How artificial intelligence improves radiological interpretation in suspected pulmonary embolism.

OBJECTIVES: To evaluate and compare the diagnostic performances of a commercialized artificial intelligence (AI) algorithm for diagnosing pulmonary embolism (PE) on CT pulmonary angiogram (CTPA) with those of emergency radiologists in routine clinical practice. METHODS: This was an IRB-approved retrospective multicentric study including patients with suspected PE from September to December 2019 (i.e., during a preliminary evaluation period of an approved AI algorithm). CTPA quality and conclusions by emergency radiologists were retrieved from radiological reports. The gold standard was a retrospective review of CTPA, radiological and clinical reports, AI outputs, and patient outcomes. Diagnostic performance metrics for AI and radiologists were assessed in the entire cohort and depending on CTPA quality. RESULTS: Overall, 1202 patients were included (median age: 66.2 years). PE prevalence was 15.8% (190/1202). The AI algorithm detected 219 suspicious PEs, of which 176 were true PEs, including 19 true PEs missed by radiologists. In the cohort, the highest sensitivity and negative predictive values (NPVs) were obtained with AI (92.6% versus 90% and 98.6% versus 98.1%, respectively), while the highest specificity and positive predictive value (PPV) were found with radiologists (99.1% versus 95.8% and 95% versus 80.4%, respectively). Accuracy, specificity, and PPV were significantly higher for radiologists except in subcohorts with poor-to-average injection quality. Radiologists positively evaluated the AI algorithm to improve their diagnostic comfort (55/79 [69.6%]). CONCLUSION: Instead of replacing radiologists, AI for PE detection appears to be a safety net in emergency radiology practice due to high sensitivity and NPV, thereby increasing the self-confidence of radiologists. KEY POINTS: • Both the AI algorithm and emergency radiologists showed excellent performance in diagnosing PE on CTPA (sensitivity and specificity ≥ 90%; accuracy ≥ 95%). • The AI algorithm for PE detection can help increase the sensitivity and NPV of emergency radiologists in clinical practice, especially in cases of poor-to-moderate injection quality. • Emergency radiologists recommended the use of AI for PE detection in satisfaction surveys to increase their confidence and comfort in their final diagnosis.

The accuracy of teleradiologists in diagnosing COVID-19 based on a French multicentric emergency cohort.

OBJECTIVES: To evaluate the accuracy of diagnoses of COVID-19 based on chest CT as well as inter-observer agreement between teleradiologists during on-call duty and senior radiologists in suspected COVID-19 patients. MATERIALS AND METHODS: From March 13, 2020, to April 14, 2020, consecutive suspected COVID-19 adult patients who underwent both an RT-PCR test and chest CT from 15 hospitals were included in this prospective study. Chest CTs were immediately interpreted by the on-call teleradiologist and were systematically blind reviewed by a senior radiologist. Readings were categorised using a five-point scale: (1) normal; (2) non-infectious findings; (3) infectious findings but not consistent with COVID-19 infection; (4) consistent with COVID-19 infection; and (5) typical appearance of COVID-19 infection. The diagnostic accuracy of chest CT and inter-observer agreement using the kappa coefficient were evaluated over the study period. RESULTS: In total, 513 patients were enrolled, of whom 244/513 (47.6%) tested positive for RT-PCR. First readings were scored 4 or 5 in 225/244 (92%) RT-PCR+ patients, and between 1 and 3 in 201/269 (74.7%) RT-PCR- patients. The data were highly consistent (weighted kappa = 0.87) and correlated with RT-PCR (p < 0.001, AUC1st-reading = 0.89, AUC2nd-reading = 0.93). The negative predictive value for scores of 4 or 5 was 0.91-0.92, and the PPV for a score of 5 was 0.89-0.96 at the first and second readings, respectively. Diagnostic accuracy was consistent over the study period, irrespective of a variable prevalence rate. CONCLUSION: Chest CT demonstrated high diagnostic accuracy with strong inter-observer agreement between on-call teleradiologists with varying degrees of experience and senior radiologists over the study period. KEY POINTS: • The accuracy of readings by on-call teleradiologists, relative to second readings by senior radiologists, demonstrated a sensitivity of 0.75-0.79, specificity of 0.92-0.97, NPV of 0.80-0.83, and PPV of 0.89-0.96, based on "typical appearance," as predictive of RT-PCR+. • Inter-observer agreement between the first reading in the emergency setting and the second reading by the senior emergency teleradiologist was excellent (weighted kappa = 0.87).

COVID-19 impact assessment on the French radiological centers: a nationwide survey.

PURPOSE: To determine the impact of the COVID-19 on the CT activities in French radiological centers during the epidemic peak. MATERIALS AND METHODS: A cross-sectional prospective CT scan survey was conducted between March 16 and April 12, 2020, in accordance with the local IRB. Seven hundred nine radiology centers were invited to participate in a weekly online survey. Numbers of CT examinations related to COVID-19 including at least chest (CTcovid) and whole chest CT scan activities (CTchest) were recorded each week. A sub-analysis on French departments was performed during the 4 weeks of the study. The impact of the number of RT-PCRs (reverse transcriptase polymerase chain reactions) on the CT workflow was tested using two-sample t test and Pearson's test. RESULTS: Five hundred seventy-seven structures finally registered (78%) with mean response numbers of 336 ± 18.9 (323; 351). Mean CTchest activity per radiologic structure ranged from 75.8 ± 133 (0-1444) on week 12 to 99.3 ± 138.6 (0-1147) on week 13. Mean ratio of CTcovid on CTchest varied from 0.36 to 0.59 on week 12 and week 14 respectively. There was a significant relationship between the number of RT-PCR performed and the number of CTcovid (r = 0.73, p = 3.10-16) but no link with the number of positive RT-PCR results. CONCLUSION: In case of local high density COVID-19, CT workflow is strongly modified and redirected to the management of these specific patients. KEY POINTS: • Over the 4-week survey period, 117,686 chest CT (CTtotal) were performed among the responding centers, including 61,784 (52%) CT performed for COVID-19 (CTcovid). • Across the country, the ratio CTcovid/CTtotal varied from 0.36 to 0.59 and depended significantly on the local epidemic density (p = 0.003). • In clinical practice, in a context of growing epidemic, in France, chest CT was used as a surrogate to RT-PCR for patient triage.

Relationship between atrial scar on cardiac magnetic resonance and pulmonary vein reconnection after catheter ablation for paroxysmal atrial fibrillation.

INTRODUCTION: Pulmonary vein (PV) reconnection is frequent in patients showing atrial fibrillation (AF) recurrence after PV isolation (PVI). Its detection with cardiac magnetic resonance (CMR) may help predict outcome and guide redo procedures. We assessed the relationship between scar on CMR and PV reconnection after catheter ablation for paroxysmal AF. METHODS AND RESULTS: Fifty-one patients with paroxysmal AF underwent CMR before PVI using either a conventional single-electrode catheter (N = 28) or a circular multielectrode catheter (N = 23). At 3 months, a second CMR study was performed, followed by a systematic electrophysiological procedure to look for PV reconnection, regardless of AF recurrence. Preablation fibrosis and postablation scar were quantified and mapped from late gadolinium-enhanced CMR. CMR results were compared to the distribution and extent of PV reconnection. CMR and electrophysiological findings were compared between catheter types. Three months after successful PVI, scar gaps were found in 39 (76%) patients, and 78 (39%) veins. Electrical PV reconnection was detected in 45 (88%) patients, and 99 (50%) veins. The extent of PV reconnection related closely to the number of gaps (R = 0.55; P < .001), and to scar burden (R = -0.63; P < .001). However, the agreement was only fair for the localization of PV reconnection (k = 0.37; P < .001), scar gaps particularly lacking sensitivity in areas of pre-existing fibrosis. The circular catheter was associated with shorter procedures (P < .001), more scar (P = .01), less gaps (P = .01), and less reconnected veins (P = .03). CONCLUSION: PV reconnection is extremely frequent after PVI. CMR scar imaging accurately predicts its extent, but poorly predicts its location. Multielectrode circular catheters induce more complete ablation.

Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome.

BACKGROUND: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. METHODS: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. RESULTS: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing. CONCLUSIONS: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.

The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome.

Cerebello-oculo-renal syndrome (CORS), also called Joubert syndrome type B, and Meckel (MKS) syndrome belong to the group of developmental autosomal recessive disorders that are associated with primary cilium dysfunction. Using SNP mapping, we identified missense and truncating mutations in RPGRIP1L (KIAA1005) in both CORS and MKS, and we show that inactivation of the mouse ortholog Rpgrip1l (Ftm) recapitulates the cerebral, renal and hepatic defects of CORS and MKS. In addition, we show that RPGRIP1L colocalizes at the basal body and centrosomes with the protein products of both NPHP6 and NPHP4, known genes associated with MKS, CORS and nephronophthisis (a related renal disorder and ciliopathy). In addition, the RPGRIP1L missense mutations found in CORS individuals diminishes the interaction between RPGRIP1L and nephrocystin-4. Our findings show that mutations in RPGRIP1L can cause the multiorgan phenotypic abnormalities found in CORS or MKS, which therefore represent a continuum of the same underlying disorder.

Age, atrial fibrillation, and structural heart disease are the main determinants of left atrial fibrosis detected by delayed-enhanced magnetic resonance imaging in a general cardiology population.

INTRODUCTION: We studied the extent and distribution of left atrial (LA) fibrosis on delayed-enhanced (DE) MRI in a general cardiology population. METHODS AND RESULTS: One hundred ninety consecutive patients referred for cardiac MRI underwent DE imaging using a free breathing method. The population comprised 60 AF patients and 130 patients without AF, including 75 with structural heart disease (SHD). DE was quantified using histogram thresholding, expressed in % of the wall. Regression analysis was performed to identify predictors of DE. Additionally, DE was registered on a template to study its distribution in subpopulations. In the total population, age, AF, and SHD were independently associated with DE. DE was increasingly observed from 11.1 ± 4.7% in patients with no SHD nor AF, 18.8 ± 7.8% in SHD and no AF history, 22.9 ± 7.8% in paroxysmal AF, to 27.8 ± 7.7% in persistent AF. Among non-AF patients, age and SHD were independently associated with DE. Among AF patients, female gender and AF persistence were independently associated with DE. DE was variably distributed but more frequently detected in the posterior wall. CONCLUSION: Age, history of AF, and SHD are the most powerful predictors of atrial fibrosis, as detected by MRI, in a general cardiology population. Atrial fibrosis predominates in the posterior LA wall.

Clinical characteristics and outcomes of childhood-onset ANCA-associated vasculitis: a French nationwide study.

BACKGROUND: Data on anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis are scarce in children. The current study is aimed at describing the clinical features and outcomes of childhood-onset ANCA-associated vasculitis (AAV). METHODS: We conducted a retrospective French multicentre study involving patients in whom AAV was diagnosed before the age of 18 years. Inclusion criteria were (i) granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to classification criteria of the European League Against Rheumatism/Paediatric Rheumatology European Society, and (ii) ANCA positivity. Patient and renal survival were analysed. RESULTS: Among 66 children included, 80% were female, 42% had GPA and 58% MPA including renal-limited vasculitis, 67% were pANCA+ and 33% cANCA+. The mean incidence of reported cases increased to 0.45 per million children/year in the period 2006-10. Median age at diagnosis was 11.5 years, and median time to diagnosis was 1 month. Initial symptoms included fever and fatigue (79%), skin lesions (41%), arthritis (42%), pulmonary (45%) and renal involvement (88%). Clinical features were similar between GPA and MPA with the exception of upper airway impairment (28%) specific of GPA. Ninety percent of the patients achieved remission after induction treatment. After a median follow-up of 5.2 years, 4 patients (6%) died, corresponding to a mortality rate of 1.2 per 100 person-years, and 22 patients (34%) developed end-stage renal disease (ESRD). Renal survival was 74, 70 and 59% at 1, 5 and 10 years, respectively. In a multivariable Cox regression model, baseline glomerular filtration rate, ethnic origin, histopathological classification and era of treatment were associated with the occurrence of ESRD. Relapse-free survival was 57% at 5 years and 34% at 10 years of follow-up. Patient and renal outcome did not significantly differ between GPA and MPA. CONCLUSION: Childhood-onset AAV is a rare disease characterized by female predominance, delayed diagnosis, frequent renal impairment and a high remission rate. Baseline GFR and new histopathological classification system are strong predictors of ESRD. Renal survival in childhood AAV has improved over time.

C3 nephritic factor associated with C3 glomerulopathy in children.

BACKGROUND: C3 glomerulopathy (C3G) is characterized by predominant C3 deposits in glomeruli and dysregulation of the alternative pathway of complement. Half of C3G patients have a C3 nephritic factor (C3NeF). C3G incorporated entities with a range of features on microscopy including dense deposit diseases (DDD) and C3 glomerulonephritis (C3GN). The aim of this work was to study children cases of C3G associated with C3NeF. METHODS: We reviewed 18 cases of C3G with a childhood onset associated with C3NeF without identified mutations in CFH, CFI, and MCP genes. RESULTS: Clinical histories started with recurrent hematuria for seven patients, nephrotic syndrome for four, acute post-infectious glomerulonephritis for three and acute renal failure for four. Twelve patients had a low C3 at first investigation. Kidney biopsy showed ten C3GN and eight DDD. Twenty-three percent of the patients tested presented elevated sC5b9. Seven patients relapsed 3 to 6 years after the onset. At the end of follow-up, two patients were under dialysis, 11 had a persistent proteinuria, five had none; four patients did not follow any treatment. Steroids were first used in 80 % of cases. CONCLUSIONS: C3NeF associated C3G has a heterogeneous presentation and outcome. Anti-proteinuric agents may control the disease during follow-up, even after nephrotic syndrome at the onset. The efficiency of immunosuppressive therapy remains questionable.

Emergency department CT examinations demonstrate no evidence of early viral circulation at the start of the COVID-19 pandemic-a multicentre epidemiological study.

BACKGROUND: Biological studies suggested that the COVID-19 outbreak in France occurred before the first official diagnosis on January 24, 2020. We investigated this controversial topic using a large collection of chest CTs performed throughout French emergency departments within 6 months before the 1st lockdown. RESULTS: Overall, 49,311 consecutive patients (median age: 60 years, 23,636/49,311 [47.9%] women) with available chest CT images and reports from 61 emergency departments between September 1, 2020, and March 16, 2020 (day before the 1st French lockdown), were retrospectively included in this multicentre study. In the macroscopic analysis of reports automatically (labelled for presence of ground glass opacities [GGOs], reticulations, and bilateral and subpleural abnormalities), we found a significant breakpoint on February 17, 2020, for the weekly time series with 1, 2 and ≥ 3 of these 4 radiological features, with 146/49,311 (0.3%) patients showing bilateral abnormalities and ground glass opacities (GGOs) from that day. According to radiologists, 22/146 (15.1%) CT images showed typical characteristics of COVID-19, including 4/146 (2.7%) before February 2020. According to hospital records, one patient remained without microbial diagnosis, two patients had proven influenza A and one patient had concomitant influenza A and mycoplasma infection. CONCLUSION: These results suggest that SARS-CoV-2 was not circulating in the areas covered by the 61 emergency departments involved in our study before the official beginning of the COVID-19 outbreak in France. In emergency patients, the strong resemblance among mycoplasma, influenza A and SARS-CoV-2 lung infections on chest CT and the nonspecificity of CT patterns in low prevalence periods is stressed. CRITICAL RELEVANCE STATEMENT: We proposed here an innovative approach to revisit a controversial 'real' start of the COVID-19 pandemic in France based on (1) a population-level approach combining text mining, time series analysis and an epidemiological dataset and (2) a patient-level approach with careful retrospective reading of chest CT scans complemented by analysis of samples performed contemporarily to the chest CT. We showed no evidence that SARS-CoV-2 was actively circulating in France before February 2020.

Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination.

Nephronophthisis (NPHP), an autosomal recessive cystic kidney disease, leads to chronic renal failure in children. The genes mutated in NPHP1 and NPHP4 have been identified, and a gene locus associated with infantile nephronophthisis (NPHP2) was mapped. The kidney phenotype of NPHP2 combines clinical features of NPHP and polycystic kidney disease (PKD). Here, we identify inversin (INVS) as the gene mutated in NPHP2 with and without situs inversus. We show molecular interaction of inversin with nephrocystin, the product of the gene mutated in NPHP1 and interaction of nephrocystin with beta-tubulin, a main component of primary cilia. We show that nephrocystin, inversin and beta-tubulin colocalize to primary cilia of renal tubular cells. Furthermore, we produce a PKD-like renal cystic phenotype and randomization of heart looping by knockdown of invs expression in zebrafish. The interaction and colocalization in cilia of inversin, nephrocystin and beta-tubulin connect pathogenetic aspects of NPHP to PKD, to primary cilia function and to left-right axis determination.

Interferon gamma licensing of human dendritic cells in T-helper-independent CD8+ alloimmunity.

The high frequency of allogeneic reactive CD8(+) T cells in human and their resistance to immunosuppression might be one of the reasons why successful tolerance-inducing strategies in rodents have failed in primates. Studies on the requirement for T-helper cells in priming CD8(+) T-cell responses have led to disparate findings. Recent studies have reported CD8(+)-mediated allograft rejection independently of T-helper cells; however, the mechanisms that govern the activation of these T cells are far from being elucidated. In this study, we demonstrated that lipopolysaccharide-treated dendritic cells (DCs) were able to induce proliferation and cytotoxic activity of allogeneic CD8(+) T cells independently of CD4(+) T cells, while adding mycophenolic acid (MPA) to LPS abolished this capacity and resulted in anergic CD8(+) T cells that secreted high levels of interleukin-4 (IL-4), IL-5, IL-10, and transforming growth factor-ß. Interestingly, we demonstrated that MPA inhibited the LPS-induced synthesis of tumor necrosis factor-α, IL-12, and interferon-γ (IFN-γ) in DCs. Importantly, we found that adding exogenous IFN-γ to MPA restored both the synthesis of cytokines and the ability to activate CD8(+) T cells. However, adding IL-12 or tumor necrosis factor-α had no effect. These results suggest that IFN-γ has an important role in licensing DCs to prime CD4-independent CD8 allogeneic T cells via an autocrine loop.

Renal resistive index as a new independent risk factor for new-onset diabetes mellitus after kidney transplantation.

Pulse pressure and urinary albumin excretion were recently identified as risk factors of new-onset diabetes after renal transplantation (NODAT), suggesting that microvascular injury may be implicated in NODAT. However, the relationship between of microvascular injury and NODAT is unknown. In the present long-term (median follow-up: 5.7years; observation period: 4908 patient-years) retrospective study in 656 renal transplant recipients, the association between baseline renal resistance index (RI, used as a marker of widespread microvascular damage) and the incidence of NODAT was assessed. The incidence of NODAT was 11.2% and 14.6% at 5 and 10years, respectively, after transplantation. RI at 3months was a risk factor for NODAT [hazard ratio (HR) per 0.1: 2.19 (1.55-3.09), P<0.0001]. RI >0.75 (vs. 0≤0.75) was a potent a predictor of NODAT [HR: 3.29 (1.91-5.67), P<0.0001], even after adjustments [HR: 3.29 (1.50-7.24), P=0.0030] on age, weight, glucose, nephropathy, and arterial pressure. Similar results were observed when RI was measured at 1month [HR per 0.1:1.74 (1.33-2.27), P<0.0001] and 12months [HR per 0.1:1.74 (1.33-2.27), P<0.0001] after transplantation. High RI early after renal transplantation is a long-term risk factor for NODAT, and could be used to refine the individual risk of NODAT.

Spectrum of mutations in Gitelman syndrome.

Gitelman's syndrome (GS) is a rare, autosomal recessive, salt-losing tubulopathy caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCC). Because 18 to 40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements may account for unidentified mutations. Here, we directly sequenced genomic DNA from a large cohort of 448 unrelated patients suspected of having GS. We found 172 distinct mutations, of which 100 were unreported previously. In 315 patients (70%), we identified two mutations; in 81 patients (18%), we identified one; and in 52 patients (12%), we did not detect a mutation. In 88 patients, we performed a search for large rearrangements by multiplex ligation-dependent probe amplification (MLPA) and found nine deletions and two duplications in 24 of the 51 heterozygous patients. A second technique confirmed each rearrangement. Based on the breakpoints of seven deletions, nonallelic homologous recombination by Alu sequences and nonhomologous end-joining probably favor these intragenic deletions. In summary, missense mutations account for approximately 59% of the mutations in Gitelman's syndrome, and there is a predisposition to large rearrangements (6% of our cases) caused by the presence of repeated sequences within the SLC12A3 gene.

Kidney transplant with multiple renal artery grafts from deceased donors: are long-term graft and patient survival compromised?

BACKGROUND: Kidneys with multiple arteries are often transplanted. However, the long-term outcome of such kidneys recovered exclusively from deceased donors is not clear. OBJECTIVE: To determine whether use of renal grafts with multiple arteries affects long-term graft survival and function. METHODS: The outcomes of 259 consecutive kidney transplants between 1996 and 2000 were retrospectively reviewed. Patients were divided into 2 groups, multiple renal artery graft recipients (n = 70) and single renal artery graft recipients (n = 189). Short-term complications and long-term outcomes (survival rates, blood pressure after transplant, creatinine clearance, and proteinuria levels at 1, 3, 5, and 7 years after transplant) were compared between the 2 groups. RESULTS: Early vascular complications were more common (P = .02) in multiple artery graft recipients (18.6%) than in single artery graft recipients (7.9%), mainly because of occlusion of a polar artery in grafts with multiple renal arteries (7.1%). Urologic complications were no more frequent in one group than in the other (5.7% vs 5.3%; P = .89). The 2 groups did not differ significantly (P = .33) in long-term graft survival, with a median follow-up of 9.05 years (range, 0.1-12.7 years). Mean (SD) for creatinine clearance (59.4 [22.6] vs 55.9 [20.3] mL/min; P = .47), proteinuria (0.77 [2.1] vs 0.4 [0.8] g/24 h; P = .19), and systolic blood pressure (133.6 [14.5] vs 133.7 [17.5] mm Hg; P = .85) did not differ significantly between the 2 groups 7 years after transplant. CONCLUSIONS: Kidney transplant with grafts containing multiple renal arteries rather than grafts with a single renal artery does not significantly influence patient and graft outcomes.

Left atrial shape is independent predictor of arrhythmia recurrence after catheter ablation for atrial fibrillation: A shape statistics study.

BACKGROUND: Markers of left atrial (LA) shape may improve the prediction of postablation outcomes in atrial fibrillation (AF). Correlations to LA volume and AF persistence limit their incremental value over current clinical predictors. OBJECTIVE: To develop a shape score independent from AF persistence and LA volume using shape-based statistics, and to test its ability to predict postablation outcome. METHODS: Preablation computed tomography (CT) images from 141 patients with paroxysmal (57%) or persistent (43%) AF were segmented. Deformation of an average LA shape into each patient encoded patient-specific shape. Local analysis investigates regional differences between patient groups. Linear regression was used to remove shape variations related to LA volume and AF persistence, and to build a shape score to predict postablation outcome. Cross-validation was performed to evaluate its accuracy. RESULTS: Ablation failure rate was 23% over a median 12-month follow-up. Regions associated with ablation failure mostly consisted of a large area on posteroinferior LA, mitral isthmus, and left inferior vein. On univariate analysis, strongest predictors were AF persistence (P = .005), LA indexed volume (P = .02), and the proposed shape score (P = .001). On multivariate analysis, all 3 were independent predictors of ablation failure, with the LA shape score showing the highest predictive value (odds ratio [OR] = 6.2 [2.5-15.8], P < .001), followed by LA indexed volume (OR = 3.1 [1.2-7.9], P = .019) and AF persistence (OR = 2.9 [1.2-7.6], P = .022). CONCLUSION: Posteroinferior LA, mitral isthmus, and left inferior vein are the regions whose shape have the highest impact on outcome. LA shape predicts AF ablation failure independently from, and more accurately than, atrial volume and AF persistence.

Emergency teleradiological activity is an epidemiological estimator and predictor of the covid-19 pandemic in mainland France.

BACKGROUND: COVID-19 pandemic highlighted the need for real-time monitoring of diseases evolution to rapidly adapt restrictive measures. This prospective multicentric study aimed at investigating radiological markers of COVID-19-related emergency activity as global estimators of pandemic evolution in France. We incorporated two sources of data from March to November 2020: an open-source epidemiological dataset, collecting daily hospitalisations, intensive care unit admissions, hospital deaths and discharges, and a teleradiology dataset corresponding to the weekly number of CT-scans performed in 65 emergency centres and interpreted remotely. CT-scans specifically requested for COVID-19 suspicion were monitored. Teleradiological and epidemiological time series were aligned. Their relationships were estimated through a cross-correlation function, and their extremes and breakpoints were compared. Dynamic linear models were trained to forecast the weekly hospitalisations based on teleradiological activity predictors. RESULTS: A total of 100,018 CT-scans were included over 36 weeks, and 19,133 (19%) performed within the COVID-19 workflow. Concomitantly, 227,677 hospitalisations were reported. Teleradiological and epidemiological time series were almost perfectly superimposed (cross-correlation coefficients at lag 0: 0.90-0.92). Maximal number of COVID-19 CT-scans was reached the week of 2020-03-23 (1 086 CT-scans), 1 week before the highest hospitalisations (23,542 patients). The best valid forecasting model combined the number of COVID-19 CT-scans and the number of hospitalisations during the prior two weeks and provided the lowest mean absolute percentage (5.09%, testing period: 2020-11-02 to 2020-11-29). CONCLUSION: Monitoring COVID-19 CT-scan activity in emergencies accurately and instantly predicts hospitalisations and helps adjust medical resources, paving the way for complementary public health indicators.

Practical clinical and radiological models to diagnose COVID-19 based on a multicentric teleradiological emergency chest CT cohort.

Our aim was to develop practical models built with simple clinical and radiological features to help diagnosing Coronavirus disease 2019 [COVID-19] in a real-life emergency cohort. To do so, 513 consecutive adult patients suspected of having COVID-19 from 15 emergency departments from 2020-03-13 to 2020-04-14 were included as long as chest CT-scans and real-time polymerase chain reaction (RT-PCR) results were available (244 [47.6%] with a positive RT-PCR). Immediately after their acquisition, the chest CTs were prospectively interpreted by on-call teleradiologists (OCTRs) and systematically reviewed within one week by another senior teleradiologist. Each OCTR reading was concluded using a 5-point scale: normal, non-infectious, infectious non-COVID-19, indeterminate and highly suspicious of COVID-19. The senior reading reported the lesions' semiology, distribution, extent and differential diagnoses. After pre-filtering clinical and radiological features through univariate Chi-2, Fisher or Student t-tests (as appropriate), multivariate stepwise logistic regression (Step-LR) and classification tree (CART) models to predict a positive RT-PCR were trained on 412 patients, validated on an independent cohort of 101 patients and compared with the OCTR performances (295 and 71 with available clinical data, respectively) through area under the receiver operating characteristics curves (AUC). Regarding models elaborated on radiological variables alone, best performances were reached with the CART model (i.e., AUC = 0.92 [versus 0.88 for OCTR], sensitivity = 0.77, specificity = 0.94) while step-LR provided the highest AUC with clinical-radiological variables (AUC = 0.93 [versus 0.86 for OCTR], sensitivity = 0.82, specificity = 0.91). Hence, these two simple models, depending on the availability of clinical data, provided high performances to diagnose positive RT-PCR and could be used by any radiologist to support, modulate and communicate their conclusion in case of COVID-19 suspicion. Practically, using clinical and radiological variables (GGO, fever, presence of fibrotic bands, presence of diffuse lesions, predominant peripheral distribution) can accurately predict RT-PCR status.

Genotype-phenotype correlation in primary hyperoxaluria type 1: the p.Gly170Arg AGXT mutation is associated with a better outcome.

We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation.

Mutations in complement C3 predispose to development of atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. We report here mutations in the central component of the complement cascade, C3, in association with aHUS. We describe 9 novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level. We have demonstrated that 5 of these mutations are gain-of-function and 2 are inactivating. This establishes C3 as a susceptibility factor for aHUS.