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Background and Aims: The U.S. legal cannabis market is saturated with products containing high levels of tetrahydrocannabinol (THC), with no distinction between medical and recreational programs. This omnipresence of potent cannabis products seems to be driven by the recreational realm, where cannabis with the highest THC content is prized. This prevalence of highly potent cannabis is conveyed to medical programs, which places consumers (patients) at higher risk for over consumption and cannabis use disorder. Thus, understanding what factors influence the market that patients face in medical cannabis programs could shed light on the risks of legal cannabis. The supply and demand dynamic of the US for-profit cannabis market could explain the current market composition; therefore, we postulate that a financial gain could influence the perpetuation of the prevalence of high THC products in legal cannabis dispensaries. We investigate whether THC content in popular cannabis products correlates with higher prices and assess whether some attributes (type of product, chemovars, or presence of cannabidiol (CBD) affect the association of THC with price., Methods: We focus on the world's largest cannabis market, California. We randomly selected dispensaries across the state, screened for a web presence and product menu, determined the most prevalent product type, and collected THC and CBD concentration, price, and other product attributes., Results: We observed that herbal products were more common, they had THC concentrations greater than 10%, and THC concentrations positively correlated with price. This correlation existed in flower and preroll presentations, all chemovar, and independently of the level of CBD. CBD did not correlate with price; however, the presence of CBD diminished the THC and price correlation particularly in products with high THC (>15%)., Conclusions: Overall, highly potent herbal cannabis products (>15% THC) are the majority of products offered and more expensive regardless of product type or chemovar in California dispensaries, suggesting that a financial gain contributes to the current market composition. Efforts to limit the availability of highly potent THC products and educate consumers about potential harms are needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dobbins, Rakkar, Cunnane, Pennypacker, Wagoner, Reboussin and Romero-Sandoval.)

Background and aims: The effects exuded by cannabis are a result of the cannabinoids trans-Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD), and is dependent upon their pharmacological interaction and linked to the two cannabinoids' concentrations and ratios. Based on current literature and trends of increasing cannabis potency, we postulate that most medical cannabis products with THC and CBD have ratios capable of producing significant acute intoxication and are similar to recreational products. We will test this by organizing products into clinically distinct categories according to TCH:CBD ratios, evaluating the data in terms of therapeutic potential, and comparing the data obtained from medical and recreational programs and from states with differing market policies. Methods: We utilized data encompassing online herbal dispensary product offerings from nine U.S. states. The products were analyzed after being divided into four clinically significant THC:CBD ratio categories identified based on the literature: CBD can enhance THC effects (THC:CBD ratios ≥1:1), CBD has no significant effect on THC effects (ratios ∼ 1:2), CBD can either have no effect or can mitigate THC effects (ratios 1:>2 < 6), or CBD is protective against THC effects (ratios ≤1:6). Results: A significant number of products (58.5%) did not contain any information on CBD content. Across all states sampled, the majority (72-100%) of both medical and recreational products with CBD (>0%) fall into the most intoxicating ratio category (≥1:1 THC:CBD), with CBD likely enhancing THC's acute effects. The least intoxicating categories (1:>2 < 6 and ≤1:6 THC:CBD) provided the smallest number of products. Similarly, the majority of products without CBD (0%) contained highly potent amounts of THC (>15%). These results were consistent, regardless of differing market policies in place. Conclusions: Despite the distinct goals of medical and recreational cannabis users, medical and recreational program product offerings are nearly identical. Patients seeking therapeutic benefits from herbal cannabis products are therefore at a substantial risk of unwanted side effects, regardless of whether they obtain products from medical or recreational programs. Efforts are needed to better inform patients of the risks associated with high potency cannabis and the interaction between THC and CBD, and to help shape policies that promote more therapeutic options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pennypacker, Cunnane, Cash and Romero-Sandoval.)

Cannabis related online searches are associated with positive attitudes toward medical cannabis, particularly when information is obtained from dispensaries. Since pain is the main reason for medicinal cannabis use, information from dispensary websites has the potential to shape the attitude of pain patients towards cannabis. This is relevant because cannabis has demonstrated efficacy in neuropathic pain with low tetrahydrocannabinol (THC) concentrations (< 5-10%), in contrast to potent cannabis (>15% THC), which is highly rewarded in the recreational realm. The role of CBD in pain is not clear, however it has gained popularity. Thus, we hypothesize that the potency of medical cannabis that is advertised online is similar to the cannabis advertised for recreational purposes, which would potentially create a misconception towards medical cannabis. The current lack of knowledge surrounding advertised potencies in the legal cannabis market limits the ability to generate clear policies regarding online advertising to protect patients that are willing to use cannabis for their condition. Thus, we evaluated the advertised THC and CBD content of cannabis products offered online in dispensaries in the United States to determine products' suitability to medicinal use and compare the strength of products offered in legal medical and recreational programs. We recorded THC and CBD concentrations for all herb cannabis products provided by dispensary websites and compared them between or within states. Four Western states (CA, CO, NM, WA) and five Northeastern states (ME, MA, NH, RI, VT) were included. A total of 8,505 cannabis products across 653 dispensaries were sampled. Despite the clear differences between medicinal and recreational uses of cannabis, the average THC concentration advertised online in medicinal programs was similar (19.2% ±6.2) to recreational programs (21.5% ±6.0) when compared between states with different programs, or between medicinal and recreational programs within the same states (CO or WA). Lower CBD concentrations accompanied higher THC products. The majority of products, regardless of medicinal or recreational programs, were advertised to have >15% THC (70.3% - 91.4% of products). These stated concentrations seem unsuitable for medicinal purposes, particularly for patients with chronic neuropathic pain. Therefore, this information could induce the misconception that high potency cannabis is safe to treat pain. This data is consistent with reports in which THC and CBD in products from legal dispensaries or in nationwide products from the illegal market were actually measured, which indicates that patients consuming these products may be at risk of acute intoxication or long-term side effects. Our study offers grounds to develop policies that help prevent misconceptions toward cannabis and reduce risks in pain patients., Competing Interests: The authors have declared that no competing interests exist.

Large tissue damage or wounds cause serious comorbidities and represent a major burden for patients, families, and health systems. Due to the pivotal role of immune cells in the proper resolution of inflammation and tissue repair, we focus our current study on the interaction of macrophages with skin cells, and specifically on the effects of CD163 gene induction in macrophages in wound healing. We hypothesize that the over-expression of the scavenger receptor gene CD163 in human macrophages would result in a more efficient wound healing process. Using 3D human wounded skin organotypic tissues, we observed that CD163 overexpression in THP-1 and human primary macrophages induced a more efficient re-epithelization when compared to control cells. Using human primary skin cells and an in vitro scratch assay we observed that CD163 overexpression in THP-1 macrophages promoted a more rapid and efficient wound healing process through a unique interaction with fibroblasts. The addition of CD163-blocking antibody, but not isotype control, blocked the efficient wound healing process induced by CD163 overexpression in macrophages. We found that the co-culture of skin cells and CD163 overexpressing macrophages reduced monocyte chemoattractant protein (MCP)-1 and enhanced tumor growth factor (TGF)-α, without altering interleukin (IL)-6 or TGF-β. Our findings show that CD163 induces a more efficient wound healing and seems to promote a wound milieu with a pro-resolution molecular profile. Our studies set the foundation to study this approach in in vivo clinically relevant settings to test its effects in wound healing processes such as acute major injuries, large surgeries, or chronic ulcers., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier GmbH. All rights reserved.)

Background/aims: There have been recent reports of reflux esophagitis apparently occurring de novo after cure of H. pylori in peptic ulcer disease. The possibility that this phenomenon might be explained, at least in part, by unmasking of coexistent disease has not been assessed. The aim of this study was to assess the prevalence of esophagitis in H. pylori-positive peptic ulcer disease and examine the short-term impact of H. pylori therapy on the esophagus., Methodology: Esophagitis was systematically graded and the presence of hiatal hernia was noted in 244 peptic ulcer patients (duodenal 223; gastric 21) before and at least four weeks after triple therapy. H. pylori status was assessed using CLO test and histology, and esophagitis grade was assigned without knowledge of H. pylori status., Results: Of the 244 patients, 49 (20%) had esophagitis which was grade 2 or more in over two-thirds. The prevalence of esophagitis was similar in duodenal and gastric ulcer patients. The presence of hiatal hernia was strongly associated with the finding of esophagitis (P < 0.001). Of 241 patients evaluable after therapy, 215 (89%) were H. pylori-negative and 26 remained H. pylori-positive. Esophagitis tended to improve or remain stable after H. pylori therapy and worsened in only 2 of the 49 patients (4%). Of 192 patients with a normal esophagus at baseline endoscopy, 14 (7%) showed evidence of esophagitis after therapy. The presence of hiatal hernia, but not cure of H. pylori, was significantly associated with the development of esophagitis., Conclusions: Our results indicate that esophagitis can coexist with peptic ulcer disease and persists after cure of H. pylori. Development of de novo esophagitis seems uncommon in the short-term after H. pylori therapy. Esophagitis in peptic ulcer disease is strongly associated with the presence of hiatal hernia.

Background: Seven-day proton pump inhibitor triple therapy is currently the treatment of choice for Helicobacter pylori infection. It is unclear whether triple therapy for less than 7 days might preserve efficacy while at the same time improving patient acceptability and compliance., Aim: To evaluate the Helicobactericidal efficacy, ulcer healing capacity and patient acceptability of a 5-day lansoprazole-based triple therapy regimen., Methods: Sixty-nine consecutive patients with H. pylori-positive peptic ulcer received lansoprazole 30 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 250 mg twice daily for 5 days. Ulcer healing medication was not continued after the 5-day regimen. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning., Results: All 69 patients attended for repeat endoscopy and 63 were H. pylori-negative after therapy giving a cure rate of 91%, (95%, Cl: 85-98%). Of the 59 patients with active ulcers, 58 were healed at repeat endoscopy giving an ulcer healing rate of 98% (95% Cl: 92-100%). All patients fully complied with therapy and mild adverse events, mainly gastrointestinal, were reported by 11 patients (16%)., Conclusions: Five-day lansoprazole triple therapy is an effective regimen for H. pylori infection which combines a high cure rate and ulcer healing efficacy with the advantages of excellent patient acceptability and compliance.

Background: Clarithromycin, a new acid stable macrolide antibiotic with proven efficacy against Helicobacter pylori, has been widely incorporated into eradication regimens but its optimal dosage schedule remains controversial. The standard dose of clarithromycin is 250 mg twice daily., Methods: In a prospective study designed to evaluate the helicobactericidal efficacy, patient acceptability, and ulcer healing efficacy of a triple therapy regimen incorporating high dose clarithromycin, 100 consecutive patients with H. pylori-positive peptic ulcer received omeprazole 20 mg twice daily in combination with metronidazole 400 mg twice daily and clarithromycin 500 mg twice daily for seven days. H. pylori status was assessed before and at least 4 weeks after therapy by rapid urease test and histology. Adverse events and compliance were assessed by direct questioning., Results: Only two patients failed to attend for repeat endoscopy, leaving 98 evaluable patients. Of these, 94 were H. pylori-negative after therapy, giving an intention-to-treat eradication rate of 94% (95% confidence interval, 89%-99%). The ulcer healing rate was 92% (86%-98%), and ulcer healing was significantly associated with H. pylori eradication (p < 0.01). Adverse events were reported by 33% of patients of which nausea was the commonest (14%). Noncompliance with therapy was significantly associated with H. pylori treatment failure (p < 0.001)., Conclusions: Seven day triple therapy incorporating high dose clarithromycin effectively eradicates H. pylori and heals ulcers, but it is disadvantaged by a relatively high rate of adverse events. In view of these findings and the fact that no direct comparison to date has shown increased efficacy from high dose clarithromycin, we would recommend continued use of low dose clarithromycin when combined with omeprazole and a nitroimidazole.

In a prospective study designed to assess the effect of duration of antibiotic therapy on the helicobactericidal and ulcer healing efficacy of bismuth therapy, groups of patients, 10 in each group, with H. pylori-positive duodenal ulcer received a triple therapy regimen consisting of colloidal bismuth subcitrate 120 mg 4 times daily for 28 days with metronidazole 400 mg 3 times daily and tetracycline 500 mg 3 times daily for the first 3, 5 or 7 days of therapy. H. pylori infection was assessed by urease test, culture and histology performed before and 4 or more weeks after completion of therapy. Three patients (30 per cent) were H. pylori-negative after therapy in the 3 day compared with 5 (50 per cent) in the 5 day and 9 (90 per cent) in the 7 day treatment groups (3 vs 7, P = 0.01; 5 vs 7, P = 0.14). Healed ulcers were seen in 7 (70 per cent) of the 3 day, in 6 (60 per cent) of the 5 day, and in 10 (100 per cent) of the 7 day treatment groups (5 vs 7, P = 0.04). Bismuth triple therapy incorporating metronidazole and tetracycline for 7 days is associated with superior H. pylori eradication and ulcer healing rates than bismuth triple incorporating antibiotics for 3 or 5 days.

In a prospective study designed to assess the effect of Helicobacter pylori eradication on peptic ulcer healing, 85 consecutive patients with H. pylori-positive peptic ulcer disease were treated with a triple therapy regimen consisting of colloidal bismuth subcitrate 120 mg four times daily for 28 days, with metronidazole 400 mg three times daily and tetracycline 500 mg three times daily for the first seven days of treatment. H. pylori status was assessed by CLO test and histology at least four weeks after completing therapy. Of 75 patients (88%) H. pylori-negative after therapy, 69 (92%) had healed ulcers compared with only five of 10 patients (50%) who remained H. pylori-positive (p = 0.003). Cigarette smoking had no significant effect on ulcer healing. Our results suggest that H. pylori eradication may accelerate ulcer healing and provide further evidence that an effective helicobactericidal regimen is the treatment of choice in H. pylori-positive peptic ulcer.

In a prospective evaluation of the relationship between Helicobacter pylori infection and gastro-oesophageal reflux disease (GORD), 93 consecutive patients (47 female: 46 male: mean age, 46 years: range 13-93) with symptoms and endoscopic evidence of GORD were studied. A total of 50 patients (54%) were H. pylori-positive on gastric antral biopsies. No significant correlation was detected between H. pylori status and grade of oesophagitis. The prevalence of H. pylori infection showed a gradual increase with age. Of 64 patients with a hiatal hernia, 28 (44%) had histological evidence of H. pylori infection of the hernia mucosa; 27 of these patients (96%) had associated H. pylori in the gastric antrum. Of the 36 patients whose hiatal hernia was H. pylori-negative, only 6 (17%) had antral H. pylori (P < 0.001). Of the 8 patients found to have Barrett's oesophagus, only 1 had H. pylori detected on the Barrett's mucosa. Our results do not support the presence of a significant association between H. pylori infection and GORD.

The author describes a case of esophagoatrial fistula--an extremely rare condition. A 79-year-old-man had had epigastric pain for 4 weeks. Physical and roentgenographic examinations disclosed atrial fibrillation with a systolic murmur and an ulcer of the lower esophagus which, on histologic examination, was benign. No specific treatment was recommended. The patient died suddenly 3 months later from massive gastrointestinal hemorrhage which, at autopsy, was found to be due to an esophagoatrial fistula. A review of the literature showed that this case differed from others previously reported in that the duration of symptoms up to the time of death was only 4 months and the patient had no embolism.