Long-acting exenatide does not prevent cognitive decline in mild cognitive impairment: a proof-of-concept clinical trial.

PURPOSE: According to preclinical evidence, GLP-1 receptor may be an actionable target in neurodegenerative disorders, including Alzheimer's disease (AD). Previous clinical trials of GLP-1 receptor agonists were conducted in patients with early AD, yielding mixed results. The aim was to assess in a proof-of-concept study whether slow-release exenatide, a long-acting GLP-1 agonist, can benefit the cognitive performance of people with mild cognitive impairment (MCI). METHODS: Thirty-two (16 females) patients were randomized to either slow-release exenatide (n = 17; 2 mg s.c. once a week) or no treatment (n = 15) for 32 weeks. The primary endpoint was the change in ADAS-Cog11 cognitive test score at 32 weeks vs baseline. Secondary endpoints herein reported included additional cognitive tests and plasma readouts of GLP-1 receptor engagement. Statistical analysis was conducted by intention to treat. RESULTS: No significant between-group effects of exenatide on ADAS-Cog11 score (p = 0.17) were detected. A gender interaction with treatment was observed (p = 0.04), due to worsening of the ADAS-Cog11 score in women randomized to exenatide (p = 0.018), after correction for age, scholar level, dysglycemia, and ADAS-Cog score baseline value. Fasting plasma glucose (p = 0.02) and body weight (p = 0.03) decreased in patients randomized to exenatide. CONCLUSION: In patients with MCI, a 32-week trial with slow-release exenatide had no beneficial effect on cognitive performance. TRIAL REGISTRATION NUMBER: NCT03881371, registered on 21 July, 2016.

Can risk rating increase the ability of voluntary deductibles to reduce moral hazard?

Several regulated health insurance markets include the option for consumers to choose a voluntary deductible. An important motive for this option is to reduce moral hazard. In return for a voluntary deductible, consumers receive a premium rebate, which is typically community rated. Under community rating, voluntary deductibles are particularly attractive for low-risk consumers. Since these people use relatively little medical care, the total moral hazard reduction might be relatively small compared to the total healthcare spending. This paper examines the potential moral hazard reduction under risk-rated premiums. We use Chile as a case study due to institutional features that make it a valid benchmark for other countries. Our simulations show that in the presence of self-selection and under a uniform percentage moral hazard reduction across risk types, the absolute moral hazard reduction from a voluntary deductible is indeed expected to be larger in a system with risk-rated premiums than in a system with community-rated premiums. Nevertheless, sensitivity checks show that this conclusion might no longer hold as the percentage moral hazard reduction is lower for high-risk individuals compared to low-risk individuals.

Extracorporeal Membrane Oxygenation for COVID-19: Updated 2021 Guidelines from the Extracorporeal Life Support Organization.

DISCLAIMER: This is an updated guideline from the Extracorporeal Life Support Organization (ELSO) for the role of extracorporeal membrane oxygenation (ECMO) for patients with severe cardiopulmonary failure due to coronavirus disease 2019 (COVID-19). The great majority of COVID-19 patients (>90%) requiring ECMO have been supported using venovenous (V-V) ECMO for acute respiratory distress syndrome (ARDS). While COVID-19 ECMO run duration may be longer than in non-COVID-19 ECMO patients, published mortality appears to be similar between the two groups. However, data collection is ongoing, and there is a signal that overall mortality may be increasing. Conventional selection criteria for COVID-19-related ECMO should be used; however, when resources become more constrained during a pandemic, more stringent contraindications should be implemented. Formation of regional ECMO referral networks may facilitate communication, resource sharing, expedited patient referral, and mobile ECMO retrieval. There are no data to suggest deviation from conventional ECMO device or patient management when applying ECMO for COVID-19 patients. Rarely, children may require ECMO support for COVID-19-related ARDS, myocarditis, or multisystem inflammatory syndrome in children (MIS-C); conventional selection criteria and management practices should be the standard. We strongly encourage participation in data submission to investigate the optimal use of ECMO for COVID-19.

A case of dengue type 3 virus infection imported from Africa to Italy, October 2009.

In October 2009, a traveller returning from Africa to Italy was hospitalised with symptoms suggestive of a haemorrhagic fever of unknown origin. The patient was immediately placed in a special biocontainment unit until laboratory investigations confirmed the infection to be caused by a dengue serotype 3 virus. This case reasserts the importance of returning travellers as sentinels of unknown outbreaks occurring in other countries, and highlights how the initial symptoms of dengue fever resemble those of other haemorrhagic fevers, hence the importance of prompt isolation of patients until a final diagnosis is reached.

Rapid prototyping and clinical testing of a reusable face shield for health care workers responding to the COVID-19 pandemic.

Due to supply chain disruption, the COVID-19 pandemic has caused severe shortages in personal protective equipment (PPE) for health care professionals. Local fabrication based on 3D printing is one way to address this challenge, particularly in the case of simple products such as protective face shields. As a consequence, many public domain designs for face shields have become available. No clear path exists, however, for introducing a locally fabricated and unapproved product into a clinical setting. In a US health care setting, face shields are regulated by the Food and Drug Administration (FDA); similar policies exist in other countries. We describe a research protocol under which rapid iteration on an existing design, coupled with clinical feedback and real-world testing in an emergency department, allowed a face shield to be adopted by the incident command team at a major academic medical center. We describe our design and testing process and provide an overview of regulatory considerations associated with fabrication and testing of face shields and related products. All designs, materials used, testing protocols, and survey results are reported in full to facilitate the execution of similar face shield efforts in other clinical settings. Our work serves as a case study for development of a robust local response to pandemics and other health care emergencies, with implications for healthcare professionals, hospital administrators, regulatory agencies and concerned citizens.

Extracorporeal Life Support Organization Coronavirus Disease 2019 Interim Guidelines: A Consensus Document from an International Group of Interdisciplinary Extracorporeal Membrane Oxygenation Providers.

Disclaimer: The Extracorporeal Life Support Organization (ELSO) Coronavirus Disease 2019 (COVID-19) Guidelines have been developed to assist existing extracorporeal membrane oxygenation (ECMO) centers to prepare and plan provision of ECMO during the ongoing pandemic. The recommendations have been put together by a team of interdisciplinary ECMO providers from around the world. Recommendations are based on available evidence, existing best practice guidelines, ethical principles, and expert opinion. This is a living document and will be regularly updated when new information becomes available. ELSO is not liable for the accuracy or completeness of the information in this document. These guidelines are not meant to replace sound clinical judgment or specialist consultation but rather to strengthen provision and clinical management of ECMO specifically, in the context of the COVID-19 pandemic.

Effects of field bean (Vicia faba L. var. minor) dietary supplementation on plasma thyroid hormones, insulin, insulin-like growth factor-1 concentrations and mohair characteristics in growing Angora goat kids.

Twenty-two Angora kids were used to study the effect of a dietary supplementation with field bean (Vicia faba L. var. minor) on hair follicle activity, mohair characteristics and plasma total thyroxine (T4), triiodothyronine (T3), insulin (INS) and insulin-like growth factor-1 (IGF-1) concentrations. At birth, their mothers were divided in two groups (S: supplemented, C: control), the S group being supplemented with 300 g/head/day of whole field bean. At weaning, diet of kids from S group was supplemented with 80 g/head/day of whole field bean. At weaning, secondary hair follicle activity (S: 0.91 ± 0.01, C: 0.84 ± 0.02, p < 0.01) and staple length (S: 5.82 ± 0.13 cm, C: 5.16 ± 0.14 cm, p < 0.001) were greater in the S group. At 155 days of age, secondary fibre diameter (S: 16.54 ± 0.35 µm, C: 18.09 ± 0.31 µm, p < 0.01) was higher in the C kids. Concentrations of total plasma T4 and T3 were higher (p < 0.001) in S (120 ± 12 and 4.87 ± 0.92 ng/ml respectively) than in C kids (92 ± 8 and 2.97 ± 0.77 ng/ml respectively). At weaning, T4 values were negatively correlated (p < 0.05) with the secondary fibre diameter and the T3/T4 ratio was positively correlated (p < 0.05) with the secondary to primary hair follicle ratio. At 155 days of age, both T3 and T3/T4 values were positively correlated (p < 0.01) with staple length. Plasma INS (0.11 ± 0.03 ng/ml) and total IGF-1 concentrations (232 ± 13 ng/ml) were not affected by diet. Improvements of diet quality in kids positively affected fibre diameter and length and follicle activity rate. We suggest that increased circulating thyroid hormones concentrations, but not those of INS and IGF-1, may contribute to the beneficial actions of nutritional supplementation on anatomical growth and mohair production of kids.

Refractory thyrotoxicosis induced by iodinated contrast agents treated with therapeutic plasma exchange. A case report.

Excess free iodide in the blood (ingested or injected) may cause thyrotoxicosis in patients at risk. Iodinated contrast solutions contain small amounts of free iodide and may be of significance for patients affected by Graves' disease, multinodular goiter or living in areas of iodine deficiency. Herein, we report a 57 elderly woman with a clinical history of multinodular goiter presented with a thyrotoxicosis induced by an iodinate contrast agent used during computed tomography scan. Because of the patient's resistance to conventional antithyroid drugs, she was treated with therapeutic plasma exchange (TPE). TPE is used in the treatment of several immunologic and nonimmunologic disorders. Temporary improvement after TPE in cases with thyrotoxicosis has been reported. In our patient's case, we observed an improvement in the thyroid hormone laboratory values as well as clinical findings. TPE can be an addition treatment when standard therapies for thyrotoxicosis fail providing the clinician with an adjuvant tool for rapid preparation of such a patient for thyroidectomy surgery.

Liver transplantation in HIV-positive patients.

AIMS: The aim of this study was to evaluate the feasibility of liver transplantation (OLT) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) coinfected patients in Italy. METHODS: Between September 2002 and April 2006, 12 HIV(+) coinfected patients (11 men, mean age 42 years) underwent OLT at our Institute. Eleven (91%) patients were HCV-positive and one was hepatitis B virus-positive. Pre-OLT plasma HIV 1-RNA level was undetectable and CD4(+) T-cell count >200 cells/microL for 3 months in all patients. Six patients had to stop highly active antiretroviral therapy (HAART) before OLT because of liver disease severity (n = 2) and for hepato cellular carcinoma (n = 4). RESULTS: The actuarial 1-, 2-, and 3-year survival rates were 83.3%, 58.3%, and 58.3%, respectively, which were significantly lower than those observed among HIV-negative patients transplanted in our center. Six patients are alive with a mean follow-up of 26 months (range: 5 to 46 months). We recorded a low rate of opportunistic infections and rejection. All alive patients have low levels of HIV RNA, and the CD4(+) T-cell counts increased after OLT. Nine patients developed early recurrence of hepatitis C requiring combination therapy with peg-interferon plus ribavirin. Significant improvement in the quality of life was observed in 7/11 patients. CONCLUSIONS: OLT in HIV-positive patients was feasible with good results in the short and medium term. Early severe HCV recurrence may be observed. Key challenges for the management of HIV(+) patients after transplantation included treatment of severe HCV recurrence and attention to the pharmacological interactions of HAART with immunosuppressive drugs.

First-line liver resection and salvage liver transplantation are increasing therapeutic strategies for patients with hepatocellular carcinoma and child a cirrhosis.

AIM: The present study focused on nine patients with hepatocellular carcinoma (HCC) associated with Child A liver cirrhosis undergoing first-line liver resection and salvage liver transplantation (SLT) for liver tumor recurrence. PATIENTS AND METHODS: Forty-six patients with HCC underwent liver transplantation (OLT); 37 (80.5%) were primary liver transplantations (PLTs) and 9 (19.5%) were SLTs. All patients who underwent SLT received minor transabdominal liver resections. RESULTS: The posttransplant 1-, 3-, and 5-year overall survival rates for SLT (88.9%, 88.9%, and 88.9%) were similar to those for PLT (78%, 62.7%, and 62.7%). Four (10.8%) patients in the PLT group had HCC recurrence, while there was zero recurrence in the SLT group. The 1-, 3-, 5-year disease-free survival rates for PLT (89%, 74%, and 74%) were similar to those for SLT (100%, 100%, and 100%). The 1-, 3-, 5-year disease-free survival rates after PLT were 89%, 74%, and 74%, and after SLT were 100%, 100%, and 100%, respectively. The operative mortality, intraperioperative bleeding, operative time, intensive care unit stay, in-hospital stay, and overall incidence of postoperative complications were similar in the two groups. CONCLUSIONS: In our experience, SLT for HCC is a feasible procedure with similar results in terms of overall survival, disease-free survival, and postoperative complications to those reported for patients who underwent PLT at our institute. An important role exists for SLT as shown by the fact that such a strategy has been used in the 20% of the patients undergoing OLT for HCC.

Modified liver hanging maneuver during orthotopic liver transplantation with inferior vena cava preservation: results after 120 consecutive applications.

The outflow venovenous anastomosis represent a crucial aspect during orthotopic liver transplantation (OLT) with inferior vena cava (IVC) preservation. The modified Belghiti liver hanging maneuver applied to the last phase of hepatectomy, lifting the liver, provides a better exposure of the suprahepatic region and allows easier orthogonal clamping of the three suprahepatic veins with a minimal portion of IVC occlusion. The outflow anastomosis constructed with a common cloacae of the three native suprahepatic veins is associated with a lower incidence of graft related venous outflow complications. The procedure planned in 120 consecutive OLT was achieved in 118 (99%). The outflow anastomosis was constructed on the common cloaca of the three hepatic veins in 111/120 cases (92.5%). No major complications were observed (bleeding during tunnel creation, graft outflow dysfunction, etc) except in one patient with acute Budd-Chiari, who successfully underwent retransplantation.

Tenderness evaluation and mineral levels of llama (Lama glama) and alpaca (Lama pacos) meat.

Tenderness and mineral levels were determined in the Longissimus thoracis taken from 20 llama and 30 alpaca males reared in Peru and slaughtered at 25 months of age. Mineral contents were determined using an inductively coupled plasma emission spectrometer. Tenderness evaluation was determined two and seven days post slaughter using a Warner-Bratzler shear force device. Potassium is the mineral with the highest content, with a significant difference (P<0.05) between the two species of camelids. The other mineral contents were, in decreasing order, phosphorus, sodium, magnesium and calcium, in addition to smaller percentages of zinc and iron. Shear force values determined seven days post slaughter were significantly (P<0.01) lower in both the species compared with the results obtained two days post slaughter.

Meat fatty acid composition of llama (Lama glama) reared in the Andean highlands.

This study reports the results of the chemical analysis of the Longissimus thoracis and lumborum taken from 20 llama males, reared in the Andean highlands. The animals were slaughtered at 25 months and had a mean final body weight of 63kg. Llama meat shows a low fat (3.51%) and cholesterol content (56.29mg/100g). The fatty acid composition in llama meat contains 50.34% saturated fatty acids, 42.48% monounsaturated fatty acids and 7.18% polyunsaturated fatty acids. Llama meat appears to be a healthy alternative red meat choice.

Short communication: antimicrobial drug susceptibility of Staphylococcus aureus from subclinical bovine mastitis in Italy.

The antimicrobial susceptibility of 68 Staphylococcus aureus isolates collected during 2004 from milk of cows affected by subclinical mastitis was examined. The antimicrobial agents tested were the beta-lactams, penicillin G, amoxicillin, ampicillin, cloxacillin, amoxicillin + clavulanate, cephalonium, and cefoperazone; and other drugs including lincomycin, oxytetracycline, doxycycline, and kanamycin. Minimum inhibitory concentrations recorded show that only certain beta-lactamase-resistant penicillins (specifically cloxacillin) or penicillin combinations (amoxicillin + clavulanate) were consistently effective against Staph. aureus, whereas the other beta-lactam derivatives and drugs from other pharmacological groups were either moderately effective or ineffective. Thus, beta-lactamase-resistant penicillins are to be considered the antimicrobial agents of choice for treatment of bovine mastitis resulting from infection by Staph. aureus.

[Multicentre observational study on peristomal skin disorders. A proposal classification]. / Studio osservazionale multicentrico sulle alterazioni cutanee post-enterostomie (SACS) Classificazione delle alterazioni peristonali.

Disorders regarding peristomal skin have been more and more investigated in order to establish the impact on quality of life of ostomy patients. The aim of this classification is to provide an objective, standardized tool for the assessment of peristomal skin complication specifically designed on the description and localization of the lesion.

HIV/HCV co-infection: natural history.

HIV and HCV share common transmission pathways, but HCV is more efficiently transmitted through blood than with sexual exposure. Thus HCV coinfection is frequent in HIV seropositives, mainly in those with history of injection drug use and/or transfusion. HIV coinfection increases HCV replication rate, the rate of HCV vertical transmission and accelerates the course of hepatitis C towards cirrhosis and hepatocellular carcinoma. The evidence of an effect of HCV on HIV disease progression is less convincing. The results of several studies suggest that HCV coinfection does not hasten the progression of HIV infection towards AIDS. However two recent studies showed that HCV coinfection is independently associated with a lower restoration of CD4 counts during combination antiretroviral treatment. However this finding should be confirmed by additional studies.

Study of blood flow parameters measured in femoral artery after exercise: correlation with maximum oxygen uptake.

To study the recovery periods of blood flow parameters in muscles after anaerobic exercise, instantaneous and mean blood flow velocity curves were recorded in the femoral artery in 22 sportsmen at rest and during the first 4 min of recovery after exercise (Ruffier-Dickson test). A flat ultrasonic probe connected to a Doppler system (Flow-Tester) was fixed on the skin at the level of the common femoral artery. From Doppler recordings, we calculated periods of recovery (return to baseline) of femoral blood flow velocity (FBFV RP), heart rate (HR RP) and femoral stroke distance (FSD RP). Also, Ruffier-Dickson index (RDI), VO(2)max in mL/kg(-1)/min(-1) and number of training hours were determined. We observed a high correlation between FBFV RP and VO(2)max (p = 0. 0002), and significant correlation between FSD RP and VO(2)max (p = 0.0238) and RDI (p = 0.0451). In conclusion, there is a excellent correlation between blood flow velocity recovery period in femoral artery after moderate exercise and VO(2)max in high-level sportsmen. The method of testing is simple and based on conventional Doppler technique. It can be used for the follow-up of training levels in sportsmen.

Resection and transplantation: evaluation of surgical perspectives in HIV positive patients affected by end-stage liver disease.

PURPOSE: The aim of this study was to evaluate the opportunity of surgical treatment in terms of liver resection or liver transplantation in HIV positive patients affected by an end stage liver disease that referred to our liver unit. METHODS: Among 1350 outpatients who referred to our liver unit from January 2002 to September 2003, thirty-two (2,4%) were HIV positive. The routes of transmission of the viral infection, the related co-infections and the underlying liver disease were recorded. The therapeutic pathway was analysed. The kind and the duration of the surgical procedures were assessed. RESULTS: Fourteen (44%) of these thirty-two patients were not suitable for surgical treatment. Surgery was planned in 9 of 32 HIV positive patients (28%). Four patients (12%) were submitted to liver resection and OLT was performed in five patients (15%). Hepatocellular Carcinoma was present in 4 (44%) of the HIV positive patients considered for surgery. CONCLUSIONS: In conclusion in our centre the 28% of HIV positive out patients had the opportunity to receive a surgical treatment. The candidate to this surgery is mostly young, HCV and/or HBV coinfected and affected by HCC in 44% of cases.

Distortion-rate models for entropy-coded lattice vector quantization.

The increasing demand for real-time applications requires the use of variable-rate quantizers having good performance in the low bit rate domain. In order to minimize the complexity of quantization, as well as maintaining a reasonably high PSNR ratio, we propose to use an entropy-coded lattice vector quantizer (ECLVQ). These quantizers have proven to outperform the well-known EZW algorithm's performance in terms of rate-distortion tradeoff. In this paper, we focus our attention on the modeling of the mean squared error (MSE) distortion and the prefix code rate for ECLVQ. First, we generalize the distortion model of Jeong and Gibson (1993) on fixed-rate cubic quantizers to lattices under a high rate assumption. Second, we derive new rate models for ECLVQ, efficient at low bit rates without any high rate assumptions. Simulation results prove the precision of our models.