Effect of replacing a portion of inorganic chloride trace minerals with trace mineral amino acid complexes.

The objective was to determine whether replacing a portion of inorganic chloride trace minerals and cobalt carbonate in the diet with AA complexes of trace minerals and cobalt glucoheptonate will improve lactating cow performance, feed efficiency, and calf performance. In a clinical trial, 69 Holstein cows entering second lactation and greater were randomly assigned to 1 of 2 treatments, with the total dietary trace mineral concentration the same between treatments, starting 1 wk after dry off (50 to 57 d before expected parturition) until 154 d in milk (DIM): (1) an inorganic chloride trace mineral (ITM) blend consisting of Zn (75 mg/kg), Mn (65 mg/kg), and Cu (10 mg/kg) as hydroxychlorides and Co (1 mg/kg) as carbonate (n = 37) or (2) partial replacement of ITM with AA complexes of Zn (40 mg/kg), Mn (20 mg/kg), and Cu (3.5 mg/kg) and Co glucoheptonate (1 mg/kg; AATM; Availa-Dairy, Zinpro Corp.; n = 32). Dry matter intake (DMI) was recorded daily from enrollment through wk 8, and milk yields were recorded daily from calving through wk 22. Milk composition and body weights (BW) were collected weekly. Serum samples were analyzed for albumin (Alb), cholesterol (Chol), total bilirubin (Bili), aspartate aminotransferase (AST), haptoglobin, ß-hydroxybutyrate (BHB), and Ca. A liver health index (LHI) was calculated based on Bili, Chol, and Alb concentrations. A liver functionality index (LFI) was calculated to standardize changes in Alb, Chol, and Bili from 4 to 29 DIM. Greater LHI and LFI indicate better health status. Colostrum was analyzed for IgG and Brix, and calf serum was analyzed for IgG. Calf growth was monitored through 9 wk of age (AATM: n = 12, ITM: n = 10). Data were analyzed using SAS software with mixed effects models and repeated-measures analysis, when applicable. Survival analysis for pregnancy by 154 DIM was analyzed by Cox proportional and Kaplan-Meier hazards models. Disorder incidence was tested with Fisher's exact test. Prepartum DMI as a percent of BW was lower in cows fed AATM and not significant postpartum. Cows fed AATM produced more milk from wk 1 to 8 and from wk 1 to 22. Energy-corrected milk yield and colostrum measures did not significantly differ between treatments. A treatment by time interaction was seen for AST and BHB; cows fed AATM tended to have lower AST concentrations at 28 DIM and lower concentrations in BHB through 29 DIM, though not statistically significant. Cows fed AATM had greater LHI at 4 DIM. Haptoglobin, Ca, LFI, hazard of pregnancy, risk to first service, survival curves, or services per pregnancy did not significantly differ. Calf serum IgG and birth weight did not significantly differ between treatments. Calves from dams fed AATM had greater average daily gain than calves from dams fed ITM. Overall, cows fed AATM during the dry period and early lactation had improved postpartum performance and potential health improvements.

Real-life daily activity: the impact of misbeliefs on quality of life among cancer patients.

BACKGROUND: While side-effects and health-related quality of life (QoL) are routinely assessed in clinical trials, commonly used tools do not measure patients' ability to maintain normal daily activities. QoL can be severely affected directly by the disease, the treatment side-effects and by personal and societal misconceptions promoting avoidance from activities perceived as dangerous for cancer patients. We examined practices of actively treated patients with cancer. METHODS: A questionnaire was designed, assessing daily activities (11 items) and dietary limitations (7 items) distributed between October and December 2019 (before the coronavirus pandemic) among patients treated at the Oncology Division of Tel Aviv Sourasky Medical Center. RESULTS: The study population comprised 208 patients who participated in the survey. The majority reported at least one social-environmental avoidance or dietary limitation (136, 65% and 120, 57.7%, respectively), including abstaining from social contact, avoiding pets, public domains, traveling and maintaining dietary constraints. Adoption of these measures was not associated with clinical, demographic factors and treatment type. The major sources guiding restrictions came from advice of non-medical personnel (55.7%), the Internet (7.2%) and personal choice by the patients themselves (24%). CONCLUSIONS: Most cancer patients reported compromised daily activities, which are likely attributed to misbeliefs about disease and treatment, and have a deleterious impact on QoL, in its wider sense, namely, the ability to conduct a full and meaningful life. These findings call for the development and implementation of tools examining patients' real-life activity, beyond side-effects or health-related QoL (HRQoL). We propose this assessment as an integral part in the evaluation of new drugs and technologies and as an additional endpoint in pivotal clinical trials.

Response of patients with acute respiratory failure caused by COVID-19 to awake-prone position outside the intensive care unit based on pulmonary involvement.

OBJECTIVES: Since there are difficulties in establishing effective treatments for COVID-19, a vital way to reduce mortality is an early intervention to prevent disease progression. This study aimed to evaluate the performance of patients with COVID-19 with acute hypoxic respiratory failure according to pulmonary impairment in the awake-prone position, outside of the intensive care unit (ICU). METHODS: A prospective observational cohort study was conducted on COVID-19 patients under noninvasive respiratory support. Clinical and laboratory data were obtained for each patient before the treatment and after they were placed in the awake-prone position. To identify responders and non-responders after the first prone maneuver, receiver operating characteristic curves with sensitivity and specificity of the PaO2/FiO2 and SpO2/FiO2 indices were analyzed. The maneuver was considered positive if the patient did not require endotracheal intubation for ventilatory assistance. RESULTS: Forty-eight patients were included, and 64.6% were categorized as responders. The SpO2/FiO2 index was effective for predicting endotracheal intubation in COVID-19 patients regardless of lung parenchymal damage (area under the curve 0.84, cutoff point 165, sensitivity 85%, specificity 75%). Responders had better outcomes with lower hospital mortality (hazard ratio [HR]=0.107, 95% confidence interval [CI]: 0.012-0.93) and a shorter length of stay (median difference 6 days, HR=0.30, 95% CI: 0.13-0.66) after adjusting for age, body mass index, sex, and comorbidities. CONCLUSIONS: The awake-prone position for COVID-19 patients outside the ICU can improve oxygenation and clinical outcomes regardless of the extent of pulmonary impairment. Furthermore, the SpO2/FiO2 index discriminates responders from non-responders to the prone maneuver predicting endotracheal intubation with a cutoff under or below 165.

Postoperative hypothermia following non-cardiac high-risk surgery: A prospective study of temporal patterns and risk factors.

BACKGROUND AND OBJECTIVES: Hypothermia occurs commonly during surgery and can cause postoperative complications. We aimed to describe the characteristics and outcomes of hypothermia in patients undergoing major surgeries. METHODS: This prospective, observational, multicenter study of a nationally representative sample included all patients over 18 years of age admitted to an intensive care unit (ICU). Thirty ICUs were selected randomly at national level. The main outcome measure was the proportion of patients who developed postoperative hypothermia in the first 24 hours of ICU admission. Patients were divided into three groups based on temperature: <35°C, <36°C, and ≥36°C (no hypothermia). Patients' characteristics, postoperative complications, and risk factors were evaluated in all groups. To verify whether hypothermia was a strong risk factor for postoperative complications, a Kaplan-Meier curve was generated and adjusted using a Cox regression model. RESULTS: In total, 738 patients had their temperatures measured. The percentage of patients with temperature <35°C (median [Q1-Q3], 34.7°C [34.3-34.9°C]) was 19.1% (95% confidence interval [CI] = 16.1-22.5) and that of patients with temperature <36°C (median [Q1-Q3], 35.4°C [35.0-35.8°C]) was 64% (95% CI = 58.3-70.0). The percentage of surgical complications was 38.9%. Patients with hypothermia were older, had undergone abdominal surgeries, had undergone procedures of longer duration, and had more comorbidities. A postoperative temperature ≤35°C was an independent risk for composite postoperative complications (hazard ratio = 1.523, 95% CI = 1.15-2.0), especially coagulation and infection. CONCLUSIONS: Inadvertent hypothermia was frequent among patients admitted to the ICU and occurred more likely after abdominal surgery, after a long procedure, in elderly patients, and in patients with a higher number of comorbidities. Low postoperative temperature was associated with postoperative complications.

Hemipelvectomy hernia: case series and literature review.

PURPOSE: Hemipelvectomy is a major operation in which significant portions of the pelvic girdle and lower extremity are resected. The development of hernia following hemipelvectomy is a complex surgical challenge with limited published guidelines for management. We present our experience with three cases of hernia repair following internal hemipelvectomy and review the previously described ten cases of similar patients. METHODS: A systematic review of the current literature regarding hernias in the setting of hemipelvectomy was performed. A comprehensive search strategy on MEDLINE/PUBMED database searching for the key words of hemipelvectomy and hernia was used. RESULTS: There were 13 reported cases of incisional hernia after hemipelvectomy. The indication for hemipelvectomy was sarcoma in 77% of cases. The median time to presentation for hernia repair was 3 years following initial resection. Mesh repair was used in 77%. Identified risk factors for the development of incisional hernia included chemoradiation, wound infection, multiple operations, and weight gain. There was one event of hernia recurrence with a mean follow-up of 16 months. CONCLUSION: Hernia in the setting of hemipelvectomy is an infrequently reported problem. General principles in management are similar to all hernia repairs and include local approximation of tissues, avoidance of contamination or wound infection, and use of prosthetic mesh when local tissue is inadequate for a tension-free repair.

Response of patients with acute respiratory failure caused by COVID-19 to awake-prone position outside the intensive care unit based on pulmonary involvement

OBJECTIVES: Since there are difficulties in establishing effective treatments for COVID-19, a vital way to reduce mortality is an early intervention to prevent disease progression. This study aimed to evaluate the performance of patients with COVID-19 with acute hypoxic respiratory failure according to pulmonary impairment in the awake-prone position, outside of the intensive care unit (ICU). METHODS: A prospective observational cohort study was conducted on COVID-19 patients under noninvasive respiratory support. Clinical and laboratory data were obtained for each patient before the treatment and after they were placed in the awake-prone position. To identify responders and non-responders after the first prone maneuver, receiver operating characteristic curves with sensitivity and specificity of the PaO2/FiO2 and SpO2/FiO2 indices were analyzed. The maneuver was considered positive if the patient did not require endotracheal intubation for ventilatory assistance. RESULTS: Forty-eight patients were included, and 64.6% were categorized as responders. The SpO2/FiO2 index was effective for predicting endotracheal intubation in COVID-19 patients regardless of lung parenchymal damage (area under the curve 0.84, cutoff point 165, sensitivity 85%, specificity 75%). Responders had better outcomes with lower hospital mortality (hazard ratio [HR]=0.107, 95% confidence interval [CI]: 0.012-0.93) and a shorter length of stay (median difference 6 days, HR=0.30, 95% CI: 0.13-0.66) after adjusting for age, body mass index, sex, and comorbidities. CONCLUSIONS: The awake-prone position for COVID-19 patients outside the ICU can improve oxygenation and clinical outcomes regardless of the extent of pulmonary impairment. Furthermore, the SpO2/FiO2 index discriminates responders from non-responders to the prone maneuver predicting endotracheal intubation with a cutoff under or below 165.

Impact of perioperative hemodynamic optimization therapies in surgical patients: economic study and meta-analysis.

BACKGROUND: Several studies suggest that hemodynamic optimization therapies can reduce complications, the length of hospital stay and costs. However, Brazilian data are scarce. Therefore, the objective of this analysis was to evaluate whether the improvement demonstrated by hemodynamic optimization therapy in surgical patients could result in lower costs from the perspective of the Brazilian public unified health system. METHODS: A meta-analysis was performed comparing surgical patients who underwent hemodynamic optimization therapy (intervention) with patients who underwent standard therapy (control) in terms of complications and hospital costs. The cost-effectiveness analysis evaluated the clinical and financial benefits of hemodynamic optimization protocols for surgical patients. The analysis considered the clinical outcomes of randomized studies published in the last 20 years that involved surgeries and hemodynamic optimization therapy. Indirect costs (equipment depreciation, estate and management activities) were not included in the analysis. RESULTS: A total of 21 clinical trials with a total of 4872 surgical patients were selected. Comparison of the intervention and control groups showed lower rates of infectious (RR = 0.66; 95% CI = 0.58-0.74), renal (RR = 0.68; 95% CI = 0.54-0.87), and cardiovascular (RR = 0.87; 95% CI = 0.76-0.99) complications and a nonstatistically significant lower rate of respiratory complications (RR = 0.82; 95% CI = 0.67-1.02). There was no difference in mortality (RR = 1.02; 95% CI = 0.80-1.3) between groups. In the analysis of total costs, the intervention group showed a cost reduction of R$396,024.83-BRL ($90,161.38-USD) for every 1000 patients treated compared to the control group. The patients in the intervention group showed greater effectiveness, with 1.0 fewer days in the intensive care unit and hospital. In addition, there were 333 fewer patients with complications, with a consequent reduction of R$1,630,341.47-BRL ($371,173.27-USD) for every 1000 patients treated. CONCLUSIONS: Hemodynamic optimization therapy is cost-effective and would increase the efficiency of and decrease the burden of the Brazilian public health system.

Satisfaction with a therapeutic sleeve for arm lymphedema secondary to breast cancer treatment: Controlled crossover trial.

HIGHLIGHTS: Secondary lymphedema is a late iatrogenic side effect of breast cancer treatment.Despite multimodal decongestive therapy in their daily life breast cancer survivors with lymphedema have few alternatives but to use a compressive sleeve.Concerned with the well-known low compliance to the daily use of traditional sleeves, we conducted a comparative study to evaluate the subjective assessment of an innovative class 1 compression sleeve.We concluded that the PRADEX® sleeve, not being worse in its compressive efficacy, is much better with regard to patient comfort. ABSTRACT: Secondary arm lymphedema is a feared late iatrogenic side effect of breast cancer survivors with a negative impact on patient's self-image and quality of life. Its reported incidence is extremely variable, from 6% to 80%, as well as the effectiveness of the multimodal decongestive lymphedema therapy.In their daily life breast cancer survivors with lymphedema have few alternatives but to use a compressive sleeve. Concerned with the well-known low compliance to the daily use of traditional sleeves, we conducted a comparative study in a subgroup of our patients with lymphedema secondary to breast cancer treatment for the subjective assessment of PRADEX®, an innovative class 1 compression sleeve. Secondarily, we aimed to assess the non-inferiority of PRADEX® regarding subjective and objective measures of the severity of lymphedema.We studied 46 women with grade 1 secondary arm lymphedema, who used their usual sleeve and PRADEX® daily for 2 weeks each, in a crossover design.The new therapeutic sleeve was classified as having a better design and a better usability and comfort (more comfortable, thinner, fresher, softer, more flexible, comfortable, resistant to dirt and easier to dress and to wear). Women's subjective opinion about the severity of lymphedema favored their usual sleeve in detriment of PRADEX®, but this subjective feeling was contradicted by objective measurements of different perimeters of the arm at the beginning and at the end of the study.We concluded that the PRADEX® sleeve, not being worse in its compressive therapeutic efficacy, is much better with regard to patient comfort.

Anatomic and Quantitative Temporal Bone CT for Preoperative Assessment of Branchio-Oto-Renal Syndrome.

We describe the temporal bone computed tomography (CT) findings of an unusual case of branchio-oto-renal syndrome with ectopic ossicles that are partially located in the middle cranial fossa. We also describe quantitative temporal bone CT assessment pertaining to cochlear implantation in the setting of anomalous cochlear anatomy associated with this syndrome.

Endovascular treatment of visceral artery aneurysms and pseudoaneurysms: our experience.

PURPOSE: The aim of this study was to analyse our 8 years of experience with endovascular treatment of visceral aneurysms and pseudoaneurysms. MATERIALS AND METHODS: From January 2002 to September 2009, we used an endovascular approach to treat 30 patients (22 men, eight women) affected by aneurysm (n=18) or pseudoaneurysm (n=13) of the splenic (n=11), hepatic (n=6), renal (n=5), pancreaticoduodenal (n=3), left gastric (n=2), gastroduodenal (n=1), rectal (n=1) or middle colic (n=1) arteries and the coeliac axis (n=1). Of these, 26/31 were treated with metal coils, 3/31 with Cardiatis multilayer stent, 1/31 with a coated stent and 1/31 with coils and Amplatzer plug. Procedures were performed electively in 10/30 cases and during haemorrhage in 20/30 cases. Follow-up was performed clinically (cessation of bleeding) and at 1, 6 and 12 months by colour-Doppler ultrasound (CDUS) and computed tomography (CT) angiography. RESULTS: In 31/31 aneurysms and pseudoaneurysms we obtained immediate exclusion. In four patients with aneurysm and in four with pseudoaneurysm, parenchymal ischaemia occurred; one was treated with surgical splenectomy. One patient with pseudoaneurysm of the coeliac axis died 10 days later because of new bleeding. During follow-up, all aneurysms and pseudoaneurysms remained excluded. CONCLUSIONS: Percutaneous treatment is effective and safe, with a small number of complications, especially when compared with traditional surgery.

Reduction of proteinuria with mycophenolate mofetil in predominantly membranous lupus nephropathy.

INTRODUCTION: Lupus membranous nephropathy (LMN) presents a difficult clinical problem as no particular treatment has been proven to be effective. Studies have shown good results with mycophenolate mofetil (MMF) in proliferative lupus nephropathy (LN) (WHO class III and IV disease). OBJECTIVES: To study whether MMF treatment was effective in membranous predominant LN in patients resistant to or intolerant of other immunosuppressive agents. PATIENTS AND METHODS: We retrospectively studied 10 patients with systemic lupus erythematosus who had biopsy-proven predominant LMN (six Vc patients and four Va or Vb patients). Previous treatments included cyclophosphamide, azathioprine, ciclosporin and corticosteroids. The following parameters were recorded at baseline and follow-up: blood pressure, ECLAM, proteinuria, serum albumin and creatinine, routine haematology and immunology. RESULTS: The study included eight women and two men, mean age 38.4 +/- 7.1 yr (range 30-49 yr). The racial distribution was as follows: five Caucasian, and five Black patients. The mean treatment time with MMF was 18.8 +/- 15.4 months (range 3-52 months). Twenty-four-hour urinary protein excretion was reduced from median 2.26 g (range 0-7.92 g) to median 0.66 g (range 0.08-3.85 g) at follow-up (P = 0.0039). Serum albumin increased significantly after treatment from median 29.5 g/l (range 14.0-42.0 g/l) to 33.5 g/l (range 23.0-40.0 g/l) at follow-up (P = 0.04). There were no significant changes in serum creatinine (P = 0.55). CONCLUSION: MMF is a potentially useful immunosuppressive agent in reducing the proteinuria associated with membranous predominant LN.

Antithrombin activity of an algal polysaccharide.

In an effort to reduce the risks of a possible iatrogenic transmission of bovine spongiform encephalitis (BSE) through the use of bovine-derived medicinal products, we patented in the USA in 1999 a polysaccharide from brown algae, endowed with interesting pharmacological activities: (a) concentration-dependent inhibition of thromboplastin or cephalin-kaolin-induced thrombin generation from platelets, (b) concentration-dependent inhibition of thrombin-induced platelet aggregation, (c) thrombin has hypotensive effect, which was blunted and zeroed by our fucansulfate in a dose-dependent way, (d) when aortae are stimulated with thrombin, they become stickier for polymorphonucleated leukocytes (PMNs); our fucansulfate decreased concentration-dependently, PMNs sticking to autologous rabbit aortae, (e) dose-dependent inhibition of thrombin-induced thrombosis. All the above data suggest that our fucansulfate could be a heparin substitute endowed with antithrombotic and anti-inflammatory activities, devoid or the problems caused to heparin by its animal origin, i.e., possible prion protein contamination.

Defibrotide normalizes cardiovascular function hampered by established atherosclerosis in the rabbit.

In a previous paper we gave evidence that chronic oral defibrotide antagonizes the noxious effect of developing atherosclerosis in the cardiovascular system. In the present paper we give evidence that defibrotide is still capable of exerting beneficial effects on cardiovascular function once atherosclerosis is established. In fact, there was statistically significant amelioration by defibrotide infusion in the following, all of which were hampered by established atherosclerosis: in rabbit aorta relaxation to acetylcholine, prostaglandin E2, and 6-keto-prostaglandin F1alpha generation from rabbit aortas, rabbit heart left ventricular end-diastolic pressure, coronary perfusion pressure, and left ventricular developed pressure, vasopressor activity of acetylcholine and endothelin-1 on coronary perfusion pressure, and 6-keto-prostaglandin F1alpha generation from the rabbit heart. Since prostacyclin takes part in NO generation, is cellular protective, and inhibits 5-lipoxygenase product synthesis, its increase, caused by defibrotide, could explain defibrotide cardioprotective activity. Prostacyclin activity could be backed by prostaglandin E2, another cardioprotective prostaglandin.

Chronic oral defibrotide counteracts hypercholesterolemia noxious effects on cardiovascular function in the rabbit.

The aim of the present work was to assess if the cardioprotective drug defibrotide could counteract the hypercholesterolemia noxious effects on cardiovascular function. Aortas and hearts from normal- or cholesterol-fed rabbits, treated or not with chronic oral defibrotide (100 mg/kg/day) for 45 days, were used in in vitro tests throughout the experiment. Hypercholesterolemia worsened: aorta stickiness toward polymorphonuclear leukocytes, aorta relaxation to acetylcholine, heart left ventricular end-diastolic pressure and coronary perfusion pressure, heart left ventricular diastolic pressure, acetylcholine and endothelin-1 activity on coronary perfusion pressure, and heart generation of 6-Keto-prostaglandin F1alpha. Oral defibrotide counteracted and/or obliterated the above hypercholesterolemia noxious effects. Particularly, oral defibrotide counteracted the parameters associated with early endothelial cell disfunction: that is, increased adherence of leukocytes to endothelium and endothelial vasorelaxation induced by acetylcholine, which acts through the release of endothelium-derived relaxing factor. These activities of defibrotide are probably exerted through the increased generation of prostacyclin. The fact that acetylcholine induced vasorelaxation is partially protected by oral defibrotide points to a partial rescue of endothelial ability to generate endothelium-derived relaxing factor, as acethylcoline acts through the release of endothelium-derived relaxing factor, by defibrotide itself. Defibrotide's endothelial protection could, in turn, explains why defibrotide protected cardiovascular function. This is not surprising as, in a few cases, endothelial dysfunction, observed in hypercholesterolemia, was found to be prevented or reversed, pharmacologically, by PN-2001-10, a calcium channel blocker, dipyridamole, and lovastatin.

Pharmacokinetics, absorption, distribution and disposition of [125I]-oligotide following intravenous or oral administration in the rat.

Oligotide (O) was labelled with 125I. The radiolabelled compound ([125I]-Oligotide ([125I]-O)) retained the biological activity of parent O. Following single intravenous administration the half lives of radioactivity associated with O and/or O related components in plasma were 9-10 min and 9-10 h for alpha and beta phases respectively. Following single oral administration the half life of radioactivity associated with O and/or O related components in plasma was 11.45-12.76 h for beta fase. Following multiple oral administration once daily for 7 days, the half life of radioactivity associated with O and/or O related components following the 7th dose was 10-12 h for beta phase. The areas under plasma total radioactivity versus time curves were dose-dependent. Following single intravenous administration the major proportion of the administered dose was excreted via urine, while following single oral administration excretion via urine and faeces accounted for similar proportions of the administered dose. Following both single and oral administration the levels of radioactive components derived from [125I]-O in organs examined were generally highest in highly perfused organs.