Significant Difference In Survival Time Research Articles

The value of tracheostomy of critically ill COVID-19 patients - A multicentral study

PurposeTracheostomy is an aerosol-generating procedure, thus performing it during the COVID-19 pandemic arises considerations such as the most appropriate timing and the patients to whom it is suitable. Medical teams lack sufficient data to assist determining whether or not to conduct tracheostomy, its short- and long-term implications are not fully understood. This study aims to shed light on the critically ill COVID-19 patients that require tracheostomy, and to investigate its value. MethodsA retrospective multicentral case-control study of 157 hospitalized critically ill COVID-19 patients, among whom 30 patients went through tracheostomy and consisted of our study group. ResultsThe mean age was similar between study and control groups (68.9 ± 12.7 years vs 70.5 ± 15.8 years, p = 0.57), as well as comorbidity prevalence (56.7% vs 67.7%, p = 0.25). Patients in the study group were hospitalized for longer duration until defined critically ill (5 ± 4.3 vs 3 ± 3.9 days; p = 0.01), until admitted to the intensive care unit (6 ± 6.6 vs 2.5 ± 3.7 days respectively; p = 0.005), and until discharged (24 ± 9.7 vs 10.7 ± 9.1 days, p < 0.001). Mortality rate was lower in the study group (30% vs 59.8%, p = 0.003). Kaplan Meier survival analysis revealed a statistically significant difference in survival time between groups (Log rank chi-sq = 20.91, p < 0.001) with mean survival time of 41 ± 3.1 days vs 21 ± 2.2 days. Survival was significantly longer in the study group (OR = 0.37, p = 0.004). ConclusionTracheostomy allows for more prolonged survival for gradually deteriorating critically ill COVID-19 patients. This should be integrated into the medical teams' considerations when debating whether or not to conduct tracheostomy.

Canine Non-Angiogenic, Non-Myogenic Splenic Stromal Sarcoma: a Retrospective Clinicopathological Analysis and Investigation of Podoplanin as a Marker of Tumour Histogenesis

Splenic stromal sarcomas are rarely reported tumours that were previously grouped as non-angiomatous, non-lymphomatous mesenchymal neoplasms of the canine spleen. Highly variable survival times have been reported probably due to their heterogeneous nature. The purpose of this study was to assess the outcome and prognostic factors in dogs with splenic stromal sarcoma after treatment by splenectomy. Clinical data were collected retrospectively and histopathology was reviewed for 47 patients. Histological classification, based on morphology in haematoxylin and eosin-stained sections, in conjunction with immunolabelling of macrophage scavenger receptor-A (CD204), desmin, factor VIII-related antigen and smooth muscle actin ,yielded diagnoses of undifferentiated stromal sarcoma (n=22), complex nodular hyperplasia (CNH, n=9), sarcoma arising from benign complex nodular hyperplasia (n=3), histiocytic sarcoma (n=3), haemangiosarcoma (n=1) and leiomyosarcoma (n=1). Four samples were excluded from analysis due to extensive necrosis. An anti-podoplanin (PDPN) antibody was validated on canine tissue and used to assess expression of this protein as a potential indicator of the tissue of origin of the neoplasms (28/42 tumours were positive). There was a statistically significant difference in survival time between patients with stromal sarcoma (sarcoma from benign CNH and undifferentiated stromal sarcoma) and CNH (178d versus 637d, respectively; P=0.027). Dogs with stromal sarcomas and high mitotic count (≥9 per 10 high-power fields) had a significantly shorter survival time (67d versus 439d; P=0.01). Clinical diagnosis of splenic tumours should include evaluation for the presence of benign nodular hyperplasia morphology and immunohistochemistry to exclude more aggressive malignancies where adjuvant therapy is recommended. As in humans, PDPN may be an effective marker for stromal sarcomas of the canine spleen and immunopositivity suggests a fibroblastic reticular or follicular dendritic cell origin.

Prognosis of amyotrophic lateral sclerosis with cognitive and behavioural changes based on a sixty-month longitudinal follow-up.

Approximately 50% of amyotrophic lateral sclerosis (ALS) patients have cognitive and behavioural dysfunction in varying degrees and forms. Previous studies have shown that cognitive and behavioural changes may indicate a poor prognosis, and cognitive function gradually deteriorates over the course of disease, but the results of different studies have been inconsistent. In addition, there are relatively limited long-term follow-up studies tracking death as an endpoint. The purpose of this study was to investigate the clinical prognostic characteristics of ALS patients with cognitive behavioural changes through long-term follow-up in a cohort. A total of 87 ALS patients from 2014 to 2015 in the Third Hospital of Peking University were selected and divided into a pure ALS group, an ALS with behavioural variant of frontotemporal dementia (ALS-bvFTD) group, and an ALS with cognitive and behaviour changes group. All patients were followed up for 60 months. The main end point was death and tracheotomy. There was no significant difference in survival curve between pure ALS and ALS with cognitive and behavioural change group, but the survival time of ALS-bvFTD group was significantly lower than the other two groups (P < 0.001). For those who was followed up to the endpoint, the survival time of the ALS-bvFTD group was significantly shorter than that of the pure ALS group (t = 5.33, p < 0.001) or the ALS with cognitive and behaviour changes group (t = 4.25, p < 0.001). The progression rate of ALS Functional Rating Scale-Revised (FRS-R) scores from recruitment to endpoint was significantly faster in the ALS-bvFTD group than in the pure ALS group (z = 2.68, p = 0.01) or the ALS with cognitive and behavioural changes group (z = 2.75, p = 0.01). There was no significant difference in survival time (t = 0.52, P = 0.60) or FRS-R score progression rate (z = 0.31, p = 0.76) between the pure ALS group and the ALS with cognitive and behavioural changes group. The total Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) score was positively correlated with survival time (r = 0.38, p = 0.01). ALS-bvFTD patients have shorter survival time. The total ECAS score may be correlated with survival time.

Prognostic Value of Palliative Prognostic Index for Hospitalized Patients With End-of-Life Hematologic Malignancies in a Japanese University Hospital.

Uncertainty of prognosis is one reason patients with hematologic malignancies receive aggressive therapy near end of life more often than those with advanced solid tumors. It is unknown whether end-of-life prognosis prediction models are useful for patients with hematologic malignancies, especially hospitalized patients receiving chemotherapy, because most prognostic models were developed for patients with solid tumors. The purpose of this study was to evaluate the prognostic accuracy of the Palliative Prognostic Index (PPI) for end-of-life patients with advanced hematologic malignancies. We retrospectively reviewed the records of 143 patients who became resistant to standard chemotherapy and died of disease progression in our university hospital hematology ward between May 2015 and November 2019. Patients were classified according to PPI scores (groups: A, PPI ≤ 2.0; B, 2.0 < PPI ≤ 4.0; and C, PPI > 4.0) based on their clinical charts at admission. The median overall survival for each patient (95% confidence interval) was calculated using the Kaplan-Meier method. Log-rank tests were used to determine significant differences between survival curves. Median patient age was 76 years (range: 39-92 years), and 59% were men. Median overall survival times in the PPI groups A, B, and C were 58 days, 36 days, and 10 days, respectively. Statistically significant differences in survival time were observed between the groups (P < .01); prediction accuracy was similar to that for patients with different diagnoses. The usefulness of PPI was validated for near-end-of-life hospitalized patients with hematologic malignancies.

MO179ACUTE KIDNEY INJURY IN ELDERLY- PROGNOSTIC VALUES OF COMORBIDITY AND THE AGE FOR THE SHORT AND THE LONG TERM OUTCOME

Abstract Background and Aims Acute kidney injury (AKI) is defined by a rapid decline in glomerular filtration rate (GFR), resulting in disturbance of renal physiological functions including impairment of nitrogenous waste product excretion, loss of water and electrolyte regulation and loss of acid-base regulation. Coexisting disease and the structural and functional changes that occur during the aging process are disposing factors that increase the risk of AKI in elderly population. Method 101 elderly patients (≥ 65) who filling out one of the criteria of definition of AKI according to Kidney Disease Improving Global Outcome (KDIGO), were included in the study. Patients were divided into 2 groups by age, group &amp;lt;75 and group&amp;gt; 75 years old. In terms of outcome they were divided in group with short and 90-day survival. The burden of the simultaneous presence of comorbid conditions was estimated through the Charles Comorbid Index. (CHI) Results The mortality rate for the 90-day follow-up period after the AKI event was 45.5%. The intra-hospital mortality rate in adult patients with AKI was 22.8%.In our study the age was not confirmed as a risk factor for intra-hospital and 3-month outcome in elderly patients with AKI. The presence of comorbid conditions estimated through the Charles Comorbid Index (CHI), differed un-significantly between survivors and deceased patients with AKI (p = 0.39, p = 0.28 consecutive). Cox regression analysis confirmed the CCI score as a significant factor in survival in patients with ABO. (p = 0.036).The risk of letal outcome increases by 16.3% with each increase in this unit score. Cox regression analysis confirmed heart diseases as a significant prognostic factor for survival, increasing the risk of fatal outcome by about 2 times higher than patients without heart disease. Statistical analysis showed a significant difference in survival time, depending on the presence of heart disease as a comorbidity (p =0.037). Conducted Cox regression analysis showed that HR - for heart disease, as a comorbidity, is 1.837 95% CI (1.020 - 3.306) and p = 0.043. The death rate for patients with heart disease is about 2 times higher than patients without heart disease. Cumulative survival was higher in the group of patients without cardiomyopathy - 64.2% (0.07) compared to the group of patients with cardiomyopathy- 43.8% (0.07). Multivariate Cox regression analysis as significant independent predictors of survival in patients with ABO confirmed the diuresis (p = 0.029) and albumin (p = 0.006). Conclusion AKI survivors with high burden of comorbidities are at high risk for postdischarge death. Cardiomyopathy, as a risk factor, for two times increases the risk of death. CCI score is significant independent high-risk prognostic factors for poor outcome in elderly patients with AKI. Remain the recommendation for individual clinical approach, assessment and selection for the application of treatment taking into account the overall condition in adult patients with acute renal injury.

Surgery Treatment Improved the Overall Survival Rate in Locoregional Myxoid Leiomyosarcoma than Other Myxosarcomas in the United States.

Myxosarcomas are rare malignant tumors of soft connective tissues, classified into various subtypes, including myxoid liposarcoma, myxoid chondrosarcoma, and myxoid leiomyosarcoma. In this study, we proposed to study the demographic, tumor characteristics, and overall survival rate and compared the treatment modalities between these cancers. Patient data collected based on locoregional metastasis presentation of the abovementioned tumors with a cutoff study of survival duration up to 10 years were obtained from the SEER database during 1975-2016. Our results indicated that elderly patients and females were more in locoregional myxoid leiomyosarcoma than myxoid liposarcoma and myxoid chondrosarcoma with locoregional metastasis. The white race represented the most patients who suffered from these cancers than other races. The heart is the primary site for the abovementioned cancers, in addition to the female genitals to the myxoid leiomyosarcoma. Myxoid liposarcoma and myxoid chondrosarcoma patients with locoregional metastasis were suffering from grade II, while locoregional myxoid leiomyosarcoma patients with blank grading were due to missed data. Surgery was the most common treatment modality in this study compared with radiotherapy and chemotherapy. Kaplan-Meier analysis showed a significant difference in survival time between the three subtypes by using histology, and myxoid leiomyosarcoma showed prolonged survival than others. Elderly, female, white, unknown grade, surgery, no radiation, and no chemotherapy variables were independent factors associated with overall survival among these cancers. Multivariate analysis also showed significant differences in overall survival between the three tumors by histology, and myxoid leiomyosarcoma was with a better prognosis than others. Multivariate analysis of locoregional myxoid leiomyosarcoma showed the statistical significance of black race, grade, and radiotherapy, indicating them as independent prognostic factors of locoregional myxoid leiomyosarcoma. We conclude that surgery was the primary treatment modality against these cancers than radiotherapy and chemotherapy. And the locoregional myxoid leiomyosarcomas showed a better prognosis and higher survival rate than locoregional myxoid liposarcoma and locoregional myxoid chondrosarcoma.

Optineurin defects cause TDP43-pathology with autophagic vacuolar formation

We previously showed that optineurin (OPTN) mutations lead to the development of amyotrophic lateral sclerosis. The association between OPTN mutations and the pathogenesis of amyotrophic lateral sclerosis remains unclear. To investigate the mechanism underlying its pathogenesis, we generated Optn knockout mice. We evaluated histopathological observations of these mice and compared with those of OPTN- amyotrophic lateral sclerosis cases to investigate the mechanism underlying the pathogenesis of amyotrophic lateral sclerosis caused by OPTN mutations. The Optn (−/−) mice presented neuronal autophagic vacuoles immunopositive for charged multivesicular body protein 2b, one of the hallmarks of granulovacuolar degenerations, in the cytoplasm of spinal cord motor neurons at the age of 8 months and the OPTN- amyotrophic lateral sclerosis case with homozygous Q398X mutation. In addition, Optn (−/−) mice showed TAR-DNA binding protein 43/sequestosome1/p62 -positive cytoplasmic inclusions and the clearance of nuclear TAR-DNA binding protein 43. The axonal degeneration of the sciatic nerves was observed in Optn (−/−) mice. However, we could not observe significant differences in survival time, body weight, and motor functions, at 24 months. Our findings suggest that homozygous OPTN deletion or mutations might result in autophagic dysfunction and TAR-DNA binding protein 43 mislocalization, thereby leading to neurodegeneration of motor neurons. These findings indicate that the Optn (−/−) mice recapitulate both common and specific pathogenesis of amyotrophic lateral sclerosis associated with autophagic abnormalities. Optn (−/−) mice could serve as a mouse model for the development of therapeutic strategies.

Disease duration in autosomal dominant familial Alzheimer’s disease

AbstractBackgroundIn autosomal dominant Alzheimer’s disease (ADAD) an individual’s age at onset is significantly determined by causative mutation (Ryman et al. 2014). Determinants of disease duration are less well studied.MethodSymptomatic mutation carriers (N = 256: 201 PSEN1, 55 APP) from ADAD families referred to the Dementia Research Centre, UK, between 1987 and 2019 were included. Differences in disease duration were assessed using multilevel mixed effects Weibull survival model. We evaluated the effect of gene, sex, cognitive presentation and APOE ε4 status on disease duration and quantified the proportion of variance in disease duration and age at onset explained by mutation and family, using intra‐class correlation coefficients.ResultThere was no significant difference in survival time between genes (PSEN1: 9.7 years [SD 5.3] vs APP 11.2 [4.9], p = 0.474). In accordance with previous findings (Ryan et al., 2016), 67% of the variance in age at onset was explained by mutation and 72% by mutation and family together. In contrast, only 18% of the variability in disease duration was explained by family membership (p &lt; 0.001) and 6% by mutation (p = 0.188). Irrespective of gene, individuals born in later generations had longer survival (p = 0.003). Within the PSEN1 cohort, APOE ε4 carriers (N = 35) had 24% longer survival time compared to non‐carriers (N = 61) (12.9 years [6.7] vs 9.4 [4.7], p = 0.046, Figure 1)). No significant difference between APOE ε4 status was observed (p = 0.738) within APP. Mutations in PSEN1 exon eight included a number of individuals with particularly long disease durations (Figure 2) and the greatest prevalence of atypical symptoms. Overall, individuals with atypical presentations (N = 19) had 43% longer survival than those with amnestic presentations (N = 120) (15.5 years [7.1], vs 10.9 [5.5]; p = 0.014). There was no significant difference in survival time between sexes (p = 0.895).ConclusionOur results suggest, survival in ADAD appears longer in atypical presentations, has increased over time and is influenced by mutation but to a much lesser extent than age at onset. A deeper understanding of this variability may inform disease‐modifying trials and potentially highlight new avenues for targeting the disease.

Weight loss, phase angle, and survival in cancer patients undergoing radiotherapy: a prospective study with 10-year follow-up.

Cancer patients undergoing radiotherapy (RT) frequently experience weight loss and changes in body composition, which negatively affect their nutritional status, lead to a poor clinical prognosis, and reduce survival rates. This study aimed to evaluate whether changes in body weight, phase angle, and standardized phase angle are associated with longer survival in cancer patients undergoing RT. This prospective cohort study included 62 cancer patients who underwent RT between 2008 and 2009 and were followed until 2019. Anthropometric and bioelectrical impedance analysis data were assessed before and after RT. The Kaplan-Meier method was used to calculate survival, and mortality risk was assessed using the Cox proportional hazards model. Kaplan-Meier analysis indicated no significant difference in survival time after the 10-year follow-up between patients who had weight loss during RT and those with weight maintenance or weight gain during RT. Mortality risk was associated, in the adjusted multivariate analysis, with age (p = 0.023), site of treatment (p = 0.001), and weight loss during RT (p = 0.044). Every 1 kg lost increased the risk of death by 25% compared with patients who maintained or gained weight during RT. Changes in phase angle and standardized phase angle after RT were not associated with increased mortality risk. Weight loss during RT, site of treatment, and age are associated with a higher risk of death in cancer patients after the 10-year follow-up.

Early identification using the referral system prolonged the time to onset for hepatic encephalopathy after diagnosing severe acute liver injury

In 2004, we implemented a referral system for patients with acute liver injury (ALI) based on an established formula that estimates the risk of progression to acute live failure (ALF); however, the benefits of the system for patients with severe acute liver injury (SLI) remain unclear. We have evaluated the clinical significance of the referral system for SLI patients. Patients with ALI/SLI who were consecutively and prospectively listed on the system between 2004 and 2018 were analyzed. Of the 371 ALI/SLI/ALF patients on the system, 124 satisfied the criteria for SLI; 34 of these 124 progressed to SLI after registration. Multivariate analysis using age, sex, AST, ALT, creatinine, total bilirubin, prothrombin, presence of hepatic encephalopathy (HE), and SLI at registration revealed that HE was associated with high mortality. Among the 23 patients who developed HE, five who progressed to SLI after registration showed an increased time to HE development compared with patients who had SLI at the time of registration. However, there was no significant difference in survival time after HE development. We concluded that early identification of SLI patients using the referral system increased the time from SLI diagnosis to HE development.

Incidence and survival of inflammatory breast cancer between 1973 and 2015 in the SEER database.

Inflammatory breast cancer (IBC) is an aggressive variant characterized by erythema, edema, and "peau d'orange" of the skin progressing within 6 months. We assessed the incidence and survival of IBC in the US over four decades. Using SEER*Stat, a case list of IBC patients diagnosed between 1973 and 2015 (n = 29,718) was extracted from SEER 18 registries by using a combination of morphology, stage, and extent of disease criteria. M1 and M0 patients were included. Age-adjusted incidence rates, relative survival rates, and mean survival time were calculated. Significance was determined as non-overlapping 95% confidence intervals. The overall incidence of IBC from 1973 to 2015 is 2.76 (2.73, 2.79) cases per 100,000 people, with white patients having an incidence rate of 2.63 (2.60, 2.67), black patients 4.52 (4.39, 4.65), and patients of other race 1.84 (1.76, 1.93). The overall IBC relative 5-year survival rate is 40.5% (39.0%, 42.0%), 42.5% (40.7%, 44.3%), and 29.9% (26.6%, 33.3%) for white patients and black patients, respectively. Patients diagnosed in 1978-1982 have a mean survival time of 62.3 (52.0, 72.6) months, while those diagnosed in 2008-2012 have mean survival time of 99.4 (96.4, 102.4) months. There is no significant difference in survival time between T4D patients and patients with other T staging and extent of disease coding consistent with clinical IBC presentation. IBC survival has increased over four decades. Despite the improvement in survival for all racial groups, a persistent survival disparity that has not narrowed over two decades remains between white and black patients.

The association of bacteriuria with survival and disease progression in cats with azotemic chronic kidney disease.

BackgroundCats with chronic kidney disease (CKD) have an increased prevalence of positive urine cultures (PUC). Limited information is available regarding the prognosis of cats with CKD and concurrent PUC.ObjectiveTo determine the association of PUC with survival time and disease progression in cats with CKD.AnimalsMedical records of 509 cats diagnosed with azotemic CKD between 1997 and 2018.MethodsCats were classified as having “no‐PUC” or “PUC.” The PUC cats were further classified as having 1 or multiple PUC, and also were classified based on the presence or absence of clinical signs of urinary tract infection (UTI). Progression of CKD was defined as a plasma creatinine concentration increase of ≥25% within 365 days of CKD diagnosis; PUC also must have occurred within this time frame. Survival time and frequency of CKD progression were compared between groups.ResultsNo significant difference in survival time was found between cats with no‐PUC and cats with any number of PUC (P = .91), or between cats with no‐PUC, 1 PUC or multiple PUC (P = .37). Also, no significant difference was found in the frequency of CKD progression between PUC and no‐PUC cats (P = .5), or among no‐PUC, 1 PUC and multiple PUC cats (P = .22). When assessing cats with clinical signs of lower UTI, no significant difference was found in the frequency of CKD progression between cats with true UTI, subclinical bacteriuria or no‐PUC (P = .8).Conclusions and Clinical ImportanceWhen treated with antibiotics, PUC in cats with CKD do not affect disease progression or survival time.

Clinical impact of the radiological indeterminate for usual interstitial pneumonia pattern on the diagnosis of idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease associated with significant morbidity and mortality. The international clinical practice guidelines for the diagnosis of IPF have recently been revised. In this single-center retrospective study conducted between June 2006 and March 2018, 27 patients with a newly classified indeterminate for usual interstitial pneumonia (UIP) pattern on high-resolution computed tomography (HRCT) who had undergone surgical lung biopsy were enrolled at the Japanese Red Cross Medical Center. Clinical and pathological characteristics and prognosis were retrospectively analyzed from patient records. On the basis of multidisciplinary discussion (MDD), IPF was diagnosed in six patients (22%), unclassifiable interstitial pneumonia in 5 (19%), chronic hypersensitivity pneumonitis in 10 (37%), collagen vascular disease-associated interstitial lung disease in 5 (19%), and lymphoproliferative disorder in 1 (4%) patient. Ground-glass opacity, peribronchovascular distribution, upper or middle lobe distribution, mosaic attenuation, consolidation patterns, and honeycombing were found on HRCT. Histological UIP or probable UIP was observed in seven patients. The median survival time from the initial visit was 2770 days (92.3 months). There was a significant difference in survival time in the GAP stage and honeycombing on HRCT according to the log-rank test. Patients with an indeterminate for UIP pattern on HRCT were more likely to have non-IPF than IPF through pathological diagnosis and MDD. GAP stage and honeycombing on HRCT may be significant risk factors for all-cause mortality.

Association between weight change during initial chemotherapy and clinical outcome in dogs with multicentric lymphoma.

The majority of the known prognostic factors in dogs with lymphoma have been evaluated before treatment commences or at the time of diagnosis. Prognostic factors evaluated during the initial phase of treatment are less described but may provide important clinical information. In this retrospective study, 82 canine lymphoma patients were categorized according to the weight change between diagnosis and after 5 weeks of chemotherapy. Dogs that gained greater than 5% or lost greater than 5% of initial body weight were categorized as increased- or decreased-weight groups, respectively. Those in which weight changed less than 5% were categorized as the maintained-weight group. The median progression-free survival (PFS) in the increased-weight group, maintained-weight group and decreased-weight group was 226, 256 and 129 days, respectively. The decreased-weight group had significantly shorter PFS than the increased and maintained groups (P = .023, P = .003, respectively). The median survival time (ST) in the increased-weight group, maintained-weight group and decreased-weight group was 320, 339 and 222 days, respectively. There was no significant difference in ST among the three groups (P = .128). In Cox-regression results, weight change group and initial body weight were significant risk factors associated to PFS (P = .007, P = .001, respectively) while only patient's initial body weight was a significant risk factor to ST (P = .013). In conclusion, evaluation of initial body weight and weight changes over time can provide valuable information regarding PFS and ST in dogs with multicentric lymphoma.

Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis-a dangerous disease.

This study investigated the clinical characteristics of Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis (HLH-HL). Clinical data of 8 patients with HLH-HL and 20 non-HLH-HL patients were included. All eight HLH-HL patients tested positive for plasma Epstein-Barr virus (EBV)-DNA and EBV-encoded small RNA (EBER), and six patients were positive for EBV-DNA in the peripheral blood mononuclear cells (PBMCs). Two out of the 20 non-HLH-HL patients were confirmed positive for EBER, and the remaining 18 patients were negative. Among the HLH-HL patients, five patients received ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) chemotherapy regimens in other hospitals, and their conditions were considered to be worse, for which reason they were transferred to our center, and three patients were treated with DEP (doxorubicin-etoposide-methylprednisolone) regimens to target HLH and were alive as of the writing of this article. Two patients were critically ill upon admission and were not able to undergo chemotherapy. Significant differences in survival time were observed between the HLH-HL and non-HLH-HL patients (P = 0.005). HL patients found positive for EBV (plasma/PBMCs EBV-DNA(+)/EBER(+)) may be more likely to develop HLH-HL. It may be beneficial to target HLH during the acute phase of HLH, followed by treating HL once the HLH condition has stabilized. HLH-HL patients have worse prognosis and higher mortality than non-HLH-HL patients.

Prognostic value of new TNM staging and serum CA125 in malignant peritoneal mesothelioma

Objective: To explore the relationship between the new Tumor-Node-Metastasis (TNM) staging system and the serum CA125 level with the prognosis of malignant peritoneal mesothelioma (MPeM) . Methods: The clinical data of 74 patients with MPeM diagnosed by pathology and immunohistochemistry were collected from January 2005 to June 2016 in Cangzhou Central Hospital. According to the results of CT-peritoneal carcinoma index (PCI) , the tumor load was divided into T1 (PCI 1-10) , T2 (PCI 11-20) , T3 (PCI 21-30) and T4 (PCI 31-39) , combined with lymph node metastasis and extraperitoneal metastasis, a new TNM staging system was established. And serum CA125 level was measured in the same time. The median survival time of patients with MPeM, the effect of the new TNM staging system, and serum CA125 levels on their prognosis were retrospectively analyzed. Results: Among the 74 patients with MPeM, 25 (33.8%) cases were males and 49 (66.2%) cases were females. There were 8 cases with systemic chemotherapy, 8 cases with heated intraperitoneal chemotherapy, and 1 case with combination chemotherapy. 10 cases were T1, 22 cases were T2, 27 cases were T3, 15 cases were T4, 12 cases had lymph node metastasis and 10 cases had distant metastasis. The median survival time of T1, T2, T3 and T4 were 12, 10, 6 and 3 months respectively. There were 38 (77.6%) cases with high serum CA125 in all 49 cases who have been tested for CA125. The median survival time of positive group and negative group were 6 months and 11 months respectively. 68 (91.9%) patients had died by the end of collecting data. The median survival time was 8 months. Univariate analysis showed that there were significant differences in survival time between patients with different CT-PCI stages, serum CA125 levels, and with or without lymph node and extraperitoneal metastasis (P<0.05) . Multivariate analysis showed that CT-PCI was independent risk factors for the prognosis of MPeM (HR=2.203, 95%CI: 1.475-3.289) . Conclusion: The new TNM staging system and serum CA125 are important for the prognosis of patients with MPeM. Early detection, early diagnosis and comprehensive treatment can improve the survival time of patients with MPeM.

The Expression of Snail, Galectin-3, and IGF1R in the Differential Diagnosis of Benign and Malignant Pheochromocytoma and Paraganglioma.

Objective The aim of this study was to investigate the expression of Snail, galectin-3, and IGF1R in benign and malignant pheochromocytoma and paraganglioma (PPGL) and explore their role in the diagnosis of malignant PPGL. Methods We retrospectively collected and analyzed surgical tumor tissue from 226 patients initially diagnosed with PPGL who underwent surgery from Jan. 2009 to Jan. 2016 at West China Hospital, Sichuan University. We observed and quantified the expression of Snail, galectin-3, and IGF1R in paraffin-embedded samples by immunohistochemical staining. Results The significant difference in survival time among the three groups (benign PHEO, benign PGL, and potentially malignant PPGL) was compared by Kaplan-Meier survival analysis. The positive staining of Snail, galectin-3, and IGF1R in the benign PHEO group was significantly lower than that in the other three groups (P < 0.001). The Kaplan-Meier survival plots indicated that the survival time of the patients with intense positive staining was significantly lower than that of the patients with weak positive staining. Conclusion The intense expression of Snail, galectin-3, and IGF1R may be valuable indicators for the diagnosis of malignant PPGL.

A retrospective review of the effect of metformin in metastatic prostate cancer.

62 Background: Current treatments of metastatic prostate cancer are mainly hormone therapy and chemotherapy. The anticancer potential of metformin on metastatic prostate cancer remains obscure. In this study, we aim to investigate the significance of patients with prostate cancer taking metformin in addition to their current treatment. Methods: An IRB approved retrospective review of metastatic prostate cancer patients was conducted. Patients were categorized into metastatic castration resistant prostate cancer (mCRPC) or hormone-sensitive prostate cancer (mHSPC). Patients were further stratified to those who received metformin vs. those who did not. Progression free survival (PFS) was evaluated based on PCWG3 and RECIST criteria. 6-month (6MO) PSA response and overall survival (OS) were also evaluated in this study. Results: A total of 281 subjects were included for analysis with a mean age of 70±10. Patients were known to have either mHSPC (n = 205) or mCRPC (n = 75), and taking metformin (n = 66) or not (n = 215). There was no significant difference between metformin groups with respect to PSA response at 6MO (p &lt; 0.73). Among those with a recorded 6MO PSA response, 70.4% (38/54) had a response in the metformin group and 72.9% (140/192) had a response in the non-metformin group. Overall median PFS was estimated to be 17 months, with no significant difference in PFS between metformin groups (16.6 vs 17.3; p &lt; 0.88). Within the mHSPC group, metformin users had a lower risk of progression relative to non-users (HR = 0.89; 95% CI: 0.62 to 1.29). Within the mCRPC group, metformin users had a significantly higher risk of progression relative to non-users (HR = 2.65; 95% CI: 1.4 to 5.0). Median overall survival was estimated to be 81.5 months. There was a significant difference in survival time between metformin groups (148.5 vs 69.4; p &lt; 0.02). Conclusions: No significant differences were found in 6MO PSA response or PFS. There was a significant difference in OS amongst patients who were in the metformin group and those who were not.

Constructing the Logical Regression Model to Predict the Target of Jianpi Jiedu Decoction in the Treatment of Hepatocellular Carcinoma.

Objectives The purpose of this study was to identify the molecular mechanism and prognosis-related genes of Jianpi Jiedu decoction in the treatment of hepatocellular carcinoma. Methods The gene expression data of hepatocellular carcinoma samples and normal tissue samples were downloaded from TCGA database, and the potential targets of drug composition of Jianpi Jiedu decoction were obtained from TCMSP database. The genes were screened out in order to obtain the expression of these target genes in patients with hepatocellular carcinoma. The differential expression of target genes was analyzed by R software, and the genes related to prognosis were screened by univariate Cox regression analysis. Then, the LASSO model was constructed for risk assessment and survival analysis between different risk groups. At the same time, independent prognostic analysis, GSEA analysis, and prognostic analysis of single gene in patients with hepatocellular carcinoma were performed. Results 174 compounds of traditional Chinese medicine were screened by TCMSP database, corresponding to 122 potential targets. 39 upregulated genes and 9 downregulated genes were screened out. A total of 20 candidate prognostic related genes were screened out by univariate Cox analysis, of which 12 prognostic genes were involved in the construction of the LASSO regression model. There was a significant difference in survival time between the high-risk group and low-risk group (p < 0.05). Among the genes related to prognosis, the expression levels of CCNB1, NQO1, NUF2, and CHEK1 were high in tumor tissues (p < 0.05). Survival analysis showed that the high expression levels of these four genes were significantly correlated with poor prognosis of HCC (p < 0.05). GSEA analysis showed that the main KEGG enrichment pathways were lysine degradation, folate carbon pool, citrate cycle, and transcription factors. Conclusions In the study, we found that therapy target genes of Jianpi Jiedu decoction were mainly involved in metabolism and apoptosis in hepatocellular carcinoma, and there was a close relationship between the prognosis of hepatocellular carcinoma and the genes of CCNB1, NQO1, NUF2, and CHEK1.

Analysis of clinical prognosis and mutant gene phenotype in children with hemophagocytic lymphohistiocytosis

Objective To investigate the clinical manifestations, prognosis and gene mutation phenotypes of hemophagocytic lymphohistiocytosis(HLH)in children of our hospital. Methods The clinical data of 42 patients with HLH from April 2013 to December 2018, and the genetic data of 8 patients with familial HLH(FHL)were collected retrospectively.The age, clinical manifestation, laboratory examination, prognosis and the characteristics of gene mutation phenotype of patients with HLH and FHL were analyzed emphatically.Furthermore, the clinical manifestations and prognosis of patients with HLH were analyzed according to whether EB virus was infected. Results Among these 42 patients with HLH, the onset age was ranged from 1 month to 13 years old and most of them were younger than 5 years old.The main clinical manifestations included cytopenia, prolonged fever, enlargement of liver and spleen and lymph nodes enlargement and serosal effusion.Laboratory examination showed that lactate dehydrogenas, ferritin, erythrocyte sedimentation rate and triglyceride increased significantly.The survival rate of the group in ferritin exceeding 4 500 μg/L and non-chemotherapy was lower than that of the group of ferritin less than 4 500 μg/L and chemotherapy in clinical prognosis(P<0.05). Ten patients of them survived after chemotherapy, and 2 patients survived for 5 to 6 months after hematopoietic stem cell transplantation in FHL.Patients with EB virus infection were older than those without EB virus infection.They had longer fever duration and higher proportion of lymph nodes enlargement and ferritin more than 4 500 μg/L(P values were 0.01, 0.04, 0.03, 0.03 respectively). However, there was no significant difference in survival time between the two groups.Eight patients had mutations in UNC13D(50.00%), PRF1(25.00%), PRKDC(12.50%)and IL2RG(12.50%)genes respectively, and most of the mutations were complex heterozygous mutations(62.50%). All the mutations were originated from their parents. Conclusion HLH is characterized by cytopenia, prolonged fever, enlargement of liver and spleen.HLH is more common in children under 5 years old.The clinical manifestations of HLH with EB virus infection are more severe while the prognosis is not statistically significant.The incidence of FHL is higher.There are more UNC13D gene mutations and complex heterozygous mutations.Children with HLH should be detected and treated with standardized therapy as soon as possible.Hematopoietic stem cell transplantation is a good treatment for HLH, especially for FHL patients. Key words: Hemophagocytic syndrome; Exon sequencing; Gene mutation; EB virus infection; Prognosis