Single-center Cohort Of Patients Research Articles

Is COVID-19 infection more severe in kidney transplant recipients?

There are no studies which have compared the risk of severe COVID‐19 and related mortality between transplant recipients and nontransplant patients. We enrolled two groups of patients hospitalized for COVID‐19, that is, kidney transplant recipients (KTR) from the French Registry of Solid Organ Transplant (n = 306) and a single‐center cohort of nontransplant patients (n = 795). An analysis was performed among subgroups matched for age and risk factors for severe COVID‐19 or mortality. Severe COVID‐19 was defined as admission (or transfer) to an intensive care unit, need for mechanical ventilation, or death. Transplant recipients were younger and had more comorbidities compared to nontransplant patients. They presented with higher creatinine levels and developed more episodes of acute kidney injury. After matching, the 30‐day cumulative incidence of severe COVID‐19 did not differ between KTR and nontransplant patients; however, 30‐day COVID‐19‐related mortality was significantly higher in KTR (17.9% vs 11.4%, respectively, p = .038). Age >60 years, cardiovascular disease, dyspnea, fever, lymphopenia, and C‐reactive protein (CRP) were associated with severe COVID‐19 in univariate analysis, whereas transplant status and serum creatinine levels were not. Age >60 years, hypertension, cardiovascular disease, diabetes, CRP >60 mg/L, lymphopenia, kidney transplant status (HR = 1.55), and creatinine level >115 µmol/L (HR = 2.32) were associated with COVID‐19‐related mortality in univariate analysis. In multivariable analysis, cardiovascular disease, dyspnea, and fever were associated with severe disease, whereas age >60 years, cardiovascular disease, dyspnea, fever, and creatinine level>115 µmol/L retained their independent associations with mortality. KTR had a higher COVID‐19‐related mortality compared to nontransplant hospitalized patients.

Incidence and Impact of COVID-19 in MS: A Survey From a Barcelona MS Unit.

ObjectiveTo investigate the incidence of coronavirus disease 2019 (COVID-19) in a single-center cohort of patients with MS and to explore the contribution of their comorbidities and therapies to the outcome.MethodsA cross-sectional mixed-method study was conducted involving an email-based, self-administered questionnaire sent on May 21, 2020, to 586 patients with MS followed at the MS Unit of Hospital Clinic, University of Barcelona, along with telephone interview, and review of electronic medical records until June 18, 2020. The cumulative incidence of confirmed COVID-19 (positive PCR or antibody test) and all COVID-19 cases (confirmed and suspected) from the start of the pandemic was compared with the population estimates for Barcelona.ResultsA total of 407 patients (69.5%) completed the survey. Most of the responders (67%) were female. The responders had a median age of 48 years (range 19–86), relapsing-remitting disease (84%), at least 1 comorbidity (45%), and were on disease-modifying therapy (DMT; 74.7%). COVID-19 was confirmed in 5 patients (1.2%) and suspected in 46 (11.3%). The cumulative incidence of confirmed COVID-19 cases was similar to that of the general population but was almost 2-fold higher when all cases were considered (p < 0.001). Six patients (11.7%) were hospitalized, of which 5 had good recovery and 1 died. Hospitalized patients were more frequently male, had diabetes and had progressive forms of MS (p < 0.05). DMT was not associated with the risk of infection or the outcome.ConclusionsIn the studied MS cohort, the incidence of COVID-19 was higher than that of the general population; however, most patients did not require hospitalization and had a good outcome despite the frequent presence of comorbidities and treatment with DMT.

Treatment Adherence and Clinical Outcomes of Patients with Inflammatory Bowel Disease on Biological Agents During the SARS-CoV-2 Pandemic.

BackgroundThe outbreak of COVID19 evolved rapidly into a global pandemic, forcing hospitals, including inflammatory bowel disease (IBD) referral units, to change their practices to ensure quality of care. AimsTo describe the clinical outcomes and the fulfilment of the treatment schedule of patients with IBD treated with biological agents in a single-center of a red-zone of the pandemic, and to report the patients’ perceptions about COVID-19 and the measures adopted at our center.MethodsTherapeutic adherence and clinical outcomes were collected for all patients undergoing treatment with intravenous biologicals and subcutaneous biologicals at our center. A telephone survey was also performed to assess these patients’ perceptions of the COVID pandemic and the related measures adopted at their IBD unit.ResultsA total of 234 patients were included (117 on intravenous and 117 on subcutaneous biologicals). Only 10% of patients postponed intravenous infusions intentionally and 5% postponed the collection of subcutaneous biologicals at the hospital pharmacy. Only five confirmed COVID-19 cases were registered (2.1%), all of them of mild severity. One hundred and fifty-five patients participated in the survey (77 on intravenous and 78 on subcutaneous drugs). Fear of going to the hospital was the most common reason for postponing biological administrations. Among those on combination therapy, only 7% admitted to have withdrawn immunosuppressants.ConclusionsAdherence to intravenous and subcutaneous biological therapies during the pandemic was high in a single-center cohort of IBD patients even though the cumulative incidence of confirmed COVID-19 was low.

Frequent SLC35A2 brain mosaicism in mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE)

Focal malformations of cortical development (MCD) are linked to somatic brain mutations occurring during neurodevelopment. Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a newly recognized clinico-pathological entity associated with pediatric drug-resistant focal epilepsy, and amenable to neurosurgical treatment. MOGHE is histopathologically characterized by clusters of increased oligodendroglial cell densities, patchy zones of hypomyelination, and heterotopic neurons in the white matter. The molecular etiology of MOGHE remained unknown so far. We hypothesized a contribution of mosaic brain variants and performed deep targeted gene sequencing on 20 surgical MOGHE brain samples from a single-center cohort of pediatric patients. We identified somatic pathogenic SLC35A2 variants in 9/20 (45%) patients with mosaic rates ranging from 7 to 52%. SLC35A2 encodes a UDP-galactose transporter, previously implicated in other malformations of cortical development (MCD) and a rare type of congenital disorder of glycosylation. To further clarify the histological features of SLC35A2-brain tissues, we then collected 17 samples with pathogenic SLC35A2 variants from a multicenter cohort of MCD cases. Histopathological reassessment including anti-Olig2 staining confirmed a MOGHE diagnosis in all cases. Analysis by droplet digital PCR of pools of microdissected cells from one MOGHE tissue revealed a variant enrichment in clustered oligodendroglial cells and heterotopic neurons. Through an international consortium, we assembled an unprecedented series of 26 SLC35A2-MOGHE cases providing evidence that mosaic SLC35A2 variants, likely occurred in a neuroglial progenitor cell during brain development, are a genetic marker for MOGHE.

Aspergillus Tracheobronchitis in COVID-19 ARDS Patients – A Cohort Study

Background: Coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome patients are at risk for fungal infections, especially aspergillosis and mucormycosis. COVID-19-associated pulmonary aspergillosis (CAPA) is differentiated in a pulmonary form and Aspergillus tracheobronchitis (ATB). During the first wave of the pandemic, bronchoscopy for diagnosing Aspergillus superinfections was rarely performed in COVID-19 patients, so that detailed on data on ATB in CAPA patients is scarce. We analyzed prevalence and mortality of tracheobronchitis in patients with CAPA.Methods: We conducted a retrospective, single-centre study at the 14-bed intensive care unit (ICU) of the Department I of Internal Medicine of the University Hospital of Cologne, Germany from March 2020 to February 2021. CAPA patients were identified by twice weekly analysis of tracheal aspirates for Aspergillus growth, Aspergillus DNA (PCR) and galactomannan combined with serum galactomannan testing. In case of positive results, bronchoscopy with the examination of trachea and lower airways and bronchoalveolar lavage followed.Findings: A total of 69 COVID-19 patients were admitted to the ICU, with 17 patients developing probable CAPA. All CAPA patients received bronchoscopy resulting in a clinical diagnosis of tracheobronchitis in 8 patients with signs of tracheal lesions, pseudomembranes or vulnerable bloody trachea. Seven bronchoalveolar lavages revealed culture and eight PCR positivity for Aspergillus fumigatus. In 7 of 8 tracheobronchitis patients, bronchoalveolar lavage samples tested positive for galactomannan antigen optical density index of >0.5. The overall mortality of CAPA patients was 52.9% and the overall mortality of ATB patients was 75%.Interpretation: Our data indicate a substantial prevalence of tracheobronchitis in this single-center cohort of CAPA patients. To facilitate early diagnosis bronchoscopic tracheal examination is crucial as computed tomography lacks diagnostic accuracy to enable timely initiation of therapy.Funding Information: This work was in part supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de), funded by the Federal Ministry of Health (ZMVI1-2520COR201), and the project DEFEAT PANDEMICs, funded by the Federal Ministry of Education and Research (01KX2021).Declaration of Interests: PK reports grants or contracts from German Federal Ministry of Research and Education and the State of North Rhine-Westphalia; Consulting fees Ambu GmbH, Gilead Sciences, Noxxon N.V. and Pfizer Pharma; Honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; Participation on an Advisory Board from Ambu GmbH, Gilead Sciences, Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. SvS none. JGB reports scientific grants and travel expenses from Kite/Gilead outside the submitted work. FF has a clinician scientist position supported by the deans office, medical faculty, University of Cologne. JSG none. FP none. BB reports honoraria, travel expenses and advisory role from/for Astellas, Celgene, Johnson & Johnson, Kite/Gilead, MSD, Novartis, Pfizer, Takeda and financing of scientific research by Astellas, Celgene, Kite/Gilead, MSD and Takeda outside the submitted work. DAE received honoraria from Sanofi and TAKEDA outside the submitted work. ASV reports travel grants from Gilead Sciences outside the submitted work. OK reports payment or honoraria for lectures, presentations or speakers bureaus by Gilead and Pfizer and receipt of equipment, materials, drugs, medical writing, gifts or other services by Pfizer, MSD, Basilea, Gilead, Virotech and Wako Fujifilm outside the submitted work. PB none. MK reports payment or honoraria for lectures, presentations or speakers bureaus by Gilead, MSD and Pfizer outside the submitted work. OAC reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; Consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis, Seres; Honoraria for lectures from Abbott, Al 344 Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, Pfizer; Payment for expert testimony from Cidara; Participation on a Data Safety Monitoring Board or Advisory Board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI, Shionogi; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley outside the submitted work.Ethics Approval Statement: Patients with CAPA were included in the FungiScope® global registry for emerging invasive fungal infections (https://www.clinicaltrials.gov; National Clinical Trials identifier NCT01731353), which was approved by the local ethics committee of the University of Cologne, Cologne, Germany (identifier 05-102).

Risk Factors for Severe Residual Headache in Cerebral Venous Thrombosis.

Which factors will influence the presence of severe residual headache after cerebral venous thrombosis (CVT) is unclear. The purpose of this study was to identify risk factors for severe residual headache in a large single-center cohort of patients with CVT. We consecutively included eligible patients with CVT from a prospective stroke registry. Severe residual headache was defined as a residual headache attack requiring bed rest or hospital admission within 1 month before the last follow-up visit. We identified the risk factors of severe residual headache in all survivors and in those with favorable functional outcome (a modified Rankin Scale score, 0-2). A total of 325 patients' data were analyzed. At the last follow-up (median 13 months), 43 patients (13.2%) reported severe headache. In the multivariable analysis, isolated intracranial hypertension (odds ratio [OR], 3.309 [95% CI, 1.434-7.634]; P=0.005), CVT recurrence (OR, 4.722 [95% CI, 1.639-13.602]; P=0.004), and no recanalization (OR, 10.158 [95% CI, 4.194-24.600]; P<0.001) were independently associated with severe headache. Severe headache was more frequent in patients with unfavorable outcome (11/25 [44.0%] versus 32/300 [10.7%]; P<0.001). In patients with favorable outcome, the risk factors for severe headache were isolated intracranial hypertension (OR, 3.236 [95% CI, 1.268-8.256]; P=0.014) and no recanalization (OR, 7.863 [95% CI, 3.120-19.812]; P<0.001). Isolated intracranial hypertension, CVT recurrence, and no recanalization increased the risk for severe residual headache after CVT.

Neurotoxicity of subarachnoid Gd-based contrast agent accumulation: a potential complication of intraoperative MRI?

Intraoperative MRI with Gd-based contrast agent (GBCA) improves the extent of resection of contrast-enhancing brain tumors. Signal changes of CSF due to perioperative GBCA leakage in the subarachnoid space have been reported. However, although GBCA potentially exhibits neurotoxic effects, so far no associated complications have been described. In this case series, the authors report a single-center cohort of patients with subarachnoid GBCA extravasation after intraoperative MRI and discuss potential neurotoxic complications and potential ways of avoiding them. All patients with CSF signal increase on unenhanced T1-weighted and FLAIR images on postoperative MRI, who had previously undergone tumor resection with use of intraoperative MRI, were retrospectively included and compared with a control cohort. The control group was matched in age, tumor characteristics, and extent of resection; comparisons were made regarding postoperative seizures and ICU stay. A subgroup with initially diagnosed malignant glioma was additionally analyzed for potential delay of initiation of adjuvant treatment and overall survival. Seven patients with postoperative GBCA accumulation in the subarachnoid space were identified; 5 presented with focal seizures and altered mental status postoperatively. Poor patient condition led to extended ICU stay and prolonged delay of the initiation of adjuvant treatment in patients with newly diagnosed malignant glioma. Overall survival was reduced compared to the matched control group. The results suggest that there might be a risk of neurotoxic complications if GBCA that is intravenously applied during neurosurgery leaks into the subarachnoid space. Patients with highly vascularized tumors with intraoperative bleeding seem to be especially at risk for GBCA accumulation and neurotoxic complications. Therefore, awareness of the potential risk of complicating GBCA leakage is mandatory in the application of intraoperative GBCA.

Safety and effectiveness of radiofrequency ablation in pediatric patients. Fifteen years experience

Introduction and objectivesHeart rhythm disorders are a frequent cause of consultation for pediatric cardiologists all over the world. Arrhythmias can present congenitally in a structurally normal heart, consequence of a congenital heart defect itself or secondary to surgical or interventional correction. Radiofrequency ablation is a minimally invasive technique with high success rates. The objective was to evaluate short and long-term safety and effectiveness of radiofrequency ablation, as well as outcome-related factors in a single-center cohort of pediatric patients. MethodsA retrospective, observational, longitudinal, historical cohort study was performed with patients who underwent radiofrequency ablation between 2001 and 2016 at our institution. We documented clinical and electrophysiological characteristics, final diagnosis, results, time of recurrence, and complications. ResultsA total of 872 radiofrequency ablation procedures were performed between 2001 and 2016, in 762 patients, 16.9% of which had congenital heart disease. Overall success rate was 90.7%. Recurrence occurred in 16.9% of cases. The most frequent complication was atrioventricular block in 1.26%. The most common indication was accessory pathway in 69.5% of cases. ConclusionsRadiofrequency ablation is a safe and effective treatment for arrhythmias in children because of its high rate of success, safety, and low rate of complications. The presence of congenital heart disease increases the complexity of the procedure and increases the rate of recurrence.

Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma-A Single-Center Study.

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018–2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.

Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India.

There is paucity of literature on long-term follow-up of patients with hereditary angioedema (HAE) from developing countries. This study was carried out to analyze the clinical manifestations, laboratory features, and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019. Data were retrieved from medical records of Paediatric Immunodeficiency Clinic, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Median age at onset of symptoms was 6.25years (range 1-25years), and median age at diagnosis was 12years (range 2-43years). Serum complement C4 level was decreased in all patients. All patients had low C1-esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long-term prophylaxis (attenuated androgens or tranexamic acid (TA) or a combination of the 2). Life-threatening episodes of laryngeal edema were managed with fresh-frozen plasma (FPP) infusions. We recorded one disease-related mortality in our cohort. This happened in spite of long-term prophylaxis with stanozolol and TA. We report largest single-center cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents, and FPP may be used for management of HAE in resource-limited settings.

Aortic Neck Dilatation Following EVAR: Looking for a Needle in a Haystack

Key to the long term success of an endovascular aneurysm repair (EVAR) is a durable proximal sealing zone. In their paper, Oliveira et al. provide a comprehensive investigation of aortic neck dilatation (AND) in a large single centre cohort of patients, who underwent standard infrarenal EVAR with self expanding stent grafts (SESs) over a 15 year period.1 While continued AND potentially poses a significant risk to this long term durability, there remain many unanswered questions, particularly in the context of SES.

Impact of Cancer in Patients Undergoing Transcatheter Aortic Valve Replacement: A Single-Center Study

BackgroundThe use of transcatheter aortic valve replacement (TAVR) in cancer survivors and patients with active cancer (AC) in cancer survivors and patients with active cancer (AC) is expanding, suggesting a need to adjust the indications and risk assessment pre-TAVR. ObjectivesThe purpose of this study was to determine the impact of cancer on peri-procedural complications and survival in a long-term, single-center cohort of patients treated with TAVR. MethodsPatients treated with TAVR between January 2006 and December 2018 were grouped as follows: controls (patients without cancer), stable cancer (SC), and AC. The primary endpoints were peri-procedural complications and 30-day survival. A secondary endpoint was 10-year survival. ResultsA total of 1,088 patients (age 81 ± 5 years, 46.6% men) treated with transfemoral TAVR were selected: 839 controls, 196 SC, and 53 AC. Predominant malignancies were breast, gastrointestinal, and prostate cancer. No differences were observed between patients with cancer and controls regarding peri-procedural complications. Patients with AC had similar 30-day survival compared with controls and SC (94.3% vs. 93.3% vs. 96.9%, p = 0.161), but as expected, reduced 10-year survival. AC was associated with a 1.47 (95% CI 1.16 to 1.87) fold increased risk of all-cause 10-year mortality in multivariable adjusted models. ConclusionsTAVR should be performed in patients with cancer when indicated, considering that patients with cancer have similar periprocedural complications and short-term survival compared with control patients. However, patients with AC have worse 10-year survival. Future studies are needed to define cancer-specific determinants of worse long-term survival.

Well-differentiated Gastroenteropancreatic G3 NET: Findings from a large single centre cohort

Neuroendocrine neoplasms are known to have heterogeneous biological behavior. G3 neuroendocrine tumours (NET G3) are characterized by well-differentiated morphology and Ki67 > 20%. The prognosis of this disease is understood to be intermediate between NET G2 and neuroendocrine carcinoma (NEC). Clinical management of NET G3 is challenging due to limited data to inform treatment strategies. We describe clinical characteristics, treatment, and outcomes in a large single centre cohort of patients with gastroenteropancreatic NET G3. Data was reviewed from 26 cases managed at Queen Elizabeth Hospital, Birmingham, UK, from 2012 to 2019. Most commonly the site of the primary tumour was unknown and majority of cases with identifiable primaries originated in the GI tract. Majority of cases demonstrated somatostatin receptor avidity. Median Ki67 was 30%, and most cases had stage IV disease at diagnosis. Treatment options included surgery, somatostatin analogs (SSA), and chemotherapy with either platinum-based or temozolomide-based regimens. Estimated progression free survival was 4 months following initiation of SSA and 3 months following initiation of chemotherapy. Disease control was observed following treatment in 5/11 patients treated with chemotherapy. Estimated median survival was 19 months; estimated 1 year survival was 60% and estimated 2 year survival was 13%. NET G3 is a heterogeneous group of tumours and patients which commonly have advanced disease at presentation. Prognosis is typically poor, though select cases may respond to treatment with SSA and/or chemotherapy. Further study is needed to compare efficacy of different treatment strategies for this disease.

Abstract 14666: Association Between Right Ventricular Systolic Pressure and Health Status Following Transcatheter Aortic Valve Replacement

Introduction: Pulmonary hypertension (PH) was shown in multiple studies to be associated with an increased risk of mortality after transcatheter aortic valve replacement (TAVR). However, it is unclear if echocardiogram derived right ventricular systolic pressure (RVSP) is associated with health status outcomes in surviving patients after TAVR. We explored for an association between baseline RVSP and quality of life in patients before and after undergoing TAVR. Methods: We estimated RVSP by echocardiography using the modified Bernoulli equation in a single-center cohort of patients undergoing TAVR from 2012-2017 . Disease-specific health status was assessed at baseline and 1-month and 12-months after TAVR with the Kansas City Cardiomyopathy Questionnaire-Overall Summary Score (KCCQ-OS). We then explored the association between baseline RVSP and KCCQ-OS before and after TAVR using a linear mixed model with an interaction for time and baseline RVSP and adjusted for baseline mitral valve regurgitation and systolic blood pressure. Results: Among 485 patients who underwent TAVR (mean age 81.7±7.9 years, 54.8% men), baseline RVSP was 42±15 mmHg, and 73% had RVSP &gt;34 mmHg. After TAVR, mean RVSP decreased to 37±13 mmHg at 1 month and 36±14 mmHg at 12 months. Baseline KCCQ-OS was 46±25 and improved to 66.9±23.6 at 1 month and 69.5± 22.6 at 12 months. In the linear mixed model, there was a significant cross-sectional association between baseline RVSP and baseline KCCQ-OS, with higher RVSP associated with worse health status. However, baseline RVSP was not significantly associated with KCCQ-OS at 1 month or 12 months (Figure). Conclusions: RVSP is not associated with worse health status after TAVR. This suggests that while patients with high RVSP are at an increased risk for mortality after TAVR, surviving patients appear to have similar health status as those with normal RVSP.

COVID-19 and systemic sclerosis: analysis of lifestyle changes during the SARS-CoV-2 pandemic in an Italian single-center cohort.

The outbreak of SARS-CoV-2 has changed the habits and lives of people worldwide. Patients affected by systemic sclerosis (SSc) experienced constant fear because of their immunocompromised status. The aim of this study was to investigate the prevalence of SARS-CoV-2 infection and to analyze the lifestyle changes in a single-center cohort of SSc patients and if these changes were more severe than in the general population. During the Italian lockdown, we supplied two surveys to our 184 SSc patients. In the first one, filled by 110 patients, we asked if SARS-CoV-2 had infected them or if they experienced signs and symptoms consistent with COVID-19. The second survey, performed by 79 SSc patients and 63 healthy subjects, included questions about the lifestyle adopted during this specific period. Among our patients, COVID-19 was diagnosed only in one case, while three other subjects reported signs and symptoms suggestive for the disease. Regarding the second survey, our patients greatly changed their lifestyle during the pandemic, adopting more restrictive isolation measures, because of their awareness of frailty. To date, we do not dispose of enough data to speculate about the risk of COVID-19 among immunocompromised patients, although in our SSc patients their frailty seems to have been their shelter. Pending more accurate epidemiological studies, it is essential to share as much data as possible to better understand the impact of COVID-19 on SSc patients’ health.Key points• The lifestyle adopted by SSc patients during the first months of COVID-19 pandemic was characterized by more stringent isolation rules than general population.• The prudential behavior of patients with SSc during Italian lockdown should be considered as a possible bias when analyzing the risk of SARS-CoV-2 disease in these subjects, as well as a protective factor against infection.

Clinical Burden of Paroxysmal Nocturnal Hemoglobinuria Among Patients Receiving C5 Inhibitors in the United States

INTRODUCTION Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired, hematologic disease characterized by chronic complement-mediated hemolysis. Treatment with the C5 inhibitor eculizumab has resulted in a reduction in intravascular hemolysis (IVH) and improvements in morbidity and mortality. However, in a single-center cohort of patients with PNH receiving treatment with eculizumab, 72% remained anemic and 36% continued to require transfusions due to ongoing IVH and extravascular hemolysis (McKinley CE, et al.Blood. 2017;130(Suppl 1):3471; Risitano AM, et al.Front Immunol. 2019;10:1157). This study aims to describe the burden of illness in patients with PNH currently being treated with C5 inhibitors (eculizumab and ravulizumab). Overall, the study aims to understand the clinical and hematological outcomes associated with burden of illness in about 150 patients with PNH globally. In these preliminary analyses, the impact of PNH on hematologic and clinical measures is assessed from patients in the United States. METHODS A cross-sectional survey was administered to adult patients ≥18 years of age in the United States with a self-reported diagnosis of PNH, recruited through a patient advocacy group. Inclusion criteria to complete the secure online survey included current treatment with either eculizumab or ravulizumab, informed consent, and agreement to adverse event reporting. This study was initiated in July 2020 and is ongoing. Results presented herein are preliminary. Impact of PNH on hematologic and clinical measures will be assessed using the following variables: diagnosis levels; and any patient history of blood transfusions, thrombotic events, renal impairment, fatigue, and other PNH-associated symptoms as well as dosing frequency and treatment patterns. For these preliminary analyses, descriptive statistics will be reported for patients who have completed the survey. RESULTS As of August 6, 2020, 58 adult patients with a median age of 52 years (range, 21-88) completed the survey, among which 78% were female. Current medications included eculizumab (n = 20 [34.5%]) or ravulizumab (n = 38 [65.5%]), as well as concurrent anticoagulants (n = 9 [15.5%]) and/or anti-thrombotics (n = 2 [3%]). Most patients initiated treatment with eculizumab (n = 20 [100%]) or with ravulizumab (n = 34 [90%]) ≥3 months before. Median (interquartile range) last known hemoglobin level for patients on eculizumab and ravulizumab was 9.3 g/dL (8.0-11.1) and 10.1 g/dL (8.9-11.5), respectively. Overall, 45 (82%) patients reported hemoglobin values &amp;lt;12 g/dL (eculizumab: 90%; ravulizumab: 78%). Forty (69%) patients reported having ≥1 red blood cell transfusion at any point during their disease. Within the previous 12 months, 53% and 26% of eculizumab- and ravulizumab-treated patients, respectively, had ≥1 transfusion, and 12% and 17% were unsure. Among those patients who had ever received ≥1 transfusion, 6% and 13% had &amp;gt;4 transfusions in the previous 12 months for eculizumab and ravulizumab, respectively. Seventeen patients (29%) reported ≥1 thrombotic event at any point during their disease. Seven patients reported thrombotic events over the previous 12 months; six were receiving ravulizumab. The majority (77%) of patients reported fatigue. Fatigue was reported by nearly 95% of eculizumab-treated patients and 68% of ravulizumab-treated patients. CONCLUSIONS Preliminary results from this burden of illness survey demonstrate that a majority of patients with PNH report remaining anemic, despite treatment with C5 inhibitors eculizumab and ravulizumab for a period of ≥3 months. Disclosures Dingli: Sanofi-Genzyme:Consultancy;Karyopharm Therapeutics:Research Funding;Bristol Myers Squibb:Research Funding;Millenium:Consultancy;Alexion:Consultancy;Apellis:Consultancy;Rigel:Consultancy;Janssen:Consultancy.Matos:Kantar:Current Employment.Lehrhaupt:Kantar:Current Employment.Krishnan:Apellis:Current Employment, Current equity holder in publicly-traded company.Sarda:Apellis:Current Employment, Current equity holder in publicly-traded company.Baver:Apellis:Current Employment, Current equity holder in publicly-traded company.

Clinical Effects of Pediatric Clonidine Exposure: A Retrospective Cohort Study at a Single Tertiary Care Center.

Pediatric clonidine ingestions frequently result in emergency department visits and admission for cardiac monitoring. Detailed information on the clinical course and specifically time of vital sign abnormalities of these patients is lacking. The objective of this study was to provide descriptive analysis of the rates and times to vital sign abnormalities, treatment, disposition, and outcomes in a single-center cohort of pediatric patients with report of clonidine poisoning. We performed a retrospective cohort study of patients younger than 21years who presented to a large, urban, tertiary care center with a report of single substance clonidine exposure between January 2004 and November 2017. Patients were dichotomized into younger (≤9years or younger) and older (10-21years) groups based on the expected physiologic and psychologic differences between older and younger children. Eighty-eight patients met our inclusion criteria. Younger patients (≤9years or younger; n=47) were more likely to be exposed to someone else's medication (53%) and older patients (10-21years; n=41) overwhelmingly (85%) were exposed to their own medication. Thirty-nine (45%) became bradycardic, 27 (32%) became bradypneic, and 38 (44%) became hypotensive. Eighty percent of patients had depressed mental status. Thirty-three (38%) patients received at least one dose of naloxone (median 0.07mg/kg; interquartile range 0.03-0.11mg/kg). Of those who received naloxone, 50% had a documented clinical response. In this study of patients at a pediatric tertiary referral center, pediatric patients with report of clonidine exposures were likely to exhibit altered mental status and frequently develop vital sign abnormalities. Naloxone exhibited some effectiveness; given its wide safety margin, high-dose naloxone should be used in critically poisoned non-opioid-dependent patients. Because adolescents are much more likely to ingest their own clonidine medication, counseling with parents and other caregivers regarding safe medication storage is paramount.

Commentary: Machine Learning With Feature Domains Elucidates Candidate Drivers of Hospital Readmission Following Spine Surgery in a Large Single-Center Patient Cohort.

Commentary: Machine Learning With Feature Domains Elucidates Candidate Drivers of Hospital Readmission Following Spine Surgery in a Large Single-Center Patient Cohort.

Machine Learning With Feature Domains Elucidates Candidate Drivers of Hospital Readmission Following Spine Surgery in a Large Single-Center Patient Cohort.

Unplanned hospital readmissions constitute a significant cost burden in healthcare. Identifying factors contributing to readmission risk presents opportunities for actionable change to reduce readmission rates. To combine machine learning classification and feature importance analysis to identify drivers of readmission in a large cohort of spine patients. Cases involving surgical procedures for degenerative spine conditions between 2008 and 2016 were retrospectively reviewed. Of 11 150 cases, 396 patients (3.6%) experienced an unplanned hospital readmission within 30 d of discharge. Over 75 pre-discharge variables were collected and categorized into demographic, perioperative, and resource utilization feature domains. Random forest classification was used to construct predictive models for readmission from feature domains. An ensemble tree-specific method was used to quantify and rank features by relative importance. In the demographics domain, age and comorbidity burden were the most important features for readmission prediction. Surgical duration and intraoperative oral morphine equivalents were the most important perioperative features, whereas total direct cost and length of stay were most important in the resource utilization domain. In supervised learning experiments for predicting readmission, the demographic domain model performed the best alone, suggesting that demographic features may contribute more to readmission risk than perioperative variables following spine surgery. A predictive model, created using only enriched features showing substantial importance, demonstrated improved predictive capacity compared to previous models, and approached the performance of state-of-the-art, deep-learning models for readmission. This strategy provides insight into global patterns of feature importance and better understanding of drivers of readmissions following spine surgery.

Incorporation of Urinary Neutrophil Gelatinase-Associated Lipocalin and Computed Tomography Quantification to Predict Acute Kidney Injury and In-Hospital Death in COVID-19 Patients

Background: The prevalence of acute kidney injury (AKI) in COVID-19 patients is high, with poor prognosis. Early identification of COVID-19 patients who are at risk for AKI and may develop critical illness and death is of great importance. Objective: The aim of this study was to develop and validate a prognostic model of AKI and in-hospital death in patients with COVID-19, incorporating the new tubular injury biomarker urinary neutrophil gelatinase-associated lipocalin (u-NGAL) and artificial intelligence (AI)-based chest computed tomography (CT) analysis. Methods: A single-center cohort of patients with COVID-19from Wuhan Leishenshan Hospital were included in this study. Demographic characteristics, laboratory findings, and AI-assisted chest CT imaging variables identified on hospital admission were screened using least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a model for predicting the AKI risk. The accuracy of the AKI prediction model was measured using the concordance index (C-index), and the internal validity of the model was assessed by bootstrap resampling. A multivariate Cox regression model and Kaplan-Meier curves were analyzed for survival analysis in COVID-19 patients. Results: One hundred seventy-four patients were included. The median (±SD) age of the patients was 63.59 ± 13.79 years, and 83 (47.7%) were men.u-NGAL, serum creatinine, serum uric acid, and CT ground-glass opacity (GGO) volume were independent predictors of AKI, and all were selected in the nomogram. The prediction model was validated by internal bootstrapping resampling, showing results similar to those obtained from the original samples (i.e., 0.958; 95% CI 0.9097–0.9864). The C-index for predicting AKI was 0.955 (95% CI 0.916–0.995). Multivariate Cox proportional hazards regression confirmed that a high u-NGAL level, an increased GGO volume, and lymphopenia are strong predictors of a poor prognosis and a high risk of in-hospital death. Conclusions: This model provides a useful individualized risk estimate of AKI in patients with COVID-19. Measurement of u-NGAL and AI-based chest CT quantification are worthy of application and may help clinicians to identify patients with a poor prognosis in COVID-19 at an early stage.