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Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article ( http://links.lww.com/JBJS/H973 ).

Importance: Dietary supplements for weight loss, among the most popular supplement products on the market, are promoted not only for losing weight and shedding fat, but also for added benefits of energy and performance, all packed into 1 capsule with multiple combinations of ingredients. Fraudulent marketing of weight loss supplements, some with exaggerated claims, some that are potentially dangerous, and some that contain illegal ingredients, is ever present, especially through online sources, where multiple manufacturers target service members by offering military discounts., Objectives: To examine whether select dietary supplements marketed online for weight loss from companies advertising military discounts are accurately labeled according to the Supplement Facts listed ingredients, whether they contain any ingredients prohibited for use in the military, and to qualitatively describe the products' label claims., Design, Setting, and Participants: In this case series, 30 dietary supplement products marketed for weight loss were selected and purchased in June 2023 from 12 online companies advertising military discounts. Data were analyzed from July to August 2023., Main Outcomes and Measures: Liquid chromatography-mass spectrometry was used to verify whether products were accurately labeled according to the Supplement Facts listed ingredients and whether they contained any substances on the DoD Prohibited Dietary Supplement Ingredients List. A separate analysis was conducted to describe product label claims by using the Operation Supplement Safety (OPSS) Risk Assessment Scorecard., Results: Of the 30 products tested, analysis showed that 25 had inaccurate labels. Of these, 24 had ingredients listed on the label that were not detected (misbranded); 7 had hidden components not present on the label, some of which would be considered adulterated; and 10 had substances on the DoD Prohibited Dietary Supplement Ingredients List either on or hidden from the label. All products were rated as risky when applying the OPSS Scorecard., Conclusions and Relevance: In this case series study, the majority of products had inaccurate labels. Some were misbranded, others would be considered adulterated with ingredients not allowed in dietary supplements, and some contained ingredients prohibited for use in the military.

Background: Turmeric is a commonly used herbal product that has been implicated in causing liver injury. The aim of this case series is to describe the clinical, histologic, and human leukocyte antigen (HLA) associations of turmeric-associated liver injury cases enrolled the in US Drug-Induced Liver Injury Network (DILIN)., Methods: All adjudicated cases enrolled in DILIN between 2004 and 2022 in which turmeric was an implicated product were reviewed. Causality was assessed using a 5-point expert opinion score. Available products were analyzed for the presence of turmeric using ultra-high-performance liquid chromatography. Genetic analyses included HLA sequencing., Results: Ten cases of turmeric-associated liver injury were found, all enrolled since 2011, and 6 since 2017. Of the 10 cases, 8 were women, 9 were White, and median age was 56 years (range 35-71). Liver injury was hepatocellular in 9 patients and mixed in 1. Liver biopsies in 4 patients showed acute hepatitis or mixed cholestatic-hepatic injury with eosinophils. Five patients were hospitalized, and 1 patient died of acute liver failure. Chemical analysis confirmed the presence of turmeric in all 7 products tested; 3 also contained piperine (black pepper). HLA typing demonstrated that 7 patients carried HLA-B*35:01, 2 of whom were homozygous, yielding an allele frequency of 0.450 compared with population controls of 0.056-0.069., Conclusion: Liver injury due to turmeric appears to be increasing in the United States, perhaps reflecting usage patterns or increased combination with black pepper. Turmeric causes potentially severe liver injury that is typically hepatocellular, with a latency of 1 to 4 months and strong linkage to HLA-B*35:01., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Importance: Cold, flu, and immunity dietary supplement product sales have skyrocketed since the start of the COVID-19 pandemic. Supporting or boosting the immune system has become an important reason for using dietary supplements, and many consumers are purchasing products through online platforms., Objectives: To examine whether select dietary supplement products advertised as supporting or boosting the immune system are accurately labeled according to the Supplement Facts label of listed ingredients and to qualitatively describe the product labels' characteristics in terms of claims made., Design, Setting, and Participants: In this case series, 30 featured immune health dietary supplements were selected and purchased from Amazon.com in May 2021. Product analysis was performed using liquid chromatography-mass spectrometry. The list of ingredients detected through analysis for each product was compared with the ingredients on the product's Supplement Facts label to determine whether the product's label was accurate. Claims made on product labels were also evaluated by using the Operation Supplement Safety Scorecard's set of questions to describe the labels' characteristics., Results: A total of 30 select dietary supplement products were evaluated. Thirteen of the 30 products had accurate labels based on the product analysis. Of the 17 products with inaccurate labels, 13 had ingredients listed on the labels that were not detected through analysis, such that their labels were misbranded. Nine products had substances detected that were not claimed on the product labels, some of which may be considered adulterated. Five were misbranded and contained additional components not claimed on the label. No product had third-party certification seals present on the packaging. Ten of the 13 products with accurate labels received a score of 4 or more when applying the Operation Supplement Safety Scorecard, meaning the product was "likely okay/less risky.", Conclusions and Relevance: In this case series study, most of the products tested had inaccurate labels and claims that were inconsistent with requirements the US Food and Drug Administration has put forward for dietary supplements. Quality control measures seem to be insufficient for most of these select products, and claims made on labels may be misleading consumers who purchase products.

Background: Kratom is a botanical product used as an opium substitute with abuse potential., Methods: Assessment of suspected cases of kratom-induced liver injury in a prospective US cohort., Results: Eleven cases of liver injury attributed to kratom were identified with a recent increase. The majority were male with median age 40 years. All were symptomatic and developed jaundice with a median latency of 14 days. The liver injury pattern was variable, most required hospitalization and all eventually recovered. Biochemical analysis revealed active kratom ingredients., Conclusion: Kratom can cause severe liver injury with jaundice., (Copyright © 2020. Published by Elsevier B.V.)

Background: Dietary supplements targeting brain health have quickly emerged in the marketplace as cognitive performance becomes an important public health issue. While manufacturers are required to report the exact ingredients and formulations listed on the Supplement Facts labels of products, many reports have indicated such labels are not always truthful, and the content of some products is inconsistent with the ingredients listed on the Supplement Facts label. Objectives: To identify dietary supplement products and ingredients marketed for brain health and cognitive performance and perform analyses of select products to verify whether purported claims are truthful and product labels accurate. Design: A scoping review was performed to identify products and ingredients. Products were selected for content analysis, investigated for scientific-sounding claims made, and assessed using an educational tool for potential red flags when reading Supplement Facts labels. Results: Twelve products were selected from the 650 products being marketed for brain health and queried about by Service Members. Eight (67%) had at least one ingredient listed on the Supplement Facts label not detected through analysis. Compounds not reported on the label were detected in 10 (83%) products. Scientific-sounding claims made are not supported by science and red flags are presented. Conclusions: There are dietary supplements targeting brain health being marketed to consumers that should be considered adulterated and misbranded. Advertisements and product labels may be deceiving and could put the public at risk. Education is required so that the public can recognize red flags while the U.S. Food and Drug Administration works to "modernize" the current regulations for dietary supplements.

Therapies originating from traditional medical systems are widely used by patients in both India and the United States. The first India-US Workshop on Traditional Medicine was held in New Delhi, India, on March 3 and 4, 2016, as a collaboration between the Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha, and Homoeopathy (AYUSH) of the Government of India, the US National Cancer Institute (NCI), National Institutes of Health, and the Office of Global Affairs, US Department of Health and Human Services. It was attended by Indian and US policymakers, scientists, academics, and medical practitioners from various disciplines. The workshop provided an opportunity to open a dialogue between AYUSH and NCI to identify promising research results and potential topics for Indo-US collaboration. Recommendations that emerged from the workshop underlined the importance of applying rational and scientific approaches for drug development; standardizing traditional medicine products and procedures to ensure reliability and reproducibility; promotion of collaboration between Indian traditional medicine practitioners and researchers and US researchers; greater integration of evidence-based traditional medicine practices with mainstream medical practices in India; and development of training programs between AYUSH and NCI to facilitate crosstraining. Several positive developments took place after the thought-provoking deliberations.

Vinpocetine and picamilon are drugs prescribed in many countries to treat a variety of cerebrovascular disorders. In the United States, vinpocetine and picamilon have never been approved by the US Food and Drug Administration, but they are both available for sale directly to consumers as dietary supplements. We designed our study to determine the accuracy of supplement labels with regard to the presence and quantity of vinpocetine and picamilon. A validated ultra-high performance liquid chromatography-photodiode-array method was developed for the quantification of vinpocetine and picamilon. The separation was achieved using a reversed phase (C-18) column, photodiode array detection, and water/acetonitrile as the mobile phase. Vinpocetine and picamilon were detected at concentrations as low as 10 and 50 ng/mL, respectively. The presence of vinpocetine and picamilon was confirmed using reference standards. Twenty-three supplements labelled as containing vinpocetine were available for sale at two large supplement retail chains; 17 contained vinpocetine with quantities ranging from 0.3 to 32 mg per recommended daily serving. No vinpocetine was detected in six of the sampled supplements. The supplement label implied that vinpocetine was a constituent of lesser periwinkle in three of the supplements. Of the 31 picamilon supplements available for sale from a variety of retailers: 30 contained picamilon in quantities ranging from 2.7 to 721.5 mg per recommended daily serving. We found that consumers cannot obtain accurate information from supplement labels regarding the presence or quantity of vinpocetine and picamilon. Copyright © 2015 John Wiley & Sons, Ltd., (Copyright © 2015 John Wiley & Sons, Ltd.)

Certain botanical dietary supplements have been associated with idiosyncratic organ-specific toxicity. Similar toxicological events, caused by drug-induced mitochondrial dysfunction, have forced the withdrawal or U.S. FDA "black box" warnings of major pharmaceuticals. To assess the potential mitochondrial liability of botanical dietary supplements, extracts from 352 authenticated plant samples used in traditional Chinese, Ayurvedic, and Western herbal medicine were evaluated for the ability to disrupt cellular respiration. Blue cohosh (Caulophyllum thalictroides) methanol extract exhibited mitochondriotoxic activity. Used by some U.S. midwives to help induce labor, blue cohosh has been associated with perinatal stroke, acute myocardial infarction, congestive heart failure, multiple organ injury, and neonatal shock. The potential link between mitochondrial disruption and idiosyncratic herbal intoxication prompted further examination. The C. thalictroides methanol extract and three saponins, cauloside A (1), saponin PE (2), and cauloside C (3), exhibited concentration- and time-dependent mitochondriotoxic activities. Upon treatment, cell respiration rate rapidly increased and then dramatically decreased within minutes. Mechanistic studies revealed that C. thalictroides constituents impair mitochondrial function by disrupting membrane integrity. These studies provide a potential etiological link between this mitochondria-sensitive form of cytotoxicity and idiosyncratic organ damage.

Coumarin as an additive or as a constituent of tonka beans or tonka extracts is banned from food in the United States due to its potentially adverse side effects. However, coumarin in food from other natural ingredients is not regulated. "True Cinnamon" refers to the dried inner bark of Cinnamomum verum. Other cinnamon species, C. cassia, C. loureiroi, and C. burmannii, commonly known as cassia, are also sold in the U.S. as cinnamon. In the present study, coumarin and other marker compounds were analyzed in authenticated cinnamon bark samples as well as locally bought cinnamon samples, cinnamon-flavored foods, and cinnamon-based food supplements using a validated UPLC-UV/MS method. The experimental results indicated that C. verum bark contained only traces of coumarin, whereas barks from all three cassia species, especially C. loureiroi and C. burmannii, contained substantial amounts of coumarin. These species could be potential sources of coumarin in cinnamon-flavored food in the U.S. Coumarin was detected in all locally bought cinnamon, cinnamon-flavored foods, and cinnamon food supplements. Their chemical profiles indicated that the cinnamon samples and the cinnamon in food supplements and flavored foods were probably Indonesian cassia, C. burmannii.

Natural products have provided a basis for health care and medicine to humankind since the beginning of civilization. According to the World Health Organization (WHO), approximately 80% of the world population still relies on herbal medicines for health-related benefits. In the United States, over 42% of the population claimed to have used botanical dietary supplements to either augment their current diet or to "treat" or "prevent" a particular health-related issue. This has led to the development of a burgeoning industry in the U.S. ($4.8 billion per year in 2008) to supply dietary supplements to the consumer. However, many commercial botanical products are poorly defined scientifically, and the consumer must take it on faith that the supplement they are ingesting is an accurate representation of what is listed on the label, and that it contains the purportedly "active" constituents they seek. Many dietary supplement manufacturers, academic research groups, and governmental organizations are progressively attempting to construct a better scientific understanding of natural products, herbals, and botanical dietary supplements that have co-evolved with Western-style pharmaceutical medicines. However, a deficiency of knowledge is still evident, and this issue needs to be addressed in order to achieve a significant level of safety, efficacy, and quality for commercial natural products. The authors contend that a "quality by design" approach for botanical dietary supplements should be implemented in order to ensure the safety and integrity of these products. Initiating this approach with the authentication of the starting plant material is an essential first step, and in this review several techniques that can aid in this endeavor are outlined.

Whether they are being taken as dietary supplements by the general public or being evaluated in a clinical study, the authenticity of botanical products is a matter of paramount concern. Botanical specimens and the dietary supplements derived from them can vary in quality and in chemical constituent profiles because of a number of factors. Subtle variations in botanical specimens are known to have profound effects on the quality, efficacy, and safety of botanical dietary supplements and can potentially alter the results of clinical studies that rely on these materials. A complete array of authentication and evaluation tools can be utilized to provide a well-rounded scientific approach to the authentication of botanical products. It is vital that the authenticity of botanical supplements be established using appropriate analysis tools regardless of whether the end products are being considered for evaluation in clinical studies or are being developed for the consumer market.

Chagas' heart disease, caused by protozoan Trypanosoma cruzi, is a common cause of cardiomyopathy in the Americas. Transmission of T. cruzi occurs through Reduviids, the kissing bugs. Less common ways of transmission are blood transfusion, congenital transmission, organ transplantation, laboratory accident, breastfeeding, and oral contamination. Infestation results in cardiac dysautonomia, myocardial apoptosis, and myocardial fibrosis. In acute phase, death is mostly caused by myocarditis and in chronic phase, it is mostly by irreversible cardiomyopathy. A majority of the patients with Chagas' disease remain in the latent phase of disease for 10 to 30 years or even for life. Specific anti-Chagas' therapy with trypanocide drugs is useful in acute phase but the management of chronic Chagas' heart disease is mostly empirical. The mortality during the acute phase of cardiac Chagas is around 5%. Five-year mortality of chronic Chagas' disease with cardiac dysfunction is above 50%. The clinical aspects of the Chagas' heart disease are concisely reviewed.

LC-UV and LC-MS methods have been developed which permit the analysis of parthenolide in different Mexican/US feverfew samples and commercial products. The study was undertaken to confirm the presence of parthenolide in Mexican plant samples and its comparison with US feverfew samples. The best results were obtained with a Phenomenex Luna C18 (2) column using gradient mobile phase of water and acetonitrile:methanol (9 : 1). Elution was run at a flow rate of 1.0 mL per min and ultraviolet detection at 210 nm. The results obtained using LC-UV were comparable to those obtained using LC-MS. Parthenolide was detected in all the samples analyzed and is the major chemical constituent of feverfew. The samples collected in Oaxaca, Mexico (0.28%) and Puebla, Mexico (0.25%) showed the highest content of parthenolide. All Parthenium samples were also examined under light and fluorescent microscopy.

Medicinal plants have become extremely popular in the United States as botanical supplements, herbal medicines and sources of lead compounds for pharmaceutical development. It is estimated that in 1997 Americans used or consumed 5.1 billion US dollars worth of herbal medicines. For the protection of consumers, authentication of medicinal plants is a critical issue. Ideally, authentication should occur from the harvesting of the plant material to the final product. Unfortunately there is no single or superior method to assure 100 percent authentication during the entire process, but the goal can be achieved through the application of a variety of different methodologies. The whole process starts with good voucher specimens that act as reference material and to prove chain of custody. Macroscopic and microscopic examinations can be used as rapid and inexpensive identification techniques. Chemical analysis is by far the best method for the detection of contaminants and can be an excellent method for plant identification. Each of these methodologies has limitations and more analytical methods are needed to assist in the authentication process. Molecular biology offers an assortment of techniques that can be very useful for authentication of medicinal plants. This review covers various aspects of authentication methods, with special emphasis on molecular biology techniques.

Objective: To evaluate the gender influence in diagnostic and prognostic value of Holter-detected ST-segment deviation., Methods: Two-hundred seventy-seven consecutive patients (196 men) who underwent coronary angiography for evaluation of chest pain were studied with 24-h Holter monitoring within 72 h of coronary angiography, and were followed up for 65+/-21 months., Results: Men had a higher prevalence of coronary artery disease (169 of 196, 86%) compared to that of women (54 of 81, 67%), p<0.00025. Thirty-three (17%) men and 15 (19%) women had ST-segment deviation during 24-h recording. The sensitivity, specificity and positive predictive values of ST-segment deviation (elevation, depression, or both) for the detection of significant coronary artery disease were similar in men and women. The negative predictive values were significantly higher in women than men for ST-segment deviation (36% vs. 15%, p<0.001), ST-segment elevation (35% vs. 14%, p<0.001), and ST-segment depression (34% vs. 15%, p<0.001). Similarly, the diagnostic accuracies were significantly higher in women than men for ST-segment deviation (44% vs. 29%, p<0.025), ST-segment elevation (38% vs. 19%, p<0.001), and ST-segment depression (40% vs. 24%, p<0.025). There was no significant difference in composite end-point of events (mortality, nonfatal myocardial infarction, unstable angina, and coronary revascularization) in men versus women with ST-segment deviation (elevation, depression, or both)., Conclusion: Holter-detected ST-segment deviation has a higher negative predictive value and diagnostic accuracy for detection of significant coronary artery disease in women than in men, although the prognostic values are not significantly different between men and women.

Objective: To study the effect of reinforcement as a quality improvement intervention in the evidence-based management of the coronary syndromes., Methods: In the pre-intervention phase, the charts of 140 consecutive patients with ICD-9 codes 410-414 for coronary syndromes were reviewed for measurement of total cholesterol on admission and fasting low density lipoprotein (LDL) cholesterol, implementation of aspirin therapy on admission, beta-blockers' use during hospitalization, and treatment with angiotensin converting enzyme (ACE) inhibitors in patients with left ventricular systolic dysfunction. Reinforcement was used as an intervention for quality improvement. All personnel of Division of Cardiology including nursing staff, medical residents, cardiology fellows, and attending physicians were reinforced to adhere to the evidence-based management. In the post-intervention phase, charts of 140 consecutive patients with ICD-9 codes 410-414 for coronary syndromes were reviewed to assess the improvement in the same quality of care parameters., Results: By reinforcement, a significant improvement was noted in all quality of care parameters studied. Proportion of patients who had total cholesterol measured on admission increased from 78% to 92% (P<0.005), and those who had fasting LDL cholesterol measured increased from 22% to 70% (P<0.0001). Use of aspirin at admission (in 74% of patients pre- vs. 80% of patients post-intervention, P<0.05), beta-blockers during hospitalization (in 62% of patients pre- vs. 78% of patients post-intervention, P<0.001), and ACE inhibitors in patients with left ventricular systolic dysfunction (in 58% of patients pre- vs. 89% of patients post-intervention, P<0.001) improved significantly after reinforcement to the medical personal., Conclusion: Reinforcement to adhere to the evidence-based management results in a significant improvement in the quality of care provided to the patients with coronary syndromes.

Reperfusion therapy with thrombolytic agents has been a significant advancement in the management of patients with acute ST elevation myocardial infarction. The outcome of acute myocardial infarction has significantly improved by early application of thrombolytic therapy. Intracoronary streptokinase has been used for >30 years, but reawakening interest occurred in the early 1980s in the use of thrombolytic therapy to establish rapid reperfusion during an acute myocardial infarction. Initial studies aimed at direct intracoronary thrombolysis, but owing to its cumbersome process and requirement of an active round the clock cardiac catheterization laboratory, it has been replaced by regimens of intravenous thrombolytic therapy which is as efficacious as intracoronary administration. Consideration of thrombolytic therapy has become a standard treatment for patients presenting with acute ST elevation myocardial infarction and various well-controlled trials have demonstrated the importance of both early and full reperfusion in improving clinical outcome in the setting of acute myocardial infarction. The subject of intravenous thrombolysis is perhaps the most rapidly evolving area in the management of acute myocardial infarction patients in the past decade. The current review focuses on the thrombolysis in the treatment of myocardial infarction and other conditions.