CIC-rearranged sarcoma: a clinicopathological analysis of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.

Modes of contact and risk of transmission in COVID-19 among close contacts

BackgroundRapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated. MethodsWe included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts. ResultsAmong 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases. ConclusionsIn conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.

Some reflections on evidenced-based medicine, precision medicine, and big data-based research / 中华流行病学杂志

Evidence-based medicine remains the best paradigm for medical practice. However, evidence alone is not decisions; decisions must also consider resources available and the values of people. Evidence shows that most of those treated with blood pressure-lowering, cholesterol-lowering, glucose-lowering and anti-cancer drugs do not benefit from preventing severe complications such as cardiovascular events and deaths. This implies that diagnosis and treatment in modern medicine in many circumstances is imprecise. It has become a dream to identify and treat only those few who can respond to the treatment. Precision medicine has thus come into being. Precision medicine is however not a new idea and cannot rely solely on gene sequencing as it was initially proposed. Neither is the large cohort and multi-factorial approach a new idea; in fact it has been used widely since 1950s. Since its very beginning, medicine has never stopped in searching for more precise diagnostic and therapeutic methods and already made achievements at various levels of our understanding and knowledge, such as vaccine, blood transfusion, imaging, and cataract surgery. Genetic biotechnology is not the only path to precision but merely a new method. Most genes are found only weakly associated with disease and are thus unlikely to lead to great improvement in diagnostic and therapeutic precision. The traditional multi-factorial approach by embracing big data and incorporating genetic factors is probably the most realistic way ahead for precision medicine. Big data boasts of possession of the total population and large sample size and claims correlation can displace causation. They are serious misleading concepts. Science has never had to observe the totality in order to draw a valid conclusion; a large sample size is required only when the anticipated effect is small and clinically less meaningful; emphasis on correlation over causation is equivalent to rejection of the scientific principles and methods in epidemiology and a call to give up the assurance for validity in scientific research, which will inevitably lead to futile interventions. Furthermore, in proving the effectiveness of intervention, analyses of real-world big data cannot displace the role of randomized controlled trial. We expressed doubts and critiques in this article on precision medicine and big data, merely hoping to stimulate discussing on the true potentials of precision medicine and big data.

Gap between evidence and physicians' knowledge and practice regarding hypertension and its drug treatment: a survey in a Chinese city / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Evidence-based medicine has come into its second decade. How prepared clinicians are in practicing it in particular in developing countries remains unclear. Thus we conducted this survey of physicians in urban hospitals in China to determine the size of the gap between research evidence and physicians' knowledge and practice regarding antihypertensive drugs for primary prevention of cardiovascular diseases in China.</p><p><b>METHODS</b>A cross sectional survey by a face-to-face interview was conducted in 20 tertiary general hospitals in China in 2005. A total of 444 physicians (mostly cardiologists) in internal medicine who had treated at least one hypertensive patient in the past 12 months were invited for the interview on their perception of the cardiovascular risk of hypertension, the magnitude of the benefit of antihypertensive drugs, knowledge on the overall risk approach, first-line drugs used, the risk above which drug treatment is recommended, and knowledge on evidence-based medicine.</p><p><b>RESULTS</b>A total of 444 of the 468 eligible physicians were successfully interviewed with a response rate of 94.9%. They estimated that a hypertensive man with an actual 5-year cardiovascular risk of 8.4% would have a 5-year cardiovascular risk of 40% (95%CI: 38% to 42%) if not treated, and have an absolute risk reduction and relative risk reduction from drug treatment by 20% (95%CI: 18% to 22%) and 39% (95%CI: 37% to 42%) respectively, as compared to 3.3% and 33% respectively shown in research evidence. On average, the physicians would recommend drug treatment at a number needed to treat (NNT) of 368 or smaller, as compared to the actual NNT of 50 for drug treatment in an average hypertensive Chinese. Fifty-five percent (95%CI: 50% to 59%) of them had never intently used the national hypertension guidelines. The majority still prescribed drugs primarily based on blood pressure alone by ignoring other risk factors or the overall risk and 78% (95 % CI: 76% to 83%) used new expensive drugs such as calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors as first-line treatment. Only 13% (95%CI: 9% to 18%) could correctly interpret the NNT. Forty-three percent (95%CI: 39% to 48%) did not know the randomized controlled trial was scientifically the most rigorous among other study designs for evaluating the effectiveness of anti-hypertensive drugs. Ninety-two percent (95%CI: 90% to 94%) did not know they could start by searching systematic reviews when looking for evidence on the effectiveness of anti-hypertensive drugs as opposed to trials. Ninety-six percent (95%CI: 94% to 98%) did not know the Cochrane Library was an important source of systematic reviews.</p><p><b>CONCLUSIONS</b>The surveyed physicians significantly over-estimated the cardiovascular risk of hypertension and the benefit of drug treatment, and had insufficient knowledge on the overall risk approach. They recommended drug treatment at a cardiovascular risk which was even much lower than the cutoff suggested for western populations, which would make many more people eligible for drug treatment. They also tended to prescribe new expensive drugs although the older cheaper ones may be more appropriate in many patients. They showed inappropriate knowledge on the basics of evidence-based medicine.</p>