Hippocrateon Private Hospital

Abstract Background Ventricular-arterial coupling (VAC) represents a key pathophysiological component for the preservation of left ventricular (LV) contractile efficiency. Increased age, hypertension and evolving atherosclerosis may induce VAC mismatch in asymptomatic severe aortic stenosis (AS). Purpose Purpose of the study was to assess the effect of supine ergometry (Ex) on VAC in AS and to interrogate potential relationship with the clinical outcome. Methods Forty eight AS patients, followed-up on valve clinic in a tertiary center (age 66±12 years), were referred for Ex. AS-related cardiac events (independent decision for surgery, occurrence of AS-related symptoms) during a follow-up of 33±21 months occurred in 19 patients (EV group). The following parameters were estimated noninvasively both at rest-R/Ex: LV ejection fraction (EF:%), strain (SR:%), transmitral E/e ratio, peak transtricuspid systolic pressure, AV mean gradient (meanGR: mmHg), valvuloarterial impedance (Za: mm Hg·ml-1m2), effective arterial elastance (Ea: mmHg/ml), LV endsystolic elastance (Ees: mmHg/ml) and VAC as the ratio Ea/Ees. Results Event (EV) and non-event (nEV) groups had similar % target heart rate at Ex (96±17 vs 100±12), age (66±12 vs 66±12 years), women/men ratio (9/19 vs 14/29), EF-R (55±8 vs 56±7%), SR-R (15.0±4.0 vs 14.5±3.5%), SR-Ex (16±5 vs 17±4%) but lower EF-Ex (59±9 vs 64±6%, p=0.03). EV group had greater meanGR at R (45±16 vs 37±12mmHg, p=0.03), but similar Za both at R and Ex (2.3±1.0 vs 2.0±0.8mm Hg·ml-1m2 and 2.7±0.8 vs 2.7±1.0mm Hg·ml-1m2). EV group had lower Ees at Ex (4.0±2.0 vs 5.6±2.3mmHg/ml, p=0.026) but similar Ees at R (3.0±1.3 vs 3.3±1.5 mmHg/ml) as well Ea both at R and Ex (2.4±1.0 vs 2.6±1.0 mmHg/ml and 2.7±1.0 vs 3.1±1.1 mmHg/ml). Despite similar VAC at R (0.84±0.24 vs 0.79±0.25), EV group showed worsening VAC during Ex (0.75±0.29 vs 0.58±0.12, p=0.01). Binary logistic regression analysis for events, including the different parameters between groups (meanGR, VAC Ex, EF Ex), selected only the VAC Ex (exp(b)=0.01, p=0.02) as independent predictor. ROC event cut off for VAC Ex was 0.69 (area 0.68, p=0.05, sensitivity 0.6 specificity=0.9, figure 1). Kaplan Meier analysis for the greater values of the VAC Ex than 0.69 showed an increased hazard ratio for events (log rank=6.9 p=0.009, figure 2). Conclusion In asymptomatic patients with AS, noninvasive VAC at Ex provides an independent prognostic yield for cardiac outcome from conventional indices of either LV function or hydraulic aortic valve performance.

Abstract Introduction Degenerative aortic stenosis (AS) is a part of a continuum that may also include a reduction in systemic arterial compliance (Ac). Lower Ac affects cardiovascular prognosis but there are scarce data concerning AS and especially during exercise. Purpose Aim of the study was to assess the prognostic role of calculated Ac at rest (R) and during supine ergometry (Ex) in the outcome of asymptomatic severe AS. Methods Forty eight AS patients, followed-up on valve clinic in a tertiary center (age 66±12 years), were referred for Ex. AS-related cardiac events (independent decision for surgery, occurrence of AS-related symptoms) during a follow-up of 33±21 months occurred in 19 patients (EV group). The following parameters were estimated noninvasively both at R/Ex: LV ejection fraction (EF:%), strain (SR:%), transmitral E/e ratio, peak transtricuspid systolic pressure (TRPG: mmHg), AV mean gradient (meanGR: mmHg), valvuloarterial impedance (Za: mm Hg·ml-1m2), peripheral vascular resistance (PVR: Wood units) and arterial compliance (Doppler stoke volume/pulse pressure=Ac: ml/mmHg). Results Event (EV) and non-event (nEV) groups had similar % target heart rate at Ex, (96±17 vs 100±12%), age (66±12 vs 66±12 years), women/men ratio (9/19 vs 14/29), EF-R (55±8 vs 56±7%), ST-R (15.0±4.0 vs 14.5±3.5%), TRPG R/Ex (35±14 vs 30±8 and 60±15 vs 54±11mmHg), SR-Ex (16.0±5.0 vs 17.0±4.0%) but lower EF-Ex (59±9 vs 64±6%, p=0.03). EV group had greater meanGR at R (45±16 vs 37±12mmHg, p=0.03), but similar Za both at R/Ex (2.3±1.0 vs 2.0±0.8 and 2.7±0.8 vs 2.7±1.0mm Hg·ml-1m2 ). PVR at R/Ex was similar (29.3±12.0 vs 32.0±13.0 and 20.5±6.0 vs 22±9.0 Wood). Ac was similar between the 2 groups at R but it showed a greater reduction during Ex in EV group (R: 0.85±0.44 vs 0.92±0.60 and Ex: 0.70±0.60 vs 0.84±0.40, p=0.05). Binary logistic regression analysis for events, including the different parameters between groups (meanGR, Ac-Ex, EF-Ex), selected only EF-Ex [exp(b)=1.15 (1-1.3 p=0.02] as independent predictor. ROC analysis for event provided a cut off for Ac-Ex of 0.56 (area 0.65, sens=0.72, spec=0.60). ROC classification for events was better for age>70 years (cut off 0.52, area 0.82, sens=0.88, spec=0.77-figure 1). Kaplan Meier event analysis for a greater Ac-Ex than 0.56 provided an increased hazard ratio (log rank =8, p=0.003 figure 2). Conclusion Arterial compliance provides prognostic yield for the outcome of asymptomatic severe AS especially in the aged population. The additive value becomes evident when this parameter is calculated during supine ergometry.

Cholangiocarcinoma (CCA) is an invasive cancer accounting for <1% of all cancers and 10–15% of primary liver cancers. Intrahepatic CCA (iCCA) is associated with poor survival rates and high post-surgical recurrence rates whilst most diagnosed patients are not surgical candidates. There is a growing literature suggesting percutaneous ablative techniques for the management of patients with iCCA measuring ≤3 cm with contraindications to surgery as well as for recurrent or residual tumors aiming to provide local cancer treatment and control. Most used ablative therapies for iCCA include radiofrequency and microwave ablation with irreversible electroporation, cryoablation and reversible electroporation (electrochemotherapy) being less commonly encountered techniques. Due to the infiltrative margins of the lesion, there is a need for larger safety margins and ablation zone; multi-apparatus ablation or other variations of the technique such as balloon-assisted approaches can be utilized aiming to increase size of the zone of necrosis. The present review paper focuses upon the current role of percutaneous ablative techniques for the therapeutic management of iCCA. The purpose of this review is to present the current minimally invasive ablative techniques in the treatment of iCCA, including local control and survival rates.

Postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) are common complications following total knee arthroplasty (TKA) and total hip arthroplasty (THA), affecting the length of hospital stay and increasing medical complications. Although many papers have been published on both conditions in this setting, no reviews have currently been written. Thus, the purpose of our study is to summarize the current literature and provide information about POD and POCD following elective THA or TKA. Our literature search was conducted in the electronic databases PubMed and the Cochrane library. We found that POD is a common complication following elective THA or TKA, with a median incidence of 14.8%. Major risk factors include older age, cognitive impairment, dementia, preoperative (pre-op) comorbidities, substance abuse, and surgery for fracture. Diagnosis can be achieved using tools such as the confusion assessment method (CAM), which is sensitive, specific, reliable, and easy to use, for the identification of POD. Treatment consists of risk stratification and the implementation of a multiple component prevention protocol. POCD has a median incidence of 19.3% at 1 week, and 10% at 3 months. Risk factors include older age, high BMI, and cognitive impairment. Treatment consists of reversing risk factors and implementing protocols in order to preserve physiological stability. POD and POCD are common and preventable complications following TKA and THA. Risk stratification and specific interventions can lower the incidence of both syndromes. Every physician involved in the care of such patients should be informed on every aspect of these conditions in order to provide the best care for their patients.

To assess the effects of the combination of SAMe (S-adenosylmethionine) 200 mg and Lactobacillus plantarum (L. plantarum) HEAL9 1 × 10⁹ CFU for the overall symptomatology of mild-to-moderate depression. This 6-week randomized, double-blind, placebo-controlled study included subjects aged 18-60 years with mild-to-moderate depression (according to ICD-10 diagnostic criteria) recruited from September 17, 2018, to October 5, 2018. Difference between groups in change from baseline to treatment week 6 on the Zung Self-Rating Depression Scale (Z-SDS) was the primary outcome. Comparisons between groups in change from baseline to treatment week 2 of the Z-SDS and from baseline to treatment weeks 2 and 6 of other scales (related to insomnia, anxiety, irritable bowel syndrome, and health status) were also analyzed. Ninety patients were randomized to SAMe plus L. plantarum HEAL9 (n = 46) or placebo (n = 44) groups. A greater reduction for the new combination compared to placebo was seen at treatment week 6 in the Z-SDS total score (P = .0165) and the core depression subdomain (P = .0247). A significant reduction in favor of the combination was shown at treatment week 2 for the Z-SDS total score (P = .0330), the cognitive and anxiety subdomains (P = .0133 and P = .0459, respectively), and the anxiety questionnaire (P = .0345). No treatment-related adverse events occurred. Supplementation of SAMe and L. plantarum HEAL9 in adults with subthreshold or mild-to-moderate symptoms of depression resulted in fast and clinically relevant effects after 2 weeks. The combination was safe and significantly improved symptoms of depression, anxiety, and cognitive and somatic components. The effect of this novel product is independent from the severity of the symptoms unlike traditional antidepressants available on the market that have minimal benefits for subthreshold or mild-to-moderate symptoms. ClinicalTrials.gov identifier: NCT03932474.

BackgroundRecent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms.MethodsWe looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD). Two variants were genotyped in a cohort of well-studied adult TBMN patients from 19 Greek-Cypriot families, with a homogeneous genetic background. Patients were categorized as “Severe” or “Mild”, based on the presence or not of proteinuria, CRF and ESRD. A larger pooled cohort (HEMATURIA) of 524 patients, including IgA nephropathy patients, was used for verification. Additionally, three large general population cohorts [Framingham Heart Study (FHS), KORAF4 and SAPHIR] were used to investigate if the NEPH3-V353M variant has any renal effect in the general population.Results and conclusionsGenotyping for two high-scored variants in 103 TBMN adult patients with founder mutations who were classified as mildly or severely affected, pointed to an association with variant NEPH3-V353M (filtrin). This promising result prompted testing in the larger pooled cohort (HEMATURIA), indicating an association of the 353M variant with disease severity under the dominant model (p = 3.0x10-3, OR = 6.64 adjusting for gender/age; allelic association: p = 4.2x10-3 adjusting for patients’ kinships). Subsequently, genotyping 6,531 subjects of the Framingham Heart Study (FHS) revealed an association of the homozygous 353M/M genotype with microalbuminuria (p = 1.0x10-3). Two further general population cohorts, KORAF4 and SAPHIR confirmed the association, and a meta-analysis of all three cohorts (11,258 individuals) was highly significant (p = 1.3x10-5, OR = 7.46). Functional studies showed that Neph3 homodimerization and Neph3-Nephrin heterodimerization are disturbed by variant 353M. Additionally, 353M was associated with differential activation of the unfolded protein response pathway, when overexpressed in stressed cultured undifferentiated podocyte cells, thus attesting to its functional significance. Genetics and functional studies support a “rare variant-strong effect” role for NEPH3-V353M, by exerting a negative modifier effect on primary glomerular hematuria. Additionally, genetics studies provide evidence for a role in predisposing homozygous subjects of the general population to micro-albuminuria.

The relationship between bone and skeletal muscle mass may be affected by physical training. No studies have prospectively examined the bone and skeletal muscle responses to a short controlled exercise-training programme. We hypothesised that a short exercise-training period would affect muscle and bone mass together. Methods: Femoral bone and Rectus femoris Volumes (RFVOL) were determined by magnetic resonance imaging in 215 healthy army recruits, and bone mineral density (BMD) by Dual X-Ray Absorptiometry (DXA) and repeated after 12 weeks of regulated physical training. Results: Pre-training, RFVOL was smaller in smokers than non-smokers (100.9 ± 20.2 vs. 108.7 ± 24.5, p = 0.018; 96.2 ± 16.9 vs. 104.8 ± 21.3, p = 0.002 for dominant/non-dominant limbs), although increases in RFVOL with training (of 14.2 ± 14.5% and 13.2 ± 15.6%] respectively, p < 0.001) were independent of prior smoking status. Pre-training RFVOL was related to bone cortical volume (r2 = 0.21 and 0.30, p < 0.001 for dominant and non-dominant legs), and specifically to periosteal (r2 = 0.21 and 0.23, p < 0.001) volume. Pre-training dominant RFVOL was independently associated with Total Hip BMD (p < 0.001). Training-related increases in RFVOL and bone volumes were related. Whilst smokers demonstrated lower muscle mass than non-smokers, differences were abolished with training. Training-related increases in muscle mass were related to increases in periosteal bone volume in both dominant and non-dominant legs.