IDH mutations in G2-3 conventional central bone chondrosarcoma: a mono institutional experience.

BACKGROUND: Heterozygous isocitrate dehydrogenase (IDH) mutations occur in about half of conventional central bone chondrosarcomas (CCBC). Aim of this study was to assess the frequency and prognostic impact of IDH mutations in high grade CCBC patients. METHODS: 64 patients with G2 and G3 CCBC were included. DNA extraction, PCR amplification of IDH1/2 exon 4s, and sequencing analysis with Sanger were performed. RESULTS: IDH mutations were detected in 24/54 patients (44%): IDH1 in 18, IDH2 in 4, and both IDH1/2 in 2 patients. The frequency of mutations was 37% in G2 vs. 69% in G3 (p = 0.039), and 100% in three Ollier disease associated chondrosarcoma. 5-year overall survival (OS) at 124 months (range 1-166) was 51%, with no significant difference based on the IDH mutational status: 61% in IDHmut vs. 44% in IDH wild type (IDHwt). The 5-year relapse free survival (RFS) was 33% (95% CI:10-57) for IDHmut vs. 57% (95%CI: 30-77) for IDHwt. Progression free survival (PFS) was 25% (95%CI:1-65) IDHmut vs. 16% (95%CI: 0.7-52) IDHwt. 55% (5/9) of IDHmut G2 became higher grade at the recurrence, as compared with 25% (3/12) of G2 IDHwt. CONCLUSIONS: This study shows a higher frequency of IDH mutations in G3 CCBC as compared with G2. No significant differences in OS, RFS, and PFS by mutational status were detected. After relapse, a higher rate of G3 for IDH mutated CCBC was observed.

The superparamagnetic iron oxide tracer: a valid alternative in sentinel node biopsy for breast cancer treatment.

The European Union has determined that from 2016 breast cancer patients should be treated in Specialist Breast Units that achieve the minimum standards for the mandatory quality indicators as defined by Eusoma. The existing standard for axillary lymph node staging in breast cancer is sentinel node biopsy (SNB), performed using Technetium-sulphur colloid (99m Tc) alone or with blue dye. The major limits of radioisotope consist in the problems linked to radioactivity, in the shortage of tracer and nuclear medicine units. Among existing alternative tracers, SentiMag® , which uses superparamagnetic iron oxide particles, can represent a valid option for SNB. We conducted a paired, prospective, multicentre study to evaluate the non-inferiority of SentiMag® vs. 99m Tc. The primary end point was the detection rate (DR) per patient. The study sample consists of 193 women affected by breast carcinoma with negative axillary assessment. The concordance rate per patients between 99m Tc and SentiMag® was 97.9%. The DR per patient was 99.0% for 99m Tc and 97.9% for SentiMag® . SentiMag® appears to be non-inferior to the radiotracer and safe. While 99m Tc remains the standard, SentiMag® DR appears adequate after a minimum learning curve. In health care settings where nuclear medicine units are not available, SentiMag/Sienna+® allows effective treatment of breast cancer patients.

Development, acceptability and efficacy of a standardized healthy lifestyle intervention in recurrent depression.

BACKGROUND: Research evidence on the effects of integrated multifaceted lifestyle interventions for depression is scanty. The aim of the present study is to report on the development, acceptability and efficacy of a standardized healthy lifestyle intervention, including exercise, eating habits, sleep hygiene and smoking cessation in preventing relapses. METHODS: One hundred-sixty outpatients with recurrent unipolar depression or bipolar disorder were recruited after achieving full remission or recovery from the most recent depressive episode. Patients were randomized to 3-months of usual care or to an intervention aimed at promoting a healthy lifestyle (HLI), as an augmentation of pharmacological maintenance treatment. Usual care consisted of clinical management visits. At the end of the intervention, follow-up visits were scheduled at 3,6,9 and 12 months. RESULTS: During the intervention phase, 1 relapse occurred in the HLI group and 4 in the control group. Over the 12 months of follow-up, relapses were 5 in the HLI group and 16 in control group. Using an intent-to-treat approach, the overall percentage of relapses was 6/81 (7.4%) in the HLI group vs. 20/79 (25.3%) in the control group.. In a Kaplan-Meier survival analysis the risk of relapse was significantly lower in patients receiving the HLI intervention (log-rank test, p=0.003) over the 60 weeks of observation. The majority of patients assigned to HLI adhered to the program, and were highly motivated throughout the intervention. LIMITATIONS: The retention rate was low because patients were recruited during the maintenance phase and the 1-year follow-up was relatively short to detect a long-term effect of HLI. CONCLUSIONS: The HLI program proved to be efficacious in preventing relapses. Given the absence of contraindications and its cost-effectiveness in routine practice, the use of HLI should be encouraged to promote the well-being of patients with recurrent depression.

Circulating cell-free AR and CYP17A1 copy number variations may associate with outcome of metastatic castration-resistant prostate cancer patients treated with abiraterone.

BACKGROUND: This study aimed to investigate copy number variations (CNVs) of CYP17A1 and androgen receptor (AR) genes in serum cell-free DNA collected before starting abiraterone in 53 consecutive patients with castration-resistant prostate cancer (CRPC). METHODS: Serum DNA was isolated and CNVs were analysed for AR and CYP17A1 genes using Taqman copy number assays. The association between CNVs and progression-free/overall survival (PFS/OS) was evaluated by the Kaplan-Meier method and log-rank test. RESULTS: Median PFS of patients with AR gene gain was 2.8 vs 9.5 months of non-gained cases (P < 0.0001). Patients with CYP17A1 gene gain had a median PFS of 2.8 months vs 9.2 months in the non-gained patients (P = 0.0014). A lower OS was reported in both cases (AR: P < 0.0001; CYP17A1: P = 0.0085). Multivariate analysis revealed that PSA decline ⩾ 50%, AR and CYP17A1 CNVs were associated with shorter PFS (P < 0.0001, P = 0.0004 and P = 0.0450, respectively), while performance status, PSA decline ⩾ 50%, AR CNV and DNA concentration were associated with OS (P = 0.0021, P = 0.0014, P = 0.0026 and P = 0.0129, respectively). CONCLUSIONS: CNVs of AR and CYP17A1 genes would appear to be associated with outcome of CRPC patients treated with abiraterone.

Exposure to emissions from municipal solid waste incinerators and miscarriages: a multisite study of the MONITER Project.

BACKGROUND: Miscarriages are an important indicator of reproductive health but only few studies have analyzed their association with exposure to emissions from municipal solid waste incinerators. This study analyzed the occurrence of miscarriages in women aged 15-49years residing near seven incinerators of the Emilia-Romagna Region (Northern Italy) in the period 2002-2006. METHODS: We considered all pregnancies occurring in women residing during the first trimester of pregnancy within a 4km radius of each incinerator. Addresses were geocoded and exposures were characterized by a dispersion model (ADMS Urban model) producing pollution maps for incinerators based on PM10 stack measurements and for other pollution sources based on NOx ground measurements. Information on pregnancies and their outcomes was obtained from the Hospital Discharge Database. Simplified True Abortion Risks (STAR)×100 estimated pregnancies were calculated. We ran logistic regressions adjusting for maternal characteristics, exposure to other sources of pollution, and sites, considering the whole population and stratifying by miscarriage history. RESULTS: The study analyzed 11,875 pregnancies with 1375 miscarriages. After adjusting for confounders, an increase of PM10 due to incinerator emissions was associated with an increased risk of miscarriage (test for trend, p=0.042). The odds ratio for the highest quartile of exposed versus not exposed women was 1.29, 95% CI 0.97-1.72. The effect was present only for women without previous miscarriages (highest quartile of exposed versus not exposed women 1.44, 95% CI 1.06-1.96; test for trend, p=0.009). CONCLUSION: Exposure to incinerator emissions is associated with an increased risk of miscarriage. This result should be interpreted with those of a previous study on reproductive health conducted in the same area that observed an association between incinerator exposure and preterm births.

Continuity of care of cancer patients. Analysis of theoretical models and survey tools of continuity of care in people with a cancer diagnosis.

BACKGROUND: The Italian Ministry of Health declared oncology a priority and stressed the importance of ensuring continuity and integration in cancer care pathways. In order to monitor the quality of cancer care pathways, we need to explore patients' experience of the continuity of care, identifying the dimensions that define continuity. METHODS: We found 886 relevant articles in the Pubmed database from 1987 to 5 November 2013. The search strategy for the electronic database was defined using the Population, Intervention, Comparison and Outcome(s) framework (PICO) to identify keywords. Two researchers independently reviewed records identified through the search strategy, analyzing continuity dimensions, specificity and/or transversal domains. RESULTS: We selected 20 articles that measure the patients' experience of continuity of care: 7 articles including 5 questionnaires [Questionnaire by King et al. 2008; Cancer care coordination Questionnaire (Cccq); Patient Continuity of Care Questionnaire (Pccq); Medical Care Questionnaire (Mcq); Continuity and Coordination of Care Questionnaire (CCCQ)]; 6 articles evaluating the relationship between patient and his/her physician (the same across the care pathway) in terms of frequency and/or dispersion; 6 articles considering one subscale of larger scales designed to evaluate the generic cancer care service patient experience; 1 revealing four organizational indicators of care pathway continuity / discontinuity. CONCLUSIONS: We traced 3 transversal dimensions across the individual analyses: informational, organizational, relational continuity. It follows that in order to cater to the needs of cancer patients, we need to simultaneously focus on these three dimensions along the cancer care pathway. In line with these results, we promoted the "R.In.Cu.ORAM.i" study (Networks for Integrated Treatment of colorectal and breast cancer), in Area Vasta Romagna Area (Italy), and developed a continuity of care patient-experience continuity tool.

Differences in biological features of breast cancer between Caucasian (Italian) and African (Tanzanian) populations.

Information on hormone receptor and human epidermal growth factor receptor-2 (HER2) expression in breast cancer is acknowledged as mandatory for prognostic stratification and treatment planning. Data on the biological features of African breast cancers are poor. We decided to compare histopathological and biomolecular characteristics (estrogen and progesterone receptor­ER, PgR, and HER2) of Tanzanian and Italian breast cancers. Differences in proliferating index and androgen receptor (AR) expression in triple-negative patients from the two case series were also assessed. Of the 103 consecutive patients seen at the Bugando Medical Center (Mwanza, Tanzania) from 2003 to 2010, who underwent biopsy or surgical resection of primary breast cancer, 69 patients had tissue samples that were evaluable for estrogen receptor (ER), progesterone receptor (PgR), and HER2. Histopathological assessment and biomolecular determinations were performed at the Cancer Institute of Romagna (IRST IRCCS, Meldola, Italy). Caucasian breast cancers were randomly extracted from an electronic database and matched (1:2 ratio) for year of diagnosis and age at diagnosis. Median age of both populations was 51 years (range 27­84). With respect to Caucasian tumors, Tanzanian breast cancers at diagnosis more frequently showed high histological grade (mainly grade 3) (P = 0.03), advanced clinical stage (III or IV) (P\0.001), ER negativity (52.2 %, P\0.001) and high proliferation (P = 0.0002). Triple-negative tumors were over-represented in Tanzanian women. AR was positive in 38.5 and 38 %of triple-negative Tanzanian and Italian breast cancers, respectively. Our results show that histopathological and biomolecular characteristics in Tanzanian and Italian breast cancers differ substantially. The high frequency of poorly differentiated, ER-negative, highly proliferating tumors, together with advanced stage at presentation, could be considered as the main prognostic factors linked to the high mortality rates for breast cancer in the African population.

Clinical utility of preoperative screening with STOP-Bang questionnaire in elective surgery.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disease which increases the risk of perioperative complications. The aim of this study is to assess the clinical utility of preoperative screening for OSA in determining the prevalence of patients at high risk of OSA in a surgical population, the incidence of difficult airway management and the incidence of perioperative complications. METHODS: We conducted a multisite, prospective observational study on adult patients scheduled for elective surgery. All patients completed a STOP-Bang questionnaire as a part of their preoperative evaluation. Collected data included: demographic data, type of surgery, ASA class, postoperative course, complications within 48 hours, difficult intubation (DI) and difficult mask ventilation (DMV) rates. RESULTS: A total of 3452 consecutive patients were recruited; 2997 (87%) were identified as low OSA risk patients and 455 (13%) were identified as high OSA risk patients; 113 (3%) postoperative complications, 315 (9%) cases of DMV and 375 (11%) of DI were observed. The percentage of postoperative complications in patients with HR-OSA was 9%, while the percentage of DI was 20% and the percentage of DMV was 23%. High risk for OSA and higher BMI (≥30 Kg m-2) were independently associated with risk for perioperative complications. CONCLUSION: In conclusion, this study demonstrates that the prevalence of high OSA risk patients in the surgical population is high. The increase in the rates of perioperative complications justifies the implementation of perioperative strategies that use the STOP-Bang as a tool for triage.

Family recurrence and oligo-anuria predict uremic restless legs syndrome.

OBJECTIVES: To determine clinical and laboratory predictors of restless legs syndrome (RLS) in patients with end-stage kidney disease (ESKD) undergoing long-term hemodialysis (HD). MATERIALS AND METHODS: One hundred and sixty-two consecutive patients were assessed. History of sleep disturbances, neurological examination, clinical, and laboratory data were collected. Patients with and without RLS were compared, and a logistic regression model described the relations between independent predictors and RLS. RESULTS: Fifty-one patients (32%) currently had RLS (RLS+). RLS+ vs RLS- patients were more frequently women (49% vs 29%, P = 0.012), had first-degree relative with RLS (22% vs 6%, P = 0.004), insomnia (59% vs 36%, P = 0.007), peripheral neuropathy (41% vs 21%, P = 0.006), and low residual diuresis (92% vs 68% with below 500 ml/24 h, P = 0.001). Low (OR = 8.71, CI = 2.27-33.41; P = 0.002) and absent (OR = 4.96, CI = 1.52-16.20; P = 0.008) residual diuresis, peripheral neuropathy (OR = 4.00, CI = 1.44-11.14; P = 0.008), and first-degree relative with RLS (OR = 3.82, CI = 1.21-12.13; P = 0.023) significantly predicted RLS in ESKD patients undergoing HD. CONCLUSION: Positive family history for RLS together with reduced/absent residual renal function and peripheral neuropathy predicts the risk for RLS in ESKD patients undergoing HD. Longitudinal studies are warranted to correlate RLS occurrence with genetic and environmental factors.

Incidence of cancer in kidney transplantation waiting list patients: a single center experience.

INTRODUCTION: It is widely accepted that the risk of malignancies is significantly increased among patients with end-stage kidney disease (ESKD) and after kidney transplantation compared with the general population. Only a few data are available on kidney transplantation waiting list patients. The aim of this study was to investigate solid organ cancer incidence among subjects on the waiting list at a single center. MATERIALS AND METHODS: We retrospectively reviewed the records of all patients enrolled on our kidney transplantation waiting list between August 1, 2008 and July 31, 2010, seeking to evaluate the causes of withdrawal from the list, incidence of cancer, type of neoplasm, and its correlation with clinical features. We estimated the ratio of observed to expected numbers of cancers, the standardized incidence ratio (SIR). RESULTS: Among 1184 patients, we excluded 569 patients from the waiting list including 26 (4.56%) who displayed malignancies. The overall incidence of cancer was 0.11 events/person-months and the overall prevalence of cancer was 2.2%. In 97% of patients, the malignant disease was confined to the primitive organ of origin without secondary dissemination. We observed a prevalence of cancers related to ESKD (17; 65.38%). The SIR for all cancer types in our population compared with the general population was 2.22. The SIR for native kidney and thyroid cancers among our population compared with the general population was >10. CONCLUSION: The incidence of cancer was significantly increased among kidney transplantation waiting list patients compared with the general population. Our study highlighted the importance of a careful, targeted neoplastic screening. It could be particularly important for ESKD-related malignancies like native kidney tumors or thyroid cancers.

Determinants of surgical delay for hip fracture.

BACKGROUND AND OBJECTIVE: Recent guidelines recommend early surgical treatment of hip fractures in the elderly. The aim of the present study is to analyse the factors delaying surgical treatment of hip fractures in elderly patients by more than 2 days and to investigate whether these factors are consistent between a teaching and a community hospital. DESIGN: Retrospective cohort study using hospital discharge records and patients' charts. SETTING: Orthopaedics and traumatology departments of a teaching hospital and a small town hospital in Northern Italy. PARTICIPANTS: 1768 consecutive patients aged 65 years or more who underwent surgery for hip fractures between 2004 and 2007. INTERVENTIONS: Surgery for hip fracture. MAIN OUTCOME MEASURE(S): Surgery within two days from admission. RESULTS: 938 (53.1%) patients were operated within 2 days of admission to the hospital. Logistic regression models were used to examine potential predictors of surgery delay including gender, age, hospital, comorbidity, type of intervention (partial or total hip replacement, reduction and internal fixation), International Normalized Ratio (INR), Haemoglobin (Hb), American Society of Anaesthesiologists (ASA) score, and day of admission (categorized as Monday to Wednesday, Thursday-Friday, Saturday-Sunday). Age, type of intervention (partial or total hip replacement), INR score > 1.5 and an ASA score of 4 compared to 1-2, admission on Thursday-Friday or Saturday-Sunday and the interaction hospital × arrhythmia significantly predicted a surgery delay of more than 2 days. CONCLUSIONS: Both organization and medical problems accounted for delays of surgical treatment of hip fractures. Established protocols aimed to optimize the patient flow logistics and to manage comorbidities are crucial to make hospitals more patient-centred and to improve patient outcomes.

The influence of intraoperative central venous pressure on delayed graft function in renal transplantation: a single-center experience.

INTRODUCTION: Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. METHODS: One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. RESULTS: CVP at awakening of ≤8 mm Hg (odds ratio [OR] = 3.53; 95% confidence interval [CI], 1.63-7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00-4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11-6.68) were the strongest correlates of DGF. CONCLUSIONS: Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.

The Morfeo Study: A 1-year follow-up of complications of vegetative state in a dedicated facility.

OBJECTIVES: Vegetative State (VS) implies significant issues. The aim of the MORFEO study is to identify the most relevant complications in VS patients and to supply clinicians and policy-makers with data derived from the analysis of a cohort of patients treated in a dedicated long-term facility setting. METHODS: A cohort of 22 VS patients treated between 2003 and 2007 were enrolled and followed up for 1 year. The information recorded were: Disability Rating Scale (DRS), Levels of Cognitive Functioning (LCF), pressure sores, nutritional status, neurological complications, articular complications (passive range of motion-ROM), deep-vein thrombosis and infections. The Kolmogorov-Smirnov test was used to verify the normal distribution of the variables. The indicators of complications were analysed with the Friedman test (continuous variables) and with the Cochran Q test (dichotomous variables). RESULTS: DRS and LCF values showed no significant variation. The number of pressure sores decreased. The nutritional status remained satisfying. The ROM worsened in lower limb joints; a trend (p = ns) towards an improved range was observed in shoulders and elbows. Fifteen infections were recorded. CONCLUSIONS: The data that proved significant suggest a minimum set of quality-of-care indicators in VS patients: pressure sores follow-up, nutritional status, ROM and incidence of infections.

Conformational and biological characterization of human parathyroid hormone hPTH(1-34) analogues containing beta-amino acid residues in positions 17-19.

The N-terminal 1-34 fragment of parathyroid hormone (PTH) elicits the full spectrum of bone-related biological activities of the intact native sequences. It has been suggested that the structural elements essential for bioactivity are two helical segments located at the N-terminal and C-terminal sequences, connected by hinges or flexible points around positions 12 and 19. In order to assess the relevance of the local conformation around Gly(18) upon biological function, we synthesized and characterized the following human (h) PTH(1-34) analogues containing beta-amino acid residues: [analogues: see text]. Biological activity and binding affinity of analogue I are one order of magnitude lower than those of the parent compound. In analogue II, both binding affinity and biological activity are partially recovered. Analogues III and V have no binding affinity and very low biological activity. Both bioactivity and binding affinity are partially recovered in analogue IV. The conformational properties of the analogues in aqueous solution containing dodecylphosphocholine micelles were studied by CD, 2D-nuclear magnetic resonance and molecular dynamics calculations. The results confirmed the presence in all analogues of two helical segments located at the N-terminal and C-terminal sequences. The insertion of beta-amino acid residues around position 18 does not cause appreciable conformational differences in the five analogues. The differences in biological activity and binding affinity among the five analogues cannot be related to structural differences in the membrane mimetic environment reported in this study. Our results stress the importance of the side-chain functionalities in the sequence 17-19 for biological function.

Detection of chlamydial antigenic material in ovarian, prostatic, ectopic pregnancy and semen samples of culture-negative subjects.

PROBLEM: The pathogenesis of long-term sequelae in Chlamydia trachomatis infection is poorly understood. While serology indicates previous chlamydial infection, culture studies are frequently negative. We wanted to know whether in chronic cases the bacterium is absent or persists in a dormant state where it evades detection. METHODS OF STUDY: Using immunoperoxidase (IP) staining and in situ hybridization (ISH), we examined tissues of culture-negative subjects. Ovarian biopsy specimens from 19 culture-negative women with pelvic adhesions and/or tubal infertility were analyzed by both methods. Samples of prostates from 10 culture-negative men undergoing prostatectomy for benign hypertrophy, two sets of semen samples from culture-negative sexual partners of 28 women with PID and/or bacterial vaginosis (BV), and ten endometrium-tube sample-pairs from ectopic pregnancies (EPs) were examined by IP only. RESULTS: Seven of the nineteen ovarian specimens tested positive for Chlamydia antigen or deoxyribonucleic acid (DNA) (36%). Of the 10 hypertrophic prostates examined, 4 (40%) were positive. Of the 28 semen samples examined, 10 (35%) tested positive. Tissue samples of 3 cases of EP were positive by IP. CONCLUSIONS: 1. C. trachomatis antigen and nucleic acid can be frequently demonstrated in asymptomatic, culture-negative men and women with chronic infection. 2. Chlamydia antigens may have an etiologic role in benign prostate hypertrophy and EP. 3. Antigenic material may be sexually transmissible. 4. IP and ISH identify temporarily inactive bacteria that may continue to act as immunostimulants and potentially reactivate as Chlamydia infection.