High-risk Ones Research Articles

10-Year Real-World Data on Acute Myeloid Leukemia: The Paradigm of a Public Health Center in Brazil

Introduction Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and originates from hematopoietic precursor cells that suffers genetics and epigenetics alterations leading to a clone able to proliferate with survival advantages. The last years have been of great advances in AML because of more profound knowledge of its pathogenic mechanisms. This lead to a better stratification of the patients based on cytogenetics and molecular criteria and development of targeted therapy that changed its natural course. Unfortunately, the tests and new drugs are expensive and not easily available worldwide, especially in low and middle-income countries (LMIC) with distinct realities between private and public care. Methods To determine the profile and outcomes of patients in a public health center in Brazil, we did a retrospective analysis of all the cases of non-promyelocytic AML diagnosed between 2007 and 2017 in the University Hospital Professor Edgar Santos of Federal University of Bahia. 62 patients were included and we used a modified model of European LeukemiaNet 2017 classification to risk stratification, with cases of secondary AML (sAML) included in the high risk group. Results A total of 62 patients were analyzed, 1 died prior treatment and was excluded. Median age at diagnosis was 44 years (range, 16-83 years) with 58% females. 68% werede novoAML. 11% of patients were classified as favorable risk, 8% as intermediate and 42% as high risk. 39% had unknown risk because of absence of cytogenetic and/or molecular tests. The chemotherapy protocol in patients eligible to intensive treatment was 7+3 in 87%. 20% of the patients died during induction and 65% achieved response (53% complete + 12% partial remission). Analyzing only sAML, 35% were considered fit for intensive treatment and most of less intensive regimens were based in low-dose cytarabine (64%). The overall response rate of sAML after induction was 20%. During the treatment, 31% relapsed with a median time to relapse of 8 months. 43% of the relapses happened in patients classified as unknown risk. 37% of patients that survived induction were submitted to allogeneic bone marrow transplant (alloBMT) and had survival advantage (hazard ratio, HR: 2,52, 95% CI: 1.103 - 5,795;P= 0.028; Figure 1), with superior median overall survival (mOS) (49 months) when compared with the chemotherapy group (11 months) (P= 0.021). During the follow-up, 77% of the patients died and most of the deaths (61%) occurred in the first year of diagnosis. The primary cause of death was infection (52%) followed by leukemia progression (31%). The mOS was 7 months and 5-year OS was 27%. Stratifying by the risk, the mOS was shorter in patients with unknown and high risk (5 and 4 months, respectively) than in low and intermediate risk (not reached,P= 0.01; Figure 2). The median relapse free survival (RFS) was 15 months, reached only in the high risk group (14 months;P= 0.31; Figure 3). The patients with sAML had mOS of 3 months versus 11 months ofde novoAML(P =0.024; Figure 4). Discussion In summary, we found statistical difference in better OS among patients that received BMT, AMLde novoand favorable/intermediate risk. Our findings were similar to those reported by other groups of university hospitals in Brazil. An alarming data is the high proportion of patients who were not adequately stratified. Our data are from real life and this subgroup still exists because cytogenetic and molecular tests are not universally available in the brazilian public health system. Those patients had similar outcomes to high risk ones suggesting that a proportion of them were undertreated. It is important for every center to be aware of their survival curves to better individualize their approaches. We suggest that patients with inadequate risk assessment should undergo alloBMT as this remains the primary curative intervention and the main outcome changer in real-world setting of LMIC. Our high mortality rate, in comparison with data from developed countries, reflects the absence of more effective therapies, especially for high risk cases, and an inferior hospital infrastructure contributing to a higher incidence of infections. Considering the discovery of new powerful drugs, the tendency of discrepant outcomes between centers from LMIC and developed countries is considerably high. Therefore, the improvement of access to diagnostic techniques and treatment is still an unmet need in AML scenario. Disclosures No relevant conflicts of interest to declare.

SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience.

SARS-CoV-2 in Myelodysplastic Syndromes: A Snapshot From Early Italian Experience.

Measuring imported case risk of COVID-19 from inbound international flights --- A case study on China

With COVID-19 spreading around the world, many countries are exposed to the imported case risk from inbound international flights. Several governments issued restrictions on inbound flights to mitigate such risk. But with the pandemic controlled in many countries, some decide to reopen the economy by relaxing the international air travel bans. As the virus has still been prevailing in many regions, this relaxation raises the alarm to import overseas cases and results in the revival of local pandemic. This study proposes a risk index to measure one country's imported case risk from inbound international flights. The index combines both daily dynamic international air connectivity data and the updated global COVID-19 data. It can measure the risk at the country, province and even specific route level. The proposed index was applied to China, which is the first country to experience and control COVID-19 pandemic while later becoming exposed to high imported case risk after the epidemic centers switched to Europe and the US afterward. The calculated risk indexes for each Chinese province or region show both spatial and temporal patterns from January to April 2020. It is found that China's strict restriction on inbound flights since March 26 was very effective to cut the imported case risk by half than doing nothing. But the overall index level kept rising because of the deteriorating pandemic conditions around the world. Hong Kong and Taiwan are the regions facing the highest imported case risk due to their superior international air connectivity and looser restriction on inbound flights. Shandong Province had the highest risk in February and early March due to its well-developed air connectivity with South Korea and Japan when the pandemic peaked in these two countries. Since mid-March, the imported case risk from Europe and the US dramatically increased. Last, we discuss policy implications for the relevant stakeholders to use our index to dynamically adjust the international air travel restrictions. This risk index can also be applied to other contexts and countries to relax restrictions on particular low-risk routes while still restricting the high-risk ones. This would balance the essential air travels need and the requirement to minimize the imported case risk.

Current status of genetic urinary biomarkers for surveillance of non-muscle invasive bladder cancer: a systematic review

BackgroundGenetic biomarkers are a promising and growing field in the management of bladder cancer in all stages. The aim of this paper is to understand the role of genetic urinary biomarkers in the follow up of patients with non muscle invasive bladder cancer where there is increasing evidence that they can play a role in avoiding invasive techniques.MethodsFollowing PRISMA criteria, we have performed a systematic review. The search yielded 164 unique articles, of which 21 articles were included involving a total of 7261 patients. Sixteen of the articles were DNA based biomarkers, analyzing different methylations, microsatellite aberrations and gene mutations. Five articles studied the role of RNA based biomarkers, based on measuring levels of different combinations of mRNA. QUADAS2 critical evaluation of each paper has been reported.ResultsThere are not randomized control trials comparing any biomarker with the gold standard follow-up, and the level of evidence is 2B in almost all the studies. Negative predictive value varies between 55 and 98.5%, being superior in RNA based biomarkers.ConclusionsAlthough cystoscopy and cytology are the gold standard for non muscle invasive bladder cancer surveillance, genetic urinary biomarkers are a promising tool to avoid invasive explorations to the patients with a safe profile of similar sensitivity and negative predictive value. The accuracy that genetic biomarkers can offer should be taken into account to modify the paradigm of surveillance in non muscle invasive bladder cancer patients, especially in high-risk ones where many invasive explorations are recommended and biomarkers experiment better results.

Prognostic Value of Modified IHC4 Score in Patients with Estrogen Receptor-Positive Metastatic Breast Cancer

BackgroundThis study aimed to investigate whether an immunohistochemical prognostic model (IHC4 score) can predict the prognosis and the chemotherapy benefit in patients with estrogen receptor‐positive (ER+)/human epidermal growth receptor 2–negative (HER2−) metastatic breast cancer (MBC).Materials and MethodsWe developed a method to calculate the modified IHC4 (mIHC4) scores based on routine pathological reports and compared them with the original IHC4 scores that were much more difficult to calculate. Univariate and multivariate analyses were used to study the prognostic factors of progression‐free survival (PFS) and overall survival (OS). The predictive value of mIHC4 score was also investigated.ResultsThe Sun Yat‐sen Memorial Hospital data set included 315 patients with newly diagnosed ER+ MBC with a median follow‐up of 25.6 months. Univariate and multivariate analysis showed that higher mIHC4 scores in metastatic lesions, but not the ones in primary tumors, were significantly associated with worse PFS and OS. The prognostic value of mIHC4 scores for PFS was validated using an independent Chinese Society of Clinical Oncology‐ Breast Cancer (CSCO‐BC) data set. More importantly, subpopulation treatment effect pattern plot analysis showed that first‐line endocrine therapy achieved better PFS and OS than chemotherapy in low‐risk patients with ER+/HER2− MBC, whereas first‐line chemotherapy was associated with improved PFS and OS compared with endocrine therapy in high‐risk ones. The predictive value of mIHC4 score for PFS in selecting first‐line endocrine therapy versus chemotherapy was also confirmed in the CSCO‐BC data set.ConclusionmIHC4 scores in metastatic lesions are prognostic for the PFS and OS in patients with ER+ MBC. Low or high mIHC4 score may indicate the survival benefit in choosing first‐line endocrine therapy or chemotherapy in patients with ER+/HER2− MBC, respectively.Implications for PracticeThe modified IHC4 (mIHC4) score is easy to implement and able to predict patients with advanced and/or metastatic breast cancer. In addition, with the help of the mIHC4 score, physicians might be able to recommend chemotherapy or endocrine therapy as the first‐line treatment for patients with high and low risk as predicted by the mIHC4 score.

COVID-19 and Thalassaemia in Iran

Coronavirus disease 2019 (COVID-19) has had and continues to have a significant medical, public health, social and economic impact on every society around the world. Some groups of chronic patients including thalassaemia and other haemoglobin disorders were considered from the beginning of the pandemic, as vulnerable and high risk ones with regards to a more severe clinical outcome of the infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). This is because patients with thalassaemia can present with many and multiple co-morbidities including diabetes, heart, liver, endocrine and other conditions mainly secondary to iron overload and consequent to ineffective or suboptimal medical care and/or adherence to chelation treatment in particular. Transfusion dependent patients with β-thalassaemia have been greatly affected across the world, including in Iran, a country geographically situated in the so called thalassaemia belt. Iran with about 20,000 patients with β-thalassaemia and quite successful disease specific prevention and management national programmes faced challenges similar to others. Blood shortages for example consequent to COVID-19 precaution measures taken in every country to contain the virus and the difficulties in accessing drugs including lifesaving ones (iron chelation medication) constitute major challenges. In Iran however, and despite the multiple difficulties as described above, SARS-CoV-2 had a rather small impact regarding infection rates as compared to the rest of the countries, albeit a higher mortality rate reaching 26.5% amongst COVID-19 diagnosed patients. More comprehensive data however from a bigger number of patients with thalassaemia across the world infected with SARS-CoV- 2 is necessary to draw any reliable conclusions as to the level of vulnerability to SARS-CoV-2 and importantly the clinical impact of this virus in these patients.

Lifetime drug use and related factors among street children and youth in Iran in 2016

ABSTRACT Background: The prevalence and patterns of substance use and its related risk factors in street children are significant for policymakers. The present study was conducted in six cities of Iran to explore the prevalence rate of drug use disorders and their associated high-risk behaviors among street children. Methods: This cross-sectional study was conducted in 2016 among 856 street children in Iran. The samples were recruited through Time-Location Sampling (TLS) method. Trained interviewers administered the questionnaires. The applied questionnaire consisted of modules concerning sociodemographic characteristics and risky behaviors. We used bivariate and multiple logistic regression models to identify factors associated with drug use disorders. Results: Of 856 street children participants, 5.28% (CI 95%: 3.84, 7.04) reported lifetime drug use. According to the final multivariable model, factors including nationality (AOR = 4.79, 95% CI 1.57, 14.56), father’s history of drug use (AOR = 3.25, 95% CI 1.43, 7.41), and alcohol use (AOR = 5.63, 95% CI 2.43, 13.07) were independently associated with lifetime drug use. Conclusion: The children with Iranian nationality, father’s history of drug use, and alcohol use had significantly higher odds of lifetime drug use. This study calls for the development of an urgent plan to implement appropriate interventions for street children, particularly high-risk ones in Iran.

A Risk Score Based on 5 Clinico-Pathological Variables Predicts Recurrence of Atypical Meningiomas.

The use of adjuvant radiotherapy is controversial in patients with atypical meningiomas treated with gross total resection (GTR). This study aimed to determine whether clinico-pathological features could be helpful to predict the recurrence risk in this group of patients and to identify high-risk ones who could benefit from adjuvant treatment. We collected 200 patients with primary atypical meningiomas treated with GTR but with no adjuvant radiotherapy from 5 different centers. A risk score, formulated by assigning 1 point for the presence and 0 points for the absence of 5 high-risk parameters (male sex, parasagittal site, Simpson grade 3, mitotic index ≥ 6/10 HPF, and sheeting), was the most significant predictor of recurrence. A score ≥2 was associated with 4.7 risk of shorter disease-free survival (p < 0.0001). Our findings indicate that the presence of at least 2 clinico-pathological high-risk factors predicts recurrence of totally resected primary atypical meningiomas and could be helpful for identifying patients who could benefit from adjuvant radiotherapy.

Cutaneous cysts: a clinicopathologic analysis of 2,438 cases.

Benign cutaneous lesions, so-called cysts, are frequently seen in clinics and might evoke cosmetic and psychosocial concerns. This study aimed to demonstrate the clinicopathologic findings of these lesions and also the importance of histological evaluation for prevention of misdiagnosing a benign-appearing malignant lesion. A descriptive study was conducted of 2,438 cases who had a diagnosis of cyst confirmed with pathology. The data of patients over the 6-year period between 2011 and 2017, including gender, age, location, prevalence, complications, and microscopic evaluation, were gathered. From a total of 2,438 records with a clinical diagnosis of mucocutaneous cyst, 2077 had the pathologic diagnosis of cysts. They consisted of 910 women (43.8%) and 1167 men (56.1%) with a mean age of 42. The most common mucocutaneous cysts were epidermal cyst 994 (47.8%) followed by trichilemmal cyst 495 (23.8%). In 479 (19.6%) records, the clinical diagnosis was not congruent with histopathological diagnosis including 45 malignant cases. Basal cell carcinoma in 22 (48.9%) was the most common one. This study reports on clinical characteristics of cutaneous cysts and the need for a decent diagnostic investigation, like histopathology, for achieving a reliable diagnosis regarding the benign mimicking malignant lesions, especially high risk ones.

Development and validation of a nomogram for predicting overall survival of node-negative ampullary carcinoma.

The accuracy of the current staging system for predicting the overall survival (OS) of patients with ampullary carcinoma (AC) is still unsatisfactory, especially in node-negative (N0) patients. We aimed at establishing a nomogram to accurately predict OS in N0 AC. This study enrolled 697 N0 AC patients from the Surveillance, Epidemiology, and End Results database (design cohort [DC], n = 697) and the First Affiliated Hospital of Sun Yat-sen University (validation cohort [VC], n = 112), who underwent surgical resection. The nomogram was established by using prognostic factors determined by univariate and multivariate regression analyses. The nomogram for OS was developed by using four independent prognostic factors, including age, grade, T stage, and a number of examined lymph nodes. The C-index of a nomogram for OS in DC and VC was 0.665 and 0.731, respectively. Calibration curves showed good consistency of the nomogram. The nomogram had a better accuracy in predicting OS compared with conventional staging system (P < .05). On the basis of nomogram-predicted scores, the patients were stratified into groups with different risk. The OS of low-risk patients was significantly longer than high-risk ones (P ≤ .010). The nomogram could be used to predict the OS of N0 AC. It could help guide further treatment in clinical practice.

Decision tree machine learning applied to bovine tuberculosis risk factors to aid disease control decision making

Identifying and understanding the risk factors for endemic bovine tuberculosis (TB) in cattle herds is critical for the control of this disease. Exploratory machine learning techniques can uncover complex non-linear relationships and interactions within disease causation webs, and enhance our knowledge of TB risk factors and how they are interrelated. Classification tree analysis was used to reveal associations between predictors of TB in England and each of the three surveillance risk areas (High Risk, Edge, and Low Risk) in 2016, identifying the highest risk herds. The main classifying predictor for farms in England overall related to the TB prevalence in the 100 nearest cattle herds. In the High Risk and Edge areas it was the number of slaughterhouse destinations and in the Low Risk area it was the number of cattle tested in surveillance tests. How long ago the last confirmed incident was resolved was the most frequent classifier in trees; if within two years, leading to the highest risk group of herds in the High Risk and Low Risk areas. At least two different slaughterhouse destinations led to the highest risk group of herds in England, whereas in the Edge area it was a combination of no contiguous low-risk neighbours (i.e. in a 1 km radius) and a minimum proportion of 6–23 month-old cattle in November. A threshold value of prevalence in 100 nearest neighbours increased the risk in all areas, although the value was specific to each area. Having low-risk contiguous neighbours reduced the risk in the Edge and High Risk areas, whereas high-risk ones increased the risk in England overall and in the Edge area specifically. The best classification tree models informed multivariable binomial logistic regression models in each area, adding statistical inference outputs. These two approaches showed similar predictive performance although there were some disparities regarding what constituted high-risk predictors. Decision tree machine learning approaches can identify risk factors from webs of causation: information which may then be used to inform decision making for disease control purposes.

Methodology for the Start-up of a Pediatric Hematopoietic Stem Cell Transplant Unit (pHSCTU) in Middle-Income Countries (MICs): An Exportable Model?

Introduction: Blood or marrow transplantation (BMT) programs are largely insufficient to meet the growing need in MICs. Where BMT is not available families, charities or governments often seek for alternative programs, usually to send children abroad for BMT; this policy is associated with many drawbacks, including costs, and difficulties to manage transplant related complications after the patient return home. Evaluation of feasibility and sustainability plays a crucial role in the success of all cooperative projects but especially of high specialization ones. Materials and methods: In 2016 the first HSCTU inclusive of a pediatric section was developed in Iraqi Kurdistan at Hiwa Cancer Hospital of Sulaymaniah, thanks to a cooperative project funded by the Italian Agency for Development Cooperation and to the availability of professionals from specialized centers to train local personnel. After verifying with an appropriate grid that essential requirements were in place, a capacity building project was started. An intensive educational course was carried on initially and then, using a training on the job approach, all specific skills were set-up and/or implemented. A complete protocol handbook was created with involvement of the local staff; a staggered approach to the disease was chosen, starting from low risk diseases and moving later to high risk ones. After 3 years project the center is now completely autonomous; up to now they have been performed 158 transplants (autologous and allogeneic, both in adult and children) with results comparable with those of high-income countries (HICs). In a cohort of 26 pediatric patients with thalassemia the event free survival (EFS) is over 90% with a median follow up of 492 days. Next to this experience, in 2018 a new project has been activated in Paraguay, following a specific request from the pediatric hospital Ninos de Acosta Nu in Asuncion. The similar methodology has been applied. After documenting the feasibility, a 3 years project has been set-up, with an initial intensive educational course, followed by training on the job by experts in the field and also limited training of the local staff abroad. A six months continuously oversight by experienced nurses and periodically by expert physicians has been planned along with the continuous support through on line contacts; focused training in Europe on minimal residual disease, chimerism, apheresis and HLA typing has been scheduled. The first allogeneic transplant from matched sibling donor is planned in autumn 2019. Discussion: Based on our experience new centers should start with patients highly curable, low-risk matched sibling transplants, well-established context-appropriate protocols with minimal toxicity, proven high success rates and contained costs. If socio-economical context of the country and needs of the population allow to move to oncological patients, a staggered approach is suggested: from matched sibling donor transplant to mismatched ones. Minimal essential requirements for a pediatric BMT start-up activity may be affordable in many MICs, if health authorities and/or local charities/foundations are committed. This shall include good quality blood products (leuco-reduced or irradiated); drugs for conditioning regimens (busulphan, tiothepa, fludarabine, cyclophosphamide, melphalan), GVHD prophylaxis and treatment (methotrexate, thymoglobuline, cyclosporine, mycophenolate mofetil), infections control (broad spectrum antibiotics, one anti-mold drug, ganciclovir) and essential laboratory tests (at least cyclosporin levels and citomegalovirus copies count). Conclusion: The strategy described above requires the availability of expert BMT physicians and nurses willing to rotate periodically in MICs Units for training on the job and supervision. This model is replicable in different contexts, allows a fast development of BMT units in MICs, and in our opinion compares favorably with that of offering training to multiple professionals in specialized centers. Figure Disclosures No relevant conflicts of interest to declare.

Social collateral, soft information and online peer-to-peer lending: A theoretical model

Traditional credit markets have been criticized as inefficient in allocating credits to borrowers. Powered by advanced Internet technology, online Peer-to-Peer (P2P) lending has emerged as an attractive alternative, especially for small borrowers who have limited assets and are in need of funds urgently. Although several empirical studies have examined factors influencing the micro-level lending outcome, there is a lack of understanding on the overall business model of P2P lending, especially its screening mechanism, and how it helps address the deficiency of the traditional credit market. This paper fills this void. First, we develop a theoretical model incorporating two unique features of P2P lending (soft information and social collateral) and show that in P2P, low-risk borrowers could force high-risk ones off the market under very general conditions. As a result, P2P complements traditional credit markets by serving the unserved (low-risk borrowers with little assets) in the traditional credit markets. Second, we further identify the critical operational settings for P2P success, and the impacts of these settings on borrowers’ welfare. Overall, our model and analyses not only contribute to the literature by showing analytically that P2P and the traditional credit markets are complementary, but also provide practical guidance to P2P platform managers regarding their platform design to help reshape business strategies and enhance business opportunities.

Development of a Reproducible Prognostic Gene Signature to Predict the Clinical Outcome in Patients with Diffuse Large B-Cell Lymphoma

Alongside various clinical prognostic factors for diffuse large B-cell lymphoma (DLBCL) such as the international prognostic index (IPI) components (ie, age, tumor stage, performance status, serum lactate dehydrogenase concentration, and number of extranodal sites), prognostic gene signatures have recently shown promising efficacy. However, previously developed signatures for DLBCL suffer from many major inadequacies such as lack of reproducibility in external datasets, high number of members (genes) in a signature, and inconsistent association with the survival time in various datasets. Accordingly, we sought to find a reproducible prognostic gene signature with a minimal number of genes. Seven datasets—namely GSE10856 (420 samples), GSE31312 (470 samples), GSE69051 (157 samples), GSE32918 (172 samples), GSE4475 (123 samples), GSE11318 (203 samples), and GSE34171 (91 samples)—were employed. The datasets were randomly categorized into training (1219 samples comprising GSE10856, GSE31312, GSE69051, and GSE32918) and validation (417 samples consisting of GSE4475, GSE11318, and GSE34171) groups. Through the univariate Cox proportional hazards analysis, common genes associated with the overall survival time with a P value less than 0.001 and a false discovery rate less than 5% were identified in 1219 patients included in the 4 training datasets. Thereafter, the common genes were entered into a multivariate Cox proportional hazards analysis encompassing the common genes and the international prognostic index (IPI) factors as covariates, and then only common genes with a significant level of difference (P < 0.01 and z-score >2 or <−2) were selected to reconstruct the prognostic signature. After the analyses, a 7-gene prognostic signature was developed, which efficiently predicted the survival time in the training dataset (Ps < 0.0001). Subsequently, this signature was tested in 3 validation datasets. Our signature was able to strongly predict clinical outcomes in the validation datasets (Ps < 0.0001). In the multivariate Cox analysis, our outcome predictor was independent of the routine IPI components in both training datasets (Ps < 0.0001). Furthermore, our outcome predictor was the most powerful independent prognostic variable (Ps < 0.0001). We developed a potential reproducible prognostic gene signature which was able to robustly discriminate low-risk patients with DLBCL from high-risk ones.

Modeling the Switch from Hail Insurance to Anti-Hail Nets

In several areas of the world, hail is one of the most detrimental atmospheric phenomenon for agriculture, causing a significant loss of output and, consequently, of farms' revenues. Despite being a highly stochastic and localized phenomenon, thus allowing for a sustainable insurance market to hedge against its detrimental effects, this last is often subsidized. The present paper tries to figure out if the promotion of an alternative hedging instrument, anti-hail nets, could help to increase the actuarial soundness of the hail insurance market. In the first part of the paper a simple model is presented showing that the relation between the differential profitability of anti-hail nets versus insurance and the plot specific versus the average expected damage has an inverse U-shape. This implies that incentives to anti-hail nets could cause low risk farmers to exit the insurance market more likely than high risk ones. Such finding is confirmed by the empirical investigation, further showing that higher per-hectare output values and being located in an area strongly affected by hail increase the chance of a plot to be hedged through anti-hail nets.

Characteristics of the course of squamous cell carcinoma of the oral cavity depending on the HPV status.

e17579 Background: HPV infection has a positive prognostic value in the treatment of patients with oropharyngeal squamous cell carcinoma. The purpose of the study was to evaluate the effect of HPV status on the course of oral cavity cancer. Methods: Formalin-fixed paraffin-embedded tumor tissues were studied in 34 patients with cancer of the floor of the mouth aged 47-85 years, 3 (8.8%) women and 31 (91.2%) men. All patients had histologically verified squamous cell carcinoma: stage (st) I in 1 (2.9%), II st - 8 (23.5%), III st - 12 (35.3%), IV st - 13 (38.3%); G1 in 15 (44.1%), G2 - 19 (55.9%). HPV DNAs were detected by Real-time PCR. Results: HPV DNAs were found in 12 (35.3%) samples of tumor tissues, including type 6 in 1 (2.9%), 11 in 3 (8.8%), 16 in 6 (17.6%), 35 in 1 (2.9%), 16+35 in 1 (2.9%). HPV+ tumors were more often in women (66.7% vs 32.3% in men), but high-risk HPV types were detected in men only - 8 (25.8%). Among patients aged 47-55 years, HPV+ tumor status was detected in 4 (33.3%), 56-65 years in 7 (53.8%), 66 years and older - in 1 (11.1%). In st I, no HPV+ tumors were observed; st II - 3 (37.5%) HPV+ tumors, low-risk in all; st III - 3 (25%) HPV+ patients, including high-risk in 2 (16.7%); st IV - 6 (46.2%) HPV+ samples, high-risk in all. G1 tumors: HPV+ in 7 (46.7%), HPV- in 8 (53.3%) patients; G2 tumors: HPV+ in 5 (26.3%), HPV- in 14 (73.7%) patients. Among patients with HPV+ tumors, metastases were observed in 5 (41.7%), no metastases - in 7 (58.3%); for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. 4 (33.3%) patients with HPV+ tumors died, while 8 (66.7%) survived; for patients with HPV- tumors, the values were 12 (54.5%) and 10 (45.5%) respectively. Conclusions: The development of squamous cell carcinoma of the oral cavity was multidirectional and depended on the HPV status. HPV+ tumors, especially high-risk ones, were more often registered in stages III and IV. HPV+ tumors were more often lower-grade ones and less often metastasized; the mortality rate among patients with HPV+ tumors was lower than with HPV- ones.

Long-Term Carfilzomib for High-Risk Patients with Newly Diagnosed Multiple Myeloma: A Pooled Analysis of Two Phase 1/2 Studies

Long-Term Carfilzomib for High-Risk Patients with Newly Diagnosed Multiple Myeloma: A Pooled Analysis of Two Phase 1/2 Studies

Modes of death and prognostic outliers in chronic heart failure

The impact of incident sudden cardiac death (SCD) on the predictive accuracy of prognostic risk scores for patients with chronic heart failure (HF) has rarely been examined. We assessed the relationship between estimated probability of death and modes of death in this population, as well as the predictors of death and survival in prognostic outliers. The MAGGIC 3-year probability of death was estimated in 6,859 participants of the GISSI-HF trial (mean age 67±11 years, 78% men, 91% with ejection fraction <40%, mean follow-up 3.5±1.3 years, observed mortality 28.4%). The incidence of SCD progressively decreased with increased probability of death, and occurred in 52.5% of patients estimated at low-risk (N = 61 with probability <14%) vs. in 23.5% of the high-risk ones (N = 375 with probability >56%, P < .0001). On the contrary, death from worsening HF was significantly more frequent in the latter group (19.7% vs. 46.1%, P < .0001). The overall predictive accuracy of the MAGGIC model improved after excluding deaths from SCD (AUC from 0.731 to 0.760, P = .0034). Among patients estimated at low-risk (N = 61 dead, 743 alive), independent predictors of death were older age, longer history of HF, higher serum uric acid and chronic obstructive pulmonary disease. The only predictor of survival in patients estimated at high-risk (N = 210 alive, 375 dead) was higher systolic blood pressure. The MAGGIC risk score demonstrated its scarce ability to capture SCD, particularly in chronic HF patients estimated at low risk of death. Newer and better prognostic tools in the evolving horizon of HF are needed.

Mortality attributable to different Klebsiella susceptibility patterns and to the coverage of empirical antibiotic therapy: a cohort study on patients admitted to the ICU with infection.

To evaluate the prognostic importance of different Klebsiella spp. sensitivity patterns: multi-susceptible Klebsiella (MS-K), extended-spectrum cephalosporin-resistant, but carbapenem-susceptible Klebsiella (ESCR-CS-K), and carbapenem-resistant Klebsiella (CR-K). We developed a prognostic model to predict hospital mortality in patients with infection on admission to the intensive care units (ICUs), and assessed its calibration in the subgroups of interest: patients with infections due to MS-K, ESCR-CS-K, CR-K. We assessed the calibration of the model also in ESCR-CS-K treated empirically with carbapenems and with piperacillin-tazobactam. A total of 13,292 adults with an ongoing infection were admitted to 137 Italian ICUs in 2012-2013. Of 801 Klebsiella spp. infected patients, 451 had MS-K, 116 ESCR-CS-K, and 234 CR-K. The prognostic model calibrated well for the MS-K and ESCR-CS-K subgroups. In the CR-K subgroup there were more deaths than predicted (standardized mortality ratio 1.20; 95% CI 1.08-1.31), indicating a negative prognostic role of the infection, mainly in the medium and high risk-of-death patients. When infection was caused by ESCR-CS-K, treatment with piperacillin-tazobactam increased adjusted mortality among the most severe patients (similarly to CR-K), while treatment with carbapenems did not (similarly to MS-K). In low risk-of-death patients admitted to the ICU with a Klebsiella spp. infection, the appropriateness of empirical antibiotic therapy seemed uninfluential to eventual mortality, while it appeared to be crucial in high-risk ones. The use of piperacillin-tazobactam may be inappropriate in severe patients with ESCR-CS-K infection. CR-K is associated to a significant 20% increase of adjusted mortality, only for patients at higher risk of death.

Application of chest CT scan in gestational trophoblastic neoplasia with lung metastasis

Objective: To explore the role of CT scan for the diagnosis of lung metastasis in stage Ⅲ gestational trophoblastic neoplasia (GTN) . Methods: To figure out the role of CT scan for lung metastasis in GTN initial diagnosis, treatment and follow-up, 93 GTN patients with lung metastasis from January, 2015 to December, 2016 were retrospectively analyzed in Obstetrics and Gynecology Hospital of Fudan University. Results: (1) Among 93 GTN patients with lung metastasis, 70 patients with the International Federation of Gynecology and Obstetrics (FIGO) score ≤6 were defined as low risk GTN and 23 patients score score ≥7 were defined as high risk GTN. Forty nine patients had negative chest X-ray findings and 39 cases with pulmonary lesions were identified both by chest X-ray compared to CT scan. Five cases were excluded due to no consensus could make for the results of chest X-ray. The true positive rate of chest X-ray for lung metastasis were 41% (29/70) in low risk GTN and 43% (10/23) in high risk GTN patients without statistical difference (χ(2)=0.090, P=0.925) . For those patients with positive chest CT scan and negative chest X-ray finding, pulmonary lesions in 32 (65%, 32/49) cases were blocked by heart, chest wall or diaphragm in chest X-ray. Seventeen (35%,17/49) patients with lung lesions less than 5 mm had negative chest X-ray results due to the lower sensitivity compared to CT scan. (2) In 88 patients with stage Ⅲ, 78 patients had successful initial treatment, but 4 of them were recurrence in twelve months follow-up. Ten patients were chemotherapy resistance for the initial treatment. The initial chemotherapy remission rate in low risk GTN patients was higher than that in high risk ones (χ(2)=4.911, P=0.027) . In 49 cases with negative chest X-ray, there was no correlation with the rate of remission,chemotherapy resistance and recurrence in stage Ⅲ patients (P>0.05) . (3) For those patients who had poorly response to initial chemotherapy, the diameters of lesions in lung were unchanged or increased during the treatment, form (5.1±4.1) mm to (7.4±2.8) mm. The pulmonary lesions were continuously shrunk from (7.8±5.3) mm to (4.7±4.4) mm for those patients with complete and partial remission including the recurrent GTN patients (Z=-2.713, P=0.007) . Conclusions: Patients with GTN in stage Ⅲ have down staging if only use chest X-ray for imaging at the initial diagnosis. Chest CT scan is recommended for primary imaging evaluation of FIGO staging in qualified medical organization. For those patients with persistent abnormal serum hCG level and negative chest X-ray, chest CT scan is strongly recommended to identify the persist or resistant lung lesions and follow up.