Miracle-dz/UniFAR-FTUs huggingface dataset:
Efficacy of sequential high-dose doxorubicin and ifosfamide compared with standard-dose doxorubicin in patients with advanced soft tissue sarcoma: an open-label randomized phase II study of the Spanish group for research on sarcomas.

PURPOSE To assess the progression-free survival (PFS) and antitumor response to standard-dose doxorubicin compared with sequential dose-dense doxorubicin and ifosfamide in first-line treatment of advanced soft tissue sarcoma. PATIENTS AND METHODS Patients with measurable advanced soft tissue sarcoma, Eastern Cooperative Oncology Group (ECOG) performance status (PS) < 2, between the ages 18 and 65 years, and with adequate bone marrow, liver, and renal function were entered in the study. The stratifications were: ECOG PS (0 v 1), location of metastases, and potentially resectable disease. Patients were randomly assigned to either doxorubicin 75 mg/m(2) given as a bolus injection every 3 weeks for 6 cycles (arm A) or doxorubicin at 30 mg/m(2) per day for 3 consecutive days once every 2 weeks for 3 cycles followed by ifosfamide at 12.5 g/m(2) delivered by continuous infusion over 5 days once every 3 weeks for 3 cycles with filgastrim or pegfilgastrim support (arm B). RESULTS Between December 2003 and September 2007, 132 patients were entered onto the study. Febrile neutropenia, asthenia, and mucositis were more frequent in the arm B. The interim preplanned analysis for futility allowed the premature closure. Objective responses were observed in 23.4% of assessable patients in arm A and 24.1% in arm B. PFS was 26 weeks in the arm A and 24 weeks in arm B (P = .88). Overall survival did not differ between the two therapeutic arms (P = .14). CONCLUSION Single-agent doxorubicin remains the standard treatment in fit patients with advanced soft tissue sarcoma.
Home-Assistant Robot for an Aging Society

Many countries around the world face three major issues associated with their aging societies: a declining population, an increasing proportion of seniors, and an increasing number of single-person households. To explore assistive technologies that can help solve the problems faced by aging societies, we have tested several information and robot technologies. This paper introduces research on a home-assistant robot, which improves the ease and productivity of home activities. For people who work hard outside the home, the assistant robot performs chores in their home environment while they are away. A case study of a life-sized robot with a humanlike functional body performing daily chores is presented. An integrated software system incorporating modeling, recognition, and manipulation skills, as well as a motion generation approach based on the software system, is explained. Moreover, because housekeepers perform chores one after another in their daily environment, we also aim to develop a system for continuously performing a series of tasks by including failure detection and recovery.
Packed red blood cell transfusions in the intensive care unit: treating the patient or the doctor?

(LAFA-study). Ann. Surg. 2011; 254: 868–75. 10. Gustafsson UO, Scott MJ, Schwenk W et al. Guidelines for perioperative care in elective colonic surgery: enhanced recovery after surgery (ERAS) society recommendations. Clin. Nutr. 2012; 31: 783– 800. Andrew G. Hill, MBChB, MD (Thesis), EdD, FACS, FRACS Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, University of Auckland, Auckland, New Zealand
Intensive dose-dense compared with conventionally scheduled preoperative chemotherapy for high-risk primary breast cancer.

PURPOSE To compare preoperative intense dose-dense (IDD) chemotherapy with conventionally scheduled preoperative chemotherapy in high-risk primary breast cancer (BC). PATIENTS AND METHODS In this randomized phase III trial a total of 668 eligible primary BC patients stratified for tumors > or = 3 cm (n = 567) or inflammatory BC (n = 101) were randomly assigned to receive concurrent preoperative epirubicin/paclitaxel every 3 weeks or dose-dense and dose-escalated sequential epirubicin followed by paclitaxel every 2 weeks. All patients received three cycles of cyclophosphamide, methotrexate, and fluorouracil chemotherapy after surgery. RESULTS IDD treatment significantly improved pathologic complete response rate (18% v 10%; odds ratio [OR] 1.89; P = .008), disease-free survival (DFS; hazard ratio [HR], 0.71; P = .011), and overall survival (OS; HR, 0.83; P = .041) compared to epirubicin/paclitaxel. Patients with inflammatory BC had a particularly poor prognosis and did not appear to benefit from IDD therapy in this trial (DFS HR, 1.10; P = .739; OS HR, 1.25; P = .544). In contrast, patients with noninflammatory BC significantly benefited from IDD treatment (DFS HR, 0.65, P = .005; OS HR, 0.77, P = .013). Treatment effects in multivariate analysis were significant for noninflammatory BC (DFS HR, 0.65, P = .015; OS HR, 0.79, P = .034), but not for all patients (DFS HR, 0.76; P = .088; OS HR, 0.82; P = .059). IDD therapy was associated with significantly more nonhematologic toxicities, anemia, and thrombocytopenia, but with similar neutropenia and infection rates. CONCLUSION Our results support the efficacy and short-term safety of IDD as preoperative chemotherapy. IDD was less well tolerated compared to standard treatment, but improved clinical outcomes in patients with noninflammatory high-risk primary BC.
Response to Re: Augmenting pancreatic anastomosis during whipple operation with fibrin glue: a beneficial technical modification?

We were interested to read the comments of Ryan et al. accompanying the CT images of a foramen of Winslow herniation. We have managed a patient with a small bowel herniation through the foramen of Winslow (Fig. 1) and noted some similarities and differences. Our patient was a 31-year-old male who presented to Nambour Hospital Emergency Department with acute onset of epigastric pain and nausea. The pain was colicky in nature with no radiation. The pain was relieved with trunk flexion and lying in a ‘fetal’ position in a similar fashion to the Ryan et al. case. This sign is generally associated with acute pancreatitis; however, our patient’s lipase was normal. This sign has been noted in a number of similar case reports, and the diagnosis of internal herniation through the foramen of Winslow should be considered in the differential diagnosis particularly with a normal lipase. The proposed mechanism to explain the sign is that truncal flexion opens the foramen of Winslow, which reduces the compression on the herniated loop of bowel. At operation, our patient had a small intestinal herniation. This was reduced and no resection was needed. Our case, like that of Ryan et al., was diagnosed preoperatively on CT scan. The reference that radiological diagnosis is made in <10% of confirmed cases is a 1988 publication, where plain films and water-soluble enema were used as main diagnostic tools. We suspect that preoperative radiological diagnosis would well exceed 10% currently with widespread use of CT. References
Prognostic significance of copy-number alterations in multiple myeloma.

PURPOSE Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown. PATIENTS AND METHODS We performed a genome-wide analysis of malignant plasma cells from 192 newly diagnosed patients with myeloma using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis. RESULTS Our analyses revealed deletions and amplifications in 98% of patients. Amplifications in 1q and deletions in 1p, 12p, 14q, 16q, and 22q were the most frequent lesions associated with adverse prognosis, whereas recurrent amplifications of chromosomes 5, 9, 11, 15, and 19 conferred a favorable prognosis. Multivariate analysis retained three independent lesions: amp(1q23.3), amp(5q31.3), and del(12p13.31). When adjusted to the established prognostic variables (ie, t(4;14), del(17p), and serum beta(2)-microglobulin [Sbeta(2)M]), del(12p13.31) remained the most powerful independent adverse marker (P < .0001; hazard ratio [HR], 3.17) followed by Sbeta(2)M (P < .0001; HR, 2.78) and the favorable marker amp(5q31.3) (P = .0005; HR, 0.37). Patients with amp(5q31.3) alone and low Sbeta(2)M had an excellent prognosis (5-year overall survival, 87%); conversely, patients with del(12p13.31) alone or amp(5q31.3) and del(12p13.31) and high Sbeta(2)M had a very poor outcome (5-year overall survival, 20%). This prognostic model was validated in an independent validation cohort of 273 patients with myeloma. CONCLUSION These findings demonstrate the power and accessibility of molecular karyotyping to predict outcome in myeloma. In addition, integration of expression of genes residing in the lesions of interest revealed putative features of the disease driving short survival.
Future of cancer incidence in the United States: burdens upon an aging, changing nation.

PURPOSE By 2030, the United States' population will increase to approximately 365 million, including 72 million older adults (age > or = 65 years) and 157 million minority individuals. Although cancer incidence varies by age and race, the impact of demographic changes on cancer incidence has not been fully characterized. We sought to estimate the number of cancer patients diagnosed in the United States through 2030 by age and race. METHODS Current demographic-specific cancer incidence rates were calculated using the Surveillance Epidemiology and End Results database. Population projections from the Census Bureau were used to project future cancer incidence through 2030. RESULTS From 2010 to 2030, the total projected cancer incidence will increase by approximately 45%, from 1.6 million in 2010 to 2.3 million in 2030. This increase is driven by cancer diagnosed in older adults and minorities. A 67% increase in cancer incidence is anticipated for older adults, compared with an 11% increase for younger adults. A 99% increase is anticipated for minorities, compared with a 31% increase for whites. From 2010 to 2030, the percentage of all cancers diagnosed in older adults will increase from 61% to 70%, and the percentage of all cancers diagnosed in minorities will increase from 21% to 28%. CONCLUSION Demographic changes in the United States will result in a marked increase in the number of cancer diagnoses over the next 20 years. Continued efforts are needed to improve cancer care for older adults and minorities.
Gene expression profiling uncovers molecular classifiers for the recognition of anaplastic large-cell lymphoma within peripheral T-cell neoplasms.

PURPOSE To unravel the regulatory network underlying nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) -mediated lymphomagenesis of anaplastic large-cell lymphoma (ALCL) and to discover diagnostic genomic classifiers for the recognition of patients with ALK-positive and ALK-negative ALCL among T-cell non-Hodgkin's lymphoma (T-NHL). PATIENTS AND METHODS The transcriptome of NPM-ALK-positive ALCL cell lines was characterized by silencing the expression of ALK or STAT3, a major effector of ALK oncogenic activity. Gene expression profiling (GEP) was performed in a series of systemic primary T-NHL (n = 70), including a set of ALK-positive and ALK-negative ALCL (n = 36). Genomic classifiers for ALK-positive and ALK-negative ALCL were generated by prediction analyses and validated by quantitative reverse-transcriptase polymerase chain reaction and/or immunohistochemistry. RESULTS In ALCL cell lines, two thirds of ALK-regulated genes were concordantly dependent on STAT3 expression. GEP of systemic primary T-NHL significantly clustered ALK-positive ALCL samples in a separate subgroup, underscoring the relevance of in vitro ALK/STAT3 signatures. A set of genomic classifiers for ALK-positive ALCL and for ALCL were identified by prediction analyses. These gene clusters were instrumental for the distinction of ALK-negative ALCL from peripheral T-cell lymphomas not otherwise specified (PTCLs-NOS) and angioimmunoblastic lymphomas. CONCLUSION We proved that experimentally controlled GEP in ALCL cell lines represents a powerful tool to identify meaningful signaling networks for the recognition of systemic primary T-NHL. The identification of a molecular signature specific for ALCL suggests that these T-NHLs may represent a unique entity discernible from other PTCLs, and that a restricted number of genes can be instrumental for clinical stratification and, possibly, therapy of T-NHL.
Late effects of conformal radiation therapy for pediatric patients with low-grade glioma: prospective evaluation of cognitive, endocrine, and hearing deficits.

PURPOSE We conducted a prospective trial to evaluate late effects in pediatric patients with low-grade glioma (LGG) treated with conformal radiation therapy (CRT). PATIENTS AND METHODS Between August 1997 and August 2006, 78 pediatric patients with LGG (mean age, 9.7 years; standard deviation, +/-4.4 years) received 54 Gy of CRT with a 10-mm clinical target volume margin. Tumor locations were diencephalon (n = 58), cerebral hemisphere (n = 3), and cerebellum (n = 17). Baseline and serial evaluations were performed to identify deficits in cognition, endocrine function, and hearing. Deficits were correlated with clinical factors and radiation dose within specific normal tissue volumes. RESULTS Cognitive effects of CRT through 5 years after CRT correlated with patient age, neurofibromatosis type 1 status, tumor location and volume, extent of resection, and radiation dose. The effect of age exceeded that of radiation dose; patients younger than 5 years experienced the greatest decline in cognition. Before CRT, growth hormone (GH) secretion abnormality was diagnosed in 24% of tested patients, and 12% had precocious puberty. The 10-year cumulative incidence of GH replacement was 48.9%; of thyroid hormone replacement, 64.0%; of glucocorticoid replacement, 19.2%; and of gonadotropin-releasing hormone analog therapy, 34.2%. The mean +/- standard errors of the cumulative incidence of hearing loss at 10 years did not exceed 5.7% +/- 3.3% at any frequency. CONCLUSION To our knowledge, this is the largest series of prospectively followed children with LGG to undergo irradiation. Adverse effects are limited and predictable for most patients; however, this study provides additional evidence that CRT should be delayed for young patients and identifies the potential benefits of reducing radiation dose to normal brain.
Understanding and managing parkinsonism in patients with glucocerebrosidase mutations

Introduction: Identification of an association between mutations in the glucocerebrosidase gene (GBA1) and the development of parkinsonism has contributed to a greater understanding of the role of lysosomal function in neuronal degeneration. This review will discuss the phenotypic presentation of patients with GBA1-associated parkinsonism. Some treatment strategies will be discussed although treatment studies in this cohort are limited. Areas covered: Current literature suggests that parkinsonism associated with GBA1 mutations may have specific characteristics distinct from idiopathic Parkinson’s disease or parkinsonism due to other genetic mutations. In this review, we performed an electronic search in the PubMed database for papers using the terms ‘Parkinson disease’, ‘parkinsonism’, ‘Gaucher disease’, and ‘GBA1’. Papers were selected if they discussed or described clinical presentation, treatment and current research efforts related to these terms. Expert opinion: Although there are no studies identifying treatments specific to patients with GBA1-associated parkinsonism, careful phenotypic characterization is crucial for the elucidation of the interaction between glucocerebrosidase and α-synuclein as well as for proper determination of disease prognosis and appropriate clinical counseling.
Fluorouracil, epirubicin, and cyclophosphamide with either docetaxel or vinorelbine, with or without trastuzumab, as adjuvant treatments of breast cancer: final results of the FinHer Trial.

PURPOSE Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) -positive cancer are unknown. PATIENTS AND METHODS One thousand ten women with axillary node-positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. RESULTS Women assigned to docetaxel had better distant disease-free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. CONCLUSION Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.
Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma

Twenty‐three patients with advanced and heavily pretreated myeloma were treated with thalidomide. Starting dose was 200 mg/d, and 20 patients had dose escalations up to 400 (n = 5), 600 (n = 12) or 800 mg/d (n = 3), usually in divided doses. Nineteen patients were refractory to recent chemotherapy, and four had untreated relapse after prior intensive therapy. Ten out of 23 patients (43%) achieved partial response (PR; nine with refractory and one with relapsed disease), six patients had minor response or stabilization of the disease and four had disease progression. Another three patients died early from advanced myeloma at less than 3 weeks of thalidomide therapy. Of the 10 patients with PR, seven had a better response than after any prior therapy, despite vincristine–doxorubicin–dexamethasone (VAD)‐based treatment in all but one and high‐dose melphalan with autologous stem cell support in four. Time to achieve PR was rapid in patients receiving thalidomide in divided doses (median 31 d). Responses also included reduced bone marrow plasma cell infiltration and improved general status. Normalized polyclonal gammaglobulin levels were seen in four cases. Six out of 10 patients with PR remained in remission with a median time on treatment of 23 weeks (range 15–50 weeks). Sedation was common but usually tolerable, and some patients continued full‐ or part‐time work. Four patients had skin problems, three patients had pneumonia, one hypothyrosis, one sinus bradycardia and one minor sensory neuropathy. Thalidomide may induce good partial remissions in advanced refractory myeloma with tolerable toxicity, and should be evaluated in other settings for myeloma patients. Divided thalidomide doses seem to reduce time to achieve remission and may improve response rate.
Lingual Orthodontics: The Future

Lingual orthodontics has come of age; its acceptance by both the profession and the patient population continues to grow internationally. The future of lingual orthodontics is dependent on the following three important issues: (1) advances in technology related to appliance design and laboratory protocols; (2) demographic changes in population age groups—the growth in the number of adult patients seeking orthodontic treatment associated with an increase in affluence and disposable income will create a patient-driven demand for more esthetically acceptable appliances; and (3) attitudinal changes of orthodontists. There has in some countries been a reluctance of the profession to embrace the lingual technique. With education and training this resistance is starting to erode and an increasing number of clinicians are learning and adopting the lingual technique.
ITP and pregnancy

The question, “Doctor, is it safe for me to become pregnant? ” is one of the more charged issues confronting a woman with idiopathic thrombocytopenic purpura (ITP) and her physician. Maternal platelet counts can fall during even uncomplicated pregnancies. Some of the drugs commonly used to manage
Neurophilia: a fascination for neurology—a new syndrome

Neurophobia—the pathological fear of neurology—is a well recognised state of mind. This was first described in 19941 as occurring in medical students, and subsequently being demonstrated in junior doctors2 and around the world.3 ,4 While ‘neurophobia’ does not appear in the DSM-IV, the term does carry the implication that this is a disorder. However, as it is so widespread, occurring at all levels of training, across continents and through time, perhaps it should be regarded as the natural state for medical students and doctors. That certainly seems to be the presumption in many of the articles where it is discussed.2–4 In this article, I would like to explore a previously undescribed state, ‘neurophilia’, a love of neurology or more precisely a fascination by neurology. Moreover, I will argue that this is both widespread within medicine and the general population. Neurophilia is probably a precondition to become a neurologist and presumably pretty much all the readers of Practical Neurology are afflicted. How can we assess this in …
Phase II trial of pertuzumab and trastuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer that progressed during prior trastuzumab therapy.

UNLABELLED PURPOSE; Pertuzumab, a human epidermal growth factor receptor 2 (HER2) -targeted monoclonal antibody, potently inhibits HER2 dimerization and HER-mediated signaling pathways. Pertuzumab and the approved HER2-targeted monoclonal antibody trastuzumab have complementary mechanisms of action and result in enhanced antitumor activity when combined. This phase II trial assessed the efficacy and safety profile of the combination in patients with HER2-positive breast cancer whose disease had progressed during prior trastuzumab-based therapy. PATIENTS AND METHODS This was a multicenter, open-label, single-arm, Simon two-stage study. Patients with advanced HER2-positive breast cancer in whom disease progression had occurred during prior trastuzumab-based therapy received trastuzumab weekly (4 mg/kg loading dose, then 2 mg/kg every week) or every 3 weeks (8 mg/kg loading dose, then 6 mg/kg every 3 weeks) and pertuzumab every 3 weeks (840 mg loading dose, then 420 mg every 3 weeks). Treatment continued until disease progression or excessive toxicity. RESULTS All 66 patients were assessable for efficacy and safety. The objective response rate was 24.2%, and the clinical benefit rate was 50%. Five patients (7.6%) experienced a complete response, 11 patients (16.7%) experienced a partial response, and 17 patients (25.8%) experienced stable disease of > or = 6 months. Median progression-free survival was 5.5 months. Overall, the combination of pertuzumab and trastuzumab was well tolerated, and adverse events were mild to moderate. Cardiac dysfunction was minimal, and no patients withdrew as a result of cardiac-related adverse events. CONCLUSION The combination of pertuzumab and trastuzumab is active and well tolerated in patients with metastatic HER2-positive breast cancer who had experienced progression during prior trastuzumab therapy.