Outcome of rapid disease progression in the treatment break following cytoreductive nephrectomy (CN) after presurgical sunitinib in patients with primary metastatic renal cell carcinoma (RCC).

4611 Background: There is concern that interruption of tyrosine kinase inhibitors (TKI) triggers disease progression (PD) and metastasis. This is based on preclinical models and observation of rapid PD in the postsurgical treatment break in patients pretreated with TKI. Little is known about the frequency of PD during postsurgical TKI interruption and its outcome. These data may have implications for neoadjuvant or presurgical treatment concepts. Methods: Of 66 patients from two closed phase II trials investigating 2-3 months presurgical sunitinib for primary metastatic clear-cell RCC, 45 were evaluated in this retrospective analysis because they had absence of PD prior to planned surgery and underwent CN (35 [78%] MSKCC intermediate and 10 [22%] poor risk). Patients had CT scans at the end of pretreatment and at 4 weeks post-nephrectomy before restarting sunitinib. In patients with postsurgical RECIST PD at 4 weeks when compared to the preoperative CT scan overall survival (OS) was measured from the time of nephrectomy and compared to patients without treatment break PD. Results: Median OS of 45 patients from the time of surgery was 22 months (13.0-31.5 months). Overall 14 patients progressed during treatment break (31%), with new sites of disease in 5/14 (35%). Reintroduction of sunitinib resulted in disease stabilisation or better in 13. Patients with poor risk were represented in the progressors (n=4[28%]) and non-progressors (n=6 [19%]) (p=0.7 fishers exact test). The hazard ratio (HR) for death associated with PD during treatment break was 1.90 (95% CI 0.89-4.08). OS for non-progressors was 25 months (15-NA) and 13 months (6-27) for progressors. Conclusions: A significant proportion of patients develop PD upon sunitinib withdrawal in a 4 week recovery period following CN. In view of the small sample size these data suggest a strong trend toward treatment break PD being associated with a poor outcome. It is not clear whether this PD is related to interruption of TKI, surgery or a combination of factors. The EORTC SURTIME trial investigates treatment break PD after immediate CN and CN after sunitinib and may answer this question.

Download Full-text

A Study of Adherence to Restrictive RBC Transfusion and 30 Day Patient Outcomes

Blood ◽

10.1182/blood.v128.22.5037.5037 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5037-5037

Author(s):

Zhen Wang ◽

Elaine Zhai ◽

Aleksic Sandra ◽

Kibola Adam ◽

Richard May ◽

...

Keyword(s):

Cardiovascular Events ◽

Small Sample Size ◽

Small Sample ◽

University Hospital ◽

Red Blood Cell Transfusion ◽

Current Guideline ◽

Chi Square ◽

Exact Test ◽

Medicine Service ◽

Rbc Transfusion

Abstract Background: The American Association of Blood Banks (AABB) 2012 Guidelines recommend a restrictive transfusion strategy of 7 g/dL to 8 g/dL in asymptomatic, hemodynamically stable patients (pts) and for Hgb less than 8 g/dL in pts with preexisting cardiovascular disease. [1] Additional recommendations based on expert opinion include transfusion at threshold Hgb of 7 g/dL for hemodynamically stable ICU pts and Hgb less than 10 g/dL in pts with symptomatic anemia. We examined adherence to these guidelines and for differences in outcomes between restrictive and non-restrictive approaches at an academic hospital. Methods: We performed an IRB-approved retrospective review of all pts admitted to the Internal Medicine Service at University Hospital in Newark, New Jersey from July 1st to November 30th 2015 who received RBC transfusions. Charts were abstracted for demographic information, past medical history, indication for transfusion, presence of signs or symptoms of anemia (chest pain, orthostatic hypotension or tachycardia unresponsive to fluid resuscitation, or congestive heart failure), pre-transfusion Hgb, number of units transfused, and post-transfusion hgb. Outcomes were defined as requirement for additional transfusions, infections, cardiovascular events, adverse transfusion reactions, and death within 30 days of transfusion. Each transfusion was categorized as either adherent or non-adherent to the guidelines. Difference in outcomes between groups (adherent vs non-adherent) was tested using chi-square and Fisher's exact test with SAS studio version 3.4 (Cary, NC). Results: We reviewed 318 RBC transfusion records for 210 pts (median age: 55±17 years) with 157 (49%) transfusions in male and 161 (51%) in female pts. Site was ICU for 86 and the ward for 232 transfusions. The leading indication was acute bleeding (121 or 38%; pre-transfusion Hgb 6.9±1.3g/dL), followed by asymptomatic anemia (107 or 33%; pre-transfusion Hgb 6.8±0.8g/dL), and symptomatic anemia (91 or 29%; pre-transfusion Hgb 6.6±0.8g/dL). Of the 107 pts with asymptomatic anemia, 37 had pre-existing heart disease. Within this group, 35 were transfused at Hgb < 8g/dL (adherence of 95%). Seventy of the 107 transfusions were performed in pts without pre-existing cardiac disease. Fifty-nine were transfused at hgb < 7g/dL with an adherence of 84%. In the ICU, 21 of the 27 transfusions occurred for hgb < 7 g/dL in hemodynamically stable pts with an adherence of 78%. There were 91 transfusions for symptomatic anemia and all were adherent (100%). Regarding 30 day post-transfusion outcomes, there were 140 (44%) with subsequent transfusions; 54 (14%) infections; 7 (2.2%) cardiovascular events; 8 (2.5%) transfusion adverse reactions; 27(8%) deaths. No difference was detected for 30 day outcomes between the adherent group and the non-adherent group. (Table 1) Transfusion of at least 2unitsRBC in asymptomatic, symptomatic, and active bleeding pts were 25% (27/107), 44% (40/91), 57% (69/120) respectively. No difference in outcomes was found for the group receiving only 1 unit RBC (restrictive) compared to the group receiving 2 or more units RBC (non-restrictive). (Table 1) Conclusion: The majority of transfusions (92%) performed adhered to current guideline. While the restrictive approach was not associated with more complications or mortality, this study is limited by the small sample size and further work is being done. Acknowledgment: The authors are grateful to Dr. Koshy, Director of Blood Bank at University Hospital, for assistance. Reference: 1. Carson, J. L. et al. Red blood cell transfusion: a clinical practice guideline from the AABB. Ann Intern Med 157, 49-58 (2012). Disclosures Chang: Johnson and Johnson: Other: Stock; Amgen: Other: Research; Boehringer Ingelheim: Other: Research.

Download Full-text

COVID-19 potentially causes long-term deterioration of lung function: a systematic review and meta-analysis

Medical Journal of Indonesia ◽

10.13181/mji.oa.215660 ◽

2021 ◽

Vol 30 (4) ◽

pp. 279-89

Author(s):

Yudha Nur Patria ◽

Rahmaningsih Mara Sabirin

Keyword(s):

Lung Function ◽

Pulmonary Function ◽

Negative Impact ◽

Small Sample Size ◽

Meta Analysis ◽

Recovery Period ◽

Small Sample ◽

Lung Function Measurement ◽

Meta Analyses

BACKGROUND The COVID-19 is an emerging disease that commonly involves respiratory complaints, including acute respiratory distress syndrome. The effect of COVID-19 on pulmonary function is still unclear and only based on sporadic reports with a small sample size. This study aimed to compile evidence on the pulmonary function of patients who have recovered from COVID-19. METHODS Literature searching was conducted in PubMed, Embase, Google Scholar, Scopus, Web of Sciences, and CINAHL. Any types of studies published before June 26, 2020 and reported lung function tests of post-COVID-19 patients were included. Articles reporting data from early hospitalization were excluded. The risk of bias was measured using tools developed by the Joanna Briggs Institute. Meta-analysis was done using a meta statistical package in R and presented in the random effects model. RESULTS 378 recovered COVID-19 patients in 7 studies were included. The lung function measurement periods were varied, ranging from 14 days after hospitalization to 10 weeks after receiving rehabilitation. Meta-analyses found that the pooled mean of diffusion capacity of carbon monoxide in recovered COVID-19 patients was lower than 80% predicted, whereas the other parameters were normal. The forced vital capacity and total lung capacity showing restrictive lung disorders were significantly lower in the severe COVID-19 survivors. CONCLUSIONS COVID-19 has a negative impact on lung function for at least several weeks in the recovery period. Diffusion and restrictive problems could be the main long-term consequences of COVID-19.

Download Full-text

The Correlation Between DPYD*9A(c.85T>C) Genotype and Dihydropyrimidine Dehydrogenase Deficiency Phenotype in Patients With Gastrointestinal Malignancies Treated With Fluoropyrimidines

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz112.056 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S29-S30

Author(s):

Anu S Maharjan ◽

Gwendolyn McMillin ◽

Moh’d Khushman ◽

Girijesh Patel

Keyword(s):

Small Sample Size ◽

Dihydropyrimidine Dehydrogenase ◽

Small Sample ◽

Phenotype Correlation ◽

Gastrointestinal Malignancies ◽

Exact Test ◽

Genotype Phenotype Correlation ◽

Gi Cancer ◽

Racial Background ◽

Grade 3

Abstract Introduction The correlation between DPYD*9A (c.85T>C) genotype and dihydropyrimidine dehydrogenase (DPD) deficiency phenotype is controversial. In a cohort of 28 patients, DPYD*9A was the most commonly diagnosed variant (46%) and there was a noticeable genotype-phenotype correlation. Here we genotyped a larger cohort of a mixed racial background to explore the incidence of DPYD*9A variant and to further study the genotype-phenotype correlation. Methods Genotyping for high-risk DPYD variants (DPYD*2A, DPYD*13, and DPYD*9B) and the DPYD*9A variant was performed on 113 patients with gastrointestinal malignancies (GI) treated with fluoropyrimidines, using TaqMan chemistry. The prevalence of different DPYD variants was further analyzed in 1,283 retrospective data from ARUP laboratories. Fluoropyrimidines-associated toxicity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v 5.0). Fisher’s exact test was used for statistical analysis. Results In total, 1,283 were retrospectively reviewed for DPYD variants. Four patients (0.31%) carried DPYD c.-1590T>C, 10 patients (0.55%) carried DPYD c.1679T>G (*13), 36 patients (2.8%) carried DPYD c.2846A>T, and 527 patients (41.1%) carried DPYD c.85T>C (*9A). In the GI cancer cohort, DPYD variants were identified in 61 patients (54%), showing similar prevalence as the retrospective analysis. Caucasians represented 54% and African Americans represented 43%. Twenty-eight patients (46%) were females. Heterozygous DPYD*9A was identified in 46 patients (41%) and homozygous DPYD*9A was identified in 11 patients (10%). DPYD*2A was identified in 3 patients and DPYD*9B was identified in 2 patients (one patient had double heterozygous *9A and *9B). Grade 3 to 4 toxicities were experienced in 26 patients with mutant DPYD*9A (3 patients had homozygous DPYD*9A) and in 20 patients with no identified DPYD mutation (P = .7035). In patients who received full-dose fluoropyrimidines (N = 85), grade 3 to 4 toxicities were experienced in 22 patients with mutant DPYD*9A (2 patients had homozygous DPYD*9A) and in 17 patients with no identified DPYD mutation (P = .8275). Conclusion In the GI cancer population, the DPYD*9A variant was identified in 54% of patients. The correlation between DPYD*9A variant and DPD clinical phenotype was not significant. The noticeable correlation that was previously reported is likely due to small sample size and selection bias.

Download Full-text

SURG-09. CHANGING PARADIGMS IN THE MANAGEMENT OF CEREBRAL METASTASES

Neuro-Oncology ◽

10.1093/neuonc/noz175.1010 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi241-vi241

Author(s):

Edvin Telemi ◽

James Snyder ◽

Ian Lee ◽

Adam Robin

Keyword(s):

Disease Progression ◽

Cause Of Death ◽

Small Sample Size ◽

Expectant Management ◽

Initial Therapy ◽

Small Sample ◽

Cerebral Metastases ◽

Extracranial Disease ◽

The Mean ◽

Clinically Significant

Abstract INTRODUCTION Paradigms in the management of cerebral metastases (CM) are evolving, in part due to the expanded use of laser interstitial thermal therapy or LITT in lesion ablation, with treatment of CM comprising up to 34% of all LITT cases. Currently, CM are treated with LITT largely in the setting of disease progression after initial therapy with focused radiation with no standard for performing biopsy prior to LITT. In this study we aim to assess the significance of the pathology of the lesion at the time of LITT on survival. METHODS We conducted a retrospective review of our institution’s LITT/brain tumor database and identified patients who underwent LITT with concurrent biopsy. For deceased patients, we identified cause of death if secondary to neurologic causes defined as death either due to direct intracranial disease progression leading to rapid neurologic decline or due to progressive neurologic decline without significant extracranial disease burden. RESULTS We identified 16 progressive CM lesions in 15 adults treated with LITT with concurrent biopsy, predominantly with non-small cell lung cancer. The mean age at LITT was 62, median follow-up was 8.5 months and thirteen of fifteen patients had previous focused radiation therapy. Eleven of sixteen lesions demonstrated radiation necrosis(RN) without tumor and 5 with tumor progression(TP). The mean survival in patients with RN was 548 days compared with 285 days in patients with TP (p=0.15). Of the 9 deceased, 2 of 5 patients with RN and 3 of 4 patients with TP died of neurologic causes. CONCLUSIONS Although statistically not significant due to the small sample size, this preliminary analysis suggests that clinically significant differences in survival and cause of death may exist between patients with RN and TP. Further evaluation with implications for treatment, prognosis and the expectant management of the patient with CM is warranted.

Download Full-text

Analysis of Clinical Efficacy of Traditional Chinese Medicine in Recovery Stage of Stroke: A Systematic Review and Meta-Analysis

Cardiovascular Therapeutics ◽

10.1155/2020/7172052 ◽

2020 ◽

Vol 2020 ◽

pp. 1-35

Author(s):

Xue Zhang ◽

Xiao-Fei Zhang ◽

Lin Wang ◽

Dong-Yan Guo ◽

Jia-Min Zhang ◽

...

Keyword(s):

Large Scale ◽

Clinical Symptoms ◽

Small Sample Size ◽

Meta Analysis ◽

Recovery Period ◽

Small Sample ◽

Comprehensive Treatment ◽

Neural Function ◽

Routine Treatment

Background. We provide an updated meta-analysis with detailed information on a combination of TCM and routine treatment. Methods. Retrieve appropriate articles with no language restrictions on keywords until 8 July 2019 in an electronic database. All trajectories are screened according to certain criteria. The quality of certified research was also evaluated. We made a detailed record of the results of the measurement. Meta-analysis was carried out by using the Revman 5.3 software. Results. Sixty-seven RCTs were included, and 6594 subjects were analyzed. Compared with routine treatment, the total effective rate (TER) of TCM combined with routine treatment was improved, and the recovery of stroke was also significantly accelerated. Regulation of blood lipids by notably shrinking the contents of TC, TG, and LDL and enhancing the levels of HDL. The levels of serum hs-CRP, WHV, and WLV decreased significantly, indicating that the expression of thrombomodulin was decreased after the comprehensive treatment of traditional Chinese medicines (TCMs). The combination of TCM treatment could enhance the protection of neural function by decreasing the NIHSS scoring while increasing the BI scoring. Paeoniae Radix Rubra, Angeticae Sinensis Radix, etc., can effectively improve the clinical symptoms of stroke convalescent patients and promote the recovery of neurological function. ACU of Baihui, Renzhong, etc., can improve the clinical rehabilitation effect of patients. However, our findings must be handled with care because of the small sample size and low quality of clinic trials cited. Other rigorous and large-scale RCTs are in need to confirm these results. Conclusion. A combination of TCM and routine treatment in the treatment of stroke could improve TER, and it is beneficial to the rehabilitation of patients in the recovery period of apoplexy. These effects can be mediated by a combination of several mechanisms. Nevertheless, due to the limitations of this study, these results should be handled with caution.

Download Full-text

P002 Real-world experiences of biologic tapering

Rheumatology ◽

10.1093/rheumatology/keab247.001 ◽

2021 ◽

Vol 60 (Supplement_1) ◽

Author(s):

Zoe Rutter-locher ◽

Yik Long Man ◽

Lydia Marsh ◽

Scott Mercer ◽

Bina Menon ◽

...

Keyword(s):

Real World ◽

Biologic Therapy ◽

Small Sample Size ◽

Significant Proportion ◽

Small Sample ◽

Patient Choice ◽

Treat To Target ◽

Improvement Project ◽

Real World Setting

Abstract Background/Aims Biologic therapy and treat to target have significantly improved patient outcomes and we now have a proportion of patients on biologic therapy who remain in clinical remission. NICE guidance suggests “cautiously reducing drug doses or stopping drugs in those who have maintained the treatment target”. Despite this guidance, little is known about current clinical practice of biologic tapering in UK rheumatology centres. We aimed to illustrate current practice and success rates in biologic tapering in a real-world setting in patients with rheumatoid arthritis (RA), psoriatic arthritis (PSA) and ankylosing spondylitis (AS). Methods We identified patients who were potentially suitable for biologic tapering 1 week prior to their follow up appointment using the following criteria - any anti-TNFα biologic ≥ 1 year, RA patients (DAS28 CRP<3.2, CRP normal), PSA patients (no swollen joints, CRP normal, no extra-articular manifestations), AS patients (BASDAI<4, CRP normal). We then analysed how many patients were successfully tapered at one year. Tapering schedule was decided by the supervising rheumatologist. Results From December 2018 to February 2019, 66 patients were identified as being suitable for biologic tapering. 3 patients did not attend and were excluded from further analysis. Tapered group: 20 (32%) patients were tapered. Based on the retrospective review of clinic letters, the “tapering schedule” was inconsistent and the information provided to patients if they flared was also inconsistent - 9 (45%) patients were advised to return to their normal dose and only 1 (5%) patient was advised to contact the helpline. After 12 months of follow up, 11 (55%) patients remained on the tapered dose, 7 (35%) patients returned to their prior dose and 2 (10%) patients were lost to follow up. Non-tapered group: 43 (68%) patients were not tapered. The reasons for not tapering were divided into 6 broad categories: active disease (n = 15, 35%), patient choice (n = 5, 12%), DMARD was tapered instead (n = 5, 12%), discuss at next visit (n = 3, 7%), reason not mentioned (n = 12, 28%), other (n = 3, 7%) Conclusion This Quality Improvement Project has highlighted the inconsistencies in biologic tapering in a UK real-world setting. In response to this inconsistency, we have developed a departmental guideline which provides stringent criteria to identify patients at lowest risk of flaring and standardises a tapering schedule and clinical pathway. We also created a patient information leaflet that could be distributed. Only half of the patients remained on the tapered dose after 1 year, suggesting a significant proportion of patients flare following dose reduction. However, our findings may be limited by small sample size. National guidance and a thorough audit based on this guidance is welcomed. Disclosure Z. Rutter-locher: None. Y. Long Man: None. L. Marsh: None. S. Mercer: None. B. Menon: None. A. Cope: None.

Download Full-text

Fuzzy-FishNet: A highly precise distribution-free network approach for feature selection in clinical proteomics

10.1101/024430 ◽

2015 ◽

Author(s):

Wilson Wen Bin Goh

Keyword(s):

Feature Selection ◽

Small Sample Size ◽

Small Sample ◽

Clinical Proteomics ◽

P Value ◽

Fisher Exact Test ◽

Proteomics Data ◽

Exact Test ◽

Genomics And Proteomics ◽

T Distribution

Network-based analysis methods can help resolve coverage and inconsistency issues in proteomics data. Previously, it was demonstrated that a suite of rank-based network approaches (RBNAs) provides unparalleled consistency and reliable feature selection. However, reliance on the t-statistic/t-distribution and hypersensitivity (coupled to a relatively flat p-value distribution) makes feature prioritization for validation difficult. To address these concerns, a refinement based on the fuzzified Fisher exact test, Fuzzy-FishNet was developed. Fuzzy-FishNet is highly precise (providing probability values that allows exact ranking of features). Furthermore, feature ranks are stable, even in small sample size scenario. Comparison of features selected by genomics and proteomics data respectively revealed that in spite of relative feature stability, cross-platform overlaps are extremely limited, suggesting that networks may not be the answer towards bridging the proteomics-genomics divide.

Download Full-text

Relationship between overall survival and progression-free survival for recent NCCTG glioblastoma multiforme trials.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2004 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2004-2004

Author(s):

Wenting Wu ◽

Evanthia Galanis ◽

Jan C. Buckner ◽

Kurt A. Jaeckle ◽

Daniel J. Sargent

Keyword(s):

Correlation Coefficient ◽

Phase Ii ◽

Small Sample Size ◽

Progression Free Survival ◽

Small Sample ◽

Control Group ◽

Phase Ii Trials ◽

Free Survival ◽

Individual Patient Level ◽

The Individual

2004 Background: With the approval of novel agents for glioblastoma (GBM) treatment, reliable historical outcome data for the common phase II endpoint of progression free survival (PFS) is not available. In particular, the association between progression and overall survival (OS) has not been evaluated after temozolomide (TMZ) became the standard therapy for newly diagnosed GBM. Methods: Datasets from 5 TMZ-including NCCTG clinical trials in newly diagnosed GBM (n=325, 2005-2011, 1 phase I only and 4 phase I and single arm phase II trials) were pooled and analyzed to evaluate the individual level correlation between PFS and OS using correlation coefficient, landmark analyses, and time-dependent variable analyses. A historical control group was constructed by pooling datasets from 12 pre-TMZ era NCCTG clinical trials in the same patient population (n=1359, 1980-2004). Each of the 5 newer trials was compared to the control group to estimate the treatment effect (hazard ratio) on PFS and OS, which were analyzed to evaluate the trial level correlation between PFS and OS using correlation coefficient and weighted linear regression. Results: The estimated correlation coefficient between PFS and OS at individual patient level is 0.75 (95%CI, 0.7 to 0.8). The estimated hazard ratios of death in the landmark analysis at 4 and 6 months are 2.15 (95%CI, 1.47 to 3.15) and 2.17 (95%CI, 1.57 to 3.12), respectively, and the estimated hazard ratio of death is 10.1 (95%CI, 6.6 to 15.4) when progression is treated as a time-dependent variable. For trial level correlation (against the historical control group), the estimated correlation coefficient between HRos and HRpfs is 0.51 (95%CI, -0.67 to 0.96), with moderate prediction: the predicted HRos is very close to the observed HRos in 4 of 5 cases, however the predicted HRos is significantly different from 1 in only 2 out of 5 cases due to small sample size in other 3 cases. Conclusions: PFS and OS are highly associated at the individual patient level but only moderately at the trial level, the latter possibly due to small sample size in some of the trials. Additional validation in other trials could support use of PFS as a primary endpoint for randomized phase II trials in GBM.

Download Full-text

Risk of hepatotoxicity with concurrent statin and tyrosine kinase inhibitor (TKI) or mTOR inhibitor (mTORi) in patients with metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.610 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 610-610

Author(s):

Trang H. Au ◽

Erin B. Bailey ◽

Shiven B. Patel ◽

Srinivas Kiran Tantravahi ◽

Neeraj Agarwal ◽

...

Keyword(s):

Liver Enzyme ◽

Kinase Inhibitor ◽

Competitive Inhibition ◽

Small Sample Size ◽

Small Sample ◽

Exact Test ◽

Treatment Line ◽

Concurrent Use ◽

Additive Risk ◽

Observational Cohort

610 Background: TKIs and statins alone can cause liver injury. When used together, there is additive risk for hepatotoxicity, as seen with pazopanib and simvastatin, and the potential for discontinuing TKI therapy. Liver enzyme abnormalities are also associated with mTORi. Hepatotoxicity from concurrent use of statins as a class with TKI or mTORi as a class in real world practice in mRCC has not been reported. Methods: This observational cohort study included adult patients treated with a TKI or mTORi for mRCC at the Huntsman Cancer Institute from 2004-2014. We performed a treatment line analysis. For each treatment line, CTCAE criteria were used to categorize maximum AST, ALT, and total bilirubin. Highest grade of any liver enzyme was compared between TKI with and without statin and between mTORi with and without statin (Fisher’s Exact test). Results: A total of 162 treatment lines were included. For TKI and statin, the three most common treatment line combinations were sunitinib and simvastatin (7), sunitinib and atorvastatin (4), and pazopanib and simvastatin (3). For mTORi and statin, the three most common treatment line combinations involved simvastatin with temsirolimus (7) and everolimus (3). Prevalence of hepatotoxicity is shown in the table. Conclusions: Our results show a trend toward significance in the prevalence of hepatotoxicity with concomitant mTORi and statin versus mTORi alone, perhaps explained by mTORi-mediated competitive inhibition of simvastatin (sensitive CYP 3A4 substrate). There was no difference in hepatotoxicity for TKI with or without statin, although there were few pazopanib and simvastatin combinations. Study limitations include the small sample size, limited number of TKI or mTORi and statin combinations, and retrospective study design. A larger study is needed to validate these findings. [Table: see text]

Download Full-text

The Influence of Decontamination Procedures on the Surface of Two Polymeric Liners Used in Prosthodontics

Polymers ◽

10.3390/polym13244340 ◽

2021 ◽

Vol 13 (24) ◽

pp. 4340

Author(s):

Katarzyna Mańka-Malara ◽

Maciej Trzaskowski ◽

Dominika Gawlak

Keyword(s):

New York ◽

Soft Tissues ◽

Small Sample Size ◽

Polymeric Materials ◽

Small Sample ◽

Chi Square ◽

Exact Test ◽

Materials Used ◽

Cleaning Methods ◽

The Impact

Polymeric liners are materials commonly used in prosthodontics to reshape denture surfaces contacting the soft tissues of the oral cavity. The aim of the study was to determine the impact of different cleaning methods on two polymeric materials used in prosthodontics as non-adhesive permanent liners. The material for the research consisted of samples made from Mollosil Plus (Detax, Ettlingen, Germany)—direct polysiloxan liner; and Plastitanium (Pressing Dental, San Marino, Republic of San Marino)—an injection-molded liner. A total of 198 samples were made, 99 of each assessed material. They were exposed to different cleaning methods—a toothbrush, a toothbrush and soap, a toothbrush and toothpaste (BlendaMed, Procter&Gamble, Cincinnati, OH, USA), a toothpaste and denture cleaning paste (Protefix Hygiene Denture Paste, Queisser Pharma, Germany), denture cleansing tablets (Protefix Hygiene Cleaning Tablets, Queisse Pharma, Germany), and a disinfecting spray (Aftermat, Port Jefferson Station, New York City, NY, USA)—for 1 min, 5 min, 10 min, and 15 min. The image acquisition was performed with scanning electron microscopy and samples were analyzed for the homogeneity of their surfaces—the presence of holes, grooves, precipitate, and small and large separating pieces of the material marking departures from this homogeneity. For each type of damage, one point was given. Continuous data from two groups were compared with Mann–Whitney U testing. Due to a small sample size and distribution of variables other than normal, to compare more than two groups, Kruskal–Wallis testing with post hoc analysis (Dunn test with Bonferroni correction) was used. Categorical data were compared with the chi-square test and the Fisher’s exact test. The Mollosil Plus material should be decontaminated with the use of a toothbrush or toothbrush with soap, while Plastitanium material should be disinfected. Plastitanium samples are more susceptible to damage during the decontamination procedures than Mollosil Plus.

Download Full-text