Ketogenic diet for epilepsy and obesity: Is it the same?

The term "ketogenic diet" (KD) is used for a wide variety of diets with diverse indications ranging from obesity to neurological diseases, as if it was the same diet. This terminology is confusing for patients and the medical and scientific community. The term "ketogenic" diet implies a dietary regimen characterized by increased levels of circulating ketone bodies that should be measured in blood (beta-hydroxybutyrate), urine (acetoacetate) or breath (acetone) to verify the "ketogenic metabolic condition". Our viewpoint highlights that KDs used for epilepsy and obesity are not the same; the protocols aimed at weight loss characterized by low-fat, low-CHO and moderate/high protein content are not ketogenic by themselves but may become mildly ketogenic when high calorie restriction is applied. In contrast, there are standardized protocols for neurological diseases treatment for which ketosis has been established to be part of the mechanism of action. Therefore, in our opinion, the term ketogenic dietary therapy (KDT) should be reserved to the protocols considered for epilepsy and other neurological diseases, as suggested by the International Study Group in 2018. We propose to adjust the abbreviations in VLCHKD for Very Low CarboHydrate Ketogenic Diet and VLEKD for Very Low Energy Ketogenic Diet, to clarify the differences in dietary composition. We recommend that investigators describe the researchers describing efficacy or side effects of KDs, to clearly specify the dietary protocol used with its unique acronym and level of ketosis, when ketosis is considered as a component of the diet's mechanism of action.

Pathology of Ketoacidosis in Emergency of Diabetic Ketoacidosis and Alcoholic Ketoacidosis: A Retrospective Study.

This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, ß-hydroxybutyric acid, and ß-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.

Ketonuria in an adult with Prader-Willi syndrome and diabetes mellitus: A case report.

RATIONALE: Prader-Willi syndrome (PWS) is a genetic disorder affecting multiple systems. Approximately one-quarter of PWS patients will develop diabetes. Given the uncontrolled hyperphagia and resultant severe obesity in these patients, their glycemic management poses a significant challenge. CASE REPORT: We present the clinical profile of a male patient diagnosed with both PWS and diabetes. Previous administration of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor Canagliflozin resulted in improved glycemic control and weight management. But at the age of 25, the patient was hospitalized due to worsened glycemic control and the detection of ketonuria. After thorough examination and clinical observation, we discovered that the patient ketonuria was associated with enhanced lipid metabolism related to Canagliflozin. After excluding the risk of SGLT-2 inhibitor-induced euglycemic diabetic ketoacidosis, adjustments of the hypoglycemic regimen, building upon prior treatment, were recommended for the patient. CONCLUSION: It is important to note that among patients with both PWS and diabetes, the utilization of SGLT-2 inhibitors can lead to the emergence of ketonuria due to increased lipolysis. Therefore, any decision to discontinue SGLT-2 inhibitors should undergo thorough evaluation.

Prediction of key milk biomarkers in dairy cows through milk mid-infrared spectra and international collaborations.

At the individual cow level, suboptimum fertility, mastitis, negative energy balance, and ketosis are major issues in dairy farming. These problems are widespread on dairy farms and have an important economic impact. The objectives of this study were (1) to assess the potential of milk mid-infrared (MIR) spectra to predict key biomarkers of energy deficit (citrate, isocitrate, glucose-6 phosphate [glucose-6P], free glucose), ketosis (ß-hydroxybutyrate [BHB] and acetone), mastitis (N-acetyl-ß-d-glucosaminidase activity [NAGase] and lactate dehydrogenase), and fertility (progesterone); (2) to test alternative methodologies to partial least squares (PLS) regression to better account for the specific asymmetric distribution of the biomarkers; and (3) to create robust models by merging large datasets from 5 international or national projects. Benefiting from this international collaboration, the dataset comprised a total of 9,143 milk samples from 3,758 cows located in 589 herds across 10 countries and represented 7 breeds. The samples were analyzed by reference chemistry for biomarker contents, whereas the MIR analyses were performed on 30 instruments from different models and brands, with spectra harmonized into a common format. Four quantitative methodologies were evaluated to address the strongly skewed distribution of some biomarkers. Partial least squares regression was used as the reference basis, and compared with a random modification of distribution associated with PLS (random-downsampling-PLS), an optimized modification of distribution associated with PLS (KennardStone-downsampling-PLS), and support vector machine (SVM). When the ability of MIR to predict biomarkers was too low for quantification, different qualitative methodologies were tested to discriminate low versus high values of biomarkers. For each biomarker, 20% of the herds were randomly removed within all countries to be used as the validation dataset. The remaining 80% of herds were used as the calibration dataset. In calibration, the 3 alternative methodologies outperform the PLS performances for the majority of biomarkers. However, in the external herd validation, PLS provided the best results for isocitrate, glucose-6P, free glucose, and lactate dehydrogenase (coefficient of determination in external herd validation [R2v] = 0.48, 0.58, 0.28, and 0.24, respectively). For other molecules, PLS-random-downsampling and PLS-KennardStone-downsampling outperformed PLS in the majority of cases, but the best results were provided by SVM for citrate, BHB, acetone, NAGase, and progesterone (R2v = 0.94, 0.58, 0.76, 0.68, and 0.15, respectively). Hence, PLS and SVM based on the entire dataset provided the best results for normal and skewed distributions, respectively. Complementary to the quantitative methods, the qualitative discriminant models enabled the discrimination of high and low values for BHB, acetone, and NAGase with a global accuracy around 90%, and glucose-6P with an accuracy of 83%. In conclusion, MIR spectra of milk can enable quantitative screening of citrate as a biomarker of energy deficit and discrimination of low and high values of BHB, acetone, and NAGase, as biomarkers of ketosis and mastitis. Finally, progesterone could not be predicted with sufficient accuracy from milk MIR spectra to be further considered. Consequently, MIR spectrometry can bring valuable information regarding the occurrence of energy deficit, ketosis, and mastitis in dairy cows, which in turn have major influences on their fertility and survival.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Diabetic ketosis vs ketoacidosis as initial presentation of pediatric type 1 diabetes mellitus. Associated features and rate of progression during the first two years after diagnosis.

AIMS: In this study we described the clinical and laboratory features of children presented with diabetic ketosis or diabetic ketoacidosis at diagnosis of type 1 diabetes (T1DM) and evaluated its course up to 2 years after initial diagnosis to investigate the progression rate of T1DM in both groups. METHODS: This was a prospective longitudinal cohort study that included 59 children and adolescents presented with either diabetic ketosis (DK) (n = 27) or diabetic ketoacidosis (DKA) (n = 32) at their first diagnosis with T1DM. RESULTS: Apart from the metabolic state of presentation at diagnosis, differences in the other basic clinical and laboratory features of both DK and DKA were not statistically significant (age, BMI, pre- diagnosis symptomatic period, HbA1c, multiplicity of autoantibodies positivity, fasting insulin, and total IgG levels), except from the C-peptide and IgA levels which were lower in DKA (p < 0.05). Regarding family history, only the DK group had individuals with a parent diagnosed with T1DM (p = 0.001). During follow-up there was no difference in the levels of HbA1c, basal insulin dose, and insulin/carbohydrate ratio between the DK and DKA group at 3,6,12 and 24 months' time points. CONCLUSIONS: The severity of presentation of T1DM (DK or DKA) is not associated to the rate of progression of the disease course after diagnosis.

[Reversible bilateral blindness associated with alcoholic ketoacidosis: a case report].

A 51-year-old male with a history of chronic alcoholism presented to the emergency department with an abrupt onset of complete bilateral blindness lasting for one hour. Funduscopic examination yielded unremarkable findings. Systemic evaluations revealed the presence of severe ketoacidosis. The patient spontaneously regained light perception after experiencing total blindness for 3 hours; however, he subsequently developed hypothermia and entered a state of shock. Following treatment with sodium bicarbonate and aggressive fluid resuscitation, his condition stabilized, and there was a rapid improvement in his visual acuity. The diagnosis of alcoholic ketoacidosis was established based on the patient's history of chronic alcohol abuse, physical examination findings, and blood analysis results.

Evaluating variations in metabolic profiles during the dry period related to the time of hyperketonemia onset in dairy cows.

Hyperketonemia (HYK) in early lactation can have a different impact on health and productivity depending on the timing of HYK onset. While specific metabolites measured during the dry period may serve as biomarkers of HYK, the correlations between metabolites represent a challenge for the use of metabolic profiles dataset, and little has been explored on HYK. This exploratory cohort study aimed a) to characterize the correlations among metabolites measured during the late dry period in dairy cows, and b) to identify biomarkers in the late dry period associated with the onset of HYK at the first (wk1) and second (wk2) week of lactation. Individual blood samples from 440 Holstein dairy cows were collected at 21 ± 3 days before expected parturition. From each sample, 36 different metabolites were measured in serum and plasma. Hyperketonemia was diagnosed in wk1 and wk2 of lactation based on the blood concentration of beta-hydroxybutyrate (BHB > 1.2 mmol/L). Principal component analysis (PCA) was performed to reduce metabolites to a smaller number of uncorrelated components. Multivariable logistic regression models were applied to assess the associations between principal components (PC) and HYK at wk1 only (HYK+ wk1), wk2 only (HYK+ wk2), or both weeks (HYK+ wk1-2). The incidence of HYK was 16.2% in the first week, 13.0% in the second week, and 21.2% within the first two weeks of lactation. The results of PCA highlighted 10 PCs from which two were associated with HYK+ wk1 as compared with cows without HYK during the first two weeks of lactation (non-HYK); the PC a2 led by bilirubin and non-esterified fatty acids (OR = 1.29; 95%CI: 1.02-1.68), and the PC a5 led by alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) (OR = 2.77; 95%CI: 1.61-4.97). There was no evidence of an association between any PC and HYK+ wk2 (vs. non-HYK cows). Cows with elevated PC a5 (led by ALP and GGT) in the dry period were 3.18 times more likely to be HYK+ wk1 than HYK+ wk2 (OR: 3.18, 95%CI: 1.34-8.73; P = 0.013). Overall, the main hypothesis generated by our exploratory study suggests that cows with biomarkers of liver dysfunction (ALP, GGT, bilirubin) assessed by PCA at 3 weeks before calving are more likely to develop HYK during the first week of lactation compared to the second week. In addition, results suggest that cows with HYK in both of the first two weeks of lactation had an overall metabolic disbalance during the onset of the late dry period, which based on PCs, encompass biomarkers related to glucogenic and ketogenic metabolic pathways as well as liver dysfunction and fatty liver. Further research is needed to determine the underlying mechanisms associated with the different adaptations between cows that develop HYK during the first and second week of lactation.

Metabolic-digestive clinical disorders of lactating dairy cows were associated with alterations of rumination, physical activity, and lying behavior monitored by an ear-attached sensor.

The objective of this observational cohort study was to characterize the pattern of rumination time (RT), physical activity (PA), and lying time (LT) monitored by an automated health monitoring system, based on an ear-attached sensor, immediately before, during, and after clinical diagnosis (CD) of metabolic-digestive disorders. Sensor data were collected from 820 lactating Holstein cows monitored daily from calving up to 21 DIM for detection of health disorders (HD). Cows were grouped retrospectively in the no-clinical health disorder group (NCHD; n = 616) if no HD were diagnosed, or the metabolic-digestive group (METB-DIG; n = 58) if diagnosed with clinical ketosis or indigestion only. Cows with another clinical health disorder within -7 to +7 d of CD of displaced abomasum, clinical ketosis, or indigestion were included in the metabolic-digestive plus one group (METB-DIG+1; n = 25). Daily RT, PA, and LT, and absolute and relative changes within -7 to +7 d of CD were analyzed with linear mixed models with or without repeated measures. Rumination time and PA were smaller, and LT was greater for the METB-DIG and METB-DIG+1 group than for cows in the NCHD group for most days from -7 to +7 d of CD of HD. In general, daily RT, PA, and LT differences were larger between the METB-DIG+1 and NCHD groups than between the METB-DIG and NCHD groups. In most cases, RT and PA decreased to a nadir and LT increased to a peak immediately before or after CD of HD, with a return to levels similar to the NCHD group within 7 d of CD. Absolute values and relative changes from 5 d before CD to the day of the nadir for RT and PA or peak for LT were different for cows in the METB-DIG and METB-DIG+1 group than for the NCHD group. For PA, the METB-DIG+1 group had greater changes than the METB-DIG group. For cows affected by metabolic-digestive disorders, RT, PA, and LT on the day of CD and resolution of clinical signs were different than for cows in the NCHD group, but an increase in RT and PA or a decrease in LT was observed from the day of CD to the day of resolution of clinical signs. We conclude that dairy cows diagnosed with metabolic-digestive disorders including displaced abomasum, clinical ketosis, and indigestion presented substantial alterations in the pattern of RT, PA, and LT captured by an ear-attached sensor. Thus, automated health monitoring systems based on ear-attached sensors might be used as an aid for identifying cows with metabolic-digestive disorders. Moreover, RT, PA, and LT changes after CD might be positive indicators of recovery from metabolic-digestive disorders.

Subnuclear renal tubular vacuoles in alcohol use disorder.

Subnuclear vacuoles in the proximal renal tubules have been reported as a histologic sign of ketoacidosis. Originally described in diabetic ketoacidosis, renal vacuoles can be found in other ketogenic states such as alcoholic ketoacidosis (AKA), starvation, and hypothermia, underpinned by deranged fatty acid metabolism. A retrospective analysis of 133 deaths associated with alcohol use disorder (AUD) examined at autopsy between 2017 and 2020 was undertaken. This study aimed to determine the prevalence of subnuclear vacuoles in deaths of those with AUD and their specificity for deaths from AKA, and to elucidate what demographic, biochemical, and pathologic findings are associated with subnuclear vacuoles. In each case, vitreous humor biochemistry including electrolytes, glucose, and beta-hydroxybutyrate (BHB) was analyzed alongside postmortem hemoglobin A1c and renal and liver histology. Renal histology was graded for the presence of vacuoles as absent (0), scanty (1), or easily identifiable (2). Liver histology was graded for steatosis and for fibrosis if Masson trichrome staining was available. Vacuoles were commonly seen in the deaths of those with AUD. They were seen in deaths due to AKA but were not specific to that cause of death. With vacuoles present, lower vitreous sodium (139 vs. 142 mmol/L; p = 0.005), higher vitreous BHB (1.50 vs. 1.39 mmol/L; p = 0.04), severe hepatic steatosis, and severe hepatic fibrosis were seen, compared with those without renal vacuoles.

Alcoholic ketoacidosis evaluated with a point-of-care capillary beta-hydroxybutyrate measurement device.

BACKGROUND: The diagnosis of alcoholic ketoacidosis (AKA) has traditionally been made based only on clinical history and the presence of severe metabolic acidosis with a high anion gap (AG); however, the concentration of beta-hydroxybutyrate (BOHB), a pivotal ketone body in AKA, is not evaluated in most cases. The aim of this study was to clarify the clinical spectrum of AKA in terms of the severity of ketoacidosis by using a point-of-care capillary BOHB measurement device. METHODS: This retrospective case series was conducted at a Japanese private teaching hospital. Patients with suspected AKA, based on their clinical history, who underwent BOHB measurement using a point-of-care capillary measurement device in the emergency department, were included. Data on their clinical presentations, blood tests, and treatments were collected, described, and compared between patients with a BOHB concentration higher than 3.0 mmol/L (H-BOHB) and those with a concentration less than 3.0 mmol/L (L-BOHB). RESULTS: A total of 83 patients were included in this study. Sixty-eight patients were categorized as having H-BOHB and 15 as having L-BOHB. Nausea (71%), vomiting (71%), tachycardia (76%), and tachypnea (46%) were commonly observed at presentation. Hyponatremia (46%), hypokalemia (34%), hypomagnesemia (42%), and hyperphosphatemia (41%) were frequent electrolyte abnormalities upon presentation. Rehydration with balanced crystalloids and glucose-containing intravenous fluids, electrolyte supplementation, and thiamine replacement were the major treatments. The mean length of stay in the ICU and hospital were 4.4 and 7.0 days, respectively, with low overall mortality (1%). The H-BOHB and L-BOHB groups did not differ in terms of clinical data. Seventy percent of patients with L-BOHB had severe metabolic acidosis with a high AG due to hyperlactatemia (mean lactate concentration: 8.5 mmol/L). CONCLUSIONS: We described the clinical features of AKA measured by using a point-of-care capillary BOHB measurement device. Although certain patients diagnosed with AKA based only on their clinical history had predominant lactic acidosis with minor elevations in BOHB concentration, the BOHB concentration had no effect on the clinical spectrum of AKA in this study.

Defining Physiological Ketosis Following Very-Low-Calorie Diets.

INTRODUCTION: Very low-calorie diets (VLCDs) are used preoperatively in bariatric-metabolic surgery; however, this can lead to physiological ketosis. Euglycemic ketoacidosis is an increasingly recognized complication in diabetic patients on sodium-glucose-cotransporter-2 inhibitors (SGLT2i) undergoing surgery and requires assessment of ketones for diagnosis and monitoring. VLCD induced ketosis may confound monitoring in this group. We aimed to evaluate the influence of VLCD, compared to standard fasting, on perioperative ketone levels and acid-base balance. MATERIALS AND METHODS: Twenty-seven patients were prospectively recruited to the intervention group and 26 to the control group from two tertiary referral centres in Melbourne, Australia. Intervention group patients were severely obese (body mass index) (BMI) (≥35), undergoing bariatric-metabolic surgery, and prescribed 2 wk of VLCD preoperatively. Control group patients underwent general surgical procedures and prescribed standard procedural fasting only. Patients were excluded if diabetic or prescribed SGLT2i. Ketone and acid-base measurements were taken at regular intervals. Univariate and multivariate regression was utilised with significance defined as P < 0.005. CLINICALTRIALS: gov ID: NCT05442918. RESULTS: Patients on VLCD, compared to standard fasting, had an increased median preoperative (0.60 versus 0.21 mmol/L), immediate postoperative (0.99 versus 0.34 mmol/L) and day 1 postoperative (0.69 versus 0.21 mmol/L) ketone level (P < 0.001). Preoperative acid-base balance was normal in both groups, however VLCD patients were found to have a metabolic acidosis immediately postoperatively (pH 7.29 versus pH 7.35) (P = 0.019). Acid-base balance had normalized in VLCD patients on postoperative day 1. CONCLUSIONS: Preoperative VLCD resulted in increased pre- and postoperative ketone levels with immediate postoperative values consistent with metabolic ketoacidosis. This should be considered particularly when monitoring diabetic patients prescribed SGLT2i.

Fasting ketone levels vary by age: implications for differentiating physiologic from pathologic ketotic hypoglycemia.

OBJECTIVES: Ketone production is a physiological phenomenon that occurs during beta-oxidation of free fatty acids. Distinguishing physiologic ketosis from pathologic over-production/underutilization of ketones is critical as part of the diagnostic evaluation of disorders of carbohydrate metabolism, but there is limited literature on normal ketone production with fasting. Our aim is to measure fasting serum beta-hydroxybutyrate (BHB) concentrations in healthy children after an overnight fast. METHODS: Children ≤18 years of age were prospectively recruited from elective procedures through our surgery centers. Exclusion criteria included a history of diabetes, hypopituitarism, adrenal, metabolic or inflammatory disorders, dietary restrictions, trauma, or use of medications that might affect blood glucose. Serum glucose, cortisol, and BHB were assessed after an overnight fast. RESULTS: Data from 94 participants (mean 8.3 ± 5.7 years, 54 % male, 46 % female, were analyzed. Children ≤3 years of age (19) have significantly higher mean (0.40 ± 0.06 mmol/L) and median (0.4, IQR 0.2-0.6 mmol/L) BHB concentrations compared to children >3 years of age (75) with mean (0.21 ± 0.02 mmol/L) and median BHB (0.1, IQR 0.1-0.2 mmol/L) (p<0.0001). Fasting BHB levels of >1.0 mmol/L was rare (2 %, N=2) and 74 % (N=70) of participants had BHB levels <0.3 mmol/L. CONCLUSIONS: BHB concentrations are significantly higher in young children (≤3 years of age) compared to older children. Fasting BHB levels >1.0 mmol/L are rare within our population and therefore may identify a value above which there may a greater concern for pathologic ketotic hypoglycemia. It is imperative to establish the normative range in children to differentiate physiological from pathological ketotic hypoglycemia.

What is the utility of blood beta-hydroxybutyrate measurements in emergency department in patients without diabetes: a systematic review.

BACKGROUND: Ketones are synthesised as an alternative fuel source during times of energy restriction. In the absence of a hyperglycemic emergency, ketosis in patients presenting to the emergency department (ED) may indicate reduced carbohydrate intake. In the perioperative setting, excess fasting with ketosis is associated with worse outcomes; however, whether ketosis in patients without diabetes presenting to ED is also associated with worse outcomes is unclear. This systematic review aims to examine the evidence for ketosis in predicting the need for hospital admission in patients without diabetes, presenting to the ED. METHODS: A systematic review was performed using PRISMA guidelines. We searched electronic bases (OVID-Medline, OVID-EMBASE, Scopus and PubMed) up to December 2022. Eligible studies included children or adults without diabetes presenting to the ED where a point-of-care capillary beta-hydroxybutyrate (BHB) was measured and compared to outcomes including the need for admission. Outcome measures included need for admission and length of stay. Content analysis was performed systematically; bias and certainty assessed using standard tools. RESULTS: The literature search found 17,133 citations, 14,965 papers were subjected to title and abstract screening. The full text of 62 eligible studies were reviewed. Seven articles met the inclusion criteria. Six studies were conducted solely in the paediatric population, and of these, four were limited to children presenting with gastroenteritis symptoms. Median BHB was higher in children requiring hospital admission with an AUC of 0.64-0.65 across two studies. There was a weak correlation between BHB and dehydration score or duration of symptoms. The single study in adults, limited to stroke presentations, observed no relationship between BHB and neurological deficit at presentation. All studies were at risk of bias using the Newcastle-Ottawa Scale and was assessed of "very low" to "low" quality due to their study design in the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Heterogeneity amongst selected studies precluded meta-analysis. CONCLUSION: The evidence for any utility of BHB measurement in the ED in absence of diabetes is limited to the paediatric population, specifically children presenting with symptoms of gastroenteritis. Any role in adults remains unexplored.

Hyperketonemia: A Marker of Disease, a Sign of a High-Producing Dairy Cow, or Both?

This review covers the history and nomenclature of ketosis, the source and use of ketones in transition cows, and the controversial role of hyperketonemia's association with health and production outcomes in dairy cows. With the goal of assisting veterinarians with on-farm diagnostic and treatment methods, the authors present current and evolving means of direct and indirect hyperketonemia detection as well as a summary of treatment modalities and their efficacy. They encourage veterinarians to include hyperketonemia testing as part of their routine physical examinations and contemplate day in milk at hyperketonemia diagnosis when designing treatment and management strategies.

Evaluation of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care meters for measuring blood ß-hydroxybutyrate concentration in sheep.

BACKGROUND: Accurate and rapid measurement of blood ß-hydroxybutyrate (ß-OHB) concentrations is critical to identify hyperketonemia in sheep. OBJECTIVE: The objective of this study was to test the performance of Freestyle Optium Neo H and TaiDoc-TD4235 point-of-care (POC) devices for measuring blood ß-OHB concentrations in sheep. METHODS: Venous blood samples from 105 sheep were evaluated with Freestyle Optium Neo H and TaiDoc-TD4235 meters. A reference approach was the laboratory measurement of serum BHB concentrations using the Randox D-3 Hydroxybutyrate reagent kit. Data were analyzed using Passing- Bablok regression and Bland-Altman analysis. The diagnostic accuracy was assessed using serum ß-OHB concentration at a cut-off value of 0.8 mmol/L. RESULTS: Passing-Bablok regression analysis revealed an intercept of 0.066 (CI95 : 0.018-0.125) and slope of 1.242 (CI95 : 1.136-1.342) for Freestyle Optium Neo H. Intercept and slope values for the TaiDoc-TD4235 meter were 0.625 (CI95 : 0.539-0.724) and 1.265 (CI95 : 1.044-1.497), respectively. The Bland-Altman plot revealed a bias of 0.224 mmol/L and 0.737 mmol/L for Freestyle Optium Neo H and TaiDoc-TD4235 meters, respectively, compared with the reference method. Observed Total Error (TEobs ) was 56.7% for the Freestyle Optium Neo H and 168.7% for the Taidoc-TD4235. The sensitivity and specificity for the Freestyle Optium Neo H were 100% and 80.9%, respectively, at the threshold of 0.8 mmol/L. The Taidoc-TD4235 demonstrated a sensitivity of 93.3% and specificity of 8.9% at the threshold of 0.8 mmol/L. CONCLUSIONS: Because of the large TEobs , the Freestyle Optium Neo H and TaiDoc-TD4235 meters should not be used to quantify blood ß-OHB concentrations in sheep.

Diagnóstico precoce de acetonemia subclínica em vacas holandesas por mensuração de corpos cetônicos / Early diagnosis of subclinical acetonemia in holstein cows by measuring ketone bodies / Diagnóstico precoz de acetonemia subclínica en vacas holstein mediante la medición de cuerpos cetónicos

O trabalho foi realizado em uma fazenda de exploração leiteira em Castrolanda, no município de Castro ­ PR. O sistema de manejo é free-stall, com 220 vacas da raça Holandesa com RHA305 de 6.740 litros. Foram coletadas amostras de sangue de 18 vacas de pré-parto, 4 dias antes da data prevista para o parto; e nos dias 4, 7 e 12 pós-parto, mediante punção venosa coccígea, utilizando-se SnapTest digital Ketovet®, constituindo 72 amostras, no período de fevereiro a maio de 2020. Em 4 vacas o BHB do sangue total apresentou-se acima do limite para cetose subclínica no quarto dia após o parto e 17 apresentaram-se acima do limite no sétimo dia, declinando em seguida, principalmente devido às intervenções clínicas. As médias e desvios-padrão foram: D - 4: 0,89 ± 0,257061; D 4: 1,05 ± 0,283279; D 7: 1,81 ± 0,456131; e D 12: 1,19 ± 0,437762. O benefício do monitoramento de BHB foi a imediata intervenção clínica, evitando-se a severidade por instalação de quadro clínico e as enfermidades concomitantes.(AU)

The study was carried out on a dairy farm in Castrolanda, in the county of Castro - PR. The management system is free stall, with 220 Holstein cows with RHA305 of 6,740 liters. Blood samples were collected from 18 pre-calving cows, 4 days before the expected date of calving; and on days 4, 7 and 12 postpartum, by means of coccygeal venipuncture, using SnapTest digital Ketovet®, constituting 72 samples, from February to May 2020. In 4 cows the BHB of whole blood was shown above the limit for subclinical ketosis on the fourth day after delivery and 17 presented above the limit on the seventh day, then declining mainly due to clinical interventions. The means and standard deviations were D -4: 0.89 ± 0.257061; D 4: 1.05 ± 0.283279; D 7: 1.81 ± 0.456131; and D 12: 1.19 ± 0.437762. The benefit of monitoring BHB was immediate clinical intervention, avoiding clinical ketosis and concomitant illnesses.(AU)

El estudio se realizó en una explotación lechera de Castrolanda, en la comarca de Castro - PR. El sistema de manejo es estabulación libre, con 220 vacas Holstein con RHA305 de 6.740 litros. Se recogieron muestras de sangre de 18 vacas pre- parto, 4 días antes de la fecha prevista de parto; y en los días 4, 7 y 12 postparto, mediante venopunción coccígea, utilizando SnapTest digital Ketovet®, constituyendo 72 muestras, desde febrero a mayo de 2020. En 4 vacas la BHB de sangre total se mostró por encima del límite para cetosis subclínica en el cuarto día después del parto y 17 presentaron por encima del límite en el séptimo día, disminuyendo después debido principalmente a intervenciones clínicas. Las medias y desviaciones estándar fueron D -4: 0,89 ± 0,257061; D 4: 1,05 ± 0,283279; D 7: 1,81 ± 0,456131; y D 12: 1,19 ± 0,437762. El beneficio de monitorizar la BHB fue la intervención clínica inmediata, evitando la cetosis clínica y las enfermedades concomitantes.(AU)