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After more than a year of deliberation the journal of the American Society for Reproductive Medicine is to withdraw a Korean paper at the centre of a dispute about authorship and plagiarism ( BMJ 2007;334:717-20, 7 Apr doi: 10.1136/bmj.39168.517234.AD), solely on the grounds that it had been published previously in another journal. In a statement issued last week the board of Fertility and Sterility made no reference to the allegations of perjury and plagiarism that had been made by its editor in chief in the LA Times two months earlier. On 18 February Alan DeCherney had told the newspaper, “I'm sure that it's plagiarism,” and said he would be recommending to his editorial board that all the listed authors be banned from publishing in Fertility and Sterility for three years (www.latimes.com, 18 Feb, “Credit for U.S. journal article at issue,” www.latimes.com/news/local/la-me-research18feb18,0,6268481.story?coll=la-headlines-california). In the event Fertility and Sterility has announced that only one of the authors will be banned. The decision has infuriated Jeong Hwan Kim, a Korean doctor now working in Singapore, who wrote to Fertility and Sterility in March last year to alert the journal of his concerns relating to the paper “Quantification of mitochondrial DNA using real-time polymerase chain reaction in patients with premature ovarian failure” ( Fertility and …

Introduction. Prostate cancer (PCa) is one of the most commonly diagnosed cancers in elderly men, and accounts for 30% of all newly diagnosed cases of cancer. The development of the ‘clinically insignifi cant’ prostate cancer into its invasive form is still unclear, and it is believed that chronic inflammation may play its role, as proposed by De Marzo in 1999. However, there is no clear opinion on the subject of existence of dependencies between changes of the inflammatory type and PCa. Material and methods. The study involved 1,010 men, suspected of prostate cancer development by positive digital rectal examination (DRE) and/or elevated PSA value. The 10 cores, TRUS guided biopsy was performed. In those with ASAP, HG–PIN or inflammation the second biopsy was proposed. Results. In the first biopsy PCa was diagnosed in 336 patients (33.27%). ASAP was found in 58 (5.74%), HG–PIN in 82 (8.11%), and the coexistence of both was found in 19 (1.88%). Chronic prostatitis was diagnosed in 101 (10%) men. Of those who underwent second biopsy, PCa was diagnosed in six of 19 patients (31.57%) who were diagnosed with HG–PIN in the first biopsy, in four of 40 (10%) with BPH in the first biopsy, in four of 18 (22.22%) with ASAP or LG–PIN together with ASAP, and in two out of five (40%) with the coexistence of ASAP and HG–PIN. Malignancy was not confirmed in any of the patients in whom the diagnosis of BPH, HG–PIN, or ASAP was accompanied by chronic prostatitis. Conclusions. Chronic prostatitis does not significantly increase the value of PSA in patients with benign changes (BPH). The presence of prostatitis in the first biopsy did not predict cancer in subsequent bi opsy, because the second biopsy did not reveal prostate cancer in any of the patients in whom prostati tis was diagnosed in the first biopsy.

Sir, We read with interest the paper of Guarrera & Rebora (1) on the hydrosoluble antioxidant capacity (HAOC) of serum of patients with polymorphic light eruption (PLE). We were involved in a similar study that aimed to establish the role of uric acid in total HAOC. In particular, Guarrera & Rebora observed that the total HAOC is reduced in females regardless of whether they are patients or controls. We regard this novel finding as important and worthy of confirmation. We studied 55 subjects (21 men and 34 women; age range 21–62 years). Fourteen of them (3 men and 11 women; aged 40±12.8 years) had PLE and 41 were controls (18 men and 23 women; aged 41±11.1 years). All patients gave their informed consent. Triplicate HAOC measurements in the presence and absence of uricase were obtained with commercial kits, PAO and PAO-U (MED-DIA, Vercelli, Italy). All serum samples were processed at the time of collection. Statistical analysis was performed with MiniTab ver. 15. (Table I). HAOC measurements in samples deprived of uric acid (HAOC-uricase) were lower than in those with uric acid (F=205.6, p

Two papers that reported that the blood pressure drug ramipril was beneficial in patients with intermittent claudication due to peripheral artery disease have been retracted after an investigation found that data were fabricated by the studies’ lead author, Anna A Ahimastos, a researcher at the prestigious Baker IDI Heart and Diabetes Institute in Melbourne, Australia. The first paper,1 published in JAMA in …

Cardiovascular magnetic resonance (CMR) has become the primary tool for noninvasive assessment of myocardial inflammation in patients with suspected myocarditis. The International Consensus Group on CMR Diagnosis of Myocarditis was founded in 2006 to achieve consensus among CMR experts and develop recommendations on the current state-of-the-art use of CMR for myocarditis. The recommendations include indications for CMR in patients with suspected myocarditis, CMR protocol standards, terminology for reporting CMR findings, and diagnostic CMR criteria for myocarditis (i.e., “Lake Louise Criteria”).

When employees at the German drug firm Boehringer Ingelheim learnt that the conclusions of a company study clashed with a marketing claim that its new anticoagulant did not need monitoring, they sought to have the paper revised and even questioned whether it should be published at all, internal company documents released by a US court indicate. In an email one employee, whose name was redacted, complained that the paper would harm the company’s marketing efforts and make discussions with regulatory agencies more difficult. “Can’t this be avoided?” the employee asked. Another employee, Andreas Clemens, a medical team leader for the drug, wrote that he believed that the findings were important and should be published but with revision. “The world is crying for this information—but the tricky part is that we have to tailor the messages smart.” In another email Clemens expressed concern that the paper “could be a liability issue” for the company. The study involved dabigatran etexilate (marketed as Pradaxa), a thrombin inhibitor that is approved in the United States and Europe for the prevention of stroke and embolic events in patients with atrial fibrillation. One of the …

We present data on the use of filter-paper blood collection for measurement of glycosylated whole-blood proteins (gWB) (hemoglobin and plasma proteins). A capillary blood sample, obtained by fingerprick, is spotted directly onto filter paper (Schleicher & Schuell 903). The blood spot is washed briefly with alcohol (ethanol or isopropanol) to remove free glucose and dried before shipment to the laboratory. In the laboratory, the blood is eluted from the paper and analyzed for gWB by a colorimetric method. The gWB is primarily a measure of glycosylated hemoglobin (gHb) with a small contribution from glycosylated plasma protein. Concentrations of gWB and gHb are highly correlated (r = 0.91). The filter-paper method offers advantages over currently available methods for quantifying gHb and may be particularly useful in screening for diabetes and for assessing glycemic control in patients from remote areas.

In spite of many attempts to modify the filtrate reaction of Brdicka's cancer test, none of them gave better results than the original one. We already reported that in patients with acute leukemia the first maximum of Brdicka's filtrate wave was often higher than the second maximum. Such phenomenon presumably depends on the high contents of polysaccharides in molecules of these blood mucoproteins. In this paper further efforts were made to clarify the factors influencing on the shape of the protein double wave, and to find out the polarographic characteristics and clinical significance of electrophoretically separated mucoprotein with special reference to the wave form. Among many experimental conditions, the temperature in polarographic cells was found to be most sensitive factor to affect the protein wave shape, so that all experiments were carried out at the constant temperature (20°C±0.05). Serum mucoprotein was evidently separated into two fractions, M1 fraction an M2 fraction, by paper electroyhoresis in McIlvaine's buffer of pH 4, 4. These two fractions showed polarographically different shape each other. The M1 fraction, the most rapidly anodic moving one, showed left side elevation in shape; in other words, the first maximum was higher than the second maximum. On the contraly, M2 fraction showed right side elevation in shape; the second maximum was higher than the first maximum. Furthermore, it was very interesting from clinical point of view that the characteristic shape of M1 fraction was to some extent variable depending on diseases. From the clinical observation on 259 cases including 119 cases of cancer and 11 cases of leukemia, it was revealed that in neoplastic patients the wave shape of M1 fraction showed clearcut difference from those in normal; Δh (distance from the second maximum to the first maximum) of M1 fraction in neoplastic patients was larger than that in normal. Thus, the cancer detection rate has markedly elevated as compared with the original filtrate test, namely from 77% to 90%o in our study.

Research studies on the side effects of commonly prescribed drugs constituted the three most read papers published by the BMJ in 2005, according to an internal audit that assessed their use by readers. Studies that showed increased risk of myocardial infarction in patients taking cyclo-oxygenase-2 (COX 2) inhibitors and that explored the link between selective serotonin reuptake inhibitors and suicide came top. For the audit Sara Schroter, the BMJ 's senior researcher, analysed research papers using three measures: the number of citations a paper received, the number of times it was accessed on the web, and the number of rapid responses it generated. The top scoring paper was a case-control study that showed greater risk of myocardial infarction in patients taking the COX 2 inhibitor rofecoxib (Vioxx) and in patients taking diclofenac …

candidategeneandthetheorythatsympatheticoveractivityisan underestimated contributor to ESRD.Although considerable further evidence would need to fol-low to verify the putative causal chain, ideally early develop-ments would be that others would reproduce the findings inlarger populations, and longitudinal studies in patient groupsor animal models would demonstrate that sympathetic over-activity (and lower catestatin) precedes progressive decline torenal failure. Eventually, then, the value of these CHGA hap-lotypes and catestatin as markers and perhaps the benefits ofmedication that is capable of limiting the distorted sympa-thetic outflow, perhaps limiting certain adrenergic effects,might then be worth assessment in those who are at high riskfor ESRD.DISCLOSURES

THE following technique for the separation of phenols, phenolic acids and their derivatives by one-dimensional paper partition chromatography has been developed as part of a two-dimensional method (to be published shortly) for the investigation of serum and urinary phenols in patients suffering from acute uraemia.

Parathyroid hormone (PTH) determination is of greatest importance for patients suffering from parathyroid gland disorders and for the follow-up of bone turnover in patients suffering from chronic kidney disease (CKD). Two generations of PTH assays are simultaneously present on the market for PTH quantification. As these assays are not yet standardized, this results in a significant level of confusion in the care of CKD patients. One key objective of the IFCC Committee for Bone Metabolism is to improve this situation. In this position paper, we will highlight the current state of PTH testing and propose a pathway to ultimately overcome issues resulting from PTH assay variability.

Background: The present paper reports on analysis of 184 patients who were diagnosed with endometrial cancer. The main objective of this study was to address parameter V rec(30Gy) which determines a volume of the rectum irradiated with a dose of 30 Gy during radiotherapy. Material and methods: All patients were irradiated with an IMRT technique on linear accelerators. The planning target volume (PTV) contour was determined by a radiation oncologist. The clinical target volume (CTV) was drawn on CT images obtained in a prone position. For statistical analysis, appropriate tests (e.g. the Shapiro-Wilk, Wilcoxon) were used. Results and discussion: The performed analysis showed that the recommended condition for V rec(30Gy) is met only in 3% of patients and the observed median value exceeds 90%. The obtained results were compared with the studies in which the V rec(30Gy) values were related to various radiotherapy techniques. Conclusions: The analysis showed that the condition for V rec(30Gy) is satisfied in the case of only 3% of patients. Due to the difficulty with meeting the condition, it should be reconsidered based on real results.

Malignant tumors are a serious threat to human health. Surgical resection is the most effective treatment for liver cancer. However, liver cancer is mostly found at an advanced stage, is difficult to remove by surgery, and has a very high recurrence rate after surgery. The current liver cancer treatment drugs have serious side effects, and the treatment effect is not ideal, far from meeting the clinical needs. Based on this, this paper studies the effect of propofol on the proliferation and apoptosis of liver cancer cells through the TGF-B1/Smad2 signaling pathway, and explores the proliferation, adhesion and apoptosis of cancer cells in patients with propofol. This paper uses a comparative experiment. With medical imaging method, 80 rats with liver cancer in the same period were cultured. High-precision microscope and radiolocation method were used to observe and record the whole process of propofol regulating Smad2 signal pathway. The results show that propofol can effectively inhibit the proliferation of cancer cells in patients with liver cancer. Propofol can increase the activity and content of transforming growth factor-β1 by 12% and 20%, respectively, and then inhibit the proliferation rate of liver cancer cells by 10% through the Smad2 signaling pathway, and exponentially increase the apoptotic number of liver cancer cells. This shows that propofol has a significant inhibitory effect on the cycle of liver cancer cells. Under the action of propofol, the life cycle of liver cancer cells is shortened, which provides a certain theoretical basis for the treatment of liver cancer., GRAPHICAL ABSTRACT

A paper chromatographic analysis in 60 patients with muscular dystrophy from 49 families and in 351 of their relatives showed a high incidence of generalized hyperaminoaciduria in both patients and relatives. There was a higher incidence of threoninuria in patients and their relatives than in controls. One family was found to have excess histidinuria and another excess lysinuria.

Background Patients and carers should be actively involved in patient safety and empowered to use person‐centred approaches where they are asked to both identify safety concerns and partner in preventing them. Objectives The aim of this study was to co‐design a patient safety guide for primary care (PSG‐PC) to support patients and carers to address key patient safety questions and identify key points where they can make their care safer. The objectives were to i) identify when and how patients and carers can be involved in primary care patient safety, and ii) identify the relevant information to include in the PSG‐PC. Design An experience‐based co‐design approach. Setting and Participants We conducted three workshops with patients, carers, community pharmacists and general practitioners to develop and refine the PSG‐PC. Results Participants identified both explicit and implicit issues of primary care patient safety especially relating to technical and relational components of involving patients and carers. The importance of communication, understanding roles and responsibilities, and developing partnerships between patients and health‐care providers were considered essential for actively involving patients in patient safety. Co‐developing the PSG‐PC provided insight to improve care to develop the PSG‐PC. Discussion The PSG‐PC is the first guide to be developed for primary care, co‐designed with patients, carers, general practitioners and pharmacists. The PSG‐PC will support patients and carers to partner with health‐care professionals to improve patient safety addressing international and national priorities to continuously improve patient safety.

Background: A clinical decision support system (CDSS) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. Materials and methods: Prospective multicenter data from 543 consecutive (2013–2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. Results: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). Conclusions: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis. Instituto de Salud Carlos III PI16/02104 Junta de Andalucía PIN-0476-2017 Ministerio de Economía y Competitividad FPAP13-1E-2429

Vaccine hesitancy (VH) has emerged as a recognized threaten to contain the COVID-19 pandemic. Historically, low vaccine acceptance rates had been described among patients with rheumatic diseases (RMDs). The study objective was to determine COVID-19 VH among Mexican outpatients with RMDs and validate the COVID-19 VH questionnaire. This cross-sectional study was developed in three steps. Step 1 consisted of translation/cultural adaptation of the Oxford-COVID-19-VH questionnaire. Step 2 consisted of pilot testing and questionnaire feasibility, content, construct and criterion validity, reliability (internal consistency and temporal stability) and questionnaire sensitivity to change. Step 3 consisted of VH phenomenon quantification in patients from two metropolitan tertiary-care-level centers. Step 1 followed ISPOR-task-force recommendations. Patients who participated in step 2 (n = 50 for pilot testing/feasibility and n = 208 for questionnaire validation [91 in test–retest and 70 in questionnaire-sensitivity to change]) and step 3 (n = 600) were representative outpatients with RMDs. The seven-item COVID-19 VH questionnaire was found feasible, valid (experts’ agreement ≥80%; a 1-factor structure accounted for 60.73% of the total variance; rho = 0.156, p = .025 between COVID-19 VH questionnaire and score from the Spanish version of the Vaccine Hesitancy Scale; and lower questionnaire scores in patients who reported 5 years-previous influenza vaccination), reliable (Cronbach’s ɑ = 0.889, intra-class correlation coefficient = 0.933 and 95% confidence interval = 0.898–0.956) and sensitive to change (effect size = 1.17 and 0.86, respectively, in patients who decreased [n = 34] and increased [n = 31] questionnaire-score after intervention). VH phenomenon was 35.5%. VH phenomenon was present in a substantial number of Mexican patients with RMDs. The COVID-19 VH questionnaire showed good psychometric properties to assess COVID-19 VH in our population.

Objective Intraarticular (IA) administration of platelet-rich plasma (PRP) has been proposed as a new strategy to halt osteoarthritis (OA) progression. In patients with severe OA, its potential is limited because it is unable to reach the subchondral bone, so a new strategy is needed, and intraosseous (IO) infiltration has been suggested. The purpose is to assess the impact of IA together with IO infiltration of plasma rich in growth factors (PRGF) in serum hyaluronic acid (HA) and type II collagen cleavage neoepitope (C2C) levels. Design A total of 32 rabbits were included in the study and randomly divided into 2 groups: control and treatment. A 4-mm chondral defect was created in the medial femoral condyle and IA followed by IO infiltration were performed. Serum C2C and HA levels were measured using enzyme-linked immunosorbent assay (ELISA) tests before infiltration and 28, 56, and 84 days post-infiltration. Results Significant lower C2C serum levels were obtained in treatment group (IA + IO infiltration of PRGF) at 84 days post-infiltration than in control group (IA infiltration of PRGF + IO infiltration of saline solution), while no significant differences between groups were reported at any other study times. Regarding HA, at 56 days post-infiltration, greater significant levels were seen in the treatment group. However, at 84 days post-infiltration, no significant differences were obtained, although lower levels were reported in the treatment group. Conclusions Despite inconclusive, the results suggest that the combination of IA and IO infiltration with PRGF may enhance cartilage and subchondral bone regeneration, but further studies are needed.

Hepatitis B virus (HBV) middle surface antigen (MHBs) mutation or deletion occurs in patients with chronic HBV infection. However, the functional role of MHBs in HBV infection is still an enigma. Here, we reported that 7.33% (11/150) isolates of CHB patients had MHBs start codon mutations compared with 0.00% (0/146) in acute hepatitis B (AHB) patients. Interestingly, MHBs loss accounted for 11.88% (126/1061) isolates from NCBI GenBank, compared with 0.09% (1/1061) and 0.00% (0/1061) for HBV large surface antigen (LHBs) loss and HBV small surface antigen (SHBs) loss, respectively. One persistent HBV clone of genotype B (B56, MHBs loss) from a CHB patient was hydrodynamically injected into BALB/c mice. B56 persisted for >70 weeks in BALB/c mice, whereas B56 with restored MHBs (B56M+) was quickly cleared within 28 days. Serum cytokine assays demonstrated that CXCL1, CXCL2, IL-6 and IL-33 were significantly increased during rapid HBV clearance in B56M+ mice. Furthermore, the enhancers and promoters of B56 were proved to be required for B56 persistence in mice. Ablating MHBs expression improved the persistence of a new clone (HBV1.3, genotype B) which was recreated by using enhancers and promoters of B56. These data demonstrated that MHBs deletion can promote the persistence of specific HBV variants in a hydrodynamic mouse model. MHBs re-expression restored a rapid clearance of HBV, which was accompanied by cytokine responses including the elevation of CXCL1, CXCL2, IL-6 and IL-33.

Background: Leg ulcers are a frequent complication in patients with the inherited hemoglobin disorders. In thalassemia, the literature is limited, and factors associated with the development of leg ulcers in hemoglobin E (HbE) beta thalassemia, the most common form of severe beta-thalassemia worldwide, have not previously been reported. Methods: We reviewed all available medical records of patients with HbE beta thalassemia to document the onset of leg ulcers at the 2 largest treatment centers in Sri Lanka. We reviewed the literature to identify studies reporting outcomes of interventions for ulcers in severe thalassemia. Results: Of a total of 255 actively registered patients with HbE thalassemia in the 2 centers, 196 patient charts were evaluable. A leg ulcer with a documented date of onset was recorded in 45 (22%) of 196 evaluable patients, aged (mean ± SEM) 22.2 ± 1.4 years. Most had been irregularly transfused; steady-state hemoglobin was 6.4 ± 0.2 g/dL. Treatment achieving healing in 17 patients included transfusions, antibiotics, oral zinc, wound toileting, and skin grafting. Conclusion: Leg ulcers may be more common in HbE beta thalassemia than in other forms of thalassemia. A systematic approach to treatment will be needed to document the prevalence and factors placing such patients at risk for leg ulcers. Controlled trials to evaluate the optimal treatment of this common complication are indicated.

Objective To describe the clinical profile and microbiology trends in patients undergoing therapeutic keratoplasty at a multi-tier ophthalmology hospital network in India. Methods This cross-sectional hospital-based study included 3147 eyes undergoing therapeutic keratoplasty between Jan 2016 and Dec 2020 (5 years period) as cases. The demographic data, clinical profile and microbiological analysis were collected using an electronic medical record system. Results Of a total of 13,625 eyes with microbial keratitis(non-viral), 3147 (23.1%) underwent therapeutic keratoplasty during the study duration. Majority of patients were males (68.35%), from a rural geography (49.89%) and in 51–60 years age bracket (23.74%). The mean age of the patients was 50.54 ± 15.83 years. Two-thirds of patients were from lower socio-economic strata (66.63%) with an agrarian background (36.51%). Of the 3,147 eyes, fungus (51.8%) was the most common indication of therapeutic keratoplasty followed by bacteria (16.87%) and parasite (1.27%). No organisms could be identified in about a third (29.33%) of the cases. Between 2016 and 2020, the trend of therapeutic keratoplasties for fungal infections steadily grew (39.9% vs 45.49%) while the bacterial infections showed a steady decline (23.15% vs 11.81%). Conclusions Medical cure rate was seen in majority of those with microbial keratitis, and 23.1% eventually required management with therapeutic keratoplasty. Fungal keratitis was the most common indication for therapeutic keratoplasty. Male gender, rural setting, low socio-economic background and agricultural occupation are common risk factors for patients undergoing therapeutic keratoplasty in India.

Objective: This study assessed the prevalence of anaplastic lymphoma kinase (ALK) rearrangements in US oncology practices. Materials and Methods: Using a nationwide real-world database, we included adults with advanced non-small cell lung cancer (aNSCLC, stage IIIB- IV) diagnosed January 2015 – May 2019, with documented ALK testing results and smoking status. Rearrangement prevalence was assessed overall and then stratified by patient characteristics. Results: The cohort included 19,895 eligible patients with a mean age 68.5 years, majority ever-smokers (85.5%) and from community centers (92.2%). The overall ALK rearrangement prevalence was 2.6%. Positivity rate varied by histology and smoking status; it was the highest among non-smoking patients with non-squamous histology (9.3%). Differences in ALK status also varied by age and race, with young patients (18–39 years) having a higher prevalence (21.6%) vs. older patients (age ≥55 = 2.2%); Asian patients had a prevalence of 6.3%. Patients that were positive for other mutations or rearrangements had a lower ALK positivity rate (0.5%) and patients positive for PD-L1 had a rate of 3.0%. Conclusions: The likelihood of finding an ALK translocation was highest in younger patients and nonsmokers; however, age and smoking history were not discriminative enough to exclude testing based on clinical variables.

Background Insomnia is a common disorder that affects a vast number of patients; the hyperarousal theory of insomnia postulates that patients with insomnia are physiologically activated not only at nighttime but also during the daytime. We aimed to investigate the differences in the resting-state functional connectivity (RSFC) of the thalamus with cortical areas between patients with insomnia disorder and healthy controls. Methods All participants completed clinical questionnaires and underwent portable polysomnography and resting-state fMRI. Results Patients in the insomnia group (n = 50) showed increased RSFC between the thalamus and right medial superior frontal area, bilateral middle temporal areas, left rectus and right parahippocampal areas compared with controls (n = 42) after controlling for age, sex and education level. Among the pairs that showed increased connectivity, several functional connections were negatively correlated with sleep efficiency, measured by polysomnography.Limitations: We used a small sample size. Conclusion We consider these results on increased thalamocortical hyperactivity in brain areas related to sensory functions as providing evidence for the hyperarousal theory of insomnia.

Patients with new-onset stable angina constitute a substantial part of the population seen by cardiologists. Currently, the diagnostic workup of these patients depends on the pre-test probability of having obstructive coronary artery disease. It consists of either functional testing for myocardial ischaemia or anatomical testing by using coronary computed tomographic angiography (CCTA) or invasive coronary angiography. In case the pre-test probability is > 5%, the current guidelines for the management of chronic coronary syndromes do not state a clear preference for one of the noninvasive techniques. However, based on the recently published cost-effectiveness analysis of the PROMISE trial and considering the diagnostic yield in patients with angina and nonobstructive coronary artery disease, we argue a more prominent role for CCTA as a gatekeeper for patients with new-onset stable angina.

Objective: To investigate the incidence and risk factors for liver abscess formation after treatment with drug-eluting bead chemoembolization (DEB-TACE) in patients with metastatic hepatic tumors (MHT). Methods: The current study is a retrospective analysis of the clinical data of 137 patients with metastatic hepatic tumors who received DEB-TACE treatment in our institute (Union Hospital, Tongji Medical College, Huazhong University of Science and Technology) between June 2015 and September 2020. Patients were evaluated for the presence or absence of post-DEB-TACE liver abscess. Univariate and multivariate analyses were used to identify risk factors for liver abscess formation. Results: The incidence of liver abscess formation after the DEB-TACE procedure was 8.76% per patient and 5.53% per procedure. Univariate analysis showed that larger maximum tumor diameter (p = 0.004), Grade 1 artery occlusion (p < 0.001) and systemic chemotherapy within 3 months before the DEB-TACE procedure (p < 0.001) were all associated with liver abscess formation. However, only systemic chemotherapy within 3 months before the DEB-TACE procedure (OR 5.49; 95% CI 0.34–13.54; p < 0.001) was identified by multivariate analysis to be an independent risk factor. Conclusions: Tumor size, Grade 1 artery occlusion and recent systemic chemotherapy may all be associated with increased risk of liver abscess formation following DEB-TACE treatment in patients with metastatic hepatic tumors. Advances in knowledge: Identification of risk factors for liver abscess formation following DEB-TACE in patients with MHT. These findings suggest the need for caution and consideration of the aforementioned risk factors on the part of interventional radiologists when designing DEB-TACE strategies and performing post-procedure patient management.

Transcatheter aortic valve implantation (TAVI) is still developing and changing our approach to treating patients with severe symptomatic aortic stenosis. Aortic stenosis frequently coexists with coronary artery disease. Both diseases have similar risk factors for their development and one should expect a future progression of coronary artery disease. The current guidelines have expanded TAVI indications to include intermediate-risk patients, and perhaps they will be expanded to include low-risk patients in the future. Survival after TAVI in younger patients will depend on the durability of the aortic valves and methods of coronary artery disease treatment. This paper presents some aspects of performing coronary angiography and percutaneous coronary intervention in patients who had TAVI performed using the two most popular aortic valves - balloon expandable aortic valves (Edward Sapien/Edward Sapien XT/Sapien 3) and self-expandable aortic valves (CoreValve/Evolut R) - on the basis of several examples. This paper also focuses on technical aspects associated with a proper implantation of aortic valves to ensure easy access to coronary arteries, as well as on possible problems when the implantation is not optimal. We discuss interactions between the structure of the aortic valve stent, catheters, commissures of new aortic valves, and coronary ostia.

BACKGROUND AND PURPOSE In TB-HIV co-infection, prompt initiation of TB therapy is recommended but anti-retroviral treatment (ART) is often delayed due to potential drug-drug interactions between rifampicin and efavirenz. In a longitudinal cohort study, we evaluated the effects of efavirenz/rifampicin co-treatment and time of ART initiation on CYP3A induction. EXPERIMENTAL APPROACH Treatment-naive TB-HIV co-infected patients (n = 102) were randomized to efavirenz-based-ART after 4 (n = 69) or 8 weeks (n = 33) of commencing rifampicin-based anti-TB therapy. HIV patients without TB (n = 94) receiving efavirenz-based-ART only were enrolled as control. Plasma 4β-hydroxycholesterol/cholesterol (4β-OHC/Chol) ratio, an endogenous biomarker for CYP3A activity, was determined at baseline, at 4 and 16 weeks of ART. KEY RESULTS In patients treated with efavirenz only, median 4β-OHC/Chol ratios increased from baseline by 269% and 275% after 4 and 16 weeks of ART, respectively. In TB-HIV patients, rifampicin only therapy for 4 and 8 weeks increased median 4β-OHC/Chol ratios from baseline by 378% and 576% respectively. After efavirenz/rifampicin co-treatment, 4β-OHC/Chol ratios increased by 560% of baseline (4 weeks) and 456% of baseline (16 weeks). Neither time of ART initiation, sex, genotype nor efavirenz plasma concentration were significant predictors of 4β-OHC/Chol ratios after 4 weeks of efavirenz/rifampicin co-treatment. CONCLUSION AND IMPLICATIONS Rifampicin induced CYP3A more potently than efavirenz, with maximum induction occurring within the first 4 weeks of rifampicin therapy. We provide pharmacological evidence that early (4 weeks) or deferred (8 weeks) ART initiation during anti-TB therapy has no significant effect on CYP3A induction. LINKED ARTICLES This article is part of a themed issue on Oxysterols, Lifelong Health and Therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.16/issuetoc.

Background We aimed to assess feasibility of self-completion of the Patient-Generated Subjective Global Assessment Short Form (PG-SGA SF) by head and neck cancer patients, and to assess self-reported increased awareness regarding malnutrition risk after self-completion.Methods Participants were randomized to complete the PG-SGA SF by paper or app. Feasibility was assessed by time needed to complete the PG-SGA SF, perceived difficulty, and help needed during completion. Participants were asked if they knew what malnutrition was (yes/no) and if they could define "malnutrition." They were also asked 9 questions on whether they perceived increased awareness of malnutrition risk after having completed the PG-SGA SF and 2 on their intention to change lifestyle habits.Results Of all participants (n = 59; 65.9 +/- 12.6 years; 73% male), 55% completed the PG-SGA SF paper version and 46% the Pt-Global app. Median time needed for self-completion of the PG-SGA SF was 2 minutes 41 seconds (interquartile range: 1 minute 49 seconds-3 minutes 50 seconds). Forty-eight percent needed help with completion, indicating acceptable feasibility. Participants who completed the Pt-Global app needed help significantly more often (66%; 21/32) than those who completed the PG-SGA SF paper version (26%; 7/27) (P = 0.005). All difficulty scores were excellent. For 7/9 questions on malnutrition risk awareness, >50% of the participants answered positively.Conclusion The results of this study show that self-completion of the PG-SGA SF by head and neck cancer patients is feasible and that awareness regarding malnutrition risk may increase after completing the PG-SGA SF.

In light of the rapidly changing landscape of haemophilia treatment, the authors of the position paper on the “European Principles of Inhibitor Management” published in 2018 (Table 1) [1] now provide an update on the major impact of novel therapies that bypass and/or substitute clotting factor VIII (FVIII) and IX (FIX) in the care of haemophilia patients with FVIII- or FIX-neutralizing allo-inhibitory antibodies (inhibitors). [...]

Although often asymptomatic and detected incidentally, varicocele is a relatively common problem in patients who seek medical attention for infertility problems. Ultrasound (US) is the imaging modality of choice for evaluation, but there is no consensus on the diagnostic criteria, classification, and examination technique. In view of this uncertainty, the Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology (ESUR-SPIWG) undertook a systematic review of the available literature on this topic, to use as the basis for evidence-based guidelines and recommendations. This paper provides the results of the systematic review on which guidelines were constructed.

Objectives Numerous authors have expressed their interest in adjustment and social support in the context of cancer. However, none of the previous studies has directly examined the models describing the links between daily social support and adjustment fluctuation, particularly at the relational level. This study aimed to verify the additive and buffering models of daily received support regarding the relational level of patient‐caregiver relationship, that is, the relationship‐related stress and relationship satisfaction following hematopoietic cell transplantation (HCT). Methods Two hundred patient‐caregiver dyads participated in a 28‐day diary study that was started on the first day after post‐HCT discharge. The participants rated the extent of daily relationship‐related stress, relationship satisfaction, and received support every evening during the study. The analyses were based on the actor‐partner interdependence moderation model. Results Daily deviations in received support were directly associated with concurrent and lagged daily deviations in relationship satisfaction, regardless of relationship‐related stress level in both patients and caregivers. In addition, in caregivers, the effect of daily deviations in received support on relationship satisfaction depended on deviations in relationship‐related stress and was significant on the days with higher relationship‐related stress. Conclusions The findings supported both the additive (in patients and caregivers) and the buffering hypotheses (in caregivers) of daily received support in patient‐caregiver dyads during the first month following HCT. The theoretical and practical implications of the findings are further highlighted.

Sulphonylureas (SU) form an important role in management of people with type 2 diabetes. This safety history of SU was tainted for various reasons, the predominant one being lack of demonstration of cardiovascular safety. Since its introduction, SU's have never been subjected to a formal study for its cardiovascular safety. The cardiovascular safety of SUs was derived from small, inadequately powered randomised controlled trials (RCT) and observational studies. CAROLINA (CARdiovascular Outcome study of LINAgliptin versus glimepiride in patients with type 2 diabetes) trial planned as a cardiovascular outcome trial randomised people with type 2 diabetes and high cardiovascular risk to Linagliptin and Glimepiride. This opinion paper outlines the salient features of this landmark trial and its implications in general cardiology practice.

Evidence to support widespread adoption of digital health tools in hospitals is still lacking, and proof of their acceptance within the health system is largely missing. This study compared patient's pre-consultation waiting time (time spent at the pay-point, registration, and nursing-station prior to consultation) in two hospitals, one using paper based registration system and the other using an electronic (eHealth) registration system. Structured questionnaires were administered to both patients and health workers to determine and compare factors affecting care delivery wait times and how the use or non-use of eHealth in patient's registration process influence it. In addition, patient wait times were measured in both hospitals at these care points. Overall aggregate waiting time was observed to be longer in Maitama District Hospital (MDH) using the electronic hospital information system. This variance was found to be statistically significant as can be seen (t= 58.405, p=0.024). Inspite of this, wait times at registration and pay-point was significantly lower for MDH.

Purpose: To develop and validate a random forest (RF) based predictive model of early refractoriness to transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: A total of 227 patients with unresectable HCC who initially treated with TACE from three independent institutions were retrospectively included. Following a random split, 158 patients (70%) were assigned to a training cohort and the remaining 69 patients (30%) were assigned to a validation cohort. The process of variables selection was based on the importance variable scores generated by RF algorithm. A RF predictive model incorporating the selected variables was developed, and five-fold cross-validation was performed. The discrimination and calibration of the RF model were measured by a receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test. Results: The potential variables selected by RF algorithm for developing predictive model of early TACE refractoriness included patients' age, number of tumors, tumor distribution, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR). The results showed that the RF predictive model had good discrimination ability, with an area under curve (AUC) of 0.863 in the training cohort and 0.767 in the validation cohort, respectively. In Hosmer-Lemeshow test, the RF model had a satisfactory calibration with P values of 0.538 and 0.068 in training cohort and validation cohort, respectively. Conclusion: The RF algorithm-based model has a good predictive performance in the prediction of early TACE refractoriness, which may easily be deployed in clinical routine and help to determine the optimal patient of care.

Several widely recognized metabolites play a role in regulating the pathophysiological processes of various disorders. Nonetheless, the lack of effective biomarkers for the early diagnosis of polycystic ovarian syndrome (PCOS) and premature ovarian failure (POF) has led to the discovery of serum-based metabolic biomarkers for these disorders. We aimed to identify various differentially expressed metabolites (DEMs) through serum-based metabolic profiling in patients with PCOS and POF and in healthy individuals by using liquid chromatography–mass spectrometry analysis. Furthermore, heatmap clustering, correlation, and Z-score analyses were performed to identify the top DEMs. Kyoto Encyclopedia of Genes and Genomes enriched pathways of DEMs were determined using metabolite-based databases. Moreover, the clinical significance of these DEMs was evaluated on the basis of area under the receiver operating characteristic curve. Significantly dysregulated expressions of several metabolites were observed in the intergroup comparisons of the PCOS, POF, and healthy control groups. Furthermore, 6 DEMs were most frequently observed among the three groups. The expressions of these DEMs were not only directly correlated but also exhibited potential significance in patients with PCOS and POF. Novel metabolites with up/downregulated expressions can be discovered in patients with PCOS and POF using serum-based metabolomics; these metabolites show good diagnostic performance and can act as effective biomarkers for the early detection of PCOS and POF. Furthermore, these metabolites might be involved in the pathophysiological mechanisms of PCOS and POF via interplay with corresponding genes.

The main characteristics of panic disorder (PD) include recurrent panic attacks and persistent worry, accompanied by other physical and cognitive symptoms. While recent studies have revealed that gut bacteria play an important role in anxiety and depression, little is known about the relationship between oral microbiota and PD. Therefore, the objective of this study was to explore a possible correlation between oral microbiota and PD. We conducted 16S rRNA sequencing to compare differences in the oral microbiota of patients with PD (n = 26) and healthy controls (n = 40). Patients with PD exhibited higher alpha diversity (abundance and evenness) in their oral microbiota than healthy controls, while analysis of beta diversity revealed that the two groups differed in microbial community composition. Moreover, the relative abundance of 61 genera differed between them. Overall, PD resulted in distinct oral microbial profiles that could be potential diagnostic markers and therapeutic targets.