The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term ...adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the ...therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.
Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.
Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0–78.2) with nivolumab plus SOX and 76.5% (50.1–93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8–NR) and 10.6 months (5.6–12.5), respectively.
Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.
NCT02746796.
Background Current practice of adding concurrent–adjuvant chemotherapy to radiotherapy (CRT) for treating advanced nasopharyngeal carcinoma is based on the Intergroup-0099 Study published in 1998. ...However, the outcome for the radiotherapy-alone (RT) group in that trial was substantially poorer than those in other trials, and there were no data on late toxicities. Verification of the long-term therapeutic index of this regimen is needed. Methods Patients with nonkeratinizing nasopharyngeal carcinoma staged T1-4N2-3M0 were randomly assigned to RT (176 patients) or to CRT (172 patients) using cisplatin (100 mg/m2) every 3 weeks for three cycles in concurrence with radiotherapy, followed by cisplatin (80 mg/m2) plus fluorouracil (1000 mg per m2 per day for 4 days) every 4 weeks for three cycles. Primary endpoints included overall failure-free rate (FFR) (the time to first failure at any site) and progression-free survival. Secondary endpoints included overall survival, locoregional FFR, distant FFR, and acute and late toxicity rates. All statistical tests were two-sided. Results The two treatment groups were well balanced in all patient characteristics, tumor factors, and radiotherapy parameters. Adding chemotherapy statistically significantly improved the 5-year FFR (CRT vs RT: 67% vs 55%; P = .014) and 5-year progression-free survival (CRT vs RT: 62% vs 53%; P = .035). Cumulative incidence of acute toxicity increased with chemotherapy by 30% (CRT vs RT: 83% vs 53%; P < .001), but the 5-year late toxicity rate did not increase statistically significantly (CRT vs RT: 30% vs 24%; P = .30). Deaths because of disease progression were reduced statistically significantly by 14% (CRT vs RT: 38% vs 24%; P = .008), but 5-year overall survival was similar (CRT vs RT: 68% vs 64%; P = .22; hazard ratio of CRT = 0.81, 95% confidence interval = 0.58 to 1.13) because deaths due to toxicity or incidental causes increased by 7% (CRT vs RT: 1.7% vs 0, and 8.1% vs 3.4%, respectively; P = .015). Conclusions Adding concurrent–adjuvant chemotherapy statistically significantly reduced failure and cancer-specific deaths when compared with radiotherapy alone. Although there was no statistically significant increase in major late toxicity, increase in noncancer deaths narrowed the resultant gain in overall survival.
Summary
Background
Chronic hepatitis B (CHB) cannot be completely eradicated due to the presence of covalently closed circular DNA (cccDNA) in the nuclei of infected hepatocytes. While quantification ...of intrahepatic cccDNA requires liver biopsies, serological markers can be non‐invasive alternatives to reflect intrahepatic viral replicative activity. Recently, hepatitis B core‐related antigen (HBcrAg) has been advocated as a novel serum marker for disease monitoring and prognostication of CHB.
Aim
To examine the virological aspect and clinical application of HBcrAg with respect to the natural history and treatment of CHB.
Methods
We reviewed all papers published in the PubMed journal list and s from major international meetings that included the keyword “HBcrAg” or “hepatitis B core‐related antigen” until March 2017. Selected studies were compared and summarised on the basis of existing theories, as well as the authors’ experience.
Results
HBcrAg exhibited good correlation with intrahepatic (ih) cccDNA, ih total hepatitis B virus (HBV) DNA, serum HBV DNA and to a lesser extent HBV surface antigen (HBsAg). In situations where serum HBV DNA levels become undetectable or HBsAg loss is achieved, HBcrAg can still be detectable. This marker is helpful in differentiation of HBeAg‐negative chronic hepatitis from HBeAg‐negative chronic infection, predicting spontaneous or treatment‐induced HBeAg seroconversion, sustained response to nucleos(t)ide analogue (NA), risk of HBV reactivation in occult HBV infection under immunosuppressive therapies, and risk of hepatocellular carcinoma (HCC) development as well as post‐operative HCC recurrence.
Conclusions
HBcrAg is a potential surrogate marker of cccDNA. It may soon become a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B.
Linked Content
This article is linked to Wang et al and Mak and Yuen papers. To view these articles visit https://doi.org/10.1111/apt.14673 and https://doi.org/10.1111/apt.14684.
Summary
Background
The Gut and Obesity Asia (GO ASIA) workgroup was formed to study the relationships between obesity and gastrointestinal diseases in the Asia Pacific region.
Aim
To study factors ...associated with nonalcoholic steatohepatitis (NASH) and advanced fibrosis, and medical treatment of biopsy‐proven nonalcoholic fatty liver disease (NAFLD) patients.
Methods
Retrospective study of biopsy‐proven NAFLD patients from centres in the GO ASIA Workgroup. Independent factors associated with NASH and with advanced fibrosis on binary logistic regression analyses in a training cohort were used for the development of their corresponding risk score, which were validated in a validation cohort.
Results
We included 1008 patients from nine centres across eight countries (NASH 62.9%, advanced fibrosis 17.2%). Independent predictors of NASH were body mass index ≥30 kg/m2, diabetes mellitus, dyslipidaemia, alanine aminotransferase ≥88 U/L and aspartate aminotransferase ≥38 U/L, constituting the Asia Pacific NASH risk score. A high score has a positive predictive value of 80%‐83% for NASH. Independent predictors of advanced fibrosis were age ≥55 years, diabetes mellitus and platelet count <150 × 109/L, constituting the Asia‐Pacific NAFLD advanced fibrosis risk score. A low score has a negative predictive value of 95%‐96% for advanced fibrosis. Only 1.7% of patients were referred for structured lifestyle program, 4.2% were on vitamin E, and 2.4% were on pioglitazone.
Conclusions
More severe liver disease can be suspected or ruled out based on factors identified in this study. Utilisation of structured lifestyle program, vitamin E and pioglitazone was limited despite this being a cohort of biopsy‐proven NAFLD patients with majority of patients having NASH.
Linked ContentThis article is linked to Hardy and McPherson and Chan et al papers. To view these articles visit https://doi.org/10.1111/apt.14557 and https://doi.org/10.1111/apt.14572.
Nanophase materials are promising alternative implant materials in tissue engineering. Here we report for the first time the large-scale direct growth of nanostructured bioactive titanates on ...three-dimensional (3D) microporous Ti-based metal (NiTi and Ti) scaffolds via a facile low temperature hydrothermal treatment. The nanostructured titanates show characteristics of 1D nanobelts/nanowires on a nanoskeleton layer. Besides resembling cancelous bone structure on the micro/macroscale, the 1D nanostructured titanate on the exposed surface is similar to the lowest level of hierarchical organization of collagen and hydroxyapatite. The resulting surface displays superhydrophilicity and favors deposition of hydroxyapatite and accelerates cell attachment and proliferation. The remarkable simplicity of this process makes it widely accessible as an enabling technique for applications from engineering materials treatment including energy-absorption materials and pollution-treatment materials to biotechnology.
Endometrial cancer is the third most common gynecologic malignancy and the ninth most common malignancy for females overall in Hong Kong. Approximately 80% or more of these cancers are endometrioid ...endometrial adenocarcinomas. The aim of this study was to reveal genes contributing to the development of endometrioid endometrial cancer, which may impact diagnosis, prognosis and treatment of the disease. Whole-genome gene expression analysis was completed for a set of 55 microdissected sporadic endometrioid endometrial adenocarcinomas and 29 microdissected normal endometrium specimens using the Affymetrix Human U133 Plus 2.0 oligonucleotide microarray. Selected genes of interest were validated by quantitative real-time-polymerase chain reaction (qRT-PCR). Pathway analysis was performed to reveal gene interactions involved in endometrial tumorigenesis. Unsupervised hierarchical clustering displayed a distinct separation between the endometrioid adenocarcinomas and normal endometrium samples. Supervised analysis identified 117 highly differentially regulated genes (>or=4.0-fold change), which distinguished the endometrial cancer specimens from normal endometrium. Twelve novel genes including DKK4, ZIC1, KIF1A, SAA2, LOC16378, ALPP2, CCL20, CXCL5, BST2, OLFM1, KLRC1 and MBC45780 were deregulated in the endometrial cancer, and further validated in an independent set of 56 cancer and 29 normal samples using qRT-PCR. In addition, 10 genes were differentially regulated in late-stage cancer, as compared to early-stage disease, and may be involved in tumor progression. Pathway analysis of the expression data from this tumor revealed an interconnected network consisting of 21 aberrantly regulated genes involved in angiogenesis, cell proliferation and chromosomal instability. The results of this study highlight the molecular features of endometrioid endometrial cancer and provide insight into the events underlying the development and progression of endometrioid endometrial cancer.
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