Risk Of Acidosis Research Articles

A review on the potentials of using feeds rich in water-soluble carbohydrates to enhance rumen health and sustainability of dairy cattle production.

Cows are adapted to degrade structural plant carbohydrates (SC), such as cellulose and hemicelluloses, prevailing in grasses. Yet, the need for energy-dense diets in many intensive dairy production systems has shifted the dairy cattle's diet from SC-rich to high levels of starch. Feeding of starch-rich diets increases the risk of ruminal acidosis in cows, and feeding starch in the form of grains intensifies the competition over cereal grains and arable land among different livestock species, as well as between livestock and humans. Besides cellulose and hemicelluloses, grasses are also often rich in water-soluble carbohydrates (WSC), which comprise mono-, di-, oligo- and polysaccharides (fructans). Although the ruminal fermentation profile of mono- and disaccharides resembles that of starch, the degradation of oligo- and polysaccharides is slower, and their fermentation elicits a rather protecting effect on ruminal pH. When harvested in an early phase (i.e. ear emergence), grass hay and silages can reach WSC levels up to 150-200 g kg-1 dry matter and energy levels close to starch-rich diets, allowing a significantly reduced inclusion of concentrate supplements. By doing so, this will enhance both rumen health and the sustainability of milk production. However, because the WSC are chemically very heterogeneous, the patterns and extent of their ruminal fermentation are difficult to predict without a clear analytical characterization. This review article aims to summarize both the benefits and potentials, as well as the challenges, with respect to using WSC-rich feedstuffs in the nutrition of dairy cattle and their effects on ruminal fermentation characteristics and milk production. © 2021 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Safety and effectiveness of metformin in patients with reduced renal function: A systematic review.

To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function. We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient-centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than 60 mL/min/1.73m2 , was included. Post hoc meta-analysis was performed for the outcomes of mortality, cardiovascular events and acidosis. Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta-analysis showed reductions in overall mortality at an eGFR of 45 mL/min/1.73m2 or higher but not at an eGFR of less than 45 mL/min/1.73m2 . Eight retrospective studies evaluated acidosis as an outcome; meta-analysis showed no increase in risk of acidosis except at an eGFR of less than 30 mL/min/1.73m2 , in which group the HR was 1.97 (95% CI 1.03-3.77). The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45 mL/min/1.73m2 or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30 mL/min/1.73m2 . Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30 mL/min/1.73m2 , and further research on its risk-benefit profile at eGFR values approaching 30 mL/min/1.73m2 is warranted.

Effects of Metformin on Clinical outcomes in Patients with Type 2 Diabetes and Covid-19

Background: The effects of metformin therapy on the prognosis of patients with coronavirus disease 2019 (COVID-19) are unclear. Objective: To review effects of metformin on clinical outcomes, particularly mortality, in patients with type 2 diabetes and COVID-19. Methods: Review of English literature by PUBMED search until April 20, 2021. Search terms included diabetes, COVID-19, metformin, Retrospective studies, meta-analyses, pertinent reviews, and consensus guidelines are reviewed. Results: All available studies in this area are retrospective. Two population-based studies did not find significant association between metformin use and susceptibility to COVID-19. Most, but not all studies, suggest that metformin use prior to hospital admission might be associated with significant decrease in mortality in patients with type 2 diabetes and COVID-19. Continuing metformin use after hospital admission did not have significant impact on COVID-19 related death but may decrease risk of acute respiratory distress syndrome (ARDS). Meanwhile, in-hospital metformin administration may be associated with approximately 4.6 times increase risk of lactic acidosis in patients with severe symptoms of COVID-19, patients taking ≥2 gm/d of metformin, and patients with estimated glomerular filtration rate (eGFR) less than 60 ml/min/1.73 kg/m2. Conclusions: Although most retrospective studies suggest that metformin administration may be associated with decreased risk of COVID-19 mortality, these data should be confirmed by randomized trials. In patients with type 2 diabetes and COVID-19 admitted to the hospital, metformin use should be avoided in presence of severe symptoms of COVID-19, kidney dysfunction (eGFR < 60 ml/min/1.73m2), and in daily doses of ≥ 2 gm due to increased risk of lactic acidosis.

A Metagenomic Insight Into the Hindgut Microbiota and Their Metabolites for Dairy Goats Fed Different Rumen Degradable Starch.

High starch diets have been proven to increase the risk of hindgut acidosis in high-yielding dairy animals. As an effective measurement of dietary carbohydrate for ruminants, studies on rumen degradable starch (RDS) and the effects on the gut microbiota diversity of carbohydrate-active enzymes (CAZymes), and Kyoto Encyclopedia of Genes and Genomes (KEGG) Orthology functional categories are helpful to understand the mechanisms between gut microbiota and carbohydrate metabolism in dairy goats. A total of 18 lactating goats (45.8 ± 1.54 kg) were randomly divided equally into three dietary treatments with low dietary RDS concentrations of 20.52% (LRDS), medium RDS of 22.15% (MRDS), and high RDS of 24.88% (HRDS) on a DM basis for 5 weeks. Compared with the LRDS and MRDS groups, HRDS increased acetate molar proportion in the cecum. For the HRDS group, the abundance of family Ruminococcaceae and genus Ruminococcaceae UCG-010 were significantly increased in the cecum. For the LRDS group, the butyrate molar proportion and the abundance of butyrate producer family Bacteroidale_S24-7, family Lachnospiraceae, and genus Bacteroidale_S24-7_group were significantly increased in the cecum. Based on the BugBase phenotypic prediction, the microbial oxidative stress tolerant and decreased potentially pathogenic in the LRDS group were increased in the cecum compared with the HRDS group. A metagenomic study on cecal bacteria revealed that dietary RDS level could affect carbohydrate metabolism by increasing the glycoside hydrolase 95 (GH95) family and cellulase enzyme (EC 3.2.1.4) in the HRDS group; increasing the GH13_20 family and isoamylase enzyme (EC 3.2.1.68) in the LRDS group. PROBIO probiotics database showed the relative gene abundance of cecal probiotics significantly decreased in the HRDS group. Furthermore, goats fed the HRDS diet had a lower protein expression of Muc2, and greater expression RNA of interleukin-1β and secretory immunoglobulin A in cecal mucosa than did goats fed the LRDS diet. Combined with the information from previous results from rumen, dietary RDS level altered the degradation position of carbohydrates in the gastrointestinal (GI) tract and increased the relative abundance of gene encoded enzymes degrading cellulose in the HRDS group in the cecum of dairy goats. This study revealed that the HRDS diet could bring disturbances to the microbial communities network containing taxa of the Lachnospiraceae and Ruminococcaceae and damage the mucus layer and inflammation in the cecum of dairy goats.

114-LB: Metformin-Associated Lactic Acidosis Risk Assessment in Veterans on Continuous Oxygen Therapy

Metformin is the most prescribed oral medication for type 2 diabetes in the US due to its low cost, efficacy in reducing insulin resistance, and overall safety profile. However, literature shows that metformin can cause a rare but serious side effect of lactic acidosis (LA) with an incidence of 0.03-0.06 per 1000 patients. Persons requiring continuous oxygen therapy (COT) may be at risk for LA associated with hypoxia and decreased tissue perfusion, but the risk of metformin associated lactic acidosis (MALA) in persons requiring COT is unclear. Due to lack of evidence, some clinicians may empirically discontinue metformin in patients on COT, compromising glycemic stability. The objective of this drug utilization evaluation was to determine the frequency of metformin use and incidence of MALA in patients receiving COT. A retrospective review was conducted at a large regional Veterans Affairs Medical Center for patients with active prescriptions of metformin and supplemental oxygen therapy from 4/2017-4/2020. Of 578 unique patients identified, manual medical-record review was conducted for 6 patients who had serum lactate levels >4 mmol/L while using concomitant metformin and COT. All were white males with mean: age of 71, pH of 7.35, and eGFR of 56. No cases of LA or DKA were identified. In all cases, elevated lactate levels were attributed to advanced medical conditions including: COPD, sepsis, CHF, CKD, and liver disease. None had serum metformin levels drawn. In conclusion, the association of elevated serum lactate among persons using concomitant metformin and COT was low and occurred in persons with advanced medical conditions. It could not be determined if metformin use was a contributing factor without metformin levels. These findings confirm the importance of clinical judgement when prescribing and continuing metformin for persons with advanced underlying medical conditions. Further study with serum metformin levels may help to better characterize the risk of MALA for persons on COT. Disclosure S. J. Lutz-mccain: None. B. E. Desanzo: None. B. Herk: None. M. Mclinden: None. M. M. Dinardo: None. R. Codario: None.

Mitochondrial Diabetes: The Clinical Spectrum of MIDD and MELAS in Association With the A3243G Mutation

Abstract Introduction: Maternally inherited diabetes and deafness (MIDD) is a multisystem disorder characterized by insulinopenia and sensorineural hearing loss. This rare form of monogenic diabetes is most commonly associated with the A3243G mutation of mitochondrial DNA (mtDNA). The same mutation is seen in 80 percent of patients with MELAS (Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes). MIDD and MELAS have overlapping features suggesting a continuum of expression for the A3243G mutation. Clinical Case: A 41-year-old male was referred for genetic testing and counseling by his ophthalmologist following detection of bilateral punched-out retinal pigment epithelium (RPE) lesions on routine exam. His medical history was significant for type 1 diabetes mellitus (T1DM) diagnosed at the age of 21 and bilateral sensorineural hearing loss diagnosed at the age of 38. The referral was triggered by patient reported family history of MELAS in two of his brothers who were both diagnosed at the age of 10 and died at the ages of 20 and 27. Whether the patient was previously tested during early childhood remains unclear. His medical history was negative for stroke-like episodes or seizures. Neurologic evaluation revealed mild fluent aphasia with paraphasic errors and some comprehension difficulties. MRI of the brain without contrast showed no focus of restricted diffusion. Mitochondrial DNA sequence analysis was performed. A pathogenic variant (m.3243 A>G) was detected in the MT-TL1 gene at approximately 25% heteroplasmy. The patient was advised to avoid metformin given increased risk for lactic acidosis. He was also instructed against use of statins. At the age of 45, the patient presented to the emergency department (ED) with a complaint of headache, vertigo and incoordination. Physical examination revealed left homonymous hemianopsia, right horizontal nystagmus and bilateral upper extremity dysmetria. MRI of the brain without contrast showed a large area of predominantly cortical restricted diffusion involving the right temporal and occipital region with associated T2/FLAIR hyper-intensity. Cross over between the PCA and MCA territories was suggestive of a stroke-like episode related to MELAS. The patient received a bolus of IV arginine at 0.5 g/kg followed by an IV infusion of 0.5 g/kg/day for 3 days. He was later transitioned to oral arginine 5g three times daily and was discharged to a rehab facility. Clinical Lesson: This case demonstrates the evolution of MIDD to MELAS, supporting the concept that both syndromes represent a spectrum of the same disease. A few case reports describe the progression of MIDD to MELAS. Why some patients develop MELAS and others develop MIDD is unclear but may be related to heteroplasmy. Early identification of MIDD and MELAS is crucial given associated comorbidities and unique management issues.

Proposta de Protocolo para Redução dos Riscos e Otimização da Sensibilidade nos Exames de Imagem em Pessoas com Diabetes

A diabetes é uma doença crónica muito frequente na população portuguesa, sendo a sua prevalência estimada de 13,6% nos adultos. A melhor preparação e os riscos associados à realização de exames de imagem em pessoas com diabetes são frequentemente objeto de dúvidas. Neste artigo, pretendemos rever as principais precauções e sugerir um protocolo de atuação, de forma a reduzir os riscos e otimizar a sensibilidade destes exames nesta população. Revemos também a necessidade de suspensão de metformina após a administração de contraste iodado endovascular, pelo risco de acidose láctica, as precauções em pessoas com diabetes insulinotratadas ou sob fármacos que apresentam maior risco de hipoglicemia na realização de exames de imagem que obriguem a jejum, e a influência da hiperglicemia e da terapêutica anti-diabética na sensibilidade da PET-FDG. Com a revisão deste tema e apresentação de um protocolo de atuação pretendemos desmistificar a orientação dos indivíduos com diabetes que vão ser submetidos a exames de imagem, tornando mais simples a sua gestão.

Associated factors with umbilical arterial pH after cesarean delivery under spinal anesthesia: a retrospective cohort study

BackgroundMaximum decrease of blood pressure and number of minutes of hypotension were independently associated with umbilical arterial pH. However, the impact of hypotension considering the duration of it on umbilical arterial pH is unknown. MethodsPregnant women aged ≥ 20 years who delivered a baby at full-term via a cesarean delivery under a single-shot spinal anesthesia between January 2017 and March 2019 were included. The main outcome was to predict umbilical arterial pH, based on the value of the time integral of hypotension. Patient demographics, patient comorbidities, and intraoperative data, including the total dose of ephedrine and phenylephrine by fetal delivery and cumulative duration of maternal hypotension, were evaluated. Maternal hypotension was reflected as a decrease in systolic arterial pressure and mean arterial pressure to < 80% of baseline values. The systolic arterial pressure and mean arterial pressure were independently included in a multiple regression analysis along with all other explanatory factors to predict the umbilical arterial pH. ResultsOf the 416 eligible patients, 381 were enrolled. When including the systolic arterial pressure or mean arterial pressure in the model, emergency cases, the total dose of ephedrine, hypertensive disorders of pregnancy, and systolic arterial pressure or mean arterial pressure values were found to be significant predictive factors of umbilical arterial pH. ConclusionOur results suggest that an elevated time integral of maternal hypotension may have a negative impact on umbilical arterial pH. Therefore, to minimize the risk of fetal acidosis, maternal hypotension should be prevented with the consideration of vasopressors selection.

Effect of Dried Distillers Grains With Solubles and Red Osier Dogwood Extract on Fermentation Pattern and Microbial Profiles of a High-Grain Diet in an Artificial Rumen System.

The objective of this study was to evaluate the effect of dried distillers grains with solubles (DDGS) and red-osier dogwood (ROD) extract on in vitro fermentation characteristics, nutrient disappearance, and microbial profiles using the rumen simulation technique. The experiment was a completely randomized design with a 2 × 2 factorial arrangement of treatments and four replicates per treatment. A basal diet [10% barley silage, 87% dry-rolled barley grain, and 3% vitamin and mineral supplement, dry matter (DM) basis] and a DDGS diet (as per basal diet with 25% of wheat DDGS replacing an equal portion of barley grain) were supplemented with ROD extract at 0 and 1% (DM basis), respectively. The experimental period was 17 d, consisting 10 days of adaptation and 7 days of data and sample collection. The substitution of wheat DDGS for barley grain did not affect gas production; disappearances of DM, organic matter, and crude protein; total volatile fatty acid (VFA) production; and microbial protein production. However, replacing barley grain with wheat DDGS increased (P = 0.01) fermenter pH and molar proportion of branched-chain VFA, switched (P = 0.06) the fermentation pattern to higher acetate production due to increased (P = 0.01) disappearance of neutral detergent fiber (NDF), and decreased (P = 0.08) methane (CH4) production. In the basal barley diet, the ROD extract increased the acetate to propionate (A:P) ratio (P = 0.08) and reduced the disappearance of starch (P = 0.06) with no effect on any other variables. No effects of ROD in the DDGS diet were observed. The number of operational taxonomic unit (OTUs) and the Shannon diversity index of the microbial community had little variation among treatments. Taxonomic analysis revealed no effect of adding the ROD extract on the relative abundance of bacteria at the phylum level with either the basal diet or DDGS diet, while at the genus level, the microbial community was affected by the addition of both DDGS and the ROD extract. Prevotella and Fibrobacter were the most abundant genera in the basal diet; however, Treponema became the most abundant genus with the addition of the ROD extract. These results indicated that the substitution of wheat DDGS for barley grain may mitigate enteric CH4 emissions. The trend of reduced starch fermentability and increased NDF disappearance with the addition of ROD extract suggests a reduced risk of rumen acidosis and an improvement in the utilization of fiber for cattle-fed high-grain diet.

Models to predict the risk of subacute ruminal acidosis in dairy cows based on dietary and cow factors: A meta-analysis

The present research aimed at developing practical and feasible models to optimize feeding adequacy to maintain desired rumen pH conditions and prevent subacute ruminal acidosis (SARA) in dairy cows. We conducted 2 meta-analyses, one using data from recent published literatures (study 1) to investigate the prediction of SARA based on nutrient components and dietary physical and chemical characteristics, and another using internal data of our 5 different published experiments (study 2) to obtain adjustments based on cow status. The results of study 1 revealed that physically effective neutral detergent fiber inclusive of particles >8 mm (peNDF >8) and dietary starch [% of dry matter (DM)] were sufficient for predicting daily mean ruminal pH {y = 5.960 - (0.00781 × starch) + (0.03743 × peNDF >8) - [0.00061 × (peNDF >8 × peNDF >8)]}. The model for time of pH suppression (<5.8 for ruminal pH or <6.0 for reticular pH, min/d) can be predicted with additionally including DMI (kg/d): 124.7 + (1.7007 × DMI) + (20.9270 × starch) + (0.2959 × peNDF >8) - [0.0437 × (DMI × starch × peNDF >8)]. As a rule of thumb, when taken separately, we propose 15 to 18% peNDF >8 as a safe range for diet formulation to prevent SARA, when starch or NFC levels are within 20 to 25% and 35 to 40% ranges, respectively. At dietary starch content below 20% of DM, grain type was insignificant in affecting ruminal pH. However, increasing dietary starch contents by using corn as the sole grain source could lead to more severe drops of pH compared with using grain mix based on barley and wheat, as underlined by an interaction between starch content and grain type. Data from study 2 emphasized an increased risk of SARA for cows in the first and second lactation with lower mean pH (0.2 units) and double amounts of time at pH <5.8 compared with the cows with ≥3 parities. Given that a lower ruminal pH is expected in these high-risk cows, it is advisable to keep the lower end of recommended starch (20%) and higher peNDF >8 (18%) contents in the diet of these cows. Overall, the present study underlines the possibility of predicting SARA based on dietary factors including peNDF >8 and starch contents, as well as DMI of the cows, which can be practically implemented for optimal diet formulation for dairy cows. With more data available, future studies should attempt to improve the predictions by including additional key dietary and cow factors in the models.

Volume management: peri-operatively and peri-interventionally

Fluid therapy is one of the basic and most frequently performed medical therapies in everyday clinical practice. However, optimal volume management is a challenge: the application is simple, but the whole volume management is a complex process and physicians have to pay attention on underlying pathophysiology. Intravenous fluids should be prescribed like medications, i. e. the type of fluid and the amount must be adapted to each individual patient with his needs. Intravascular volume therapy is often used peri-operatively and peri-interventionally.Nowadays, crystalloid solutions are widely used and the standard is a balanced electrolyte solution. Only in selected situations 0,9 % sodium chloride solutions should be used, because they contain a high chloride concentration (154 mmol/l) and lead to increased risk of hyperchloremic metabolic acidosis.

Effect of Bicarbonate on Net Acid Excretion, Blood Pressure, and Metabolism in Patients With and Without CKD: The Acid Base Compensation in CKD Study

Patients with CKD are at elevated risk of metabolic acidosis due to impaired net acid excretion (NAE). Identifying early markers of acidosis may guide prevention in chronic kidney disease (CKD). This study compared NAE in participants with and without CKD, as well as the NAE, blood pressure (BP), and metabolomic response to bicarbonate supplementation. Randomized order, cross-over study with controlled feeding. Participants consisted of 8 patients with CKD (estimated glomerular filtration rate 30-59mL/min/1.73m2 or 60-70mL/min/1.73m2 with albuminuria) and 6 patients without CKD. All participants had baseline serum bicarbonate concentrations between 20 and 28 mEq/L; they did not have diabetes mellitus and did not use alkali supplements at baseline. Participants were fed a fixed-acid-load diet with bicarbonate supplementation (7 days) and with sodium chloride control (7 days) in a randomized order, cross-over fashion. Urine NAE, 24-hour ambulatory BP, and 24-hour urine and plasma metabolomic profiles were measured after each period. During the control period, mean NAE was 28.3±10.2 mEq/d overall without differences across groups (P=0.5). Urine pH, ammonium, and citrate were significantly lower in CKD than in non-CKD (P<0.05 for each). Bicarbonate supplementation reduced NAE and urine ammonium in the CKD group, increased urine pH in both groups (but more in patients with CKD than in those without), and increased; urine citrate in the CKD group (P< 0.2 for interaction for each). Metabolomic analysis revealed several urine organic anions were increased with bicarbonate in CKD, including 3-indoleacetate, citrate/isocitrate, and glutarate. BP was not significantly changed. Small sample size and short feeding duration. Compared to patients without CKD, those with CKD had lower acid excretion in the form of ammonium but also lower base excretion such as citrate and other organic anions, a potential compensation to preserve acid-base homeostasis. In CKD, acid excretion decreased further, but base excretion (eg, citrate) increased in response to alkali. Urine citrate should be evaluated as an early and responsive marker of impaired acid-base homeostasis. National Institute of Diabetes and Digestive and Kidney Diseases and the Duke O'Brien Center for Kidney Research. Registered atClinicalTrials.gov with study number NCT02427594.

Effect of ruminal mechanical stimulating brushes on the performance of lactating Holstein dairy cows

The aim of this study was to confirm the hypothesis that artificial brushes administered to the rumen can partially replace the function of structural fibre, and increase milk production or quality. To mitigate the risks of feeding low levels of physically effective neutral detergent fibre (peNDF) to cattle, the administration of ruminal mechanical stimulating (RMS) brushes was examined in 22 high-yielding lactating Holstein dairy cows. The cows were divided into an experimental group equipped with RMS brushes and a control group without RMS. Cows were fed four experimental total mixed rations (TMR) consisting of fixed amounts of alfalfa silage, maize silage, rush corn cob mix silage and different proportions of brewer's grains, concentrate and wheat straw. The TMRs had the following 4 peNDF contents: 10.9%. 13.0%, 12.6% and 14.0%. The duration of the experiment was 18 weeks. All cows were fed TMRs with a low structural fibre content near levels associated with a risk of subacute ruminal acidosis (SARA). For the RMS brush group, 3 RMS brushes were inserted orally into the rumen using a special applicator. The effects of RMS brushes on feed intake, rumen fermentation and milk production were evaluated. Ruminal fluid (250 mL) was taken using a stomach tube for pH, volatile fatty acids and ammonia nitrogen analysis. A significant increase was found for the feed intake and milk yield of the RMS group fed the TMRs with 13.0% peNDF although no relationship between peNDF content and RMS TMRs was found. No significant increase in milk quality, rumen pH or rumen fermentation metabolites was declared for the group with RMS brushes. Although RMS brush technology only partially reduced the requirements for peNDF, it may decrease the risk of SARA.

Influence of three microbial feed additives of Megasphaera elsdenii, Saccharomyces cerevisiae and Lactobacillus sp. on ruminal methane and carbon dioxide production, and biofermentation kinetics.

This study was performed to investigate the effects of Megasphaera elsdenii (Me), Saccharomyces cerevisiae (SC) and lactic acid bacteria (FP-Lactobacillus fermentum plus Lactobacillus plantarum) alone or in combination on biogas production and ruminal biofermentation parameter in a heterofermenter system. Eight treatments were evaluated; (i) control (without additive; CON); (ii) Me; (iii) SC; (iv) FP; (v) Me plus SC (MSC); (vi) Me plus FP (MFP); (vii) SC plus FP (SCFP) and (viii) Me plus SC plus FP (MSCFP). Doses of FP, Me and SC were 1·5×108 (CFU per ml), 1·5×108 (CFU per ml) and 1·4×107 (CFU 0·002-1 g), respectively. Biogas production in all time increased (P<0·05) by MSCFP than CON additive. The proportional methane (CH4 ) decreased (P<0·05) in MSCFP and FP, while carbon dioxide (CO2 ) was decreased (P<0·05) by SC compared MSCFP and MSC. The proportional CO2 decreased (P<0·05) by MSCFP and FP additive. The mean concentration of NH3 -N was not affected by treatments. Concentration of total volatile fatty acids and the percent of acetate and propionate was not affected by treatments. The highest (P<0·05) percent of butyrate and valerate were observed in MSCFP additive. The experiment showed that microbial additives of FP, SCFP and MSCFP reduced proportional CH4 and CO2 . Microbial additives of MFP and MSCFP had a sustainable positive efficiency on pH and volatile fatty acids and mitigate CH4 and CO2 . The use of microbial additives control on the ruminal pH (MFP) and improve VFA such as butyrate (MSC, MSCFP) and valerate (MSCFP) and reduce the greenhouse gases production showed a reduced risk of ruminal acidosis.

Is there a need to reconsider the use of metformin in COVID-19 patients with type 2 diabetes mellitus?

IntroductionDiabetes has been linked with poorer outcomes in coronavirus disease (COVID-19) patients. However, the question to whether continue or withdraw metformin therapy in COVID-19 patients with type 2 diabetes mellitus remains contentious. This study aims to investigate the association between metformin and poor COVID-19 outcomes.MethodsEligible studies published up to 21 October 2020 were included and appraised for validity, importance, and applicability. The included studies were further ranked according to the level of evidence (LOE).ResultsNine studies were included for further assessments, of which seven studies stated that metformin was not associated with poor COVID-19 outcomes (LOE II-V), while the other two with poorer designs stated otherwise (LOE V). Although metformin may increase the risk of developing acidosis and lactic acidosis (LOE IV), the observed risks were more accentuated in patients with severe COVID-19 disease or kidney impairment and in patients with > 2 daily metformin doses. Interestingly, one study revealed that metformin may even yield therapeutic role in reducing the risk of COVID-19 mortality (LOE II), although further studies are required to confirm these findings.ConclusionsOur findings indicated that metformin may be safely continued in COVID-19 patients. The benefit of metformin therapy with simultaneous continuous monitoring of COVID-19 severity and kidney function may outweigh the risks of lactic acidosis, of which incidence is relatively rare.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13410-021-00924-w.

Metformin use in patients with type 2 diabetes mellitus and chronic kidney disease: An evidence-based review

Practice guidelines advise caution on the use of metformin in patients with type 2 diabetes mellitus with chronic kidney disease (CKD). This review aims to examine the evidence for the benefits and risks of metformin use in patients with T2DM and CKD. The Cochrane Database of Systematic Reviews, the Cochrane Central Register of Controlled Trials and PubMed were searched; the references of selected papers were hand searched. Systematic reviews, randomised controlled trials, cohort studies, case series and case-control studies were included. The full text of selected articles was reviewed. The outcomes studied were all-cause mortality, cardiovascular complications, lactic acidosis and worsening of renal function. Recommendations were graded according to the Scottish Intercollegiate Guidelines Network system. A total of 139 unique articles were identified, 14 of which met the inclusion criteria and were selected for full-text review. Four cohort studies reported an association between metformin use and improved all-cause mortality in CKD stage 4 and better. Two cohort studies reported improved cardiovascular outcomes with metformin use. Four cohort studies, 1 case series and 1 case-control study reported no significant association between metformin use and an increased risk of lactic acidosis in CKD. There is a moderate level of evidence to support reduced mortality, improved cardiovascular outcomes and a low risk of lactic acidosis with metformin use in patients with T2DM and with CKD stage 4 and above. Existing recommendations to restrict metformin use in diabetes patients with CKD need to be reviewed in light of emerging evidence supporting its overall benefits in these patients.

The Effect of Thiamine Supplementation for Critically Septic Patient: An Evidence-Based Case Report

Sepsis has been accounted for various burdens worldwide, especially in critically ill patients. This could eventually lead to inflammatory response, provocation ischemia and lactic acidosis. On the other hand, thiamine was suggested as a coenzyme which could improve the outcome of those patients. Thus, we conducted an evidence-based case study with research on PubMed, ProQuest, and Scopus using a search strategy focusing on RCT or cohort study on thiamine supplementation/level towards the outcome of critically ill patients with sepsis. We found three articles eligible for review after full-text assessment. Articles were appraised using the University of Oxford’s tools for critical appraisal. It was known that all studies were good in terms of validity and applicability. This study showed that thiamine supplementation could improve lactate clearance and reduce mortality risk, moreover, thiamine deficiency could increase the risk of lactate acidosis. However, a high level of thiamine was associated with a high level of lactate in patients with liver failure. Therefore, thiamine supplementation could be recommended for critically ill patients with sepsis and normal liver function. Further research, such as RCT or systematic review on thiamine supplementation for age groups to make this study more applicable.

Maternal pre-pregnancy body mass index and foetal acidosis in vaginal and caesarean deliveries: The Japan Environment and Children\u2019s Study

A high maternal body mass index (BMI) is associated with increased risks of asphyxia-related neonatal morbidity. We evaluated the association between maternal pre-pregnancy BMI and foetal acidosis while accounting for the mode of delivery. Participants from the Japan Environment and Children’s Study with singleton pregnancies after 22 weeks of gestation who gave birth during 2011–2014 were included. The participants (n = 71,799) were categorised into five groups according to the pre-pregnancy BMI: G1 (BMI < 18.5 kg/m2), G2 (18.5 to < 20.0 kg/m2), G3 (20.0 to < 23.0 kg/m2), G4 (23.0 to < 25.0 kg/m2), and G5 (≥ 25.0 kg/m2). Foetal acidosis was defined as umbilical artery pH (UmA-pH) < 7.20 or < 7.10. Multiple logistic regression analyses were used to evaluate the effect of pre-pregnancy BMI on foetal acidosis risk, accounting for the mode of delivery. In Japanese women, pre-pregnancy BMI ≥ 25.0 kg/m2 significantly increased the likelihood of foetal acidosis in newborns delivered vaginally. We found no association between pre-pregnancy BMI and foetal acidosis in newborns delivered via caesarean section. Counselling for body weight control before pregnancy and adequate management and selection of the mode of delivery in pregnant women with a high BMI who are in labour may be essential to avoid foetal acidosis.

Short-term screening of multiple phytogenic compounds for their potential to modulate chewing behavior, ruminal fermentation profile, and pH in cattle fed grain-rich diets

In cattle, proper rumen functioning and digestion are intimately linked to chewing behavior. Yet, high grain feeding impairs chewing activity, increasing the risk of subacute ruminal acidosis and dysfermentation. This study aimed to screen 9 different phytogenic compounds for their potential to modulate chewing activity, meal size, rumino-reticular short-chain fatty acids (SCFA), and pH during consumption in a first daily meal and shortly thereafter in cattle fed a grain-rich diet. Treatments were control (total mixed ration without phytogenic) or addition of a phytogenic compound at a low or high dose. Phytogenic compounds and doses (all in mg/kg) were angelica root (6.6 and 66), capsaicin (10 and 100), gentian root (6.6 and 66), garlic oil (0.3 and 3), ginger extract (40 and 400), L-menthol (6.7 and 67), mint oil (15.3 and 153), thyme oil (9.4 and 94), and thymol (5 and 50), for the low and high groups, respectively. Before the start of the screening experiment, cows were fed to reach subacute ruminal acidosis conditions, confirmed with the time of ruminal pH <5.8 being 655 ± 148.2 min/d. During the screening experiment, the treatments were offered in a controlled meal (2.5 kg of DM for 4 h) as part of the daily diet with 65% concentrate. Each treatment was tested in 4 of the 9 cannulated Holstein cows using an incomplete Latin square design. Ruminal and reticular fluids were sampled before and after each treatment, and data collected before the meal were used as covariates. Chewing and ruminal pH were monitored during the treatment, followed by 2 h of complete feed restriction, and then 4 h of ad libitum feed intake without phytogenic. Data showed that supplementation of angelica root tended to linearly increase rumination time immediately after the first meal when feed was restricted (27.3, 41.9, and 42.6 ± 5.99 min for control, low and high groups, respectively). Capsaicin increased eating time (43.6, 49.4, and 66.4 ± 4.93 min) during consumption but did not affect ruminal total SCFA or mean ruminal pH. Garlic oil reduced the concentration of reticular total SCFA (75.7, 71.3, and 60.1 mM) and tended to decrease ruminal acetate-to-propionate ratio (2.50, 1.78, and 1.87 ± 0.177) with no effect on ruminal pH. The L-menthol affected reticular total SCFA quadratically (76.1, 64.9, and 81.0 ± 4.22%), and ruminal pH responded quadratically when feed was reintroduced ad libitum (6.0, 6.3, and 6.1 ± 0.07). Mint oil did not affect chewing or total SCFA during consumption, but the low dose increased ruminal pH (6.5, 6.7, and 6.5 ± 0.08). Thyme oil tended to lower the severity of ruminal acidosis. Overall, phytogenic compounds demonstrated distinct dose-dependent effects to beneficially influence chewing behavior, modulate fermentation, and mitigate ruminal acidosis in dairy cows under a high-grain challenge diet.

Metformin doses to ensure efficacy and safety in patients with reduced kidney function.

We aimed to develop a metformin dosing strategy to optimise efficacy and safety in patients with reduced kidney function. Metformin data from two studies stratified by kidney function were analysed. The relationship between metformin clearance and kidney function estimates was explored using a regression analysis. The maintenance dose range was predicted at different bands of kidney function to achieve an efficacy target of 1 mg/L for steady-state plasma concentrations. The dosing strategy was evaluated using simulations from a published metformin pharmacokinetic model to determine the probability of concentrations exceeding those associated with lactic acidosis risk, i.e. a steady-state average concentration of 3 mg/L and a maximum (peak) concentration of 5 mg/L. A strong relationship between metformin clearance and estimated kidney function using the Cockcroft and Gault (r2 = 0.699), MDRD (r2 = 0.717) and CKD-Epi (r2 = 0.735) equations was found. The probability of exceeding the safety targets for plasma metformin concentration was <5% for most doses and kidney function levels. The lower dose of 500 mg daily was required to maintain concentrations below the safety limits for patients with an eGFR of 15–29 mL/min. Our analysis suggests that a maximum daily dose of 2250, 1700, 1250, 1000, and 500 in patients with normal kidney function, CKD stage 2, 3a, 3b and 4, respectively, will provide a reasonable probability of achieving efficacy and safety. Our results support the cautious of use metformin at appropriate doses in patients with impaired kidney function.