Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria.

Erythropoietic protoporphyria (EPP) is a genetic disorder stemming from reduced ferrochelatase expression, the final enzyme in the pathway of heme biosynthesis. A closely related condition, X-linked protoporphyria (XLP), bears similar clinical features although it arises from the heightened activity of δ-aminolevulinic acid synthase 2 (ALAS2), the first and normally rate-controlling enzyme in heme biosynthesis in developing red blood cells. Both of these abnormalities result in the buildup of protoporphyrin IX, leading to excruciating light sensitivity and, in a minority of cases, potentially fatal liver complications. Traditionally, managing EPP and XLP involved sun avoidance. However, the emergence of innovative therapies, such as dersimelagon, is reshaping the therapeutic landscape for these conditions. In this review, we summarize salient features of the properties of dersimelagon, shedding light on its potential role in advancing our understanding of treatment options for EPP and XLP.

Elevated average maximum intrabolus pressure on high-resolution manometry is associated with esophageal dysmotility and delayed esophageal emptying on timed barium esophagram.

BACKGROUND: Intrabolus pressure (IBP) recorded by high-resolution manometry (HRM) portrays the compartmentalized force on a bolus during esophageal peristalsis. HRM may be a reliable screening tool for esophageal dysmotility in patients with elevated average maximum IBP (AM-IBP). Timed barium esophagram (TBE) is a validated measure of esophageal emptying disorders, such as esophagogastric junction outflow obstruction and achalasia. This study aimed to determine if an elevated AM-IBP correlates with esophageal dysmotility on HRM and/or delayed esophageal emptying on TBE. METHODS: A retrospective analysis of all HRM (unweighted sample n = 155) performed at a tertiary referral center from 09/2015-03/2017 yielded a case group (n = 114) with abnormal AM-IBP and a control group (n = 41) with a normal AM-IBP (pressure < 17 mmHg) as consistent with Chicago Classification 3. All patients received a standardized TBE, with abnormalities classified as greater than 1 cm of retained residual liquid barium in the esophagus at 1 and 5 min or as tablet retention after 5 min. RESULTS: AM-IBP was significantly related to liquid barium retention (p = 0.003) and tablet arrest on timed barium esophagram (p = 0.011). A logistic regression model correctly predicted tablet arrest in 63% of cases. Tablet arrest on AM-IBP correlated with an optimal prediction point at 20.1 mmHg on HRM. Patients with elevated AM-IBP were more likely to have underlying esophageal dysmotility (95.6% vs. 70.7% respectively; p < 0.001), particularly esophagogastric junction outflow obstruction disorders. Elevated AM-IBP was associated with incomplete liquid bolus transit on impedance analysis (p = 0.002). CONCLUSIONS: Our findings demonstrate that an elevated AM-IBP is associated with abnormal TBE findings of esophageal tablet retention and/or bolus stasis. An abnormal AM-IBP (greater than 20.1 mm Hg) was associated with a higher probability of retaining liquid bolus or barium tablet arrest on TBE and esophageal dysmotility on HRM. This finding supports the recent incorporation of IBP in Chicago Classification v4.0.

Distinctive Clinical Correlates of Small Intestinal Bacterial Overgrowth with Methanogens.

BACKGROUND AND AIMS: Most patients with small intestinal bacterial overgrowth (SIBO) produce hydrogen by fermentation of dietary carbohydrates; however, ∼30% of patients with SIBO are colonized with Archaea, anaerobic organisms that produce methane. SIBO is associated with a plethora of symptoms and conditions, but their diagnostic significance is unclear. We aimed to determine if specific symptoms and conditions are associated with methanogenic SIBO. METHODS: This study received institutional review board approval (IRB00059873). In this retrospective cross-sectional study, we queried a database of glucose breath tests conducted for suspected SIBO at our tertiary care medical center, which included data on the presence or absence of gastrointestinal symptoms and conditions often associated with SIBO. All patients had undergone a standardized breath testing protocol. RESULTS: In a cohort of 1461 patients, 33.1% were SIBO positive; of these, 49.8% produced only hydrogen, 38.8% produced only methane, and 11.4% produced both gases. The following factors distinguished patients with hydrogen-producing SIBO, but not methanogenic SIBO, from SIBO-negative patients: vitamin B12 deficiency (odds ratio, 1.44; confidence interval [CI], 1.01-2.06; P = .046), Roux-en-Y gastric bypass (odds ratio, 2.14; CI, 1.09-4.18; P = .027), cholecystectomy (odds ratio, 1.42; CI, 1.06-1.91; P = .020), and diabetes (odds ratio, 1.59; CI, 1.13-2.24; P = .008). The absence of vitamin B12 deficiency was the sole discriminating factor between methanogenic and hydrogenic SIBO (odds ratio, 0.57; CI, 0.34-0.97; P = .038). CONCLUSIONS: Patients with SIBO caused by methane-producing Archaea display a different spectrum of associated symptoms and clinical conditions compared with patients with SIBO caused by hydrogen-producing bacteria, particularly a lower incidence of vitamin B12 deficiency.

Food Insecurity Is an Independent Risk Factor for Depressive Symptoms in Survivors of Digestive Cancers.

BACKGROUND: Colorectal and other digestive cancer survivors are at increased risk of depression, which can negatively affect health outcomes. Food insecurity (FI), the lack of consistent access to enough food, can also contribute to these health complications. The objective of this study was to determine the relationship between FI and depressive symptoms within this population. METHODS: We conducted a cross-sectional analysis of data from the 2007-2016 National Health and Nutrition Examination Survey. We included all adults (≥20 years) with a self-reported history of a digestive cancer (including colorectal, esophageal, stomach, liver, and pancreas cancer). Our primary exposure was household FI, and our outcome of interest was depressive symptoms, as measured by the validated 9-item Patient Health Questionnaire. We used multivariable ordinal logistic regression to test the association between FI and depressive symptoms, controlling for demographic and clinical covariates. RESULTS: We included 229 adult digestive cancer survivors (weighted N = 1,510,579). The majority of the study sample was female and non-Hispanic White with mean of 11.0 years since cancer diagnosis; 14.3% reported FI. In multivariable models controlling for demographic and clinical covariates, we found that food insecure digestive cancer survivors had significantly higher odds of depressive symptoms than food secure digestive cancer survivors (OR: 3.25; 95% confidence interval: 1.24-8.55; P = 0.02). CONCLUSIONS: Among a nationally representative sample of colorectal cancer and other digestive cancer survivors, FI was associated with increased odds of depressive symptoms. IMPACT: This study adds further evidence to the negative impact FI may have on survivors' physical and mental health.

Comparative Performance of Pulmonary Ultrasound, Chest Radiograph, and CT Among Patients With Acute Respiratory Failure.

OBJECTIVES: The study goal was to concurrently evaluate agreement of a 9-point pulmonary ultrasound protocol and portable chest radiograph with chest CT for localization of pathology to the correct lung and also to specific anatomic lobes among a diverse group of intubated patients with acute respiratory failure. DESIGN: Prospective cohort study. SETTING: Medical, surgical, and neurologic ICUs at a 670-bed urban teaching hospital. PATIENTS: Intubated adults with acute respiratory failure having chest CT and portable chest radiograph performed within 24 hours of intubation. INTERVENTIONS: A 9-point pulmonary ultrasound examination performed at the time of intubation. MEASUREMENTS AND MAIN RESULTS: Sixty-seven patients had pulmonary ultrasound, portable chest radiograph, and chest CT performed within 24 hours of intubation. Overall agreement of pulmonary ultrasound and portable chest radiograph findings with correlating lobe ("lobe-specific" agreement) on CT was 87% versus 62% (p < 0.001), respectively. Relaxing the agreement definition to a matching CT finding being present anywhere within the correct lung ("lung-specific" agreement), not necessarily the specific mapped lobe, showed improved agreement for both pulmonary ultrasound and portable chest radiograph respectively (right lung: 92.5% vs 65.7%; p < 0.001 and left lung: 83.6% vs 71.6%; p = 0.097). The highest lobe-specific agreement was for the finding of atelectasis/consolidation for both pulmonary ultrasound and portable chest radiograph (96% and 73%, respectively). The lowest lobe-specific agreement for pulmonary ultrasound was normal lung (79%) and interstitial process for portable chest radiograph (29%). Lobe-specific agreement differed most between pulmonary ultrasound and portable chest radiograph for interstitial findings (86% vs 29%, respectively). Pulmonary ultrasound had the lowest agreement with CT for findings in the left lower lobe (82.1%). Pleural effusion agreement also differed between pulmonary ultrasound and portable chest radiograph (right: 99% vs 87%; p = 0.009 and left: 99% vs 85%; p = 0.004). CONCLUSIONS: A clinical, 9-point pulmonary ultrasound protocol strongly agreed with specific CT findings when analyzed by both lung- and lobe-specific location among a diverse population of mechanically ventilated patients with acute respiratory failure; in this regard, pulmonary ultrasound significantly outperformed portable chest radiograph.