Recent updates on asymptomatic and symptomatic aortic valve stenosis its diagnosis, pathogenesis, management and future perspectives.

Aortic stenosis (AS) is very common in mid-aged and elderly patients, and it has been reported to have a negative impact on both short and long-term survival with a high mortality rate. The current study identified methods of diagnosis, incidence, and causes of AS, pathogenesis, intervention and management and future perspectives of Asymptomatic and Symptomatic Aortic stenosis. A systematic literature search was conducted using PubMed, Scopus and CINAHL, using the Mesh terms and key words "Aortic stenosis", "diagnostic criteria", "pathogenesis", "incidence and causes of AS" and" intervention and management strategies". Studies were retained for review after meeting strict inclusion criteria that included studies evaluating Asymptomatic and Symptomatic AS. Studies were excluded if duplicate publication, overlap of patients, subgroup studies of a main study, lack of data on AS severity, case reports and letters to editors. Forty-five articles were selected for inclusion. Incidence of AS across the studies ranged from 3 % to 7 %. Many factors have been associated with incidence and increased risk of AS, highest incidence of AS was described after aortic valve calcification, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve and other factors. AS is common and can be predicted by aortic root calcification volume, rheumatic heart disease, degenerative aortic valve disease, bicuspid aortic valve. Intervention and management for AS patients is a complex decision that takes into consideration multiple factors. On the other hand, there is not enough progress in preventive pharmacotherapy to slow the progression of AS.

Propensity score-matched analysis of 1-year outcomes of transcarotid revascularization with dynamic flow reversal, carotid endarterectomy, and transfemoral carotid artery stenting.

OBJECTIVE: Initial studies showed no significant differences in perioperative stroke or death between transcarotid artery revascularization (TCAR) and carotid endarterectomy (CEA) and lower stroke/death rates after TCAR compared with transfemoral carotid artery stenting (TFCAS). This study focuses on the 1-year outcomes of ipsilateral stroke or death after TCAR, CEA, and TFCAS. METHODS: All patients undergoing TCAR, TFCAS, and CEA between September 2016 and December 2019 were identified in the Vascular Quality Initiative (VQI) database. The latest follow-up was September 3, 2020. One-to-one propensity score-matched analysis was performed for patients with available 1-year follow-up data for TCAR vs CEA and for TCAR vs TFCAS. Kaplan-Meier survival and Cox proportional hazard regression analyses were used to evaluate 1-year ipsilateral stroke or death after the three procedures. RESULTS: A total of 41,548 patients underwent CEA, 5725 patients underwent TCAR, and 6064 patients underwent TFCAS during the study period and had recorded 1-year outcomes. The cohorts were well-matched in terms of baseline demographics and comorbidities. Among 4180 TCAR vs CEA matched pairs of patients, there were no significant differences in 30-day stroke, death, and stroke/death. However, TCAR was associated with a lower risk of 30-day stroke/death/myocardial infarction (2.30% vs 3.25%; relative risk, 0.71; 95% confidence interval [CI], 0.55-0.91; P = .008), driven by a lower risk of myocardial infarction (0.55% vs 1.12%; hazard ratio [HR], 0.49; 95% CI, 0.30-0.81; P = .004). At 1 year, no significant difference was observed in the risk of ipsilateral stroke or death (6.49% vs 5.68%; HR, 1.14; 95% CI, 0.95-1.37; P = .157). Among 4036 matched pairs in the TCAR vs TFCAS group, TCAR was also associated with lower risk of perioperative stroke or death compared with TFCAS (1.83% vs 2.55%; HR, 0.72; 95% CI, 0.54-0.96; P = .027). At 1 year, the risks of ipsilateral stroke or death of TCAR and TFCAS were comparable (6.07% vs 7.07%; HR, 0.85; 95% CI, 0.71-1.01; P = .07). Symptomatic status did not modify the association in TCAR vs CEA. However, asymptomatic patients had favorable outcomes with TCAR vs TFCAS at 1 year (HR, 0.78; 95% CI, 0.62-0.98; P = .033). CONCLUSIONS: In this propensity score-matched analysis, no significant differences in ipsilateral stroke/death-free survival were observed between TCAR and CEA or between TCAR and TFCAS. The advantages of TCAR compared with TFCAS seem to be mainly in the perioperative period, which makes it a suitable minimally invasive option for surgically high-risk patients with carotid artery stenosis. Larger studies, with longer follow-up and data on restenosis, are warranted to confirm the mid- and long-term benefits and durability of TCAR.

Statin Use and Lower Urinary Tract Symptoms Incidence and Progression in Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial.

PURPOSE: Benign prostatic hyperplasia (BPH) is a common disease often manifested by lower urinary tract symptoms (LUTS). We previously found statins were associated with modest attenuations in prostate growth over time in REDUCE. We tested whether statins were associated with LUTS incidence in asymptomatic men and LUTS progression in symptomatic men. MATERIALS AND METHODS: We performed a post-hoc analysis of REDUCE in 3,060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) <8 and in 2,198 symptomatic men with baseline IPSS ≥8 not taking α-blockers or 5α-reductase inhibitors. We used multivariable Cox regression models to assess associations between statin use at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first reported medical or surgical treatment for BPH or sustained clinically significant LUTS (2 reports of IPSS >14). Among symptomatic men, LUTS progression was defined as IPSS increase ≥4 points from baseline, any surgical procedure for BPH, or initiation of a BPH drug. RESULTS: Among asymptomatic and symptomatic men, 550 (18%) and 392 (18%) used statins at baseline, respectively. On multivariable analysis, statin use was not associated with LUTS incidence (HR 1.05; 95% CI 0.78-1.41, p=0.74) in asymptomatic men, or with LUTS progression (HR 1.13; 95% CI 0.96-1.33, p=0.15) in symptomatic men. Similar results were seen in the dutasteride and placebo arms when stratified by treatment assignment. CONCLUSIONS: In REDUCE, statin use was not associated with either incident LUTS in asymptomatic men or LUTS progression in symptomatic men. These data do not support a role for statins in LUTS prevention or management.

Disease-Based Risk Stratification of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis for Common Bile Duct Stones.

BACKGROUND: Risk stratification of postendoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) for common bile duct (CBD) stones is needed for clinicians to adequately explain to patients regarding the risk of PEP in advance of ERCP and to proactively take preventive measures in high-risk patients. AIMS: To stratify the risk of PEP for CBD stones based on CBD-related diseases. METHODS: A total of 1551 patients with naïve papilla who underwent ERCP for CBD stones were divided into three groups: Group A: asymptomatic CBD stones, Group B: obstructive jaundice and elevated liver test values without cholangitis, and Group C: mild, moderate, and severe cholangitis. We stratified the risk of PEP by comparing its incidence among the three groups using the Holm's method. Furthermore, we performed one-to-one propensity score matching between Group A and the other groups to examine the risk of PEP in Group A. RESULTS: The incidence rates in Groups A, B, and C were 13.7%, 7.3%, and 1.8%, respectively. The Holm-adjusted p values between Groups A and B, Groups A and C, and Groups B and C were 0.023, < 0.001, and < 0.001, respectively. Propensity score matching revealed that the incidence of PEP was significantly more in Group A than in the other groups (13.3% vs. 1.5%; p < 0.001). CONCLUSIONS: The risk of PEP for CBD stones was stratified into low risk (Group C), intermediate risk (Group B), and high risk (Group A). This simple disease-based risk stratification may be useful to predict the risk of PEP in advance of ERCP.

Screening for Asymptomatic Urinary Retention in Older Adult Men at Admission to the Internal Medicine Department: A Prospective Study.

BACKGROUND: Screening for asymptomatic urinary retention (AUR) in older adult men at hospital admission to the internal medicine department has never been studied. OBJECTIVES: To assess the incidence of AUR in older adult men at hospital admission, its risk factors, and its outcome. METHODS: The study comprised 111 older adult men aged ≥ 75 years who were admitted to three internal medicine departments. All men underwent post-void residual (PVR) urine volume measurement on the morning following admission by using a portable ultrasound bladder scan. AUR was defined as a PVR urine volume of ≥ 200 ml without symptoms. Men with AUR had a follow-up phone call concerning symptoms and urinary catheter status30 days following hospitalization. RESULTS: Seven (6.3%) men had AUR. Relative to the 104 men without AUR, they had significantly higher prevalence of severe dependency (6/7 vs. 33/104, 85.7% vs. 31.7%, (P = 0.007), cognitive impairment (5/7 vs. 19/104, 71.4% vs. 18.3%, P = 0.005), and use of anticholinergic agents (4/7 vs. 19/104, 57.1% vs. 18.3%, P = 0.033). A urinary catheter was inserted in one man (14.3%), but it was removed later during hospitalization. No symptoms were reported and no urinary catheter was inserted following hospitalization in men with AUR. CONCLUSIONS: AUR in older adult men at hospital admission is uncommon and has a favorable outcome. Hence, screening for AUR in all older adult men at admission is not recommended, but it may be considered in severely dependent older adult men with cognitive impairment who use anticholinergic agents.

Optimal Medical Management of Asymptomatic Carotid Stenosis.

Asymptomatic carotid stenosis (ACS) due to atherosclerosis is a risk factor for ipsilateral ischemic cerebrovascular events and cognitive impairment. The prognosis of ACS has improved over the past 4 decades due largely to improvements in medical management. Most patients with ACS can be managed without revascularization, but some patients with vulnerable plaque should be considered for revascularization. Regardless of the decision to refer for revascularization, all patients with ACS should receive intensive medical management. This includes lifestyle modification (Mediterranean diet, exercise, and smoking cessation) and pharmacological therapy (antiplatelets, lipid-lowering agents, blood pressure reduction, and glycemic control). Patients with ACS often have atherosclerosis in other critical locations, and thus optimal medical therapy is likely to reduce events outside the carotid arteries. The nature of optimal medical therapy is described.

Optimizing Timing of Valve Intervention in Patients With Asymptomatic Severe Valvular Heart Disease.

The management of valvular heart disease has changed dramatically over the past decade with advances in cardiac imaging, the use of novel biomarkers, and the development of transcatheter valve repair and replacement technology. International society guidelines have kept pace to provide recommendations for diagnosis, follow-up, and timing of intervention. The most challenging patient cohort for clinicians are patients with asymptomatic severe disease in whom the optimal timing of intervention can be ill-defined. It is a fine balance between the risks of early intervention on asymptomatic patients and improving patient outcomes by preventing long-term cardiac complications. The key in optimal patient management is gathering the necessary information on patient risk and combining that with the risk, efficacy, and durability of valve interventions to arrive at the appropriate timing for intervention. This group of patients will be the focus of this review as we delve into the natural history, recommended follow-up, and indications for intervention in patients with degenerative aortic and mitral valve disease.

Capillaria hepatica (syn. Calodium hepaticum) as a Cause of Asymptomatic Liver Mass.

Capillaria hepatica (syn. Calodium hepaticum) is a parasitic nematode of rodents, rarely infecting humans. An asymptomatic Israeli adult male with extensive travel history was diagnosed with a liver mass on routine post-thymectomy follow-up. Imaging and computer tomography (CT) guided biopsy were inconclusive. Surgical excision revealed an eosinophilic granuloma with fragments of a nematode suspected to be C. hepatica. Molecular methods verified the diagnosis, and the patient was treated empirically. This is the first case of hepatic capillariasis described in Israel, and the first to be diagnosed using molecular methods.

Natural History of Post-Treatment Kidney Stone Fragments: A Systematic Review and Meta-Analysis.

PURPOSE: We assessed the literature around post-treatment asymptomatic residual stone fragments and performed a meta-analysis. The main outcomes were intervention rate and disease progression. MATERIALS AND METHODS: We searched Ovid®, MEDLINE®, Embase™, the Cochrane Library and ClinicalTrials.gov using search terms: "asymptomatic", "nephrolithiasis", "ESWL", "PCNL", "URS" and "intervention." Inclusion criteria were all studies with residual renal fragments following treatment (shock wave lithotripsy, ureteroscopy or percutaneous nephrolithotomy). Analysis was performed using 'metafor' in R and bias determined using Newcastle-Ottawa scale. RESULTS: From 273 articles, 18 papers (2,096 patients) had details of intervention rate for residual fragments. Aggregate intervention rates for ≤4 mm fragments rose from 19% (20 months) to 22% (50 months), while >4 mm fragments rose from 22% to 47%. Aggregate disease progression rates for ≤4 mm rose from 25% to 47% and >4 mm rose from 26% to 88%. However, there was substantial difference in definition of "disease progression." Meta-analysis comparing >4 mm against ≤4 mm fragments: intervention rate for >4 mm (vs ≤4 mm): OR=1.50 (95% CI 0.70-2.30), p <0.001, I2=67.6%, tau2=0.48, Cochran's Q=11.4 (p=0.02) and Egger's regression: z=3.11, p=0.002. Disease progression rate for >4 mm: OR=0.06 (95% CI -0.98-1.10), p=0.91, I2=53.0%, tau2=0.57, Cochran's Q=7.11 (p=0.07) and Egger's regression: z=-0.75, p=0.45. Bias analysis demonstrated a moderate risk. CONCLUSIONS: Larger post-treatment residual fragments are significantly more likely to require further intervention especially in the long term. Smaller fragments, although less likely to require further intervention, still carry that risk. Notably, there is no significant difference in disease progression between fragment sizes. Patients with residual fragments should be appropriately counselled and informed decision-making regarding further management should be done.

Outcomes in asymptomatic, severe aortic stenosis.

BACKGROUND AND AIM OF THE STUDY: Patients with asymptomatic, severe aortic stenosis are presumed to have a benign prognosis. In this retrospective cohort study, we examined the natural history of contemporary patients advised against aortic valve replacement due to a perceived lack of symptoms. MATERIALS AND METHODS: We reviewed the medical records of every patient given the ICD-10-code for aortic stenosis (I35.0) at Oslo University Hospital, Rikshospitalet, between Dec 1st, 2002 and Dec 31st, 2016. Patients who were evaluated by the heart team due to severe aortic stenosis were categorized by treatment strategy. We recorded baseline data, adverse events and survival for the patients characterized as asymptomatic and for 100 age and gender matched patients scheduled for aortic valve replacement. RESULTS: Of 2341 patients who were evaluated for aortic valve replacement due to severe aortic stenosis, 114 patients received conservative treatment due to a lack of symptoms. Asymptomatic patients had higher mortality than patients who had aortic valve replacement, log-rank p<0.001 (mean follow-up time: 4.0 (SD: 2.5) years). Survival at 1, 2 and 3 years for the asymptomatic patients was 88%, 75% and 63%, compared with 92%, 83% and 78% in the matched patients scheduled for aortic valve replacement. 28 (25%) of the asymptomatic patients had aortic valve replacement during follow-up. Age, previous history of coronary artery disease and N-terminal pro B-type natriuretic peptide (NT-proBNP) were predictors of mortality and coronary artery disease and NT-proBNP were predictors of 3-year morbidity in asymptomatic patients. CONCLUSIONS: In this retrospective study, asymptomatic patients with severe aortic stenosis who were advised against surgery had significantly higher mortality than patients who had aortic valve replacement.

Natural History of Asymptomatic Superior Mesenteric Arterial Stenosis Depends on Coeliac and Inferior Mesenteric Artery Status.

OBJECTIVE: The benefit of preventive treatment for superior mesenteric artery (SMA) stenosis remains uncertain. The latest European Society for Vascular Surgery (ESVS) guidelines remain unclear given the lack of data in the literature. The aim of this study was to evaluate asymptomatic SMA stenosis prognosis according to the presence of associated coeliac artery (CA) and/or inferior mesenteric artery (IMA) stenosis. METHODS: This was a single academic centre retrospective study. The entire computed tomography (CT) database of a single tertiary hospital was reviewed from 2009 to 2016. Two groups were defined: patients with isolated > 70% SMA stenosis (group A) and patients with both SMA and CA and/or IMA > 70% stenosis (group B). Patient medical histories were reviewed to determine the occurrence of mesenteric disease (MD) defined as development of acute mesenteric ischaemia (AMI) or chronic mesenteric ischaemia (CMI). RESULTS: Seventy-seven patients were included. Median follow up was 39 months. There were 24 patients in group A and 53 patients in group B. In group B, eight (10.4%) patients developed MD with a median onset of 50 months. AMI occurred in five patients with a median of 33 months and CMI in three patients with a median of 88 months. Patients of group B developed more MD (0% vs. 15.1%; p = .052). The five year survival rate was 45% without significant difference between groups. CONCLUSION: Patients with SMA stenosis associated with CA and/or IMA seem to have a higher risk of developing mesenteric ischaemia than patients with isolated SMA stenosis. Considering the low life expectancy of these patients, cardiovascular risk factor assessment and optimisation of medical treatment is essential. Preventive endovascular revascularisation could be discussed for patients with non-isolated > 70% SMA stenosis, taking into account life expectancy.

Low-grade ductal carcinoma in situ (DCIS) arising in a fibroadenoma of the breast during 5 years follow-up: A case report.

RATIONALE: Fibroadenoma (FA) is a common type of benign breast tumors but ductal carcinoma in situ (DCIS) rarely arises within this tumor type. PATIENT CONCERNS: This case report presents a non-symptomatic 61-year-old woman with FA that was coincidentally found during a breast cancer screening program performed 5 years ago by her city of residence. She had subsequently been followed-up with mammography and breast ultrasound (US). US showed a slightly enlarged tumor and dynamic magnetic resonance imaging (MRI) indicated malignancy within the FA. DIAGNOSIS: The pathological examination revealed low-grade DCIS within the FA. INTERVENTIONS: The patient underwent a core needle biopsy followed by breast-conserving therapy with sentinel lymph node biopsy and then postoperative radiation therapy. OUTCOMES: Currently, she has been followed-up for 2 years without no signs of recurrence. LESSONS: Careful observation with US followed by dynamic MRI is essential in the early diagnosis of DCIS originating in a FA.

An open label, randomized clinical trial to compare the tolerability and efficacy of ivermectin plus diethylcarbamazine and albendazole vs. diethylcarbamazine plus albendazole for treatment of brugian filariasis in Indonesia.

Improved treatments for lymphatic filariasis (LF) could accelerate the global elimination program for this disease. A triple drug combination of the anti-filarial drugs ivermectin, diethylcarbamazine (DEC) and albendazole (IDA) has been shown to be safe and effective for achieving sustained clearance of microfilariae (Mf) of the filarial parasite Wuchereria bancrofti from human blood. However, the triple drug combination has not been previously been evaluated for treatment of brugian filariasis, which accounts for about 10% of the global LF burden. This hospital-based clinical trial compared the safety and efficacy of IDA with that of the standard treatment (DEC plus albendazole, DA) in persons with Brugia timori infections on Sumba island, Indonesia. Fifty-five asymptomatic persons with B. timori Mf were treated with either a single oral dose of IDA (28 subjects) or with DEC plus albendazole (DA, 27 subjects). Participants were actively monitored for adverse events (AE) for two days after treatment by nurses and physicians who were masked regarding treatment assignments. Passive monitoring was performed by clinical teams that visited participant's home villages for an additional five days. Microfilaremia was assessed by membrane filtration of 1 ml night blood at baseline, at 24h and one year after treatment. IDA was more effective than DA for completely clearing Mf at 24 hours (25/28, 89% vs. 8/27, 30%, P < 0.001). By 12 months after treatment, only one of 27 IDA recipients had Mf in their blood (4%) vs. 10 of 25 (40%) in persons treated with DA (P = 0.002). Approximately 90% of participants had antibodies to recombinant filarial antigen BmR1 at baseline. Antibody prevalence decreased to approximately 30% in both treatment groups at 12 months. About 45% of persons in both treatment groups experienced AE such as fever, muscle aches, lower back, joint and abdominal pain. These were mostly mild and most common during the first two days after treatment. No participant experienced a severe or serious AE. This study showed that IDA was well-tolerated and significantly more effective for clearing B. timori Mf from the blood than DA. Larger studies should be performed to further assess the safety and efficacy of IDA as a mass drug administration regimen to eliminate brugian filariasis. Trial Registration: NCT02899936.

Total vascular resistance increases during volume-unloading in asymptomatic single ventricle patients.

OBJECTIVE: While the surgical stages of single ventricle (SV) palliation serve to separate pulmonary venous and systemic venous return, and to volume-unload the SV, staged palliation also results in transition from parallel to series circulation, increasing total vascular resistance. How this transition affects pressure loading of the SV is as yet unreported. METHODS: We performed a retrospective chart review of Stage I, II, and III cardiac catheterization (CC) and echocardiographic data from 2001-2017 in all SV pts, with focus on systemic, pulmonary, and total vascular resistance (SVR, PVR, TVR respectively). Longitudinal analyses were performed with log-transformed variables. Effects of SVR-lowering medications were analyzed using Wilcoxon rank-sum testing. RESULTS: There were 372 total patients who underwent CC at a Stage I (median age of 4.4 months, n=310), Stage II (median age 2.7 years, n = 244), and Stage III (median age 7.3 years, n = 113). Total volume loading decreases with progression to Stage III (P< 0.001). While PVR gradually increases from Stage II to Stage III, and SVR increases from Stage I to Stage III, TVR dramatically increases with progress towards series circulation. TVR was not affected by use of systemic vasodilator therapy. TVR, PVR, SVR, and CI did not correlate with indices of SV function at Stage III. CONCLUSIONS: TVR steadily increases with an increasing contribution from SVR over progressive stages. TVR was not affected by systemic vasodilator agents. TVR did not correlate with echo-based indices of SV function. Further studies are needed to see if modulating TVR can improve exercise tolerance and outcomes.