Search

Background The previous second-line treatment for HER2-positive metastatic breast cancer were ado-trastuzumab emtansine (T-DM1); however, its activity is decreased in tumors with heterogenous, reduced, or loss of HER2 expression. Trastuzumab deruxtecan (T-DXd) has recently been developed as a novel antibody-drug conjugate to overcome resistance to T-DM1. However, clinical evidence on its ability to overcome this resistance is limited. Materials and methods We retrospectively analyzed data for patients with HER2-positive metastatic breast cancer who received T-DXd at our institution from April 2020 to March 2021. We evaluated the associations between clinicopathological and molecular biomarkers and the efficacy of T-DXd. Results Twenty-two patients were enrolled in this study. The median progression-free survival (PFS) was 9.7 months (95% confidence interval [CI], 7.0–not reached [NR]), and the objective response rate (ORR) was 61.9%. The ORR and PFS were comparable between patients with HER2 immunohistochemistry scores of 3+ and 2+/1+ at initial diagnosis (ORR: 50.0% vs. 72.7%, p = 0.39; median PFS, 9.7 months [95%CI, 2.6–NR] vs. 8.3 months [95%CI, 7.1–NR]; hazard ratio, 1.86 [95%CI, 0.53–6.57], p = 0.34). Two patients with heterogenous HER2 expression had a partial response or long stable disease (≥6 months). Three of four patients with re-biopsy samples after anti-HER2 targeted therapy and with latest HER2 immunohistochemistry scores of 1+ experienced partial responses (75.0%) to T-DXd, but none had responded to prior T-DM1. Conclusions T-DXd demonstrated favorable activity in clinical practice. Moreover, T-DXd showed meaningful benefit in patients with heterogeneity, reduction, or loss of HER2 expression., Highlights • T-DXd showed favorable clinical activity against HER2-positive metastatic breast cancer. • T-DXd showed benefit in patients with heterogeneity, reduction, or loss of HER2 expression. • Patients with liver metastasis tended to have worse outcomes.

Introduction The severity of coronavirus disease (COVID-19) in Japanese patients is unreported. We retrospectively examined significant factors associated with disease severity in symptomatic COVID-19 patients (COVID-Pts) admitted to our institution between February 20 and April 30, 2020. Methods All patients were diagnosed based on the genetic detection of severe acute respiratory syndrome coronavirus 2. Information on the initial symptoms, laboratory data, and computed tomography (CT) images at hospitalization were collected from the patients’ records. COVID-Pts were categorized as those with critical or severe illness (Pts-CSI) or those with moderate or mild illness (Pt-MMI). All statistical analyses were performed using R software. Results Data from 61 patients (16 Pt–CSI, 45 Pt-MMI), including 58 Japanese and three East Asians, were analyzed. Pt–CSI were significantly older and had hypertension or diabetes than Pt-MMI (P

Background Immune checkpoint inhibitor (ICI)-related cardiotoxicity (iRC) is uncommon but can be fatal. There have been few reports of iRC from a rural cancer population and few data for iRC and inflammatory biomarkers. Objectives The purpose of this study was to characterize major adverse cardiac events (MACE) in ICI-treated lung cancer patients based in a rural setting and to assess the utility of C-reactive protein (CRP) and neutrophil-lymphocyte ratio (NLR) in the diagnosis of iRC. Methods Patients with lung cancer treated with ICIs at Vidant Medical Center/East Carolina University (VMC/ECU) between 2015 and 2018 were retrospectively identified. MACE included myocarditis, non-ST-segment elevated myocardial infarction (NSTEMI), supraventricular tachycardia (SVT), and pericardial disorders. Medical history, laboratory values, pre-ICI electrocardiography (ECG), and echocardiography results were compared in patients with and without MACE. Results Among 196 ICI-treated patients, 23 patients (11%) developed MACE at a median of 46 days from the first ICI infusion (interquartile range [IQR]: 17 to 83 days). Patients who developed MACE experienced myocarditis (n = 9), NSTEMI (n = 3), SVT (n = 7), and pericardial disorders (n = 4). Ejection fraction was not significantly different at the time of MACE compared to that at baseline (p = 0.495). Compared to baseline values, NLR (10.9 ± 8.3 vs. 20.7 ± 4.2, respectively; p = 0.032) and CRP (42.1 ± 10.1 mg/l vs. 109.9 ± 15.6 mg/l, respectively; p = 0.010) were significantly elevated at the time of MACE. Conclusions NLR and CRP were significantly elevated at the time of MACE compared to baseline values in ICI-treated patients. Larger datasets are needed to validate these findings and identify predictors of MACE that can be used in the diagnosis and management of ICI-related iRC., Central Illustration

Background Most articles describing the effect of the coronavirus disease 2019 (COVID-19) pandemic on neurosurgical services have been from developed countries. We report our experience in carrying out neurosurgical services at Dr. Sardjito General Hospital, Yogyakarta, Indonesia, during the time of the pandemic. Methods To collect information on the effect of the pandemic in Indonesia and Yogyakarta, we gathered data from the Indonesian Ministry of Health's online database for the national data and local government records for the local data (including records of Dr. Sardjito General Hospital Division of Neurosurgery). Results Compared with other countries, Indonesia has not been severely hit by the impact of COVID-19. To increase our understanding of the natural history of the pandemic, we divided the period into 4 phases: phase 1 (when there were confirmed cases in Indonesia but no cases in Yogyakarta), phase 2 (when the first case in Yogyakarta was detected), phase 3 (when the cumulative cases surpass their peak), and phase 4 (when the pandemic ends). At the time of this writing, we were still in phase 2 and in this phase, we experienced a decrease in the number of emergency surgical procedures, from an average of 4 to 2.4 per week. Moreover, the number of elective operations dropped from an average of 12 to 9 per week. Conclusions A pandemic, such as COVID-19, reduces both inpatient and outpatient neurosurgical activities. A comprehensive plan can improve both utilization and safety of the neurosurgical staff.

Diabetes & Metabolism - Sous presse. Manuscrit accepte. Disponible en ligne depuis le jeudi 4 juin 2020

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)., Highlights • In December 2019, a novel coronavirus of SARS-CoV-2 emerged in Wuhan, Hubei, China, rapidly dispersed and even exported to neighboring countries. • SARS-CoV-2 generally causes a mild lower respiratory tract infection in humans, however, in some sever cases, signs of dysfunctions in multiple organs have been discovered. • Overproduction of cytokines, termed cytokine storm, may involve in disease progression and even be responsible for deaths. • Application of immune-modulators might become a complement to support treatment and flip on the light switch for severe patients.

Highlights • A high platelet-to-lymphocyte ratio (PLR; >124) before curative surgical resection was found to be associated with reduced disease-free survival (DFS) in non-metastatic colon cancer patients. • A high PLR was predominant among patients with circulating tumor microemboli (CTM). • This prospective study revealed a mechanism of interaction between circulating tumor cells (CTCs) and other blood components, and implicated platelets in CTC survival. • The present findings support the use of blood biomarkers to better identify and follow high-risk colon cancer patients., Colorectal cancer is a common and often deadly cancer. Circulating tumor cells (CTCs) have been implicated as a potentially valuable prognosis factor. The detection of circulating tumor microemboli (CTM) and of simple blood component parameters that reflect inflammatory status, such as the platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR), may provide information about tumor progression. The aim of this study was to explore the importance of CTCs, CTM, PLR, and NLR prospectively in non-metastatic colon cancer progression. CTCs were enriched using ISETⓇ (Isolation by SizE of Tumor cells) and identified by immunocytochemical exclusion of leukocytes. We evaluated CTCs and blood cell parameters in a cohort of 69 stage I–III colon cancer patients (52.2% men; median age, 61 years; age range, 19–87 years) at a baseline timepoint prior to resection surgery. The median of CTC levels at baseline was 20 cells/8 mL (0–94) and higher levels were associated with CTM presence (p = 0.02). CTM were found in 18 (26.1%) patients. Of 18 stage I patients, 33.3% had CTM and of 51 stages II or III patients, 13.7% had CTM (p = 0.08). Patients with a high PLR (>124) were mostly (75.6%) diagnosed with high-risk stages II/III cancer (stages I/low-risk II, 24.4%; p = 0.014). All 8 patients that had disease recurrence during follow-up had a high PLR (p = 0.02 vs. low PLR). NLR was not significantly associated with disease stage or recurrence. The present results indicate that CTCs and PLR analyses may be clinically useful for colon cancer management and risk stratification.

Immune checkpoint inhibitors (ICIs) are clinically used for treating advanced lung cancer, and some patients have achieved complete remission (CR) with ICI therapy in clinical trials. However, reports summarizing the clinical courses of such patients are limited. We report two cases of lung adenocarcinoma in which CR was achieved with first-line pembrolizumab monotherapy, and the therapeutic effect was maintained after treatment completion. Specific patients can achieve CR, even those who do not meet the previously reported predictors of treatment response other than high programmed death-ligand 1 expression. Thus, biomarkers that can accurately predict the clinical efficacy of ICIs are warranted.

Aims: Inflammation has been implicated in the pathogenesis of diabetic peripheral neuropathy (DPN) as suggested in various cross-sectional studies. However, more convincing prospective studies in diabetes patients are scarce. Therefore, we aimed to evaluate whether proinflammatory cytokines could predict the incidence of DPN through a prospective study with a five-year follow-up. Methods: We followed up 315 patients with diabetes who did not have DPN, recruited from five community health centers in Shanghai in 2014, for an average of 5.06 years. Based on the integrity of blood samples, 106 patients were selected to obtain the proinflammatory cytokines. Plasma markers of proinflammatory cytokines at baseline included interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and intercellular adhesion molecule 1 (ICAM-1). Neuropathy was assessed by MSNI at baseline and during follow-up. Results: Among the 106 randomly chosen patients, 63 developed DPN after 5.06±1.14 years of follow-up. The baseline plasma levels of TNF-α, IL-6, and ICAM-1 were higher in the neuropathic group (P

Background Patients with severe 2019 novel coronavirus disease (COVID-19) have a high mortality rate. The early identification of severe COVID-19 is of critical concern. In addition, the correlation between the immunological features and clinical outcomes in severe cases needs to be explored. Objective To build a nomogram for identifying patients with severe COVID-19 and explore the immunological features correlating with fatal outcomes. Methods We retrospectively enrolled 85 and 41 patients with COVID-19 in primary and validation cohorts, respectively. A predictive nomogram based on risk factors for severe COVID-19 was constructed using the primary cohort and evaluated internally and externally. In addition, in the validation cohort, immunological features in patients with severe COVID-19 were analyzed and correlated with disease outcomes. Results The risk prediction nomogram incorporating age, C-reactive protein, and D-dimer for early identification of patients with severe COVID-19 showed favorable discrimination in both the primary (area under the curve [AUC] 0.807) and validation cohorts (AUC 0.902) and was well calibrated. Patients who died from COVID-19 showed lower abundance of peripheral CD45RO+CD3+ T cells and natural killer cells, but higher neutrophil counts than that in the patients who recovered (P = .001, P = .009, and P = .009, respectively). Moreover, the abundance of CD45RO+CD3+ T cells, neutrophil-to-lymphocyte ratio, and neutrophil-to-natural killer cell ratio were strong indicators of death in patients with severe COVID-19 (AUC 0.933 for all 3). Conclusion The novel nomogram aided the early identification of severe COVID-19 cases. In addition, the abundance of CD45RO+CD3+ T cells and neutrophil-to-lymphocyte and neutrophil-to-natural killer cell ratios may serve as useful prognostic predictors in severe patients.

Graphical abstract, The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), appears with a wide spectrum of mild-to-critical clinical complications. Many clinical and experimental findings suggest the role of inflammatory mechanisms in the immunopathology of COVID-19. Hence, cellular and molecular mediators of the immune system can be potential targets for predicting, monitoring, and treating the progressive complications of COVID-19. In this review, we assess the latest cellular and molecular data on the immunopathology of COVID-19 according to the pathological evidence (e.g., mucus and surfactants), dysregulations of pro- and anti-inflammatory mediators (e.g., cytokines and chemokines), and impairments of innate and acquired immune system functions (e.g., mononuclear cells, neutrophils and antibodies). Furthermore, we determine the significance of immune biomarkers for predicting, monitoring, and treating the progressive complications of COVID-19. We also discuss the clinical importance of recent immune biomarkers in COVID-19, and at the end of each section, recent clinical trials in immune biomarkers for COVID-19 are mentioned.

Purpose To clarify the epidemiological, clinical, and therapeutic features of patients with severe COVID-19. Methods In this study, we enrolled 681 patients with confirmed cases of severe COVID-19. The epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected. Results The median age of the study participants was 65 years, 53.2% were male, and 104 (15.3%) died. Age, Neutrophil-To-Lymphocyte Ratio (NLR), acute myocardial injury, and levels of C-reactive protein (CRP), lactate dehydrogenase (LDH), and CD3 T cells counts were independently and negatively associated with death, while arbidol and ribavirin were protective from death. The combination of NLR and acute myocardial injury on admission (AUC = 0.914) predicted mortality better than NLR, CRP, LDH, and acute myocardial injury. There were 312 (45.8%) patients with cardiovascular disease, of whom 23.4% died. β-blockers, ACEI/ARB, arbidol, and ribavirin might have a beneficial effect for severe COVID-19 patients with cardiovascular disease. Conclusion The combination of NLR and acute myocardial injury on admission was highly predictive of mortality and survival. Clinicians should adopt more aggressive strategies for patients with a high NLR (>6.66) combined with myocardial injury. β-blockers and ACEI/ARB, as well as arbidol and ribavirin, were effective in COVID-19 patients with cardiovascular disease., Highlights • Combination of NLR and acute myocardial injury could predict mortality. • Patients combined with higher NLR and myocardial injury need aggressive strategies. • Arbidol and ribavirin may be benefit to severe COVID-19. • β-blockers and ACEI/ARB are effective for patients with cardiovascular disease.

Highlights • Coronavirus pandemic has created a global alarming situation. • SARS-CoV shares sequence homology with bats, therefore, considered as origin. • Scientists are burning midnight's oil to discover drug or vaccine against this deleterious virus. • Medicinal plants should be explored to find a cure for this disease. • Phyto-constituents are ubiquitously synthesised in plants, effective against SARS-CoV-2. • Clinical trials for herbal formulations are promoted to find drug or vaccine. • Other armours like physical fitness, balanced diet are promoted for boosting immunity., Current scenario depicts that world has been clenched by COVID-19 pandemic. Inevitably, public health and safety measures could be undertaken in order to dwindle the infection threat and mortality. Moreover, to overcome the global menace and drawing out world from moribund stage, there is an exigency for social distancing and quarantines. Since December, 2019, coronavirus, SARS-CoV-2 (COVID-19) have came into existence and up till now world is still in the state of shock.At this point of time, COVID-19 has entered perilous phase, creating havoc among individuals, and this has been directly implied due to enhanced globalisation and ability of the virus to acclimatize at all conditions. The unabated transmission is due to lack of drugs, vaccines and therapeutics against this viral outbreak. But research is still underway to formulate the vaccines or drugs by this means, as scientific communities are continuously working to unravel the pharmacologically active compounds that might offer a new insight for curbing infections and pandemics. Therefore, the topical COVID-19 situation highlights an immediate need for effective therapeutics against SARS-CoV-2. Towards this effort, the present review discusses the vital concepts related to COVID-19, in terms of its origin, transmission, clinical aspects and diagnosis. However, here, we have formulated the novel concept hitherto, ancient means of traditional medicines or herbal plants to beat this pandemic., Graphical abstract Image, graphical abstract

Introduction: Anemia has long been associated with poor prognosis in patients with cervical cancer. Recently, additional hematologic parameters have emerged as potential indicators of worse outcome in this patient group. In a cohort of cervical cancer patients treated with chemoradiotherapy (CRT) and brachytherapy, we report on the prognostic significance of hematologic parameters including anemia, leukocytosis, neutrophil to lymphocyte ratio (NLR), and thrombocytosis, the effect of combining anemia with other hematologic parameters, and the effect of changes in hemoglobin levels during treatment. Materials and methods: Two-hundred fifty-seven cervical cancer patients were retrospectively identified from a single cancer institution’s database. Hematologic parameters were categorized as: anemia (hemoglobin ≤115 g/L), leukocytosis (white blood cell count >10 × 109/L), thrombocytosis (platelets >400 × 109/L), and NLR (ratio >5). The association between clinical factors and hematologic parameters on progression-free survival (PFS) and overall survival (OS) were assessed at 5 years. Results: At 5 years, both pre-treatment anemia (PFS: 60% vs 34%, p

Highlights • A literature search was conducted using PubMed, Web of Science and CNKI. • Increased NLR was a strong predictor for overall survival and disease-free survival. • Subgroup analyses stratified by ethnicity, analysis method and metastasis were conducted. • NLR could be considered as a predictive factor for patients with breast cancer., Inflammation is an essential component of pathogenesis and progression of cancer. A high neutrophil-to-lymphocyte ratio (NLR) is considered as a prognostic indicator for breast cancer. This meta-analysis was conducted to establish the overall accuracy of the NLR test in the diagnosis of breast cancer. A comprehensive search of the literature was conducted by using PubMed, Web of Science and China National Knowledge Infrastructure (CNKI). Published studies dating up to July 2014 and 4,293 patients were enrolled in the present study. In order to evaluate the association between NLR and overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) or cancer specific survival (CSS), the hazard ratios (HRs) and their 95% confidence intervals (CIs) were extracted. OS was the primary outcome. The results suggested that increased NLR was a strong predictor for OS with HR of 2.28 (95% CI = 1.08–4.80, Pheterogeneity

Lactobacillus plantarum HOKKAIDO (HOKKAIDO strain) was isolated from well-pickled vegetables in Hokkaido, Japan. We report a randomized, double-blind, placebo-controlled study evaluating the effects of L. plantarum HOKKAIDO on immune function and stress markers in 171 adult subjects. Subjects were divided into three groups: the L. plantarum HOKKAIDO yogurt group, the placebo-1 group who ingested yogurt without the HOKKAIDO strain, and the placebo-2 group who ingested a yogurt-like dessert without the HOKKAIDO strain. Hematological tests and body composition measurements were performed before and after 4 and 8 weeks of blinded ingestion. Although no significant differences in natural killer cell activity were observed, it was found that neutrophil ratio significantly decreased and lymphocytes tended to increase in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. In addition, the neutrophil-to-lymphocyte ratio, a stress marker, tended to improve in the HOKKAIDO strain yogurt group compared with the yogurt-like dessert group. These results suggest that the ingestion of HOKKAIDO strain yogurt tends to improve immune activity and decrease stress markers., Graphical abstract