Minimally invasive surgery versus standard posterior approach in the treatment of adolescent idiopathic scoliosis: a 2-year follow-up retrospective study.

PURPOSE: This is a monocentric retrospective controlled study that compares the safety and efficacy of posterior minimally invasive surgery (MISS) to standard posterior spinal fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively collected 111 patients with Lenke type 1-6 AIS who were treated with MIS (n = 47) or PSF (n = 64) between February 2019 and January 2021 with a 2-year clinical and radiological follow-up. MIS technique was applied via two midline noncontiguous skin incisions ranging from 3 to 7 cm in length, so we obtained the arthrodesis only in the exposed tract, passing the rods below the fascia, avoiding the complete muscular sparing. Values of Cobb angles degrees were collected to study the correction rate of the structural major curve. Postoperative AP direct radiography and preoperative AP direct radiography were compared with the last follow-up examination. Operative time, preoperative hemoglobin (Hb) and second postoperative day Hb, full length of hospitalization, time to achieve verticalization and time to remove the drainage were recorded. NRS medium score was assessed immediately after surgery and during the whole postoperative rehabilitation treatment to estimate pain reduction. Complications were collected postoperatively and throughout the whole follow-up period. RESULTS: There was no significant difference between the two groups in terms of radiographic and clinical features. The correction rates of the structural curve resulted to be not significantly different between MISS and PSF (64.6 ± 11.7 vs 60.9 ± 13.2, p = 0.1292) as well as for the correction rate of the secondary curve between the two compared techniques (59.1 ± 13.2 vs 59.2 ± 12.4, p = 0.9865). The two groups had comparable operative time (210 min vs 215 min). The MIS group had a significantly lower reduction of postoperative Hb in comparison with PSF group (2.8 ± 1.3 mg/dl vs 4.3 ± 1.5 mg/dl, p < 0.0001). The postoperative NRS score was lower in MIS group (1.9 ± 0.8 vs 3.3 ± 1.3). PSF group was observed to have a significantly longer period of hospitalization than MIS (5.2 ± 1.4 days vs 6.3 ± 2.9 days, p = 0.206). Complications were more frequent in PSF group rather than in MFS group. CONCLUSIONS: MISS is a safe and capable alternative to PSF for AIS patients with curves < 70°, with analogue capacity of scoliosis correction and same operative time and with advantages in blood loss, length of stay and postoperative pain.

Factors associated with increased length of stay and risk of complications in 336 patients submitted to spine surgery. The role of a validated capture system (SAVES v2) as a first-line tool to properly face the problem.

PURPOSE: In this study, we analyzed the use of a validated capture system (Spinal Adverse Events Severity system, SAVES V2) as a first non-technical skill to properly face the relevant problem of surgical complications (SCs) and adverse events (AEs) in spinal surgery. METHODS: We retrospectively collected AEs occurring in a tertiary referral center for spine surgery from January 2017 to January 2018 and classified them according to SAVES V2 system. We compared this collection of AEs with a prospective collection performed without any classification system. Univariate and multivariate logistic regression models were used to determined odds ratio (ORs) for selected potential risk factors of AEs and prolonged length of stay. RESULTS: Overall a higher number of AEs was retrospectively recorded using SAVES system compared to the prospective recording without the use of any capture system (97/336 vs 210/336, p < 0.001). The length of stay (LOS) increased in the group of complicated patients for all the procedures examined. In the non-oncological group, LOS was significantly higher for complicated patients compared to uncomplicated patients (F = 44.11, p = 0.0000). Similar results have been obtained in the oncological group of patients. In the multivariate regression model surgical time and postoperative AEs emerged as risk factors for prolonged LOS, while only the presence of previous surgeries was confirmed as risk factor for AEs. CONCLUSION: Considering that the rate of AEs and SCs in spinal surgery is still high despite the improvement of technical skills, we suggest the use of SAVES V2 capture system as a first-line tool to face the problem.

Outcome of rare primary malignant bone sarcoma treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S.).

BACKGROUND: Rare primary malignant bone sarcomas (RPMBS) account for 5%-10% of primary high-grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO-B.O.S.S) is presented. METHODS: Inclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high-grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2 , ifosfamide 9 g/m2 , and cisplatin 90 mg/m2 ; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan-Meier curves, log-rank tests, and univariate Cox regression models were used. RESULTS: In total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40-66 years), and 67 patients were men. Eighty-eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty-three of 113 tumors were located in the extremities. Ninety-five of 113 patients presented with no evidence of metastases. After a median follow-up of 6.8 years (interquartile range [IQR], 3.5-9.8 years), the 5-year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%-77.5%), and it was 71.7% (IQR, 58.1%-81.6%) for patients with UPS and 54.9% (IQR, 29.5%-74.5%) for patients with leiomyosarcoma. Grade III-IV hematologic toxicity was reported in 81% patients; 23% had grade II-III neurotoxicity, and 37.5% had grade I-II nephrotoxicity. Five-year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities. CONCLUSIONS: The survival of patients who had RPMBS in the current series was similar to that of age-matched patients who had high-grade osteosarcoma treated according to the same protocol. An osteosarcoma-like chemotherapy may be proposed in patients who have RPMBS.

Phase 2 study for nonmetastatic extremity high-grade osteosarcoma in pediatric and adolescent and young adult patients with a risk-adapted strategy based on ABCB1/P-glycoprotein expression: An Italian Sarcoma Group trial (ISG/OS-2).

BACKGROUND: According to retrospective osteosarcoma series, ABCB1/P-glycoprotein (Pgp) overexpression predicts for poor outcomes. A prospective trial to assess a risk-adapted treatment strategy using mifamurtide in Pgp+ patients was performed. METHODS: This was a phase 2, multicenter, uncontrolled trial including patients 40 years old or younger with nonmetastatic extremity high-grade osteosarcoma stratified according to Pgp expression. All patients received high-dose methotrexate, doxorubicin, and cisplatin (MAP) preoperatively. In Pgp+ patients, mifamurtide was added postoperatively and combined with MAP for a good histologic response (necrosis ≥ 90%; good responders [GRs]) or with high-dose ifosfamide (HDIFO) at 3 g/m2 /d on days 1 to 5 for a histologic response < 90% (poor responders [PRs]). Pgp- patients received MAP postoperatively. After an amendment, the cumulative dose of methotrexate was increased from 60 to 120 g/m2 (from 5 to 10 courses). The primary end point was event-free survival (EFS). A postamendment analysis was performed. RESULTS: In all, 279 patients were recruited, and 194 were included in the postamendment analysis: 70 (36%) were Pgp-, and 124 (64%) were Pgp+. The median follow-up was 51 months. For Pgp+ patients, 5-year EFS after definitive surgery (null hypothesis, 40%) was 69.8% (90% confidence interval [CI], 62.2%-76.2%): 59.8% in PRs and 83.7% in GRs. For Pgp- patients, the 5-year EFS rate was 66.4% (90% CI, 55.6%-75.1%). CONCLUSIONS: This study showed that adjuvant mifamurtide, combined with HDIFO for a poor response to induction chemotherapy, could improve EFS in Pgp+ patients. Overall, the outcomes compared favorably with previous series. Mifamurtide and HDIFO as salvage chemotherapy are worth further study.

Synovial chondrosarcoma: a single-institution experience with molecular investigations and review of the literature.

AIMS: To evaluate the available diagnostic histological criteria for synovial chondrosarcoma and to screen for the presence of IDH1/IDH2 mutations in a series of cases of this malignant cartilaginous neoplasm. METHODS AND RESULTS: Ten cases of synovial chondrosarcoma diagnosed at our institute were reviewed. At presentation, all tumours occurred in adults (median age, 62 years). The most common location was the knee joint (five cases), and the size at diagnosis ranged from 30 mm to 170 mm. Eight patients had secondary synovial chondrosarcomas associated with pre-existing/recurrent or concomitant synovial chondromatosis. Five patients had local recurrences and three had lung metastases. All patients with intralesional excisions developed local recurrences, whereas those who underwent wide resections did not. At last follow-up (mean, 91 months), available for nine patients, seven patients were alive and disease-free, one patient had died of disease, and one was alive with paravertebral metastases. Frequent histological features observed included loss of clustering of chondrocytes (nine cases), the presence of variable amounts of myxoid matrix (eight cases), peripheral hypercellularity (eight cases), tumour necrosis (six cases), and spindling of chondrocytes (four cases). Of the seven cases for which it was possible to evaluate bone permeation, six showed infiltration of bone marrow. All seven cases screened for mutations of exon 4 of IDH1 and IDH2 were found to be wild-type. CONCLUSIONS: Histological criteria in correlation with clinical and radiological features allow the recognition of synovial chondrosarcoma. IDH1/IDH2 mutations were not present in synovial chondrosarcoma. Adequate surgical margins are important for disease control.

Bronchoscopic Lung Cryobiopsy Increases Diagnostic Confidence in the Multidisciplinary Diagnosis of Idiopathic Pulmonary Fibrosis.

RATIONALE: Surgical lung biopsy is often required for a confident multidisciplinary diagnosis of idiopathic pulmonary fibrosis (IPF). Alternative, less-invasive biopsy methods, such as bronchoscopic lung cryobiopsy (BLC), are highly desirable. OBJECTIVES: To address the impact of BLC on diagnostic confidence in the multidisciplinary diagnosis of IPF. METHODS: In this cross-sectional study we selected 117 patients with fibrotic interstitial lung disease without a typical usual interstitial pneumonia pattern on high-resolution computed tomography. All cases underwent lung biopsies: 58 were BLC, and 59 were surgical lung biopsy (SLB). Two clinicians, two radiologists, and two pathologists sequentially reviewed clinical-radiologic findings and biopsy results, recording at each step in the process their diagnostic impressions and confidence levels. MEASUREMENTS AND MAIN RESULTS: We observed a major increase in diagnostic confidence after the addition of BLC, similar to SLB (from 29 to 63%, P = 0.0003 and from 30 to 65%, P = 0.0016 of high confidence IPF diagnosis, in the BLC group and SLB group, respectively). The overall interobserver agreement in IPF diagnosis was similar for both approaches (BLC overall kappa, 0.96; SLB overall kappa, 0.93). IPF was the most frequent diagnosis (50 and 39% in the BLC and SLB group, respectively; P = 0.23). After the addition of histopathologic information, 17% of cases in the BLC group and 19% of cases in the SLB group, mostly idiopathic nonspecific interstitial pneumonia and hypersensitivity pneumonitis, were reclassified as IPF. CONCLUSIONS: BLC is a new biopsy method that has a meaningful impact on diagnostic confidence in the multidisciplinary diagnosis of interstitial lung disease and may prove useful in the diagnosis of IPF. This study provides a robust rationale for future studies investigating the diagnostic accuracy of BLC compared with SLB.

Evaluating patient safety indicators in orthopedic surgery between Italy and the USA.

OBJECTIVE: To compare patient safety in major orthopedic procedures between an orthopedic hospital in Italy, and 26 US hospitals of similar size. DESIGN: Retrospective analysis of administrative data from hospital discharge records in Italy and Florida, USA, 2011-13. Patient Safety Indicators (PSIs) developed by the Agency for Healthcare Quality and Research were used to identify inpatient adverse events (AEs). We examined the factors associated with the development of each different PSI, taking into account known confounders, using logistic regression. SETTING: One Italian orthopedic hospital and 26 hospitals in Florida with ≥ 1000 major orthopedic procedures per year. PARTICIPANTS: Patients ≥ 18 years who underwent 1 of the 17 major orthopedic procedures, and with a length of stay (LOS) > 1 day. INTERVENTION: Patient Safety management between Italy and the USA. MAIN OUTCOME MEASURE: Patient Safety Indicators. RESULTS: A total of 14 393 patients in Italy (mean age = 59.8 years) and 131 371 in the USA (mean age = 65.4 years) were included. US patients had lower adjusted odds of developing a PSI compared to Italy for pressure ulcers (odds ratio [OR]: 0.21; 95% confidence interval [CI]: 0.10-0.45), hemorrhage or hematoma (OR: 0.42; CI 0.23-0.78), physiologic and metabolic derangement (OR: 0.08; CI 0.02-0.37). Italian patients had lower odds of pulmonary embolism/deep vein thrombosis (OR: 3.17; CI 2.16-4.67) compared to US patients. CONCLUSIONS: Important differences in patient safety events were identified across countries using US developed PSIs. Though caution about potential coding differences is wise when comparing PSIs internationally, other differences may explain AEs, and offer opportunities for cross-country learning about safe practices.

Efficacy of endocrine therapy in relation to progesterone receptor and Ki67 expression in advanced breast cancer.

We assessed whether progesterone receptor (PgR) and Ki67 in primary tumors and/or matched metastases are predictors of clinical benefit from first-line endocrine therapy (ET) in advanced breast cancer. We evaluated patients treated at our institute with first-line ET (2002-2011), excluding those receiving concomitant chemotherapy or trastuzumab or pretreated with >2 lines of chemotherapy. A cut-off of 20 % immunostained cells was used for PgR and Ki67. The main endpoint was time-to-progression (TTP). Groups were compared by the log-rank test and Cox multivariate analysis. In the 135 assessable patients (93 % were receiving an aromatase inhibitor; biomarker assessment had been performed on primary tumors in 77 cases, on metastases in 23 and on both in 35), median TTP was 16 months (median follow-up 43 months). The overall discordance rate between primary tumors and metastases was 23 % for Ki67 and 31 % for PgR. A longer median TTP (24 vs. 12 months, P = 0.012) was seen for PgR >20 % in metastases. Ki67 showed a trend for TTP prediction in the entire case series (P = 0.062). Patients with high Ki67 and low PgR in metastases had a median TTP of only 5 months. High Ki67 in primary tumors (P = 0.026) or metastases (P = 0.01) predicted disease progression at the first evaluation. PgR in metastases remained a significant independent predictor of TTP at multivariate analysis (HR 2.45). In an ER-high population, PgR >20 % in metastases identified patients with a long TTP on endocrine treatment, while Ki67 >20 % was associated with an increased risk of non-response.

Is a clear benefit in survival enough to modify patient access to the surgery service? A retrospective analysis in a cohort of gastric cancer patients.

BACKGROUND: Surgery has become an important tool for cancer treatment, requiring many available resources and a good organization of the surgery service. The aim of this study was to provide robust data for policymakers on the impact of hospital volume on survival, taking into account different sources of information. METHODS: We performed a retrospective study in a cohort of patients with gastric cancer submitted to partial or total gastrectomy. Data for the analysis were retrieved from regional administrative databases, the regional death registry, and histological reports. The main outcome measures were operative mortality and long-term survival. The associations between hospital volume and risk of mortality were calculated using a Cox multiple regression analysis. RESULTS: The estimated relationship between operative mortality and volume was not statistically significant. Conversely, high-volume hospitals had an increased likelihood of long-term survival compared to low-volume institutions: hazard ratio 0.79 (95% confidence interval, 0.66-0.94, p = 0.01). The percentage variation between crude and adjusted HRs using only administrative data or administrative and histological data was very small. However, the combined use of administrative and clinical data provided a more accurate model for estimating risk-adjusted mortality. CONCLUSIONS: A positive association between hospital volume and survival was evident for long-term outcome after adjusting for patient and tumor confounding. Moreover, the patient's choice of hospital was not guided by specific care pathways or screening programs, and prognosis was not poorer for patients in high-volume hospitals. These findings suggest that there is leeway for improving access to surgery for gastric cancer patients.

Chromogranin A is a potential prognostic marker in prostate cancer patients treated with enzalutamide.

BACKGROUND: In this retrospective study, we assessed chromogranin A (CgA) baseline value as a possible factor associated with poor prognosis in metastatic castration-resistant prostate cancer (CRPC). METHODS: Thirty-five patients with metastatic CRPC progressing after docetaxel chemotherapy treated with enzalutamide are subdivided into three groups: serum CgA level was normal when <120 ng/ml (group A, n = 10), within three times the upper normal value (UNV) when between 120 and 360 (group B, n = 17), more than three times the UNV when ≥360 ng/ml (group C, n = 8). RESULTS: No correlation was observed in three groups among CgA baseline values and PSA response rates (RR) (P = 0.4648), whereas a significative difference was associated with median progression-free survival (PFS) and overall survival (OS) among three CgA groups (P = 0.0301 and P = 0.0011, respectively). In the multivariate analysis, PSA RR (nonresponsive vs. responsive) and CgA levels (group 3 vs. groups 1 + 2) were predictors of OS (P = 0.0029 and P = 0.0025, respectively), whereas they only were not significantly correlated with PFS, even had a borderline significance (P = 0.0628 and P = 0.0772, respectively). CONCLUSIONS: In CRPC patients treated with enzalutamide, the evaluation of serum CgA levels could be an useful prognostic factor because of the strong association between CgA value more than three times the UNV and clinical outcome, independently from PSA response.

Taxanes as a risk factor for acute adverse reactions to iodinated contrast media in cancer patients.

BACKGROUND: The impact of cytotoxic agents on the risk of acute allergy-like adverse reactions (ARs) to intravenous iodinated contrast media (ICM) injections is unknown. METHODS: We retrospectively reviewed 13,565 computed tomography (CT) scans performed in a consecutive cohort of cancer patients from January 1, 2010 to December 31, 2012. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. The following matched comparisons were made: tax code, gender, primary tumor, antineoplastic therapy, and date of last cycle. Concomitant antineoplastic treatment was classified into five groups: platinum, taxane, platinum plus taxane, other, and no treatment group (no therapy had been administered in the previous 24 months). Logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) to evaluate the risk of acute ICM-related ARs. RESULTS: Of 10,472 contrast-enhanced CT scans, 97 (0.93%; 95% CI: 0.74-1.11) ICM-related ARs were reported, 11 of which (0.1%) were severe, including one fatality. The overall incidence was significantly higher in patients aged <65 years (p = .0062) and in the platinum plus taxane and taxane groups (p = .007), whereas no correlation was found with gender, number of previous CT scans, site of disease, or treatment setting. Multivariate analysis confirmed an increased risk for patients aged <65 years (OR: 1.73; 95% CI: 1.14-2.63) and for the taxane group (in comparison with the no treatment group; OR: 2.06; 95% CI: 1.02-4.16). CONCLUSION: Among cancer patients, concomitant treatment with taxanes and younger age would seem to be risk factors for ICM-related ARs.

Does the time between CT scan and chemotherapy increase the risk of acute adverse reactions to iodinated contrast media in cancer patients?

BACKGROUND: Cancer patients undergo routine computed-tomography (CT) scans and, therefore, iodinated contrast media (ICM) administration. It is not known whether a time-dependent correlation exists between chemotherapy administration, contrast enhanced CT and onset of acute ICM-related adverse reactions (ARs). METHODS: All consecutive contrast-enhanced CTs performed from 1 January 2010 to 31 December 2012 within 30 days of the last chemotherapy administration were retrospectively reviewed. Episodes of acute ICM-related ARs were reported to the pharmacovigilance officer. We analyzed time to CT evaluation calculated as the time elapsed from the date of the CT performed to the date of the last chemotherapy administration. Patients were classified into 4 groups based on the antineoplastic treatment: platinum-based, taxane-based, platinum plus taxane and other group. RESULTS: Out of 10,472 contrast-enhanced CTs performed, 3,945 carried out on 1,878 patients were considered for the study. Forty acute ICM-related ARs (1.01%; 95% CI, 0.70-1.33) were reported. No differences were seen among immediate (within 10 days of the last chemotherapy administration), early (11-20 days) and delayed (21-30 days) CTs. Median time to CT in patients who experienced an acute ICM-related AR by treatment group was not statistically different: 20 days (range 6-30), 17 days (range 5-22), 13 days (range 8-17), 13 days (range (2-29) for the platinum, taxane, platinum plus taxane and other group, respectively (P =0.251). CONCLUSIONS: Our results did not reveal any correlation between time to CT and risk of acute ICM-related ARs in cancer patients.

Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

Does breast cancer screening level health inequalities out? A population-based study in an Italian region.

BACKGROUND: Although population-based screening has the potential to reduce inequalities in breast cancer survival, evidence on this topic is controversial. The objective of this study was to evaluate whether the full implementation of a mammography screening programme in Emilia-Romagna in Italy had an impact on variations in breast cancer survival by educational level. METHODS: A cohort study was performed, including all women <70 years and residing in Emilia-Romagna who had infiltrating breast cancer registered in 1997-2000 (transitional screening period) or 2001-03 (consolidation screening period). Cancer cases were retrieved from the regional Breast Cancer Registry and followed up for 5 years. Educational level was determined from census data and allocated to cancer cases by individual record linkage. Age at diagnosis was classified into two groups (30-49, 50-69: screening target population). RESULTS: A total of 9639 cases were analyzed. In the 1997-2000 period, low-educated women had significantly lower survival compared with high-educated women, both in the younger and in the older age-groups. After the full implementation of the screening programme, these differences decreased in both age-groups, until disappearing completely among women in the age-group invited to screening. CONCLUSIONS: Our findings suggest that a fee-free population-based organized mammography screening programme with active invitation of the whole target population could be effective in reducing differences in survival in the population targeted by the screening.

Copy number analysis of 24 oncogenes: MDM4 identified as a putative marker for low recurrence risk in non muscle invasive bladder cancer.

Patients with non-muscle invasive bladder cancer (NMIBC) generally have a high risk of relapsing locally after primary tumor resection. The search for new predictive markers of local recurrence thus represents an important goal for the management of this disease. We studied the copy number variations (CNVs) of 24 oncogenes (MDM4, MYCN, ALK, PDGFRA, KIT, KDR, DHFR, EGFR, MET, SMO, FGFR1, MYC, ABL1, RET, CCND1, CCND2, CDK4, MDM2, AURKB, ERBB2, TOP2A, AURKA, AR and BRAF) using multiplex ligation probe amplification technique to verify their role as predictive markers of recurrence. Formalin-fixed paraffin-embedded tissue samples from 43 patients who underwent transurethral resection of the bladder (TURB) were used; 23 patients had relapsed and 20 were disease-free after 5 years. Amplification frequencies were analyzed for all genes and MDM4 was the only gene that showed significantly higher amplification in non recurrent patients than in recurrent ones (0.65 vs. 0.3; Fisher's test p=0.023). Recurrence-free survival analysis confirmed the predictive role of MDM4 (log-rank test p=0.041). Our preliminary results indicate a putative role for the MDM4 gene in predicting local recurrence of bladder cancer. Confirmation of this hypothesis is needed in a larger cohort of NMIBC patients.

Air pollution from incinerators and reproductive outcomes: a multisite study.

BACKGROUND: The few studies that have investigated the relationship between emissions from municipal solid-waste incinerators and adverse pregnancy outcomes have had conflicting results. We conducted a study to assess the effects of air emissions from the eight incinerators currently in operation in the Emilia-Romagna Region of Italy on reproductive outcomes (sex ratio, multiple births, preterm births, and small for gestational age [SGA] births). METHODS: We considered all births (n = 21,517) to women residing within a 4-km radius of an incinerator at the time of delivery during the period 2003-2010 who were successfully linked to the Delivery Certificate database. This source also provided information on maternal characteristics and deliveries. Each newborn was georeferenced and characterized by a specific level of exposure to incinerator emissions, categorized in quintiles of PM10, and other sources of pollution (NOx quartiles), evaluated by means of ADMS-Urban system dispersion models. We ran logistic regression models for each outcome, adjusting for exposure to other pollution sources and maternal covariates. RESULTS: Incinerator pollution was not associated with sex ratio, multiple births, or frequency of SGA. Preterm delivery increased with increasing exposure (test for trend, P < 0.001); for the highest versus the lowest quintile exposure, the odds ratio was 1.30 (95% confidence interval = 1.08-1.57). A similar trend was observed for very preterm babies. Several sensitivity analyses did not alter these results. CONCLUSIONS: Maternal exposure to incinerator emissions, even at very low levels, was associated with preterm delivery.

Prediction of three-year outcome of renal transplantation from optimal donors versus expanded criteria donors.

BACKGROUND/AIMS: The shortage in organ supply has required the use of expanded criteria donors (ECD) for kidney transplantation. Current pre-transplant evaluations of ECD organs are based on histological, clinical or mixed criteria. This monocentric study investigates the predictivity of Karpinski's histological score on 3-year graft function in renal transplant. Ex-post classification using Nyberg's score was carried out to assess the reliability of a purely clinical score and its applicability for organ allocation. METHODS: We evaluated 407 deceased donors (251 optimal and 156 ECD) for renal transplants performed between 2001 and 2006. The differences in creatinine levels and MDRD-GFR at transplant and 1, 2 and 3 years post-transplant between optimal donors and ECD were recorded. Amongst ECD organs, the effect of different Karpinski score classes (0-1, 2, 3, 4, double transplants) on 3-year graft outcomes was analyzed. We then compared renal function over time across the Nyberg grades (A, B, C, and D). RESULTS: Karpinski scores 0-1 and 2 and double transplants were associated with improved graft function compared to scores 3 and 4. Nyberg's clinical score shows a good fit with medium-term outcome and Karpinski's score, but among the donors with a high Nyberg grade (C and D), it fails to differentiate between allocable or non-allocable organs (due to Karpinski's score ≥7). CONCLUSIONS: Our data demonstrate a correlation of histological damage at the time of transplant with 3-year graft function, but at present we are unable to provide any supposition on the possible outcome of the discarded kidneys.

Risk adjustment for cesarean delivery rates: how many variables do we need? An observational study using administrative databases.

BACKGROUND: Various studies indicate that inter-hospital comparisons have to take case mix into account and that risk adjustment procedures are necessary to control for potential predictors of cesarean delivery (CD). Different data sources have been used to retrieve information on potential predictors of CD. The aim of this study was to compare the discrimination capacity and fit of predictive models of CD created using different sources and to assess whether more complex models improve inter-hospital comparisons. METHODS: We created 4 predictive models of CD. One model included only variables from Hospital Discharge Records of the index hospitalization, one included also information from previous hospitalizations, one also clinical variables from birth certificates (BC) and one also socio-demographic variables. We compared the four models using the Receiver Operator Curve and the Akaike and Bayesian Information Criteria. RESULTS: Information from Birth Certificates improved the discrimination and model fit. Adding socio-demographic variables or past comorbidities did not improve the discrimination capacity or the model fit. Hospital-specific CD resulting from the models were highly correlated. CONCLUSIONS: Record linkage improves the performance of the models but does not affect inter-hospital comparisons.

Adaptation and Validation of the Spine Oncology Study Group Outcomes Questionnaire in Italian Language.

STUDY DESIGN: Prospective observational study. OBJECTIVE: The population of patients with advanced stages of cancer, including metastatic spinal disease, is growing because of better treatment options allowing for longer control of disease. The main goal of treatment for these patients is to improve or maintain their health-related quality of life (HRQOL). A spine oncology-specific outcome measure has been developed by the Spine Oncology Study Group and validated through international studies. We proposed to translate and validate the questionnaire in Italian language. METHODS: The cross-cultural adaptation of the questionnaire has been performed according to guidelines previously proposed. After this process, an observational prospective study has been conducted to validate the efficacy of SOSGOQ in Italian language. SOSGOQ has been compared to SF-36 (Short Form Health Survey-36), a generic validated questionnaire to assess HRQOL. Starting from January 2020, SOSGOQ and SF-36 questionnaires were auto-administered to 150 patients affected by spinal metastases who provided written informed consent for study participation. RESULTS: The confirmatory factor analysis on the 4 domains examined showed a good model fit (comparative fit index, .95; RMSEA .07 (90% CI, .05-.09) and SRMR, .05), endorsing construct validity. The analysis of concurrent validity demonstrated strong correlation for physical function, pain and mental health domains with the corresponding domain scores of SF-36. The reliability across item was high with a Cronbach's alpha coefficient of .91. CONCLUSIONS: The statistical analysis of the results will allow to accept the Italian version of SOSGOQ as a specific and efficient tool to measure HRQOL in Italian-speaking patients affected by spinal metastases.

SMARCB1/INI1 loss in skull base conventional chordomas: a clinicopathological and molecular analysis.

Introduction: The loss of SMARCB1/INI1 protein has been recently described in poorly differentiated chordoma, an aggressive and rare disease variant typically arising from the skull base. Methods: Retrospective study aimed at 1) examining the differential immunohistochemical expression of SMARCB1/INI1 in conventional skull base chordomas, including the chondroid subtype; 2) evaluating SMARCB1 gene deletions/copy number gain; and 3) analyzing the association of SMARCB1/INI1 expression with clinicopathological parameters and patient survival. Results: 65 patients (35 men and 30 women) affected by conventional skull base chordoma, 15 with chondroid subtype, followed for >48 months after surgery were collected. Median age at surgery was 50 years old (range 9-79). Mean tumor size was 3.6 cm (range 2-9.5). At immunohistochemical evaluation, a partial loss of SMARCB1/INI1 (>10% of neoplastic examined cells) was observed in 21 (32.3%) cases; the remaining 43 showed a strong nuclear expression. Fluorescence in situ hybridization (FISH) analysis was performed in 15/21 (71.4%) cases of the chordomas with partial SMARCB1/INI1 loss of expression. Heterozygous deletion of SMARCB1 was identified in 9/15 (60%) cases and was associated to copy number gain in one case; no deletion was found in the other 6 (40%) cases, 3 of which presenting with a copy number gain. No correlations were found between partial loss of SMARCB1/INI1 and the clinicopathological parameters evaluated (i.e., age, tumor size, gender, tumor size and histotype). Overall 5-year survival and 5-year disease-free rates were 82% and 59%, respectively. According to log-rank test analysis the various clinico-pathological parameters and SMARCB1/INI1 expression did not impact on overall and disease free-survival. Discussion: Partial loss of SMARCB1/INI1, secondary to heterozygous deletion and/or copy number gain of SMARCB1, is not peculiar of aggressive forms, but can be identified by immunohistochemistry in a significant portion of conventional skull base chordomas, including the chondroid subtype. The variable protein expression does not appear to correlate with clinicopathological parameters, nor survival outcomes, but still, it could have therapeutic implications.