Effects of bempedoic acid on markers of inflammation and Lp(a).

PURPOSE OF REVIEW: To study the effect of bempedoic acid on markers of inflammation and lipoprotein (a) to help determine if the drug would be useful to treat patients with elevated cardiovascular risks and residual cardiovascular risk despite optimal low-density lipoprotein cholesterol (LDL-C) levels. RECENT FINDINGS: Bempedoic acid is found to cause significant reduction in LDL-C and high-sensitivity C-reactive protein (hs-CRP) in various randomized clinical trials. Multiple meta-analyses have also found that bempedoic acid therapy leads to reduction in non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol (TC) and apolipoprotein B (ApoB) levels. However, it has minimal effect on lipoprotein (a) (Lp(a)) level. SUMMARY: Bempedoic acid is a new lipid-lowering agent that inhibits enzyme ATP-citrate lyase in the cholesterol biosynthesis pathway. Major risk of cardiovascular events and its associated morbidity and mortality are proportional to LDL-C and inflammatory markers levels. It was found that bempedoic acid significantly lowers LDL-C, hs-CRP and other inflammatory markers levels. This drug could potentially be used in patients with elevated cardiovascular risk, in patients with residual cardiovascular risk despite attaining LDL-C goal and in statin intolerant patients.

The Enhanced Cardiac Outcome of Conjugated SGLT2 Inhibitors and GLP-1RA Therapy in Diabetic Patients.

PURPOSE OF REVIEW: Cardiovascular disease secondary to diabetes continues to threaten the survivability of many people all over the world. We assess the most recent findings of synergistic effects of combined glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in lowering cardiac complications in the diabetic population. We describe drug therapies' mechanism of action, postulated cardioprotective process, the additive value of conjugated therapy, and analyze recently reported study and its limitation. RECENT FINDINGS: SGLT2 inhibitors and GLP-1RAs have gained popularity due to their ability to reduce major adverse cardiovascular events in diabetic patients. There is emerging evidence of the additional cardiovascular benefit from the combined application of SGLT2 inhibitors and GLP-1RAs therapy demonstrated by a recent real-world cohort study. Reducing cardiac mortality in patients with diabetes by administering dual antihyperglycemic therapies (GLP-1Rs and SGLT2 inhibitors) might play a key role in the future treatment of the diabetic population.

Updates in Anti-anginal and Anti-ischemic Therapies for Acute Coronary Syndromes.

PURPOSE OF REVIEW: Acute coronary syndrome is a major health problem affecting ~ 1.5 million individuals a year in the USA. We review the contemporary role of anti-anginal and anti-ischemic therapies in the management of an individual presenting with an acute coronary syndrome. RECENT FINDINGS: Early diagnosis and appropriate evidence-based therapies significantly improve clinical outcomes in acute coronary syndrome patients. Typically, acute coronary syndrome is associated with rupture of an atherosclerotic plaque and either partial or complete thrombotic occlusion of a coronary artery. Management of an acute coronary syndrome is targeted towards this underlying pathophysiology. The last few years have seen significant advances in anti-anginal and anti-ischemic therapies in the management of patients with acute coronary syndrome. It is important to have a team effort to target risk reduction measures and to emphasize medication and dietary compliance. Long-term pharmacotherapy should include aspirin, beta-blocker, DAPT (for at least 1 year), statins, and ACE inhibitors and PCSK9 inhibitors if indicated.

Dairy Intake and Risk of Cardiovascular Disease.

PURPOSE OF REVIEW: Due to inconsistent findings on dairy consumption and CVD and all-cause mortality, we performed a narrative literature review to the current literature on dairy and its association with CVD. RECENT FINDINGS: Due to their complex biochemistry, dairy consumption is a rather heterogeneous exposure. Multiple pathways have been proposed from dairy consumption and CVD. Current guidelines advocate for consumption of low-fat dairy products particularly milk, cheese, and yogurt, although the evidence for this is scant. Randomized clinical trials and large prospective studies on lipid-related cardiometabolic disease risk factors are consistent with results from most meta-analyses of prospective cohort studies, which suggest null or inverse relationship between CVD risk and mortality with dairy consumption although there is no clear dose response relationship. Most of current evidence suggests that dairy products are neutral or positive effect on human cardiovascular diseases.

COLORECTAL CANCER IN HISPANICS LIVING NEAR THE U.S.-MEXICO BORDER.

BACKGROUND: The incidence of colorectal cancer (CRC) in the US has declined. The decreasing trend is observed in non-Hispanic Whites, Blacks, and Hispanics. However, close analysis of the trends demonstrates that the decline among Hispanics is less than other races/ethnicities. We investigate the burden of CRC in Hispanics living near the U.S.-Mexico border, a subpopulation of Hispanics composed primarily of individuals of Mexican origin. OBJECTIVES: The objective of this study was to investigate and compare incidence rates of CRC in non-Hispanic Whites and Hispanics living in counties along the U.S.-Mexico border. METHODS: Data from the National Institutes of Health National Cancer Institute and State Cancer Profiles were analyzed to obtain CRC incidence rates (per 100,000 population) for persons ≥ 50 years of age residing in counties along the U.S.-Mexico border by race (non-Hispanic White and Hispanic) and gender from 2011 to 2015. RESULTS: Incidence rates of CRC in Hispanic men ≥ 50 years of age, living in counties along the U.S.-Mexico border, were higher than the national average for Hispanic men of similar age. In contrast, the incidence of CRC declined or remained stable in non-Hispanic Whites and women. CONCLUSIONS: Our study unveils a significant disparity in CRC incidence among Hispanics living near the U.S.-Mexico border, disproportionally affecting men ≥ 50 years of age. Socioeconomic and cultural/lifestyle factors are likely contributing to these disparities.

New Algorithm for the Prediction of Cardiovascular Risk in Symptomatic Adults with Stable Chest Pain.

PURPOSE OF REVIEW: To review the landmark studies in predicting obstructive coronary artery disease (CAD) in symptomatic patients with stable chest pain and identify better prediction tools and propose a simplified algorithm to guide the health care providers in identifying low risk patients to defer further testing. RECENT FINDINGS: There are a few risk prediction models described for stable chest pain patients including Diamond-Forrester (DF), Duke Clinical Score (DCS), CAD Consortium Basic, Clinical, and Extended models. The CAD Consortium models demonstrated that DF and DCS models overestimate the probability of CAD. All CAD Consortium models performed well in the contemporary population. PROMISE trial secondary data results showed that a clinical tool using readily available ten very low-risk pre-test variables could discriminate low-risk patients to defer further testing safely. In the contemporary population, CAD Consortium Basic or Clinical model could be used with more confidence. Our proposed simple algorithm would guide the physicians in selecting low risk patients who can be managed conservatively with deferred testing strategy. Future research is needed to validate our proposed algorithm to identify the low-risk patients with stable chest pain for whom further testing may not be warranted.

Common Variable Immunodeficiency and Hodgkin Lymphoma in a 50-Year-Old Male.

Common variable immunodeficiency (CVID) is a primary immunodeficiency with the involvement of B cells, T cells, and antigen-presenting cells. Patients with CVID are more susceptible to malignancies and bacterial infections in the gastrointestinal and respiratory tracts. We discuss a case of a 50-year-old male who presented to the emergency department with a history of intermittent abdominal pain, diarrhea, night sweats, fever, nausea, and weight loss of 40 pounds over six months. A CT of the abdomen revealed splenomegaly with several infiltrated solid nodules as well as enlarged mediastinal, hilar, periesophageal, cervical, and left supraclavicular lymph nodes, findings suggestive of lymphoma. The diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma was confirmed by immunohistology, which revealed that CD20 and CD3 were both positive in small lymphocytes. Immunoglobulin (Ig) levels were low for IgG and IgM, findings highly suggestive of CVID. We want to shed light on the importance of performing the clinical workup for CVID when Hodgkin lymphoma and recurrent infections are present, as the immunodeficiency remains underdiagnosed and underreported.

Acute-Onset Blindness in a Patient Diagnosed With Myelin Oligodendrocyte Glycoprotein Antibody Disease (MOG-AD): A Case Report.

Myelin oligodendrocyte glycoprotein antibody disease (MOG-AD) poses a diagnostic challenge, often masquerading as other neurological disorders such as multiple sclerosis and aquaporin-4-positive neuromyelitis optica spectrum disorder. The deceptive clinical similarities demand a nuanced approach to differentiate these conditions effectively. This entails an extensive evaluation encompassing a meticulous medical history, advanced magnetic resonance imaging (MRI), cerebrospinal fluid analysis, and serum studies. In this context, we present a compelling case involving a 28-year-old Hispanic female with a history of migraine headache. She sought medical attention due to acute peripheral vision loss, ultimately diagnosed as MOG-AD through a comprehensive clinical assessment coupled with specific diagnostic tests. This case underscores the critical importance of precision in diagnostic procedures to ensure accurate identification and subsequent tailored treatment for MOG-AD, avoiding potential pitfalls associated with its resemblance to other neurological disorders.

Hyperammonemic Encephalopathy in Multiple Myeloma: A Case Report.

Multiple myeloma (MM) typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Only a few cases of hyperammonemic encephalopathy (HE) attributed to multiple myeloma have been reported. We report a case of a 68-year-old Hispanic female diagnosed with multiple myeloma and presented with altered mental status and elevated ammonia levels found to have HE. The pathology behind HE is associated with higher ammonia levels produced by myeloma cell lines in the absence of liver disease. Due to the wide range of differentials for altered mental status (AMS), HE often gets missed and causes delayed treatment and the associated higher mortality. The primary treatment is chemotherapy. Lactulose and rifaximin must be initiated; however, it is ineffective if solely used. In our case, chemotherapy was not considered a treatment option in light of the patient's pancytopenia and infection. Our case is unique, as despite adequately treating other commonly suspected causes of AMS such as infection, there was no expected improvement in the patient's clinical status noticed, eventually leading to intubation due to worsening AMS. Given the patient's history of multiple myeloma, non-compliance with chemotherapy before presentation, and elevated ammonia levels raised suspicion for HE. Clinicians are encouraged to acquaint themselves with HE as a differential for patients presenting with MM flare and AMS, specifically when other potential causes of AMS are ruled out and addressed.

Polymicrobial Infection in an Immigrant Female at the United States-Mexico Border.

Malaria is a highly infectious disease transmitted through the bite of the Anopheles mosquito carrying the parasite of the Plasmodium genus; it presents with cyclical fevers, myalgias, and headaches. In the United States, the vast majority of malaria cases are reported in people who travel abroad, mainly to Africa. These cases are predominantly linked to Plasmodium falciparum or ovale and can be medically treated with artemisinin, chloroquine, or atovaquone-proguanil. We discuss a case of a 38-year-old female immigrant from Venezuela living at an immigration facility who presented to a hospital located on the United States-Mexico border with a two-day history of watery diarrhea, headache, and subjective fever. She had experienced mosquito bites and likely contracted the illness in Chiapas, Mexico during her trek from Peru to the United States. Her case was unique as she tested positive for dengue fever antibodies acquired from a previous infection and also contracted rhinovirus during her clinical course. Her diagnosis of malaria was confirmed with a peripheral blood smear that revealed ring forms with no gametocytes. This in tandem with her route of travel suggested infection with Plasmodium vivax. She was treated with chloroquine while the malaria culture was pending and continued to spike fevers every 24-36 hours while on medication. Once the culture was confirmed, she was treated with atovaquone-proguanil as maintenance therapy. She was subsequently discharged on primaquine for 14 days to prevent relapse.

A Case of Prolonged Recovery for Post-percutaneous Coronary Intervention (PCI) Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitor-Induced Euglycemic Diabetic Ketoacidosis in a 28-Year-Old.

Euglycemic diabetic ketoacidosis (DKA) is a rare, but clinically important, presentation that can lead to significant morbidity and mortality in patients with diabetes mellitus. It has been associated with multiple etiologies, including sodium-glucose cotransport-2 (SGLT2) inhibitor use. This case report details the presentation of a 28-year-old male patient who was recently diagnosed with non-ST elevated myocardial infarction (NSTEMI) status post-percutaneous coronary intervention (PCI) to left anterior descending (LAD) and type 2 diabetes mellitus (T2DM) and discharged on a new medical regiment that included an SGLT2 inhibitor. The patient presented five days later with dyspnea, nausea, and vomiting. On initial evaluation, he had tachycardia and hypertension. Lab work revealed hyperkalemia, metabolic anion gap acidosis, and the presence of ketones and glucose in the urine, which led to the diagnosis of euglycemic DKA. The patient was started on intravenous (IV) insulin, bicarbonate, and D5 ½ normal saline (NS) and required five days of continuous treatment for the anion gap to close. Considering studies have shown that SGLT2 inhibitors are associated with euglycemic DKA, it is proposed that the use of an SGLT2 inhibitor in this newly diagnosed, post-PCI patient led to the development of euglycemic DKA. DKA most commonly resolves within 24 hours of treatment; however, our patient did not recover until after 120 hours of treatment. Recent studies have suggested that SGLT2-inhibitor euglycemic DKA may be associated with longer recovery time; however, there is still a need to further research the consistency of these findings and quantify the estimated duration of treatment across populations. There is also a need for investigation into how co-morbid factors, such as a recent NSTEMI and PCI, may affect recovery times or predispose patients who are taking SGLT2-inhibitors to develop euglycemic DKA as SGLT2 inhibitors are being more widely prescribed. This case report highlights the importance of creating more detailed and evidence-based guidelines for prescribing SGLT2 inhibitors for patients with diabetes and encourages more research into the expected duration of treatment for patients with SGLT2-induced euglycemic DKA and factors that may affect it.

Frequency of GLP-1 receptor agonists use in diabetic patients diagnosed with delayed gastric emptying and their demographic profile.

Advances in the management of diabetes mellitus have come a long way in the 21st century. One of the most important developments in diabetes management has been the discovery of glucagon-like peptide-1 (GLP-1) receptor agonists. The most common side effects of GLP-1 receptor (GLP-1R) agonists are nausea and vomiting which have been attributed to delayed gastric emptying. While the effects of GLP-1R agonists on gastric emptying have prompted further research in this field, there are limited studies evaluating their effects on patients with pre-existing gastroparesis. Additionally, the frequency of GLP-1R agonist use among patients with gastroparesis has not been assessed in the past and this study aims to identify that percentage along with evaluating for possible iatrogenic gastroparesis. A retrospective review of all the gastric emptying studies performed at one academic medical center between January 2019 and January 2021 was performed. We found that although patients on GLP-1R agonists were more likely to have delayed gastric emptying, we could not establish a statistical significance. This could be due to the small sample size in the study. However, GLP-1R agonists use was associated with delayed gastric emptying in patients with diabetes for <10 years. Moreover, a significant proportion (24%) of patients with diabetes with delayed gastric emptying were on a GLP-1R agonist. Recently, semaglutide (GLP-1R agonist) gained Food and Drug Administration approval as a weight loss medication in both patients with and without diabetes. This should prompt further research to evaluate the safety profile of these medications in patients with and without pre-existing gastroparesis.

Effect of Mineralocorticoid Receptor Antagonists in Heart Failure with Preserved Ejection Fraction and with Reduced Ejection Fraction - A Narrative Review.

BACKGROUND: Heart failure is a major cause of morbidity and mortality globally. By the end of this decade, ~8 million Americans will have heart failure with an expenditure of $69.8 billion. OBJECTIVE: In this narrative review, we evaluate the benefits, potential risks and the role of Mineralocorticoid Receptor Antagonists (MRAs) in the management of both Heart Failure with Preserved Ejection Fraction (HFpEF) and Heart Failure with Reduced Ejection Fraction (HFrEF). METHODS: We performed a comprehensive literature review to assess the available evidence on the role of MRAs in heart failure using the online databases (PubMed, Embase, Scopus, CINAHL and Google Scholar). RESULTS: Clinical evidence shows that MRAs such as spironolactone and eplerenone reduce mortality and readmissions for patients with HFrEF compared with placebo. Furthermore, one trial reported that MRAs reduce heart failure hospitalization in patients with HFpEF. The American College of Cardiology/American Heart Association Guidelines strongly recommend using MRA in patients with reduced Left Ventricular Ejection Fraction (LVEF) with Class II-IV symptoms, estimated glomerular filtration rate >30 ml/min/1.73 m2, and absence of hyperkalemia. Despite this, MRAs are underutilized in the management of heart failure. CONCLUSIONS: MRAs improve outcomes in patients with both HFpEF and HFrEF but remain underutilized.

A Rare Culprit of Methemoglobinemia.

Methemoglobinemia is a rare cause of hypoxia and can be a diagnostic challenge early in the disease course. The incidence of medication-induced methemoglobinemia is more common than congenital-related methemoglobinemia. The most common cause of methemoglobinemia is exposure to household detergents, illicit drugs, or medications with nitrate or sulfonamide chemical groups. The 2 main medications accounting for up to 45% of medication-induced cases are dapsone and benzocaine. We report a case of hypoxia and diarrhea with an arterial blood gas (ABG) showing methemoglobinemia at 26%. Infectious and autoimmune workup were negative. Methemoglobinemia level returned to normal level within 2 weeks of hydrochlorothiazide discontinuation, suggesting medication-induced methemoglobinemia at appropriate hypertension dosage. In this case, there was an acute rise in methemoglobin levels following initiation of an hydrochlorothiazide-losartan combination, which improved following the discontinuation of hydrochlorothiazide. Extensive workup ruled out cytochrome b5 reductase (Cb5R) and Glucose-6-phosphate dehydrogenase (G6PD) deficiency, which raised the suspicion of hydrochlorothiazide-induced methemoglobinemia, as it is part of the sulfa drug family.

When Worlds Collide: An Interesting Case of Rhinocerebral Mucormycosis Exacerbated by COVID-19 and Diabetic Ketoacidosis Complicated by Intraorbital Hematoma.

Mucormycosis is a devastating fungal infection seen in patients who are immunosuppressed or in severe inflammatory states. Mucormycosis has been increasingly seen in the setting of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. We describe a 68-year-old male with a past medical history of uncontrolled diabetes mellitus who presented with acute vision loss and was found to have concomitant diabetic ketoacidosis (DKA) and coronavirus disease 2019 (COVID-19) infection on presentation. Rhinocerebral mucormycosis was suspected given the patient's presentation and was confirmed with an ethmoidal sinus biopsy. Our case was further complicated by the presence of cavernous sinus thrombosis, cerebral infarcts, and, later, the development of a left orbital hematoma following therapeutic anticoagulation. This case report aims to address the rare but now increasing incidence of rhinocerebral mucormycosis in the setting of COVID-19, further complicated by DKA, cerebral thrombosis, and intraorbital hematoma.

From Chemical Burn to Below Knee Amputation: Amputation Secondary to Application of Over-the-Counter Topical Analgesic With Menthol and Methyl Salicylate.

Topical analgesics and topical rubefacients are widely used to control acute as well as chronic pain every day. Due to their availability without a prescription, consumers often overlook any potentially harmful effects and consider them largely benign. Here, we present a rare case of chemical burn triggered by a typical over-the-counter (OTC) analgesic containing menthol and methyl salicylate resulting in chemical burn, complicated by necrotizing infection treated by below the knee amputation.

Fecal microbiota transplantation in irritable bowel syndrome: A systematic review and meta-analysis.

Background: Modulating gut microbiota is a potential treatment for irritable bowel syndrome (IBS). This meta-analysis explored whether fecal microbiota transplantation (FMT) is successful in treating IBS. Methods: A systematic review was performed to find trials on FMT in IBS. Ratios and relative ratios (RR) of improvement for single-arm trials (SATs) and randomized controlled trials (RCTs) were calculated, respectively. Changes in IBS Severity Scoring System (IBS-SSS) and IBS Quality of Life (IBS-QOL) instrument compared to baseline in FMT versus placebo groups were pooled. Results: In SATs, 59.5% (95% confidence interval (CI) 49.1-69.3) of IBS patients showed significant improvement. In RCTs, there were no differences between FMT and control in improvement (RR=0.93 (95% CI 0.50-1.75)) or changes in the IBS-SSS and IBS-QOL. Conclusions: FMT was not effective in IBS. Variations in FMT methods and patient factors may contribute to the heterogeneous results of the trials.

Mast cells are increased in the small intestinal mucosa of patients with irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND: Colonic mast cells have been proposed to be related to the pathophysiology of irritable bowel syndrome (IBS). Whether mast cell counts are altered in the small intestine, a less-explored region in patients with IBS is not completely clear. METHODS: PubMed and EMBASE were searched for case-control studies on mast cell count/density in the small intestine of patients with IBS vs controls through February 2019. Mast cell counts were separately analyzed in the duodenum, jejunum, and ileum. Data were pooled using the standardized mean difference (SMD) method. When zero was not within the 95% confidence interval (CI), the SMD was considered significant. KEY RESULTS: Data from 344 patients with IBS and 229 healthy controls from three studies in the duodenum, six in the jejunum, and five in the ileum were pooled in this meta-analysis. The number of mast cells was significantly higher in the ileum (SMD: 1.78 [95% CI: 0.89, 2.66]) of patients with IBS. Mast cell counts were not significantly different in the duodenum (SMD: 0.81 [-0.06, 1.67]) or the jejunum (SMD: 0.58 [-0.03, 1.19]) of patients with IBS vs healthy controls. CONCLUSIONS AND INFERENCES: Mast cells are increased in the small intestine of IBS vs controls, mainly in the ileum. Future studies should address whether such findings are IBS subtype or gender-dependent. Methodological variations, single-center bias, and the limited number of studies included in this meta-analysis may affect the final results.

Colorectal cancer in hispanics living near the U.S. - Mexico Border

Background The incidence of colorectal cancer (CRC) in the US has declined. The decreasing trend is observed in non-Hispanic Whites, Blacks, and Hispanics. However, close analysis of the trends demonstrates that the decline among Hispanics is less than other races/ethnicities. We investigate the burden of CRC in Hispanics living near the U.S.–Mexico border, a subpopulation of Hispanics composed primarily of individuals of Mexican origin. Objectives The objective of this study was to investigate and compare incidence rates of CRC in non-Hispanic Whites and Hispanics living in counties along the U.S.–Mexico border. Methods Data from the National Institutes of Health National Cancer Institute and State Cancer Profiles were analyzed to obtain CRC incidence rates (per 100,000 population) for persons ≥ 50 years of age residing in counties along the U.S.–Mexico border by race (non-Hispanic White and Hispanic) and gender from 2011 to 2015. Results Incidence rates of CRC in Hispanic men ≥ 50 years of age, living in counties along the U.S.–Mexico border, were higher than the national average for Hispanic men of similar age. In contrast, the incidence of CRC declined or remained stable in non-Hispanic Whites and women. Conclusions Our study unveils a significant disparity in CRC incidence among Hispanics living near the U.S.–Mexico border, disproportionally affecting men ≥ 50 years of age. Socioeconomic and cultural/lifestyle factors are likely contributing to these disparities.