Vertebral Fractures in Pediatric Suicidal Jumpers: A Retrospective Study with Epidemiological and Clinical Analysis before and after the COVID-19 Pandemic.

BACKGROUND: From the beginning of the COVID-19 pandemic, reports in the literature confirm a significant increase in suicide attempts in children and adolescents. At the Bambino Gesù Pediatric Hospital Emergency Department (Rome, Italy), there was a dramatic increase in suicidal jumpers. Many of these presented vertebral fractures. METHODS: This retrospective study includes all suicidal jumpers with vertebral fractures treated from April 2017 to March 2023. We collected and compared data from three years before to three years after the pandemic, analyzing vertebral fractures. RESULTS: From April 2019 to March 2020, 141 cases of suicide attempt arrived at the emergency department. Five of these were suicidal jumpers without vertebral fractures. From April 2020 to March 2023, 362 cases of suicide were hospitalized and 19 were suicidal jumpers; 12 reported vertebral fractures (mean age 14 years). Seven patients were treated by percutaneous pedicle fixation. Three patients needed an open spinal surgery by posterior approach. One case with cervical fractures was treated by Halo-Vest. CONCLUSIONS: This is the first report that shows a sharp increase in vertebral body fractures due to suicide jumping attempts in children and adolescents. This could be a new epidemiological phenomenon persisting or even increasing over time in the pediatric population as a consequence of the COVID-19 pandemic.

Clinical report and predictors of sequelae of 319 cases of pediatric bacterial osteomyelitis.

Pediatric osteomyelitis is an insidious disease that can lead to permanent sequelae, the management of which still relies on lengthy intravenous antibiotic therapy. The purpose of this study is to report and describe the clinical course and outcome of pediatric bacterial osteomyelitis in our experience. We reported the clinical, diagnostic, and treatment characteristics of all cases of osteomyelitis in children younger than 18 years of age who were hospitalized between January 2010 and December 2021 at the Bambino Gesù Children's Hospital in Rome, Italy, we compared patients with and without complications at follow-up, to identify any predictive factor for sequelae. The study sample included 319 cases of pediatric bacterial osteomyelitis. The median age was 7.77 years. Males (60.8%) were more affected than females. The most affected bones were the femur, tibia, and spine. Etiology was identified in 40.1% of cases, with S.aureus as the most common causative agent. Sequelae were reported in 43 cases (13.5%). The main predictors of sequelae were sepsis on admission and hypergammaglobulinemia. Our results show that a severe presentation with sepsis and hypergammaglobulinemia on admission may be associated with a higher frequency of late sequelae. Early recognition and aggressive treatment of this subgroup of patients may lead to a reduction in complications.

High Prevalence of Scoliosis in a Large Cohort of Patients with Prader-Willi Syndrome.

The characteristics of scoliosis were investigated in a large cohort of children and adults with Prader-Willi syndrome (PWS), analysing the role of age, gender, puberty, body mass index (BMI), genotype and growth hormone therapy (GHT) on its onset and severity. A retrospective cross-sectional study was performed in 180 patients with genetically confirmed PWS (96 females), aged 17.6 ± 12 years. Eighty-five subjects (47%) were obese. One hundred and fifty subjects (83.3%) were on GHT, while 30 patients had never been treated. Overall, 150 subjects (83.3%) were affected by scoliosis, 80.2% of children and adolescents and 87.8% of adults. A mild degree of scoliosis was observed in 58 patients (38.7%), moderate in 43 (28.7%) and severe in 49 (32.6%). Median age at diagnosis of scoliosis was 6.3 years, while the severe forms were diagnosed earlier (median age: 3.8 years). The cumulative probability at 5 years of age was equal to 0.403 and almost doubled at 15 years. No significant associations were found between scoliosis and genotype, gender, pubertal stage, GHT and BMI. A corset was prescribed to 75 subjects (50%) at a median age of 7.5 years, while 26 subjects (17.3%) underwent surgery at a median age of 13.1 years. Our data indicate that scoliosis is one of the major concerns for PWS patients that increases with age, and therefore suggest the need for regular systematic monitoring of spinal deformity from paediatric age.

Hemivertebra Resection and Spinal Arthrodesis by Single-Stage Posterior Approach in Congenital Scoliosis and Kyphoscoliosis: Results at 9.6 Years Mean Follow-up.

BACKGROUND: Congenital kyphoscoliosis due to hemivertebra is generally treated surgically because of high risk of curve progression and high risk of nervous system complications. Modern posterior access surgical techniques, including total hemivertebra resection, can completely correct deformity without additional anterior access surgeries. The purpose of this study was to evaluate midterm results of hemivertebra resection and spinal arthrodesis; the hypothesis was that it is a safe, effective, and reproducible procedure. MATERIALS AND METHODS: From 2006 to 2019, hemivertebra resection and instrumented spinal arthrodesis with pedicle screws was performed on 82 patients with congenital vertebral deformities (62 scoliosis and 20 kyphoscoliosis) by posterior approach. Mean age at surgery was 8.6 years, and 22 patients were under 10 years of age. After stabilization patients have been braced for a period from 3 to 5 months. RESULTS: Mean follow-up was 9.6 years (range 1.2-12.8 years); mean kyphosis curve after surgery was reduced to 20° Cobb; and mean scoliosis curve was reduced to 11° Cobb. We experienced no major complications (postsurgical infection, instrumentation failure, severe neurological impairment, severe blood loss) at latest follow-up . CONCLUSION: We strongly advocate one-time posterior hemivertebra resection and arthrodesis as the most suitable surgical procedure for congenital scoliosis due to hemivertebra. Posterior approach interventions with pedicle screws instrumentation are less invasive than combined anterior-posterior approach interventions. We think that posterior approach procedures can lead to excellent deformity correction in both frontal and sagittal views, optimal stability, and low risk of nervous injury. CLINICAL RELEVANCE: Congenital scoliosis treatment is one of the most challeging conditions a spine surgeon has to face. We advocate that a one-stage posterior approach for hemivertebrectomy and fusion is a reliable, safe tachnique, whom excellent results remain stable at a mid/long-term follow-up. LEVEL OF EVIDENCE: Level 4.

Spondylodiscitis in Children: A Retrospective Study and Comparison With Non-vertebral Osteomyelitis.

Objectives: The aim of this study is to provide new data on pediatrics spondylodiscitis for an optimal clinical management of this site-specific osteomyelitis. Methods: We reported 48 cases of pediatric spondylodiscitis and made three comparisons between: (1) tubercular and non-tubercular cases; (2) patients aged more or less than 5 years; (3) children with spondylodiscitis and 62 controls with non-vertebral osteomyelitis. Results: A higher rate of sequelae was reported in patients with tubercular spondylodiscitis, but no significant differences were noted at the cut-off of 5 years of age. Compared to non-vertebral osteomyelitis, pediatric spondylodiscitis affects younger children of both genders, usually presenting with afebrile back pain, and requiring longer time to admission, hospitalization, and antibiotic therapy. Conclusion: Pediatric spondylodiscitis is an insidious disease with a non-specific presentation in childhood and peculiarities of its own. However, when clinical remission is obtained by an early start of broad-spectrum antibiotics, prolonging the therapy does not improve, nor worsens, the outcome. Surgical management is mandatory in case of vertebral instability and neurological signs but can be avoided when the infection is promptly treated with antibiotic therapy.

The expression of YWHAZ and NDRG1 predicts aggressive outcome in human prostate cancer.

Some prostate cancers (PCas) are histo-pathologically grouped within the same Gleason Grade (GG), but can differ significantly in outcome. Herein, we aimed at identifying molecular biomarkers that could improve risk prediction in PCa. LC ESI-MS/MS was performed on human PCa and benign prostatic hyperplasia (BPH) tissues and peptide data was integrated with omic analyses. We identified high YWHAZ and NDRG1 expression to be associated with poor PCa prognosis considering all Gleason scores (GS). YWHAZ and NDRG1 defined two subpopulations of PCa patients with high and intermediate risk of death. Multivariable analyses confirmed their independence from GS. ROC analysis unveiled that YWHAZ outperformed GS beyond 60 months post-diagnosis. The genomic analysis of PCa patients with YWHAZ amplification, or increased mRNA or protein levels, revealed significant alterations in key DNA repair genes. We hereby state the relevance of YWHAZ in PCa, showcasing its role as an independent strong predictor of aggressiveness.

Natural Course and Diagnosis of Lumbar Spinal Stenosis: WFNS Spine Committee Recommendations.

Lumbar spinal stenosis (LSS) is defined as a degenerative disorder showing a narrowing of the spinal canal. The diagnosis is straightforward in cases with typical neurogenic claudication symptoms and unequivocal imaging findings. However, not all patients present with typical symptoms, and there is obviously no correlation between the severity of stenosis and clinical complaint. The radiologic diagnosis of LSS is widely discussed in the literature. The best diagnostic test for the diagnosis of LSS is magnetic resonance imaging (MRI). However, canal diameter measurements have not gained much consensus from radiologists, whereas qualitative measures, such as cerebrospinal fluid space obliteration, have achieved greater consensus. Instability can best be defined by standing lateral radiograms and flexion-extension radiograms. For cases showing typical neurogenic claudication symptoms and unequivocal imaging findings, the diagnosis is straightforward. However, not all patients present with typical symptoms, and there is obviously no correlation between the severity of stenosis (computed tomography and MRI) and clinical complaint. In fact, recent MRI studies have shown that mild-to-moderate stenosis can also be found in asymptomatic individuals. Routine electrophysiological tests such as lower extremity electromyography, nerve conduction studies, F-wave, and H-reflex are not helpful in the diagnosis and outcome prediction of LSS. The electrophysiological recordings are complementary to the neurologic examination and can provide confirmatory information in less obvious clinical complaints. However, in the absence of reliable evidence, imaging studies should be considered as a first-line diagnostic test in the diagnosis of degenerative LSS.

Lumbar Spine Osteoblastoma with Secondary Aneurysmal Bone Cyst Causing Severe Trunk Imbalance and Radiculopathy: A Case Report.

INTRODUCTION: Osteoblastomas are primary bone tumors, rarer than osteoid osteomas, and <10% of these lesions occurs in the spine. Aneurysmal bone cysts (ABCs) are rare, benign lesion of the bone and approximately 8-30% of ABCs arise in the spine, mostly in the thoracic and the lumbar regions. The association between them is quite rare in the general population. CASE REPORT: We report a case of a 14-year-old boy, soccer player, with an osteoblastoma of the left posterior neural arc of L2 and a secondary aneurismal bone cyst compressing the left L2 nerve root, causing severe antalgic scoliosis and back pain with radiculopathy. A complete surgical excision with radicular decompression has been performed, and the histologic examination confirmed the diagnostic hypothesis (osteoblastoma + ABC). At 6 months follow-up, the patient presented a complete resolution of symptoms, but the trunk imbalance was not completely resolved. CONCLUSION: Spine localization of osteoblastoma + ABC is rare and its diagnosis and treatment are often challenging. Complete surgical excision seems to be confirmed as the gold standard of treatment, but the option of instrumented arthrodesis should be carefully evaluated.

Conservative versus surgical treatment of Gartland type 2 supracondylar humeral fractures: What can help us choosing?

BACKGROUND: Pediatric supracondylar humeral fractures (PSHF) are most common elbow fractures among children and adolescents. While there is substantial agreement on treating type 1 and type 3 fractures (conservatively and surgically, respectively), the debate on optimal treatment of Gartland type 2 fractures is still open.We wanted to review our cases, analyzing outcomes and seeking for parameters that could help surgeons treating these injuries. METHODS: We retrospectively reviewed 41 patients treated with reduction and casting (group A) and matched to 38 patients treated with closed reduction and percutaneous pining (CRPP, group B) for Gartland type 2 fractures between 2009 and 2013. At a mean follow-up of more than 6 years patients were analyzed by an accurate clinical exam and evaluation scales. Radiographic parameters at time of cast or pins removal were studied too. RESULTS: There were no statistically significant differences in clinical exam and evaluation scales between groups. Two patients in group A developed a cubitus varus deformity and one patient in group B had a superficial pin-tract infection. Baumann angle (BA) was out of normal range in two cases of conservative group and anterior humeral line (AHL) bisected capitellum in 42.1% of patients in group A and 73.2% in group B (p < .05). CONCLUSION: It is reasonable to expect satisfactory outcomes both after conservative and surgical treatment of type 2 fractures, if cornerstones of both treatments are applied. Parameters that should be focused are probably two: complications (2 cases of cubitus varus in group A versus one superificial pin-tract infections in group B) and the better trend in surgical group in regards to loss of flexion and hyperextension of the affected elbow, likely related to the other notable datum, that is the percentage of cases in which AHL bisects capitellum. We think that, in absence of vascolonervous lesions and important swelling, BA and AHL are the most important parameters that can help us choosing the optimal treatment, as clarified in the algorithm we developed. LEVEL OF EVIDENCE: Level III - retrospective comparative study.

Spine challenges in mucopolysaccharidosis.

PURPOSE: Mucopolysaccharidosis (MPS) are rare inherited metabolic diseases, causing lysosomal storage of mucopolysaccharides; clinical presentation involves skeletal system and particularly the spine. Anomalies include developing kyphosis at thoracolumbar junction, that can causes nervous symptoms, and dens hypoplasia with associated atlantoaxial subluxation that can cause myelopathy. We present our experience in the treatment of spine pathology in MPS. METHODS: Medical treatments of MPS seem to have little impact on spine disease: treatment of cervical instability often includes surgical decompression and stabilization, as in patient MPS1 that we present, while thoracic lumbar kyphosis is treated by bracing and, in severe cases, with surgery. Bracing is more effective in kyphosis under 40° Cobb. Our surgical cases with thoracic lumbar kyphosis over 40° Cobb, treatment include the first one ever described by only posterior approach with vertebrectomy in MPS and a case of lateral costo-transverse approach instrumented correction. RESULTS: Surgical patients had no major complications after surgery and CT scan at follow-up showed complete fusion without loss of correction, even if in a cervical case we used an adult rigid instrumentation in a four year-and-six month-old girl (11 years follow-up) and in thoracic lumbar kyphosis case treated by vertebrectomy due to diminutive anatomy we positioned interbody cage in suboptimal position. CONCLUSIONS: Bracing is a viable treatment strategy in thoracic lumbar kyphosis and can obtain good clinical results at medium terms follow-up even if kyphosis deformity remains in radiographs. Surgical treatment is effective in severe evolving cases both at cervical and thoracic lumbar level, main difficulties arose from unavailability of dedicated instrumentation in very young patient, as even smallest devices available are often too big.

Human Periprostatic Adipose Tissue: Secretome from Patients With Prostate Cancer or Benign Prostate Hyperplasia.

BACKGROUND/AIM: Periprostatic adipose tissue (PPAT) directs tumour behaviour. Microenvironment secretome provides information related to its biology. This study was performed to identify secreted proteins by PPAT, from both prostate cancer and benign prostate hyperplasia (BPH) patients. PATIENTS AND METHODS: Liquid chromatography-mass spectrometry-based proteomic analysis was performed in PPAT-conditioned media (CM) from patients with prostate cancer (CMs-T) (stage T3: CM-T3, stage T2: CM-T2) or benign disease (CM-BPH). RESULTS: The highest number and diversity of proteins was identified in CM-T3. Locomotion was the biological process mainly associated to CMs-T and reproduction to CM-T3. Immune responses were enriched in CMs-T. Extracellular matrix and structural proteins were associated to CMs-T. CM-T3 was enriched in proteins with catalytic activity and CM-T2 in proteins with defense/immunity activity. Metabolism and energy pathways were enriched in CM-T3 and those with immune system functions in CMs-T. Transport proteins were enriched in CM-T2 and CM-BPH. CONCLUSION: Proteins and pathways reported in this study could be useful to distinguish stages of disease and may become targets for novel therapies.

Adolescent idiopathic scoliosis correction by instrumented vertebral arthrodesis with autologous bone graft from local harvesting without bone substitute use: results with mean 3 year follow-up.

PURPOSE: Bone substitutes' advantage is enhancing arthrodesis biologic support without further autologous bone graft harvested from other skeleton sites, as from posterior iliac crests; however, in our experience, bone substitutes' integration is often incomplete. METHODS: From 2012 to 2017, we operated 108 patients by posterior instrumented vertebral arthrodesis in adolescent idiopathic scoliosis (AIS) correction, mean main curve 80° Cobb, and mean age 12 years and 6 months, with all pedicle screws instrumentation in main curve/curves area and hooks at upper tip of implant; bone graft has been harvested only at vertebral level, without bone substitutes or autologous graft from other patient sites or allogenic bone graft. We matched this group with 98 patients previously operated in which we used calcium triphosphate. RESULTS: At 3 year mean follow-up, all patients in group treated with autologous bone graft only have complete and stable arthrodesis without loss of correction (mean curve 27° Cobb) or instrumentation failure. At 6 year mean follow-up in the group treated with autologous bone graft augmented by calcium triphosphate, 96 patients have stable arthrodesis without loss of correction (mean curve 24°), 1 case has implant break, and 1 case has 8° Cobb loss of correction. CONCLUSION: Bone substitutes are a further cost in arthrodesis surgery and suboptimal integration leaves foreign bodies on vertebras. Our experience shows that all pedicle screw instrumentation and bracing after surgery obtain stable correction showing in time a solid arthrodesis with autologous bone only, harvested at local site, without bone substitutes or further bone graft.

Prostate Cancer, High Cortisol Levels and Complex Hormonal Interaction.

Prostate cancer (PCa) is one of the most common diseases in men. It is important to assess prognostic factors and whether high cortisol levels and complex hormonal interactions could be responsible for PCa development. We evaluated the relationship between cortisol, leptin and estrogens in 141 men, 71 with PCa and the remaining 70 constituting a low risk group (LRG). They were recruited for this study from a total of 2906 middleaged men (ages 4570 years) who completed an evaluation for prostatic diseases at the Urology Division, Hospital de Clinicas "Jose de San Martin", University of Buenos Aires, in May 2009. In this cross sectional study, cortisol, PSA, totaltestosterone, freetestosterone, bioavailable testosterone, LH and estradiol were measured in serum. We observed increased cortisol levels in PCa patients as compared to LRG cases (p=0.004,). Leptin and estradiol levels were also higher in PCa patients (p=0.048; p<0.0001, respectively). Logistic regression analysis indicated that serum cortisol (OR: 1.110 (95% CI 1.0161.213), p=0.022), estradiol (OR: 1.044 (95% CI 1.0081.081), p=0.016) and leptin (OR: 1.248 (95% CI 1.0481.487), p=0.013) explained 27% of the variance of dependent variables, even after adjusting for age, smoking, BMI and waist circumference. We found increased cortisol levels in PCa patients as compared to LRG, as well as an altered circulating hormonal profile.

Complex relationship between sex hormones, insulin resistance and leptin in men with and without prostatic disease.

OBJECTIVES: To assess sex hormones, leptin and insulin-resistance in men with prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and to study associations between androgens and histologic score of prostate tissue in PCa. SUBJECTS AND METHODS: Two hundred ten men older than 45 years selected from 2906 participants of a population screening for PCa were studied: 70 with PCa, 70 with BPH and 70 controls (CG), matched by body mass index and age. Insulin, IGF-1, PSA, leptin, total, free (fT) and bioavailable testosterone (bT) and estradiol were measured. Each group was subdivided into two subgroups considering the presence of metabolic syndrome (MS); androgens and leptin levels were analyzed in the subgroups. RESULTS: Prostate cancer and BPH patients presented higher total, fT and bT levels than CG. IGF-1, insulin and HOMA index were higher in BPH than in the other two groups. PCa presented higher leptin [median (range) 6.5 (1.3-28.0) versus 4.8 (1.1-12.3) ng/ml; p < 0.01] and estradiol [median (range) 37.0 (20-90) versus 29.0 (20-118) pg/ml; p = 0.025] levels than CG. After dividing men considering the presence of MS, leptin was higher and total testosterone was lower in MS patients in all the groups. CONCLUSIONS: It was observed a coexistence of an altered hormone profile with increased sex hormones and leptin in PCa patients, in accordance with the new perspective of PCa pathogenesis.

Detection of a tadalafil analogue as an adulterant in a dietary supplement for erectile dysfunction.

INTRODUCTION: Several cases of adulteration of dietary supplements with tadalafil, sildenafil, and vardenafil, or their unapproved analogues have been reported worldwide. Mainly, the presence of the latter represents a serious health risk to consumers as their efficacy and toxic effects have not been assessed and may result in unpredictable adverse effects. AIM: To investigate the suspected adulteration with synthetic phosphodiesterase type 5 (PDE-5) inhibitors in a dietary supplement marketed in Argentina for the treatment of erectile dysfunction (ED). METHODS: The content of the capsules of the dietary supplement (sample A) was analyzed by thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) diode-array detection. From the organic extract of sample A, a major compound was purified by column chromatography (CC). The isolated compound was identified by proton nuclear magnetic resonance (1H NMR) and carbon NMR (13C NMR), heteronuclear single quantum coherence, distortionless enhancement by polarization transfer (DEPT 135), electrospray ionization mass spectrometry, and ultraviolet, and infrared (Fourier transform infrared spectroscopy) spectroscopy. MAIN OUTCOME MEASURE: Proof of adulteration of herbal products with synthetic PDE-5 inhibitors. RESULTS: By TLC and HPLC analysis, a major compound was detected in sample A organic extract. The purification of this extract by CC led to the isolation of a pure compound which was identified according to its spectral data as (6R,12aR)-2-amino-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydropyrazino [1',2':1,6] pyrido [3,4-b] indole-1,4-dione or aminotadalafil. CONCLUSIONS: An unapproved PDE-5 inhibitor analogue, which was identified as aminotadalafil, has been detected in a dietary supplement. This study represents the first report in Latin America and one of the few independent studies of an adulteration with an unapproved PDE-5 inhibitor of an herbal product for ED treatment.

Life events are positively associated with luteinizing hormone in middle age adult men: role of cortisol as a third variable.

Previous studies have tested the relationship between chronic stress and sex hormones, but inconsistent results have been found. One possibility is that this association may depend on other biological factors. This study examined the relationship between stressful life events (LE) and sex hormones in men, and whether cortisol is involved in this relationship. From a total number of 2906 men who completed a screening for the early detection of prostate cancer, 139 healthy men (mean ± SD age, 57.8 ± 5.7 years) were included in this study. Participants were assessed with the Holmes and Rahe questionnaire in relation to their experience of LE during the previous 1-5 years. Salivary and serum cortisol was measured at 08:00-09:00 h, as well as luteinizing hormone (LH), total testosterone, epinephrine (E) and norepinephrine (NE). LE weight sum and LE number positively correlated with LH (r = 0.293, p = 0.004; r = 0.220, p = 0.031, respectively). In a multiple regression analysis, LE-sum explained an additional and significant 10.4% of the variance in LH levels, after statistically controlling for the effects of age, waist circumference (WC) and BMI (F(1,90) = 6.61, p < 0.05). Importantly, cortisol interacted with LE in relation to total testosterone. In men with high cortisol values (≥15.4 µg/dl), there was a statistically significant positive relationship between LE number and total testosterone levels (p = 0.05), while LE were unrelated to total testosterone in men with low cortisol. LE correlated with sex hormones, predicting LH values, and in men with high cortisol levels shows a possible moderator effect of cortisol on the relationship between LE and total testosterone.

Association between testosterone levels and the metabolic syndrome in adult men.

OBJECTIVE: To evaluate the relationship between testosterone levels and the metabolic syndrome (MS) in men older than 45 years. METHODS: Six hundred and sixty men (45-70 years) selected from 2906 participants of a population screening for prostate cancer were included in this study. Testosterone and the components of MS were assessed in all men. MS was diagnosed according to NCEP-ATP III criteria. Triglycerides (TG)/HDL-cholesterol (chol) index was calculated. RESULTS: The presence of MS was inversely associated with testosterone (χ2, p < 0.001), independently of age (OR 0.802, CI 95%: 0.724-0.887, p < 0.0001). Hypertension was the most frequent abnormality observed followed by elevated TG and waist circumference (WC). Testosterone correlated positively with HDL-chol (r: 0.14, p < 0.0001) and negatively with body mass index (BMI)(r: -0.29, p < 0.0001), WC (r: -0.26, p < 0.0001), TG (r: -0.20, p < 0.0001), TG/HDL-chol (r: -0.20, p < 0.0001), glucose (r: -0.11, p = 0.005) and MS score (r: -0.23, p < 0.0001). CONCLUSIONS: Our results show that in men older than 45 years, as long as testosterone levels decline, the prevalence of MS increases, independently of age. The correlations found between testosterone and four of the five components of MS, as well as with BMI and TG/HDL-chol ratio, a surrogate marker of insulin resistance, suggest considering male hypogonadism as a determinant of developmental abnormalities typical of MS.

Prostate tumor growth is impaired by CtBP1 depletion in high-fat diet-fed mice.

PURPOSE: Clinical and epidemiologic data suggest that obesity is associated with more aggressive forms of prostate cancer, poor prognosis, and increased mortality. C-terminal-binding protein 1 (CtBP1) is a transcription repressor of tumor suppressor genes and is activated by NADH binding. High calorie intake decreases intracellular NAD(+)/NADH ratio. The aim of this work was to assess the effect of high-fat diet (HFD) and CtBP1 expression modulation over prostate xenograft growth. EXPERIMENTAL DESIGN: We developed a metabolic syndrome-like disease in vivo model by feeding male nude mice with HFD during 16 weeks. Control diet (CD)-fed animals were maintained at the same conditions. Mice were inoculated with PC3 cells stable transfected with shCtBP1 or control plasmids. Genome-wide expression profiles and Gene Set Enrichment Analysis (GSEA) were performed from PC3.shCtBP1 versus PC3.pGIPZ HFD-fed mice tumors. RESULTS: No significant differences were observed in tumor growth on CD-fed mice; however, we found that only 60% of HFD-fed mice inoculated with CtBP1-depleted cells developed a tumor. Moreover these tumors were significantly smaller than those generated by PC3.pGIPZ control xenografts. We found 823 genes differentially expressed in shCtBP1 tumors from HFD-fed mice. GSEA from expression dataset showed that most of these genes correspond to cell adhesion, metabolic process, and cell cycle. CONCLUSIONS: Metabolic syndrome-like diseases and CtBP1 expression cooperate to induce prostate tumor growth. Hence, targeting of CtBP1 expression might be considered for prostate cancer management and therapy in the subset of patients with metabolic syndromes.