Combination of computed tomography angiography with coronary artery calcium score for improved diagnosis of coronary artery disease: a collaborative meta-analysis of stable chest pain patients referred for invasive coronary angiography.

OBJECTIVES: Coronary computed tomography angiography (CCTA) has higher diagnostic accuracy than coronary artery calcium (CAC) score for detecting obstructive coronary artery disease (CAD) in patients with stable chest pain, while the added diagnostic value of combining CCTA with CAC is unknown. We investigated whether combining coronary CCTA with CAC score can improve the diagnosis of obstructive CAD compared with CCTA alone. METHODS: A total of 2315 patients (858 women, 37%) aged 61.1 ± 10.2 from 29 original studies were included to build two CAD prediction models based on either CCTA alone or CCTA combined with the CAC score. CAD was defined as at least 50% coronary diameter stenosis on invasive coronary angiography. Models were built by using generalized linear mixed-effects models with a random intercept set for the original study. The two CAD prediction models were compared by the likelihood ratio test, while their diagnostic performance was compared using the area under the receiver-operating-characteristic curve (AUC). Net benefit (benefit of true positive versus harm of false positive) was assessed by decision curve analysis. RESULTS: CAD prevalence was 43.5% (1007/2315). Combining CCTA with CAC improved CAD diagnosis compared with CCTA alone (AUC: 87% [95% CI: 86 to 89%] vs. 80% [95% CI: 78 to 82%]; p < 0.001), likelihood ratio test 236.3, df: 1, p < 0.001, showing a higher net benefit across almost all threshold probabilities. CONCLUSION: Adding the CAC score to CCTA findings in patients with stable chest pain improves the diagnostic performance in detecting CAD and the net benefit compared with CCTA alone. CLINICAL RELEVANCE STATEMENT: CAC scoring CT performed before coronary CTA and included in the diagnostic model can improve obstructive CAD diagnosis, especially when CCTA is non-diagnostic. KEY POINTS: • The combination of coronary artery calcium with coronary computed tomography angiography showed significantly higher AUC (87%, 95% confidence interval [CI]: 86 to 89%) for diagnosis of coronary artery disease compared to coronary computed tomography angiography alone (80%, 95% CI: 78 to 82%, p < 0.001). • Diagnostic improvement was mostly seen in patients with non-diagnostic C. • The improvement in diagnostic performance and the net benefit was consistent across age groups, chest pain types, and genders.

Understanding the biases to sepsis surveillance and quality assurance caused by inaccurate coding in administrative health data.

PURPOSE: Timely and accurate data on the epidemiology of sepsis are essential to inform policy decisions and research priorities. We aimed to investigate the validity of inpatient administrative health data (IAHD) for surveillance and quality assurance of sepsis care. METHODS: We conducted a retrospective validation study in a disproportional stratified random sample of 10,334 inpatient cases of age ≥ 15 years treated in 2015-2017 in ten German hospitals. The accuracy of coding of sepsis and risk factors for mortality in IAHD was assessed compared to reference standard diagnoses obtained by a chart review. Hospital-level risk-adjusted mortality of sepsis as calculated from IAHD information was compared to mortality calculated from chart review information. RESULTS: ICD-coding of sepsis in IAHD showed high positive predictive value (76.9-85.7% depending on sepsis definition), but low sensitivity (26.8-38%), which led to an underestimation of sepsis incidence (1.4% vs. 3.3% for severe sepsis-1). Not naming sepsis in the chart was strongly associated with under-coding of sepsis. The frequency of correctly naming sepsis and ICD-coding of sepsis varied strongly between hospitals (range of sensitivity of naming: 29-71.7%, of ICD-diagnosis: 10.7-58.5%). Risk-adjusted mortality of sepsis per hospital calculated from coding in IAHD showed no substantial correlation to reference standard risk-adjusted mortality (r = 0.09). CONCLUSION: Due to the under-coding of sepsis in IAHD, previous epidemiological studies underestimated the burden of sepsis in Germany. There is a large variability between hospitals in accuracy of diagnosing and coding of sepsis. Therefore, IAHD alone is not suited to assess quality of sepsis care.

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission.

SLC4A10 is a plasma-membrane bound transporter that utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of CSF. Using next generation sequencing on samples from five unrelated families encompassing nine affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorder including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioural abnormalities including delayed habituation and alterations in the two-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggest an important role of SLC4A10 in the production of the CSF. However, it is notable that despite diverse roles of the CSF in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies, which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties.

Understanding health care pathways of patients with sepsis: protocol of a mixed-methods analysis of health care utilization, experiences, and needs of patients with and after sepsis.

BACKGROUND: Sepsis is associated with about 20% of deaths worldwide. It often presents with non-specific initial symptoms, making its emergency treatment an interdisciplinary and cross-sectoral challenge. Three in four sepsis survivors suffers from new cognitive, psychological, or physical sequelae for which specific treatment concepts are scarce. The AVENIR project aims to improve the understanding of patient pathways, and subjective care experiences and needs along the entire healthcare pathway before, with and after sepsis. Based on this, concrete recommendations for the organization of care and patient information materials will be developed with close patient participation. METHODS: Mixed-methods study including (1) analysis of anonymized nationwide health claims data from Germany, (2) linkage of health claims data with patient care reports (PCR) of emergency medical services from study regions in two federal states within Germany, and (3) qualitative exploration of the patient, relative, and care provider perspective on sepsis care. In (1), we analyze inpatient and outpatient health care utilization until 30 days pre-sepsis; clinical sepsis care including intra- and inter-hospital transfers; and rehabilitation, inpatient and outpatient aftercare of sepsis survivors as well as costs for health care utilization until 24 months post-sepsis. We attempt to identify survivor classes with similar health care utilization by Latent Class Analyses. In (2), PCR are linked with health claims data to establish a comprehensive database outlining care pathways for sepsis patients from pre-hospital to follow-up. We investigate e.g., whether correct initial assessment is associated with acute (e.g., same-day lethality) and long-term (e.g., new need for care, long-term mortality) outcomes of patients. We compare the performance of sepsis-specific screening tools such as qSOFA, NEWS-2 or PRESEP in the pre-clinical setting. In (3), semi-structured interviews as well as synchronous and asynchronous online focus groups are conducted and analyzed using qualitative content analyses techniques. DISCUSSION: The results of the AVENIR study will contribute to a deeper understanding of sepsis care pathways in Germany. They may serve as a base for improvements and innovations in sepsis care, that in the long-term can contribute to reduce the personal, medical, and societal burden of sepsis and its sepsis sequelae. TRIAL REGISTRATION: Registered at German Clinical Trial Register (ID: DRKS00031302, date of registration: 5th May 2023).

Surgery for patients with facial palsy in Germany: a diagnosis-related-groups-based nationwide analysis, 2005-2019.

PURPOSE: Chronic flaccid paralysis of the facial nerve leads to permanent dysfunction of eye closure, problems with drinking and eating, and lack of emotional expression. Modern facial surgery can help those affected. An analysis of the development of facial surgery in Germany over time is presented. METHODS: Nation-wide population-baes diagnosis-related case group (DRG) data of virtually all inpatients who underwent facial surgery for facial palsy between 2005 and 2019 were included. Binomial regression models for changes in surgery rates over time were calculated in relation to gender and treating specialty. RESULTS: Between 2005 and 2019, there were 28,622 inpatient stays for facial surgery. Most surgeries were provided by otolaryngology (39%) and ophthalmology or dentistry, oral and maxillofacial surgery (20% each). The mean treatment rate was 2.33 ± 0.53 surgeries per 100,000 person-years. The surgery rate was highest for nerve reconstruction surgery (0.46 ± 0.15) and static sling surgery (0.44 ± 0.0.16). The greatest increase was seen in men for nerve surgery (3.9-fold; relative risk [RR] = 3.68; confidence interval [CI] = 3.18-4.26) and sling surgery (5.0-fold; RR = 4.25; CI = 3.38-5.33). CONCLUSIONS: While nerve and sling surgery increased significantly over time, this was less true or not true at all for surgical techniques. Surgical rates and their change over time were greater in men, without explanation from the data.

[The adaptive use of the Freiburg monosyllabic speech test in noise with a reduced number of test lists]. / Die adaptive Messung des Freiburger Einsilbertests im Störschall mit einer verringerten Anzahl an Testlisten.

BACKGROUND: Considering the different calibration and masking of the noise, the adaptive Freiburg monosyllabic speech test in noise (aFBE-S) and the Oldenburg sentence test in noise (OLSA-S) were shown to be comparable with respect to the accuracy of both tests in a previous study. However, the time requirement of the aFBE-S was significantly greater than that of the OLSA-S due to the adaptive measurement method. The purpose of this study is to theoretically determine whether the aFBE-S can be used with fewer test lists, given the low scatter of results, and to compare the results with those of the OLSA-S. METHODS: Using the results of 40 otologically healthy subjects who had already been tested in randomized order with the OLSA-S and aFBE-S, the mean difference of the 95 % confidence interval (95 % CI) of the signal-to-noise ratio for 50% speech understanding (S/N50) of the aFBE-S was calculated for three, four, and five test lists instead of 7.5. In addition, the time required for the reduced number of test lists was determined and the results were examined in comparison with those of the OLSA-S. RESULTS: In each case, no significant difference between the difference mean of the 95 %-CI of the S/N50 of the original aFBE-S, the aFBE-S shortened to 3, 4, or 5 test lists and the OLSA-S could be found. The time required for the aFBE-S with a reduced number of test lists was significantly less than for the OLSA-S in each case. CONCLUSION: The aFBE-S is not inferior with a reduced number of test lists in comparison to the OLSA-S. This would allow to use the shortened aFBE-S theoretically.

Association between hospital onset of infection and outcomes in sepsis patients - A propensity score matched cohort study based on health claims data in Germany.

BACKGROUND: Hospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. OBJECTIVE: We aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. METHODS: This retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. RESULTS: We matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001). CONCLUSIONS: HAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control.

Acute effects of lithium augmentation on the kidney in geriatric compared with non-geriatric patients with treatment-resistant depression.

INTRODUCTION: Lithium augmentation (LA) of antidepressants is a first-line therapy option for treatment-resistant depression (TRD). Nevertheless, it is rarely used in geriatric patients mostly because of the fear of kidney toxicity. The purpose of this study is to investigate estimated glomerular filtration rate (eGFR) changes and number of acute kidney injuries (AKI) using LA in geriatric compared with non-geriatric patients. METHODS: In a prospective multicenter cohort study, eGFR changes were measured in 201 patients with unipolar depression (nage≥65years  = 29; nage<65years  = 172) at baseline and over 2-6 weeks of LA. We used linear mixed models to investigate changes in eGFR upon LA and assessed the number of AKIs, according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: Both age groups showed a significant eGFR decline over the course of treatment with lower eGFR in geriatric patients. The lithium serum level (interpretable as "effect of LA") had a significant effect on eGFR decline. Both effects (age group and lithium serum level) on eGFR decline did not influence each other, meaning the effect of LA on eGFR decline did not differ between age groups. Two AKIs were observed in the geriatric age group when serum lithium levels exceeded the therapeutic range of >0.8 mmol/L. CONCLUSION: This is the first study investigating eGFR change and AKI upon LA for TRD in geriatric compared with non-geriatric patients. Our data suggest that LA, as an effective treatment option in geriatric patients, should be closely monitored to avoid AKIs.

Tutorial: statistical methods for the meta-analysis of diagnostic test accuracy studies.

This tutorial shows how to perform a meta-analysis of diagnostic test accuracy studies (DTA) based on a 2 × 2 table available for each included primary study. First, univariate methods for meta-analysis of sensitivity and specificity are presented. Then the use of univariate logistic regression models with and without random effects for e.g. sensitivity is described. Diagnostic odds ratios (DOR) are then introduced to combine sensitivity and specificity into one single measure and to assess publication bias. Finally, bivariate random effects models using the exact binomial likelihood to describe within-study variability and a normal distribution to describe between-study variability are presented as the method of choice. Based on this model summary receiver operating characteristic (sROC) curves are constructed using a regression model logit-true positive rate (TPR) over logit-false positive rate (FPR). Also it is demonstrated how to perform the necessary calculations with the freely available software R. As an example a meta-analysis of DTA studies using Procalcitonin as a diagnostic marker for sepsis is presented.

S2k Guideline - Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) - Update 2022.

Merkel cell carcinoma (MCC, ICD-O M8247/3) is a rare, malignant, primary skin tumor with epithelial and neuroendocrine differentiation. The tumor cells share many morphologic, immunohistochemical, and ultrastructural features with cutaneous Merkel cells. Nevertheless, the cell of origin of MCC is unclear. MCC appears clinically as a reddish to purple spherical tumor with a smooth, shiny surface and a soft to turgid, elastic consistency, usually showing rapid growth. Spontaneous and often complete regressions of the tumor are observed. These likely immunologically-mediated regressions explain the cases in which only lymph node or distant metastases are found at the time of initial diagnosis and why the tumor responds very well to immunomodulatory therapies even at advanced stages. Due to its aggressiveness, the usually given indication for sentinel lymph node biopsy, the indication of adjuvant therapies to be evaluated, as well as the complexity of the necessary diagnostics, clinical management should already be determined by an interdisciplinary tumor board at the time of initial diagnosis.

Electrocardiographic Changes During Initiation of Lithium Augmentation of Antidepressant Pharmacotherapy.

PURPOSE/BACKGROUND: Lithium augmentation of antidepressants represents a common strategy to overcome treatment resistance in patients with major depressive disorder. The use of lithium has been associated with cardiovascular adverse effects such as QTc prolongation and tachyarrhythmia. Although the previous studies investigated monotherapy with lithium, the aim of this study was to investigate electrocardiographic changes in LA. METHODS/PROCEDURES: A 12-lead surface electrocardiogram (ECG) was obtained from 38 patients with major depressive disorder before and during LA. Changes in heart rate, PQ, QRS and QTc interval, QT dispersion, ST segment, and T- and U-wave alterations were analyzed using a linear mixed model. FINDINGS/RESULTS: The ECG readings of 33 patients were evaluated. Lithium augmentation was not significantly associated with changes in heart rate, QTc, PQ, or QRS interval. We found a significant decrease in QT dispersion. These results were independent of sex, age, stable comedication, and comorbidities. During LA, we observed 9 cases of T-wave alterations and 2 cases of new U waves. CONCLUSIONS: Our data provide no evidence for serious ECG abnormalities at therapeutic serum lithium levels in patients treated with LA. In particular, we did not find evidence for QTc time lengthening or tachyarrhythmia, such as torsades des pointes. The recommended intervals for ECG checks should be considered to detect long-term effects of LA.

Computed tomography angiography versus Agatston score for diagnosis of coronary artery disease in patients with stable chest pain: individual patient data meta-analysis of the international COME-CCT Consortium.

OBJECTIVES: There is conflicting evidence about the comparative diagnostic accuracy of the Agatston score versus computed tomography angiography (CTA) in patients with suspected obstructive coronary artery disease (CAD). PURPOSE: To determine whether CTA is superior to the Agatston score in the diagnosis of CAD. METHODS: In total 2452 patients with stable chest pain and a clinical indication for invasive coronary angiography (ICA) for suspected CAD were included by the Collaborative Meta-analysis of Cardiac CT (COME-CCT) Consortium. An Agatston score of > 400 was considered positive, and obstructive CAD defined as at least 50% coronary diameter stenosis on ICA was used as the reference standard. RESULTS: Obstructive CAD was diagnosed in 44.9% of patients (1100/2452). The median Agatston score was 74. Diagnostic accuracy of CTA for the detection of obstructive CAD (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) was significantly higher than that of the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). Among patients with an Agatston score of zero, 17% (101/600) had obstructive CAD. Diagnostic accuracy of CTA was not significantly different in patients with low to intermediate (1 to < 100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). CONCLUSIONS: Results in our international cohort show CTA to have significantly higher diagnostic accuracy than the Agatston score in patients with stable chest pain, suspected CAD, and a clinical indication for ICA. Diagnostic performance of CTA is not affected by a higher Agatston score while an Agatston score of zero does not reliably exclude obstructive CAD. KEY POINTS: • CTA showed significantly higher diagnostic accuracy (81.1%, 95% confidence interval [CI]: 77.5 to 84.1%) for diagnosis of coronary artery disease when compared to the Agatston score (68.8%, 95% CI: 64.2 to 73.1%, p < 0.001). • Diagnostic performance of CTA was not affected by increased amount of calcium and was not significantly different in patients with low to intermediate (1 to <100, 100-400) versus moderate to high Agatston scores (401-1000, > 1000). • Seventeen percent of patients with an Agatston score of zero showed obstructive coronary artery disease by invasive angiography showing absence of coronary artery calcium cannot reliably exclude coronary artery disease.

Statistics in diagnostic medicine.

This tutorial gives an introduction into statistical methods for diagnostic medicine. The validity of a diagnostic test can be assessed using sensitivity and specificity which are defined for a binary diagnostic test with known reference or gold standard. As an example we use Procalcitonin with a cut off value ≥ 0.5 g/L as a test and Sepsis-2 criteria as a reference standard for the diagnosis of sepsis. Next likelihood ratios are introduced which combine the information given by sensitivity and specificity. For these measures the construction of confidence intervals is demonstrated. Then, we introduce predictive values using Bayes' theorem. Predictive values are sometimes difficult to communicate. This can be improved using natural frequencies which are applied to our example. Procalcitonin is actually a continuous biomarker, hence we introduce the use of receiver operator curves (ROC) and the area under the curve (AUC). Finally we discuss sample size estimation for diagnostic studies. In order to show how to apply these concepts in practice we explain how to use the freely available software R.

Disease recurrence in patients with Crohn's disease after biologic therapy or surgery: a meta-analysis.

BACKGROUND: Relapse is a problem in patients with Crohn's disease (CD) after medical therapy (including biologics) and after surgery to treat acute inflammation. It is unclear whether the recurrence rate over time is higher after surgical therapy than after continuous drug treatment. AIM: We sought to compare clinical relapse rates and the need for re-interventions (resection or therapeutic endoscopic intervention) in patients with CD. METHODS: A meta-analysis was performed according to PRISMA guidelines. RESULTS: The need for one of the three re-interventions (surgery, biologics or both) increased over time. The recurrence rates in patients after ileocecal resection were lower than the rates under biologic therapy. The odds ratio for clinical recurrence under biologics versus after surgical treatment was 2.50 (95% confidence interval [CI] 1.53-4.08, p-value < 0.001). The odds ratio for surgical recurrence under biologics versus after surgery was 3.60 (95% CI 1.06-12.3, p-value 0.041). CONCLUSION: These findings support surgical resection as a treatment option in patients with CD with limited disease.

Evaluation of the post-processing algorithms SimGrid and S-Enhance for paediatric intensive care patients and neonates.

BACKGROUND: Post-processing software can be used in digital radiography to achieve higher image quality, especially in cases of scattered radiation. SimGrid is a grid-like software based on a Convolutional Neuronal Network that estimates the distribution and degree of scattered radiation in radiographs and thus improves image quality by simulating an anti-scatter grid. S-Enhance is an algorithm programmed to improve contrast visibility of foreign material. OBJECTIVE: The objective of this study was to evaluate the SimGrid and S-Enhance digital radiography post-processing methods for neonatology and paediatric intensive care. MATERIALS AND METHODS: Two hundred and ten radiographs from the neonatal (n = 101, 0 to 6 months of age) and paediatric (n = 109, 6 months to 18 years of age) intensive care units performed in daily clinical routine using a mobile digital radiography system were post-processed with one of the algorithms, anonymized and then evaluated comparatively by two experienced paediatric radiologists. For every radiograph, patient data and exposure data were collected and analysed. RESULTS: Analysis of different radiographs showed that SimGrid significantly improves image quality for patients with a weight above 10 kg (range: 10-30 kg: odds ratio [OR] = 6.683, P < 0.0001), especially regarding the tracheobronchial system, intestinal gas, and bones. Utilizing S-Enhance significantly advances the assessment of foreign material (OR = 136.111, P < 0.0001) and bones (OR = 34.917, P < 0.0001) for children of all ages and weight, whereas overall image quality decreases. CONCLUSION: SimGrid offers a differentiated spectrum in image improvement for children beyond the neonatal period whereas S-Enhance especially improves visibility of foreign material and bones for all patients.

Cones and sleeves present good survival and clinical outcome in revision total knee arthroplasty: a meta-analysis.

PURPOSE: The fixation of revision total knee arthroplasties (rTKA) tends to be difficult, leading to a reduction in implant survival. One option for achieving a more stable anchorage is to use metaphyseal cones and sleeves. The objective of the present paper is to provide a current comparative meta-analysis on survival and clinical results of cones vs. sleeves, with a differentiation between the short- and long-term outcome. METHODS: A search of the literature was conducted systematically to include original papers from 2010 to June 2021. The following parameters were taken into account: revision for aseptic loosening, revision for any reason, periprosthetic joint infections (PJI), KSS as well as KSFS. Studies with a mean follow-up of at least 60 months were defined to be long-term follow-up studies (LT). All other studies were included in the short-term (ST) study analysis. A pooled incidence was used as a summary statistic using a random intercept logistic regression model. RESULTS: The present meta-analysis included 43 publications with 3008 rTKA. Of these, 23 publications with 1911 cases were allocated to the sleeve group (SG) and 20 papers with 1097 cases to the cone group (CG). CG showed overall numerically higher complication rates in short- and long-term follow-up, compared with SG. Aseptic loosening occurred at a rate of 0.4% in SG (LT) and 4.1% in CG (LT) (p = 0.09). Periprosthetic joint infection (PJI) was more frequent in the cone group (7% in ST and 11.7% in LT) than in the sleeve group (3.4% in ST and 4.9% in LT, p = 0.02 both). The total revision rate was 5.5% in SG (LT) and 14.4% in CG (LT) (p = 0.12). The clinical scores were also comparable between the two groups. Hinged prothesis were used more frequent in the cone group (ST p < 0.001; LT p = 0.10), whereas CC type protheses were used more frequently in the sleeve group (ST p < 0.001; LT p < 0.11). CONCLUSIONS: This meta-analysis takes into account the longest follow-up periods covered to date. Both cones and sleeves represent a reliable fixation method in the case of severe bone loss in rTKA, although the higher rate of PJI after cone fixation remains a source of concern. A metaphyseal fixation of hinged implants should be taken into account. LEVEL OF EVIDENCE: II (meta-analysis).

Clinical pre-test probability for obstructive coronary artery disease: insights from the European DISCHARGE pilot study.

OBJECTIVES: To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting. METHODS: Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA. RESULTS: In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1-90.6%), updated D+F 47.3% (34.2-59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70-0.76 versus AUC of 0.70 CI 0.67-0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29-1.86, net reclassification index 0.11 CI 0.05-0.16, p < 0.001). CONCLUSIONS: Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed. TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT02400229 KEY POINTS: • Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT. • Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F. • Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.

Weather conditions associated with subarachnoid hemorrhage: a multicenter case-crossover study.

BACKGROUND: Most spontaneous subarachnoid hemorrhages (SAH) occur unexpectedly and independently of classical risk factors. In the light of increasing climate variability and change, we investigated weather and rapid weather changes as possible short-term risk factors for SAH. METHODS: Seven hundred ninety one patients admitted to three major hospitals in Germany for non-traumatic SAH with a determinable onset of SAH symptoms were included in this hospital-based, case-crossover study. The effects of atmospheric pressure, relative air humidity, and ambient temperature and their 24 h changes on the onset of SAH under temperate climate conditions were estimated. RESULTS: There was no association between the risk of SAH and 24 h weather changes, mean daily temperature or mean relative air humidity in the overall population. For every 11.5 hPa higher mean daily atmospheric pressure, the risk of SAH increased by 15% (OR 1.15, 95% confidence interval (CI) 1.01-1.30) in the entire study population with a lag time of three days. CONCLUSION: Our results suggest no relevant association between 24 h-weather changes or absolute values of ambient temperature and relative humidity and the risk of SAH. The medical significance of the statistically weak increase in SAH risk three days after exposure to high atmospheric pressure is unclear. However, as the occurrence of stable high-pressure systems will increase with global warming and potentially affect SAH risk, we call for confirming studies in different geographical regions to verify our observations.

Temperatures in Pigs During 3 T MRI Temperatures, Heart Rates, and Breathing Rates of Pigs During RF Power Deposition in a 3 T (128 MHz) Body Coil.

Exposure to radiofrequency (RF) power deposition during magnetic resonance imaging (MRI) induces elevated body-tissue temperatures and may cause changes in heart and breathing rates, disturbing thermoregulation. Eleven temperature sensors were placed in muscle tissue and one sensor in the rectum (measured in 10 cm depth) of 20 free-breathing anesthetized pigs to verify temperature curves during RF exposure. Tissue temperatures and heart and breathing rates were measured before, during, and after RF exposure. Pigs were placed into a 60-cm diameter whole-body resonator of a 3 T MRI system. Nineteen anesthetized pigs were divided into four RF exposure groups: sham (0 W/kg), low-exposure (2.7 W/kg, mean exposure time 56 min), moderate-exposure (4.8 W/kg, mean exposure time 31 min), and high-exposure (4.4 W/kg, mean exposure time 61 min). One pig was exposed to a whole-body specific absorption rate (wbSAR) of 11.4 W/kg (extreme-exposure). Hotspot temperatures, measured by sensor 2, increased by mean 5.0 ± 0.9°C, min 3.9; max 6.3 (low), 7.0 ± 2.3°C, min 4.6; max 9.9 (moderate), and 9.2 ± 4.4°C, min 6.1, max 17.9 (high) compared with 0.3 ± 0.3°C in the sham-exposure group (min 0.1, max 0.6). Four time-temperature curves were identified: sinusoidal, parabolic, plateau, and linear. These curve shapes did not correlate with RF intensity, rectal temperature, breathing rate, or heart rate. In all pigs, rectal temperatures increased (2.1 ± 0.9°C) during and even after RF exposure, while hotspot temperatures decreased after exposure. When rectal temperature increased by 1°C, hotspot temperature increased up to 42.8°C within 37 min (low-exposure) or up to 43.8°C within 24 min (high-exposure). Global wbSAR did not correlate with maximum hotspot. Bioelectromagnetics. 2021;42:37-50. © 2020 The Authors. Bioelectromagnetics published by Wiley Periodicals LLC on behalf of Bioelectromagnetics Society.

Meta-analysis on the immunohistological detection of inflammatory cardiomyopathy in endomyocardial biopsies.

Meta-analysis on immunohistological (IHC) concepts for the detection of inflammatory cardiomyopathy (InfCM) in endomyocardial biopsies (EMB). We included 61 publications, with 10,491 patients (mean age 47.1 years; men 66%) who underwent EMB and IHC evaluation. The 460 control patients were devoid of IHC proof of InfCM. The mean IHC detection rate of InfCM was 50.8% (95% CI 47.7-53.8%; range 18.4-91.7%). A publication bias was excluded (Funnel Plot p = 0.4264). This IHC detection rate was significantly (p < 0.0001) higher compared to the histological detection of myocarditis according to the Dallas criteria (mean 8.04%; 95% CI 5.08-12.5%; subset of 3274 patients in 30 publications). However, 13 different diagnostic IHC criteria were described in the publications, with various thresholds of diverse phenotypes of quantified infiltrates, and endothelial expression of diverse cell adhesion molecules (CAM), quantified either visually or by digital image analysis (DIA). The comparison of IHC with cardiac magnetic resonance (CMR) data available in a subset of 13 publications with 1185 patients revealed a sensitivity for CMR of 69% (95% CI 58-79%), a specificity of 73% (95% CI 59-84%), and a ROC-AUC of 0.77 (95% CI 0.73-0.81). This meta-analysis encompassing 10,491 patients confirms a mean detection rate of InfCM in 50.8% of EMB, being significantly more sensitive compared to the histological Dallas criteria. IHC cannot be fully substituted by CMR. However, standardization of the diverse IHC markers and protocols seems pertinent, especially considering the published adverse prognostic impact of IHC-confirmed InfCM and its published suitability for the selection of candidates responding favorably to immunosuppression.