Heart failure ejection fraction class conversions: impact of biomarkers, co-morbidities, and pharmacotherapy.

AIMS: Temporal conversions among ejection fraction (EF) classes can occur across the heart failure (HF) spectrum reflecting amended structural and functional outcomes unaccounted for by current taxonomy. This retrospective study aims to investigate the differences in serum laboratory values, guideline-directed medical therapy (GDMT), and co-morbidity burden across EF conversion groups. METHODS AND RESULTS: Heart failure patients at least 18-year-old who obtained at least two echocardiograms between January 2018 and January 2020 were identified using ICD-10 codes. Analysis of variance, chi-square tests, and analysis of means for proportions were used as appropriate to identify associations with class conversion groups. A total of 874 patients who underwent 1748 echocardiograms on unique visits were categorized according to initial EF as HF with preserved EF (HFpEF) (n = 531, 61%), HF with mildly reduced or midrange EF (HFmrEF) (n = 132, 15%), or HF with reduced EF (HFrEF) (n = 211, 24%). In accordance with follow-up EF, class conversions were categorized into HF with improved EF (HFiEF) (n = 143, 16%), HF with worsened EF (HFwEF) (n = 171, 20%), or HF with stable EF (HFsEF) (n = 560, 64%). The average age was 75 ± 13 years old; 54% were male, 85% were Caucasian, 11% were African American, and 4% other. The mean time between EF assessments was 208.6 ± 170.2 days. Serum sodium levels were greater in HFwEF (139 ± 3 mmol/L) when compared with HFsEF (138 ± 4 mmol/L) (P = 0.05). Pro-BNP levels were higher in HFiEF (12 150 ± 19 554 pg/mL) versus HFsEF (6671 ± 10 525 pg/mL) (P = 0.007). Angiotensin receptor-neprilysin inhibitors (ARNI) were more frequently ordered on index visit in HFiEF (P = 0.03), but no other significant differences in GDMT were identified. Despite similar Elixhauser Co-morbidity Measure (ECM) scores, ECM categorical analysis revealed that HFwEF was more likely to have an established diagnosis of depression (P = 0.03) and a spectrum of psychiatric illnesses (P = 0.03) on preliminary visit. HFsEF was less likely to have an established diagnosis of blood loss anaemia (P = 0.04). Metastatic cancer was more likely to have been diagnosed in HFiEF and less likely in HFsEF (P = 0.002). CONCLUSIONS: Despite similar ECM scores, EF class conversion groups demonstrated salient differences in average serum sodium and pro-BNP levels. Inpatient ARNI orders, psychiatric, hematologic, and oncologic co-morbidity patterns were also significantly different. Findings demonstrate blood-based biomarker patterns and targetable co-morbid conditions which may play a role in future EF class conversion. Dedicated studies evaluating measurements related to GDMT dose-titration, quality of life, and functionality are the next steps in this field of HF.

The impact of a high-fat diet on physical activity and dopamine neurochemistry in the striatum is sex and strain dependent in C57BL/6J and DBA/2J mice.

BACKGROUND: Obesity has been linked to behavioral and biochemical changes, such as reduced physical activity, dysregulated dopamine metabolism, and gene expression alterations in the brain. The impact of a continuous high-fat diet and resulting state of obesity may vary depending on sex and genetics. OBJECTIVE: The aim of this study was to investigate the impact of a high-fat diet on physical activity, gene expression in the striatum, and dopamine neurochemistry using male and female mice from different strains as a model to examine sex and strain influences on dopamine-mediated behavior and neurobiology. METHODS: Male and female mice from the C57BL/6J (B6J) and DBA/2J (D2J) strains were randomly assigned a control low-fat diet with 10% kcal fat or a high-fat diet with 60% kcal fat for 16 weeks. We assessed ambulation and habituation using the open field test; dopamine release and reuptake using ex-vivo fast scan cyclic voltammetry; and striatal mRNA expression of dopamine receptor D2, alpha synuclein, and tyrosine hydroxylase. RESULTS: Mice fed a high-fat diet exhibited reduced motor activity, but only obese B6J male mice displayed reduced habituation. Dopamine clearance in the dorsal striatum was reduced only in obese D2J mice, while dopamine clearance in the nucleus accumbens core was reduced only in male obese D2J mice. Striatal dopamine receptor D2 gene expression was upregulated exclusively in obese male B6J mice. CONCLUSION: Our study provides evidence for important sex and strain influences on the impact of a high-fat diet and obesity-induced behavior alterations and neurobiology dysregulation in the striatum.

The influence of sex and strain on trace element dysregulation in the brain due to diet-induced obesity.

BACKGROUND: The objective of this study was to identify interaction effects between diet, sex, and strain on trace element dysregulation and gene expression alterations due to diet-induced obesity (DIO) in the hippocampus, striatum, and midbrain. METHODS: Male and female C57BL/6 J (B6 J) and DBA/2 J (D2 J) mice were fed either a low fat (10 % kcal) diet (LFD) or high fat (60 % kcal) diet (HFD) for 16 weeks, then assessed for trace element concentrations and gene expression patterns in the brain. RESULTS: In the hippocampus, zinc was significantly increased by 48 % in D2 J males but decreased by 44 % in D2 J females, and divalent metal transporter 1 was substantially upregulated in B6 J males due to DIO. In the striatum, iron was significantly elevated in B6 J female mice, and ceruloplasmin was significantly upregulated in D2 J female mice due to DIO. In the midbrain, D2 J males fed a HFD had a 48 % reduction in Cu compared to the LFD group, and D2 J females had a 37 % reduction in Cu compared to the control group. CONCLUSIONS: The alteration of trace element homeostasis and gene expression due to DIO was brain-region dependent and was highly influenced by sex and strain. A significant three-way interaction between diet, sex, and strain was discovered for zinc in the hippocampus (for mice fed a HFD, zinc increased in male D2 Js, decreased in female D2 Js, and had no effect in B6 J mice). A significant diet by sex interaction was observed for iron in the striatum (iron increased only in female mice fed a HFD). A main effect of decreased copper in the midbrain was found for the D2 J strain fed a HFD. These results emphasize the importance of considering sex and genetics as biological factors when investigating potential associations between DIO and neurodegenerative disease.

Diet-Induced Obesity Disrupts Trace Element Homeostasis and Gene Expression in the Olfactory Bulb.

The aim of this study was to determine the impact of diet-induced obesity (DIO) on trace element homeostasis and gene expression in the olfactory bulb and to identify potential interaction effects between diet, sex, and strain. Our study is based on evidence that obesity and olfactory bulb impairments are linked to neurodegenerative processes. Briefly, C57BL/6J (B6J) and DBA/2J (D2J) male and female mice were fed either a low-fat diet or a high-fat diet for 16 weeks. Brain tissue was then evaluated for iron, manganese, copper, and zinc concentrations and mRNA gene expression. There was a statistically significant diet-by-sex interaction for iron and a three-way interaction between diet, sex, and strain for zinc in the olfactory bulb. Obese male B6J mice had a striking 75% increase in iron and a 50% increase in manganese compared with the control. There was an increase in zinc due to DIO in B6J males and D2J females, but a decrease in zinc in B6J females and D2J males. Obese male D2J mice had significantly upregulated mRNA gene expression for divalent metal transporter 1, alpha-synuclein, amyloid precursor protein, dopamine receptor D2, and tyrosine hydroxylase. B6J females with DIO had significantly upregulated brain-derived neurotrophic factor expression. Our results demonstrate that DIO has the potential to disrupt trace element homeostasis and mRNA gene expression in the olfactory bulb, with effects that depend on sex and genetics. We found that DIO led to alterations in iron and manganese predominantly in male B6J mice, and gene expression dysregulation mainly in male D2J mice. These results have important implications for health outcomes related to obesity with possible connections to neurodegenerative disease.

Nitrous Oxide-Induced Vitamin B12 Deficiency Resulting in Myelopathy.

Nitrous oxide, primarily used in the medical field and in the food industry, can cause symptoms of euphoria and analgesia. Recreational use of nitrous oxide is rising, as are reports of its adverse effects, including neurologic complaints secondary to an evoked vitamin B12 deficiency. We outline a case of a patient presenting with several neurologic symptoms and found to have myelopathy secondary to vitamin B12 deficiency in the presence of prolonged recreational nitrous oxide use.

Assessing treatment and monitoring of musculoskeletal conditions using opioid versus nonopioid therapy: A cross-sectional study.

The purpose of this study is to examine the treatment of noncancer musculoskeletal pain in different clinical settings by assessing patient demographics, pain diagnoses, opioid analgesic monitoring, and alternative treatments.Data was collected in a retrospective chart review involving 300 randomly selected charts with an active musculoskeletal diagnosis based on the 10th revision of the International Statistical Classification of Diseases and Related Health Problems codes. The population consisted of primary care outpatient clinic and emergency department encounters during the timeframe of January 1, 2016 to March 31, 2016 in a predominantly rural community in Michigan. Variables included prescription medications, musculoskeletal conditions, and prescription drug monitoring modalities. Statistical analysis was accomplished using means, standard deviations, proportions, 2-sample proportional tests, multivariable logistic regression, and multinomial regression models.Opioid prescribing was observed in 64% of outpatient and 68.9% of emergency department encounters. Back pain was the most common problem with 61.9% patients prescribed opioids having at least 1 diagnosis of back pain. Patients on opioids were older (mean age 58) than patients taking nonopioids (mean age 50). For every year of increasing age, there is a 3.1% increase in the odds of an opioid being prescribed (odds ratio 1.03, confidence interval 1.012-1.049, P = .001). Documentation was extremely low with only 15.2%, 1.5%, and 1.5% of patient charts prescribed opioids demonstrating documentation of urine drug screens, pain agreements, and review of a state prescription drug monitoring program, respectively.Despite drug monitoring recommendations, low rates of monitoring were observed. Back pain was the largest contributing pain location and had higher opioid use compared to other sites. Many patients had additional pain medications being concurrently prescribed with opioids suggesting that musculoskeletal pain is not often controlled by a single medication type. Reported alcohol abuse, active tobacco use, and illicit substance use can serve as predictors when assessing patients for pain management options. The use of alternative measures and integrative treatment modalities (which saw low utilization in this study) should be implemented as either primary or supplementary therapy as a way to reduce the pharmacologic burden on the patient.