Adrenal function in relation to cytokines and outcome in non-critically ill patients with COVID-19.

PURPOSE: We aimed to identify whether hypothalamic-pituitary-adrenal (HPA) axis dysfunction is related to deterioration in a percentage of patients who progress to severe COVID-19. METHODS: In this cohort observational study, we evaluated HPA axis activation by measuring cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulfate (DHEA-S) levels, whole blood expression levels of the key glucocorticoid receptor, GCR-α, and the glucocorticoid-induced leucine zipper (GILZ), and cytokines, as markers of the inflammatory phase, in 149 patients with respiratory infection admitted in the ward, without known adrenal disease and/or confounding medications (glucocorticoids). One hundred and four (104) patients were SARS-CoV-2 positive (C +) and controls consisted of 45 SARS-CoV-2-negative patients (NC). RESULTS: No differences in cortisol levels were observed between the C + and the NC patients. Cortisol levels correlated with ACTH (r = 0.284, p = 0.001) and IL-6 (r = 0.289, p = 0.04). In C + patients, cortisol levels mainly correlated with IL-6 levels (r = 0.28; p = 0.017). GCR-α expression was significantly higher in C + patients compared to NC. Patients with higher cortisol levels were more likely to progress to respiratory function deterioration or die. Both GCR-α and GILZ expression were significantly higher in C + non-survivors. CONCLUSION: Our findings indicate that cortisol serves as an indicator of disease severity. GILZ expression appears to be a more effective marker of mortality prediction in moderate COVID-19 cases. However, routine measurement of GILZ levels is currently unavailable. Elevated levels of cortisol may be indicative of patients with moderate COVID-19 who are at a higher risk of deterioration. This information can aid in identifying individuals who require early medical attention.

Giant cell arteritis: incidence and phenotypic distribution in Western Norway 2013-2020.

Objectives: There is an increasing awareness of the spectrum of phenotypes in giant cell arteritis (GCA). However, there is sparse evidence concerning the phenotypic distribution which may be influenced by both genetic background and the environment. We established a cohort of all GCA-patients in the Bergen Health Area (Western Norway), to describe the phenotypic distribution and whether phenotypes differ with regards to incidence and clinical features. Methods: This is a retrospective cohort study including all GCA-patients in the Bergen Health Area from 2013-2020. Data were collected by reviewing patient records, and patients considered clinically likely GCA were included if they fulfilled at least one set of classification criteria. Temporal artery biopsy (TAB) and imaging results were used to classify the patients according to phenotype. The phenotype "cranial GCA" was used for patients with a positive TAB or halo sign on temporal artery ultrasound. "Non-cranial GCA" was used for patients with positive findings on FDG-PET/CT, MRI-, or CT angiography, or wall thickening indicative of vasculitis on ultrasound of axillary arteries. Patients with features of both these phenotypes were labeled "mixed." Patients that could not be classified due to negative or absent examination results were labeled "unclassifiable". Results: 257 patients were included. The overall incidence of GCA was 20.7 per 100,000 persons aged 50 years or older. Overall, the cranial phenotype was dominant, although more than half of the patients under 60 years of age had the non-cranial phenotype. The diagnostic delay was twice as long for patients of non-cranial and mixed phenotype compared to those of cranial phenotype. Headache was the most common clinical feature (78% of patients). Characteristic clinic features occurred less frequently in patients of non-cranial phenotype compared to cranial phenotype. Conclusion: The overall incidence for GCA was comparable to earlier reports from this region. The cranial phenotype dominated although the non-cranial phenotype was more common in patients under 60 years of age. The diagnostic delay was longer in patients with the non-cranial versus cranial phenotype, indicating a need for examination of non-cranial arteries when suspecting GCA.

Access to beds for interventional radiology patients: improving patient care.

This review describes the rationale in support of admitting rights for interventional radiologists and presents options for the management of interventional radiology (IR) inpatients. The manuscript also discusses wider aspects of IR involvement in inpatient treatment, such as income and funding for IR services, and the implications for IR as a clinical specialty.

Developing day-case units: imperative for optimal patient care in interventional radiology.

As interventional radiology (IR) treatments have evolved, they have become less invasive, enabling rapid recovery, which expedites ambulation and promotes same-day discharge. As a result of this, a significant proportion of IR elective work can be provided using a day-case service model. Reconfiguration of IR services to increase day-case procedures using a dedicated IR day-case unit (RDU) to facilitate the passage of patients is vital to ensure best medical practice. The aim of this review is to discuss the benefits of day-case IR procedures, the optimal structure of an RDU, and to inform radiologists how to introduce and/or improve day-case IR services in their IR practice.

The Impact of COVID-19 on Interventional Radiology Practice Worldwide: Results from a Global Survey.

BACKGROUND: The COVID-19 pandemic had an unprecedented impact on clinical practice and healthcare professionals. We aimed to assess how interventional radiology services (IR services) were impacted by the pandemic and describe adaptations to services and working patterns across the first two waves. METHODS: An anonymous six-part survey created using an online service was distributed as a single-use web link to 7125 members of the Cardiovascular and Interventional Radiological Society of Europe via email. Out of 450 respondents, 327 who completed the survey at least partially including 278 who completed the full survey were included into the analysis. RESULTS: Interventional radiologists (IRs) reported that the overall workload decreased a lot (18%) or mildly (36%) or remained stable (29%), and research activities were often delayed (30% in most/all projects, 33% in some projects). Extreme concerns about the health of families, patients and general public were reported by 43%, 34% and 40%, respectively, and 29% reported having experienced significant stress (25% quite a bit; 23% somewhat). Compared to the first wave, significant differences were seen regarding changes to working patterns, effect on emergency work, outpatient and day-case services in the second wave. A total of 59% of respondents felt that their organisation was better prepared for a third wave. A total of 19% and 39% reported that the changes implemented would be continued or potentially continued on a long-term basis. CONCLUSION: While the COVID-19 pandemic has negatively affected IR services in terms of workload, research activity and emotional burden, IRs seem to have improved the own perception of adaptation and preparation for further waves of the pandemic.

Acute kidney injury following endovascular intervention for peripheral artery disease.

BACKGROUND: The incidence of, and risk factors for, acute kidney injury (AKI) after endovascular intervention for peripheral artery disease (PAD) remain unknown. The aim of this study was to assess the proportion of patients who develop AKI and explore the risk factors. METHODS: Prospectively collected data on patients undergoing femoropopliteal endovascular intervention for symptomatic PAD across three vascular centres were analysed. The proportion of patients developing AKI (according to the Kidney Disease Improving Global Outcomes definition) within 48 h, and the proportion developing the composite Major Adverse Kidney Events (MAKE) endpoints (death, dialysis, drop in estimated glomerular filtration rate at least 25 per cent) at 30 days (MAKE30) and remains 90 days (MAKE90) were calculated. Multivariable regression analysis was used to assess predictors of AKI, and the association between AKI and death. RESULTS: Some 2041 patients were included in the analysis. AKI developed in 239 patients (11.7 per cent), with 47 (2.3 per cent) requiring dialysis within 30 days, and 18 (0.9 per cent) requiring ongoing dialysis. The MAKE30 and MAKE90 composite endpoints were reached in 358 (17.5 per cent) and 449 (22.0 per cent) patients respectively. Risk factors for AKI were age, sex, congestive heart failure, chronic limb-threatening ischaemia, emergency procedure, and pre-existing chronic kidney disease. AKI, dementia, congestive heart failure, and major amputation were risk factors for medium-term mortality. CONCLUSION: AKI is a common complication after intervention for PAD and is associated with medium-term mortality.

Transarterial chemoembolization for hepatocellular carcinoma: a bibliometric analysis of the most cited articles.

PURPOSE: Bibliometric analysis is a quantitative assessment of the academic literature in a particular field. The aim of our study was to characterize the 100 top-cited articles regarding transarterial chemoembolization (TACE) for the treatment of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The 'Web of Science' database was used to identify the leading articles regarding TACE for HCC. We determined the top 100 articles according to citations and performed an analysis on year of publication, authorship, department affiliation, publishing journal, institution and country of origin, subject matter and article type. RESULTS: The top-cited articles received between 92 and 2254 citations (median 283.4). The top 100 papers were published in 32 journals between 1983 and 2016. Cancer, Radiology and Hepatology published the most articles (n = 40). Internal medicine was the department affiliation of the first author in 49%. The country providing the most highly cited articles was Japan (n = 24). CONCLUSION: We performed an analysis of the 100 top-cited articles dealing with TACE for HCC, presenting a detailed list of the most influential and historically significant papers. Japan was the country that produced the most top-cited articles, highlighting its key contribution to this field of the literature.

Cost-Effectiveness Analysis of Nintedanib Versus Pirfenidone in Idiopathic Pulmonary Fibrosis in Belgium.

BACKGROUND: Nintedanib (Ofev®) and pirfenidone (Esbriet®) are recommended by international guidelines as treatment options for idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To compare the cost-effectiveness of nintedanib with that of pirfenidone for the treatment of IPF from a Belgian healthcare payer perspective. METHODS: The economic analysis used a Markov model that calculated outcomes over patient lifetime. Overall survival was assumed to be the same for the two comparators. Data from a network meta-analysis were used for loss of lung function, acute exacerbation events, safety and treatment discontinuation (for any reason). The health-state utility estimates in the model were calculated from EQ-5D scores collected in nintedanib studies. The assumed resource use for background care was also based on patient-level data that were categorised to fit the health states in the model and synthesised with costs and tariffs from Belgian national databases. RESULTS: Treatment with nintedanib resulted in an estimated total cost of €102,315, which was less than the total cost of treatment with pirfenidone (€113,313). Given the similarities in the survival and progression outcomes obtained with nintedanib and pirfenidone, the model predicted near equivalence in total QALYs (3.353 QALYs for the nintedanib arm and 3.318 for the pirfenidone arm). Results were largely driven by model assumptions underlying mortality, acute exacerbations and treatment discontinuation. CONCLUSIONS: After performing a synthesis of the most recently published evidence for IPF patients and assuming a Belgian healthcare payer perspective, we found nintedanib to be more cost-saving than pirfenidone.

Survival and death causes of patients with giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Our objective was to determine the survival and causes of death in a large and well-characterized cohort of patients with giant cell arteritis (GCA). METHODS: This is a hospital-based, retrospective, observational cohort study including patients diagnosed with GCA in Western Norway during 1972-2012. Patients were identified through computerized hospital records using the International Classification of Diseases (ICD)-coding system. Medical records were reviewed. Patients were randomly assigned population controls matched on age, sex, and geography from the Central Population Registry of Norway (CPRN). Date and cause of death were obtained from the Norwegian Cause of Death Registry (NCoDR). The survival was analyzed using Kaplan-Meier methods with the Gehan-Breslow test and the causes of death using cumulative incidence and Cox models for competing risks. RESULTS: We identified 881 cases with a clinical diagnosis of GCA of which 792 fulfilled the American College of Rheumatology (ACR) 1990 classification criteria. Among those fulfilling the ACR criteria, 528 were also biopsy-verified. Cases were matched with 2577 population controls. A total of 490 (56%) GCA patients and 1517 (59%) controls died during the study period. We found no difference in the overall survival of GCA patients compared to controls, p = 0.413. The most frequent underlying causes of death in both groups were diseases of the circulatory system followed by cancer. GCA patients had increased risk of dying of circulatory disease (HR 1.31, 95% CI 1.13-1.51, p < 0.001) but lower risk of dying of cancer (HR 0.56, 95% CI 0.42-0.73, p < 0.001) compared to population controls. CONCLUSIONS: We found no difference in the overall survival of GCA patients compared to matched controls, but there were differences in the distribution of underlying death causes.

Correction to: Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

Following publication of the original article [1], the authors reported an error.

Incidence of giant cell arteritis in Western Norway 1972-2012: a retrospective cohort study.

BACKGROUND: Giant cell arteritis (GCA) is the most common systemic vasculitis in persons older than 50 years. The highest incidence rates of the disease have been reported in Scandinavian countries. Our objective was to determine the epidemiology of GCA in an expected high-incidence region during a 41-year period. METHODS: This is a hospital-based, retrospective, cohort study. Patients diagnosed with GCA in Bergen health area during 1972-2012 were identified through computerized hospital records (n = 1341). Clinical information was extracted from patients' medical journals, which were reviewed by a standardized method. We excluded patients if data were unavailable (n = 253), if the reviewing rheumatologist found GCA to be an implausible diagnosis (n = 207) or if the American College of Rheumatology (ACR) 1990 classification criteria for GCA were not fulfilled (n = 89). Descriptive methods were used to characterize the sample. Incidence was analyzed by graphical methods and Poisson regression. RESULTS: A total of 792 patients were included. The average annual cumulative incidence of GCA was 16.7 (95% CI 15.5-18.0) per 100,000 of the population ≥ 50 years old. The corresponding incidence for biopsy-verified GCA was 11.2 (95% CI 10.2-12.3). The annual cumulative incidence increased with time in the period 1972-1992 (relative risk (RR) 1.1, p < 0.001) but not in 1993-2012 (RR 1.0, p = 0.543). The incidence was higher in women compared to men (average annual incidence 37.7 (95% CI 35.8-39.6) vs. 14.3 (95% CI 13.2-15.5), p < 0.001) with women having a twofold to threefold higher incidence rate throughout the study period. Average annual incidence increased with age until the 7th decade of life in both sexes throughout the study period (2.8 (95% CI 2.3-3.3) for age <60, 15.5 (95% CI 14.4-16.8) for age 60-69, 34.5 (95% CI 32.8-36.4) for age 70-79 and 26.8 (95% CI 25.3-28.4) for age ≥80 years, p < 0.001 for all age adjustments). CONCLUSIONS: Our study confirms an incidence of GCA comparable to previous reports on Scandinavian populations. Our results show increasing incidence from 1972 through 1992, after which the incidence has levelled out.

Settings and artefacts relevant for Doppler ultrasound in large vessel vasculitis.

Ultrasound is used increasingly for diagnosing large vessel vasculitis (LVV). The application of Doppler in LVV is very different from in arthritic conditions. This paper aims to explain the most important Doppler parameters, including spectral Doppler, and how the settings differ from those used in arthritic conditions and provide recommendations for optimal adjustments. This is addressed through relevant Doppler physics, focusing, for example, on the Doppler shift equation and how angle correction ensures correctly displayed blood velocity. Recommendations for optimal settings are given, focusing especially on pulse repetition frequency (PRF), gain and Doppler frequency and how they impact on detection of flow. Doppler artefacts are inherent and may be affected by the adjustment of settings. The most important artefacts to be aware of, and to be able to eliminate or minimize, are random noise and blooming, aliasing and motion artefacts. Random noise and blooming artefacts can be eliminated by lowering the Doppler gain. Aliasing and motion artefacts occur when the PRF is set too low, and correct adjustment of the PRF is crucial. Some artefacts, like mirror and reverberation artefacts, cannot be eliminated and should therefore be recognised when they occur. The commonly encountered artefacts, their importance for image interpretation and how to adjust Doppler setting in order to eliminate or minimize them are explained thoroughly with imaging examples in this review.

Frequent COL4 mutations in familial microhematuria accompanied by later-onset Alport nephropathy due to focal segmental glomerulosclerosis.

Familial microscopic hematuria (FMH) is associated with a genetically heterogeneous group of conditions including the collagen-IV nephropathies, the heritable C3/CFHR5 nephropathy and the glomerulopathy with fibronectin deposits. The clinical course varies widely, ranging from isolated benign familial hematuria to end-stage renal disease (ESRD) later in life. We investigated 24 families using next generation sequencing (NGS) for 5 genes: COL4A3, COL4A4, COL4A5, CFHR5 and FN1. In 17 families (71%), we found 15 pathogenic mutations in COL4A3/A4/A5, 9 of them novel. In 5 families patients inherited classical AS with hemizygous X-linked COL4A5 mutations. Even more patients developed later-onset Alport-related nephropathy having inherited heterozygous COL4A3/A4 mutations that cause thin basement membranes. Amongst 62 heterozygous or hemizygous patients, 8 (13%) reached ESRD, while 25% of patients with heterozygous COL4A3/A4 mutations, aged >50-years, reached ESRD. In conclusion, COL4A mutations comprise a frequent cause of FMH. Heterozygous COL4A3/A4 mutations predispose to renal function impairment, supporting that thin basement membrane nephropathy is not always benign. The molecular diagnosis is essential for differentiating the X-linked from the autosomal recessive and dominant inheritance. Finally, NGS technology is established as the gold standard for the diagnosis of FMH and associated collagen-IV glomerulopathies, frequently averting the need for invasive renal biopsies.

A Cost-Effectiveness Analysis of Nintedanib in Idiopathic Pulmonary Fibrosis in the UK.

BACKGROUND: International guidelines recommend nintedanib (OFEV®) as an option for the treatment of idiopathic pulmonary fibrosis (IPF). OBJECTIVE: The objective of this study was to assess the cost effectiveness of nintedanib versus pirfenidone, N-acetylcysteine and best supportive care (BSC) for the treatment of IPF from a UK payer's perspective. METHODS: A Markov model was designed to capture the changes in the condition of adults with IPF. Efficacy outcomes included mortality, lung function decline and acute exacerbations. Treatment safety (serious adverse events) and tolerability (overall discontinuation) were also considered. The baseline risk of these events was derived from patient-level data from the placebo arms of nintedanib clinical trials (TOMORROW, INPULSIS-1, INPULSIS-2). A network meta-analysis (NMA) was conducted to estimate the relative effectiveness of the comparator treatments. Quality of life and healthcare resource use data from the clinical trials were also incorporated in the economic model. RESULTS: Nintedanib showed statistically significant differences against placebo on acute exacerbation events avoided and lung function decline. In the cost-effectiveness analysis, the results were split between two treatments with relative low costs and modest effectiveness (BSC and N-acetylcysteine) and two that showed improved effectiveness (lung function) and higher costs (nintedanib and pirfenidone). All comparators were assumed to have similar projected survival and the difference in quality-adjusted life-years (QALYs) was driven by the acute exacerbations and lung function estimates. In the base-case deterministic pairwise comparison with pirfenidone, nintedanib was found to have fewer acute exacerbations and resulted in less costs and more QALYs gained. CONCLUSIONS: Compared with BSC (placebo), nintedanib and pirfenidone were the only treatments to show statistical significance in the efficacy parameters. We found substantial uncertainty in the overall cost-effectiveness results between nintedanib and pirfenidone. N-Acetylcysteine was largely similar to BSC but with a worse survival profile. INPULSIS-1 and INPULSIS-2 ClinicalTrials.gov numbers, NCT01335464 and NCT01335477.

Comparison of angioplasty and bypass surgery for critical limb ischaemia in patients with infrapopliteal peripheral artery disease.

BACKGROUND: Both infrapopliteal (IP) bypass surgery and percutaneous transluminal angioplasty have been shown to be effective in patients with critical limb ischaemia (CLI). The most appropriate method of revascularization has yet to be established, as no randomized trials have been reported. The aim of this study was to compare the outcomes of patients with similar characteristics treated using either revascularization method. METHODS: Consecutive patients undergoing IP bypass and IP angioplasty for CLI (Rutherford 4-6) at a single institution were compared following propensity score matching. The study endpoints were primary, assisted primary and secondary patency, and amputation-free survival at 12 months, calculated by Kaplan-Meier analysis. RESULTS: Some 279 limbs in 243 patients were included in the study. The two groups differed significantly with respect to the incidence of diabetes (P = 0·024), estimated glomerular filtration rate (P = 0·006), total lesion length (P < 0·001) and Rutherford classification (P = 0·008). These factors were used to construct the propensity score model, which yielded a matched cohort of 125 legs in each group. Primary patency (54·4 versus 51·4 per cent; P = 0·014), assisted primary patency (77·5 versus 62·7 per cent; P = 0·003), secondary patency (84·4 versus 65·8 per cent; P < 0·001) and amputation-free survival (78·7 versus 74·1 per cent; P = 0·043) were significantly better after bypass than angioplasty. However, limb salvage was similar (90·4 versus 94·2 per cent; P = 0·161), and overall complications (36·0 versus 21·6 per cent; P = 0·041) as well as length of hospital stay (18(4-134) versus 5(0-110); P = 0·001) were worse in the surgical bypass group. CONCLUSION: There was no difference in limb salvage rates, but patency and amputation-free survival rates were better 1 year after bypass surgery.

Atherectomy of the femoropopliteal artery: a systematic review and meta-analysis of randomized controlled trials.

A systematic review was performed to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing debulking atherectomy versus balloon angioplasty for treatment of femoropopliteal artery occlusive disease. PubMed (MEDLINE), EMBASE, AMED, Scopus, online content and meeting abstracts were searched in May 2014 for eligible RCTs following the PRISMA selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Pooled risks were calculated with a random effects model to account for clinical and conceptual heterogeneity. Sensitivity analysis was employed to test the robustness of the results. Six RCTs comprising 287 patients (328 lesions) treated with either debulking atherectomy or balloon angioplasty for femoropopliteal artery disease were analyzed and synthesized. Technical success was similar between the atherectomy and the angioplasty group (93.6% vs. 96.2%, RR: 0.99. 95%CI: 0.95-1.03, P=0.57, I(2)=0%). Need for bail-out stenting and distal arterial embolization were largely similar between atherectomy and balloon angioplasty alone. After a median follow-up of 9 months the 2 groups showed similar primary patency (RR: 0.90, 95%CI: 0.56-1.46, P=0.68, I(2)=69%). Only 2 low-quality studies reported amputation and mortality rates, both of which were found significantly less in the atherectomy arms. Analysis of a limited body of low quality evidence with high risk of bias showed that debulking atherectomy of the femoropopliteal artery does not seem to confer any procedural advantage or improvement of clinical outcomes over balloon angioplasty alone.

Paclitaxel-coated balloons for failing peripheral bypass grafts: the BYPACS study.

AIM: Aim of the present study was to report the imaging and clinical outcomes of a prospective single-center study investigating paclitaxel-coated balloons (PCB) for the treatment of failing peripheral bypass grafts (BYPACS study). METHODS: In total, 32 patients had their failing peripheral native or synthetic bypass graft treated with PCB angioplasty (Group PCB). Basic inclusion criteria were any significant proximal or distal anastomotic stenosis confirmed by Duplex ultrasound (DUS; PSVR>2.5) associated with significantly reduced in-graft velocities (<45 cm/s) putting the graft at risk of thrombosis. Results were compared with a similar historical control group of 24 patients who had their failing peripheral bypass treated with plain uncoated balloon angioplasty (Group PTA). Primary endpoint was binary lesion restenosis defined as >50% stenosis of the treated lesion on DUS. Secondary endpoints included freedom from target lesion revascularization (TLR) defined as a patent peripheral bypass graft regardless of restenosis but without any repeat intervention (driven by reduced in-graft velocities <45 cm/s), major amputations and graft thrombosis. Multivariable Cox proportional hazards regression analysis was applied to adjust for confounding factors of heterogeneity. Results are reported as Cox-adjusted hazard ratios (HR and 95% CI). RESULTS: Baseline variables were equally distributed between the two groups. Median follow-up was 7 months in group PCB and 8 months in group PTA. Rates of binary restenosis were similar between the 2 groups (HR=1.08, 95% CI=0.49-2.40; P=0.84). Freedom from TLR was also similar (HR=0.97, 95% CI=0.36-2.66; P=0.88). One amputation occurred in the PCB group and 2 in the PTA (P=0.58). Four events of bypass thrombosis occurred in each group (P=0.71). CONCLUSION: PCB does not significantly inhibit restenosis or improve freedom from repeat angioplasty after treatment of failing peripheral arterial vein or synthetic bypass grafts.