In Germany the coronavirus disease 2019 (COVID-19) pandemic situation is unique among large European countries in that incidence and case fatality rate are distinctly lower. We describe the clinical ...course and examine factors associated with outcomes among patients hospitalized with COVID-19 in Germany.
In this retrospective cohort study we included patients with COVID-19 admitted to a national network of German hospitals between February 12 and June 12, 2020. We examined demographic characteristics, comorbidities and clinical outcomes.
We included 1904 patients with a median age of 73 years, 48.5% (924/1904) of whom were female. The mortality rate was 17% (317/1835; 95% confidence interval (95%CI) 16–19), the rate of admission to the intensive care unit (ICU) was 21% (399/1860; 95%CI 20–23), and the rate of invasive mechanical ventilation was 14% (250/1850: 95%CI 12–15). The most prominent risk factors for death were male sex (hazard ratio (HR) 1.45; 95%CI 1.15–1.83), pre-existing lung disease (HR 1.61; 95%CI 1.20–2.16), and increased patient age (HR 4.11 (95%CI 2.57–6.58) for age >79 years versus <60 years). Among patients admitted to the ICU, the mortality rate was 29% (109/374; 95%CI 25–34) and higher in ventilated (33% 77/235; 95%CI 27–39) than in non-ventilated ICU patients (23%, 32/139; 95%CI 16–30; p < 0.05).
In this nationwide series of patients hospitalized with COVID-19 in Germany, in-hospital and ICU mortality rates were substantial. The most prominent risk factors for death were male sex, pre-existing lung disease, and greater patient age.
Objective: To compare the survival of palliative stage IV colorectal cancer patients selected for primary tumor resection and systemic treatment (PTR+SYST) to patients with systemic treatment only ...(SYST). Background: About 20-25% of all colorectal cancer patients are diagnosed with stage IV disease. The benefit of primary tumor resection in the palliative situation is therefore of high concern. However, empirical evidence from randomized and observational studies is inconsistent. Methods: Mortality after PTR and systemic treatment was compared to systemic treatment alone in a retrospective observational cohort of patients diagnosed 2012-2020 from the cancer registry in the federal state of Brandenburg (Germany), excluding patients with rectal cancer of the lower two-thirds, emergency procedures, unknown ECOG status, ECOG >2, unknown metastatic status or unclear grading. Results: Of 480 patients, 416 died during an average follow-up of 23 months in mean. 12-months survival was 75% after PTR+SYST compared with 49% after SYST (HR=0.39, 95% CI 0.29-0.53, P <0.001). The difference persisted to 36 months (28% vs. 13%, HR=0.53, 95% CI 0.43-0.66, P <0.001). Results were similar after multivariate adjustment, propensity score matching and delayed entry. Conclusion and Relevance: Patients with stage IV colorectal carcinoma who are selected for primary tumor resection in combination with systemic therapy and who receive such treatment survive longer compared with patients who receive only systemic treatment. Whether the difference is due to selection of patients or PTR remains unclear. At present, current practice of selecting patients for PTR appears to do no harm.
Background: Although genes involved in apoptosis pathways and DNA repair pathways are both essential for maintaining genomic
integrity, genetic variants in DNA repair have been thought to increase ...susceptibility to radiation carcinogenesis, but similar
hypotheses have not generally been raised about apoptosis genes. For this reason, potential modification of the relationship
between ionizing radiation exposure and breast cancer risk by polymorphic apoptosis gene variants have not been investigated
among radiation-exposed women.
Methods: In a case-control study of 859 cases and 1,083 controls within the U.S. Radiologic Technologists cohort, we assessed
breast cancer risk with respect to 16 candidate variants in eight genes involved in apoptosis, inflammation, and proliferation.
Using carefully reconstructed cumulative breast dose estimates from occupational and personal diagnostic ionizing radiation,
we also investigated the joint effects of these polymorphisms on the risk of breast cancer.
Results: In multivariate analyses, we observed a significantly decreased risk of breast cancer associated with the homozygous
minor allele of CASP8 D302H rs1045485, odds ratio (OR), 0.3; 95% confidence interval (95% CI), 0.1-0.8. We found a significantly increased breast
cancer risk with increasing minor alleles for IL1A A114S (rs17561); heterozygote OR 1.2 (95% CI, 1.0-1.4) and homozygote OR 1.5 (95% CI, 1.1-2.0), P trend = 0.008. Assuming a dominant genetic model, IL1A A114S significantly modified the dose-response relationship between cumulative personal diagnostic radiation and breast cancer
risk, adjusted for occupational dose ( P interaction = 0.004).
Conclusion: The U.S. Radiologic Technologists breast cancer study provided a unique opportunity to examine the joint effects
of common genetic variation and ionizing radiation exposure to the breast using detailed occupational and personal diagnostic
dose data. We found evidence of effect modification of the radiation and breast cancer dose-response relationship that should
be confirmed in studies with more cases and controls and quantified radiation breast doses in the low-to-moderate range. (Cancer
Epidemiol Biomarkers Prev 2007;16(10):2000–7)
Studies have shown that breast cancer incidence rates among Asian migrants to the United States approach US incidence rates over several generations, implicating potentially modifiable exposures such ...as moderate alcohol use that has been linked to excess breast cancer risk in other populations. The goal of this study was to investigate the effect of alcohol intake, primarily low levels, on breast cancer risk in Asian-American women and explore whether smoking and alcohol contributed to the breast cancer incidence rates observed among Asian migrants to the United States. Study subjects in this population-based case-control study included 597 incident cases of breast cancer of Chinese, Japanese, and Filipino ethnicity living in San Francisco-Oakland, Los Angeles, and Oahu, Hawaii, and 966 population controls frequency matched on age, ethnicity, and area of residence. The fraction of smokers and drinkers was significantly higher in women born in Western compared with Eastern countries. However, breast cancer risk was not significantly associated with smoking (odds ratio (OR) = 1.2, 95% confidence interval (95% CI) = 0.9-1.6) or alcohol drinking (OR = 0.9, 95% CI = 0.7-1.1) in this population of low consumers of alcohol (median intake among drinkers in grams per day was 0.48 for cases and 0.40 for controls). These data suggest that low alcohol intake is not related to increased breast cancer risk in Asian-American women and that neither alcohol nor cigarette use contributed to the elevated risks in Asian-American women associated with migration patterns and Westernization.
Hodgkin lymphoma (HL) survivors are at increased risk of developing valvular heart disease (VHD). We evaluated the determinants of the risk and the radiation dose-response.
A case-control study was ...nested in a cohort of 1852 five-year HL survivors diagnosed at ages 15 to 41 years and treated between 1965 and 1995. Case patients had VHD of at least moderate severity as their first cardiovascular diagnosis following HL treatment. Control patients were matched to case patients for age, gender, and HL diagnosis date. Treatment and follow-up data were abstracted from medical records. Radiation doses to heart valves were estimated by reconstruction of individual treatments on representative computed tomography datasets. All statistical tests were two-sided.
Eighty-nine case patients with VHD were identified (66 severe or life-threatening) and 200 control patients. Aortic (n = 63) and mitral valves (n = 42) were most frequently affected. Risks increased more than linearly with radiation dose. For doses to the affected valve(s) of less than or equal to 30, 31-35, 36-40, and more than 40 Gy, VHD rates increased by factors of 1.4, 3.1, 5.4, and 11.8, respectively (P trend < .001). Approximate 30-year cumulative risks were 3.0%, 6.4%, 9.3%, and 12.4% for the same dose categories. VHD rate increased with splenectomy by a factor of 2.3 (P = .02).
Radiation dose to the heart valves can increase the risk of clinically significant VHD, especially at doses above 30 Gy. However, for patients with mediastinal involvement treated today with 20 or 30 Gy, the 30-year risk will be increased by only about 1.4%. These findings may be useful for patients and doctors both before treatment and during follow-up.
Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms ...in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFss1, IGFBP3) were evaluated.
Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N = 748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported.
Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR) = 2.3; 95% CI 1.3-3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR = 1.9; 1.1-3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR = 6.9; 1.6-29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3 -202A>C; TGFss1 L10P, P25R, and T263I; BRCA2 N289H and T1915M; BRIP1 -64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P.
Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of breast cancer and BRCA2 N372H and functional observations for APEX D148E ran counter to our findings of decreased risks. Due to the many comparisons, cautious interpretation and replication of these relationships are warranted.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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