Subclinical atherosclerosis and endothelial dysfunction in patients with polymyalgia rheumatica: a pilot study.

Objective: The aim of the study was to investigate endothelial function in treatment-naïve polymyalgia rheumatica (PMR) patients and its modification during steroid therapy, in relation to changes in clinical and laboratory parameters.Method: This prospective observational study involved patients with a new diagnosis of PMR according to provisional American College of Rheumatology/European League Against Rheumatism 2012 criteria, who were naïve to steroid therapy, and control subjects matched for age, gender, and comorbidities. All participants underwent clinical and vascular ultrasound evaluations at baseline and after 1, 3, 6, and 12 months of steroid therapy. For the study of endothelial function, we evaluated the brachial artery reactivity, which has emerged as the most well-established technique used in adults, by assessing flow-mediated dilatation (FMD), which measures the endothelium-dependent vasodilatation.Results: Sixteen newly diagnosed PMR patients were compared with a population of 16 matched controls. FMD values in all subjects showed an inverse correlation with the values of erythrocyte sedimentation rate and C-reactive protein. At baseline, the FMD of PMR patients was significantly lower than controls and remained significantly lower with respect to controls until the sixth month of therapy, despite a clinical improvement already being evident after 1 month of therapy.Conclusions: PMR is characterized by an important chronic subclinical inflammatory component. This pilot study demonstrates that affected patients show endothelial dysfunction that slowly responds to steroid therapy. Further studies are needed to investigate the clinical relevance of these observations and, in particular, to monitor the cardiovascular risk profile of PMR patients.

Histotype influences emergency presentation and prognosis in colon cancer surgery.

AIM: To investigate whether differences in histotype in colon cancer correlate with clinical presentation and if they might influence oncological outcomes and survival. METHODS: Data regarding colon cancer patients operated both electively or in emergency between 2009 and 2014 were retrospectively collected from a prospectively maintained database and analyzed for the purpose of this study. Rectal cancer was excluded from this analysis. Statistical univariate and multivariate analyses were performed to investigate possible significant variables influencing clinical presentation, as well as oncological outcomes and survival. RESULTS: Data from 219 patients undergoing colorectal resection for cancer of the colon only were retrieved. One hundred seventy-four patients had an elective procedure and forty-five had an emergency colectomy. Emergency presentation was more likely to occur in mucinous (p < 0.05) and signet ring cell (p < 0.01) tumors. No definitive differences in 5-year overall (44.7% vs. 60.6%, p = 0.078) and disease-free (51.2% vs. 64.4%, p = 0.09) survival were found between the two groups as a whole, but the T3 emergency patients showed worse prognosis than the elective (p < 0.03). Lymph node invasion, laparoscopy, histology, and blood transfusions were independent variables found to influence survival. Distribution assessed for pTNM stage showed T3 cancers were more common in emergency (p < 0.01). CONCLUSIONS AND DISCUSSION: Mucinous and signet ring cell tumors are related to emergency presentation, pT3 stage, poorest outcomes, and survival. Disease-free survival in patients who had emergency surgery for T3 colon cancer seems related to the histotype.

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium.

BACKGROUND: Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. METHODS: This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). RESULTS: Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (ß std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. CONCLUSIONS: Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Positive symptoms associate with cortical thinning in the superior temporal gyrus via the ENIGMA Schizophrenia consortium.

OBJECTIVE: Based on the role of the superior temporal gyrus (STG) in auditory processing, language comprehension and self-monitoring, this study aimed to investigate the relationship between STG cortical thickness and positive symptom severity in schizophrenia. METHOD: This prospective meta-analysis includes data from 1987 individuals with schizophrenia collected at seventeen centres around the world that contribute to the ENIGMA Schizophrenia Working Group. STG thickness measures were extracted from T1-weighted brain scans using FreeSurfer. The study performed a meta-analysis of effect sizes across sites generated by a model predicting left or right STG thickness with a positive symptom severity score (harmonized SAPS or PANSS-positive scores), while controlling for age, sex and site. Secondary models investigated relationships between antipsychotic medication, duration of illness, overall illness severity, handedness and STG thickness. RESULTS: Positive symptom severity was negatively related to STG thickness in both hemispheres (left: ßstd = -0.052; P = 0.021; right: ßstd = -0.073; P = 0.001) when statistically controlling for age, sex and site. This effect remained stable in models including duration of illness, antipsychotic medication or handedness. CONCLUSION: Our findings further underline the important role of the STG in hallmark symptoms in schizophrenia. These findings can assist in advancing insight into symptom-relevant pathophysiological mechanisms in schizophrenia.

Fulminant hepatic failure of autoimmune aetiology in children.

OBJECTIVE: Autoimmune hepatitis (AIH) is considered an underdiagnosed cause of fulminant hepatic failure (FHF). Autoimmune FHF (AI-FHF) is believed to lead invariably to liver transplantation (LTX) or death. We aimed to describe the autoimmune features of children diagnosed as having AI-FHF and indeterminate FHF (ID-FHF), and describe the outcome of patients with AI-FHF treated with immunosuppressive drugs. METHODS: In this case-control study, the files of patients with AI-FHF and ID-FHF were reviewed and compared. AIH was diagnosed based on positive autoantibodies, raised immunoglobulin G, and histology when available. FHF was defined by raised transaminases, international normalised ratio ≥ 2.0, presence of encephalopathy, and no previously recognised liver disease. RESULTS: A total of 46 children with FHF were managed in the last 15 years: 10/46 (22%) had AI-FHF, 20/46 (43%) ID-FHF, and 16 had other diagnosis. The mean follow-up time was 4.6 years. AI-FHF and ID-FHF differed for the presence of autoantibodies (10/10, 6/10 liver/kidney microsome [LKM]-type, vs 3/20, none LKM, P < 0.0001), immunoglobulin G level (1845 vs 880 mg/dL, P < 0.001), median age at diagnosis (6.4 vs 1.8 years, P = 0.017), and alanine aminotransferase level (1020 vs 2386 IU/L, P = 0.029). Liver histology did not allow to differentiate the 2 conditions. Among the patients with AI-FHF, 4/9 who received steroids recovered; 5/9 required LTX and 1 died awaiting treatment. CONCLUSIONS: AIH is a much more common cause of FHF than previously suggested, and a complete autoantibody testing including LKM-type is essential in this setting. Autoantibodies are uncommon in ID-FHF, and histology cannot distinguish it from AI-FHF. A cautious steroid trial may avoid LTX in some of the patients with AI-FHF.

Long-term results after proactive management for locoregional control in patients with colonic cancer at high risk of peritoneal metastases.

PURPOSE: A major problem in treating patients with peritoneal spread from colorectal cancer is that at diagnosis wide peritoneal involvement often precludes all curative attempts. A possible solution is to identify those patients at risk for peritoneal metastases and intervene early to prevent locoregional disease spread before it develops and, thus, to improve outcome. METHODS: We analyzed long-term results from a previous study and compared outcomes in 25 patients with advanced colon cancer considered at high risk for peritoneal spread (pT3/pT4 and mucinous or signet ring cell histology) prospectively included and managed with a proactive surgical approach including target organ resection for peritoneal spread plus hyperthermic intraperitoneal chemotherapy (HIPEC) and in 50 retrospectively well-matched controls who underwent standard surgical resection during the same period and in the same hospital by different surgical teams. RESULTS: At 48 months after the study closed, peritoneal metastases and local recurrence developed significantly less often in proactively managed patients than in controls (4 vs 28%) (p < 0.03). Patients in the proactive group also survived longer than control patients (median overall survival 59.5 vs 52 months). Despite similar morbidity, Kaplan-Meier survival curves disclosed significantly longer disease-free and overall survival in the proactive than in the control group (p < 0.05 and <0.04). CONCLUSIONS: In patients with advanced colon cancer at risk for peritoneal recurrence, the proactive surgical approach plus HIPEC seems to achieve good locoregional control preventing peritoneal spread thus improving outcome without increasing morbidity. These advantages merit investigation in a multicentric randomized trial.

Axillary lymph node metastasis as first presentation of peritoneal carcinomatosis from serous papillary ovarian cancer: case report and review of the literature.

Ovarian cancer usually spreads into abdominal cavity and to the loco-regional lymph nodes. Extra-abdominal metastases are less frequent and isolated axillary metastases are very rare. The authors describe the case of a 49-year-old woman who was diagnosed with a peritoneal carcinomatosis from ovarian cancer by mean of an enlarged axillary lymph node biopsy, whose histological examination identified as a ovarian cancer metastasis. Patient was treated by peritonectomy and intraperitoneal chemohyperthermic perfusion (HIPEC). Although patients with axillary lymph node metastasis from ovarian cancer are though to be metastatic (FIGO Stage IV), surgical radical treatment and adjuvant systemic chemotherapy can achieve the same prognosis of Stage IIIb-c patients, suggesting they could be a particularly good prognosis subset of patients. Early differential diagnosis between ovarian or breast cancer in axillary lymph node metastasis is crucial but not always very simple, because of the very different course and treatment of these tumours.

Prognostic value of specific KRAS mutations in patients with colorectal peritoneal metastases.

BACKGROUND: There is little evidence on KRAS mutational profiles in colorectal cancer (CRC) peritoneal metastases (PM). This study aims to determine the prevalence of specific KRAS mutations and their prognostic value in a homogeneous cohort of patients with isolated CRC PM treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. MATERIALS AND METHODS: Data were collected from 13 Italian centers, gathered in a collaborative group of the Italian Society of Surgical Oncology. KRAS mutation subtypes have been correlated with clinical and pathological characteristics and survival [overall survival (OS), local (peritoneal) disease-free survival (LDFS) and disease-free survival (DFS)]. RESULTS: KRAS mutations occurred in 172 patients (47.5%) out of the 362 analyzed. Two different prognostic groups of KRAS mutation subtypes were identified: KRASMUT1 (G12R, G13A, G13C, G13V, Q61H, K117N, A146V), median OS > 120 months and KRASMUT2 (G12A, G12C, G12D, G12S, G12V, G13D, A59E, A59V, A146T), OS: 31.2 months. KRASMUT2 mutations mainly occurred in the P-loop region (P < 0.001) with decreased guanosine triphosphate (GTP) hydrolysis activity (P < 0.001) and were more frequently related to size (P < 0.001) and polarity change (P < 0.001) of the substituted amino acid (AA). When KRASMUT1 and KRASMUT2 were combined with other known prognostic factors (peritoneal cancer index, completeness of cytoreduction score, grading, signet ring cell, N status) in multivariate analysis, KRASMUT1 showed a similar survival rate to KRASWT patients, whereas KRASMUT2 was independently associated with poorer prognosis (hazard ratios: OS 2.1, P < 0.001; DFS 1.9, P < 0.001; LDFS 2.5, P < 0.0001). CONCLUSIONS: In patients with CRC PM, different KRAS mutation subgroups can be determined according to specific codon substitution, with some mutations (KRASMUT1) that could have a similar prognosis to wild-type patients. These findings should be further investigated in larger series.

Interaction between catechol-O-methyltransferase (COMT) Val158Met genotype and genetic vulnerability to schizophrenia during explicit processing of aversive facial stimuli.

BACKGROUND: Emotion dysregulation is a key feature of schizophrenia, a brain disorder strongly associated with genetic risk and aberrant dopamine signalling. Dopamine is inactivated by catechol-O-methyltransferase (COMT), whose gene contains a functional polymorphism (COMT Val158Met) associated with differential activity of the enzyme and with brain physiology of emotion processing. The aim of the present study was to investigate whether genetic risk for schizophrenia and COMT Val158Met genotype interact on brain activity during implicit and explicit emotion processing. METHOD: A total of 25 patients with schizophrenia, 23 healthy siblings of patients and 24 comparison subjects genotyped for COMT Val158Met underwent functional magnetic resonance imaging during implicit and explicit processing of facial stimuli with negative emotional valence. RESULTS: We found a main effect of diagnosis in the right amygdala, with decreased activity in patients and siblings compared with control subjects. Furthermore, a genotype × diagnosis interaction was found in the left middle frontal gyrus, such that the effect of genetic risk for schizophrenia was evident in the context of the Val/Val genotype only, i.e. the phenotype of reduced activity was present especially in Val/Val patients and siblings. Finally, a complete inversion of the COMT effect between patients and healthy subjects was found in the left striatum during explicit processing. CONCLUSIONS: Overall, these results suggest complex interactions between genetically determined dopamine signalling and risk for schizophrenia on brain activity in the prefrontal cortex during emotion processing. On the other hand, the effects in the striatum may represent state-related epiphenomena of the disorder itself.

Evidence that hippocampal-parahippocampal dysfunction is related to genetic risk for schizophrenia.

BACKGROUND: Abnormalities in hippocampal-parahippocampal (H-PH) function are prominent features of schizophrenia and have been associated with deficits in episodic memory. However, it remains unclear whether these abnormalities represent a phenotype related to genetic risk for schizophrenia or whether they are related to disease state. METHOD: We investigated H-PH-mediated behavior and physiology, using blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI), during episodic memory in a sample of patients with schizophrenia, clinically unaffected siblings and healthy subjects. RESULTS: Patients with schizophrenia and unaffected siblings displayed abnormalities in episodic memory performance. During an fMRI memory encoding task, both patients and siblings demonstrated a similar pattern of reduced H-PH engagement compared with healthy subjects. CONCLUSIONS: Our findings suggest that the pathophysiological mechanism underlying the inability of patients with schizophrenia to properly engage the H-PH during episodic memory is related to genetic risk for the disorder. Therefore, H-PH dysfunction can be assumed as a schizophrenia susceptibility-related phenotype.

Observational study on preoperative surgical field disinfection: povidone-iodine and chlorhexidine-alcohol.

BACKGROUND AND OBJECTIVES: Surgical site infection (SSI) rate is reported to range around 16%. Preoperative skin disinfection is keystone for SSI reduction. Chlorhexidine-alcohol has been reported to be more effective than Povidone-iodine (PVI). However, in many countries established habits and the inferior costs of PVI restrain the employment of chlorhexidine disinfection kits (ChloraPrep®) for the preparation of the surgical field. MATERIALS AND METHODS: The costs of surgical field preparation in clean-contaminated surgery utilizing PVI (Betadine) and chlorhexidine alcohol and the evaluation of surgeon compliance and satisfaction, were studied by a observational study on 50 surgical operations in which surgical field was prepared with PVI checking established guidelines, and on 50 surgical operations in which chlorhexidine-alcohol (ChloraPrep) was employed. The use of auxiliary material was tabulated as well as the timing of the phases of disinfection and the surgeon's opinions. RESULTS: The use of auxiliary material (gloves, gauzes, paper towels, surgical instruments, small swabs for umbilical cleaning) is associated with the type of disinfectant, with major use of auxiliary materials recorded in PVI disinfection. PVI disinfection does not follow stringent guidelines, in particular waiting for the disinfectant to dry. PVI guidelines are more demanding than those relative to ChloraPrep. The time necessary for the preparation of the field is significantly longer for PVI. Auxiliary material and guideline compliance must be taken into account when calculating costs; the former are direct costs (even though marginal) and the latter can determine major infective risk. CONCLUSIONS: Chlorhexidine in kits is easier and faster to use than PVI, requires less auxiliary material and has been shown previously to reduce SSI in clean contaminated surgery.

Peritoneal carcinomatosis: imaging with 64-MDCT and 3T MRI with diffusion-weighted imaging.

Peritoneal carcinomatosis is usually associated with a poor overall survival rate. Recently, introduction of more aggressive surgical treatment and intraperitoneal chemotherapy appears to significantly increase the overall survival rate for these patients. A detailed preoperative assessment of peritoneal carcinomatosis could be very challenging in the field of imaging, but a new aggressive surgical approach requires an accurate preoperative assessment of the disease. Cross-sectional imaging using CT and MRI with diffusion-weighted imaging (DWI) sequences is important for appropriate management of patients with peritoneal carcinomatosis. Appreciation of the spectrum of diagnostic patterns and pitfalls as well as different sites of involvement of peritoneal carcinomatosis using CT and DWI is crucial for appropriate surgical treatment.

Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery for gastric carcinoma at high risk of peritoneal carcinomatosis: short and long-term outcomes (GOETH STUDY)-a collaborative randomized controlled trial by ACOI, FONDAZIONE AIOM, SIC, SICE, and SICO.

INTRODUCTION: At the time of diagnosis, 15-20% of gastric carcinomas are in stage T4 or T4b. Furthermore, 5-20% of patients undergoing potentially curative surgery suffer from synchronous or metachronous peritoneal metastases. To date, neither surgery nor systemic chemotherapy successfully controls peritoneal dissemination, offering a limited impact on survival. Peritoneal metastases are in fact responsible for death in around 60% of gastric cancer patients. Several Eastern studies in the past have focused on hyperthermic intraperitoneal chemotherapy (HIPEC) as a prophylactic measure in patients with serosal extension, nodal involvement, and positive peritoneal fluid cytology. Therefore, a new multimodal therapeutic strategy based on aggressive surgery plus new locoregional treatment may prolong survival in this particular clinical scenario. METHODS: This study compares the efficacy of prophylactic surgery (radical gastric resection, appendectomy, resection of the round ligament of the liver, and bilateral adnexectomy) plus hybrid CO2 HIPEC system versus standard surgery in patients with T3-T4 N0-N + gastric adenocarcinoma. Patients will be randomly assigned (1:1 ratio) to the experimental arm or standard surgery. The primary endpoint is to establish the difference in disease-free survival between the groups. The secondary objective is to compare the safety and tolerability of prophylactic surgery plus HIPEC CO2 versus standard surgery. DISCUSSION: Considering the poor prognosis of patients with peritoneal dissemination from gastric cancer, a prophylactic strategy to prevent peritoneal metastases may be beneficial. In patients with gastric cancer at high risk of peritoneal carcinomatosis, we propose aggressive surgical treatment with radical gastrectomy, removal of organs at risk of harbouring tumour cells, and HIPEC. TRIAL REGISTRATION: ClinicalTrials.gov NCT03917173. Registered on 16 April 2019. PROTOCOL VERSION: v1, March 27, 2019. Protocol number: IRFMN-GCC-7813. EudraCT number: 2019-001478-27.

Catechol-O-methyltransferase Val(158)Met association with parahippocampal physiology during memory encoding in schizophrenia.

BACKGROUND: Catechol-O-methyltransferase (COMT) Val158Met has been associated with activity of the mesial temporal lobe during episodic memory and it may weakly increase risk for schizophrenia. However, how this variant affects parahippocampal and hippocampal physiology when dopamine transmission is perturbed is unclear. The aim of the present study was to compare the effects of the COMT Val158Met genotype on parahippocampal and hippocampal physiology during encoding of recognition memory in patients with schizophrenia and in healthy subjects. METHOD: Using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we studied 28 patients with schizophrenia and 33 healthy subjects matched for a series of sociodemographic and genetic variables while they performed a recognition memory task. RESULTS: We found that healthy subjects had greater parahippocampal and hippocampal activity during memory encoding compared to patients with schizophrenia. We also found different activity of the parahippocampal region between healthy subjects and patients with schizophrenia as a function of the COMT genotype, in that the predicted COMT Met allele dose effect had an opposite direction in controls and patients. CONCLUSIONS: Our results demonstrate a COMT Val158Met genotype by diagnosis interaction in parahippocampal activity during memory encoding and may suggest that modulation of dopamine signaling interacts with other disease-related processes in determining the phenotype of parahippocampal physiology in schizophrenia.

Endothelial dysfunction as assessed by flow-mediated dilation in patients with cardiac syndrome X: role of inflammation.

BACKGROUND: Endothelial dysfunction, reduced coronary flow reserve and increased markers of inflammation are detectable in cardiac syndrome X (CSX). In this study we investigated the relation between inflammation and systemic endothelial function in CSX patients. METHODS: We studied 42 CSX patients (55 +/- 6 years, 14 men) and 20 healthy subjects (52 +/- 7 years, 9 men). Systemic endothelial function was assessed by flow-mediated dilation (FMD) of the brachial artery after 5-minute of forearm cuff inflation. Serum C-reactive protein (CRP) was measured by a high-sensitivity method. RESULTS: FMD was significantly lower in CSX patients compared to controls (4.8 +/- 4.4 vs. 13.7 +/- 4%, p < 0.001), whereas CRP levels were higher in CSX patients than in controls (2.7 +/- 2.4 vs. 0.7 +/- 0.4 mg/L, p = 0.001). In CSX patients FMD showed a significant inverse correlation with CRP levels, even after adjustment for potentially confounding variables (r = -0.34, p = 0.006). CONCLUSION: An impaired FMD is detectable in CSX patients, suggesting a generalized abnormality in vascular function. Subclinical inflammation se is to play a significant role in the impairment of endothelium-dependent vasodilator function of these patients.

Hyperthermic intrathoracic chemotherapy combined to iterative cytoreductive surgery to treat a pleural carcinosis from psudomixoma peritonei. A case report.

Pseudomyxoma peritonei (PMP) is an uncommon disease with locally-invasive attitude. Intrathoracic spread is rarely reported and its management extremely challenging. A 51-year-old Caucasian female presented with left pleural carcinosis 9-months after two sequential abdominal surgical procedures combined with HIPEC for low-grade PMP. Cytoreductive surgery (pleurectomy/decortication) was followed by 60-minutes hyperthermic intrathoracic chemotherapy mitomycin-C (215 mg/m2) infusing at same temperature (42°C) and intrapleural pression (2-4 mmH2O). No intra-operative complication occurred, the post-op stay was uneventful and no sign of recurrence was observed 9-months after surgery. Cytoreductive thoracic surgery and hyperthermic chemotherapy (HITHOC) could be a feasible therapeutic option in very selected cases.

Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Synthetic small-molecule RNA ligands: future prospects as therapeutic agents.

RNA is one of the most intriguing and promising biological targets for the discovery of innovative drugs in many pathologies and various biologically relevant RNAs that could serve as drug targets have already been identified. Among the most important ones, one can mention prokaryotic ribosomal RNA which is the target of several marketed antibiotics, viral RNAs or oncogenic microRNAs that are tightly involved in the development and progression of various cancers. Oligonucleotides are efficient and specific RNA targeting agents but suffer from poor pharmacodynamic and pharmacokinetic properties. For this reason, a number of synthetic small-molecule ligands have been identified and studied upon screening of chemical libraries or focused design of RNA binders. In this review, we report the most relevant examples of synthetic compounds bearing sufficient selectivity to envisage clinical studies and future therapeutic applications with a particular attention for the main strategies that can be undertaken toward the improvement of selectivity and biological activity.

Fertility preservation in chemo-radiotherapy for rectal cancer: A combined approach.

INTRODUCTION: Colorectal cancer is a very common form of cancer worldwide, affecting an increasing number of young women. Standard treatment for locally advanced rectal cancer (LARC) can pose a threat to fertility in these patients. CASE PRESENTATION: We present the case of a young woman affected by LARC who expressed a desire for child-bearing. The treatment she was proposed, according to guidelines, was neoadjuvant chemo-radiotherapy (CRT) followed by delayed surgery, carrying with it a high risk for amenorrhea. Counselling was performed before the initiation of treatment, with the aim of preserving fertility by the proposal of GnRH agonist administration, ovarian transposition and ovarian tissue cryopreservation, which the patient accepted. Treatment was then successfully completed. The patient presented regular menstrual period from before the surgery. DISCUSSION: Ovarian tissue is very sensitive to radiations. Transposition of the organ can prevent ovarian insufficiency by placing it outside the radiation field, while ovarian tissue cryopreservation and orthotopic transplantation offers the possibility to restore fertility in the case of organ failure. We performed both of the techniques. GnRH analogs administration allowed to diminish the risk of ovarian cytotoxicity. Radiation treatment plan was optimized in order to minimize the dose to organs at risk (ovary and vagina in particular); position of the uterus, which is quite radiosensitive too, was monitored with daily cone-beam CT (CBCT). CONCLUSION: The strategy proposed seemed safe and effective, resulting in radical treatment and persistence of regular menstrual period. Further studies are needed.

Association between peripheral arterial disease and cardiovascular risk factors: role of ultrasonography versus ankle-brachial index.

OBJECTIVE: Most studies on atherosclerotic processes include peripheral arterial disease diagnosis only if patients report symptoms suggestive of peripheral arterial disease and/or an instrumental demonstration of lower limbs perfusion deficit is provided, rather than the sole presence of atherosclerotic lesions localized at lower limbs, this attitude leading to ignore early stages of the disease. To overcome these limitations, we have proposed a new ultrasonographic semiquantitative score to better identify all disease stages. The aim of this study is to compare ultrasonography versus ankle-brachial index in the association between peripheral arterial disease and cardiovascular risk factors. PATIENTS AND METHODS: This cross-sectional observational study included subjects undergoing lower limbs evaluation through ultrasonography and ankle-brachial index determination because of symptoms suggestive of peripheral arterial disease or presence of known cardiovascular risk factors. Associations between ultrasonography and ankle-brachial index with cardiovascular risk factors were assessed by first fitting logistic regression models and then comparing the respective areas under the Receiver Operating Characteristic and 95% confidence intervals. RESULTS: The areas under the Receiver Operating Characteristic for each cardiovascular risk factors were consistently larger in magnitude for ultrasonography compared with ankle-brachial index, this comparison being statistically significant for age, male gender, smoking status, hypertension, diabetes mellitus and previous cardiovascular events. CONCLUSIONS: Our study demonstrates that ultrasonography is a better method to screen peripheral arterial disease respect to ankle-brachial index in order to identify all disease stages. These findings are useful in particular when including peripheral arterial disease as organ damage marker in cardiovascular risk stratification.