Prognostic factors for patients with metastatic urothelial carcinoma treated with cisplatin and 5-fluorouracil-based regimens

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14583-14583
Author(s):  
Y. Tsai ◽  
C. Lin ◽  
C. Hsu ◽  
K. Huang ◽  
C. Huang ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Median Survival ◽  
Survival Duration ◽  
Visceral Metastasis ◽  
Term Survival ◽  
Significant Difference ◽  
Metastatic Urothelial Carcinoma

14583 Background: Combination of cisplatin and 5-fluorouracil (5-FU) has activity in metastatic urothelial carcinoma (UC). To identify patient subgroups most likely to benefit and compare survival to that in previously described patient series, long-term survival, as a function of known and suspected prognostic variables, was determined. Methods: The survival status of 79 patients with metastatic urothelial cancer treated on two phase II trials of cisplatin and 5-FU-based regimens was updated. P-HDFL regimen (n = 35) was cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,600 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8, 15; repeated every 28 days (Cancer 2006, in press). TP-HDFL regimen (n = 44) was paclitaxel 70 mg/m2 IV 1hr D1, 8; cisplatin 35 mg/m2 IV 24hr D1, 8; 5-FU 2,000 mg/m2 and leucovorin 300 mg/m2 IV 24hr D1, 8; repeated every 21 days (Proc ASCO 22:407b, 2003 [abstr 1637]). Univariate and multivariate Cox proportional hazards models were constructed. Results: Karnofsky performance status (KPS) <80%, presence of visceral metastasis, and alkaline phosphatase ≥220 U/l are three significant poor prognostic factors for survival. The percentage of patients who harbored zero-risk, one- or two-risk, and three-risk categories was 27%, 61%, and 13%, respectively. Among patients with no risk factors, the median survival time was not reached yet after a median follow-up of 43.0 months. Patients with one or two risk factors had a median survival duration of 12.3 months (95% CI 8.6–16.0). Patients with all three risk factors had a median survival of 4.6 months (95% CI 1.4–7.9). There was a significant difference in survival between the three groups (P < .0001). Conclusions: Previously described prognostic factors, including KPS <80%, visceral metastasis, and alkaline phosphatase ≥220 U/l, for survival in metastatic UC were confirmed in patients treated with cisplatin and 5-FU-based regimen. No significant financial relationships to disclose.

Simple prognostic model to predict survival in patients with undifferentiated carcinoma of unknown primary site.

1995 ◽  
Vol 13 (7) ◽  
pp. 1720-1725 ◽  
Author(s):  
A van der Gaast ◽  
J Verweij ◽  
A S Planting ◽  
W C Hop ◽  
G Stoter
Keyword(s):  
Alkaline Phosphatase ◽  
Prognostic Factors ◽  
Median Survival ◽  
Performance Status ◽  
Primary Site ◽  
Survival Duration ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Carcinoma Of Unknown Primary ◽  
Median Survival Duration

PURPOSE We performed this study to identify prognostic factors in a subgroup of patients with carcinoma of unknown primary site treated with cisplatin combination chemotherapy. PATIENTS AND METHODS Seventy-nine patients with poorly differentiated adenocarcinoma or undifferentiated carcinoma of unknown primary site were treated on two consecutive phase II chemotherapy protocols. The first protocol consisted of treatment with 3-week courses of cisplatin, etoposide, and bleomycin (BEP). In the second protocol, cisplatin was administered weekly combined with oral administration of etoposide (DDP/VP). To identify prognostic factors, univariate and multivariate analyses were conducted. RESULTS In the univariate analysis, performance status, histology, liver or bone metastases, and serum levels of alkaline phosphatase and AST were significant variables to predict survival. In the multivariate analysis, performance status and alkaline phosphatase were the most important prognostic factors. CONCLUSION Good-prognosis patients had a performance score of 0 (World Health Organization [WHO]) and an alkaline phosphatase serum level less than 1.25 times the upper limit of normal (N). These patients had a median survival duration greater than 4 years. Intermediate-prognosis patients were characterized by either a WHO performance status < or = 1 or an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of 10 months and a 4-year survival rate of only 15%. The poor-prognosis group had both a WHO performance status > or = 1 and an alkaline phosphatase level > or = 1.25 N. These patients had a median survival duration of only 4 months and none survived beyond 14 months. Treatment strategies for these three groups are discussed. It is suggested that this prognostic model be validated in other patients series.

Prognostic factors in patients with metastatic urothelial carcinoma who have treated with Atezolizumab

2021 ◽  
Author(s):  
Deniz Tural ◽  
Ömer Fatih Ölmez ◽  
Ahmet Taner Sümbül ◽  
Nail Özhan ◽  
Burcu Çakar ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Metastatic Urothelial Carcinoma

Low Geriatric Nutritional Risk Index as a Poor Prognostic Marker for Second-Line Pembrolizumab Treatment in Patients with Metastatic Urothelial Carcinoma: A Retrospective Multicenter Analysis

Oncology ◽  
2020 ◽  
Vol 98 (12) ◽  
pp. 876-883
Author(s):  
Toshiki Etani ◽  
Taku Naiki ◽  
Yosuke Sugiyama ◽  
Takashi Nagai ◽  
Keitaro Iida ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Urothelial Carcinoma ◽  
Group Performance ◽  
Risk Index ◽  
Nutritional Risk ◽  
Second Line ◽  
Geriatric Nutritional Risk Index ◽  
Platinum Based Chemotherapy ◽  
Nutritional Risk Index ◽  
Metastatic Urothelial Carcinoma

<b><i>Background:</i></b> We evaluated the prognostic efficacy of the Geriatric Nutritional Risk Index (GNRI) in second-line pembrolizumab (PEM) therapy for patients with metastatic urothelial carcinoma (mUC). <b><i>Patients and Methods:</i></b> From January 2018 to October 2019, 52 mUC patients, treated previously with platinum-based chemotherapy, underwent second-line PEM therapy. Peripheral blood parameters were measured at the start of treatment: serum neutrophil-to-lymphocyte ratio (NLR), serum albumin, serum C-reactive protein (CRP), and body height and weight. PEM was intravenously administered (200 mg every 3 weeks). The patients were organized into two groups based on their GNRI (&#x3c;92 [low GNRI] and ≥92 [high GNRI]), and the data were retrospectively analyzed. Adverse events (AEs) were evaluated and imaging studies assessed for all patients. Analyses of survival and recurrence were performed using Kaplan-Meier curves. Potential prognostic factors affecting cancer-specific survival (CSS) were assessed by univariate and multivariate Cox regression analyses. <b><i>Results:</i></b> patients’ baseline characteristics, except for their BMI and objective response rate, did not significantly differ between the two groups. The median total number of cycles of PEM therapy was significantly higher for the high-GNRI group (<i>n</i> [range]: 6 [2–20] vs. 3 [1–6]). The median CSS with second-line PEM therapy was 3.6 months (95% confidence interval [CI]: 2.5–6.1) and 11.8 months (95% CI: 6.2–NA) in the low-GNRI and the high-GNRI group (<i>p</i> &#x3c; 0.01), respectively. Significant differences in CSS between the low- and high-CRP or -NRL groups were not found. Multivariate Cox proportional-hazards regression analysis revealed that a poor Eastern Cooperative Oncology Group performance status, visceral metastasis, and a low GNRI were significant prognostic factors for short CSS (95% CI: 1.62–6.10, HR: 3.14; 95% CI: 1.13–8.11, HR: 3.03; 95% CI: 1.32–8.02, HR: 3.25, respectively). Of the AEs, fatigue showed a significantly higher incidence in the low-GNRI group. <b><i>Conclusions:</i></b> For mUC patients receiving second-line PEM therapy, the GNRI is a useful predictive biomarker for survival outcome.

scholarly journals Az ellenoldali csípőtáji törésig eltelt időt befolyásoló prognosztikai tényezők vizsgálata

2018 ◽  
Vol 159 (38) ◽  
pp. 1543-1547
Author(s):  
Krisztina Juhász ◽  
Imre Boncz ◽  
Péter Kanizsai ◽  
Andor Sebestyén
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Hip Fracture ◽  
Femoral Neck ◽  
Femoral Neck Fracture ◽  
Hip Fractures ◽  
Age Groups ◽  
Significant Difference ◽  
Neck Fracture ◽  
The Impact

Abstract: Introduction: Although several national studies reported on the risk factors for contralateral hip fracture, there are no data about the prognostic factors of the time until contralateral hip fractures. Aim: The aim of the study was to analyse the impact of different prognostic factors on the time until the development of contralateral fracture and to determine the incidence of contralateral hip fractures after femoral neck fractures. Method: Patients aged 60 years and over with contralateral hip fracture between 01 Jan 2000 and 31 Dec 2008 were identified among those who suffered their femoral neck fracture in Hungary in 2000. Risk factors as age, sex, comorbidities, type of fracture and surgery, place of living and hospitals providing treatment for primary fracture were analysed by one way ANOVA focusing on the time until the development of contralateral hip fracture. Results: 312 patients met the inclusion criteria. The incidence of contralateral hip fracture after femoral neck fracture ranged between 1.5% and 2.1%, the cumulative incidence was 8.24%. The mean time until the development of contralateral hip fracture was 1159.8 days. The incidence of contralateral hip fracture showed no significant deviation. Significantly shorter time (p = 0.010) was detected until the contralateral hip fracture in older patients with femoral neck fracture. Conclusions: The yearly incidence of contralateral hip fracture showed no significant difference by patients with femoral neck fracture over 60 years. The shorter time until the contralateral hip fracture by the older age groups highlights the need of elaboration of prevention strategies. Orv Hetil. 2018; 159(38): 1543–1547.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Cancer-specific survival in patients with urothelial carcinoma of the bladder with recurrence after radical cystectomy: External validation of the prognostic risk stratification model.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 325-325 ◽  
Author(s):  
Tohru Nakagawa ◽  
Haruki Kume ◽  
Atsushi Kanatani ◽  
Masaomi Ikeda ◽  
Akihiko Matsumoto ◽  
...  
Keyword(s):  
Risk Factors ◽  
Urothelial Carcinoma ◽  
Radical Cystectomy ◽  
Median Survival ◽  
Prognostic Value ◽  
Risk Group ◽  
Cancer Specific Survival ◽  
Poor Risk ◽  
Carcinoma Of The Bladder ◽  
Metastatic Sites

325 Background: Prognosis of the patients with urothelial carcinoma of the bladder (UCB) who developed recurrence after radical cystectomy (RC) is generally poor, but can be variable. We previously showed that shorter time to recurrence (TTR) after RC, presence of symptoms on recurrence, more than one metastatic sites (organs), high serum C-reactive protein (CRP) level were associated with decreased survival in those patients, and proposed a model to stratify patients into 3 separate risk groups (Nakagawa et al. J Urol. 2013; 189:1275). The aim of this study was to evaluate the prognostic value of this model in a multi-institutional cohort of patients. Methods: We identified 267 patients who experienced disease recurrence after RC for UCB from 9 academic and community hospitals. Patients were categorized into three groups based on the presence of four risk factors, TTR of <1 year, presence of symptoms on recurrence, more than one metastatic sites (organs), and CRP level of ≥0.5 mg/dl: the favourable risk group included patients with none or one of these risk factors; the intermediate risk group with 2 risk factors; and those with 3 or 4 risk factors were assigned to the poor risk group. Results: Overall, median survival time (MST) of the entire cohort was 8.3 months (95%CI, 6.4-9.1). Two hundred and nineteen patients died of their disease with a median survival of 5.9 months. In a multivariate analysis, all of the 4 risk factors were statistically significant for the cancer-specific survival. Sixty-five (27.4%), 84 (35.4%), and 88 (37.1%) patients were in the favorable, intermediate and poor risk group, respectively. Thirty patients were excluded because CRP value was not obtained. MSTs of the patients in the favorable, intermediate and poor risk group were 22.2 (95% CI 16.1-28.3), 7.6 (95% CI 6.3-9.5), and 3.6 (95% CI 2.6-4.4) months, respectively, and the difference was statistically significant (p<0.001, log-rank test). Conclusions: We confirmed the prognostic value of our previous criteria based on the four variables in patients with recurrence after RC for UCB. This criteria would help in patient counseling and clinical trial design.

scholarly journals LONG-TERM SURVIVAL AND PROGNOSTIC FACTORS FOR UNFAVORABLE OUTCOME IN PATIENTS WITH SYSTEMIC SCLEROSIS.A PROSPECTIVE SINGLE-CENTER STUDY

2017 ◽  
Vol 26 (2) ◽  
pp. 60-64
Author(s):  
Alexandra Daniela Radu ◽  
◽  
Ana Maria Gheorghiu ◽  
Raida Oneata ◽  
Alina Soare ◽  
...  
Keyword(s):  
Risk Factors ◽  
Prognostic Factors ◽  
Systemic Sclerosis ◽  
Lung Involvement ◽  
Term Survival ◽  
Long Term Survival ◽  
Male Sex ◽  
Cox Analysis

Background. Systemic sclerosis (SSc) is a complex chronic autoimmune disease, with an unpredictable evolution and high morbidity and mortality rates. Objective. Evaluation of long-term survival and identification of prognostic factors in patients with systemic sclerosis. Methods. All patients with SSc of the EUSTAR100 center, having at least one visit between 2004 and 2016, were included. Data were analyzed for survival, cause of death, as well as for the following events defining disease worsening: increase in modified Rodnan score (mRSS) with at least 25% and 5 points (compared to baseline visit), decrease with at least 10% (compared to baseline) of predicted forced vital capacity (FVC) and predicted diffusing capacity of the lungs for carbon monoxide (DLCO), and presence of new digital ulcers (DUs). Logistic regression (LR), Cox proportional hazards regression and Kaplan-Meier survival curves were used in univariate and multivariate analysis to study survival and identify prognostic factors. Results. 137 patients were included in the study (89.1% females, mean age ± SD 56.7 ± 12.6 years, disease duration 9.7 ± 7.1 years), with a follow-up duration of up to 19 years. 96 patients had at least one follow-up visit and 66 (not including patients who died earlier than 2 years after the first presentation) had follow-up data at 2 years (± 6 months) after the first visit in the clinic. There were 19 reported deaths (13.9%), 11 attributed to SSc (of whom 8 were due to lung involvement). Risk factors for death were diffuse cutaneous subset and mRSS>14 at baseline (identified by LR adjusted for age and sex), male sex and proteinuria (Cox analysis). While in over half of the patients FVC and mRSS were stable or improved (86% and 96% respectively), and no new DUs occurred (64%), 52% of the patients presented significant worsening of DLCO during the entire followup. Risk factors for DLCO worsening at 2 years, by LR adjusted for sex and age, were male sex and diffuse cutaneous subset, while Cox analysis identified only male sex. The only risk factor identified for appearance of new DUs was the history of DUs at the first presentation. Conclusions. SSc often presents an unfavorable disease course, particularly due to lung involvement. Risk factors for disease worsening were male sex, diffuse cutaneous subset, and mRSS>14 at baseline. SSc-related deaths were mainly due to lung involvement, thus underlining the necessity of identifying predictive factors for lung function deterioration at the first presentation.

scholarly journals Incidence and Risk Factors for Nontuberculous Mycobacteria Infection after Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1917-1917 ◽  
Author(s):  
Jennifer M. Beswick ◽  
Elizabeth Shin ◽  
Jieun Uhm ◽  
Fotios V. Michelis ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Risk Factors ◽  
Median Survival ◽  
Research Funding ◽  
Nontuberculous Mycobacteria ◽  
Fungal Infections ◽  
Conditioning Regimen ◽  
Significant Risk ◽  
Hematopoietic Cell ◽  
Survival Duration ◽  
Clinically Significant

Abstract Introduction: Nontuberculous mycobacteria (NTM) are ubiquitous environmental organisms that are increasingly recognized as clinically significant pathogens in the allogenic hematopoietic cell transplanted (alloHCT) population. The incidence of NTM infection post alloHCT has increased from 0.49-1.0% in early studies to 2.8-8.7% in more recent investigations, possibly due to improvements in NTM detection, varying pre-transplant conditioning regimens and regional epidemiology of different NTM species. We investigated incidence and risk factors of NTM infection after alloHCT. Methods & Patients: Medical records for 1097 consecutive patients who underwent alloHCT at Princess Margaret Cancer Centre from 2000 to 2013 were reviewed to determine the frequency, risk factors and outcomes associated with NTM infections. Clinically significant NTM infection was differentiated from colonization according to the American Thoracic Society guidelines, and was classified as pulmonary, non-pulmonary, or disseminated. Acute and chronic graft versus host disease (aGVHD and cGVHD) were diagnosed and graded using established and NIH consensus criteria respectively. The cumulative incidence of NTM was calculated considering competing risks of death. Multivariate analysis comprised Cox proportional hazards regression, modeling NTM risk. Statistical analyses were performed using EZR software (Saitama, Japan). Results: Of 1097 patients, NTM were isolated in 45 (4.1%) and judged clinically significant in 30 (2.7%). The incidence of NTM infection by competing risk analysis was 2.8% at 5 years (95% CI, 1.9-4.0%). The median (range) time to diagnosis was 343 (19-1967) days, and in 83% of patients, was diagnosed within 2 years of alloHCT. Of the 30 clinically significant NTM infections, 28 (93.3%) were pulmonary and 2 (6.7%) were disseminated. With respect to the latter group, one patient had NTM isolated from blood, while the second case was presumed disseminated based on characteristic skin findings, but with no confirmed microbiologic diagnosis. The most common species/groups isolated were Mycobacterium avium complex (n=11, 36.7%), M. xenopi (n=5, 16.7%), and M. fortuitum (n=5, 16.7%). 22/30 patients (73.3%) were on systemic immunosuppression at the time of diagnosis, and 95.7% had concurrent infections (30.4% pulmonary, 17.3% extra-pulmonary, and 47.8% both), with fungal infections occurring most frequently (53.3%). Significant risk factors (HR 95% CI) for NTM included aGVHD grades 2-4 (3.25 [1.33-7.96] p=0.036), cGVHD (3.20 [1.06-9.68] p=0.010), age (1.05 [1.02-1.07], p <0.001), and CMV viremia (4.64 [1.90-11.37] p=0.001). 76.7% of patients with clinically significant NTM had a diagnosis of cGVHD (23/30), in comparison to 47.4% (520/1097) of patients without a diagnosis of NTM infection (p=0.003), and cGVHD severity by NIH global score correlated with NTM risk. Among all patients with cGVHD, severe cGVHD was present in 39% (9/23) of NTM patients, versus 17% (89/520) of non-NTM patients (p=0.012). Pre-alloHCT diagnosis (p=0.34), conditioning regimen (p=0.81), T-cell depletion (p=0.66), HLA matching (p=0.62), or donor type (p=0.63), did not reach statistical significance. Median survival duration after a diagnosis of clinically significant NTM was 398 (range, 20-764) days, with a survival rate of 40.8±10.8% at 2 years. Conclusion: Clinically significant NTM infection after alloHCT was relatively common in our study population. GVHD (acute and chronic), age, and CMV bacteremia were significant risk factors. Given a median survival of approximately 1 year following diagnosis, NTM infection may be of greater clinical significance than previously thought. A high index of suspicion for NTM infection in patients with pulmonary symptoms, particularly within 2 years after HCT and in the presence of cGVHD, may lead to prompt diagnosis and treatment, and potentially better outcomes. Disclosures Lipton: Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding; Teva: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding. Kim:Novartis Pharmaceuticals: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding.

scholarly journals Trends in Incidence and Survival of Patients with Pancreatic Neuroendocrine Neoplasm, 1987–2016

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jingxuan Wang ◽  
Jianhua Liu ◽  
Chao He ◽  
Tiantian Sun ◽  
Yan Yan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Large Scale ◽  
Proportional Hazards ◽  
Survival Rates ◽  
Relative Survival ◽  
Cox Proportional Hazards ◽  
Neuroendocrine Neoplasm ◽  
Survival Duration ◽  
Term Survival ◽  
Pancreatic Neuroendocrine Neoplasm

Background. Pancreatic neuroendocrine neoplasm (pNEN), with the lowest 5-year survival rates in neuroendocrine tumors (NETs), exerts great threat to human health. Because large-scale population research aimed at pNEN is rare, we aimed to explore the tendencies and differences of changes in incidences and survival rates of pNEN in each decade from 1987 to 2016 and evaluate the impacts of age, sex, race, socioeconomic status (SES), and grade. Methods. Data on pNEN cases from 1987 to 2016 were extracted from the Surveillance, Epidemiology, and End Results Program (SEER) database. Kaplan–Meier, Cox proportional hazards regression analyses, and relative survival rates (RSRs) were used to identify risk factors for pNEN. Results. The incidence and survival duration of pNEN increase every decade due to medical developments. The disparities of long-term survival in different age, sex, and grade groups expanded over time while that in race and SES groups narrowed. Older age and higher grade are independent risk factors for poorer survival. Females have lower incidence and longer survival than males. Prognosis of Black patients and poor (medium and high poverty) patients improved. Conclusions. This study depicted changes in incidence and survival rates of pNEN over the past three decades and evaluated potential risk factors related to pNEN, benefiting future prediction of vulnerable and clinical options.

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