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Background & Aims Sustained virological response (SVR) by direct‐acting antivirals (DAAs) may reverse the hypercoagulable state of HCV cirrhosis and the portal vein thrombosis (PVT) risk. We evaluated the incidence and predictive factors of de novo, non‐tumoral PVT in patients with cirrhosis after HCV eradication. Methods Patients with HCV‐related cirrhosis, consecutively enrolled in the multi‐center ongoing PITER cohort, who achieved the SVR using DAAs, were prospectively evaluated. Kaplan‐Meier and competing risk regression analyses were performed. Results During a median time of 38.3 months (IQR: 25.1–48.7 months) after the end of treatment (EOT), among 1609 SVR patients, 32 (2.0%) developed de novo PVT. A platelet count ≤120,000/μL, albumin levels ≤3.5 mg/dL, bilirubin >1.1 mg/dL, a previous liver decompensation, ALBI, Baveno, FIB‐4, and RESIST scores were significantly different (p < 0.001), among patients who developed PVT versus those who did not. Considering death and liver transplantation as competing risk events, esophageal varices (subHR: 10.40; CI 95% 4.33–24.99) and pre‐treatment ALBI grade ≥2 (subHR: 4.32; CI 95% 1.36–13.74) were independent predictors of PVT. After HCV eradication, a significant variation in PLT count, albumin, and bilirubin (p < 0.001) versus pre‐treatment values was observed in patients who did not develop PVT, whereas no significant differences were observed in those who developed PVT (p > 0.05). After the EOT, esophageal varices and ALBI grade ≥2, remained associated with de novo PVT (subHR: 9.32; CI 95% 3.16–27.53 and subHR: 5.50; CI 95% 1.67–18.13, respectively). Conclusions In patients with HCV‐related cirrhosis, a more advanced liver disease and significant portal hypertension are independently associated with the de novo PVT risk after SVR.

Recurrent FUO (fever of unknown origin) is a rare subtype of FUO for which diagnostic procedures are ill-defined and outcome data are lacking. We performed a retrospective multicentre study of patients with recurrent FUO between 1995 and 2018. By multivariate analysis, we identified epidemiological, clinical and prognostic variables independently associated with final diagnosis and mortality. Of 170 patients, 74 (44%) had a final diagnosis. Being ≥ 65 years of age (OR = 5.2; p < 0.001), contributory history (OR = 10.4; p < 0.001), and abnormal clinical examination (OR = 4.0; p = 0.015) independently increased the likelihood of reaching a diagnosis, whereas lymph node and/or spleen enlargement decreased it (OR = 0.2; p = 0.004). The overall prognosis was good; 58% of patients recovered (70% of those with a diagnosis). Twelve (7%) patients died; patients without a diagnosis had a fatality rate of 2%. Being ≥ 65 years of age (OR = 41.3; p < 0.001) and presence of skin signs (OR = 9.5; p = 0.005) significantly increased the risk of death. This study extends the known yield of recurrent FUO and highlights the importance of repeated complete clinical examinations to discover potential diagnostic clues during follow-up. Moreover, their overall prognosis is excellent.

Although testosterone replacement therapy (TRT) is the first-choice method used worldwide for late-onset hypogonadism (LOH), clinical benefits are not seen in all cases. This study was conducted to determine the predictors of TRT efficacy for LOH. Fifty-six patients who visited our Men's Health Clinic (Kawanishi City Medical Center, Kawanishi and Hyogo Medical University, Nishinomiya, Hyogo, Japan) between November 2003 and June 2021 with data available before and after TRT were enrolled. They were divided into responders (Group 1; n = 45, accounting for 80.4%) and nonresponders (Group 2; n = 11, accounting for 19.6%) based on the clinical response to TRT, including patient satisfaction. Factors noted before TRT included age, body mass index, aging males' symptoms score, sexual health inventory for men, luteinizing hormone, follicular-stimulating hormone, testosterone, free testosterone, prolactin (PRL), estradiol (E2), and testosterone/estradiol (T/E2) ratio in serum. For statistical analysis, a multivariable logistic regression model was used. Univariate analysis revealed PRL (odds ratio [OR]: 0.9624; 95% confidence interval [CI]: 0.9316-0.9943, P < 0.05), E2 (OR: 0.8692; 95% CI: 0.7745-0.9754, P < 0.05), and T/E2 ratio (OR: 1.1312; 95% CI: 1.0106-1.2661, P < 0.05) to be predictive factors. Multivariate analyses showed that T/E2 ratio was an independent predictive factor (OR: 1.1593; 95% CI: 1.0438-1.2875, P < 0.01). The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT. The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics (ROC) curve analysis was shown to be 17.3. Although additional studies with larger number of patients are necessary, we propose the determination of serum E2 level and testosterone level prior to performing TRT.

Predictive factors including risk perception for mid-term mental health after a nuclear disaster remain unknown. The purpose of this study was to examine the association between perceived radiation risk and other factors at baseline and mid-term mental health after the Fukushima Daiichi nuclear disaster of 2011 in Japan. A mail-based questionnaire survey was conducted in January 2012 and January 2013. Mental health status was assessed using the K6 scale. Psychological distress over the 2-year period was categorized into the following four groups: chronic, recovered, resistant, or worsened. Most participants (80.3%) were resistant to the disaster. A positive association was found between the radiation risk perception regarding immediate effects and the worsened group in women. Baseline post-traumatic stress disorder (PTSD) or a history of psychiatric disease predicted being in the chronic or worsened group in mid-term course. These results suggest that evacuees who believed that their health was substantially affected by the nuclear disaster were at an increased risk of having poor mid-term mental health in women. Careful assessment of risk perception after a nuclear disaster, including the presence of PTSD or a history of psychiatric disease, is needed for appropriate interventions.

This study aimed to clarify local recurrence (LR) predictive factors following intraoperative microwave ablation (MWA) for colorectal liver metastases. The data from 195 patients with 1392 CRLM lesions, who were preoperatively diagnosed by gadolinium-enhanced MRI with diffusion-weighted imaging and dynamic CT and treated with intraoperative MWA (2450 MHz) with or without hepatectomy, from January 2005 to December 2019, were retrospectively reviewed and analyzed using logistic regression. In addition, the margins were measured on contrast-enhanced CT 6 weeks post-ablation. Overall, 1066 lesions were ablated. The LRs occurred in 44 lesions (4.1%) among 39 patients (20.0%). The multivariate analysis per patient showed that tumor size > 20 mm and ablation margin < 5 mm were significant predictors for LR. Furthermore, multivariate analysis per lesion revealed that segments 1, 7, and 8 and tumor size > 15 mm, ablation margin < 5 mm, tumor size > 20 mm, and proximity to the Glisson were significant LR predictors. Finally, the outcome of this study may help determine indications for MWA.

Previous data have revealed an association between eosinopenia and mortality of acute ischemic stroke. However, the relationship of eosinopenia with infarct volume, infection rate, and poor outcome of acute ischemic stroke is still unknown. The retrospective study included 421 patients (273 males, 65%; mean age, 68.0 ± 13.0 years) with first acute ischemic stroke who were hospitalized in the Second Affiliated Hospital of Soochow University, China, from January 2017 to February 2018. Laboratory data, neuroimaging results, and modified Rankin Scale scores were collected. Patients were divided into four groups according to their eosinophil percentage level (< 0.4%, 0.4-1.1%, 1.1-2.3%, ≥ 2.3%). Spearman's correlation analysis showed that the percentage of eosinophils was negatively correlated with infarct volume (rs = −0.514, P < 0.001). Receiver operating characteristic analysis demonstrated that eosinopenia predicted a large infarct volume more accurately than neutrophilia; the area under curve was 0.906 and 0.876, respectively; a large infarct was considered as that with a diameter larger than 3 cm and involving more than two major arterial blood supply areas. Logistic regression analysis revealed that eosinophil percentage was an independent risk factor for acute ischemic stroke (P = 0.002). Moreover, eosinophil percentage was significantly associated with large infarct volume, high infection rate (pulmonary and urinary tract infections), and poor outcome (modified Rankin Scale score > 3) after adjusting for potential confounding factors (P-trend < 0.001). These findings suggest that eosinopenia has the potential to predict the severity of acute ischemic stroke. This study was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, China (approval number: K10) on November 10, 2015.

Background: To test the hypotheses that breast cancer patients with one to three positive lymph nodes (pN1) consist of heterogeneous prognostic subsets and that the ratio of positive nodes to total nodes dissected (lymph node ratio, LNR) might discriminate patients with a higher risk as candidates for post-mastectomy radiation therapy (PMRT). Methods: Using information from 7741 node-positive patients, we first identified cutoff values of the LNR using the nonparametric bootstrap method. Focusing on 3477 patients with pN1 disease, we then evaluated the clinical relevance of the LNR categorised by the estimated cutoff values (categorised LNR, cLNR). Results: Among 3477 patients with pN1 disease, 3059 and 418 patients were assigned into the low and intermediate cLNR groups, respectively, based on a cutoff value of 0.18. The prognostic factors associated with poor overall survival (OS) included younger age, T2 stage, negative oestrogen/progesterone receptors, high histologic grade, and intermediate cLNR. Post-mastectomy radiation therapy significantly increased OS in patients assigned to the intermediate cLNR (hazard ratio, 0.39; 95% confidence interval, 0.17–0.89; P =0.0248), whereas patients in the low cLNR group derived no additional survival benefit from PMRT. Conclusion: This study suggests that PMRT should be recommended for patients with pN1 disease and an intermediate cLNR.

Background Accurate and practical outcome measures for clinical trials in systemic lupus erythematosus (SLE) are lacking. The SLE Disease Activity Score (SLE-DAS) is a recently validated 17-item instrument, with high accuracy and sensitivity to changes in SLE disease activity. The SLE-DAS definitions of remission and low disease activity (LDA) were newly validated in the clinical setting1,2. These definitions may constitute accurate and easy to apply endpoints for SLE trials. Objectives (1) To evaluate the ability of SLE-DAS remission and LDA definitions to discriminate drug from placebo in SLE phase 3 trials; (2) To determine if attainment of these SLE-DAS targets are associated with better health-related quality of life (HR-QoL). Methods Post-hoc analysis of the merged study population in the BLISS-52 and -76 trials (NCT00424476; NCT00410384) of intravenous belimumab versus placebo for moderate to severe SLE disease activity. We analyzed the British Isles Lupus Assessment Group (BILAG), Physician Global Assessment (PGA), Functional Assessment of Chronic Illness Therapy (FACIT) and 36-Item Short Form Survey (SF-36) trial data. The fulfillment of SLE-DAS remission and LDA definitions were retrospectively assessed from the individual participants’ data. Proportion of patients attaining SLE-DAS Boolean remission (defined as absence of all SLE-DAS clinical items and prednisone ≤5mg/day) and LDA (defined as SLE-DAS≤2.48 and prednisone ≤7.5mg/day), at week 52, was compared between belimumab and placebo arms, using likelihood ratio chi-square test. We further compared the SF-36 physical component summary (PCS) and mental component summary (MCS) and domain scores and the FACIT score between patients attaining SLE-DAS remission vs non-remission and SLE-DAS LDA vs non-LDA, using t-test and Mann-Whitney test. Results A total of 1684 SLE patients were included: 562 on placebo, 559 on belimumab 1mg/Kg and 563 on belimumab 10mg/Kg. At week 52, significantly more patients attained SLE-DAS LDA on belimumab 1mg/Kg and 10mg/Kg as compared with placebo (13.0% vs 17.9%, OR=1.459, p=0.023, and 13.0% vs 21.7%, OR=1.853, p<0.001, respectively). Likewise, more patients attained SLE-DAS remission on belimumab 10mg/Kg as compared with placebo (10.1% vs 14.7%, OR= 1.532, p=0.019) (Table 1). Importantly, none of the patients achieving SLE-DAS remission or LDA presented a new BILAG A or more than 1 new B domain score, neither a worsening in PGA≥0.3. Conclusion The SLE-DAS remission and LDA showed discriminant validity for identifying patients receiving active drug in clinical trials. These treatment targets are associated with better HR-QoL and lower fatigue.

KRAS mutations are the most frequent gain-of-function alterations in patients with lung adenocarcinoma (LADC) in the Western world. Although they have been identified decades ago, prior efforts to target KRAS signaling with single-agent therapeutic approaches such as farnesyl transferase inhibitors, prenylation inhibition, impairment of KRAS downstream signaling, and synthetic lethality screens have been unsuccessful. Moreover, the role of KRAS oncogene in LADC is still not fully understood, and its prognostic and predictive impact with regards to the standard of care therapy remains controversial. Of note, KRAS-related studies that included general non-small cell lung cancer (NSCLC) population instead of LADC patients should be very carefully evaluated. Recently, however, comprehensive genomic profiling and wide-spectrum analysis of other co-occurring genetic alterations have identified unique therapeutic vulnerabilities. Novel targeted agents such as the covalent KRAS G12C inhibitors or the recently proposed combinatory approaches are some examples which may allow a tailored treatment for LADC patients harboring KRAS mutations. This review summarizes the current knowledge about the therapeutic approaches of KRAS-mutated LADC and provides an update on the most recent advances in KRAS-targeted anti-cancer strategies, with a focus on potential clinical implications.

The majority of academic papers are scarcely cited while a few others are highly cited. A large number of studies indicate that there are many factors influencing the number of citations. An actual review is missing that provides a comprehensive review of the factors predicting the frequency of citations. In this review, we performed a search in WoS, Scopus, PubMed and Medline to retrieve relevant papers. In overall, 2087 papers were retrieved among which 198 relevant papers were included in the study. Three general categories with twenty eight factors were identified to be related to the number of citations: Category one: “paper related factors”: quality of paper; novelty and interest of subject; characteristics of fields and study topics; methodology; document type; study design; characteristics of results and discussion; use of figures and appendix in papers; characteristics of the titles and abstracts; characteristics of references; length of paper; age of paper; early citation and speed of citation; accessibility and visibility of papers. Category two: “journal related factors”: journal impact factor; language of journal; scope of journal; form of publication. Category three: “author(s) related factors”: number of authors; author’s reputation; author’s academic rank; self-citations; international and national collaboration of authors; authors’ country; gender, age and race of authors; author’s productivity; organizational features; and funding. Probably some factors such as the quality of the paper, journal impact factor, number of authors, visibility and international cooperation are stronger predictors for citations, than authors’ gender, age and race; characteristics of results and discussion and so on.