Carotid Duplex Ultrasonography to Assess Severity of Low-Flow Low-Gradient Aortic Stenosis.

BACKGROUND: Patients with low-flow, low-gradient aortic valve stenosis constitute a substantial subset of all severe aortic stenosis patients. However, assessment of true severity of these patients can be challenging. In this analysis, we study the utility of the common carotid artery waveforms to distinguish true from pseudo-severe low-flow low-gradient aortic stenosis. METHODS: This is an observational analysis that included patients who underwent a transthoracic echocardiogram (TTE) and duplex carotid ultrasonography (DCUS) and had low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction (LVEF) on the index TTE (LVEF <50%, calculated aortic valve area [AVA] of ≤1.0 cm2, mean and peak gradient of <40 and <64 mm Hg, respectively, and stroke volume index <35 mL/m2). Patients were classified as pseudo-severe and true-severe aortic stenosis based on additional subsequent testing. Differences in various TTE and DCUS waveform parameters across the aortic valve and the common carotid artery were compared between the 2 groups. RESULTS: The study included 30 patients (60 carotid arteries). Fifteen patients were categorized as pseudo-severe and 15 as true severe aortic stenosis. There were no significant differences in calculated AVA, LVEF, stroke volume/stroke volume index, and Doppler Velocity Index in the 2 groups. Mean and peak gradient were higher in patients with true-severe aortic stenosis. Carotid acceleration time (cAT) was significantly prolonged in patients with true-severe compared with pseudo-severe aortic stenosis. A cAT ≥80 ms was 83.3% sensitive and 83.3% specific for true-severe aortic stenosis. CONCLUSION: cAT acceleration time may be used to distinguish true from pseudo-severe low-flow, low-gradient aortic valve stenosis.

Worsening heart failure: a concept in evolution.

PURPOSE OF REVIEW: Worsening heart failure (WHF) has developed as a unique definition within heart failure (HF) in recent years. It captures the disease as a dynamic process. This review describes what is currently known about WHF, why it should be considered a discrete scientific endpoint, and future directions for research. RECENT FINDINGS: There is no single agreed upon definition for WHF. It can be identified as being due to treatment side-effects, related to concomitant comorbidity, or true disease progression. Risk scores based on criteria like those already developed for HF can be created to stratify risk for WHF. CONCLUSIONS: WHF is an emerging entity within HF that defines itself as a unique point of interest. Understanding it as a clinical measure of where a patient's HF is evolving allows for identifying patients that require a refreshed approach to their care. Keeping this in mind will help redefine more patient-centric outcome measures in research to come.

Management of nondysplastic Barrett's esophagus: When to survey? When to ablate?

Barrett's esophagus (BE), a precursor for esophageal adenocarcinoma (EAC), is defined as salmon-colored mucosa extending more than 1 cm proximal to the gastroesophageal junction with histological evidence of intestinal metaplasia. The actual risk of EAC in nondysplastic Barrett's esophagus (NDBE) is low with an annual incidence of 0.3%. The mainstay in the management of NDBE is control of gastroesophageal reflux disease (GERD) along with enrollment in surveillance programs. The current recommendation for surveillance is four-quadrant biopsies every 2 cm (or 1 cm in known or suspected dysplasia) followed by biopsy of mucosal irregularity (nodules, ulcers, or other visible lesions) performed at 3- to 5-year intervals. Challenges to surveillance include missed cancers, suboptimal adherence to surveillance guidelines, and lack of strong evidence for efficacy. There is minimal role for endoscopic eradication therapy in NDBE. The role for enhanced imaging techniques, artificial intelligence, and risk prediction models using clinical data and molecular markers is evolving.

Prediction of mortality among patients with chronic kidney disease: A systematic review.

BACKGROUND: Chronic kidney disease (CKD) is a common medical condition that is increasing in prevalence. Existing published evidence has revealed through regression analyses that several clinical characteristics are associated with mortality in CKD patients. However, the predictive accuracies of these risk factors for mortality have not been clearly demonstrated. AIM: To demonstrate the accuracy of mortality predictive factors in CKD patients by utilizing the area under the receiver operating characteristic (ROC) curve (AUC) analysis. METHODS: We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through January 2021. Studies were included based on the following criteria: (1) Study nature was observational or conference abstract; (2) Study populations involved patients with non-transplant CKD at any CKD stage severity; and (3) Predictive factors for mortality were presented with AUC analysis and its associated 95% confidence interval (CI). AUC of 0.70-0.79 is considered acceptable, 0.80-0.89 is considered excellent, and more than 0.90 is considered outstanding. RESULTS: Of 1759 citations, a total of 18 studies (n = 14579) were included in this systematic review. Eight hundred thirty two patients had non-dialysis CKD, and 13747 patients had dialysis-dependent CKD (2160 patients on hemodialysis, 370 patients on peritoneal dialysis, and 11217 patients on non-differentiated dialysis modality). Of 24 mortality predictive factors, none were deemed outstanding for mortality prediction. A total of seven predictive factors [N-terminal pro-brain natriuretic peptide (NT-proBNP), BNP, soluble urokinase plasminogen activator receptor (suPAR), augmentation index, left atrial reservoir strain, C-reactive protein, and systolic pulmonary artery pressure] were identified as excellent. Seventeen predictive factors were in the acceptable range, which we classified into the following subgroups: predictors for the non-dialysis population, echocardiographic factors, comorbidities, and miscellaneous. CONCLUSION: Several factors were found to predict mortality in CKD patients. Echocardiography is an important tool for mortality prognostication in CKD patients by evaluating left atrial reservoir strain, systolic pulmonary artery pressure, diastolic function, and left ventricular mass index.

Hepatitis E in solid organ transplant recipients: A systematic review and meta-analysis.

BACKGROUND: Hepatitis E virus (HEV) infection is underdiagnosed due to the use of serological assays with low sensitivity. Although most patients with HEV recover completely, HEV infection among patients with pre-existing chronic liver disease and organ-transplant recipients on immunosuppressive therapy can result in decompensated liver disease and death. AIM: To demonstrate the prevalence of HEV infection in solid organ transplant (SOT) recipients. METHODS: We searched Ovid MEDLINE, EMBASE, and the Cochrane Library for eligible articles through October 2020. The inclusion criteria consisted of adult patients with history of SOT. HEV infection is confirmed by either HEV-immunoglobulin G, HEV-immunoglobulin M, or HEV RNA assay. RESULTS: Of 563 citations, a total of 22 studies (n = 4557) were included in this meta-analysis. The pooled estimated prevalence of HEV infection in SOT patients was 20.2% [95% confidence interval (CI): 14.9-26.8]. The pooled estimated prevalence of HEV infection for each organ transplant was as follows: liver (27.2%; 95%CI: 20.0-35.8), kidney (12.8%; 95%CI: 9.3-17.3), heart (12.8%; 95%CI: 9.3-17.3), and lung (5.6%; 95%CI: 1.6-17.9). Comparison across organ transplants demonstrated statistical significance (Q = 16.721, P = 0.002). The subgroup analyses showed that the prevalence of HEV infection among SOT recipients was significantly higher in middle-income countries compared to high-income countries. The pooled estimated prevalence of de novo HEV infection was 5.1% (95%CI: 2.6-9.6) and the pooled estimated prevalence of acute HEV infection was 4.3% (95%CI: 1.9-9.4). CONCLUSION: HEV infection is common in SOT recipients, particularly in middle-income countries. The prevalence of HEV infection in lung transplant recipients is considerably less common than other organ transplants. More studies examining the clinical impacts of HEV infection in SOT recipients, such as graft failure, rejection, and mortality are warranted.

The clinical impacts of sleep apnea on mortality and allograft function in kidney transplant patients: A meta-analysis.

BACKGROUND: Sleep apnea (SA) is common in patients with advanced chronic kidney disease. However, its prevalence and clinical significance in kidney transplant patients are unknown. OBJECTIVE: To demonstrate the clinical impacts of SA on kidney allograft and mortality from current evidence to date. MATERIALS AND METHODS: Ovid -MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications. Kidney transplant recipients aged ≥ 18 years with SA were included. The outcomes included overall mortality, graft failure, and graft loss. Graft loss was attributed by either 1) graft failure requiring renal replacement therapy (RRT)or 2) death. RESULTS: Four observational studies (n = 5,259) were included in the meta-analyses. The mean age was 49.6 ± 0.4 years. Most patients were male (58.3%) and white (82.1%). Up to 25.1% had diabetes, 15.2% had SA, and 36.8% had history of smoking. The mean body mass index was 26.9 ± 0.9 kg/m2. With the mean follow-up duration of 14.4 ± 4.2 years, the pooled adjusted odds ratios (ORs) for graft failure and mortality among kidney transplant patients with SA were 1.061 (95% CI, 0.851 - 1.322; I2 = 41.3%) and 1.044 (95% CI, 0.853 - 1.278; I2 = 0%), respectively. The pooled adjusted OR for graft loss was 0.837 (95% CI, 0.597 - 1.173; I2 = 0%). On subgroup analyses, the ORs for graft failure were similar after adjusted by study year, country, study design, sample size, ethnicity, and sex. No potential publication bias was detected. CONCLUSION: With 14-year follow-up, SA in kidney transplant patients was not associated with worsening clinical and allograft outcomes, such as graft loss, graft failure, and mortality. However, additional observational studies are needed to confirm this finding.

Bidirectional association between chronic kidney disease and sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Previous data have suggested a link between chronic kidney disease (CKD) and sleep apnea (SA). However, the prevalence and risk association of both disease entities are not uniformly described. METHODS: Ovid MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications that included patients aged ≥ 18 years diagnosed with CKD or SA. Included studies were divided into two cohorts: (1) a cohort of CKD or end-stage kidney disease (ESKD) patients reporting the prevalence of SA or odds ratio (OR) for SA (CKD cohort) and (2) a cohort of SA patients reporting the prevalence of CKD/ESKD or OR for CKD/ESKD (SA cohort). RESULTS: CKD cohort: Of 16 studies (n = 340,587), the pooled estimated prevalence of SA among CKD/ESKD patients was 47.5% (95% CI 28.8-66.9). The pooled adjusted OR for SA among CKD/ESKD patients was 1.961 (95% CI 1.702-2.260). Male sex, history of diabetes, and lower BMI were associated with increased prevalence of SA. SA cohort: Of 12 studies (n = 3,103,074), the pooled prevalence of CKD/ESKD among patients with SA was 8.2% (95% CI 4.7-13.7), whereas the pooled adjusted OR for CKD/ESKD among patients with SA was 2.088 (95% CI 1.777-2.452). Increasing age, higher BMI, male sex, white race, and history of diabetes were associated with higher prevalence of CKD/ESKD. CONCLUSION: There was a bidirectional association between CKD/ESKD and SA. Interventions aiming to prevent the progression of either CKD or SA are important.

Incidence and Impacts of Inflammatory Bowel Diseases among Kidney Transplant Recipients: A Meta-Analysis.

BACKGROUND: The incidence of inflammatory bowel diseases (IBD) and its significance in kidney transplant recipients is not well established. We conducted this systematic review and meta-analysis to assess the incidence of and complications from IBD in adult kidney transplant recipients. METHODS: Eligible articles were searched through Ovid MEDLINE, EMBASE, and the Cochrane Library from inception through April 2020. The inclusion criteria were adult kidney transplant patients with reported IBD. Effect estimates from the individual studies were extracted and combined using the fixed-effects model when I2 ≤ 50% and random-effects model when I2 > 50%. RESULTS: of 641 citations, a total of seven studies (n = 212) were included in the systematic review. The mean age was 46.2 +/- 6.9 years and up to 51.1% were male. The mean duration of follow-up was 57.8 +/- 16.8 months. The pooled incidence of recurrent IBD was 27.6% (95% CI, 17.7-40.5%; I2 0%) while the pooled incidence of de novo IBD was 18.8% (95% CI, 10.7-31.0%; I2 61.3%). The pooled incidence of post-transplant IBD was similar across subgroup analyses. Meta-regression analyses showed no association between the incidence of IBD and age, male sex, and follow-up duration. For post-transplant complications, the pooled incidence of post-transplant infection was 4.7% (95% CI, 0.5-33.3%; I2 73.7%). The pooled incidence of graft rejection and re-transplantation in IBD patients was 31.4% (95% CI, 14.1-56.1%; I2 76.9%) and 30.4% (95% CI, 22.6-39.5%; I2 0%). CONCLUSION: Recurrent and de novo IBD is common among kidney transplant recipients and may result in adverse outcomes.

The Use of Transient Elastography Technology in the Bariatric Patient: a Review of the Literature.

Transient elastography (TE) is a non-invasive technology that demonstrates promise in assessing liver steatosis and fibrosis without the risks of traditional percutaneous liver biopsy. Many studies have examined its reliability in respect to liver biopsy, but fewer have examined using TE in obese and bariatric surgery patients. With evidence showing that bariatric surgery can lead to improvement of liver steatosis and fibrosis, TE has the potential to provide a simple avenue of hepatic assessment in patients before and after procedures. This review article investigates what is known about the reliability of TE and its implementation in obese and bariatric surgery patients.

Triple-Negative Essential Thrombocythemia Complicated by Thrombosis and Acquired von Willebrand Disease in a Young Man.

BACKGROUND Essential thrombocythemia (ET) is a type of myeloproliferative neoplasm (MPN) characterized by sustained thrombocytosis in peripheral blood. Patients typically have gene mutations like JAK2V617F, CALR, and MPLW515L/K. This report describes a young man with ET without any of the above mutations who had paradoxical bleeding due to acquired Von-Willebrand disease. CASE REPORT A young man with a medical history of thrombocytosis on aspirin presented with acute chest pain and was found to have had a myocardial infarction. Emergency cardiac catheterization revealed a thrombotic occlusion of the left anterior descending (LAD) artery and the right posteriolateral system, with an ejection fraction of 25%. He underwent thrombectomy and balloon angioplasty with LAD stenting, and an Impella 2.5 was inserted due to severe left ventricular dysfunction with akinesia. Aspirin and ticagrelor were administered, but the patient later experienced postoperative bleeding from the site of the Impella device. The bleeding was attributed to acquired Von-Willebrand disease secondary to ET. Emergency plateletpheresis was recommended. Further workup demonstrated that he was triple-negative for JAK2, MPL, and CALR gene mutations. CONCLUSIONS The paradoxical bleeding resulting from acquired Von-Willebrand disease was likely an entirely separate entity from the hyper-thrombotic state expected from ET. Careful assessment of clinical symptoms and laboratory markers, in addition to a high degree of suspicion, are needed to diagnose acquired Von-Willebrand disease as a complication of ET.

Chronic kidney disease and concomitant sleep apnea are associated with increased overall mortality: a meta-analysis.

PURPOSE: Sleep apnea (SA) is common in advanced chronic kidney disease (CKD) patients. However, the association between CKD with concomitant SA and overall mortality remains inconclusive. METHODS: Ovid MEDLINE, EMBASE, and the Cochrane Library were searched for eligible publications, including non-transplant CKD patients aged > 18 years with co-existing SA. CKD is defined by estimated glomerular filtration rate of < 60 mL/min/1.73 m2. RESULTS: Seven observational studies (n = 186,686) were included in the meta-analyses. 94.2% had end-stage kidney disease (ESKD) requiring hemodialysis (HD), 5.0% had ESKD requiring peritoneal dialysis (PD), and 0.8% had non-dialysis CKD. The mean age was 76.8 ± 2.2 years. Most patients were male (53.4%) and white (76.8%). Up to 39.3% had diabetes. The mean body mass index was 26.0 ± 0.6 kg/m2. Among patients with advanced CKD and SA, the pooled estimated odds ratios (OR) for overall mortality and cardiovascular events were 2.092 (95% CI, 1.594-2.744) and 1.020 (95% CI, 0.929-1.119), respectively, compared to patients with CKD alone. The OR was 2.145 (95% CI, 1.563-2.944) when studies with polysomnography-diagnosed SA were examined independently. No potential publication bias was detected. There were no significant differences in odds ratios for overall mortality, based on subgroup analyses. CONCLUSION: Co-existence between advanced CKD and SA is associated with increased overall mortality, but not cardiovascular (CV) events when compared with CKD alone. The analysis of CV events requires additional studies to confirm our findings. Moreover, clinical interventions aiming to prevent the progression of SA and CKD are encouraged.

Pancytopenia as a Complication of Low-Dose Methotrexate in a Septuagenarian: A Rare Presentation.

Methotrexate (MTX) is an antimetabolite that was initially developed as a chemotherapeutic agent to treat malignancies but later used extensively to treat rheumatological conditions. MTX-induced toxicity is dose- and duration-dependent. Myelosuppression is a rare but fatal complication of MTX that can occur even with low doses used for inflammatory conditions. Multiple factors such as age, renal impairment, and nutritional status increase the risk of developing MTX toxicity. Frequent monitoring of symptoms and lab values are the hallmarks of prompt diagnosis and prevention of complications. Clinicians should have a high degree of suspicion to diagnose pancytopenia secondary to MTX especially in patients with multiple confounding comorbidities. We present the case of a 79-year-old male who presented with mucositis and pancytopenia diagnosed to be secondary to weekly MTX for giant cell arteritis leading to anemia and septic shock causing death.

A meta-analysis of clinical predictors for renal recovery and overall mortality in acute kidney injury requiring continuous renal replacement therapy.

PURPOSE: To determine clinical predictors for continuous renal replacement therapy (CRRT) discontinuation in patients with acute kidney injury (AKI). MATERIALS AND METHODS: Ovid MEDLINE, EMBASE, and Cochrane Library were searched. The protocol is registered on researchregistry.com (reviewregistry909). Our criteria included non-end-stage kidney disease adults who required CRRT for AKI. Renal recovery was defined by CRRT discontinuation. Risk of bias was assessed using ROBINS-I tool. RESULTS: We classified our analyses into renal recovery cohort and overall mortality cohort. All studies were observational. For renal recovery cohort, increasing urine output at time of CRRT discontinuation, elevated initial SOFA score and serum creatinine at CRRT initiation were predictive of renal recovery with OR 1.021 (95%CI = 1.011-1.031), 0.869 (95%CI = 0.811-0.932) and 0.995 (95%CI = 0.996-0.999), respectively. For overall mortality cohort, age and presence of sepsis were significantly associated with overall mortality with OR of 1.028 (95%CI = 1.008-1.048) and 2.160 (95%CI = 0.973-1.932), respectively. CONCLUSIONS: Urine output at CRRT discontinuation, lower initial SOFA score, and lower serum creatinine levels at CRRT initiation were associated with higher likelihood of renal recovery. Increasing age and the presence of sepsis were associated with increased overall mortality from AKI on CRRT. However, there were limited data on co-morbidities which might preclude their inclusion in our analysis.

Efficacy of abatacept treatment for focal segmental glomerulosclerosis and minimal change disease: A systematic review of case reports, case series, and observational studies
.

INTRODUCTION: The efficacy of abatacept has been demonstrated mainly in case reports, case series, and observational studies with small sample size. With current evidence, it is premature to conclude that abatacept is an effective treatment for nephrotic syndrome. MATERIALS AND METHODS: We searched MEDLINE, SCOPUS, and Cochrane Library until December 2019 for studies including patients with focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD) treated with abatacept. Proteinuria recovery and remission were outcomes of interest. Presence of urinary CD80 level of B7-1 staining on kidney biopsies was also reported. RESULTS: A total of 11 studies (n = 32) were included in the systematic review. 60% of patients were male. The median age was 27.5 years (range 5.2 - 72 years). Approximately 90.6% had FSGS, while 9.4% had MCD. With median follow-up of 12 months (IQR 6.38), only 15 patients (46.9%) showed response in proteinuria reduction, and 12 patients (43.8%) achieved remission with abatacept. Serious adverse events were reported in 12.5%. Additionally, we observed that patients with positive B7-1 staining on kidney biopsies had higher odds of achieving remission with abatacept (likelihood ratio 18.25; p < 0.001). We found no significant correlation between elevated CD80 levels and remissions. CONCLUSION: The efficacy of abatacept therapy for FSGS or MCD was only 43.8%. Serious adverse effects are common. However, our study suggested that abatacept should be considered only in patients with positive B7-1 staining on kidney biopsy because these patients tend to respond to treatment.

Extremely High Creatine Kinase Activity in Rhabdomyolysis without Acute Kidney Injury.

BACKGROUND Elevation of creatine kinase (CK) activity has been shown to be predictive of acute kidney injury (AKI) in rhabdomyolysis. Patients with extremely high CK activity with preserved renal function are uncommon. This report describes a case of non-traumatic rhabdomyolysis, with a markedly elevated CK activity, without associated AKI. CASE REPORT A 22-year-old male presented with severe generalized myalgias and darkened urine for 1 week prior to his admission. The patient presented to the Emergency Department with initial CK activity of >40 000 U/L and a serum creatinine level of 0.77 mg/dL. Urinalysis was positive for myoglobinuria. Serum cystatin C confirmed an estimated glomerular filtration rate of 144 mL/min/1.73 m². Several causes of rhabdomyolysis, including viral infections, Lyme disease, viral hepatitis, hypothyroidism, and cocaine abuse were investigated; however, all were negative. He was given a bolus of 2 liters of normal saline and continued on intravenous normal saline at 250 mL/hour throughout his hospital stay. Urine output remained adequate. We were able to quantify his serum CK activity by dilution method, which revealed a serum CK activity of >150 000 U/L. His CK levels consistently trended down with treatment. CONCLUSIONS An extremely high CK activity in rhabdomyolysis may lead to AKI. However, preserved kidney function is possible. Young age, no concurrent cocaine use, and adequate oral fluid hydration may prevent AKI in rhabdomyolysis. Physicians need to remain vigilant for cases of rhabdomyolysis that have not yet caused renal compromise.