of the Italian version of the FSFI. The study population was a convenience sample of 409 Italian women. MAIN OUTCOME MEASURES: The reliability of the questionnaire was calculated using Cronbach's alpha, which was considered weak, moderate, or high if its value was found less than 0.6, between 0.6 and 0.8, or equal to or greater than 0.8, respectively. The test-retest reliability was assessed for all women in the sample by calculating Pearson's concordance correlation coefficient for each domain and for the total score, both at baseline and after 15 days (r range between -1.00 to +1.00, where +1.00 indicates the strongest positive association). RESULTS: Cronbach's alpha coefficients for total and domain score were sufficiently high, ranging from 0.92 to 0.97 for the total sample. The test-retest procedure revealed that the concordance correlation coefficient was very high both for FSFI-I total score (Pearson's P = 0.93) and for each domain (Pearson's P always >0.92). CONCLUSION: For the first time in the literature, our study has produced a validated and reliable Italian version of the FSFI questionnaire. Consequently, the Italian FSFI can be used as a reliable tool for preliminary screening for female sexual dysfunction for Italian women.

Breastfeeding Following Spinal Cord Injury: Consumer Guide for Mothers.

The World Health Organization (WHO) recommends that infants be breastfed exclusively for the first 6 months of age. However, there are few resources available on the effects a spinal cord injury (SCI) can have for breastfeeding mothers. It is difficult to find information to address the unique challenges women with SCI experience when planning or trying to breastfeed. Our international team, including women with SCI, health care providers, and SCI researchers, aims to address the information gap through the creation of this consumer guide. The purpose of this consumer guide is to share the most common issues women with SCI experience during breastfeeding and provide information, practical suggestions, recommendations, and key resources in lay language. General information about breastfeeding is available on the internet, in books, or from friends and health care providers. We do not intend to repeat nor replace general breastfeeding information or medical advice. Breastfeeding for mothers with SCI is complex and requires a team of health care providers with complementary expertise. Such a team may include family physician, obstetrician, physiatrist, neurologist, occupational and physical therapist, lactation consultant, midwife, and psychologist. We hope this consumer guide can serve as a quick reference guide for mothers with SCI planning of trying to breastfeed. This guide will also be helpful to health care providers as an educational tool.

Motherhood after Spinal Cord Injury: Breastfeeding, Autonomic Dysreflexia, and Psychosocial Health: Clinical Practice Guidelines.

The World Health Organization (WHO) recommends that children be breastfed exclusively for the first 6 months of age. This recommendation may prove challenging for women with spinal cord injury (SCI) who face unique challenges and barriers to breastfeeding due to the impact of SCI on mobility and physiology. Tailored provision of care from health care professionals (HCPs) is important in helping women navigate these potential barriers. Yet, HCPs often lack the confidence and SCI-specific knowledge to meet the needs of mothers with SCI. An international panel of clinicians, researchers, consultants, and women with lived experience was formed to create an accessible resource that can address this gap. A comprehensive survey on breastfeeding complications, challenges, resources, and quality of life of mothers with SCI was conducted, along with an environmental scan to evaluate existing postpartum guidelines and assess their relevance and usability as recommendations for breastfeeding after SCI. Building on this work, this article provides evidence-based recommendations for HCPs, including but not limited to general practitioners, obstetricians, pediatricians, physiatrists, lactation consultants, nurses, midwives, occupational therapists, and physiotherapists who work with prospective and current mothers with SCI.

Brush border myosin Ia inactivation in gastric but not endometrial tumors.

Brush border Myosin Ia (MYO1A) has been shown to be frequently mutated in colorectal tumors with microsatellite instability (MSI) and to have tumor suppressor activity in intestinal tumors. Here, we investigated the frequency of frameshift mutations in the A8 microsatellite in exon 28 of MYO1A in MSI gastric and endometrial tumors and found a high mutation rate in gastric (22/47; 46.8%) but not endometrial (3/48; 6.2%) tumors. Using a regression model, we show that MYO1A mutations are likely to confer a growth advantage to gastric, but not endometrial tumors. The mutant MYO1A(7A) protein was shown to lose its membrane localization in gastric cancer cells and a cycloheximide-chase assay demonstrated that the mutant MYO1A(7A) protein has reduced stability compared to the wild type MYO1A. Frequent MYO1A promoter hypermethylation was also found in gastric tumors. Promoter methylation negatively correlates with MYO1A mRNA expression in a series of 58 non-MSI gastric primary tumors (Pearson's r = -0.46; p = 0.0003) but not in a cohort of 54 non-MSI endometrial tumors and treatment of gastric cancer cells showing high MYO1A promoter methylation with the demethylating agent 5-aza-2'-deoxycytidine, resulted in a significant increase of MYO1A mRNA levels. We found that normal gastric epithelial cells, but not normal endometrial cells, express high levels of MYO1A. Therefore, when considered together, our findings suggest that MYO1A has tumor suppressor activity in the normal gastric epithelium but not in the normal endometrium and inactivation of MYO1A either genetically or epigenetically may confer gastric epithelial cells a growth advantage.

Intravesical Gentamicin: An Option for Therapy and Prophylaxis against Recurrent UTIs and Resistant Bacteria in Neurogenic Bladder Patients on Intermittent Catheterization.

This is a retrospective study of our experience with Gentamicin intravesical instillation as therapy and prophylaxis in patients with lower urinary tract infections (UTIs) undergoing clean intermittent catheterization because of a neurogenic bladder. It is an alternative therapy when all other systemic treatments have failed as it is still an off-label prescription.

A survey of clinical practice concerning long-term follow-up of neurogenic lower urinary tract dysfunction due to spinal cord injury in Italy.

CONTEXT/OBJECTIVE: This study aimed to assess the clinical practice for long-term follow-up (FU) of neurogenic lower urinary tract dysfunction (NLUTD) due to spinal cord injury (SCI) in Italy and compare this practice with the clinical practice in other countries and with the international guidelines. DESIGN: Data concerning the long-term urological FU of individuals with SCI were collected using a questionnaire and analyzed by means of descriptive and inferential statistics. SETTING: Twenty-one Italian centers following SCI patients. PARTICIPANTS: One physician at each center (either a permanent staff member or chief). OUTCOME MEASURES: Questions addressed the treatment of urinary tract infections (UTI), frequency of visits, urinary tract imaging examinations and urodynamic tests (UD), distinguishing between suprasacral and sacral SCI. RESULTS: Nineteen out of 21 centers completed the survey. In most centers, patients were recommended to undergo a visit and an ultrasound examination of urinary tract (UT) at least once a year. While the median interval between FU visits was identical (12 months) for individuals with suprasacral and sacral SCI, the two interval distributions were significantly different (suprasacral SCI: min-max 4-18, IQR = 6; sacral SCI: min-max 6-24; IQR = 8.5; P = 0.02), showing people with suprasacral SCI are followed up more often. Approximately 80% of the surveyed centers performed scheduled UD, with a yearly median frequency of 12 months (range 6-36) for patients with suprasacral SCI, as compared to a median frequency of 18 months for sacral SCI (range 0-36, P = 0.04). VideoUD and antibiotic prophylaxis for recurrent UTIs are carried out only by urologists in 63% and 47.4% of the centers, respectively. Overall, Italian centers share common strategies that compare to standards, including yearly visits, yearly UT examinations and stricter follow-up of people with suprasacral SCI, but may not have standard protocols for antibiotic prophylaxis of UTI, and in few cases control visits and UD are carried out too often. CONCLUSIONS: Even though most Italian centers follow up patients with NLUTD secondary to SCI according to international guidelines, heterogeneity in frequency of FU examinations still exists. A tailored approach to the SCI patient that minimizes unnecessary examinations and groups different tests in a single access could improve patients' compliance with FU and reduce costs for the Health system.

Antimuscarinics for neurogenic overactive bladder in multiple sclerosis: real-life data.

Background: Antimuscarinics (AMs) represent the mainstay of treatment for storage lower urinary tract symptoms (LUTS) but few data are available on their impact in multiple sclerosis (MS) patients. Objective: To assess effectiveness and tolerability of AMs in MS patients with neurogenic detrusor overactivity (NDO). Methods: Sixty consecutive outpatients, who started treatment with AMs at one centre, were recruited. The primary endpoint was change in Patient's Perception of Intensity of Urgency Scale (PPIUS) at 6 months; secondary endpoints were post-void residual urine (PVR) and pads used daily. Incidence and severity of adverse events (AEs) were recorded. Results: Significant reduction (p < 0.001) of mean PPIUS and pads use were detected, as well as a significant increase (p < 0.001) of PVR (143 ±â€„42 ml).AEs, recorded in 53% of patients, were frequently multiple and caused suspension of AM in 10% of cases, mainly for xerostomia, which has been the commonest AE (26.6%). Neurological AEs appeared in 11.7% of subjects, mostly with oxybutynin. Worsening/onset of voiding LUTS, reported by 8.3% of MS, resulted to be the unique AE correlated to AM dosage. Conclusion: This study suggests that AMs are effective in MS patients, but their use should be tailored on every patient as even low dosages can be poorly tolerated. AEs, including neurological ones, are common.

The role of clean intermittent catheterization in rehabilitation setting: a survey of healthcare operators' perception in Italy.

BACKGROUND: Clean intermittent catheterization (CIC) is defined as the repetitive temporary placement of a catheter to empty the bladder. It has become the first-line and preferred method of drainage in patients with neurogenic lower urinary tract dysfunction. AIM: We investigated the use of CIC in the real-life setting in Italy. METHODS: We administered interviews to health operators of centers for urinary rehabilitation. RESULTS: Overall, 110 healthcare professionals were invited to fill the questionnaire and 109 (72% males) answered it. Answers to the questionnaire showed that 65.2% of patients with urinary retention used CIC, 22.3% used a transurethral indwelling catheter, and 5.5% used a suprapubic catheter; 6.3% of patients used CIC during the daytime and used the indwelling catheter during the night. The most relevant factor, pertaining the patient, to decide to propose the use of CIC was manual ability, followed by good cognitive function, adequate anatomical condition, age, available adequate caregiver, psychological consistency and good socio-cultural level. Lubrification, usability and easy insertion were the most relevant characteristics of a catheter that favored the choice of the device for CIC. In addition, in the opinion of interviewed operators, the line of catheters with glycerin-water based lubrification had the main characteristics to be preferred for CIC. CONCLUSIONS: CIC is a preferential intervention for urinary retention in the clinical practice in Italy, is chosen on the basis of patient's characteristics, and lubrification, usability and easy insertion are the most important features of catheters.

Investigation of the role of tyrosine kinase receptor EPHA3 in colorectal cancer.

EPH signaling deregulation has been shown to be important for colorectal carcinogenesis and genome-wide sequencing efforts have identified EPHA3 as one of the most frequently mutated genes in these tumors. However, the role of EPHA3 in colorectal cancer has not been thoroughly investigated. We show here that ectopic expression of wild type EPHA3 in colon cancer cells did not affect their growth, motility/invasion or metastatic potential in vivo. Moreover, overexpression of mutant EPHA3 or deletion of the endogenous mutant EPHA3 in colon cancer cells did not affect their growth or motility. EPHA3 inactivation in mice did not initiate the tumorigenic process in their intestine, and had no effects on tumor size/multiplicity after tumor initiation either genetically or pharmacologically. In addition, immunohistochemical analysis of EPHA3 tumor levels did not reveal associations with survival or clinicopathological features of colorectal cancer patients. In conclusion, we show that EPHA3 does not play a major role in colorectal tumorigenesis. These results significantly contribute to our understanding of the role of EPH signaling during colorectal carcinogenesis, and highlighting the need for detailed functional studies to confirm the relevance of putative cancer driver genes identified in sequencing efforts of the cancer genome.

Loss of the EPH receptor B6 contributes to colorectal cancer metastasis.

Although deregulation of EPHB signaling has been shown to be an important step in colorectal tumorigenesis, the role of EPHB6 in this process has not been investigated. We found here that manipulation of EPHB6 levels in colon cancer cell lines has no effect on their motility and growth on a solid substrate, soft agar or in a xenograft mouse model. We then used an EphB6 knockout mouse model to show that EphB6 inactivation does not efficiently initiate tumorigenesis in the intestinal tract. In addition, when intestinal tumors are initiated genetically or pharmacologically in EphB6+/+ and EphB6-/- mice, no differences were observed in animal survival, tumor multiplicity, size or histology, and proliferation of intestinal epithelial cells or tumor cells. However, reintroduction of EPHB6 into colon cancer cells significantly reduced the number of lung metastasis after tail-vein injection in immunodeficient mice, while EPHB6 knockdown in EPHB6-expressing cells increased their metastatic spread. Consistently, although EPHB6 protein expression in a series of 130 primary colorectal tumors was not associated with patient survival, EPHB6 expression was significantly lower in lymph node metastases compared to primary tumors. Our results indicate that the loss of EPHB6 contributes to the metastatic process of colorectal cancer.

Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment.

PURPOSE: The clinical management of colorectal cancer patients has significantly improved because of the identification of novel therapeutic targets such as EGFR and VEGF. Because rapid tumor proliferation is associated with poor patient prognosis, here we characterized the transcriptional signature of rapidly proliferating colorectal cancer cells in an attempt to identify novel candidate therapeutic targets. EXPERIMENTAL DESIGN: The doubling time of 52 colorectal cancer cell lines was determined and genome-wide expression profiling of a subset of these lines was assessed by microarray analysis. We then investigated the potential of genes highly expressed in cancer cells with faster growth as new therapeutic targets. RESULTS: Faster proliferation rates were associated with microsatellite instability and poorly differentiated histology. The expression of 1,290 genes was significantly correlated with the growth rates of colorectal cancer cells. These included genes involved in cell cycle, RNA processing/splicing, and protein transport. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protoporphyrinogen oxidase (PPOX) were shown to have higher expression in faster growing cell lines and primary tumors. Pharmacologic or siRNA-based inhibition of GAPDH or PPOX reduced the growth of colon cancer cells in vitro. Moreover, using a mouse xenograft model, we show that treatment with the specific PPOX inhibitor acifluorfen significantly reduced the growth of three of the seven (42.8%) colon cancer lines investigated. CONCLUSIONS: We have characterized at the transcriptomic level the differences between colorectal cancer cells that vary in their growth rates, and identified novel candidate chemotherapeutic targets for the treatment of colorectal cancer.

Usefulness of sacral nerve modulation in a series of multiple sclerosis patients with bladder dysfunction.

OBJECTIVE: Bladder dysfunctions are common in multiple sclerosis (MS) often causing the most distressing symptoms. The aim of this paper was to evaluate the effectiveness of sacral nerve modulation (SNM) in this disease. METHODS: We conducted an observational retrospective survey in 17 patients treated with SNM in the north-east of Italy, all complaining of bladder symptoms (storage in 41%, voiding in 24%, mixed in 35%) unresponsive to conventional therapies, with a mean follow-up of 52 ± 26 months and mean Expanded Disability Status Scale score of 5.8 ± 1.8. RESULTS: 75% of patients reported significant and lasting improvement in bladder symptoms and in quality of life. We observed a statistically significant improvement in frequency, urgency, number of pads, residual volumes, number of catheterizations and in the voided volumes. In 5 out of 6 cases with mixed symptoms the stimulation was discontinued (device totally explanted or turned off) after a mean time of 66 months (range 10-84 months) after the implant, for disease progression or loss of efficacy. CONCLUSION: SNM could be an option in very selected cases of storage and voiding symptoms refractory to conservative treatments caused by a stable or slowly progressive MS considering its minimal invasiveness and reversibility. The poor results observed suggest avoiding this therapy in mixed symptoms and in cases of advanced disability.

RHOA inactivation enhances Wnt signalling and promotes colorectal cancer.

Activation of the small GTPase RHOA has strong oncogenic effects in many tumour types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/ß-catenin signalling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of ß-catenin from the membrane to the nucleus and enhanced Wnt/ß-catenin signalling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared with primary human colon tumours. Therefore, we have identified a new mechanism of activation of Wnt/ß-catenin signalling and characterized the role of RHOA as a novel tumour suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumour progression and metastasis.