bluuebunny/crossref_metadata_2025_split huggingface dataset:
5-FLUOROURACILE E TUMORI DEL COLON-RETTO: IMPIEGO NELLA PRATICA CLINICA E PROGETTO “MISURA”
Authors: Labianca Roberto , Poletti Paola 
Published: April 2018

5-fluorouracil, an antimetabolite inhibiting timidilate synthetase, is one of the most used drugs in the treatment of many solid tumor types. In particular it is still central in the treatment of colorectal cancer. Nevertheless 5-FU efficency is limited, this is due to the rapidity of its metabolism (T1/2 10 min). Many attempts have been done to increase its efficency: 1) combinations with other antitumor drugs have been tested, but no one showed improved response rates with respect to 5-FU alone; 2) use of biological modifiers such as folinic acid and methotrexate. They interact with the biological actions of 5-FU improving its therapeutic effects. These combinations appear to be more effective than 5-FU alone; 3) continuous infusion increases the percentage of susceptible tumor cells, it makes possible the use of a high intensity dose which is active in patients resistant to 5-FU administered as bolus-injection. There are many schedules and methods of administration of 5-FU in the treatment of CRC, each of them showing different types of toxicities. This explains why there is the need to obtain a profile of 5-FU in clinical practice. The project called MISURA is thought to give us this kind of information. It will be a collection of data regarding patients affected by colorectal cancer and treated with 5-FU. The collected information will be about diagnosis; ways of use, schedules, doses and tolerability of the drug; obtained responses. The aims of the study are: 1) to evaluate the use of 5-FU in clinical practice; 2) to collect data about the use of supportive therapy; 3) to know the effective incidence and prevalence of CRC in Italy. The study is retrospective, the sample consists of all patients from the oncological departments chosen to represent the national territory. The analysis of the data will be descriptive.
Ultrasound-Guided Fine-Needle Aspiration Biopsy for Breast Tumors: Needle Guide versus Freehand Technique
Authors: Hatada Takuya , Ishii Hiromitsu , Ichii Shigetoshi , Okada Kaoru , Yamamura Takehira 
Published: April 2018

Background We retrospectively studied whether a needle guide is necessary when performing ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in patients with breast tumors. Methods A total of 47 patients (50 lesions) with breast tumors underwent US-FNAB with a needle guide and 127 patients (143 lesions) underwent the procedure without a needle guide (freehand biopsy). The diagnoses obtained by US-FNAB were compared with the surgical findings. Results The sensitivity of freehand biopsy for tumors <3 cm in diameter was significantly higher than that of the needle guide technique. Conclusions We recommend performing US-FNAB without a needle guide (freehand biopsy) in order to maximize the correct preoperative diagnosis rate, especially in patients with tumors <3 cm in diameter.
Pitfalls in Frozen Section Interpretation: A Retrospective Study of Palpable Breast Tumors
Authors: Cserni Gábor 
Published: April 2018

Aims and background The use of frozen sections for purposes of diagnosis is recognized to involve a degree of uncertainty. A retrospective study of breast specimen frozen section diagnoses was undertaken in order to analyse the major pitfalls. Methods Hard copy files from our archives relating to symptomatic (palpable) breast specimens obtained between 1983 and 1996 were reviewed. Results The review revealed 23 errors among the diagnoses on 2110 frozen specimens. Twenty-two of them were false-negative and 1 (a case of multiple intraductal papillomatosis with atypical ductal hyperplasia) was false-positive for malignancy. The factors contributing to the pitfalls were: 1) misinterpretation; 2) poor quality of the frozen sections (artifacts making the diagnosis difficult); 3) sampling errors during sectioning; 4) ignorance of the macroscopic features; 5) lesions difficult to interpret; 6) ductal carcinoma in situ as the only lesion in the specimen; and 7) sections not deep enough. Several of the factors sometimes occurred simultaneously. Conclusions Although the number of errors is relatively low, more stress should be placed on the preoperative diagnosis of breast lesions. Breast surgery frozen section should be used as rarely as possible for diagnostic purposes, despite the generally good diagnostic accuracy. However, it is reasonable to use frozen sections widely until the given preoperative diagnostic tools allow an appropriate preoperative workup, because it is the only way to keep histopathologists trained to interpret frozen sections.
Serum-Soluble E-Cadherin Fragments in Lung Cancer
Authors: Cioffi Michele , Gazzerro Patrizia , Di Finizio Bruno , Vietri Maria Teresa , Di Macchia Catia , Puca Giovanni Alfredo , Molinari Anna Maria 
Published: April 2018

Aims and background E-cadherin, also known as uvomorulin or cell-CAM 120/80, is one of the subclasses of cadherins, CA2+-dependent cell adhesion molecules. Several recent studies have suggested that loss of E-cadherin may be associated with tumor progression, such as in lung, gastric, hepatocellular, breast and prostatic carcinoma. Assessment of E-cadherin serum levels in lung cancer showed a relation to histologic type. Methods and study design Using an enzyme immunoassay, we determined E-cadherin serum levels in 79 patients affected with lung cancer (stage l–IV), 9 patients with breast cancer, 23 patients with different benign diseases, and 20 healthy patients. Results At a specificity level of 90%, E-cadherin diagnostic sensitivity was 66.6%, 47.6% and 43.7% in patients affected with squamous cell carcinoma, small cell carcinoma and adenocarcinoma, respectively. Conclusions Preliminary results suggest the use of serum E-cadherin as a prospective tumor marker.
Neutropenia following Perioperative Intraperitoneal Chemotherapy
Authors: Schnake Klaus J. , Sugarbaker Paul H. , Yoo Dal 
Published: April 2018

Introduction The purpose of this retrospective report was to evaluate clinical features associated with profound neutropenia in patients with peritoneal carcinomatosis who were treated with heated intraoperative intraperitoneal chemotherapy (HIIC) followed by early postoperative intraperitoneal chemotherapy (EPIC). Common clinical denominators for significant neutropenia were analyzed. Materials and Methods A retrospective study of all available clinical data of six patients with postoperative neutropenia out of a total of 242 was undertaken. All patients underwent cytoreductive surgery, HIIC with mitomycin C (n = 4) or cisplatin (n = 1) and EPIC with 5-fluorouracil (5-FU) for 4 (n = 1) or 5 (n = 5) days. Results All six patients presented with hematologic toxicity of WHO criteria grade 4; four of them died postoperatively. Two of the patients who died, and one who did not die, developed bowel perforations. Five patients had prior chemotherapy with 5-FU; three of them had toxic side effects. All patients were overweight, and three patients were anemic preoperatively. The neutropenia presented with fever, leukopenia and thrombocytopenia on postoperative days 10–15. The leukocyte count courses showed a pattern suggesting the 5-FU as the cause of leukopenia. There was no consistent warning signal for predicting severe neutropenia. Discussion Neutropenia following cytoreductive surgery combined with HIIC and EPIC has a high mortality (66%). Patients who are at special risk and should have a dose reduction include patients who had toxicities from prior chemotherapy, who present with obesity and anemia. The groups have an increased risk of developing postoperative profound neutropenia. This condition can result in a prohibitively high mortality and morbidity rate. Therefore, reduced doses of chemotherapy in selected patients are necessary to prevent this condition from developing.
Mitoxantrone, L-Leucovorin and 5-Fluorouracil: An Effective and Well Tolerated First-Line Treatment for Advanced Breast Cancer
Authors: Lorusso Vito , Mancarella Sergio , Catino Annamaria , Brandi Mario , Paradiso Angelo , Latorre Agnese , Mastria Antonella , De Mitrio Alessandra , Guida Michele , De Lena Mario 
Published: April 2018

Aims and background The combination of mitoxantrone plus leucovorin/fluorouracil in heavily pretreated patients with advanced breast cancer has shown significant activity and extremely good tolerability. The aim of this study was to evaluate the activity of this combination in patients not previously submitted to chemotherapy. Methods From May 1993 to December 1995 we treated 80 patients with advanced breast cancer with a combination of mitoxantrone, l-leucovorin and 5-fluorouracil. All patients had histologically or cytologically proven breast cancer, WHO performance status 0–3, normal hematological parameters and normal serum bilirubin. Prior chemotherapy for metastatic disease was not allowed, whereas adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or adjuvant anthracycline (doxorubicin or epirubicin) therapy was allowed; a single prior hormone treatment was permitted. Chemotherapy consisted of mitoxantrone 12 mg/m2 i.v. day 1, l-leucovorin 150 mg/m2 i.v. days 1, 2 and 3 and 5-fluorouracil 350 mg/m2 i.v. days 1, 2 and 3. The courses were repeated every 3 weeks. Results Objective response (CR + PR) was observed in 46/80 (57%) patients (95% CI, 46%–68%). Complete response (CR) was observed in 21/80 cases (26%). Response was observed in 14/24 (58%) patients with soft tissues as the dominant site of disease, in 22/34 (65%) patients with visceral involvement and in 10/22 (45%) of those with bone as the dominant site of disease. The median duration of response and survival was 9 months (range, 3–16) and 22 months (range, 2–48+), respectively. Toxicity was very manageable, with grade 4 leukopenia and thrombocytopenia in 6/80 (7.5%) and 1/80 (1.25%) patients, respectively, and negligible non-hematological toxicity. Conclusions The combination of mitoxantrone, 5-fluorouracil and high-dose l-leucovorin is a safe and effective regimen for first-line treatment of advanced breast cancer.
Actinomycin D Revisited in Testicular Cancer. A Case Report
Authors: Srinivas Sandy , Freiha Fuad S. 
Published: April 2018

Background Between 20–30% of patients with advanced germ cell tumors relapse or fail to achieve a complete response to conventional cisplatin based chemotherapy. Ifosphamide has been used very effectively in combination with cisplatin and etoposide (VIP) or in combination with cisplatin and vinblastine (VeIP). Actinomycin D with chlorambucil and methotrexate was widely used in the 1960s with complete responses in 20% of patients and long term survival of 6–10%. There exists no information on the use of actinomycin as a salvage in cisplatin refractory patients. Methods and Results One patient with metastatic germ cell tumor who failed chemotherapy with cisplatin and ifosphamide was successfully treated with an actinomycin D based regimen. Conclusions Actinomycin D is an active agent in testicular cancer and maybe used in patients refractory to platinum.
Assessment of Endothelial Dysfunction With Flow-Mediated Dilatation in Myeloproliferative Disorders
Authors: Yildiz Abdulkerim , Güryildirim Melike , Pepeler Mehmet Sezgin , Yazol Merve , Oktar Suna Özhan , Acar Kadir 
Published: April 2018

Background:Thrombosis is the most important cardiovascular complication of classical myeloproliferative disorders (MPDs). Endothelial dysfunction (ED) is known to play a major role in the mechanism of thrombophilia in MPDs.Methods:Endothelial dysfunction and its associations with other parameters were investigated. A total of 18 patients with polycythemia vera (PV), 24 with essential thrombocytosis (ET), 7 with primary myelofibrosis (PMF), and 30 healthy patients as a control group were included in the study. To assess the ED, flow-mediated dilatation (FMD) measurements were used.Results:The FMD (%) result showing ED was determined as 9.9 (0.0-21.6) in the patients with PV, 7.3 (0.0-30.5) in patients with ET, 7.5 (0.0-18.0) in patients with PMF, and 13.9 (6.2-26.7) in the control group. The FMD (%) was markedly impaired in all patients with MPD compared to the control patients (7.8 [0.0-30.5] vs 13.9 [6.15-26.8], P = .02). According to the disease subtypes, FMD (%) was significantly lower in the ET group than in the control group ( P = .01).Conclusion:Endothelial function was assessed in patients with MPD having FMD and was determined to demonstrate ED. Lower FMD was associated with older age, leukocytosis, thrombocytosis, and thrombosis history.
32-mm ceramic-on-ceramic total hip arthroplasty versus 28-mm ceramic bearings: 5- to 15-year follow-up study
Authors: Higuchi Yoshitoshi , Seki Taisuke , Hasegawa Yukiharu , Takegami Yasuhiko , Morita Daigo , Ishiguro Naoki 
Published: April 2018

Introduction: This study aimed to compare the clinical and radiographic results of 28-mm ceramic-on-ceramic (CoC) total hip arthroplasty (THA) to those of 32-mm CoC during a 5- to 15-year follow-up period. Methods: 107 joints (95 women and 6 men) underwent 28-mm CoC, and 60 (49 women and 7 men) underwent 32-mm CoC. The average patient age at the time of surgery was 56.1 and 55.7 years in the 28-mm and 32-mm CoC groups, respectively. Clinical and radiologic measurements of all patients were analysed. Results: The mean preoperative Harris hip score (HHS) was similar in the 2 groups (28-mm, 58.9; and 32-mm, 58.5). However, at final follow-up, the mean HHS of the 32-mm CoC (91.8) was significantly better than that of the 28-mm CoC (88.2) ( p = 0.003), as were the ranges of motion (ROM) for flexion (98.3 ± 13.5° vs. 87.3 ± 19.3°, p < 0.001) and abduction (27.8 ± 14.9° vs. 22.1 ± 19.3°, p = 0.007). The mean wear rate was 0.0044 mm/year for the 28-mm CoC and 0.0044 mm/year for the 32-mm CoC. No ceramic fractures were found in the 2 groups. One joint in the 28-mm CoC (0.9%) required revision owing to progressive osteolysis. Kaplan-Meier survival at 10 years, with implant loosening or revision THA as the endpoint, was 98.3% for 28-mm CoC and 100% for 32-mm CoC ( p = 0.465). Conclusion: There was no significant difference in ceramic-related complications between the 2 groups. Our study demonstrated that the 32-mm and 28-mm CoC are safe and are associated with good clinical outcomes.
Chlorhexidine-coated peripherally inserted central catheters reduce fibroblastic sleeve formation in an in vivo ovine model
Authors: Sylvia Charles J , Wagel Molly A , Giare-Patel Kamna , Spangler Taylor A , Breznock Eugene M , Gupta Nisha 
Published: April 2018

Purpose: This study compared an antimicrobial and anti-thrombogenic peripherally inserted central catheter treated with a chlorhexidine-based technology, a peripherally inserted central catheter with bulk distributed fluoro-oligomers, and a poly 2-methoxyethyl acrylate–based peripherally inserted central catheter to an untreated peripherally inserted central catheter (control) in an ovine model at 14 and 30 days post-implant. Methods: One of four types of peripherally inserted central catheters was surgically implanted into the left jugular vein of each of 18 sheep for 14 or 30 days. Blood analysis consisted of complete blood counts, serum chemistries, and coagulation (fibrinogen, prothrombin time, and partial thromboplastin time) profiles. Sheep were sacrificed to examine the vein and thorax. Histological analysis was performed on serial catheter sections using standard microscopy on hematoxylin and eosin–stained tissues. Results: All catheters developed fibroblastic sleeves at both 14 and 30 days. The chlorhexidine-peripherally inserted central catheter showed a 64% lower mean fibroblastic sleeve weight and a 66% shorter mean fibroblastic sleeve length compared to the untreated control at 14 days. By 30 days, compared to untreated control, the chlorhexidine-peripherally inserted central catheter showed 81% lower mean fibroblastic sleeve weight with 75% shorter mean fibroblastic sleeve length, the fluoro-oligomer-peripherally inserted central catheter showed 54% lower mean sheath weight with 40% shorter mean fibroblastic sleeve length, and the poly 2-methoxyethyl acrylate-peripherally inserted central catheter had 41% lower mean fibroblastic sleeve weight with 57% lower fibroblastic sleeve length. Conclusion: Among the three anti-thrombogenic peripherally inserted central catheter technologies, the chlorhexidine-peripherally inserted central catheter had the smallest fibroblastic sleeves, followed by the fluoro-oligomer-peripherally inserted central catheter, poly 2-methoxyethyl acrylate-peripherally inserted central catheter, and control peripherally inserted central catheter.
Deconstruction of HLA-DRB1*04:01:01 and HLA-DRB1*15:01:01 class II haplotypes using next-generation sequencing in European-Americans with multiple sclerosis
Authors: Creary Lisa E , Mallempati Kalyan C , Gangavarapu Sridevi , Caillier Stacy J , Oksenberg Jorge R , Fernández-Viňa Marcelo A 
Published: April 2018

Background: The association between HLA-DRB1*15:01 with multiple sclerosis (MS) susceptibility is well established, but the contribution of the tightly associated HLA-DRB5*01:01 allele has not yet been completely ascertained. Similarly, the effects of HLA-DRB1*04:01 alleles and haplotypes, defined at the full-gene resolution level with MS risk remains to be elucidated. Objectives: To characterize the molecular architecture of class II HLA-DR15 and HLA-DR4 haplotypes associated with MS. Methods: Next-generation sequencing was used to determine HLA-DQB1, HLA-DQA1, and HLA-DRB1/4/5 alleles in 1403 unrelated European-American patients and 1425 healthy unrelated controls. Effect sizes of HLA alleles and haplotypes on MS risk were measured by odds ratio (OR) with 95% confidence intervals. Results: HLA-DRB1*15:01:01:01SG (OR = 3.20, p < 2.2E–16), HLA-DRB5*01:01:01 (OR = 2.96, p < 2.2E–16), and HLA-DRB5*01:01:01v1_STR1 (OR = 8.18, p = 4.3E–05) alleles all occurred at significantly higher frequencies in MS patients compared to controls. The most significant predis-posing haplotypes were HLA-DQB1*06:02:01~ HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01 and HLA-DQB1*06:02:01~HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01v1_STR1 (OR = 3.19, p < 2.2E–16; OR = 9.30, p = 9.7E–05, respectively). Analyses of the HLA-DRB1*04 cohort in the absence of HLA-DRB1*15:01 haplotypes revealed that the HLA-DQB1*03:01:01:01~HLA-DQA1*03:03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was protective (OR = 0.64, p = 0.028), whereas the HLA-DQB1*03:02:01~HLA-DQA1*03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was associated with MS susceptibility (OR = 1.66, p = 4.9E–03). Conclusion: HLA-DR15 haplotypes, including genomic variants of HLA-DRB5, and HLA-DR4 haplotypes affect MS risk.
Polymorphism in the serotonin transporter gene polymorphisms (5-HTTLPR) modifies the association between significant life events and depression in people with multiple sclerosis
Authors: Saul Alice , Taylor Bruce , Simpson Steve , Ponsonby Anne-Louise , Blizzard Leigh , Dwyer Terence , McMorran Brendan , Wood Brenda , van der Mei Ingrid AF 
Published: April 2018

Background: In the general population, variation in the serotonin-transporter-linked polymorphic region ( 5-HTTLPR) has been shown to modify the association between stressful events and depression/anxiety. This has not been examined in people with multiple sclerosis (MS). Objective: We examined the interaction between significant life events (SLE), 5-HTTLPR and depression/anxiety. Methods: A population-based longitudinal cohort of 198 people with MS was followed biannually for 2.5 years. Depression and anxiety symptoms were measured at each review using the Hospital Anxiety and Depression Scale (HADS). SLEs were assessed using a questionnaire based on the Social Readjustment Rating Scale. Results: We found an interaction between SLE load in the previous 12 months and functional variation in the 5-HTTLPR allele type in predicting depression, with the association between SLE load and depression being stronger for those with S/S allele type (β = 0.21 (95% confidence interval (CI): 0.09–0.33) per 10-unit increase) and S/L (β = 0.14 (95% CI: 0.05–0.24)) compared to L/L allele type (β = 0.04 (95% CI: −0.05 to 0.24); pinteraction < 0.001). No convincing evidence of an interaction was found with anxiety. Conclusion: We found that the association between SLE load and MS depression severity was stronger among those with one or two copies of the short allele of the 5-HTTLPR. The identification of a gene–environment interaction between SLEs and depression in a population where depression is partly disease-driven is novel.
Recognizing disparities in health care for children with special health care needs
Authors: Crump Christie 
Published: April 2018

Introduction There is a significant disparity in the United States between the health care received by children with special health care needs versus physically healthy children. Objective The objective of the paper is to show that children with special needs receive less than adequate health care overall. This disparity affects the quality of life for these children and influences their ability to live their lives to their full potential. Methods Research was conducted by examining multiple studies with a focus on six major factors that play a role in creating this disparity. Results The findings show an alarming trend in the access and delivery of health care to children with special health care needs. Conclusions Solutions to correcting the disparities are possible, but it will take a full understanding of the issues, perseverance, dedication, and hard work on the part of families, physicians, legislators, and others genuinely interested in creating an equal health care system for all children.
Efficacy and safety of the combination of isosorbide dinitrate spray and chitosan gel for the treatment of diabetic foot ulcers: A double-blind, randomized, clinical trial
Authors: Totsuka Sutto Sylvia Elena , Rodríguez Roldan Yunuen Itzet , Cardona Muñoz Ernesto German , Garcia Cobian Teresa Arcelia , Pascoe Gonzalez Sara , Martínez Rizo Abril , Mendez del Villar Miriam , García Benavides Leonel 
Published: April 2018

Aim: To evaluate whether a combination of isosorbide dinitrate spray and chitosan gel (10%) topically applied can have additive benefits for management of diabetic foot ulcers. Methods: In a randomized, placebo-controlled, double-blinded clinical trial, 68 patients were divided into four groups: Group 1: treated with chitosan gel; Group 2: isosorbide dinitrate spray; Group 3: combination of isosorbide dinitrate spray and chitosan gel; Group 4: placebo. Results: Histological analyses showed a significant regeneration in all groups ( p < 0.001). On the final assessment of the ulcer, using the combination was found a wound closure percentage of 71 ± 30, 70 ± 27 using isosorbide dinitrate, 58 ± 30 with chitosan and 50 ± 16 with placebo. The number of patients who achieved complete ulcer closure was six using the combination, four with isosorbide dinitrate, three with chitosan and one with placebo. The progression in the healing process of the ulcer showed marked inmunohistochemical differences of Von Willebrand Factor, desmin, vascular endothelial growth factor-A and α-smooth muscle actin in all groups ( p < 0.001), but without notable differences between them. Conclusion: The combination was better than placebo to reduce the dimensions of the ulcer, accelerate healing and increase the number of patients who achieved complete closure of the ulcer, but the combination was not better than chitosan or isosorbide dinitrate used separately.