bluuebunny/crossref_metadata_2025 huggingface dataset:
The risk of venous thromboembolism in patients with heart failure
Authors: Vereina N. K. , Agasyan D. G. , Chulkov V. S.
Published: February 2020

Aim. To quantify the risk of venous thromboembolism (VTE) in hospitalized patients, depending on the severity of heart failure (HF).

Material and methods. Current cross-sectional study included 132 patients hospitalized in the cardiology department in 2019. All participants were divided into 2 groups: group 1 (n=48) — patients with class I-II HF; group 2 (n=84) — patients with class III-IV HF. A total quantitative assessment of the VTE risk was carried out according to the Caprini risk scoring method.

Results. All patients hospitalized in the cardiology department, regardless of HF class, had a moderate and high risk of VTE and required prophylactic anticoagulation. High VTE risk had 85% of patients with class I-II HF; 97,6% — patients with a class III-IV HF. Mean score of ≥10 was observed in every fifth patient. Atrial fibrillation requiring long-term anticoagulant therapy was observed in 51,5% of patients. There were no absolute contraindications for parenteral prophylactic anticoagulation at the time of hospitalization in the study population.

Conclusion. All patients admitted to the cardiology department had a moderate and high according to the Caprini risk score, regardless of HF class. More than half of the patients had indications for long-term anticoagulant therapy. The remaining patients required the parenteral prophylactic anticoagulation.
Comparative pharmacoeconomic analysis of medication for patients after acute decompensated heart failure
Authors: Zyryanov S. K. , Ushkalova E. A.
Published: February 2020

Aim. Pharmacoeconomic comparison of medication management strategies (valsartan+ sacubitril) for patients with heart failure (HF), stabilized after an episode of acute decompensated heart failure (ADHF).

Material and methods. “Cost — effectiveness analysis” and “Budget impact analysis” were used. The study is conducted in terms of the interests of Russian Federation health care system and budgets of individual regions.

Results. The use of valsartan+sacubitril combination will require an increase in direct medical costs for 1 year by 38,5% compared with enalapril. The cost of one life year gained when using the valsartan+sacubitril combination was 307,294 rubles. When estimating data for the target ADHF population (n=200,769), valsartan+sacubitril will require additional 4,4 billion rubles per year. At the same time, this will save almost 17 thousand lives and prevent 126 thousand ambulance calls and 33,9 thousand rehospitalizations, including more than 6,5 thousand in the intensive care unit.

Conclusion. The use of valsartan+sacubitril combination in HF patients hospitalized with ADHF is cost-effective management strategy that significantly improves the prognosis in this category of patients.
Evaluation of ST2 as an early marker of heart failure with a preserved left ventricular ejection fraction in patients with persistent atrial fibrillation
Authors: Polyanskaya E. A. , Koziolova N. A. , Mironova S. V.
Published: February 2020

Aim. To assess the diagnostic value of soluble ST2 (sST2) for early detection of heart failure with a preserved ejection fraction (HFpEF) in patients with persistent atrial fibrillation (AF).

Material and methods. A total of 165 patients hospitalized with AF paroxysm were examined. The inclusion criteria were the persistent AF and LVEF >50% according to echocardiography. A cohort of 60 patients with persistent AF and preserved LVEF was formed. Patients were divided into 2 equal groups of 30 people depending on the HF presence, assessed on the basis of LV diastolic dysfunction with or without left atrial enlargement >34 ml/m2 or left ventricular mass index >110 g/m2 in men and 95 g/m2 in women, as well as an increase in the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) >125 pg/ml. LVEF was calculated using the Simpson method; assessment of LV diastolic function was carried out with determination of transmitral flow velocity characteristics and visualization of mitral annulus motion. The NT-proBNP concentration was determined in blood serum using the Biomedica Group reagent (Austria), sST2 — using Presage ST2 (Critical Diagnostics, USA) by enzyme-linked immunosorbent assay on an Immulite 1000 analyzer (DPC, USA).

Results. In patients with HFpEF and persistent AF, the correlation analysis showed a direct strong relationship between NT-proBNP and sST2 (r=0,726; p<0,05). To assess sST2 as a diagnostic criterion for HF, ROC curve was constructed. It was shown that with sST2 ≥16 ng/ml (AUC=0,89), the sensitivity of the method was 80%, the specificity — 83%.

Conclusion. In patients with a persistent AF, serum sST2 concentration ≥16 ng/ml can be used as an alternative to the NT-proBNP criterion for early diagnosis of HFpEF.
Guidelines for Hospitalization for Chemotherapy
Authors: Dollinger Malin
Published: February 2020

Administration of cancer chemotherapeutic agents has shifted from the hospital to outpatient settings, usually the oncologist's office. Hospitalization for chemotherapy is now limited to specific situations, reflecting the need for prolonged direct observation, prevention or treatment of anticipated or real side effects, the use of special facilities and the minimization of certain treatment risks which cannot be effectively dealt with in an outpatient setting. New financial guidelines also have a significant impact on the location of chemotherapy administration. Outpatient chemotherapy has the advantages of allowing safe, easy drug administration, respecting the patient's wish to avoid hospitalization and providing a familiar facility, which enhances the patient's physical comfort and psychological well-being. The oncologist has direct and immediate control of drug administration, assistance is immediately available if problems arise, care is less expensive than inpatient care and overnight stay can be avoided. It also facilitates monitoring and control of treatment costs and allows treatment to be administered at the patient's convenience. Specific circumstances which justify hospitalization for chemotherapy, as detailed in Table 1, include: higher dosage cisplatin, special procedure chemotherapy, induction therapy for acute leukemia, high-dosage chemotherapy with or without stem cell/bone marrow transplantation, severely emetogenic chemotherapy, ifosfamide therapy, combination radiation therapy plus chemotherapy programs, coexistent medical problems (comorbidities), complex chemotherapy programs, the initial dose of chemotherapy while hospitalized for diagnosis of cancer, a scheduled dose of chemotherapy occurring during hospitalization for an unrelated problem, special measures required to prevent significant side effects, high-dose methotrexate protocols, intraperitoneal chemotherapy, certain investigational treatment protocols, and if chemotherapy administration is mandatory despite comorbidities that would ordinarily delay or contraindicate chemotherapy.
New Antifolates: Pharmacology and Clinical Applications
Authors: Takimoto Chris H.
Published: February 2020

Many new antifolate compounds with unique clinical properties are currently in clinical development. Some of these agents have been rationally designed to circumvent known mechanisms of resistance to methotrexate, the most useful and extensively studied antifolate in clinical practice. Resistance to methotrexate can result from decreased active transport into cells, decreased polyglutamation resulting in enhanced drug efflux from cells, mutations in dihydrofolate reductase which reduce drug binding affinity, and increased expression of dihydrofolate reductase due to gene amplification or increased translational efficiency. As a consequence, the newer antifolates may differ from methotrexate because of increased lipid solubility, improved cellular uptake or increased ability to undergo polyglutamation. Several of these newer agents also uniquely target specific folate-dependent enzymes such as thymidylate synthase or glycinamide ribonucleotide transformylase. Antifolates currently in clinical development include trimetrexate, edatrexate, piritrexim, ZD1694, lometrexol, AG337, LY231514 and 1843U89. This report summarizes the basic pharmacology and potential clinical applications of these promising new agents.
Recombinant Human Erythropoietin (rHuEPO) for the Treatment of the Anemia of Cancer
Authors: Abels R. I. , Larholt Kay M. , Krantz Kenneth D. , Bryant Edward C.
Published: February 2020

Advanced cancer is frequently associated with a significant anemia that may be due to the disease itself or the effect of concomitantly administered chemotherapeutic agents. In a series of double-blind, placebo-controlled trials, three populations of anemic cancer patients were randomized to rHuEPO or placebo. The three populations were: A) patients not receiving concomitant chemotherapy, B) patients receiving chemotherapeutic regimens which did not contain cisplatin, and C) patients receiving chemotherapeutic regimens which contained cisplatin. In the no-chemotherapy trials, patients were treated with rHuEPO (100 U/kg) or placebo s.c. three times a week for up to eight weeks. In the two types of chemotherapy trials, patients were treated with rHuEPO (150 U/kg) or placebo SC three times a week for 12 weeks.

A total of 413 patients were enrolled in these trials (124 in the no-chemotherapy group, 157 in the no-cisplatin chemotherapy group and 132 in the cisplatin chemotherapy group). In each trial, patients randomized to rHuEPO had a significantly greater (p < .004) increase in hematocrit than placebo-treated patients. In the two types of chemotherapy trials combined, utilizing an rHuEPO dose of 150 U/kg, rHuEPO-treated patients had significantly lower (p ≤ .009) transfusion requirements (percentage of patients transfused and mean units of blood transfused per patient) than placebo-treated patients during months two and three, but not during month one. Quality-of-life parameters measured on a 100 mm visual analog scale significantly improved (p<.05) in rHuEPO-treated patients whose hematocrit increased ≥6 percentage points, compared to corresponding quality-of-life changes in placebo-treated patients. rHuEPO was well tolerated compared to placebo.

The above results suggest that rHuEPO may be a useful agent to palliate the morbid consequences of the anemia that is often found in association with advanced cancer.
In response to: Professor Cassileth's manuscript on “Alternative and Complementary Cancer Treatments,” featured in The Oncologist 1996;1:173-179.
Authors: Quah Thuan-Chong
Published: February 2020

Alternative and complementary therapies differ importantly, and the distinction between the two is crucial for clinical oncologists. “Alternative” or unproven therapies are treatments used independent of surgery, radiation and chemotherapy. They can be dangerous directly and also by delaying patients' receipt of mainstream care. In contrast, complementary therapies typically are adjuncts to mainstream medicine. They can provide symptom control and noninvasive palliation with minimal side effects, improve patients' well-being and enhance cancer medicine. Complementary therapies represent a desired addition and balance to technologically sophisticated cancer care.
Optimal Surgical Treatment of Breast Cancer
Authors: Veronesi Umberto , Zurrida Stefano
Published: February 2020

Large-scale, controlled trials in the 1970s and 1980s demonstrated that wide resection (for example, quadrantectomy) was as effective as mastectomy for the treatment of breast cancer up to 3 cm in maximum diameter. Conservative treatment may also be extended to larger cancers following pre-operative chemotherapy to reduce tumor mass and leave sufficiently wide resection margins to ensure oncological radicality. Quadrantectomy is an operation of curative intent, distinct from “lumpectomy” or “tumorectomy,” whose main aim is to debulk the tumor mass; nevertheless, wide resection should, in most cases, be flanked by radiotherapy to sterilize the tumor bed and by complete axillary dissection to remove any metastatic nodes and provide full prognostic information. This triple approach provides a high cure rate and low relapse rate for breast cancer, while providing an acceptable cosmetic outcome; we believe it is the optimal treatment for breast cancer at the present time. Modifications include simultaneous remodeling of the affected breast if, because of tumor position, the result of conservative surgery is less than satisfactory; and use of radioguided surgery to detect the sentinel node which, if not involved, may indicate that full axillary dissection is unnecessary.
The Myelodysplastic Syndromes
Authors: Cheson Bruce D.
Published: February 2020

The myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by peripheral blood cytopenias with a hypercellular bone marrow exhibiting dyspoiesis. The MDS range from those with a relatively indolent course (e.g., refractory anemia with or without ringed sideroblasts) to more aggressive disorders (e.g., refractory anemia with excess blasts [RAEB], and RAEB in transformation [RAEB-T]), which may exhibit a clinical course indistinguishable from acute myeloid leukemia (AML). Supportive care is the standard treatment for most patients, particularly those who are elderly, with the judicious use of blood components and antibiotics. For younger patients with RAEB and RAEB-T, antileukemic therapy might be considered, since the outcome is similar to that of patients with AML. Promising new chemotherapy agents currently in clinical trials include the topoisomerase I inhibitor, topotecan. The only curative treatment for MDS is allogeneic bone marrow transplantation, with long-term survival in approximately 40%, but with treatment-related deaths in 25%-40%. Factors predicting outcome include age, cytogenetics, number of blasts, and others. Myeloid growth factors (e.g., G-CSF, GM-CSF), increase the granulocyte count in most patients and may be useful in the setting of an active infection, although the prophylactic use of these agents does not improve survival. Erythropoietin increases the hematocrit in about 20% of patients. Growth factors being evaluated for their role in enhancing platelet counts include interleukin 11, stem cell factor, and megakaryocyte growth and development factor (thrombopoietin). Newer strategies to improve the outcome of patients with MDS should be based on an increased understanding of the biology of these disorders.
Long-Term Spinal Opioid Therapy in Terminally Ill Cancer Pain Patients
Authors: Wagemans Michel F.M. , Zuurmond Wouter W.A. , Lange Jaap J.
Published: February 2020

In terminally ill cancer patients with refractory pain, long-term spinal opioid therapy may provide a profound analgesia with minimal side effects. The reversibility of the technique and its efficacy throughout the body and for different types of pain are important advantages. For epidural administration, it is preferable to use lipid soluble opioids (sufentanil). For intrathecal administration, morphine is the best choice. The advantages of intrathecal administration over epidural administration are the need for lower doses because of a more direct administration at the receptor site, the easy positioning of the catheter, and less risk for migration of the catheter. In severe refractory pain which does not respond to spinal opioids, the use of non-opioids (e.g., a local anesthetic or an alpha-2 adrenoreceptor agonist) as coanalgesics may be recommended for improving pain relief. Long-term spinal opioid therapy at home has been made possible by technical and organizational development. In home care, only one physician should be the manager for the patient. Coordination should be optimized among patient, family, general practitioner, oncologist, anesthesiologist, home nurse, technician, and pharmacist.
Classification of Non-Hodgkin's Lymphoma: A Proposal
Authors: Hernández José , Krueger Jo Ellen Cottey , Glatstein Eli
Published: February 2020

The pathology community has traditionally classified the non-Hodgkin's lymphomas (NHL) according to their histogenetic characteristics, an approach that has fostered the proliferation of multiple, often conflicting, lymphoma classification schemes with limited clinical relevance. The scientific acceptance of these histogenetically pure schemes is based on an implicit belief that all that is scientifically sound must adhere to linear dynamic theory; that is, that the elemental components of a system in a linear and direct fashion control the behavior of the whole. Non-linear dynamic theory, however, which has recently acquired acceptance within the scientific community, offers another equally valid approach to the classification of the NHL by acknowledging the inherent indeterminacy of nature. In other words, rather than classifying the NHL according to their cell of origin in the hopes that the elemental unit will predict the clinical outcome, we propose that pathologists accept the premise that nature is inherently unpredictable and define the NHL according to their clinical characteristics, such as natural history and response to therapy. Using these criteria, a proposed classification is discussed containing two major subtypes of lymphomas (indolent and aggressive) which can be further subdivided into five groups: the low-grade, or indolent, group includes the small lymphocytic and the follicular cleaved cell (small, and small, mixed) categories, while the high-grade, or aggressive, group includes the large-cell, the Burkitt's lymphoma, and the lymphoblastic lymphomas. Each of these groups is discussed in detail, with comparisons to the Revised European American Lymphoma classification to demonstrate clinical relevance. Although it is clear to us that the proposed scheme presented in this manuscript is not the only clinically valid one that can be constructed, it is equally clear that any scheme that is developed—in order to be considered valid—must be guided principally by its clinical relevance.
Vaccine Trials for the Clinician: Prospects for Tumor Antigens
Authors: Osanto Susanne
Published: February 2020

Recent insights in antigen presentation, the identification of human tumor antigens, and the demonstration of MHC class-I-restricted cytotoxic T lymphocyte (CTL) recognition of peptides encoded by tumor antigen have renewed the interest and enthusiasm for the development of cancer vaccines. Melanoma serves as a paradigm of an immunogenic human tumor, and several tumor antigens, including MAGE, MART-1/Melan-A and gp100, recognized by CTLs, have now been isolated. Candidate antigens for novel vaccine trials may include HLA class-I-binding tumor peptides that serve as CTL epitopes, whole tumor protein, or DNA-based vaccines. Requirements for the use of peptides are that the patient's tumor presents the relevant CTL epitopes as used in the vaccine and expresses the appropriate MHC class-I-restricting molecule. Immunological monitoring may be facilitated when using peptide-based vaccines. Because optimal presentation of tumor antigens may depend on provision of appropriate costimulatory signals, it may be more advantageous to administer professional antigen-presenting cells (APCs), such as dendritic cells (DCs) pulsed with tumor peptide or protein, to cancer patients.

Developments in molecular genetics have led to a new approach in vaccines consisting of cancer cells genetically engineered to express immunomodulatory molecules. This may result in increased antitumor responses to both gene-modified as well as unmodified tumor cells.

The therapeutic approach is extended to vaccination trials with recombinant viruses containing the genes encoding tumor antigens, minigenes containing multiple CTL epitopes, or double recombinant vectors engineered to express both the tumor antigen and immunostimulatory molecules.

Clinical peptide, protein, and DNA-based vaccine trials have recently been initiated. Thus far, exciting clinical remissions were obtained in melanoma patients following vaccination with HLA-A1-binding MAGE-3 peptide and in B-cell lymphoma patients immunized with autologous DCs pulsed with anti-idiotype protein, i.e., the individual patient's unique tumor antigen. Also, following injection of foreign HLA-B7 DNA into cutaneous melanoma metastases, T-cell migration into treated lesions and enhanced cellular immunity at the site of the tumor were shown in some patients. These encouraging results suggest that effective new vaccines in cancer will be identified.
Understanding the Myelodysplastic Syndromes
Authors: Kouides Peter A. , Bennett John M.
Published: February 2020

The myelodysplastic syndrome (MDS) remains challenging to the clinician in terms of diagnosis and management. The diagnosis is essentially one of exclusion in first ruling out other disorders that can also cause peripheral blood/bone marrow cell dysplasia and cytopenias. The distinguishing biological characteristic of MDS is that it is a clonal disorder of the marrow with impaired differentiation. Recent studies implicate extensive apoptosis as the explanation of the paradoxical observation of marrow hyperplasia but peripheral blood cytopenia. Neutropenia and/or neutrophil dysfunction account for the primary clinical manifestation of MDS in terms of an increased risk for infection, which is the leading cause of death in MDS. The clonal nature of MDS places it also at continual risk for transformation to acute leukemia. Predicting overall survival as well as the risk of AML transformation has been improved by the recent development of a scoring system (International Prognostic Scoring System) that incorporates three laboratory variables: percent of marrow blasts, degree of cytopenias, and presence of chromosomal abnormalities. Based on these variables, four prognostic subgroups can be delineated ranging from low risk with a median survival of 5.7 years, to high risk with a median survival of 0.4 years. Management of MDS can now be based on the patient's respective prognostic subgrouping, with low-risk patients being considered for hematopoietic growth factor singly or in combination if at the point of red cell transfusion dependence and/or neutropenia with recurrent infections, while high-risk patients should be offered AML-induction therapy or novel agents such as Topotecan. One must individualize further in patients in the remaining intermediate groups, I and II, in choosing the most appropriate therapy. Future advances upon understanding the molecular details of the MDS clone should ultimately improve the care of patients with MDS.
When Does the Responsibility of Our Care End: Bereavement
Authors: Penson Richard T. , Green Kara M. , Chabner Bruce A. , Lynch Thomas J.
Published: February 2020

Learning Objectives

After completing this course, the reader will be able to:Understand the effect of grief on the bereaved and on staff.Understand the responsibilities of compassionate cancer care.Recognize the resources available for uncomplicated and complicated grief.

Access and take the CME test online and receive one hour of AMA PRA category 1 credit in Risk Management at CME.TheOncologist.com

Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded the Kenneth B. Schwartz Center. The Schwartz Center is a non-profit organization dedicated to supporting and advancing compassionate health care delivery, which provides hope to the patient, support to caregivers, and sustenance to the healing process. The center sponsors the Schwartz Center Rounds, a monthly multidisciplinary forum where caregivers reflect on important psychosocial issues faced by patients, their families, and their caregivers, and gain insight and support from fellow staff members.

Two vignettes are presented of a caregiver's response to the death of a patient, contrasting the extremes of involved compassion for the family and fractured relationships. Grief for loss is an inevitable part of life and a common part of cancer care. Support of the bereaved may be one of the hardest tasks for cancer care professionals, who are confronted with the limits of modern medicine. There is a responsibility to provide grieving families with support and care; care that goes beyond the death. A compassionate response helps both those who suffer and those who care. Complicated and uncomplicated bereavement, grief reactions, resources for bereavement counseling, and the role of condolence letters are reviewed.
Integrated, Multidisciplinary Management of Pulmonary Nodules Can Streamline Care and Improve Adherence to Recommendations
Authors: Roberts Thomas J. , Lennes Inga T. , Hawari Saif , Sequist Lecia V. , Park Elyse R. , Willers Henning , Frank Angela , Gaissert Henning , Shepard Jo-Anne , Ryan David
Published: February 2020

Every year millions of pulmonary nodules are discovered incidentally and through lung cancer screening programs. Management of these nodules is often suboptimal, with low follow-up rates and poor provider understanding of management approaches. There is an emerging body of literature about how to optimize management of pulmonary nodules. The Pulmonary Nodule and Lung Cancer Screening Clinic (PNLCSC) at Massachusetts General Hospital was founded in 2012 to manage pulmonary nodules via a multidisciplinary approach with optimized support staff. Recommendations from clinic providers and treatment details were recorded for all patients seen at the PNLCSC. Adherence to recommendations and outcomes were also tracked and reviewed. From October 2012 to September 2019, 1,136 patients were seen at the PNLCSC, each for a mean of 1.8 appointments (range, 1–10). A total of 356 procedures were recommended by the clinic and 271 patients were referred for surgery and/or radiation. The majority of interventions (74%) were recommended at the initial PNLCSC appointment. In total, 211 patients (19%) evaluated at the PNLCSC had pathologically confirmed pulmonary malignancies or were treated empirically with radiation. Among patients followed by the clinic, the adherence rate to clinic recommendations was 95%. This study shows how a multidisciplinary approach to pulmonary nodule management can streamline care and optimize follow-up. The PNLCSC provides a template that can be replicated in other health systems. It also provides an example of how multidisciplinary approaches can be applied to other complex conditions.

Implications for Practice

This work demonstrates how an integrated, multidisciplinary approach to management of pulmonary nodules can streamline patient care and improve adherence to provider recommendations. This approach has the potential to improve patient outcomes and reduce health care costs.
A Systematic Review of Pediatric Phase I Trials in Oncology: Toxicity and Outcomes in the Era of Targeted Therapies
Authors: Cohen Julia W. , Akshintala Srivandana , Kane Eli , Gnanapragasam Helen , Widemann Brigitte C. , Steinberg Seth M. , Shah Nirali N.
Published: February 2020

Background

Pediatric phase I oncology trials have historically focused on safety and toxicity, with objective response rates (ORRs) <10%. Recently, with an emphasis on targeted approaches, response rates may have changed. We analyzed outcomes of recent phase I pediatric oncology trials.

Materials and Methods

This was a systematic review of phase I pediatric oncology trials published in 2012–2017, identified through PubMed and EMBASE searches conducted on March 14, 2018. Selection criteria included full-text articles with a pediatric population, cancer diagnosis, and a dose escalation schema. Each publication was evaluated for patient characteristics, therapy type, trial design, toxicity, and response.

Results

Of 3,431 citations, 109 studies (2,713 patients) met eligibility criteria. Of these, 78 (72%) trials incorporated targeted therapies. Median age at enrollment/trial was 11 years (range 3–21 years). There were 2,471 patients (91%) evaluable for toxicity, of whom 300 (12.1%) experienced dose-limiting toxicity (DLT). Of 2,143 patients evaluable for response, 327 (15.3%) demonstrated an objective response. Forty-three (39%) trials had no objective responses. Nineteen trials (17%) had an ORR >25%, of which 11 were targeted trials and 8 were combination cytotoxic trials. Targeted trials demonstrated a lower DLT rate compared with cytotoxic trials (10.6% vs. 14.7%; p = .003) with similar ORRs (15.0% vs. 15.9%; p = .58).

Conclusion

Pediatric oncology phase I trials in the current treatment era have an acceptable DLT rate and a pooled ORR of 15.3%. A subset of trials with target-specific enrollment or combination cytotoxic therapies showed high response rates, highlighting the importance of these strategies in early phase trials.

Implications for Practice

Enrollment in phase I oncology trials is crucial for development of novel therapies. This systematic review of phase I pediatric oncology trials provides an assessment of outcomes of phase I trials in children, with a specific focus on the impact of targeted therapies. These data may aid in evaluating the landscape of current phase I options for patients and enable more informed communication regarding risk and benefit of phase I clinical trial participation. The results also suggest that, in the current treatment era, there is a rationale to increase earlier access to targeted therapy trials for this refractory patient population.
Mistaking the Trees for the Forest?
Authors: Strohbehn Garth W. , Daugherty Christopher K.
Published: February 2020

This letter to the editor comments on the recently published article by Flynn et al. about shared decision making as related to discontinuation of tyrosine kinase inhibitors for chronic myeloid leukemia.
Weekly Chemotherapy of 5-Fluorouracil plus Cisplatin Concurrent with Radiotherapy for Esophageal Squamous Cell Carcinoma Patients with Postoperative Locoregional Recurrence: Results from a Phase II Study
Authors: Chen Baoqing , Li Qiwen , Li Qiaoqiao , Qiu Bo , Xi Mian , Liu Mengzhong , Hu Yonghong , Zhu Yujia
Published: February 2020

Lessons Learned

Weekly treatment with 5-fluorouracil and cisplatin, concurrent with radiotherapy, achieved promising response rates in patients with postoperative recurrent esophageal squamous cell carcinoma. Superior toxicity results were also found.

Background

Concurrent chemoradiotherapy (CCRT) is one of the treatment strategies for patients with esophageal squamous cell carcinoma (ESCC) with postoperative locoregional recurrence. However, the once every 3 weeks chemotherapy regimen causes a high incidence of toxicity. The aim of this study was to evaluate the efficacy and toxicity of weekly 5-fluorouracil (5-FU) and cisplatin concurrent with radiotherapy in postoperative locoregional recurrent ESCC.

Materials and Methods

Patients received four weekly chemotherapy cycles of cisplatin (25 mg/m2, day 1) plus 5-FU (1,176 mg/m2, day 1–3), and concurrent with radiotherapy (50.4–60 Gy). The primary endpoint was objective response rate (ORR). Secondary objectives were toxicity, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).

Results

Between January 2013 and December 2015, 48 patients were enrolled. The ORR was 68.8% (12 patients with complete response, 21 patients with partial response), with DCR 68.8%. No treatment-related grade 4 adverse events occurred. Grade 3 hematologic toxicities were observed in eight (17%) patients. Grade 3 vomiting or esophagitis occurred in four (8%) patients each. The median PFS and OS were 13.94 months (95% confidence interval [CI], 0.75–51.05) and 27.43 months (95% CI, 5.278–49.58; Fig. 1).

Conclusion

Weekly 5-FU and cisplatin concurrent with radiotherapy achieved a promising response rate and improved toxicity in patients with postoperative locoregional recurrent ESCC.
Extending the Platinum-Free Interval in Recurrent Ovarian Cancer: The Role of Topotecan in Second-Line Chemotherapy
Authors: Bookman Michael A.
Published: February 2020

Although the combination of platinum and paclitaxel offers effective chemotherapy for advanced ovarian cancer, the majority of women will eventually relapse with development of drug-resistant disease. Topotecan is the most extensively studied agent currently available for management of recurrent ovarian cancer and has been approved by the FDA for that particular indication. Early use of topotecan offers an effective and tolerable strategy that can prolong the platinum-free interval and optimize subsequent retreatment with platinum.
New Treatment Strategies for Malignant Gliomas
Authors: Avgeropoulos Nicholas G. , Batchelor Tracy T.
Published: February 2020

Although survival in patients with malignant gliomas remains limited, there is renewed optimism with the emergence of novel treatment strategies. Cytotoxic agents such as temozolomide and CPT-11 have shown promising clinical activity. Biological treatments for brain tumors, including antisense oligonucleotides, gene therapy, and angiogenesis inhibitors, are also being evaluated in clinical trials. Delivery strategies have been developed to overcome challenges presented by the blood-brain barrier. These noteworthy treatments, alone or in combination, may ultimately prolong survival and enhance quality of life in this group of patients.
Cancers in Children Infected With the Human Immunodeficiency Virus
Authors: Mueller Brigitta U.
Published: February 2020

The AIDS epidemic continues unabated in Africa, Asia, and South America, and since patients survive longer, the number of chronically immunocompromised individuals is increasing in Europe and the United States. The number of children with HIV infection who will ultimately develop a malignancy is not known. Currently, tumors represent about 2% of the AIDS-defining events in children in the United States, but the incidence might be different in developing countries. The most common tumors in HIV-infected children are non-Hodgkin's lymphoma, smooth muscle tumors (leiomyosarcomas), and Kaposi's sarcoma (only in Africa). This article provides an overview of epidemiology and clinical and pathological presentations, as well as preliminary data regarding treatment options in children with HIV-associated malignancies.
Chronic Lymphocytic Leukemia
Authors: Kalil Nelson , Cheson Bruce D.
Published: February 2020

The diagnosis and management of chronic lymphocytic leukemia (CLL) is reviewed, including the basic aspects of epidemiology, molecular biology, and cytogenetics with clinical relevance. The importance of immunophenotype in the differential diagnosis of other lymphoproliferative disorders related to CLL, staging, prognostic factors, promising new drugs, and approaches is summarized.
T-Cell Immunodeficiency Following Cytotoxic Antineoplastic Therapy: A Review
Authors: Mackall Crystal L.
Published: February 2020

Although cancer itself is immunosuppressive, cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency observed in cancer patients. The immunodeficiency induced by cytotoxic antineoplastic therapy is primarily related to T-cell depletion, with CD4 depletion generally more severe than CD8 depletion. Myeloablative therapy, dose-intensive alkylating agents, purine nucleoside analogs, and corticosteroids substantially increase the risk of therapy-induced immunosuppression. Restoration of T-cell populations following cytotoxic antineoplastic therapy is a complex process. Efficient recovery of CD4+ T cell populations requires thymic-dependent pathways which undergo an age-dependent decline resulting in prolonged CD4+ T-cell depletion in adults following T-cell-depleting therapy. Total CD8+ T-cell numbers recover in both children and adults relatively quickly post-therapy; however, CD8+ subset disruptions often remain for a prolonged period. The clinical management of patients with therapy-induced T-cell depletion involves the maintenance of a high index of suspicion for opportunistic pathogens, irradiation of blood products, prophylaxis for viral infections, and reimmunization in selected clinical circumstances. Future research avenues include efforts to rapidly rebuild immunity following cytotoxic antineoplastic therapy so that immune-based therapies may be utilized immediately following cytotoxic therapy to target minimal residual neoplastic disease.
Single-Agent Paclitaxel in the Treatment of Advanced Non-Small Cell Lung Cancer
Authors: Socinski Mark A.
Published: February 2020

Paclitaxel was the first identified member of a new class of anticancer drugs known as the taxanes. This compound has significant single-agent activity against a number of solid tumors including nonsmall cell lung cancer (NSCLC). In the first-line setting, single-agent paclitaxel has been studied on a number of different schedules and dose levels. Initial studies were done on the 24-h infusion schedule with doses of 200-250 mg/m2. Response rates were 21%-24%. Median survival ranged from six to nine months with one-year survival rates of 38%-42%. The major toxicity of this infusion schedule was myelosuppression, mainly neutropenia. Subsequent single-agent studies employed shorter infusion durations (three hours), with doses ranging from 175-225 mg/m2. The cumulative experience of the 3-h infusion schedule shows an overall response rate of 28.5% with median survival of 6-11 months and a one-year survival of 37.5%. Similar results were obtained in the one study examining the 1-h infusion schedule with doses ranging from 135-200 mg/m2. The major toxicities of the shorter infusion schedule include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Weekly administration of paclitaxel also showed significant activity in advanced, metastatic NSCLC. Overall response rates have ranged from 30%-56% in the phase I/II setting with one-year survival rates of 42%-53%. A recently completed phase III trial comparing single-agent paclitaxel at 200 mg/m2 over three hours every three weeks to best supportive care (BSC) in advanced or metastatic NSCLC has shown a survival advantage for the single-agent paclitaxel arm (median survival 6.8 months for paclitaxel versus 4.8 months for BSC, p = 0.045). An ongoing phase III trial is comparing single-agent paclitaxel to the combination of carboplatin and paclitaxel (CALGB 9730) in advanced, metastatic NSCLC. Paclitaxel has also been studied in the second-line setting. Infusion schedules have ranged from 1 h, 24 h and 96 h on an every-three-week schedule. Weekly paclitaxel has also been evaluated in the second-line setting. Although the overall experience is limited, response rates have ranged from 0%-38%. The overall role of single-agent paclitaxel in prolonging survival and improving quality of life remains uncertain in this setting.

The cumulative experience of single-agent paclitaxel in advanced, metastatic NSCLC suggests that it is a highly active cytotoxic agent in this setting. The consistent finding of a 35%-40% one-year survival rate is notable. The major toxicities include neutropenia, neuropathy, and myalgia/arthralgia syndrome. Given the overall activity and impact on survival along with an acceptable toxicity profile, single-agent paclitaxel warrants comparison to other active agents and combination regimens in advanced, metastatic NSCLC.
Failure analysis of earthen, masonry and concrete buildings during the 2017 Tripura earthquake
Authors: Tripura Deb Dulal , Sangma Sangketa
Published: February 2020

This paper reports on an evaluation of failures of non-engineered earthen buildings, timber-framed buildings with bamboo matting, unreinforced load-bearing masonry buildings and framed reinforced-concrete structures with brick infill during the 5·7 magnitude 2017 Tripura earthquake in India. Field observations showed that some of the concrete and masonry buildings, and many of the non-engineered earthen buildings in the Dhalai and Unokoti districts, suffered damage due to this moderate earthquake. Out-of-plane failure, corner cracks, shear cracks and damage of infill wall materials were among the predominant forms of seismic damage. On the basis of the analysis, some remedial measures are proposed in this paper, which will require future research and testing.
The Comparison of Measurements of the Wrist, Hand and Finger Parameters Between Female and Male
Authors: YOLDAŞ Atila , DEMİR Mehmet , ÇALIŞGAN Elisa , ATAY Emre , GEÇGİL Esin , ÇİÇEK Mustafa , ERTEKİN Tolga , DOĞANER Adem
Published: February 2020

Objectives: The purpose of this
study was to compare measurements of the wrist, hand
and finger parameters between female and male.Methods:
This randomized trial included 318  healthy participants  (n:210 female, n:108 male) aged 25 to 72
years as
a result of examination participated in the study. Tape measure, digital caliper with 0.01 sensitivity used in
the study were obtained at Kahramanmaraş Sütçü
Imam University, Faculty of Medicine, Department
of Anatomy. The measurements taken from
the  participants were right and left
wristh circumference, breadth and  length,
palm breadth, length and fingers length.Result:
Regarding the scores between female and male, no
statistically significant difference was found between the female and male in
terms of age and body mass index (BMI) parameters (p>0.05). In the
comparison analysis results of the measurements of wrist, hand and finger
parameters in female and male, statistically significant difference was found
in wrist circumference, breadth, length, palm breadth and length, fingers
length. The
points of all parameters of female were significantly lower than male
(p<0.05).

Conclusion:
As
a result of the study, statistically significant
difference was found between female and male in terms of right and left wrist,
hand and finger parameters.
Simulation Model of the Cutting Speed Stabilization System for CNC Metal-Cutting Machine Tools
Authors: Ivanov V. M.
Published: February 2020

In this paper a simulation model of cutting speed stabilization for numerical control machines was developed. The mode of cutting speed stabilization allows solving a number of technological problems, including the increase in machining productivity and the quality of the part surface, the increase in durability of the cutting tool.

Access to the functions of the basic software of CNC systems is limited. Taking this into account, this paper considers the functional and algorithmic features of the power parameter stabilization systems, as the basis for the further development of intelligent algorithmic support and software. The existing guidance on cutting conditions is based on empirical dependencies, the use of which for direct application in algorithms for the cutting process automatic control is difficult, since these dependencies determine the predicted, not the current, parameters. The non-stationary model was adopted as the basic structure of the process of shaping parts, the main non-stationary model parameters are determined by the three-dimensional kinematics of the universal machine. The generalized approach to the power parameter systems and the synthesis of the regulators of their main circuits made it possible to identify the simplest version of the structures based on the use of the regulators with parametric feedback. The functional model contains the main components of the CNC system: an interpolator, servo drives of feeds and main motion, as well as additional cycle and analysis modules. The high-speed processing of end surfaces and the conditions for the implementation of cyclic control tasks are considered. The simulation results confirming the performance of functional algorithms and the possibility of their use in intelligent CNC systems are presented.
Modifi cation of the CGR-Algorithm on Data Routing in a Communication Network of Satellite Constellation
Authors: Karsaev O. V.
Published: February 2020

Communication networks in space systems involving the use of satellite constellations are DTN networks (Delay and Disruption Tolerant Networks). The establishment of communication channels in space communication networks has certain specifics: communication channels can be planned. In this regard, the CGR approach (Contact Graph Routing) is considered as the most promising solution to the problem of data routing. At the basis of this approach, taking into account this specificity, the calculation of the contact plan is considered. On the basis of this plan in the network nodes contact graphs are calculated, which are used to search the shortest data transmission routes. The paper proposes two interrelated solutions as a modification of this approach: the route search based on the contact plan, i.e. without calculation and use of the contact graph, and an adaptive method of finding the set of shortest routes required for routing. The essence of the first solution is as follows. In the standard CGR approach, the graph vertices correspond to the planned contacts between the network nodes, and the edges correspond to the data storage processes in the network nodes. In contrast, in the proposed approach, the vertices of the graph correspond to the nodes of the network, and the edges of the graph and their weight are determined dynamically, in the process of finding the shortest routes. The second solution is based on the concept of the planning front, which means a list of the closest contacts in time. The required routes are divided into a certain number of pools. Each pool combines the routes that use the specified contact from the planning front. The planning front is updated in two cases. If the network topology changes, the completed or not established contacts are replaced by subsequent ones with the same network nodes that are closest in time. If message traffic grows, a certain extension of the planning front and the use of additional route pools are performed. The article concludes with a description and justification of the expected advantages of the proposed approach.
Automatic Control of Aircraft Engine in Conditions of Stand Test
Authors: Shibanov G. P.
Published: February 2020

The general principles of automatic control of aircraft engines and functionally related systems in the conditions of their stand tests are suggested. These principles are prospectively reduced to six sequentially implemented procedures or steps. In accordance with these principles, the control of aircraft engine parameters is carried out by a computer-aided test equipment (CTE) based on a computer complex that implements algorithms based on Boolean algebra and the algebra of events and states. These algorithms allow control procedures to be carried out in dynamic mode in accordance with the schedule of testing an aircraft engine. With this control, the specified sequence of operating modes of the aircraft engine undergoing testing is observed without fixing them in time and with the possibility of skipping or repeating individual modes. Parameters are monitored at each of the next aircraft engine operating modes only after all parameters are checked in the previous mode and the value of the main determining parameter reaches the value determined for this mode. During the period of transient processes, parameters are controlled only at the points of extremum of the values of the main determining parameter with fixing the time of transient processes and determining that. "In the tolerance" or "not in the tolerance" is the checked parameter and the fixed time interval. Upon arrival of the signals from the monitoring object, the time of occurrence of which is unknown, and only the time interval during which they can appear is known, any of the CTE operation modes are terminated, tolerance control of the parameters provided by the program is performed, and the previously interrupted mode is restored. Simultaneously with the tolerance control of the parameters, the time of arrival of the above signals is recorded. The group of emergency parameters is monitored continuously throughout the entire period of stand test.
Contribution of the Kursk Psychological School of Youth Leaders to the Youth Movement and Human Resources of the Region
Authors: Chernyshev S.S. , Sarychev S.V. , Grebenkov N.N.
Published: February 2020

The article presents the psychological foundations, technologies of working with socially gifted adolescents and high schoolers (organizing leaders) and summarizes the work of the Psychological School of Youth Leaders in the Kursk region. The authors described the features of social learning as a kind of psychological assistance to the younger generation.