Prevention of febrile neutropenia: use of granulocyte colony-stimulating factors

There is good evidence to suggest that dose intensity is important when considering the effectiveness of adjuvant chemotherapy in patients with breast cancer. However, the development of chemotherapy-induced febrile neutropenia can lead to reduction in dose intensity and other treatment modifications, which may negatively affect patient outcomes. Febrile neutropenia can be prevented by the use of primary prophylactic treatment, notably with granulocyte colony-stimulating factors. This practice is supported by international guidelines, all of which recommend that primary prophylaxis with granulocyte colony-stimulating factors should be used with chemotherapy where the risk of febrile neutropenia is 20% or greater

Sense of coherence and diabetes: A prospective occupational cohort study

<p>Abstract</p> <p>Background</p> <p>Sense of coherence (SOC) is an individual characteristic related to a positive life orientation leading to effective coping. A weak SOC has been associated with indicators of general morbidity and mortality. However, the relationship between SOC and diabetes has not been studied in prospective design. The present study prospectively examined the relationship between a weak SOC and the incidence of diabetes.</p> <p>Methods</p> <p>The relationship between a weak SOC and the incidence of diabetes was investigated among 5827 Finnish male employees aged 18–65 at baseline (1986). SOC was measured by questionnaire survey at baseline. Data on prescription diabetes drugs from 1987 to 2004 were obtained from the Drug Imbursement Register held by the Social Insurance Institution.</p> <p>Results</p> <p>During the follow-up, 313 cases of diabetes were recorded. A weak SOC was associated with a 46% higher risk of diabetes in participants who had been =<50 years of age on entry into the study. This association was independent of age, education, marital status, psychological distress, self-rated health, smoking status, binge drinking and physical activity. No similar association was observed in older employees.</p> <p>Conclusion</p> <p>The results suggest that besides focusing on well-known risk factors for diabetes, strengthening SOC in employees of =<50 years of age can also play a role in attempts to tackle increasing rates of diabetes.</p

Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

Contains fulltext : 108207.pdf (publisher's version ) (Open Access)Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP). Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw) followed by 24 h urine collection. Doses of >/=275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT) values (p<0.0001). Proteomic profiling resulted in the identification of 12 differentially excreted proteins in urine of mice with acute liver injury (p<0.001), including superoxide dismutase 1 (SOD1), carbonic anhydrase 3 (CA3) and calmodulin (CaM), as novel biomarkers for APAP-induced liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT levels, but urinary CaM was already present in mice treated with high dose of APAP without elevated plasma ALT levels. Importantly, we showed in human urine after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001) in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury

Tissue responses to an experimental calcium phosphate cement and mineral trioxide aggregate as materials for furcation perforation repair: a histological study in dogs

The aim was to evaluate histologically the inflammatory reactions and tissue responses to an experimental tricalcium phosphate cement (TCP) and mineral trioxide aggregate (MTA) when used as repair materials in furcation perforations in dogs. Perforations were performed in 24 mandibular premolars of six anaesthetised dogs and filled either with ProRoot MTA (grey) or TCP. The root canals were subsequently shaped and filled, and the access cavities were closed with a bonded composite resin. The animals were killed at 12 weeks. After radiological examination, the teeth and surrounding structures were processed for light microscopy. Concerning the grades of inflammation, MTA exhibited significantly better results than TCP (chi-square test according to Pearson). No furcation was free of inflammatory cells. Mild inflammation was observed in nine of twelve cases with MTA and only twice in those with TCP. No significant differences were revealed between MTA and TCP in terms of bone reorganization or deposition of fibrous connective tissue (Mantel-Haenszel chi-square test). The grade of radiological examination corresponded with the grade of inflammation or differed by only one grade plus or minus. Perforations located in the furcation of teeth remain an endodontic and a periodontal problem with an uncertain prognosis, in spite of the promising modern materials applied

Effects of Clinical and Tumor Characteristics on Survival in Patients with Hepatocellular Carcinoma with Bone Metastasis

Muhammet Ozer,1 Suleyman Yasin Goksu,2 Rick Y Lin,3 Ruveyda Ayasun,4 Doga Kahramangil,5 Sherise C Rogers,5,6 Jesus C Fabregas,5,6 Brian H Ramnaraign,5,6 Thomas J George,5,6 Michael Feely,7 Roniel Cabrera,8 Sergio Duarte,9 Ali Zarrinpar,9 Ilyas Sahin5,6 1Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA; 2Division of Hematology/Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA; 3Department of Medicine, University of Florida Health Cancer Center, Gainesville, FL, USA; 4Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY, USA; 5Division of Hematology/Oncology, Department of Medicine, University of Florida, Gainesville, FL, USA; 6University of Florida Health Cancer Center, Gainesville, FL, USA; 7Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL, USA; 8Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainesville, FL, USA; 9Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, USACorrespondence: Ilyas Sahin, Department of Medicine, University of Florida, Gainesville, FL, 32608, USA, Email [email protected]: Advanced hepatocellular carcinoma (HCC) generally has a dismal prognosis. Bone metastases from HCC are infrequent, with a poorer prognosis. However, the survival influencing factors are not yet well understood.Aim: The aim of the present study was to assess the clinical features and tumor characteristics of HCC patients with bone metastasis.Methods: A cohort of 170,576 adult patients with HCC was studied using the National Cancer Database (NCDB) spanning from 2010 to 2019, and within this group, 5285 patients (3.1%) were diagnosed with bone metastasis. We performed the Kaplan–Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics.Results: Of a total of 5285 HCC patients with bone metastasis, 86.2% were male and 61.2% were non-Hispanic white. Most patients (55.1%) were below 65, and 89% had a total Charlson-Deyo comorbidity score of under 3. Among patients with known tumor grade, 24.8% had well-differentiated tumors, and 36.1% had poorly differentiated tumors. Chemotherapy was administrated to 39.5% of patients. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 months vs 3.0 months, p = 0.001). Patients who received single or multiagent chemotherapy were significantly associated with improved OS compared to patients who did not receive chemotherapy (7.0 and 8.5 months vs 1.94 months, respectively). We also found mortality difference between age, comorbidity scores, facility types and race groups.Conclusion: In this cohort analysis of NCDB data, we found better OS in treatment receipt, lower tumor grade, younger age, non-Hispanic Black and Hispanic race, treatment at academic facility and lower comorbidity score in HCC patients with bone metastasis. The study results may have a consequential impact on the treatment decisions for HCC patients with bone metastasis.Keywords: hepatocellular carcinoma, HCC, bone metastasi

Timely withdrawal of G-CSF reduces the occurrence of thrombocytopenia during dose-dense chemotherapy.

Contains fulltext : 48504_pub.pdf (publisher's version ) (Open Access) Contains fulltext : 48504.pdf (publisher's version ) (Open Access)BACKGROUND: Post chemotherapy Granulocyte colony stimulating factor (G-CSF) reduces leucopenia, while G-CSF priming shortly before chemotherapy increases myelotoxicity. We performed a trial with a two-schedule crossover design to determine the optimal G-CSF schedule for densified 2-weekly chemotherapy. METHODS: During 2-weekly chemotherapy days 1 and 2, G-CSF was given on days 3-10, with a G-CSF-free interval before the next chemotherapy cycle of 5 days, or on days 3-13, with a G-CSF-free interval of 2 days. In schedule A, cycle II was preceded by a 5 days, cycle III and IV by a 2 days and cycle V by a 5 days G-CSF free interval. In schedule B, this was 2, 5, 5, and 2 days, respectively. RESULTS: Intra-patient comparison for cycles II versus III and cycles IV versus V showed that platelet (PLT) nadir count was significantly lower for cycles preceded by a 2-days compared to a 5-days G-CSF free interval: mean difference 45.7 x 10(9)/l (95% CI 33.2-58.2, p = 0.0001). Neutrophil count did not differ significantly (p = 0.85). CONCLUSION: Timely withdrawal of G-CSF in dose-dense chemotherapy reduces chemotherapy-related thrombocytopenia. Leucopenia was not aggravated, reflecting a protective effect of post-chemotherapy G-CSF