Impact of Sequencing Targeted Therapies With High-dose Interleukin-2 Immunotherapy: An Analysis of Outcome and Survival of Patients With Metastatic Renal Cell Carcinoma From an On-going Observational IL-2 Clinical Trial: PROCLAIM

BACKGROUND: This analysis describes the outcome for patients who received targeted therapy (TT) prior to or following high-dose interleukin-2 (HD IL-2). PATIENTS AND METHODS: Patients with renal cell carcinoma (n = 352) receiving HD IL-2 were enrolled in Proleukin RESULTS: Overall, there were 4% complete response (CR), 13% partial response (PR), 39% stable disease (SD), and 43% progressive disease (PD) with HD IL-2. The median overall survival (mOS) was not reached in patients with CR, PR, or SD, and was 15.5 months in patients with PD (median follow-up, 21 months). Sixty-one patients had prior TT before HD IL-2 with an overall response rate (ORR) to HD IL-2 of 19% (1 CR, 9 PR) and an mOS of 22.1 months. One hundred forty-nine patients received TT only after HD IL-2 with an mOS of 35.5 months. One hundred forty-two patients had no TT before or after HD IL-2, and mOS was not reached. The mOS was 8.5 months in PD patients who received HD IL-2 without follow-on TT and 29.7 months in PD patients who received follow-on TT after HD IL-2. CONCLUSIONS: HD IL-2 as sole front-line therapy, in the absence of added TT, shows extended clinical benefit (CR, PR, and SD). Patients with PD after HD IL-2 appear to benefit from follow-on TT. Patients who progressed on TT and received follow-on HD IL-2 experienced major clinical benefit. HD IL-2 therapy should be considered in eligible patients

Frequency of significant fibrosis in various chronic liver diseases: an evaluation with Transient Elastography (TE)

INTRODUCTION: Liver biopsy has long been the gold standard to evaluate liver fibrosis. TE was developed as a non- invasive method to assess liver fibrosis by measuring liver stiffness using shear wave velocity. Many studies have proven its’ effectiveness as a method for evaluating liver fibrosis.1-2 The use of TE in UMMC began in 2013. OBJECTIVE: To determine the frequency and aetiology of liver fibrosis and cirrhosis in our local population METHOD: This was a retrospective study conducted at UMMC. Inclusion criteria was all patients who had TE performed from 1 January 2013 to 31 December 2021. Their demographics, clinical characteristics and TE findings were charted. RESULTS: A total of 3066 patients were included, in which 51.7% were males and 48.3% were females. The median CAP value was 271 dB/m. The median E value was 6.5kPa. 11.2% and 11.3% of patients had significant fibrosis (10.1-14.9kPa) and cirrhosis(≥15kPa) respectively. Non-alcoholic fatty liver disease (NAFLD) was noted to be the most common aetiology for fibrosis (32.8%), followed by chronic hepatitis B (CHB) at 25.2%, chronic hepatitis C (CHC) at 6.7% and alcoholic liver disease (ALD) with 1.3%. This finding was also found to be similar in the cirrhosis group (NAFLD 32.5%, CHB 17.2%, CHC 11.9% and ALD 1.4%). 219 DISCUSSION: Our study shows that the most common cause for significant fibrosis and cirrhosis is NAFLD. This is in contrast with previous studies, that reported the most common aetiology being CHB.3-4 This is likely due to the availability of effective treatment for hepatitis B and C. This may also be attributed to the initiation of the national Hepatitis B vaccination program for newborns and the improvement in blood transfusion safety. CONCLUSION: NAFLD has the greatest frequency of fibrosis compared with other aetiologies of liver disease - mainly as there is no effective treatment, unlike viral hepatitis

Frequency of significant steatosis in various chronic liver diseases: an evaluation with Transient Elastography (TE)

INTRODUCTION: TE was developed as a non-invasive method to assess liver fibrosis and steatosis using shear wave velocity. Many studies have proven its’ effectiveness as a method for evaluating liver fibrosis and steatosis.1-2 OBJECTIVE: To determine the prevalence and aetiology of steatosis in our local population. METHOD: This study was conducted as a retrospective review on all patients who had TE performed at UMMC from 1 January 2013 to 31 December 2021. Their demographics, clinical characteristics and TE findings were charted. RESULTS: A total of 3066 patients were included. 51.7% were males and 48.3% were females. The median CAP value was 271 dB/m. The median E value was 6.5kPa. 61.2% of patients had steatosis, with a staggering number of of these patients having significant steatosis (51.8%). 6.3% of patients had S2 steatosis whereas 45.5% of patients had severe (S3) steatosis. Interestingly, in those with S2 steatosis, 34.7% had chronic hepatitis B (CHB), 31.5% had non-alcoholic fatty liver disease (NAFLD), 5.2% with chronic hepatitis C (CHC) and 1% had alcoholic liver disease (ALD). In the S3 steatosis group, 66.7% had NAFLD, followed by ALD (36.6%), CHB (30.1%) and CHC (27.7%). 221 DISCUSSION: It is important to highlight that a large proportion of our patients has significant steatosis. This is likely in keeping with the global rise of obesity and sedentary lifestyle.3 NAFLD is a 4-decades old nomenclature that does not appropriately address the heterogenous pathogenicity of fatty liver disease. Our study reflects this heterogeneity, as it shows that steatosis often co-exists with other diverse aetiologies. CONCLUSION: Whilst NAFLD clearly has the greatest frequency of severe steatosis, it is also present in other aetiologies. These findings support the new terminology of metabolic associated fatty liver disease (MAFLD), which reflects the fact that NAFLD commonly co-exists with other aetiologies

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Reticulocyte hemoglobin content as a function of iron stores at 35–36 weeks post menstrual age in very premature infants

Background: Premature infants are born with lower iron stores and are at risk for iron deficiency during early infancy. To prevent iron deficiency, premature infants are routinely supplemented with 2 mg/kg/day oral elemental iron. Reticulocyte hemoglobin content (RET-He), a measure of iron deficiency, has not been well evaluated prior to discharge in premature infants. Objectives: Our objectives were to evaluate RET-He and its correlation with serum ferritin (SF), an index of iron stores, at 35–36 weeks postmenstrual age (PMA) in ≤32 weeks gestational age (GA) infants. Methods: We performed a prospective nested study involving 24–32 weeks GA infants who were receiving 2 mg/kg/day oral elemental iron with full enteral feedings at 35–36 weeks PMA. Infants with the following conditions were excluded: craniofacial malformation, chromosomal disorders, TORCH (toxoplasmosis, other infections, rubella, cytomegalovirus, and herpes simplex), culture-proven sepsis, C-reactive protein \u3e5 mg/l within 10 days of iron status assessment, or erythropoietin therapy. SF and RET-He were measured at 35–36 weeks PMA using chemiluminescence immunoassay and Sysmex XN hematology analyzer, respectively. RET-He \u3c27 pg was deemed indicative of iron deficiency. Results: Ninety-eight infants were studied, of which 21 infants had RET-He \u3c27 pg. There was a positive correlation between RET-He and SF (coefficient 0.22, p =.03) that remained significant after controlling for GA (coefficient 0.21, p =.03) and frequency of prior erythrocyte transfusions (coefficient 0.21, p =.03). On stratified analysis, there was a positive correlation between SF and RET-He in females (N = 52, coefficient 0.23, p =.02), but not in males (N = 46, coefficient 0.05). Conclusions: Most premature infants receiving 2 mg/kg/day oral elemental iron are iron replete for erythropoiesis at 35–36 weeks PMA. RET-He increases with an increase in iron stores, suggesting that additional iron supplementation prior to discharge to very premature infants with borderline low RET-He may help prevent iron deficiency during early infancy