Retrospective multicenter clinical study of risk factors for cetuximab-related infusion reaction in Japanese patients
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ABSTRACT:
DISEASE(S): Colorectal Cancer, Head And Neck Cancer
PROVIDER: 2612869 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:Local adaptation and its underlying molecular basis has long been a key focus in evolutionary biology. There has recently been increased interest in the evolutionary role of plasticity and the molecular mechanisms underlying local adaptation. Using transcriptome analysis, we assessed differences in gene expression profiles for three brown trout (Salmo trutta) populations, one resident and two anadromous, experiencing different temperature regimes in the wild. The study was based on an F2 generation raised in a common garden setting. A previous study of the F1 generation revealed different reaction norms and significantly higher QST than FST among populations for two early life-history traits. In the present study we investigated if similar reaction norm patterns were present at the transcriptome level. Eggs from the three populations were incubated at two temperatures (5 and 8 degrees C) representing conditions encountered in the local environments. Global gene expression for fry at the stage of first feeding was analysed using a 32k cDNA microarray. The results revealed differences in gene expression between populations and temperatures and population × temperature interactions, the latter indicating locally adapted reaction norms. Moreover, the reaction norms paralleled those observed previously at early life-history traits. We were able to identify 90 cDNA clones among the genes with an interaction effect that were differently expressed between the ecologically divergent populations. These included genes involved in immune- and stress response. We observed less plasticity in the resident as compared to the anadromous populations, possibly reflecting that the degree of environmental heterogeneity encountered by individuals throughout their life cycle will select for variable level of phenotypic plasticity at the transcriptome level. Our study demonstrates the usefulness of transcriptome approaches to identify genes with different temperature reaction norms. The responses observed suggest that populations may vary in their susceptibility to climate change.
2013-11-14 | GSE52341 | GEO
Project description:Local adaptation and its underlying molecular basis has long been a key focus in evolutionary biology. There has recently been increased interest in the evolutionary role of plasticity and the molecular mechanisms underlying local adaptation. Using transcriptome analysis, we assessed differences in gene expression profiles for three brown trout (Salmo trutta) populations, one resident and two anadromous, experiencing different temperature regimes in the wild. The study was based on an F2 generation raised in a common garden setting. A previous study of the F1 generation revealed different reaction norms and significantly higher QST than FST among populations for two early life-history traits. In the present study we investigated if similar reaction norm patterns were present at the transcriptome level. Eggs from the three populations were incubated at two temperatures (5 and 8 degrees C) representing conditions encountered in the local environments. Global gene expression for fry at the stage of first feeding was analysed using a 32k cDNA microarray. The results revealed differences in gene expression between populations and temperatures and population M-CM-^W temperature interactions, the latter indicating locally adapted reaction norms. Moreover, the reaction norms paralleled those observed previously at early life-history traits. We were able to identify 90 cDNA clones among the genes with an interaction effect that were differently expressed between the ecologically divergent populations. These included genes involved in immune- and stress response. We observed less plasticity in the resident as compared to the anadromous populations, possibly reflecting that the degree of environmental heterogeneity encountered by individuals throughout their life cycle will select for variable level of phenotypic plasticity at the transcriptome level. Our study demonstrates the usefulness of transcriptome approaches to identify genes with different temperature reaction norms. The responses observed suggest that populations may vary in their susceptibility to climate change. Brown trout populations from three rivers in Denmark were studied: the Karup (KAR), Norring Moellebaek (NOR) and Lilleaa Rivers (LIL). These rivers experience different temperature regimes during the period lasting from egg incubation until fry emergence. During the autumn of 2004 and the winter of 2004/2005, adults from the three populations were collected by electro fishing. The fish were stripped for milt and eggs to establish an F1 generation. In autumn/winter 2008/2009, mature F1s were used to establish F2 offspring for each of the three populations. For KAR and LIL, 20 full-sib families were established, whereas for NOR, 15 full-sib families were established. Eggs from each full sib family were divided into two pools that were incubated at 5 and 8M-BM-!C in separate hatching troughs. At the time of first feeding (ca. 750-780 day-degrees), 10 individuals from each family and temperature were collected and transferred to separate tubes containing RNAlater (QIAGEN, Hilden, Germany). A 32K cDNA microarray developed for salmonids by cGRASP was used for the analyses. Ten families were randomly selected from each population. From each family two individuals were analyzed for each temperature (5 and 8oC, respectively), amounting to a total of 120 individuals. Of the two individuals from each temperature treatment within a family, one was labeled with CY5 and the other with CY3. For each family there were two comparisons of individuals representing different temperatures, but with dyes swapped between comparisons.
2013-11-14 | E-GEOD-52341 | biostudies-arrayexpress
Project description:This study investigated the trends in idiopathic peptic ulcers, examined the characteristics of refractory idiopathic peptic ulcer, and identified the optimal treatment. The characteristics of 309 patients with idiopathic peptic ulcer were examined. We allocated idiopathic peptic ulcers that did not heal after 8 weeks' treatment (6 weeks for duodenal ulcers) to the refractory group and those that healed within this period to the healed group. The typical risk factors for idiopathic peptic ulcer (atherosclerosis-related underlying disease or liver cirrhosis complications) were absent in 46.6% of patients. Absence of gastric mucosal atrophy (refractory group: 51.4%, healed group: 28.4%; p = 0.016), and gastric fundic gland polyps (refractory group: 17.6%, healed group: 5.9%; p = 0.045) were significantly more common in the refractory group compared to the healed group. A history of H. pylori eradication (refractory group: 85.3%, healed group: 66.0%; p = 0.016), previous H. pylori infection (i.e., gastric mucosal atrophy or history of H. pylori eradication) (refractory group: 48.5%, healed group: 80.0%; p = 0.001), and potassium-competitive acid blocker treatment (refractory group: 28.6%, healed group, 64.1%; p = 0.001) were significantly more frequent in the healed group compared to the refractory group. Thus, acid hypersecretion may be a major factor underlying the refractoriness of idiopathic peptic ulcer.
| S-EPMC10822756 | biostudies-literature
Project description:Ecological restoration reaction system Raw sequence reads
| PRJNA1143158 | ENA
Project description:Primary biliary cholangitis (PBC) is diagnosed mainly in female individuals, and risk factors for PBC recurrence (rPBC) after liver transplantation (LT) from cadaveric donors have been reported. We conducted a retrospective multicenter study of rPBC in female patients after living-donor LT (LDLT). A total of 388 female patients undergoing LDLT for end-stage PBC were enrolled, and the effects of preoperative and operative factors were evaluated. Postoperative factors were evaluated in 312 patients who survived for more than 1 year post-LDLT. rPBC was defined as abnormal hepatic enzyme levels with typical histological findings in liver biopsies. Fifty-eight patients (14.9%) developed rPBC with a median of 4.6 (0.8-14.5) years post-LT. Cox hazard analysis (P < 0.05) showed that younger recipient age (hazard ratio, 0.95; 95% confidence interval, 0.920-0.982), shorter operative time (1.00; 0.995-0.999), higher serum immunoglobulin M level (1.00; 1.001-1.002), donor sex mismatch (2.45; 1.268-4.736), human leukocyte antigen B60 (2.56; 1.336-4.921) and DR8 (1.98; 1.134-3.448), and initial treatment with cyclosporine A (3.14; 1.602-6.138) were significantly associated with rPBC. The frequencies of Child-Turcotte-Pugh class C (0.46; 0.274-0.775), the model of end-stage liver disease score (0.96; 0.914-0.998), and updated Mayo risk score (1.02; 1.005-1.033) were significantly lower in rPBC. Posttransplantation use of steroids decreased and that of antimetabolites increased the frequency of rPBC. Conclusion: The timing of LT, recipient conditions, donor characteristics, and immunosuppressive medications may be associated with rPBC in LT recipients. (Hepatology Communications 2017;1:394-405).
| S-EPMC5721413 | biostudies-literature
Project description:Background: Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention. However, a small proportion of pediatric patients develop a severe clinical condition, Multisystem Inflammatory Syndrome in Children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C. Methods: Peripheral blood samples were recruited from 43 confirmed MIS-C patients with a median age of 7.7 years, most of whom were of West-Eurasian origin. Four or more organ systems were involved in the majority of patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants. Findings: The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2. The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with also a possible viral trigger, that shares many of the clinical features of MIS-C. Interpretation: We have characterized DNA methylation loci that are associated with the onset of MIS-C. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.
2022-06-26 | GSE193879 | GEO
Project description:PurposeTo describe clinical and biological features and the outcomes of patients admitted for histoplasmosis in two intensive care units (ICU) in French Guyana and in the French West Indies (Guadeloupe).MethodsAll patients admitted to these two ICUs for culture-proven histoplasmosis between January 2014 to August 2022 were included in the study. Using univariate and multivariate analysis, we assessed risk factors at ICU admission that were associated with death.ResultsForty patients were included (65% men). Median age was 56 years and simplified acute physiologic score (SAPS) II was 65. HIV was found in 58%, another immunodeficiency was identified in 28%, and no underlying immunodeficiency could be identified in 14% of patients. Within the first 24 h of ICU admission, 85% of patients had acute respiratory failure, 78% had shock, 30% had coma, and 48% had hemophagocytic lymphohistiocytosis. Mechanical ventilation was instituted in 78% of patients and renal replacement therapy in 55%. The 30-day mortality was 53%. By multivariate analysis, factors independently associated with 30-day mortality were SOFA score (odds ratio [OR] 1.5, 95% confidence interval [CI] [1.1-2.1]), time between symptom onset and treatment per day (OR 1.1, 95% CI 1.0-1.1), and hemophagocytic lymphohistiocytosis (OR 6.4, 95% CI 1.1-47.5).ConclusionHistoplasmosis requiring ICU admission is a protean disease with multiple and severe organ involvement. Immunodeficiency is found in most patients. The prognosis remains severe despite appropriate treatment and is worsened by late treatment initiation.
| S-EPMC10121956 | biostudies-literature
Project description:AimThis study aimed to investigate the association between level of impaired consciousness and severe hypothermia (<28°C) and to evaluate the association between level of impaired consciousness and inhospital mortality among accidental hypothermia patients.MethodsThis was a multicenter retrospective study using the J-Point registry database, which includes data regarding patients whose core body temperature was 35.0°C or less and who were treated as accidental hypothermia in emergency departments between April 1, 2011 and March 31, 2016. We estimated adjusted odds ratios of the level of impaired consciousness for severe hypothermia less than 28°C and inhospital mortality using a logistic regression model.ResultsThe study included 505 of 572 patients in the J-Point registry. Relative to mildly impaired consciousness (Glasgow Coma Scale [GCS] 13-15), the adjusted odds ratios for severe hypothermia less than 28°C were: moderate (GCS 9-12), 3.26 (95% confidence interval [CI], 1.69-6.25); and severe (GCS < 9), 4.68 (95% CI, 2.40-9.14). Relative to mildly impaired consciousness (GCS 13-15), the adjusted odds ratios for inhospital mortality were: moderate (GCS9-12), 1.65 (95% CI, 0.95-2.88); and severe (GCS < 9), 2.10 (95% CI, 1.17-3.78).ConclusionThe level of impaired consciousness in patients with accidental hypothermia was associated with severe hypothermia and inhospital mortality.
| S-EPMC8836211 | biostudies-literature
Project description:BackgroundInternal medicine (IM) doctors in Japan play the role of primary care physicians; however, the shortage of rural physicians continues. This study aims to elucidate the association of age, sex, board certification, type of work, and main clinical work with the retention or migration of IM doctors to rural areas.MethodsThis retrospective cohort study included 82,363 IM doctors in 2010, extracted from the national census data of medical doctors. The explanatory variables were age, sex, type of work, primary clinical work, and changes in board certification status. The outcome was retention or migration to rural areas. The first tertile of population density (PD) of municipalities defined as rural area. After stratifying the baseline ruralities as rural or non-rural areas, the odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. The analyses were also performed after age stratification (<39, 40-59, ≥60 years old).ResultsAmong the rural areas, women had a significantly higher OR for retention, but obtaining board certification of IM subspecialties had a significantly lower OR. Among the non-rural areas, physicians who answered that their main work was IM without specific subspecialty and general had a significantly higher OR, but obtaining and maintaining board certification for IM subspecialties had a significantly lower OR for migration to rural areas. After age stratification, the higher OR of women for rural retention was significant only among those aged 40-59 years. Those aged under 40 and 40-59 years in the non-rural areas, who answered that their main work was IM without specific subspecialty had a significantly higher OR for migration to rural areas, and those aged 40-59 years in the rural areas who answered the same had a higher OR for rural retention.ConclusionsObtaining and maintaining board certification of IM subspecialties are possible inhibiting factors for rural work, and IM doctors whose main work involves subspecialties tend to work in non-rural areas. Once rural work begins, more middle-aged female IM doctors continued rural work compared to male doctors.
| S-EPMC9922564 | biostudies-literature
Project description:BACKGROUND:Nonadherence to dietary and fluid restrictions, hemodialysis (HD), and medication treatment has been shown to increase the risks of hospitalization and mortality significantly. Sociodemographic and biochemical parameters as well as psychosocial conditions such as depression and anxiety are known to affect nonadherence in HD patients. However, evidence related to the relative importance and actual impact of these factors varies among studies. PURPOSE:The aim of this study was to identify the factors that affect nonadherence to dietary and fluid restrictions, HD, and medication treatment. METHODS:This descriptive study was conducted on 274 patients who were being treated at four HD centers in Turkey. The parameters used to determine nonadherence to dialysis treatment were as follows: skipping multiple dialysis sessions during the most recent 1-month period, shortening a dialysis session by more than 10 minutes during the most recent 1-month period, and Kt/V < 1.4. The parameters used to determine nonadherence to dietary and fluid restriction were as follows: serum phosphorus level > 7.5 mg/dl, predialysis serum potassium level > 6.0 mEq/L, and interdialytic weight gain > 5.7% of body weight. The Morisky Green Levine Medication Adherence Scale was performed to determine nonadherence to medication treatment. A patient was classified as nonadherent if he or she did not adhere to one or more of these indices. The Hospital Anxiety and Depression Scale was used to identify patient risk in terms of anxiety and depression. Logistic regression was used to determine the predictors of nonadherence. RESULTS:The nonadherence rate was 39.1% for dietary and fluid restrictions, 33.6% for HD, and 20.1% for medication. The risk of nonadherence to dietary and fluid restriction was found to be 4.337 times higher in high school graduates (95% CI [1.502, 12.754], p = .007). The risk of nonadherence to HD treatment was 2.074 times higher in men (95% CI [1.213, 3.546], p = .008) and 2.591 times higher in patients with a central venous catheter (95% CI [1.171, 5.733], p = .019). Longer duration in HD resulted in 0.992 times decrease in risk of nonadherence to treatment (95% CI [0.986, 0.998], p = .005). CONCLUSIONS/IMPLICATIONS FOR PRACTICE:Educational status, being male, having a central venous catheter, and having a short HD duration were found to be risk factors for nonadherence. Nurses must consider the patient's adherence to the dietary and fluid restrictions, HD, and medication treatment at each visit.
| S-EPMC6641098 | biostudies-other