Lower Proportion Of Patients Research Articles

Subcutaneous Emphysema, Pneumomediastinum, and Pneumothorax in Critically Ill Patients With Coronavirus Disease 2019: A Retrospective Cohort Study.

Management of severe coronavirus disease 2019 relies on advanced respiratory support modalities including invasive mechanical ventilation, continuous positive airway pressure, and noninvasive ventilation, all of which are associated with the development of subcutaneous emphysema, pneumomediastinum, and pneumothorax (herein collectively termed barotrauma). To assess the occurrence rate of barotrauma in severe coronavirus disease 2019 and to explore possible associated factors. A retrospective, single-center cohort study with nested case series, conducted at University Hospital Lewisham: a 450-bed general hospital in London, United Kingdom. All patients with confirmed coronavirus disease 2019 admitted to the critical care department from March 12, to April 12, 2020, were included. Patients were retrospectively screened for radiological evidence of barotrauma. Admission characteristics, modalities of respiratory support, and outcomes were compared between barotrauma and nonbarotrauma groups. Respiratory parameters in the period preceding barotrauma identification were recorded. Of 83 admissions with coronavirus disease 2019, eight suffered barotrauma (occurrence rate 9.6%; 95% CI 4.3%-18.1%). Barotrauma cases had longer illness duration prior to critical care admission (10 vs 7 d; interquartile range, 8-14 and 6-10, respectively; p = 0.073) and were more often treated with continuous positive airway pressure or noninvasive ventilation as the initial modality of advanced respiratory support (87.5% vs 36.0%; p = 0.007). Patients managed with continuous positive airway pressure or noninvasive ventilation prior to the development of barotrauma had median minute ventilation of 16.2-19.9 and 21.3-22.7 L/min, respectively. Compared with the nonbarotrauma group, a higher proportion of patients with barotrauma had died (62.5% vs 43.2%), and a lower proportion of patients had been discharged (25.0% vs 53.3%) at 3-month follow-up. Barotrauma appears to be a common complication of severe coronavirus disease 2019. Determining whether high minute ventilation while using continuous positive airway pressure or noninvasive ventilation predisposes patients to barotrauma requires further investigation.

Adipocytes and membranous fat necrosis within native cardiac valves: Clinicopathologic characterization of histologic constituents

The constituents of normal cardiac valves as well as those involved by active and/or chronic processes have been detailed previously, however minor attention has been provided toward mature adipocytes within valves and correlation with other histologic, clinical, and echocardiographic data. The literature also contains a paucity of investigations examining the presence of a particular form of degenerative change of mature adipocytes termed membranous fat necrosis. We retrospectively reviewed the histologic findings of 1042 native cardiac valves which included identification of the presence of adipocytes and membranous fat necrosis within them, as well as correlation with other histopathologic features, and clinical and echocardiographic findings. Notable observations included that membranous fat necrosis was only present in valves with adipocytes, adipocytes and membranous fat necrosis were seen in older patients, and that Caucasians made up a greater proportion of patients while African Americans made up a lower proportion of patients when valves were found with adipocytes and membranous fat necrosis. Aortic valves contained adipocytes and membranous fat necrosis at a greater rate than compared to other valves, and aortic valves with adipocytes and membranous fat necrosis were more commonly tricuspid (as opposed to bicuspid) and with larger aortic valve area and lower peak and mean gradients. Further investigation is required to determine potential physiologic and/or pathologic consequence of their presence.

Progression of Stage 2 and 3 Acute Kidney Injury in Patients With Decompensated Cirrhosis and Ascites

Progression of stages 2 and 3 acute kidney injury (AKI) in cirrhosis has not been characterized adequately. Patients with higher stages of AKI are believed to have worse outcomes. We assessed outcomes and factors associated with stages 2 and 3 AKI in patients with cirrhosis in the North American Consortium for the Study of End-stage Liver Disease cohort. We collected data from 2297 hospitalized patients with cirrhosis and ascites from December 2011 through February 2017. Our final analysis included 760 patients who developed AKI per the International Ascites Club 2015 definition (419 with maximum stage 1 and 341 with maximum stage 2 or 3; 63% male; mean age, 58 y). We compared demographic features, laboratory values, AKI treatment response, and survival between patients with maximum stage 1 vs patients with stage 2 or 3 AKI. Patients with stage 2 or 3 AKI had higher Model for End-Stage Liver Disease scores (25.9 ± 7.3) than patients with stage 1 AKI (21.9 ± 7.5) (P < .0001). More patients fulfilled systemic inflammatory response syndrome criteria on admission, and more developed a second nosocomial infection (P < .05 for both comparisons). More patients with stage 2 or 3 AKI also had progression of AKI and required dialysis and admission into intensive care units when compared to stage 1 AKI patients (P < .0001 for both). A lower proportion of patients with stage 2 or 3 AKI survived their hospital stay (80% vs 99% with stage 1 AKI; P < .0001), or survived for 30 days without a liver transplant (56% vs 81%; P < .0001). The development of stage 2 or 3 AKI was associated with a higher Model for End-Stage Liver Disease score at the time of admission (P < .0001), presence of systemic inflammatory response on admission (P= .039), and second infection (P < .0001). Based on an analysis of data from the North American Consortium for the Study of End-stage Liver Disease cohort, we found that patients with cirrhosis and more advanced liver disease, as well as a second infection, are more likely to develop stages 2 or 3 AKI, with a progressive course associated with decreased 30-day transplant-free survival. Prevention of AKI progression in patients with cirrhosis and stage 2 or 3 AKI might improve their outcomes.

Cardiac Rehabilitation for Patients Treated for Atrial Fibrillation With Ablation Has Long-Term Effects: 12-and 24-Month Follow-up Results From the Randomized CopenHeartRFA Trial

ObjectiveTo assess outcomes at 12 and 24 months after participation in a multidisciplinary cardiac rehabilitation program plus usual care compared with usual care alone for patients treated for atrial fibrillation with catheter ablation. DesignLong-term follow-up on the randomized CopenHeartRFA trial. SettingPatients were enrolled and outcome assessed at the hospital and the intervention were carried out at the hospital or at local rehabilitation centers. ParticipantsPatients (N=210) treated for atrial fibrillation with catheter ablation included in the CopenHeartRFA trial. InterventionsA 6-month cardiac rehabilitation program consisting of physical exercise and psychoeducational consultations plus usual care or usual care alone. Main Outcome MeasuresPhysical capacity was measured by peak oxygen uptake (Vo2peak) at 12 months, and patient-reported outcomes on perceived health, anxiety, and depression were collected by validated questionnaires at 12 and 24 months. Information on hospital admissions and mortality was collected through national registers up to 24 months. ResultsMean Vo2peak was higher at 12 months in the cardiac rehabilitation group (cardiac rehabilitation group: 25.82 mL/kg/min vs usual care group, 22.43 mL/kg/min, P=.003). A lower proportion of patients had high levels of anxiety at 24 months in the cardiac rehabilitation group compared to usual care (12% vs 24%, P=.004). There was no difference in mortality or hospital admissions at 24 months between groups. ConclusionsThis long-term follow-up of a comprehensive multidisciplinary cardiac rehabilitation program for patients treated for atrial fibrillation with catheter ablation found sustained improvements with respect to physical capacity and anxiety compared to usual care but no difference on mortality or hospital admission.

Genetics of Transposition of Great Arteries: Between Laterality Abnormality and Outflow Tract Defect.

Transposition of great arteries (TGA) is a complex congenital heart disease whose etiology is still unknown. This defect has been associated, at least in part, with genetic abnormalities involved in laterality establishment and heart outflow tract development, which suggest a genetic heterogeneity. In animal models, the evidence of association with certain genes is strong but, surprisingly, genetic anomalies of its human orthologues are found only in a low proportion of patients and in nonaffected subjects, so that the underlying causes remain as an unexplored field. Evidence related to TGA suggests different pathogenic mechanisms involved between patients with normal organ disposition and isomerism. This article reviews the most important genetic abnormalities related to TGA and contextualizes them into the mechanism of embryonic development, comparing them between humans and mice, to comprehend the evidence that could be relevant for genetic counseling. Graphical abstract.

Clinical Differences of Recent Myocardial Infarction Compared With Acute Myocardial Infarction - Insights From the Tokyo CCU Network Multicenter Registry.

Characteristics and treatment outcomes of acute myocardial infarction (AMI) patients have been studied; however, those of recent myocardial infarction (RMI) patients remain unclear. This study aimed to clarify characteristics, treatment strategy, and in-hospital outcomes of RMI patients in the Tokyo CCU network database. In total, 1,853 RMI and 12,494 AMI patients from the Tokyo CCU network database during 2013-2016 were compared. Both RMI and AMI were redefined by onset times of 2-28 days and ≤24 h, respectively. The RMI group had a higher average age (70.4±12.9 vs. 68.0±13.4 years, P<0.001), more women (27.6% vs. 23.6%, P<0.001), lower proportion of patients with chest pain as the chief complaint (75.2% vs. 83.6%, P<0.001), higher prevalence of diabetes mellitus (35.9% vs. 31.0%, P<0.001), and higher mechanical complication incidence (3.0% vs. 1.5%, P<0.001) than did the AMI group. Thirty-day mortality was comparable (5.3% vs. 5.8%, P=0.360); major causes of death were cardiogenic shock and mechanical complications in the AMI and RMI groups, respectively. Death from mechanical complications (not onset time) in the AMI group plateaued almost 1 week after hospitalization, whereas it continued to increase in the RMI group. Both RMI and AMI patients have distinctive clinical features, sequelae, and causes of death. Although treatment of RMI patients adhered to guidelines, it was insufficient, and death from mechanical complications continues to increase.

Characteristics and anticoagulant treatment status of elderly non-valvular atrial fibrillation patients with a history of catheter ablation in Japan: Subanalysis of the ANAFIE registry

BackgroundBenefits of catheter ablation (CA) have been shown for patients with atrial fibrillation (AF), including elderly patients. However, data in patients aged ≥75 years who have undergone CA for non-valvular AF (NVAF) are lacking. This cross-sectional subanalysis of the ANAFIE registry determined the characteristics and status of anticoagulant treatment in elderly NVAF patients with a history of CA at enrollment. MethodThe ANAFIE registry was a multicenter, prospective, non-interventional cohort study in which elderly ambulatory patients (≥75 years) diagnosed with NVAF by electrocardiogram were enrolled between October 2016 and January 2018. Treatment was prescribed per routine clinical practice by individual treating physicians. The patients were stratified into two groups: the CA and No-CA groups. ResultsAmong 32,726 NVAF patients aged ≥75 years, 3002 (9.2%) underwent CA before enrollment. Patients who underwent CA were significantly younger (78.9 years vs 81.7 years; p < 0.0001), had significantly greater height and body weight, as well as creatinine clearance rate (CCr) compared with those who did not undergo CA. In both the CA and No-CA groups, the most common type of AF was paroxysmal AF (72.9% and 38.9%). In the CA group, a significantly larger proportion of patients did not receive anticoagulant therapy compared with the No-CA group (13.3% vs 7.6%; p < 0.0001). Direct oral anticoagulant (DOAC) use was similar in the CA (69.9%) and No-CA (66.0%) groups, and standard doses of DOACs were administered more frequently in the CA group than in the No-CA group. A lower proportion of patients in the CA group received warfarin (16.9% vs 26.4%) compared with the No-CA group. ConclusionsThis ANAFIE registry subanalysis showed that patients with NVAF in the CA group tended to have paroxysmal AF; be significantly younger; have greater weight, height, and CCr; receive standard doses of DOACs; and have not used anticoagulant medication compared with No-CA patients.

Bacterial and host determinants of cough aerosol culture positivity in patients with drug-resistant versus drug-susceptible tuberculosis.

A burgeoning epidemic of drug-resistant tuberculosis (TB) threatens to derail global control efforts. Although the mechanisms remain poorly clarified, drug-resistant strains are widely believed to be less infectious than drug-susceptible strains. Consequently, we hypothesized that lower proportions of patients with drug-resistant TB would have culturable Mycobacterium tuberculosis from respirable, cough-generated aerosols compared to patients with drug-susceptible TB, and that multiple factors, including mycobacterial genomic variation, would predict culturable cough aerosol production. We enumerated the colony forming units in aerosols (≤10 µm) from 452 patients with TB (227 with drug resistance), compared clinical characteristics, and performed mycobacterial whole-genome sequencing, dormancy phenotyping and drug-susceptibility analyses on M. tuberculosis from sputum. After considering treatment duration, we found that almost half of the patients with drug-resistant TB were cough aerosol culture-positive. Surprisingly, neither mycobacterial genomic variants, lineage, nor dormancy status predicted cough aerosol culture positivity. However, mycobacterial sputum bacillary load and clinical characteristics, including a lower symptom score and stronger cough, were strongly predictive, thereby supporting targeted transmission-limiting interventions. Effective treatment largely abrogated cough aerosol culture positivity; however, this was not always rapid. These data question current paradigms, inform public health strategies and suggest the need to redirect TB transmission-associated research efforts toward host-pathogen interactions.

Inverse Association Between Fatty Liver at Baseline Ultrasonography and Remission of Type 2 Diabetes Over a 2-Year Follow-up Period

Improvement of fatty liver may be required for remission of type-2 diabetes. However, there is no longitudinal evidence on whether fatty liver reduces the chances for remission of type-2 diabetes. We investigated the association between fatty liver and remission of type-2 diabetes (the primary analysis), and also the association between improvement of fatty liver and remission of type-2 diabetes (the secondary analysis). We collected data from 66961 people who underwent screening for type-2 diabetes from 2008 through 2016 at a single center in Japan. The primary analysis included 2567 patients with type-2 diabetes without chronic renal failure or a history of hemodialysis who underwent ultrasonography to detect fatty liver, all of whom had follow-up testing, including blood testing, for a median 24.5 months after the baseline ultrasonography. The secondary analysis included 1833 participants with fatty liver at baseline who underwent a second ultrasonography, and participants who had fatty liver at baseline but not at the second visit were considered to have had improvement of fatty liver. Remission of type-2 diabetes was defined as a fasting plasma glucose level below 126 mg/dL and an HbA1c level below 6.5% for more than 6 months without anti-diabetic drugs. Odds ratios (ORs) of remission of type-2 diabetes were estimated using logistic-regression models. A lower proportion of patients who had fatty liver detected by ultrasonography at baseline (8.7%, 167/1910) had remission of type-2 diabetes during the follow-up period than patients without fatty liver (13.1%, 86/657). Fatty liver at baseline was associated with a lower odds of remission of type-2 diabetes (multivariable-adjusted OR, 0.51; 95% CI, 0.37-0.72). A higher proportion of patients who had improvement of fatty liver had remission of type-2 diabetes (21.1%, 32/152) than patients with no improvement of fatty liver (7.7%, 129/1681). Improvement of fatty liver was associated with a higher odds of remission of type-2 diabetes (multivariable-adjusted OR, 3.08; 95% CI, 1.94-4.88). Over a follow-up period of approximate 2 years, remission of type-2 diabetes was less common in people with fatty liver detected by ultrasonography, and improvement of fatty liver was independently associated with type-2 diabetes remission.

Tu1510 LYMPHOCYTIC GASTRITIS AND ASSOCIATION WITH ATOPIC SYMPTOMS: A CASE SERIES

Lymphocytic gastritis is rare, characterized by >25 intraepithelial lymphocytes per 100 epithelial cells, specifically CD8+ T-cells. Prevalence has been reported as <0.3%. Little is known about the pathophysiology, however up to 80% may be found with Helicobacter pylori infections or celiac disease. Endoscopically, the gastric mucosa is classically described as nodular with hypertrophied rugae, with or without erosions and plaques. Lymphocytic gastritis is a histologic diagnosis and when encountered, clinical management is ill-defined. We sought to identify clinical characteristics of this disease. Patients with histological diagnosis of lymphocytic gastritis were identified from January 2007 to August 2019 at our tertiary-care, medical center. Each patient’s chart was reviewed. Demographic information, medical history and outcomes, medications, endoscopic findings, and pathologic results were recorded. Serologic tests for human immunodeficiency virus (HIV) were reviewed. Serologic or duodenal biopsies were used to screen for celiac disease. Twenty-six patients were identified with lymphocytic gastritis. Fifty percent were male and age ranged from 2 years to 77 years, averaging 49 years at time of upper endoscopy. Atopy (e.g. asthma, allergies, or eczema) was noted in 46% of patients. Five (19%) patients had history of autoimmune disorders. The most common indications for upper endoscopy included abdominal pain (30%) and anemia (23%). Fifteen percent of the patients had concomitant Helicobacter pylori infections based on gastric biopsies. Low proportions of patients were tested for celiac disease (50%) and HIV (26.9%); none were positive. Endoscopically, 75% had erythema and erosions and only 20% demonstrated the classically described nodular mucosa. Histologically, lymphocytic gastritis was commonly seen with chronic inflammation (65.4%). Among the 11 patients with duodenal biopsies, 36.4% had increased lymphocytes in the duodenum. Nearly half of the patients in our case series were noted to have atopy. Although lymphocytes are not typically associated with atopic illnesses, there are several studies elucidating the roles of CD4+ and CD8+ T cells in relation to eosinophils and mast cells in atopic dermatitis and asthma. Current management revolves around symptom control, however, further studies are needed to evaluate the implications of this pathological finding.Demographic information, clinical history, endoscopic findings, and pathologic results of patients diagnosed with lymphocytic gastritis.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Comparison of Silodosin, Tadalafil and Combinations Prior to Ureteroscopic Management of Ureteral Stones

The present paper, aims to assess and compare the therapeutic efficacies of silodosin, Tadalafil, and their combination for the negotiation of large semi-arid ureteroscopic through ureteric orifice during ureteral stone management. During endoscopy, the patients in groups A, B, and C exhibited wider ureteric orifice than the patients of group D. About 70.6%, 60.6%, 62.9% and 32.4% of patients belonging to groups A, B, C, and D, respectively, exhibited easy negotiation. Significantly lower proportions of patients in groups A, B, and C (35.3%, 39.4%, and 28.6%, respectively) exhibited the need for ureteral dilation compared to those in group D (61.8%). In addition, the duration of surgery for groups A, B, and C was less than that for group D. Preoperative silodosin and Tadalafil administration in patients undergoing ureteroscopic for ureteral stones improves the access of large size duretero scope and reduced the need for ureteral dilatation with less surgical duration and minimal adverse events.

Endovascular Intervention Versus Surgery in Ruptured Intracranial Aneurysms in Equipoise

Background and Purpose- The benefits of endovascular intervention over surgery in the treatment of ruptured aneurysms of anterior circulation remains uncertain. Recently, published studies did not find superiority of endovascular intervention, challenging earlier evidence from a clinical trial. The earlier evidence also had a higher than average proportion of patients in good clinical status, leading to uncertainty about external validity of earlier trials. Methods- We performed a systematic review of studies after 2005 under a protocol published in the International Prospective Register of Systematic Reviews. Primary outcomes were posttreatment rebleeding and adverse events (procedural complications). Secondary outcomes were dependency at 3 to 6 and 12 months, delayed cerebral ischemia, and seizures. Results- Rebleeding was more frequent after endovascular intervention (Peto OR, 2.18 [95% CI, 1.29-3.70]; 3104 participants; 15 studies; I2=0%, Grading of Recommendations, Assessment, Development and Evaluation: very low certainty of evidence). Fewer adverse events were reported with the endovascular intervention (RR, 0.71 [95% CI, 0.53-0.95]; 1661 participants; 11 studies; I2=14%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence). Three to six months dependency (RR, 0.82 [95% CI, 0.73-0.93]; 4081 participants; 18 studies; I2=15%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence) and 12-month dependency (RR, 0.76 [95% CI, 0.66-0.86]; 1981 participants; 10 studies; I2=0%, Grading of Recommendations, Assessment, Development and Evaluation: low certainty of evidence) were lower after endovascular intervention. Conclusions- This study found consistent results between recent studies and the earlier evidence, in that endovascular intervention results in lower chance of dependency compared with surgery for repair of ruptured anterior circulation aneurysms. A lower proportion of patients in good clinical status in this review supports the application of the earlier evidence. Registration- URL: https://www.crd.york.ac.uk/PROSPERO. Unique identifier: CRD42018090396.

Type 2 Diabetes and Metformin Use Associate With Outcomes of Patients With Nonalcoholic Steatohepatitis–Related, Child–Pugh A Cirrhosis

Factors that affect outcomes of patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis are unclear. We studied associations of type 2 diabetes, levels of hemoglobin A1c (HbA1c), and use of antidiabetic medications with survival and liver-related events in patients with NASH and compensated cirrhosis. We collected data from 299 patients with biopsy-proven NASH with Child-Pugh A cirrhosis from tertiary hospitals in Spain, Australia, Hong Kong, and Cuba, from April 1995 through December 2016. We obtained information on the presence of type 2 diabetes, level of HbA1c, and use of antidiabetic medications. Cox proportional and competing risk models were used to estimate and compare rates of transplant-free survival, hepatic decompensation, and hepatocellular carcinoma (HCC). A total of 212 patients had type 2 diabetes at baseline and 8 of 87 patients developed diabetes during a median follow-up time of 5.1 years (range, 0.5-10.0 y). A lower proportion of patients with diabetes survived the entire follow-up period (38%) than of patients with no diabetes (81%) (adjusted hazard ratio [aHR], 4.23; 95% CI, 1.93-9.29). Higher proportions of patients with diabetes also had hepatic decompensation (51% vs 26% of patients with no diabetes; aHR, 2.03; 95% CI, 1.005-4.11) and HCC (25% vs 7% of patients with no diabetes; aHR, 5.42; 95% CI, 1.74-16.80). Averaged annual HbA1c levels over time were not associated with outcomes. Metformin use over time was associated with a significant reduction in risk of death or liver transplantation (aHR, 0.41; 95% CI, 0.26-0.45), hepatic decompensation (aHR, 0.80; 95% CI, 0.74-0.97), and HCC (aHR, 0.78; 95% CI, 0.69-0.96). Metformin significantly reduced the risk of hepatic decompensation and HCC only in subjects with HbA1c levels greater than 7.0% (aHR, 0.97; 95% CI, 0.95-0.99 and aHR, 0.67; 95% CI, 0.43-0.94, respectively). In an international cohort of patients with biopsy-proven NASH and Child-Pugh A cirrhosis, type 2 diabetes increased the risk of death and liver-related outcomes, including HCC. Patients who took metformin had higher rates of survival and lower rates of decompensation and HCC.

Diarrhea Is Associated With Prolonged Symptoms and Viral Carriage in Corona Virus Disease 2019

Background & AimsWe compared clinical, laboratory, radiological, and outcome features of patients with SARS-CoV-2 infection (COVID-19) with pneumonia, with vs without diarrhea.MethodsWe performed a retrospective, single-center analysis of 84 patients with SARS-CoV-2 pneumonia in Wuhan Union Hospital, China, from January 19 through February 7, 2020. Cases were confirmed by real-time reverse-transcriptase PCR of nasal and pharyngeal swab specimens for SARS-CoV-2 RNA. Blood samples were analyzed for white blood cell count, lymphocyte count, alanine aminotransferase, creatine kinase, lactate dehydrogenase, D-dimer, C-reactive protein, and in some cases, immunoglobulins, complement, lymphocyte subsets, and cytokines. Virus RNA was detected in stool samples by real-time PCR.ResultsOf the 84 patients with SARS-CoV-2 pneumonia, 26 (31%) had diarrhea. The duration of fever and dyspnea in patients with diarrhea was significantly longer than those without diarrhea (all P < .05). Stool samples from a higher proportion of patients with diarrhea tested positive for virus RNA (69%) than from patients without diarrhea (17%) (P < .001). As of February 19, a lower proportion of patients with diarrhea had a negative result from the latest throat swab for SARS-CoV-2 (77%) than patients without diarrhea (97%) (P = .010), during these patients’ hospitalization. Of 76 patients with a negative result from their latest throat swab test during hospitalization, a significantly higher proportion of patients with diarrhea had a positive result from the retest for SARS-CoV-2 in stool (45%) than patients without diarrhea (20%) (P = .039).ConclusionsAt a single center in Wuhan, China, 31% of patients with SARS-CoV-2 pneumonia had diarrhea. A significantly higher proportion of patients with diarrhea have virus RNA in stool than patients without diarrhea. Elimination of SARS-CoV-2 from stool takes longer than elimination from the nose and throat.

The Utility of Oncotype DX for Adjuvant Chemotherapy Treatment Decisions in Estrogen Receptor-positive, Human Epidermal Growth Factor Receptor 2-negative, Node-negative Breast Cancer.

IntroductionBreast cancer is the most common cancer diagnosis in the UK. Recently, there has been a reduction in breast cancer-specific mortality and recurrence attributed, in part, to the delivery of adjuvant chemotherapy. The National Institute for Health and Care Excellence (NICE) recommends the use of genetic profiling with Oncotype DX (ODX) to guide decisions to offer adjuvant chemotherapy after surgery in intermediate-risk early breast cancer patients. This study aimed to evaluate the utility of ODX testing in routine clinical practice in a National Health Service (NHS) hospital. MethodsConsecutive early breast cancer patients, identified through the multidisciplinary team (MDT) records, treated in our institution over 12 months (October 2017-September 2018) were included. PREDICT and Nottingham prognostic index (NPI) scores (from online clinicopathological recurrence risk tools) were calculated for each patient, and ODX data obtained through Genomic Health, Inc. (Redwood City, California). Patients were divided into two groups, those that underwent ODX testing (ODX group) and those that did not (non-ODX group). Descriptive statistics were used to analyse patient and tumour characteristics. The Gaussian distribution of each data set was assessed using the Anderson-Darling test. For comparisons between patient groups, the non-parametric equivalent of the two-tailed t-test (Mann-Whitney) was used. Dichotomous variables (e.g. chemotherapy decisions) were compared using chi-squared tests.ResultsOne-hundred thirty-three patients (mean age 62 years) treated for 152 early breast cancers, were included in the final analysis. Breast cancers in the ODX group were of greater median tumour size (24 vs 16 mm; P<0.0001) and higher median tumour grade (3 vs 2; P<0.0001). PREDICT scores (3 vs 1, P<0.0001) and NPI scores (3.40 vs 2.30, P<0.0001) for the ODX group were also significantly higher than the non-ODX group. A greater proportion of patients were offered chemotherapy in the ODX group (39.9% vs 6.9%, P<0.001). However, for the PREDICT-calculated intermediate-risk patients, ODX testing resulted in a lower proportion of patients being offered chemotherapy compared to the intermediate-risk patients who were not genetically profiled (54.5% vs 83.3%, P=0.3547), although this result was not statistically significant.ConclusionsPatients selected for ODX testing were younger, with significantly higher-grade and larger-sized tumours compared to patients not selected for genetic profiling. ODX testing significantly impacted the delivery of chemotherapy, as the recurrence score generated through ODX testing guided the final decision.

Abstract P3-11-07: A randomized phase II trial of reparixin, a CXCR1 inhibitor, in combination with paclitaxel in the treatment of mTNBC

Abstract Background: CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer Cancer Stem Cells (CSC): In a phase 1b study, the combination of reparixin (R), an investigational oral inhibitor of CXCR1, and weekly paclitaxel (P) was well tolerated with a sizeable ORR and TTP in metastatic HER-2-ve breast cancer, with some long-term responders (Schott AF et al., CCR 2017). fRida (NCT02370238) is a phase 2, randomized, double-blind study evaluating the safety and efficacy of R+P vs placebo +P in untreated metastatic (m) TNBC. Trial Design: Patients with untreated mTNBC were stratified by prior (neo)adjuvant chemotherapy and randomized 1:1 to R 1200 mg or placebo three times per day dd1-21 and weekly P 80 mg/m2 dd 1, 8, 15 q28dd. Response was assessed per RECIST 1.1 (by central review). The primary endpoint was PFS. Secondary endpoints were OS, ORR and safety. This is the final analysis for PFS (data cut off 2/20/2019). Results: A total of 123 patients were randomized (62 to R+P and 61 to placebo + P). Patient characteristics (safety population) are summarized in Table 1. Median follow-up was 14.5 months. 74 PFS events (R+P 40, placebo+P 34), were observed in the ITT population. Median PFS was not significantly different between the 2 groups [median 5.5 and 5.7 months, HR 1.14 (95% C.I. 0.71-1.81), p=.589]. OS is not expected to reach statistical significance based on the results at the data cut off after 71 events (37 in R+P and 34 in placebo+P groups, respectively) [HR 1.03 (95% C.I. .64-1.56), p=.897). Findings were consistent across de novo stage IV and relapsed patients. BOR was similar between the two groups (R+P 28.1% vs placebo+P 25.9%). Median duration of response was longer in R+P than placebo+P group (median 293 vs 172 days, p=0.767). Among exploratory endpoints, a lower proportion of patients in the R+P group vs the placebo+P group had new metastatic lesions at disease progression (17/39 vs 23/34, respectively, p=.172). In patients where metastatic tissue was available at baseline (n=55), ALDH+ and CD24−/CD44+ CSC centrally evaluated by IHC were found in 17 and 29 patients respectively, with 9 patients displaying both CSC populations. G≥3 ADRs, which occurred in 21.3% and 10% of patients in R+P and placebo+P group, respectively, represented 6% of all ADRs in both groups. Conclusions: fRida is the first randomized, double-blind placebo-controlled clinical trial of a CSC-targeting agent in combination with chemotherapy in breast cancer. The primary endpoint of prolonged PFS was not met. Sensitivity analyses are ongoing. The safety profile was consistent with that previously reported for this combination. ALDH+ and CD24−/CD44+ appeared to be largely non-overlapping CSC populations in metastatic tissue, similar to primary breast cancer (Goldstein LJ et al., AACR 2016). Table 1.R+Pplacebo+Page, median (range)57 (29, 79)57.5 (36, 77)PS 0/1 (n)37/2441/19de novo stage IV (n)148relapsed after (neo)adjuvant chemotherapy (n)4752prior taxane (n)4045Liver mets (n)1411Lung mets (n)1224≥3 metastatic sites(n)39 Citation Format: Lori J Goldstein, Mauro Mansutti, Christelle Levy, Jenny C Chang, Stephanie Henry, Isaura Fernandez-Perez, Giuseppe Viale, Guiseppe Viale, Beth Butler, Susan McCanna, Pier A Ruffini, Max Wicha, Anne F Schott. A randomized phase II trial of reparixin, a CXCR1 inhibitor, in combination with paclitaxel in the treatment of mTNBC [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-11-07.

Real-world experience of regorafenib in patients with hepatocellular carcinoma: A multicenter United Kingdom study.

499 Background: Regorafenib was the first treatment to demonstrate a survival benefit in patients with HCC after progression on sorafenib. The RESORCE trial found that regorafenib improved overall survival with acceptable toxicity, in patients with disease progression on sorafenib who tolerated ≥400mg sorafenib daily and had Child-Pugh A liver function. Methods: We performed a multicentre, retrospective, observational study of patients with HCC receiving regorafenib in the UK, following its availability in April 2018. Results: Data on a total of 104 patients were included from April 2018–August 2019, and 80.8% were male. Age was collected in 85 patients, with a median of 68 years (range 22–86). 23.5% had NAFLD, 21.2% had ALD, 12.9% had HBV, and 3.5% had HCV. Prior management included sorafenib (100%), TACE (30.8%), resection (12.9%). Duration of sorafenib treatment was evaluable in 99/104 patients, and reported a median of 8.7 months (range 1.8–76.6). Duration of regorafenib treatment was evaluable in 92/104 patients, and reported a median of 3.9 months (range 0.0–15.7). Following treatment with regorafenib, 6 patients (5.8%) achieved partial response, 37 (35.6%) achieved stable disease and 45 (43.3%) had progressive disease as the best response. 15 (14.4%) were not assessed and 1 (1.1%) had mixed response. Survival data is immature with 62/101 (61.4%) patients alive at the time of census with median survival currently 6.5 months. Fatigue was the most frequent AE, with 69/88 patients (85.2%) for all grades. 12/88 patients (14.8%) had Grade 3 fatigue. Other significant AEs include hand-foot syndrome (6/85 patients [7.3%] had Grade 3) and diarrhoea (4/83 patients [4.9%] had Grade 3). Conclusions: The population in our real-world experience of regorafenib for HCC had a similar duration of prior sorafenib to those in the RESORCE trial. However, there was different balance of aetiologies with a lower proportion of patients with HBV and HCV. The rate of partial response is similar to the RESORCE trial with fewer patients achieving stable disease. The incidence of fatigue was higher, but the incidence of hand-foot syndrome and diarrhoea were lower. Further expansion and follow-up of this population is warranted.

Outcomes of lactulose plus branched-chain amino acid infusion and lactulose alone for hepatic encephalopathy: A retrospective cohort study using a national inpatient database.

Previous randomized controlled trials of branched-chain amino acid infusion for hepatic encephalopathy involved a small number of patients, and the effectiveness of branched-chain amino acid infusion has not been clarified. We evaluated whether branched-chain amino acid infusion in addition to lactulose treatment was associated with short-term outcomes in a large population of patients. Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients with hepatic encephalopathy who received lactulose within 2days of admission from July 2011 to March 2017. We divided the patients into those who received branched-chain amino acid infusion within 2days of admission in addition to lactulose treatment and those who did not. We conducted propensity-score inverse probability of treatment weighting analyses to compare in-hospital mortality, consciousness at discharge, in-hospital complications, length of stay, and total hospitalization costs between the groups. We identified 8051 patients with hepatic encephalopathy treated with lactulose, including 7560 patients who received lactulose plus branched-chain amino acid infusion and 491 who received lactulose alone. The lactulose plus branched-chain amino acid infusion group had a significantly lower mortality than the lactulose alone group (9.6% vs. 15.0%, odds ratio 0.60, 95% confidence interval 0.44-0.82). The lactulose plus branched-chain amino acid infusion group also had a lower proportion of patients with impaired mental status at discharge, and lower total hospitalization costs than the lactulose alone group. Branched-chain amino acid infusion together with lactulose may improve the prognosis of hepatic encephalopathy.

Cerebrospinal Fluid Early Fungicidal Activity as a Surrogate Endpoint for Cryptococcal Meningitis Survival in Clinical Trials.

In cryptococcal meningitis phase 2 clinical trials, early fungicidal activity (EFA) of Cryptococcus clearance from cerebrospinal fluid (CSF) is used as a surrogate endpoint for all-cause mortality. The Food and Drug Administration allows for using surrogate endpoints for accelerated regulatory approval, but EFA as a surrogate endpoint requires further validation. We examined the relationship between rate of CSF Cryptococcus clearance (EFA) and mortality through 18 weeks. We pooled individual-level CSF data from 3 sequential cryptococcal meningitis clinical trials conducted during 2010-2017. All 738 subjects received amphotericin + fluconazole induction therapy and had serial quantitative CSF cultures. The log10-transformed colony-forming units (CFUs) per mL CSF were analyzed by general linear regression versus day of culture over the first 10 days. Mortality through 18 weeks was 37% for EFA > = 0.60 (n = 170), 36% for 0.40-0.59 (n = 182), 39% for 0.30-0.39 (n = 112), 35% for 0.20-0.29 (n = 87), and 50% for those with EFA < 0.20 CFU/mL/day (n = 187). The hazard ratio for 18-week mortality, comparing those with EFA < 0.20 to those with EFA > = 0.20, was 1.60 (95% confidence interval, 1.25, 2.04; P = .002). The lowest EFA group had lower median CD4 T-cell counts (P < .01) and lower proportion of patients with CSF pleocytosis (P < .001). EFA is associated with all-cause mortality in cryptococcal meningitis. An EFA threshold of > = 0.20 log10 CFU/mL/day was associated with similar 18-week mortality (37%) compared to 50% mortality with EFA < 0.20. This EFA threshold may be considered a target for a surrogate endpoint. This builds upon existing studies to validate EFA as a surrogate endpoint.

Co-Infections in People with COVID-19: A Systematic Review and Meta-Analysis

Background: In previous influenza pandemics, bacterial co-infections have been a major cause of mortality. The significance of co-infecting pathogens in COVID-19 is unknown. Methods: We systematically searched for studies of any design which reported numeric data on co-infections in patients with confirmed COVID-19 published from 1 January 2020 to 17 April 2020. The main outcome was the proportion of patients who had a bacterial, fungal or viral co-infection. We included patients of all ages, in all settings. Pooled estimates were derived using random effects meta-analysis where appropriate. The protocol is registered on PROSPERO (CRD4202040178398). Findings: Our search retrieved 1188 records with 30 eligible for inclusion. From 18 studies, the pooled proportion of hospitalised COVID-19 patients with a bacterial co-infection was 7% (95% CI 3-12%, n=2183, I2 =92∙2%). Subgroup analysis indicated a higher proportion of ICU patients with bacterial co-infections than patients in mixed ward/ICU settings (14%, 95% CI 5-26, I2 =74∙7% versus 4%, 95% CI 1-9, I2 = 91∙7%). The commonest bacteria were Mycoplasma pneumonia, Pseudomonas aeruginosa and Haemophilus influenzae. The pooled proportion with a viral co-infection was 3% (95% CI 1-6, n=1014, 16 studies, I2 =62∙3%), with Respiratory Syncytial Virus and influenza A the commonest. Ascertainment of outcomes was a potential cause of bias in most studies as many patients remained hospitalised at censor date. Interpretation: A low proportion of patients with COVID-19 have a bacterial co-infection; much less than in previous influenza pandemics. These findings do not support the routine use of antibiotics in the management of confirmed COVID-19 infection. Funding Statement: LL and VB are funded by the National Institute for Health Research (NIHR) Nottingham Biomedical Research Centre, UK. Declaration of Interests: LL, BL and VB declare no competing interests. WSL’s institution has received unrestricted investigated-initiated research funding from Pfizer for an unrelated pneumonia cohort study in which he is the Chief Investigator.