Plasmatic tryptophan/large neutral amino acids ratio in domestic dogs is affected by meal composition

Tryptophan (Trp) is involved in the synthesis of serotonin and melatonin and it competes with other large neutral amino acids (LNAAs) for its uptake into the brain [1]. The aim of this study was to assess the impact of three different diets on plasmatic Trp/LNAAs ratio. This study included five female Labrador Retrievers (2 spayed, 8.6 ± 3.8 years old) from the same bloodline, who were usually fed the same commercial dry food once a day. Each dog received three different diets for one single day each. Isocaloric and isonitrogenous diets, with a carbohydrates content of 47% and proteins content of 28% on dry matter basis, were provided in two meals, one in the morning and one after 12 hours. Dogs received the first diet (D1) and then they returned to their normal diet for 30 days. After that “washout” period, dogs were fed with the second diet (D2), and after 30 more days they received the third diet (D3). D1 was composed of a mix of puffed rice, minced meat and olive oil equally divided into the two meals. D2 was made up of two different meals. The morning meal was composed of puffed rice and olive oil, whereas the evening meal consisted of minced meat and olive oil. D3 consisted of two identical meals of the commercial dry food usually consumed by the sample dogs. Blood was collected right before the first meal (t0) and after 2, 4, 6, 8, 10 and 24 hours. Plasma samples were used for HPLC quantification of Trp and other LNAAs (isoleucine + leucine + phenylalanine + tyrosine + valine) using a method described in literature [2]. Their levels and ratios at t0 and after D1, D2 and D3 were compared using a mixed model for repeated measures (p<0.05). Trp concentrations showed no significant difference between D1, D2 and D3 samples at any sampling times. LNAAs levels were similar at t0 in the three experimental days, but they showed different trends depending on the composition of the meal provided. In particular, D2 led to a decrease in LNAAs levels and therefore to higher Trp/LNAAs ratios in the 6 hours period after the provision of carbohydrates. In detail, mean Trp/LNAAs ratio of D2 was statistically higher compared to both D1 and D3 at t2 (D1=0.224; D2=0.306; D3=0.217; p<0.001), t4 (D1=0.225; D2=0.327; D3=0.197; p<0.001), and t6 (D1=0.244; D2=0.303; D3=0.205; p<0.015). In addition, mean Trp/LNAAs ratio after D2 was higher than after D3 also at t8 (D2=0.280; D3=0.206; p<0.001) and t10 (D2=0.294; D3=0.224; p<0.001). The trend was different at t24, when Trp/LNAAs ratio was found to be significantly lower after being fed D2 compared to D1 (D1=0.210; D2=0.155; p=0.041). These results indicate that the diet affects Trp bioavailability. Therefore, it is worthwhile to investigate the effects of diet on Trp bioavailability at the brain level, serotonin and melatonin secretion and the real impact of Trp/LNAAs ratio on dog behaviour

Similar long-term results of mitral valve repair for anterior compared with posterior leaflet prolapse

ObjectiveThe results of mitral valve repair for anterior leaflet prolapse have been less gratifying than those reported for posterior leaflet prolapse. We compared the long-term durability of 2 different surgical techniques: the edge-to-edge repair, which is used for the treatment of anterior leaflet prolapse, and quadrangular resection, which has been adopted for correction of posterior leaflet prolapse.MethodsFrom 1991 through April 2004, 133 patients with anterior leaflet prolapse and 605 with posterior leaflet prolapse caused by degenerative mitral disease underwent valve repair. The edge-to-edge repair was used for correction of anterior leaflet prolapse, and quadrangular resection of the posterior leaflet, with or without sliding plasty, was used for correction of posterior leaflet prolapse. All patients received a concomitant annuloplasty procedure.ResultsNo hospital deaths occurred in the anterior leaflet prolapse group, whereas 2 (0.3%) patients died in the posterior leaflet prolapse group (P = .7). Follow-up was 100% and 97.2% complete in the anterior and posterior leaflet prolapse groups, respectively. At 10 years, overall survival was 91% ± 4.06% for anterior leaflet prolapse and 93.5% ± 1.81% for posterior leaflet prolapse (P = .18), and freedom from cardiac death was 95.8% ± 2.83% for anterior leaflet prolapse and 97.4% ± 0.95% posterior leaflet prolapse (P = .27). Freedom from reoperation was 96% ± 2.3% in the anterior leaflet prolapse group and 96.5% ± 1.18% in the posterior leaflet prolapse group (P = .37). At follow-up (mean, 4.5 ± 3.12 years; range, 1 month-13.2 years), New York Heart Association functional class I or II was documented in 93.2% of patients in the anterior leaflet prolapse group and 92.8% in the posterior leaflet prolapse group (P = .98).ConclusionsThe long-term results of the edge-to-edge repair in the setting of anterior leaflet prolapse are similar to those obtained with quadrangular resection for the treatment of posterior leaflet prolapse

Transapical Mitral Valve Replacement: 1-Year Results of the Real-World Tendyne European Experience Registry.

BACKGROUND Early studies of the Tendyne transcatheter mitral valve replacement (TMVR) showed promising results in a small selective cohort. OBJECTIVES The authors present 1-year data from the currently largest commercial, real-world cohort originating from the investigator-initiated TENDER (Tendyne European Experience) registry. METHODS All patients from the TENDER registry eligible for 1-year follow-up were included. The primary safety endpoint was 1-year cardiovascular mortality. Primary performance endpoint was reduction of mitral regurgitation (MR) up to 1 year. RESULTS Among 195 eligible patients undergoing TMVR (median age 77 years [Q1-Q3: 71-81 years], 60% men, median Society of Thoracic Surgeons Predicted Risk of Mortality 5.6% [Q1-Q3: 3.6%-8.9%], 81% in NYHA functional class III or IV, 94% with MR 3+/4+), 31% had "real-world" indications for TMVR (severe mitral annular calcification, prior mitral valve treatment, or others) outside of the instructions for use. The technical success rate was 95%. The cardiovascular mortality rate was 7% at 30 day and 17% at 1 year (all-cause mortality rates were 9% and 29%, respectively). Reintervention or surgery following discharge was 4%, while rates of heart failure hospitalization reduced from 68% in the preceding year to 25% during 1-year follow-up. Durable MR reduction to ≤1+ was achieved in 98% of patients, and at 1 year, 83% were in NYHA functional class I or II. There was no difference in survival and major adverse events between on-label use and "real-world" indications up to 1 year. CONCLUSIONS This large, real-world, observational registry reports high technical success, durable and complete MR elimination, significant clinical benefits, and a 1-year cardiovascular mortality rate of 17% after Tendyne TMVR. Outcomes were comparable between on-label use and "real-world" indications, offering a safe and efficacious treatment option for patients without alternative treatments. (Tendyne European Experience Registry [TENDER]; NCT04898335)

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis.

peer reviewedOBJECTIVE: To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN: Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES: Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE: All cause mortality. RESULTS: 100 trials in 93,553 patients with 262,090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION: Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment

Acute Delta Hepatitis in Italy spanning three decades (1991–2019): Evidence for the effectiveness of the hepatitis B vaccination campaign

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p &lt; .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p &lt; .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come

Effect of meal composition on tryptophan:large neutral amino acids ratio in dogs

Tryptophan is involved in the synthesis of serotonin and melatonin, and it competes with the other large neutral aminoacids for uptake into the brain. The aim of this study was to assess the impact of meal composition on the plasma ratio between tryptophan and five other large neutral amino acids (5LNAAs): isoleucine, leucine, valine, tyrosine and phenylalanine

Plasma tryptophan/large neutral amino acids ratio in domestic dogs is affected by a single meal with high carbohydrates level

Aim of this study was to evaluate the plasma ratio between L-tryptophan (TRP) and five large neutral amino acids (isoleucine + leucine + phenylalanine + tyrosine + valine) (5LNAAs) after a single meal with high carbohydrates level. Five female Labrador Retrievers were involved. Each dog was fed three different meals: M1 (a mix of puffed rice, minced meat and olive oil), M2 (puffed rice and olive oil) and M3 (commercial dry food usually consumed) once in the morning for one single day every 30 days. Blood was collected right before the first meal (t0) and after 2, 4, 6, 8, 10 and 24 h. Plasma amino acids’ concentrations were measured using an HPLC (High-performance liquid chromatography) method with fluorimetric detection. Plasmatic TRP concentrations showed no significant difference between M1, M2 and M3 samples at any sampling time. M2 led to a decrease in 5LNAAs levels and consequently led to a significant higher TRP/5LNAAs ratios in the 6 h period after the provision of carbohydrates, compared to both M1 and M3. In addition, the mean TRP/5LNAAs ratio was significantly higher in M2 than in M3 at t8 and t10. These results indicate that meal composition affects TRP/5LNAAs ratio and possibly, TRP bioavailability