Sarcopenia as a predictor of chemotherapy toxicity in patients with ovarian cancer receiving platinum and taxane-based chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17035-e17035
Author(s):  
Katherine Tucker ◽  
Stuart-Allison Moffat Staley ◽  
Meredith Newton ◽  
Michelle Ertel ◽  
Yingao Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Skeletal Muscle ◽  
Small Sample Size ◽  
Lumbar Vertebrae ◽  
Small Sample ◽  
Oncologic Outcomes ◽  
Skeletal Muscle Index ◽  
Chemotherapy Toxicity ◽  
Age Related ◽  
Significant Difference

e17035 Background: Sarcopenia (age-related loss of skeletal muscle mass) is associated with worse oncologic outcomes and adverse events in patients with solid tumors. Limited research in epithelial ovarian cancer (EOC) has shown that sarcopenia is associated with worse patient outcomes. The purpose of this study was to investigate the association of sarcopenia with chemotherapy toxicity in patients with EOC. Methods: EOC patients diagnosed between 6/2000 and 2/2017 who received platinum and taxane-based chemotherapy were included. Age, race, stage, grade, BMI, comorbidities, treatment, and outcomes were collected. Chemotherapy toxicities and associated grades, as well as treatment modifications were recorded. Computed tomography (CT) images within 3 months of diagnosis were evaluated for Skeletal Muscle Area (SMA) at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision(R) radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. This preliminary analysis generated descriptive statistics and compared the distributions of toxicity assessments by sarcopenia, with t-tests, rank-sum, chi-square and fisher’s exact tests. Results: 144 patients were evaluated. The majority presented with Stage III /IV, HGSOC (75%, 73%). Median age was 63 yrs and median BMI was 27.2 (IQR = 23.7-32.8). 61% of patients were sarcopenic. The median SMI was 40 (IQR = 34.2-46.2). There was no significant difference between sarcopenic (S) and nonsarcopenic (NS) patients with respect to dose adjustment (p = 0.37), regimen change (p = 0.998), need for blood transfusion (p = 0.60), toxicity-related hospitalization (p = 0.84) or delay in treatment (p = 0.37). Grade 3-4 toxicity was found in 56.8% of S and 58.9% of NS patients (p = 0.992). Similarly, the distributions of grade 1-2 toxicities in S and NS patients were comparable. Conclusions: In this cohort of patients, there was no significant association between sarcopenia and chemotherapy related toxicities. However, given high prevalence of sarcopenia in ovarian cancer patients, our relatively small sample size, and challenges with retrospective collection of chemotherapy toxicity, further prospective exploration is warranted.

Sarcopenia as a predictor of survival in patients with epithelial ovarian cancer (EOC) receiving platinum and taxane-based chemotherapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17030-e17030 ◽  
Author(s):  
Stuart-Allison Moffat Staley ◽  
Katherine Tucker ◽  
Meredith Newton ◽  
Michelle Ertel ◽  
Yingao Zhang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Skeletal Muscle ◽  
Lumbar Vertebrae ◽  
Advanced Ovarian Cancer ◽  
Metastatic Breast ◽  
Survival Outcomes ◽  
Muscle Area ◽  
Skeletal Muscle Index ◽  
Kaplan Meier ◽  
Skeletal Muscle Area

e17030 Background: Severe skeletal muscle loss (sarcopenia) is associated with poor cancer outcomes, including reduced survival and increased treatment toxicity. This relationship has recently been demonstrated in women with metastatic breast cancer, but there is a paucity of data regarding this correlation in women with EOC. Thus, our goal was to evaluate if sarcopenia, as assessed by computed tomography (CT) morphometric measurements, was associated with worse survival outcomes in EOC patients undergoing primary platinum and taxane-based chemotherapy. Methods: EOC patients diagnosed between 06/2000 and 02/2017 who received treatment with platinum and taxane-based chemotherapy were included. CT abdominal images closest to the time of diagnosis were retrospectively evaluated for skeletal muscle area at the 3rd lumbar vertebrae. Measurements were obtained with use of TomoVision® radiological software (SliceOmatic – version 5.0, Quebec, Canada). Sarcopenia was defined as Skeletal Muscle Index (SMI = SMA/height2) ≤ 41. Data analysis included Kaplan-Meier plots to assess survival, and descriptive statistics was utilized to describe characteristics between the two groups. Results: 201 EOC patients were evaluated. Sixty-four percent (128/201) met criteria for sarcopenia (SMI ≤ 41) at time of diagnosis. Seventy-six percent of patients were diagnosed with Stage III or IV disease, with high-grade serous as the most common histology (74%). Median age at diagnosis was 61 years. Approximately one third were obese. Body mass index was greater in the SMI > 41 group compared to the SMI ≤ 41 group (31.3 vs 26.3, p < 0.001). There was no difference in the prevalence of chronic conditions, including diabetes, coronary artery disease, hypertension, chronic kidney disease, or tobacco use, between the two groups. The mean overall survival did not differ between patients with SMI > 41 and SMI ≤ 41 (36.5 vs 40.8 months, p = 0.4, respectively). Conclusions: Based on this patient cohort, sarcopenia was not associated with worse survival outcomes in EOC patients receiving first-line platinum and taxane-based chemotherapy. Further prospective studies are needed to explore other diagnostics that may allow us to provide improved accuracy and individualization in the care of women with advanced ovarian cancer.

Is age-related worsening in ovarian cancer prognosis linked to changes in body composition and pharmacokinetics?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17553-e17553
Author(s):  
Martine Extermann ◽  
Christine Marie Walko ◽  
Asmita Mishra ◽  
Kerry Thomas ◽  
Biwei Cao ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Plasma Concentrations ◽  
Tumor Biology ◽  
The Body ◽  
Skeletal Muscle Index ◽  
Age Related ◽  
Total Fat ◽  
Total Muscle

e17553 Background: The prognosis of ovarian cancer worsens markedly with age. Yet few data are available to explain this phenomenon. Two hypotheses can be made. Changes in pharmacokinetics and treatment tolerance limit the dosing of chemotherapy. And/or changes in tumor and host-tumor biology limit treatment efficacy. Methods: We conducted a prospective cohort study of women with stage III/IV high-grade serous ovarian cancers treated with neoadjuvant intravenous carboplatin(C) AUC 5 every 3 weeks and paclitaxel(P) dosed either weekly at 80 mg/m2 or every 3 weeks at 175 mg/m2. Body composition was assessed using baseline CT scans at the L3 level. Total muscle mass, total fat mass, skeletal muscle index (SMI) and fat index were computed. Plasma concentrations were collected at pre-established time points for both C1D1 of C and P and concentration-time data was analyzed by non-compartmental methods. Area under the curve (AUC)0-INF, volume of distribution(Vd), clearance (Cl), half-life, and mean residence time were calculated. Free C concentrations were determined in plasma ultrafiltrate and assayed, along with P plasma concentrations, by liquid chromatography-tandem mass spectrometry. Toxicity was assessed as first cycle nadir ANC and G4 hematologic(H) or grade 3-4 non-hematologic(NH) toxicity by CTCAE 4.0 criteria over a 3 cycles follow-up. The correlation between continuous measures was assessed by Spearman correlation coefficient, and the association with toxicity was evaluated by Wilcoxon rank sum test. Results: Seventeen patients, ages 38 to 86 (median 61) were eligible. All patients but one received 3 cycles of chemotherapy and median dose intensity was 100% (range 33.3-100%). Mean 1st cycle nadir ANC was 1.29 (range 0.06-9.0). 10/17 (59%) patients experienced G4 H and/or G3-4 NH toxicity. SMI was associated with C AUC (r -0.50, p < 0.05), and both total muscle (r = 0.61) and total fat (r = 0.53) were associated with C Vd. We did not find a correlation of P pharmacokinetics with body composition. A lower SMI was associated with 1st cycle G4H toxicity (p = 0.02), while C AUC had a borderline trend only (p = 0.15). Age was associated with a lower Vd (r -0.63, p = 0.009) and Cl (r -0.67, p = 0.004) of C. There was no significant age trend in the body composition parameters. Conclusions: Neoadjuvant treatment delivery was high in an academic setting. Toxicity appeared driven by low skeletal muscle index, in part via affecting carboplatin pharmacokinetics, and showed no significant age trend. The explanation for age-related changes in prognosis is more likely to lay with changes in tumor and host-tumor biology, which are being analyzed.

scholarly journals Quantitation of circulating GDF-11 and β2-MG in aged patients with age-related impairment in cognitive function

2017 ◽  
Vol 131 (15) ◽  
pp. 1895-1904 ◽  
Author(s):  
Rungong Yang ◽  
Shuhong Fu ◽  
Liang Zhao ◽  
Bei Zhen ◽  
Ling Ye ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Function ◽  
Small Sample Size ◽  
Small Sample ◽  
Advanced Age ◽  
Ageing Process ◽  
Aged Patients ◽  
Healthy Elderly ◽  
Age Related ◽  
Significant Difference

Growth differentiation factor 11 (GDF-11) has been implicated in reverse effects of ageing on the central nervous system of humans. β2-microglobulin (β2-MG) has been reported to negatively regulate cognition. However, there is a lot of controversy about the role of GDF-11 and β2-MG in ageing and cognitive regulation. To examine the involvement of GDF-11 and β2-MG in the ageing process and cognitive dysfunction, a total of 51 healthy subjects and 41 elderly patients with different degrees of age-related cognitive impairment participated in the study. We measured plasma GDF-11 and β2-MG levels using ELISA and immunoturbidimetry, respectively. The results were statistically analyzed to evaluate the associations between levels of GDF-11 and β2-MG, and ageing and cognitive impairments. Circulating GDF-11 levels did not decline with age or correlate with ageing in healthy Chinese males. We did not detect differences in circulating GDF-11 levels amongst the healthy advanced age and four cognitive impairment groups. β2-MG levels increased with age, but there was no significant difference between healthy elderly males and advanced age males. Increased levels of β2-MG were observed in the dementia group compared with the healthy advanced age group. Our results suggest that circulating GDF-11 may not exert a protective effect during the ageing process or on cognitive function, and β2-MG may play a role in ageing and cognitive impairment. However, it is possible that the relatively small sample size in the present study affected the quality of the statistical analysis, and future studies are needed to further validate our findings.

scholarly journals Blinding in electric current stimulation in subacute neglect patients with current densities of 0.8 A/m2: a cross-over pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Anna Gorsler ◽  
Ulrike Grittner ◽  
Nadine Külzow ◽  
Torsten Rackoll
Keyword(s):  
Pilot Study ◽  
Electric Fields ◽  
Standard Care ◽  
Small Sample Size ◽  
Small Sample ◽  
Related Factors ◽  
Attentional Deficits ◽  
Age Related ◽  
Current Densities ◽  
Improve Standard

Abstract Objective Neglect after stroke is a disabling disorder and its rehabilitation is a major challenge. Transcranial direct current stimulation (tDCS) seems to be a promising adjuvant technique to improve standard care neglect therapy. Since electric fields are influenced by age-related factors, higher current densities are probably needed for effective treatment in aged stroke patients. Validation of treatment efficacy requires sham-controlled experiments, but increased current densities might comprise blinding. Therefore, a pilot study was conducted to test sham adequacy when using current density of 0.8 A/m2. Whether especially neglect patients who mainly suffer from perceptual and attentional deficits are able to differentiate beyond chance active from sham tDCS was investigated in a randomized cross-over design (active/sham stimulation) in 12 early subacute patients with left-sided hemineglect. Stimulation (0.8 A/m2) was performed simultaneous to standard care neglect therapy. Results Odds ratio of correct guessing an atDCS condition compared to wrongly judge an atDCS condition as sham was 10.00 (95%CI 0.65–154.40, p = 0.099). However, given the small sample size and high OR, although likely somewhat overestimated, results require careful interpretation and blinding success in neglect studies with current densities of 0.8 A/m2 should be further confirmed.

scholarly journals NI-19 Use of 11C-methionine PET for decision of discontinuation of adjuvant chemotherapy with temozolomide

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii14-ii14
Author(s):  
Takaaki Beppu ◽  
Yuichi Sato ◽  
Toshiaki Sasaki ◽  
Kazunori Terasaki ◽  
Kuniaki Ogasawara
Keyword(s):  
Adjuvant Chemotherapy ◽  
Small Sample Size ◽  
Standardized Uptake Value ◽  
Progression Free Survival ◽  
Residual Tumor ◽  
Small Sample ◽  
Tumor Type ◽  
Diffuse Astrocytoma ◽  
Significant Difference ◽  
Met Pet

Abstract Background: The aim was to clarify whether positron emission tomography with 11C-methyl-L-methionine (met-PET) is useful to decide on discontinuation of TMZ-adjuvant therapy in patients with residual diffuse astrocytic tumor. Methods: Subjects were 44 patients with residual tumor comprising 17 with IDH1-mutant diffuse astrocytoma (DA), 13 with IDH1-mutant anaplastic astrocytoma (AA), and 14 with IDH1-wild glioblastoma (GB). All patients received TMZ-adjuvant chemotherapy (median, 12 courses), and whether to discontinue or continue TMZ-adjuvant chemotherapy was decided on the basis of the tumor-to-normal ratio in standardized uptake value from met-PET (T/N); patients with T/N &lt; 1.6 immediately discontinued TMZ, and patients with T/N &gt; 1.6 were either to continued or discontinued TMZ. Progression-free survival (PFS) was compared between patients with T/N &gt; 1.6 and T/N &lt; 1.6 in each tumor type. Median observation period was 434 days after met-PET scanning. Results: The number of patient who underwent recurrence was 10 in DA, 7 in AA, and 11 in GB. All patients showing T/N &gt; 1.6 underwent tumor recurrence. PFS was significantly longer in patients with T/N &lt; 1.6 than T/N &gt; 1.6 in DA and AA (p &lt; 0.01 in both types), but was no significant difference between 2 groups in GB (p = 0.06). Sixteen of 17 patients (94%) in DA and AA showed recurrence from residual tumor, whereas 4 of 11 patients (36%) in GB showed recurrent tumor at remote regions which were different from residual tumor. Conclusions: The present study suggested that met-PET is beneficial to decide to discontinue adjuvant chemotherapy with TMZ in patients with residual tumors of DA and AA, but not useful for patients with GB. Reasons for unsuccessful results in GB might have been small sample size, failure of establishing the cut off value in T/N, recurrences at remote regions where not be assessed by met-PET.

scholarly journals 1611. Evaluating Clinical Outcomes and Efficacy of Daptomycin in Combination with a Beta-Lactam for the Treatment of Vancomycin-Resistant Enterococcus (VRE) Bacteremia

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S799-S800
Author(s):  
Nerea Irusta ◽  
Ana Vega ◽  
Yoichiro Natori ◽  
Lilian M Abbo ◽  
Lilian M Abbo ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Small Sample Size ◽  
Univariate Analysis ◽  
Small Sample ◽  
Significant Difference ◽  
Vancomycin Resistant ◽  
Secondary Outcomes ◽  
Related Mortality

Abstract Background In-vitro studies have shown synergistic bactericidal activity with daptomycin (DAP) plus β-lactam antimicrobials against vancomycin resistant enterococci (VRE). There is a paucity of data regarding clinical outcomes with this combination in VRE bloodstream infections (BSI). The purpose of this study was to assess the efficacy of DAP plus a β-lactam with in-vitro activity vs. other therapies for treatment of VRE BSI. Methods IRB-approved, single-center, retrospective study of patients with VRE BSI from 01/2018-09/2019. Patients were excluded if &lt; 18 years old, pregnant, or incarcerated. The primary outcome was time-to-microbiological clearance. Secondary outcomes included infection-related mortality, 30-day all-cause mortality, and incidence of recurrent BSI within 30 days of index culture. Targeted DAP doses were ≥ 8mg/kg and based on MIC. Factors associated with significance for outcomes, via univariate analysis, were evaluated with multivariable logistic regression (MLR), removed in a backward-step approach. Results A total of 85 patients were included, 23 of which received DAP plus a β-lactam. The comparator arm included linezolid or DAP monotherapy. Patients with combination therapy had significantly higher Charlson Comorbidity Index (CCI) (p=0.013) and numerically higher Pitt Bacteremia scores (PBS) (p=0.087) (Table 1). There was no difference seen in the primary outcome (Table 2). Secondary outcomes are provided in Table 2. The presence of polymicrobial infection and higher PBS were significantly associated with infection-related mortality (p=0.008 and p=0.005, respectively) by MLR. A Mann Whitney U test indicated that presence of infection-related mortality was greater for patients with higher MICS (U=20.5, p=0.06). The presence of an underlying source may be related to recurrence of BSI (p=0.075). Table 1: Patient Characteristics Table 2. Primary and Secondary Outcomes Conclusion We did not find a significant difference in time-to-microbiological clearance, although patients treated with DAP and a β-lactam had higher CCI and PBS. These results are limited by retrospective design, small sample size, and potential selection bias. Prospective randomized studies are needed to further validate these findings. Disclosures All Authors: No reported disclosures

scholarly journals Perioperative Outcomes Following Kidney-Pancreas Transplantation in Alberta, Canada: Research Letter

2021 ◽  
Vol 8 ◽  
pp. 205435812110293
Author(s):  
Danielle E. Fox ◽  
Robert R. Quinn ◽  
Paul E. Ronksley ◽  
Tyrone G. Harrison ◽  
Hude Quan ◽  
...  
Keyword(s):  
Patient Outcomes ◽  
Postoperative Care ◽  
Pancreas Transplantation ◽  
Type I Diabetes ◽  
Small Sample Size ◽  
Small Sample ◽  
Perioperative Outcomes ◽  
Type I ◽  
Patient Safety Indicators ◽  
Significant Difference

Background: Simultaneous kidney-pancreas transplantation (SPK) has benefits for patients with kidney failure and type I diabetes mellitus, but is associated with greater perioperative risk compared with kidney-alone transplantation. Postoperative care settings for SPK recipients vary across Canada and may have implications for patient outcomes and hospital resource use. Objective: To compare outcomes following SPK transplantation between patients receiving postoperative care in the intensive care unit (ICU) compared with the ward. Design: Retrospective cohort study using administrative health data. Setting: In Alberta, the 2 transplant centers (Calgary and Edmonton) have different protocols for routine postoperative care of SPK recipients. In Edmonton, SPK recipients are routinely transferred to the ICU, whereas in Calgary, SPK recipients are transferred to the ward. Patients: 129 adult SPK recipients (2002-2019). Measurements: Data from the Canadian Institute for Health Information Discharge Abstract Database (CIHI-DAD) were used to identify SPK recipients (procedure codes) and the outcomes of inpatient mortality, length of initial hospital stay (LOS), and the occurrence of 16 different patient safety indicators (PSIs). Methods: We followed SPK recipients from the admission date of their transplant hospitalization until the first of hospital discharge or death. Unadjusted quantile regression was used to determine differences in LOS, and age- and sex-adjusted marginal probabilities were used to determine differences in PSIs between centers. Results: There were no perioperative deaths and no major differences in the demographic characteristics between the centers. The majority of the SPK transplants were performed in Edmonton (n = 82, 64%). All SPK recipients in Edmonton were admitted to the ICU postoperatively, compared with only 11% in Calgary. There was no statistically significant difference in the LOS or probability of a PSI between the 2 centers (LOS for Edmonton vs Calgary:16 vs 13 days, P = .12; PSIs for Edmonton vs Calgary: 60%, 95% confidence interval [CI] = 0.50-0.71 vs 44%, 95% CI = 0.29-0.59, P = .08). Limitations: This study was conducted using administrative data and is limited by variable availability. The small sample size limited precision of estimated differences between type of postoperative care. Conclusions: Following SPK transplantation, we found no difference in inpatient outcomes for recipients who received routine postoperative ICU care compared with ward care. Further research using larger data sets and interventional study designs is needed to better understand the implications of postoperative care settings on patient outcomes and health care resource utilization.

scholarly journals Effects of Age and Serum 25-OH-Vitamin D on Serum Parathyroid Hormone Levels

2012 ◽  
Vol 97 (11) ◽  
pp. 3989-3995 ◽  
Author(s):  
A. Valcour ◽  
F. Blocki ◽  
D. M. Hawkins ◽  
Sudhaker D. Rao
Keyword(s):  
Vitamin D ◽  
Calcium Absorption ◽  
Small Sample Size ◽  
International Workshop ◽  
Large Population ◽  
Small Sample ◽  
Reference Laboratory ◽  
Population Database ◽  
Age Related ◽  
Serum Pth

Context: Several studies define optimal serum 25-hydroxyvitamin D (25-OHD) levels based on serum PTH level reaching an asymptote. However, results differ widely, ranging from 25-OHD levels of 12–44 ng/ml: many studies are constrained by small sample size. Objective: The objective of the study was to determine the relationship between serum PTH and 25-OHD levels and age in a very large reference laboratory database. Design: This was a detailed cross-sectional analysis of 312,962 paired serum PTH and 25-OHD levels measured from July 2010 to June 2011. Results: Median PTH levels and the proportion of patients (PTH &gt; 65 pg/ml), from 63 successive 25-OHD frequency classes of 5000 patients, provide smooth, exceptionally well-fitted curves (R2 = 0.994 and R2 = 0.995, respectively) without discernible inflection points or asymptotes but with striking age dependencies. Serum 25-OHD was below the recent Institute of Medicine sufficiency guidance of 20 ng/ml in 27% (85,000) of the subjects. More importantly, 40 and 51% of subjects (serum 25-OHD &lt;20 and 10 ng/ml, respectively) had biochemical hyperparathyroidism (PTH &gt; 65 pg/ml). Conclusions: This analysis, despite inevitable inherent limitations, introduces several clinical implications. First, median 25-OHD-dependent PTH levels revealed no threshold above which increasing 25-OHD fails to further suppress PTH. Second, the large number of subjects with 25-OHD deficiency and hyperparathyroidism reinforces the Third International Workshop on Asymptomatic Primary Hyper parathyroidism's recommendations to test for, and replete, vitamin D depletion before considering parathyroidectomy. Third, strong age dependency of the PTH-25-OHD relationship likely reflects the composite effects of age-related decline in calcium absorption and renal function. Finally, this unselected large population database study could guide clinical management of patients based on an age-dependent, PTH-25-OHD continuum.

The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17551-e17551
Author(s):  
Marta Castiglia ◽  
Lorena Incorvaia ◽  
Alessandro Perez ◽  
Chiara Brando ◽  
Antonio Galvano ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Risk ◽  
Small Sample Size ◽  
Female Genital Tract ◽  
Brca1 Gene ◽  
Small Sample ◽  
Clinicopathological Features ◽  
Age At Diagnosis ◽  
Ovarian Cancer Risk

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determine specific clinicopathological features in OC patients harboring BRCA1/2 PVs. Methods: From 2015 to 2021, 338 patients diagnosed with epithelial OC (not mucinous, not borderline) were subjected to BRCA1/2 analysis. After obtaining informed consent, blood samples were processed for genomic DNA isolation; DNA was used for library preparation with the BRaCa Screen kit. Sequencing was performed on the IonS5 platform; variant annotation was performed with Amplicon Suite software. We collected data of both PVs and polymorphisms in BRCA1/2 genes with the aim to evaluate whether a cluster of specific polymorphisms could impact clinicopathological features in BRCA1 PVs carriers. Results: Among the 338 screened EOC, BRCA1/2 PVs were reported in 85 patients (25%). 66% of patients harbored BRCA1 PVs and 34% in BRCA2. The most frequent BRCA1 PVs were the c.4964_4982del (5083del19), c.514delC and c.181T > G; the first and the last are known for their founder effect in Italy and Eastern Europe. Looking at BRCA1 gene, in 75% of patients we identified a polymorphisms cluster (c.2082C > T, c.2311T > C, c.2612C > T, c.3113A > G, c.3548A > G, c.4308T > C, c.4837A > G). The c.514delC and c.181T > G PVs are always associated with the cluster and two additional polymorphisms, the c.2077G > A and the c.1067A > G respectively. Conversely, the cluster seems not to be associated with the PVs 5083del19. Interestingly in BRCA1-5083del19 PV carriers median age at OC diagnosis was 50 years (range 45-69). On average, these patients developed ovarian cancer 6 years earlier than other BRCA1 PV carriers (median age at diagnosis 57 years; range 30-81). Bilateral tumors were frequent and occurred in 57% of the patients versus 33% in OC patients carrying other BRCA1 PVs. Therefore, it seems that the cluster has a “protective” effect and that its absence reduces age at diagnosis. Conclusions: Despite this study has the main limitation of a small sample size, we have reported a possible association between polymorphisms cluster and clinicopathological features in BRCA1 PVs carriers. By further investigating this aspect in a larger cohort, we might be able to prove the role of this cluster in increasing or reducing OC risk and providing clinicians more information useful for patients’ stratification.

scholarly journals Nutritional Support and Clinical Outcome of Severe and Critical Patients With COVID-19 Pneumonia

2020 ◽  
Vol 7 ◽  
Author(s):  
Xiangfeng Yue ◽  
Min Li ◽  
Yu Wang ◽  
Jing Zhang ◽  
Xinyi Wang ◽  
...  
Keyword(s):  
Protein Intake ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Antiviral Treatment ◽  
Small Sample ◽  
Nutrition Support ◽  
Calorie Intake ◽  
Viral Shedding ◽  
Significant Difference ◽  
Critical Patients

Background: In 2020, a novel coronavirus has spread throughout the world. More than four hundred thousand people have died of SARS-CoV-2 pneumonia, most of which were severe and critical patients. No effective antiviral treatment has been verified thus far. Nutrition support has become one of the important treatments for severe and critical patients.Methods: In this retrospective study, 26 severe patients and 22 critical patients with laboratory confirmed COVID-19 were enrolled. We recorded the diet and nutritional treatments in severe and critical patients. Baseline characteristics and clinical outcomes of severe and critical patients were also collected.Results: Average calorie intake of severe patients (19.3 kcal/kg/d) was higher than critical patients (15.3 kcal/kg/d) (P = 0.04). Protein intake was similar in the two groups (0.65 and 0.62 g/kg per day, respectively; P = 0.29). There was no significant difference in the median duration of viral shedding between the severe and critical patients (P = 0.354).Conclusions: A permissive underfeeding strategy that restricts non-protein calories but preserves protein intake is feasible for critical patients with SARS-CoV-2 pneumonia. Viral shedding duration of critical patients was the same as severe patients who received standard feeding. Nevertheless, evidence of the conclusion is not sufficient because of small sample size. To show the real clinical benefit of permissive low-calorie and adequate protein intake in critical SARS-CoV-2 pneumonia patients, a large and pragmatic randomized controlled trial is needed.

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