scholarly journals Transcriptome dynamics predict thermotolerance in Caenorhabditis elegans

2019 ◽  
Author(s):  
Katharina Jovic ◽  
Jacopo Grilli ◽  
Mark G. Sterken ◽  
Basten L. Snoek ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Intrinsic Property ◽  
Recovery Process ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome

AbstractBackgroundThe detrimental effects of a short bout of stress can persist, and potentially turn lethal, long after the return to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme temperatures, is influenced by the response during stress exposure, as well as the recovery process afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal tolerance remains a challenge.ResultsHere, we use the nematode Caenorhabditis elegans to measure transcriptional resilience to heat stress and predict thermotolerance. Using high dimensionality reduction techniques in combination with genome-wide gene expression profiles collected in three high resolution time-series during control, heat stress and recovery conditions, we infer a quantitative scale capturing the extent of stress-induced transcriptome dynamics in a single value. This scale provides a basis for evaluating transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival after heat stress.ConclusionOur findings imply that thermotolerance is an intrinsic property that pre-determines long term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies after stresses such as disease and trauma.

scholarly journals Transcriptome resilience predicts thermotolerance in Caenorhabditis elegans

BMC Biology ◽  
2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Katharina Jovic ◽  
Jacopo Grilli ◽  
Mark G. Sterken ◽  
Basten L. Snoek ◽  
Joost A. G. Riksen ◽  
...  
Keyword(s):  
Heat Stress ◽  
Caenorhabditis Elegans ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Principal Component ◽  
Intrinsic Property ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome

Abstract Background The detrimental effects of a short bout of stress can persist and potentially turn lethal, long after the return to normal conditions. Thermotolerance, which is the capacity of an organism to withstand relatively extreme temperatures, is influenced by the response during stress exposure, as well as the recovery process afterwards. While heat-shock response mechanisms have been studied intensively, predicting thermal tolerance remains a challenge. Results Here, we use the nematode Caenorhabditis elegans to measure transcriptional resilience to heat stress and predict thermotolerance. Using principal component analysis in combination with genome-wide gene expression profiles collected in three high-resolution time series during control, heat stress, and recovery conditions, we infer a quantitative scale capturing the extent of stress-induced transcriptome dynamics in a single value. This scale provides a basis for evaluating transcriptome resilience, defined here as the ability to depart from stress-expression dynamics during recovery. Independent replication across multiple highly divergent genotypes reveals that the transcriptional resilience parameter measured after a spike in temperature is quantitatively linked to long-term survival after heat stress. Conclusion Our findings imply that thermotolerance is an intrinsic property that pre-determines long-term outcome of stress and can be predicted by the transcriptional resilience parameter. Inferring the transcriptional resilience parameters of higher organisms could aid in evaluating rehabilitation strategies after stresses such as disease and trauma.

Impact of age on early outcomes and long-term survival of patients undergoing aortic repair with Stanford A dissection

Perfusion ◽  
2018 ◽  
Vol 33 (8) ◽  
pp. 687-695 ◽  
Author(s):  
Julia Merkle ◽  
Anton Sabashnikov ◽  
Carolyn Weber ◽  
Georg Schlachtenberger ◽  
Johanna Maier ◽  
...  
Keyword(s):  
Surgical Repair ◽  
Age Groups ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival ◽  
Cerebrovascular Events ◽  
Short And Long Term ◽  
Male Patients

Objectives: Stanford A acute aortic dissection (AAD) is a life-threatening emergency, typically occurring in older patients and requiring immediate surgical repair. The aim of this study was to evaluate early outcome and short- and long-term survival of patients under and above 65 years of age. Methods: Two hundred and forty patients with Stanford A AAD underwent aortic surgical repair from January 2006 to April 2015 in our center. After statistical analysis and logistic regression analysis, Kaplan-Meier survival estimation was performed, with up to 9-year follow-up, comprising patients under and above 65 years of age. Results: The proportion of patients above 65 years of age suffering from Stanford A AAD was 50% (n=120). The group of patients above 65 years of age compared to the group under 65 years of age showed statistically significant differences in terms of higher odds ratios (OR) for hypertension (p=0.012), peripheral vascular disease (p=0.026) and tachyarrhythmia absoluta (p=0.004). Patients over 65 years of age also showed significantly poorer short- and long-term survival. Our subgroup analysis revealed that male patients (Breslow p=0.001, Log-Rank p=0.001) and patients suffering with hypertension (Breslow p=0.003, Log-Rank p=0.001) were reasonable for these results whereas younger and older female patients showed similar short- and long-term outcome (Breslow p=0.926, Log-Rank p=0.724). After stratifying all patients into 4 age groups (<45; 55-65; 65-75; >75years), short-term survival of the patients appeared to be significantly poorer with increasing age (Breslow p=0.026, Log-Rank p=0.008) whereas long-term survival of patients free from cerebrovascular events (Breslow p=0.0494, Log-Rank p=0.489) remained similar. Conclusions: All patients referred to our hospital for repair of Stanford A AAD with higher age had poorer short- and long-term survival, caused by male patients and patients suffering from hypertension, whereas survival of women and survival free from cerebrovascular events of the entire patient cohort was similar, irrespective of age.

scholarly journals 1026 Prognostic implications of global and regional RV strain in patients with heart failure and conduction delays

2020 ◽  
Vol 21 (Supplement_1) ◽  
Author(s):  
A Janicijevic ◽  
I Stankovic ◽  
A Zivanic ◽  
M Stefanovic ◽  
B Putnikovic ◽  
...  
Keyword(s):  
Heart Failure ◽  
Nyha Class ◽  
Cardiac Resynchronization ◽  
Cardiac Mortality ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Patients With Heart Failure ◽  
Rv Function

Abstract Background Right ventricular (RV) dysfunction is present in a substantial proportion of candidates for cardiac resynchronization therapy (CRT) but its prognostic implication has not been fully determined. We investigated the association of different echocardiographic indices of RV function and survival in patients with heart failure (HF) and conduction delays. Methods A total of 122 HF patients with bundle branch blocks (BBB), not treated with device therapy, were included in this retrospective observational study. RV function was assessed by measuring the tricuspid annular plane systolic excursion (TAPSE) and RV free wall longitudinal strain (RVFWSL). Patients were followed for cardiac mortality during a median period of 33 months. Results Both TAPSE ≤ 18 mm and RVFWSL≥-25% were associated with unfavorable long-term survival (log rank p &lt; 0.05 for both, Figure A and B). Importantly, in patients with normal TAPSE, RVFWSL remained predictive of long-term outcome (HR 1.15, 95% CI 1.003-1.327; p = 0.045). In the multivariate regression analysis, only NYHA class (HR 2.21, 95%CI (1.122 – 4.357; p = 0.022) and RVFWSL (HR 1.11, 95%CI 1.029 – 1.204; p = 0.008) were independently associated with cardiac mortality. Significant differences among segmental RVFWLS values were observed, including a basal-to-apical gradient with the highest strain values in the base and the lowest in the apex (Figure C). Conclusions RV dysfunction is associated with unfavorable survival in HF patients with BBB. RVFWSL appears to be stronger predictor of mortality than TAPSE. Different segments of the RV may contribute differently to RV dysfunction in patients with conduction delays. Abstract 1026 Figure.

scholarly journals Chemotherapy-Free Initial Treatment of Advanced Indolent Lymphoma Has Durable Effect With Low Toxicity: Results From Two Nordic Lymphoma Group Trials With More Than 10 Years of Follow-Up

2018 ◽  
Vol 36 (33) ◽  
pp. 3315-3323 ◽  
Author(s):  
Sandra Lockmer ◽  
Bjørn Østenstad ◽  
Hans Hagberg ◽  
Harald Holte ◽  
Ann-Sofie Johansson ◽  
...  
Keyword(s):  
Optimal Timing ◽  
Indolent Lymphoma ◽  
First Line ◽  
Term Outcome ◽  
Cross Sectional ◽  
Term Survival ◽  
Long Term Outcome ◽  
New Therapy

Purpose For indolent lymphoma, the optimal timing, sequence, and choice of therapeutic regimens remain a matter of debate. In two Nordic Lymphoma Group randomized trials, symptomatic or clearly progressing patients were treated first line with a rituximab-containing regimen without chemotherapy. The purpose of this study was to assess long-term survival, risk of transformation, and need of new therapies. Methods Data were collected at cross-sectional follow-up for 321 patients with indolent lymphoma (84% with follicular lymphomas [FL]) included in one of two Nordic Lymphoma Group trials (accrual 1998 to 1999 and 2002 to 2008). All patients received first-line therapy with one or two cycles of four weekly infusions of rituximab 375 mg/m2, and 148 were randomly allocated to the addition of interferon alfa-2a. Follow-up data were retrieved from initial trial databases and medical records on repeated clinical evaluations. Results At the end of follow-up, 73% of patients were alive, with a median follow-up after random assignment of 10.6 years. Among all, 36% (38% with FL) had never needed chemotherapy. For patients with FL who required new therapy within 24 months because of early disease progression, the 10-year survival rate was 59% versus 81% for those with longer remission. Interferon was not shown to improve long-term outcome. Transformation was diagnosed in 20% of all patients (2.4% per person-year) and in 18% with FL. An additional malignancy was found in 12%. Conclusion Approximately one third of patients with symptomatic indolent lymphoma (30% with FL, 23% without FL) did not need new therapy in the long term after first-line rituximab without chemotherapy. In the entire cohort, 10-year survival was excellent with no major safety issues, which suggests that chemotherapy can be delayed safely in the majority of patients.

scholarly journals Locally Advanced Pancreatic Head Cancer: Margin-Positive Resection or Bypass?

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ulrich Friedrich Wellner ◽  
Frank Makowiec ◽  
Dirk Bausch ◽  
Jens Höppner ◽  
Olivia Sick ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Pancreatic Head ◽  
Resection Margins ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Pancreatic Head Cancer ◽  
Margin Positive

Pancreatic cancer is a highly aggressive disease with poor survival. The only effective therapy offering long-term survival is complete surgical resection. In the setting of nonmetastatic disease, locally advanced tumors constitute a technical challenge to the surgeon and may result in margin-positive resection margins. Few studies have evaluated the implications of the latter in depth. The aim of this study was to compare the margin-positive situation to palliative bypass procedures and margin-negative resections in terms of perioperative and long-term outcome. By retrospective analysis of prospectively maintained data from 360 patients operated for pancreatic cancer at our institution, we provide evidence that margin-positive resection still yields a significant survival benefit over palliative bypass procedures. At the same time, perioperative severe morbidity and mortality are not significantly increased. Our observations suggest that pancreatic cancer should be resected whenever technically feasible, including, cases of locally advanced disease.

Long Term Outcome of Allogeneic Hematopoietic Stem Cell Transplantation for Beta Thalassemia Major

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4606-4606
Author(s):  
Fouzia NA ◽  
Sindhuvi E ◽  
Kavitha ML ◽  
Korula A ◽  
Abraham A ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Endocrine Disorders ◽  
Term Outcome ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Outcome

Abstract Introduction:Allogeneic hematopoietic stem cell transplantation (HSCT) cures beta thalassemia major (TM). Such individuals, ex-thalassemics, have good long term survival. However, there is limited data on long term outcome (LTO) of this therapy. This is particularly relevant as these patients often have organ dysfunction pre-transplant due to secondary hemosiderosis apart from the impact of post-transplant factors such as chronic GVHD, chimerism status and iron depletion therapy (IDT). In this report, we describe the LTO of patients with TM who underwent HSCT with busulfan (Bu) and cyclophosphamide (Cy) conditioning at our center from 2000 to 2011 and had a minimum of 2 year follow-up. Method: Data was extracted from prospectively maintained standardized case record forms for details of HSCT and long term follow-up with particular reference to GVHD, chimerism (evaluated at day +30, +60, +100 and thereafter as indicated), IDT (initiated at variable periods post-HSCT) and metabolic and endocrine disorders evaluated on physician discretion or as per clinical indications. Results:A total of 190 patients underwent matched related donor HSCT from 2001 to 2011 with Bu/Cy based conditioning. After excluding those who expired or had primary graft failure or did not have at least 2 years of follow-up, 124 patients were available for analysis of LTO. 44 patients (35.5%) class 3, 69 patients (55.6%) class 2 and 11 patients (8.9%) class 1. The median age was 7 years (range: 2-24) with 81 males (65.3%). The median follow-up was 7 years (range: 2 to 14). Chronic GVHD was present in 22 patients (17.7%]. Mixed chimerism (MC) occurred in 40 patients (32%) in the first year after HSCT: level I in 21 (52.5%), level II in 10 (25%), level III in 7 (17.5%), and level unknown in 2(5%). At last follow-up, 20/40 (50%) patients with MC went on to CC, 18 maintained stable MC (level I-5, level II-9 and level III-4) with hemoglobin of 11.35g/dl (range: 9-13.5), while 2 (5%) with level 3 MC remained transfusion dependent. Median serum ferritin (SF) at HSCT was 2367 ng/ml (range: 685-7660). IDT was initiated in 90 (72.6%) patients at a median of 15 months (range: 6-53) post-HSCT - 13 patients (14.4%) were treated with phlebotomy alone, while 39 (43.3%) received chelation and 38 (42.2%) the combination. Reduction in SF/month [absolute quantity (ng/ml/month) and percent] was as follows: 40.5 (range: 11.68 - 125.78); 1.67% (range: 0.5-4.58), 54.9 (range: 9.3- 278.7); 2.1% (range: 0.41- 13.8) and 36.6 (range: 3.51-590.7); 1.3% (range: 0.42-42.99), in the phlebotomy, chelation and combination groups, (p=0.077 & 0.017, respectively). SF level of <300 ng/ml was achieved in 33 patients (31%) at last follow-up. Anthropometry measurements (at last follow up) revealed short stature in 53 patients (42.7%; 38M/15F), underweight in 32 patients (25.8%; 20M/12F) and overweight in 14 (11.3%) patients (11M/3F). A total 48 patients (38.7%) had the following endocrine disorders: hypogonadism in 33 (73.3%), primary hypothyroidism in 9 (18.8%), hypopituitarism in 4 (8.3%), diabetes mellitus in 3 (6.2%), and hypoparathyroidism, dyslipidemia and hypertension in 1 patients each. 40 patients were vitamin D deficient (83.3%). Endocrine complications were more common in female patients (55.8% versus 29.6%; p=0.006). Two patients (1.3%) developed malignancies at 7 and 8 years, post-HSCT. Among different patient, donor and graft characteristics, there were no predictors of MC, nor did the ferritin levels or chelation therapy post-HSCT affect the incidence of endocrine complications in this cohort. Conclusion: Our data shows that even though the long term survival of ex-thalassemics is extremely good, at least 40% of them suffer from several co-morbidities related to iron overload and various metabolic and endocrine disorders which requires a coordinated plan for their management. The aim therefore should be to transplant these patients as early as possible before such complications occur and implement IDT intensively early after HSCT. Disclosures No relevant conflicts of interest to declare.

Long-term outcome of hypothalamic/chiasmatic astrocytomas in children treated with conservative surgery

1995 ◽  
Vol 83 (4) ◽  
pp. 583-589 ◽  
Author(s):  
Leslie N. Sutton ◽  
Patricia T. Molloy ◽  
Heidi Sernyak ◽  
Joel Goldwein ◽  
Peter L. Phillips ◽  
...  
Keyword(s):  
Radical Surgery ◽  
Conservative Surgery ◽  
Low Grade ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Content Type ◽  
Fine Print

✓ The feasibility of radical surgery for astrocytomas of the optic chiasm/hypothalamus has been reported by several groups. Such surgery carries significant risks, however, including permanent damage to the pituitary gland, optic apparatus, hypothalamic structures, and carotid arteries. The benefits of radical surgery, both in terms of efficacy and toxicity, should, therefore, be evaluated against standard therapy, as is usually done for new chemotherapeutic protocols. To this end, a retrospective review was performed of 33 patients treated at Children's Hospital of Philadelphia between 1976 and 1991 who met criteria that would have made them eligible for radical surgery in many centers today, but were treated with either no surgery or conservative surgery (< 50% resection) or biopsy followed by adjuvant therapy with local radiation therapy (29 patients) and/or chemotherapy with actinomycin-D and vincristine (18 patients). The review encompassed all children with a globular enhancing mass of at least 2 cm in the hypothalamic/chiasmatic region, no evidence of optic nerve involvement or involvement of the optic radiations by computerized tomography or magnetic resonance imaging, and follow up of at least 3 years. All but one patient had tissue confirmation of a low-grade or pilocytic astrocytoma. Thirteen of the patients were 2 years of age or younger at diagnosis. Five individuals died: three of tumor progression, one of acute shunt malfunction, and one of intercurrent infection. The remaining 28 were alive at last follow up, a mean of 10.9 years from diagnosis. Twenty-three surviving patients have functional vision in at least one eye, 12 require no endocrine replacement, and 16 are in or have completed schooling with regular academic requirements. If radical surgery is to become standard care for children with low-grade astrocytomas of the hypothalamic/chiasmatic region, long-term survival and functional outcome will have to equal or surpass those of historical controls who were treated conservatively.

scholarly journals Management and outcome of Ebstein's anomaly in children

2012 ◽  
Vol 23 (1) ◽  
pp. 27-34 ◽  
Author(s):  
Angela Oxenius ◽  
Christine H. Attenhofer Jost ◽  
René Prêtre ◽  
Hitendu Dave ◽  
Urs Bauersfeld ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Operative Mortality ◽  
Ebstein’S Anomaly ◽  
Tertiary Institution ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Ebstein's Anomaly ◽  
Included Patient

AbstractObjectivesTo assess clinical presentation, treatment, and outcome of children with Ebstein's anomaly.BackgroundData on long-term outcome of children with Ebstein's anomaly are scarce.MethodsRetrospective analysis of all children with Ebstein's anomaly treated between February, 1979 and January, 2009 in a single tertiary institution. Primary outcomes included patient survival and need for intervention, either cardiac surgery or catheter intervention.ResultsA total of 42 patients were diagnosed with Ebstein's anomaly at a median age of 5 days ranging from 1 day to 11.7 years. Symptoms included cyanosis, heart murmur, and/or dyspnoea. Associated cardiac anomalies occurred in 90% of the patients. Average follow-up was 9.5 plus or minus 7.0 years. The overall mortality rate was 14%. Of the six patients, three died postnatally before treatment. Cardiac surgery and/or catheter-guided interventions were required in 33 patients (79%). Cardiac surgery was performed in 21 (50%) patients at a median age of 9.1 years (range 0.1–16.5 years), including biventricular repair in 13 (62%), one-and-a-half chamber repair in seven (33%), and a staged single-ventricle repair in one. Peri-operative mortality was 4%. Catheter-guided interventions consisted of device closure of an atrial septal defect in three cases and radiofrequency ablation of accessory pathways in nine patients. The estimated 10-year survival was 85.3 plus or minus 5.6%.ConclusionIn children, Ebstein's anomaly is usually diagnosed in the first year of age. Even though children with Ebstein's anomaly often require an intervention, their peri-operative mortality is low and long-term survival is good. Symptomatic newborns requiring an intervention may have a worse outcome.

Surgical resection of pulmonary inflammatory pseudotumors: long-term outcome

2017 ◽  
Vol 25 (6) ◽  
pp. 440-445 ◽  
Author(s):  
Marine Peretti ◽  
Dana M Radu ◽  
Karel Pfeuty ◽  
Antoine Dujon ◽  
Marc Riquet ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Survival Rates ◽  
R0 Resection ◽  
Term Outcome ◽  
Term Survival ◽  
Long Term Outcome ◽  
Long Term Survival ◽  
Inflammatory Pseudotumors

Background Pulmonary inflammatory pseudotumors are rare lesions that remain problematic in several aspects, especially regarding the therapeutic strategy. The goal of this study was to evaluate long-term survival in a multicenter series of patients who required surgery for pulmonary inflammatory pseudotumors. Methods Thirty-six cases of pulmonary inflammatory pseudotumors, operated on in 3 French thoracic surgery departments between 1989 and 2015, were studied retrospectively. We recorded pre-, peri- and postoperative data for each patient, and long-term survival was analyzed. Results There were 22 men and 14 women. Mean age was 53.5 years (range 14–81 years). Three pneumonectomies, 1 bilobectomy, 19 lobectomies, 2 segmentectomies, 10 wedge resections, and 1 biopsy were performed. Complete resection was carried out in 32 (88.8%) patients. Median follow-up was 76 months. Five-year and 10-year survival rates were respectively 86.8% and 81.7% (96% and 90% for patients with R0 resection). Conclusions Long-term survival was excellent for patients with pulmonary inflammatory pseudotumors who benefited from surgery, especially when surgical resection was complete. These results confirm that surgical resection must be proposed as the first-line treatment for patients with pulmonary inflammatory pseudotumors.

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