Current and emerging pharmacotherapy for the treatment of gastroparesis.

INTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.

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.

The Association Between Non-Clinically Apparent Liver Fibrosis and Pulmonary Arterial Hypertension in Hispanic Patients.

Background: Pulmonary arterial hypertension (PAH) is a deadly cardiopulmonary disease with multi-organ involvement including impaired liver function. Liver dysfunction in PAH is poorly understood but significantly associated with morbidity and mortality. Hispanics have a significantly higher prevalence of non-alcoholic fatty liver disease (NAFLD) and evidence of more advanced disease in comparison to other ethnic groups. The clinical impact of NAFLD in Hispanic PAH patients is unknown. We aimed to investigate the impact of a validated scoring system, non-alcoholic fatty liver disease fibrosis score (NFS), to predict the degree of liver fibrosis in a Hispanic PAH population and its relationship to hemodynamics, functional class, and outcomes. Methods: A retrospective review of all treatment-naive Hispanic patients with group I World Health Organization (WHO) pulmonary hypertension (PH) at a single academic center between February 2016 and March 2021 was performed. Patients with history of substance or alcohol abuse, non-group I WHO PH, pre-existent liver disease, chronic kidney disease, atrial fibrillation, thyroid disease, and warfarin use were excluded from the study. The diagnosis of group I WHO PH was determined by cardiac catheterization after the exclusion of other etiologies. NFS was calculated for each patient and correlated with functional capacity, hemodynamics, N-terminal-pro-B-type natriuretic peptide (NT-proBNP), and survival. Results: A total of 96 Hispanic patients were included in our study. The median age of patients in our cohort was 49 years (interquartile range: 15) and 69% of our cohort were females. Higher NFSs indicating advanced hepatic fibrosis (F3-F4) were found to correlate with elevated right-sided cardiac filling pressures (r = 0.27, P = 0.03), elevated levels of NT-proBNP (r = 0.32, P = 0.01), lower 6-minute walk distance (6MWD) (r = -0.49, P = 0.001), lower functional capacity (World Health Organization functional class, WHO-FC, r = -0.35, P = 0.051), a higher prevalence of diabetes (21.1% versus 51.9%, P = 0.001), a higher prevalence of risk factors for metabolic syndrome (81.5% versus 65.0%, P = 0.035), and worse 5-year survival rates. Conclusion: In Hispanic patients with PAH, NFSs correlate with the degree of right-sided pressure overload. In addition, advanced NFSs were independently associated with lower 5-year survival rates and added prognostic information to other established risk parameters in PAH. This study suggests that screening for liver disease in this vulnerable patient population can aid in earlier detection leading to discussion of lifestyle modifications and possible escalation of PAH-targeted therapies, thus leading to potential improvement in survival rates.

Virtual Reality and Mindfulness Approaches in the Treatment of Rumination Syndrome.

Rumination syndrome (RS) is the repeated, effortless food regurgitation during or immediately after eating or drinking, which could be followed by rechewing, reswallowing, or spitting out of the regurgitant gastric contents. The mechanism by which RS ensues is because of the habitual contraction of the abdominal wall muscles leading to increased intra-abdominal pressure and regurgitation of gastric contents. Therefore, diaphragmatic breathing techniques and biofeedback are helpful in these patients to counteract the habitual abdominal contractions. We present a case of a 26-year-old woman diagnosed with RS unresponsive to conventional therapy (antiemetics and antispasmodics).

Vascular complications of pancreatitis.

More than 200000 hospital admissions happen per year for acute pancreatitis and more than 50000 for chronic pancreatitis in the United States of America. Necrotizing pancreatitis accounts for 20%-30% of the cases. One-quarter of the patients with pancreatitis develop vascular complications, which carries a high mortality. This mini-review will address these complications that can help primary care physicians and hospitalists in managing their patients effectively.

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.

Colorectal Carcinoma in the Background of Pelvic Inflammatory Disease.

Colorectal carcinoma (CRC) is a common malignancy with steadily declining incidence rates and mortality, secondary to improved screening and lifestyle changes (eg, decreased smoking rates). The association between pelvic inflammatory disease (PID) and CRC has been unclear in the past. However, multiple studies showed a positive association between PID and underlying malignancy (gynecologic and pelvic primarily). Several studies evaluated the relation between PID and CRC, but the results were conflicting. We describe a case of a 33-year-old female patient, with a history of PID and recurrent pelvic abscesses, who was found to have CRC. Of note, the patient's diagnosis was based on abnormal computed tomography findings, which were further investigated (by colonoscopy and biopsy), rather than on symptoms suggestive of CRC, such as rectal bleeding, constipation, symptomatic anemia, or abdominal pain.

A Perfect Storm: Abdominal Pain and Ileus Explained by Acute Intermittent Porphyria Caused by Prehospitalization and Intrahospitalization Factors.

Acute intermittent porphyria (AIP) is a rare autosomal dominant inherited disease, predominantly seen in female patients, caused by mutations in the hydroxymethylbilane synthase gene. When impaired, elevated heme biosynthesis precursor levels accumulate in the liver, resulting in neurological symptoms, psychiatric disturbances, darkened urine color, abdominal pain, nausea, vomiting, and ileus. We present a 22-year-old Hispanic female with diffuse abdominal pain and no bowel movements for 8 days. She reported recent antibiotic and oral contraceptive pill use. Computerized tomography of her abdomen revealed a dilated small bowel and marked colonic distension. A colonoscopy found mild nonspecific inflammation in the rectosigmoid and terminal ileum. Her abdominal pain persisted despite interventions and improvements in appetite, bowel movements, abdominal imaging, and treatment of an identified Clostridium difficile infection. A random urine porphobilinogen was then obtained and found to be elevated. Fractionation of plasma and urine porphyrins was suggestive of AIP. Her symptoms improved with 3 days of intravenous (IV) hematin and IV dextrose. This is a unique case of a rare disease due to her clinical presentation with ileus, unremarkable past medical history, family history, and the prehospitalization and intrahospitalization factors that likely exacerbated the patient AIP.

Post-cholecystectomy Mirizzi Syndrome.

Post-cholecystectomy Mirizzi syndrome (PCMS) is characterized by symptoms of recurrent abdominal pain, jaundice, and fever in patients who underwent cholecystectomy. Imaging is crucial in the diagnosis of PCMS and Mirizzi syndrome. Imaging modalities have evolved over the years with abdominal ultrasonography, computed tomography of the abdomen, and magnetic resonance cholangiopancreatography being used in the diagnosis of PCMS and Mirizzi syndrome. The imaging findings show obstruction of the common hepatic duct due to impingement by a stone in the cystic duct or gallbladder infundibulum. PCMS management has evolved over the years with the current first-line management being endoscopic intervention. This case describes a 61-year-old male presenting with recurrent right upper quadrant pain two years after undergoing cholecystectomy due to cholelithiasis. The patient was later diagnosed with PCMS, and endoscopic management was performed with complete resolution of the symptoms.

Medical Management of Septic Arthritis of the Sternoclavicular Joint With Extended-Spectrum Beta-Lactamase-Producing Escherichia coli: A Case Report.

The sternoclavicular joint (SCJ) is an uncommon location for septic arthritis to occur in. Due to the rarity of the condition and the nonspecific symptoms, SCJ septic arthritis can be missed or mislabeled as osteoarthritis or muscle strain. Accurate history and physical examination is crucial for recognizing this condition. With the potential life-threatening complications that may ensue, SCJ septic arthritis has traditionally been managed surgically. This ranges from simple incision and drainage to resection of the joint. However, in cases where there is not enough fluid for incision and drainage, a trial of medical management with antibiotics can be attempted. We herein describe a case of a 58-year-old male who presented with nonspecific anterior chest wall and neck pain. Chest X-ray and ultrasound of the anterior chest wall was normal; however, magnetic resonance imaging (MRI) of the chest showed a small effusion without other complications. His blood cultures grew extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, rendering this as his hematogenous source of septic arthritis. The ESBL was from a left-sided obstructing kidney stone that resulted in pyelonephritis, which was confirmed via computed tomography of the abdomen. His effusion was too minimal to drain; therefore, he was managed medically with intravenous (IV) antibiotics along with a left ureteral stent placement, and he had a full recovery. This case represents the ability for SCJ septic arthritis to be managed medically with IV antibiotics, especially when the diagnosis is caught early without complications. The role of MRI is indispensable for coming to the diagnosis, as it is capable of detecting complications that ultimately dictate management. Additionally, this case highlights the unique microorganism, ESBL-producing E. coli causing the SCJ septic arthritis, a finding that has been rarely reported in the literature as the majority of microorganisms that have been previously documented are either Staphylococcus aureus or Pseudomonas aeruginosa.

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.

Abnormal liver enzymes: A review for clinicians.

Liver biochemical tests are some of the most commonly ordered routine tests in the inpatient and outpatient setting, especially with the automatization of testing in this technological era. These tests include aminotransferases, alkaline phosphatase, gamma-glutamyl transferase, bilirubin, albumin, prothrombin time and international normalized ratio (INR). Abnormal liver biochemical tests can be categorized based on the pattern and the magnitude of aminotransferases elevation. Generally, abnormalities in aminotransferases can be classified into a hepatocellular pattern or cholestatic pattern and can be further sub-classified based on the magnitude of aminotransferase elevation to mild [< 5 × upper limit of normal (ULN)], moderate (> 5-< 15 × ULN) and severe (> 15 × ULN). Hepatocellular pattern causes include but are not limited to; non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, alcohol use, chronic viral hepatitis, liver cirrhosis (variable), autoimmune hepatitis, hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency, celiac disease, medication-induced and ischemic hepatitis. Cholestatic pattern causes include but is not limited to; biliary pathology (obstruction, autoimmune), other conditions with hyperbilirubinemia (conjugated and unconjugated). It is crucial to interpret these commonly ordered tests accurately as appropriate further workup, treatment and referral can greatly benefit the patient due to prompt treatment which can improve the natural history of several of the diseases mentioned and possibly reduce the risk of progression to the liver cirrhosis.

Medication-Induced Gastroparesis: A Case Report.

Gastroparesis is a commonly diagnosed gastrointestinal disorder with a high prevalence globally and high disease burden to those afflicted with it. Etiologies are variable with idiopathic and diabetes being the most common causes of gastroparesis. Management of gastroparesis depends on the etiology, and accurate diagnosis is required for better targeted therapy. Medication-induced gastroparesis is reversible, and discontinuing the medication is generally curative. This case report discusses 2 cases of medication-induced gastroparesis which were initially diagnosed as diabetic gastroparesis, and thorough history taking revealed the cause to be medication induced. Repeat studies following medication discontinuation revealed improvement in symptoms and resolution of gastroparesis. Further research needs to be done to assess the frequency of misdiagnosing diabetic patients with gastroparesis due to medications, specifically glucagon-like peptide-1 receptor agonists which are increasingly being used in diabetics.

Incidental Diagnosis of Duodenal Giardiasis.

Giardia lamblia is a protozoan that results in the commonly diagnosed giardiasis. Due to its prevalence and incidence worldwide, it is essential to recognize the different presentations of giardiasis, routes of transmission, modalities of diagnosis, treatments, and complications. Diagnostic modalities have evolved over the years and can be achieved reliably through noninvasive stool testing. Endoscopic duodenal aspirate and biopsies can also be used; however, they yield lower sensitivity and specificity rates and are therefore not used as a first-line modality for diagnosing giardiasis. Nonetheless, its use should be considered in cases with high suspicion and unremarkable stool testing. Herein, we discuss the case of a 27-year-old male with chronic weight loss and abdominal pain for six months diagnosed with G. lamblia through a duodenal biopsy.