First Infection with Absidia Corymbifera in a CLL Patient - Ibrutinib As Risk Factor?

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 38-38
Author(s):  
Matthes Marquardt ◽  
Maren Thiel ◽  
Silke Kerl ◽  
Michael Wöhlke ◽  
Katrin Gröpler ◽  
...  
Keyword(s):  
Risk Factor ◽  
Clinical Outcome ◽  
Patient Group ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Left Kidney ◽  
Significant Risk ◽  
Invasive Infection ◽  
Normal Range ◽  
Absidia Corymbifera

Introduction Targeted therapy as ibrutinib, alone or in combination, is the new standard of care in CLL and has improved the clinical outcome. However, the rate of infectious side effects in the "real world" is still under debate. Several retrospective trials have observed a significant risk of invasive fungal infections (IFD) in this patient group, mostly caused by Aspergillus sp., Cryptococcus sp. or Pneumocystisjiroveci and often occurring early after initiation of the drug. Here we report the first case of an invasive infection with Absidia corymbifera, a member of the zygomyces group, in a CLL patient. The life-threatening infection occurred six years after initiation of ibrutinib treatment infiltrating and destroying the left kidney. Invasive infections with Absidia corymbifera are extremely rare and mostly reported from patients with acute leukemia or severe immunosuppression after organ transplantation. This species is not sensitive to echinoncandins and azoles with the exception of posaconazol. Thus, uncommon IFD has to be suggested in patients treated with ibrutinib treatment and invasive diagnostics should be performed early. Patient characteristics The patient, a 70 years old male, was diagnosed in 2005 with B-CLL harbouring high risk cytogenetics (deletion 17p). CLL was treated since 2005 with R-CHOP, R-bendamustine and ofatumumab before ibrutinib was started in 2014. Due to secondary antibody deficiency, the patient was substituted with IVIG every 4 weeks. At the beginning of 2020 the patient suffered three weeks from cough, fever and abdominal pain before he was admitted to our ward. We found elevated CRP (362 mg/l, normal range: < 5) and procalcitonin (2.02 µg/l, normal range: < 0.5), leukocytosis dominated by CLL cells, mild neutropenia (> 1000 mm3) and an IgG level of 4 g/l (normal range: 7-16). A CT scan showed a barely vascularized tumor at the left kidney, peri-renal inflammation, atypical pneumonic infiltrates and multiple enlarged abdominal lymph nodes. Clinical outcome: The patient was initially treated with antibiosis and caspofungin without success. A fine-needle biopsy of the renal tumor was performed, where fungal structures were identified. Since a renal scintigraphy showed loss of function of the infected kidney, a nephrectomy was conducted to reduce the fungal load while the anti-mycotic treatment was changed to liposomal amphotericin B for three weeks. The molecular analysis of the infected kidney showed an infection with Absidia corymbifera. The patient recovered from fever and all other signs of infection under this treatment, so that he could be discharged after 4 weeks but oral posaconazole was given for additional 6 weeks. Conclusion: Here we report the first infection of a CLL patient with Absidia corymbifera, a germ only found in heavily immunosuppressed patients so far. However, ibrutinib should be considered as risk factor for uncommon invasive fungal infection. Thus, in all cases with fever of unknown origin in this patient group, lesions suspicious for IFD has to be carefully investigated and a biopsy should be taken to characterize the infectious agent. Treatment has to combine surgery and long-term antimycotic treatment. Disclosures No relevant conflicts of interest to declare.

Association Between Elevated Hemolysis at Diagnosis and Early Mortality and Risk of Thrombosis In Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients with Cytopenia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4241-4241 ◽  
Author(s):  
Jin Seok Kim ◽  
Jong Wook Lee ◽  
Sung-Soo Yoon ◽  
Je-Hwan Lee ◽  
Deog-Yeon Jo ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Risk Factor ◽  
Abdominal Pain ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Poor Quality ◽  
Severe Fatigue ◽  
Life Threatening

Abstract Abstract 4241 Introduction: PNH is a rare, progressive and life threatening disease driven by chronic hemolysis leading to thrombosis, renal impairment, pain, severe fatigue, poor quality of life and premature death. Thrombosis is the leading cause of death (accounting for 40–67% of PNH-related deaths) and was recently identified as a significant risk factor for mortality in Asian PNH patients. Abdominal pain is a common and distressing symptom in PNH and has also been found to be risk factor for thrombosis and mortality in PNH patients. In PNH patients with concomitant aplasia/cytopenias (PNH-cytopenia), the symptoms associated with hemolytic PNH (i.e., severe fatigue and anemia) may be attributed to a hypocellular marrow, potentially masking the life threatening risk of hemolysis-mediated thrombosis and abdominal pain. Here we evaluate the correlation of clinical risk factors with hemolytic symptoms in cytopenic PNH patients. Methods: We retrospectively analyzed medical charts of 286 PNH patients from the National Data Registry in South Korea to identify aplastic PNH patients with evidence of hemolytic symptoms at the time of diagnosis. We defined PNH-cytopenia patients with evidence of at least 2 of the following hematological values at diagnosis: Hgb <10 g/dL; ANC <1.5×109/L; thrombocytopenia <100×109/L. Hemolysis was defined as LDH °Ã1.5 fold above the upper limit of normal (ULN). Results: The median patient age was 37 years (range: 8 to 88 years) and median PNH duration was 7.8 years. At diagnosis, median PNH granulocyte clone was 49% and LDH was 3.9-fold above ULN. Median platelet count was 99×109/L and median ANC was 1.2×109/L, 21% with ANC <1.0×109/L. PNH-cytopenia was identified at diagnosis in 42% of PNH patients. PNH-cytopenic patients experienced a similar prevalence of hemolytic symptoms and mortality compared to PNH patients with no evidence of cytopenia (PNH) (see table below). Thrombosis was equally prevalent in PNH-cytopenia compared to PNH (12% vs18%; P=0.175). Abdominal pain was equally prevalent in PNH-cytopenia and PNH (52% vs 42%; P=0.112) and there was similar mortality between the 2 groups (13% vs 11%; P=0.631). There was a significantly higher prevalence of mortality (14% vs 4%; p=0.048), thrombosis (22% vs 4%; p=0.003) and abdominal pain (53% vs 32%; p=0.007) in patients with elevated hemolysis (°Ã LDH 1.5 above ULN) compared to patients without hemolysis. We found that 69% of PNH-cytopenia patients demonstrated elevated hemolysis at diagnosis. Thrombosis was identified in 17% of PNH-cytopenia patients with elevated hemolysis compared to 3% with no evidence of elevated LDH (p=0.051); abdominal pain (59% vs 32%; p= 0.012) and death (16% vs 3%; p=0.070) were higher in PNH-cytopenia patients with hemolysis compared to PNH-cytopenia patients without hemolysis. CONCULSION: These data demonstrate that the presence of hemolysis at diagnosis is associated with of life-threatening thrombosis, poor quality of life, and mortality in PNH patients. Despite the evidence of hypoplasia, PNH-cytopenia patients with hemolysis demonstrate a higher risk of life-threatening thrombosis, pain, and mortality. These data indicate that hemolysis is a potential risk factor for life- threatening complications independent of the presence of cytopenia in patients with PNH. Treatment for PNH patients with cytopenias should focus on both controlling hemolysis as well as improving hypoplasia. Disclosures: No relevant conflicts of interest to declare.

Activity of a Heptad of Transcription Factors Is Associated with Stem Cell Programs and Clinical Outcome in Acute Myeloid Leukaemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3525-3525
Author(s):  
Eva Diffner ◽  
Dominik Beck ◽  
Emma Gudgin ◽  
Julie Thoms ◽  
Kathy Knezevic ◽  
...  
Keyword(s):  
Risk Factor ◽  
Stem Cell ◽  
Transcription Factors ◽  
Clinical Outcome ◽  
Hematopoietic Stem Cell ◽  
Conflicts Of Interest ◽  
Leukemic Cells ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Acute Myeloid

Abstract Abstract 3525 Leukaemic transformation is driven by aberrant transcriptional programs often in combination with abnormal proliferative signalling. These programs operate in normal hematopoiesis where they are involved in hematopoietic stem cell (HSC) proliferation and maintenance. ERG is a component of normal and leukemic stem cell signatures and high ERG expression has been proposed as a risk factor for poor prognosis in acute myeloid leukemia (AML). However, mechanisms that underlie ERG expression in AML and how its expression relates to leukemic stemness are unknown. We report that ERG expression in AML is associated with activity of the ERG+85 stem cell enhancer (SCE) and a heptad of transcription factors that combinatorially regulate genes in normal HSCs. Gene expression signatures derived from ERG+85 stem cell enhancer (Fig A) and heptad activity (Fig B) predict clinical outcome in a cytogenetically normal cohort of AML (CN-AML) patients when ERG expression alone fails. The heptad signature is an independent risk factor for poor overall and event-free survival (Fig C). There were no long-term survivors amongst patients with a heptad signature, FLT3 mutations and wild-type NPM1 (Fig D) pointing to a hitherto unappreciated link between aberrant signaling and transcriptional mediators of hematopoietic stem cell identity. In two independent cohorts, the heptad signature was as closely associated with wild-type NPM1 AML as the HOX signature was with mutant NPM1 AML (Fig E–F) suggestive of a collective role for these transcription factors in mediating the leukemic signature in the former. Taken together, these results show that key transcriptional regulators cooperate in establishing stem cell signatures in leukemic cells and that the underlying spectrum of somatic mutations contributes to the development of these signatures and modulate their influence on clinical outcome. Disclosures: No relevant conflicts of interest to declare.

Title: Pretreatment ADAMTS13 Activity Predicts Clinical Outcome in Patients with Acquired Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2224-2224
Author(s):  
Spero R Cataland ◽  
Susan Geyer ◽  
Shangbin Yang ◽  
Haifeng Wu
Keyword(s):  
Clinical Outcome ◽  
Roc Analysis ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Laboratory Data ◽  
Significant Risk ◽  
Optimal Threshold ◽  
Suppressive Therapy ◽  
Adamts13 Activity ◽  
Increased Risk

Abstract Abstract 2224 Background: Acquired TTP is characterized by a significant risk for exacerbation (recurrent TTP within 30 days of last plasma exchange (PEX)). An algorithm applied early in the course of treatment that detects patients at increased risk for exacerbation could identify patients most likely to benefit from more intensive upfront therapy (PEX, immune-suppressive therapy) to prevent recurrence of disease after tapering PEX. We have previously reported in a small cohort study that pretreatment ADAMTS13 activity was significantly lower (0.8% v. 1.4%) in patients suffering an exacerbation, but the difference was primarily mediated by race (EJH 2009 Dec 1;83(6):559–64). We performed a study to analyze data from a large cohort of TTP patients to assess the potential prognostic utility of pretreatment ADAMTS13 activity for risk of exacerbation. Patients: Patients presenting with a clinical diagnosis of acquired TTP (platelets < 100K/uL, microangiopathic hemolytic anemia) between May 2002 and August 2010 with pretreatment ADAMTS13 activity data (86 acute TTP episodes from 49 patients evaluable for exacerbation, and 94 episodes for other factors associated with ADAMTS13 activity) were included in these analyses. Methods: Demographic and laboratory data obtained prior to starting PEX in patients with acute TTP were analyzed retrospectively to determine their relationship to early recurrences (exacerbation) of TTP. Based on these data, ROC analysis and recursive partitioning algorithms were used to determine an optimal cutoff of pretreatment ADAMTS13 activity that was prognostic for exacerbation of TTP. Subsequently, the acute TTP episodes with pretreatment ADAMTS13 <1.15% were compared to the cohort with ADAMTS13 >1.15% with respect to clinical outcomes and presenting clinical symptoms and laboratory data. Impact of these factors on exacerbation were also analyzed using generalized estimating equation models to account for multiple episodes from the same patients. Results: Overall, there were 22 exacerbation events observed in the 86 TTP episodes. There were no significant differences between subjects that suffered an exacerbation in terms of clinical laboratory data (platelet count, LDH, creatinine) at presentation. However, mean ADAMTS13 activity at presentation was significantly lower in patients that suffered exacerbations compared to those that did not [1.4% (0.5 –7.2) v. 2.9% (0.5–13.3); p=0.002]. ROC analysis of all study subjects indicated that the optimal threshold for pretreatment ADAMTS13 activity to predict the risk of exacerbation is 1.15%, which provides a test sensitivity of 64% and specificity of 62%. Subset analyses also defined the optimal threshold for AA and female populations to predict an increased risk of relapse to be 2% for both groups, giving rise to a sensitivity of 100% (AA)/82%(F) and specificity of 42% (AA)/50% (F), respectively. When using an ADAMTS13 activity threshold of 1.15% to risk stratify for increased risk for exacerbation, there were no significant differences in presenting clinical symptoms and laboratory values (Table 1). However, subjects with pretreatment ADAMTS13 activity <1.15% were more likely to suffer an exacerbation and require a greater number of PEX procedures to achieve a clinical response (platelets >150 K/uL). Conclusions: These data are among the first to suggest pretreatment ADAMTS13 activity may predict clinical outcome from an acute episode of TTP. The optimal ADAMTS13 activity threshold was 1.15%, with ADAMTS13 activity below this level being associated with an increased risk for exacerbation. Furthermore, incorporating this threshold of ADAMTS13 activity into a model with race and gender will significantly improve risk stratification and identify patients at greatest risk for early treatment failure who may be more likely to benefit from the early addition of immune-based therapy to PEX. Disclosures: No relevant conflicts of interest to declare.

Invasive Fungal Infections in Adults with Newly Diagnosed AML Undergoing Intensive Chemotherapy: Characterization, Risk Factors, and Outcomes in a Single Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4254-4254
Author(s):  
Kit Lu ◽  
Dionissios Neofytos ◽  
Amanda Blackford ◽  
Amy Seung ◽  
Judith E. Karp
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Significant Risk ◽  
Invasive Fungal Infections ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
European Organization

Abstract Abstract 4254 Background: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML) undergoing chemotherapy treatment. However, the epidemiology, risk factors, and outcomes of IFI in these patients have been poorly described. Methods: A single-center retrospective analysis was performed to study the epidemiology, risk factors, clinical outcomes, and mortality predictors of IFIs in AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST) between January 2005 and June 2010. Newly diagnosed AML patients, with exception of acute promyelocytic leukemia, were studied. IFIs were defined using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Results: 254 consecutive patients (57% male; median age 54, range 20–78) were analyzed. 123 (48%) of patients had an IFI; of which, 15 patients (12%) had a proven candidal infection, and 108 patients (88%) had a mould infection (5 proven/probable (5%) and 103 (95%) possible mould infections). 237 (93%) patients received antifungal therapy during their treatment course (median day 8, range day -15 to 30). Of those, 63 (27%) received monotherapy (46% liposomal amphotericin, 44% voriconazole) and the rest received multiple antifungal agents. Significant risk factors and trends for developing +IFI shown from univariate analyses are listed in Table 1. Prolonged neutropenia, duration of mucositis, and concurrent bacterial infections did not significantly affect the development of +IFI. Using multivariate analyses, mortality was impacted by patients’ baseline organ function (p=0.002 [1.3,3.1]), specifically, by bilirubin < 2 mg/dL (p=0.003 [1.38,4.57]) and creatinine < 1.5 mg/dL (p=0.01 [1.23,5.4]). Patients with +IFI did not significantly impact overall survival. However, patients with candidal IFIs had a significantly lower overall survival compared to patients with mould IFIs and no IFI (HR 2.01 [1.06, 3.8]) (Figure 1). Candida colonization prior to or during the first week of chemotherapy, and development of mucositis were associated with the development of candidal IFIs (p=0.07). Conclusion: IFIs, particularly mould infections, remain a significant problem in patients with AML. Although overall survival did not appear to be significantly affected by mould infections, patients with candidal infections were more likely to die. Identification of risk factors for each type of IFIs may help to develop effective targeted preventive antifungal strategies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical outcome and risk factor predictive for failure of autologous PRP injections for low-to-moderate knee osteoarthritis

2021 ◽  
Vol 29 (2) ◽  
pp. 230949902110219
Author(s):  
Mattia Alessio-Mazzola ◽  
Stefano Lovisolo ◽  
Beatrice Sonzogni ◽  
Andrea Giorgio Capello ◽  
Ilaria Repetto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Clinical Outcome ◽  
Knee Osteoarthritis ◽  
Significant Risk ◽  
Lower Grade ◽  
Knee Oa ◽  
Significant Independent Risk Factor ◽  
Grade 3

Purpose: To report the 5-year clinical efficacy of PRP intra articular injections in knee osteoarthritis (OA) and to investigate the risk factors predictive for treatment failure and poor clinical outcome. Methods: We retrospectively evaluated 118 patients treated for low to moderate knee OA demonstrated by X-Ray and magnetic resonance imaging (MRI) with autologous PRP injection from 2014 to 2018 with a mean 51.1 ± 14.8 (range 29 to 89) months follow-up. All the patients were evaluated with Lysholm and WOMAC score. The role of Kellgren Lawrence (KL) grade, patello-femoral (PF) degeneration, age, body mass index (BMI), relevant comorbilities, smoking status, gender, previous surgery or conservative measures were analyzed with univariate and multivariate analysis. Results: There was a significant improvement of all outcome measures at final follow-up and high satisfaction rate (79.7%). The overall failure rate was of 15.3% after a mean of 57.7 ± 15.1 (range 33 to 85) months. The BMI and the KL grade were identified as significant independent risk factor related to failure of autologous PRP injection. Patients under 60 reported significantly higher Tegner activity scale ( p = 0.032) at final follow-up. Patients with KL grade 3 and patients with PF MRI-KL grade 3 had significantly lower Lysholm scores ( p = 0.026 and p = 0.042 respectively) at final assessment. Younger patients with lower BMI and lower grade of radiographic OA had significantly longer therapeutic benefit ( p < 0.05). Conclusion: Intra articular PRP injections led to a significant clinical improvement in middle-aged adults with a low to moderate knee OA. BMI and high KL grade have been identified as significant risk factors predictive for failure at mid-term follow-up.

scholarly journals Intensive Chemotherapy for High-Risk ALL in Children - the Nordic Collaborative Approach

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 742-742
Author(s):  
Atte Nikkilä ◽  
Olli Lohi ◽  
Ólafur Gísli Jónsson ◽  
Bendik Lund ◽  
Jonas Abrahamsson ◽  
...  
Keyword(s):  
High Risk ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Fungal Infections ◽  
Cell Lineage ◽  
Significant Risk ◽  
Study Cohort ◽  
Cox Models ◽  
Childhood All ◽  
Entire Cohort

OS for childhood ALL is now &gt;90%, but high-risk (HR) cases still need to improve. The NOPHO ALL2008 protocol restricted very intensive HR chemotherapy to patients with an inferior early minimal residual disease (MRD) response or HR genetics, and we here report the results for this subset. HR patients had WBC &gt;100K at diagnosis and/or T-ALL; and an MRD of either &gt;25% day 15 or &gt;0.1% day 29; and/or a KMT2A-re or hypodiploidy (&lt;45 chr). MRD was assessed by flow cytometry (BCP) or PCR (T-ALL). If no marker was found with one, the alternative method was used. Thus, &gt;98% had a suitable MRD marker. All HR patients received a 3-drug induction chemotherapy (VCR 2 mg/m2 x5), DOX (40 mg/m2 x2), PRED (60 mg/m2/d for 4 weeks for BCP-ALL with WBC &lt;100K) or DEXA (10 mg/m2/d for 3 weeks for all others). This was followed by 9 (A1-B1-C1-A2-B2-C2-A3-B3-C3) or 7 (if MRD after 1st HR block &lt;0.1%; C2/C3 deleted) blocks, 60 weeks of interim maintenance with oral 6MP/MTX and HD-MTX x3 (5g/m2/d), delayed intensification, and maintenance therapy until a total of 2.5 years from diagnosis. Post-induction, a total of 12 doses of i.m. Peg-asp (1,000 IU/m2) was given (Toft, Leukemia 2018). A-blocks included cyclophosphamide (440 mg/m2/d x5), etoposide (100 mg/m2/d x5), and Peg-asp (1000 IU/m2). B-blocks consisted of HD-MTX (5g/m2), HD-AraC (2x2g/m2 /d x2), 6MP (100 mg/m2/d x5), DEXA (20 mg/m2/d x5), VCR (2 mg/m2 x2), Peg-asp (1000 IU/m2). C-blocks included idarubicin (8 mg/m2), fludarabine (30 mg/m2/d x5), HD-AraC (2g/m2 /d x5), Peg-asp (1000 IU/m2). Patients were allocated to hSCT if MRD &gt;5% at end of induction, or &gt;0.1% after 2 HR-blocks or ~3 months of LR-chemotherapy. HSCT-patients are not included here. Data on 18 toxic adverse events was prospectively collected at three-month intervals. The Kaplan-Meier method was used for OS and EFS analyses. CI of Rel (CIR) and TRM (CITRM) were estimated accounting for competing events. Cox-models were used to compute hazard ratios and proportional hazard assumptions were evaluated using Schoenfeld residuals. 132 subjects 1-≤18 years of age at diagnosis were eligible for HR chemotherapy accounting for 16% of the study cohort with a median age of 6.6 years as compared to 4.6 years in the entire cohort. Of the HR chemotherapy subjects 26% received PRED in induction. Five-year EFS was 67% (95% CI, 59-76%) and OS was 74% (95% CI, 67-82%) in the HR chemo cohort. CIR at five years was 18% (95% CI, 11-24%). We found no difference in EFS by cell lineage (BCP-ALL: 69%, 95% CI, 59-80% vs. T-ALL 65%, 95% CI 52-77%). KMT2A-re occurred in 34 patients, 62% of whom had MRD &lt;0.1% after induction. Their five-year EFS and OS were 88% (95% CI, 77-99%). KMT2A-re patients with a leukocyte count &lt;100K and EOI MRD &lt;0.1% had no relapses, but toxic deaths resulting in a 5-year EFS of 80% (95% CI, 55-100%). Hypodiploid patients had a five-year EFS and OS of 55% (95% CI, 34%-76%) and 58% (95% CI, 39-78%), respectively. Strikingly, KMT2A-re and hypodiploid patients with a negative MRD at EOI, suffered no relapses. 29 patients shifted to HR-blocks at day 15 due to MRD &gt;25% (T-ALL (N=17), BCP with WBC &gt;100K (N=7), KMT2A-re (N=4), or hypodiploid ALL (N=1). Their five-year EFS was 47% (95% CI, 21-73%) and CIR 44% (95% CI, 18-70%). During the HR chemotherapy blocks, 70% (N=93) of patients encountered at least one toxic event beyond bacteremia and febrile neutropenia, the most common of which was fungal infections (25%), referral to intensive care (23%), and asparaginase associated anaphylaxis (21%). The NOPHO ALL2008 stratification strategy led to allocation of 16% of patients to the HR arm with an EFS of 67% and OS of 74%. Due to the intensity of chemotherapy a significant risk of toxic death was encountered, and the risks of toxic death and relapse were very similar. Patients with rearranged KMT2A and a low EOI MRD could be candidates for future reduction of treatment intensity. These findings are integrated into the upcoming European ALLTogether1 protocol opening in 14 European countries early 2020, where the use of the NOPHO ALL2008 HR blocks will be restricted to the 3% of patients with the poorest prognosis. Figure - EFS with 95% Cis, CITRM (short dash) and CIR (long dash) for the NOPHO ALL-2008 high-risk chemotherapy patients Disclosures No relevant conflicts of interest to declare.

Physical Illness and Suicide Risk in Rural Residents of Contemporary China

Crisis ◽  
2014 ◽  
Vol 35 (5) ◽  
pp. 330-337 ◽  
Author(s):  
Cun-Xian Jia ◽  
Lin-Lin Wang ◽  
Ai-Qiang Xu ◽  
Ai-Ying Dai ◽  
Ping Qin
Keyword(s):  
Risk Factor ◽  
Family Income ◽  
Rural China ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Health Condition ◽  
Physical Illness ◽  
Rural Residents ◽  
Increased Risk ◽  
Study Population

Background: Physical illness is linked with an increased risk of suicide; however, evidence from China is limited. Aims: To assess the influence of physical illness on risk of suicide among rural residents of China, and to examine the differences in the characteristics of people completing suicide with physical illness from those without physical illness. Method: In all, 200 suicide cases and 200 control subjects, 1:1 pair-matched on sex and age, were included from 25 townships of three randomly selected counties in Shandong Province, China. One informant for each suicide or control subject was interviewed to collect data on the physical health condition and psychological and sociodemographic status. Results: The prevalence of physical illness in suicide cases (63.0%) was significantly higher than that in paired controls (41.0%; χ2 = 19.39, p < .001). Compared with suicide cases without physical illness, people who were physically ill and completed suicide were generally older, less educated, had lower family income, and reported a mental disorder less often. Physical illness denoted a significant risk factor for suicide with an associated odds ratio of 3.23 (95% CI: 1.85–5.62) after adjusted for important covariates. The elevated risk of suicide increased progressively with the number of comorbid illnesses. Cancer, stroke, and a group of illnesses comprising dementia, hemiplegia, and encephalatrophy had a particularly strong effect among the commonly reported diagnoses in this study population. Conclusion: Physical illness is an important risk factor for suicide in rural residents of China. Efforts for suicide prevention are needed and should be integrated with national strategies of health care in rural China.

scholarly journals Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ting-Chun Huang ◽  
Po-Tseng Lee ◽  
Mu-Shiang Huang ◽  
Pei-Fang Su ◽  
Ping-Yen Liu
Keyword(s):  
Risk Factor ◽  
Dose Response ◽  
Cox Model ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Cardiovascular Death ◽  
Specific Model ◽  
Distribution Model ◽  
All Cause Mortality ◽  
Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

scholarly journals Serum syndecan-1 reflects organ dysfunction in critically ill patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Keiko Suzuki ◽  
Hideshi Okada ◽  
Kazuyuki Sumi ◽  
Hiroyuki Tomita ◽  
Ryo Kobayashi ◽  
...  
Keyword(s):  
Risk Factor ◽  
Critically Ill ◽  
Organ Dysfunction ◽  
Critically Ill Patients ◽  
Repeated Measures ◽  
Significant Risk ◽  
Mixed Effects ◽  
Mixed Effects Models ◽  
Endothelial Glycocalyx ◽  
Outcome Variable

AbstractSyndecan-1 (SDC-1) is found in the endothelial glycocalyx and shed into the blood during systemic inflammatory conditions. We investigated organ dysfunction associated with changing serum SDC-1 levels for early detection of organ dysfunction in critically ill patients. To evaluate the effect of SDC-1 on laboratory parameters measured the day after SDC-1 measurement with consideration for repeated measures, linear mixed effects models were constructed with each parameter as an outcome variable. A total of 94 patients were enrolled, and 831 samples were obtained. Analysis using mixed effects models for repeated measures with adjustment for age and sex showed that serum SDC-1 levels measured the day before significantly affected several outcomes, including aspartate aminotransferase (AST), alanine transaminase (ALT), creatinine (CRE), blood urea nitrogen (BUN), antithrombin III, fibrin degradation products, and D-dimer. Moreover, serum SDC-1 levels of the prior day significantly modified the effect between time and several outcomes, including AST, ALT, CRE, and BUN. Additionally, increasing serum SDC-1 level was a significant risk factor for mortality. Serum SDC-1 may be a useful biomarker for daily monitoring to detect early signs of kidney, liver and coagulation system dysfunction, and may be an important risk factor for mortality in critically ill patients.

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