Surgical marker navigation system in breast conserving surgery and excision of non-palpable lesions: first Spanish single-center experience.

BACKGROUND: Due to the establishment of screening mammography for breast cancer detection, the number of non-palpable lesions has increased. Thus, an optimal localization system is mandatory for the excision of non-palpable breast tumors. OBJECTIVE: The aim of the study is to report the feasibility Surgical Marker Navigation (SMN) system Sirius Pintuition® for the excision of non-palpable breast tumors and non-palpable axillary lymph nodes. METHODS: A retrospective observational study of patients undergoing breast-conserving surgery and lymph node excision guided by SMN between December 2022 and May 2023 was performed. RESULTS: A total of 84 patients underwent excision of non-palpable breast tumors (77; 91.7%) or non-palpable axillary lymph-nodes (7; 8.3%) using SMN. In total, 94 markers were placed, in 74 patients (88.1%) only one marker was placed, whereas in 10 patients (11.9%) two markers were placed to correctly localize the lesion in the operating room. Most markers were placed using ultrasonographic guidance (69; 82.1%). Seventy-seven patients underwent breast-conserving surgery (91.7%) and 7 (8.3%) lymph node excision. In 10 cases (11.9%), the marker was accidentally displaced during surgery due to the use of magnetized instruments, although the specimen could be removed. In sum, all the markers were removed from the patients, although the marker retrieval rate, as we defined it (percentage of patients in whom the initial excised specimen contained the marker divided by the total number of patients), was 88.1%. CONCLUSION: The use of Sirius Pintuition® SMN for non-palpable breast tumors and non-palpable lymph nodes is feasible, with a retrieval rate of 88.1%.

The Leu/Val6.51 Side Chain of Cannabinoid Receptors Regulates the Binding Mode of the Alkyl Chain of Δ9-Tetrahydrocannabinol.

(-)-Δ9-trans-tetrahydrocannabinol (THC), which is the principal psychoactive constituent of Cannabis, mediates its action by binding to two members of the G-protein-coupled receptor (GPCR) family: the cannabinoid CB1 (CB1R) and CB2 (CB2R) receptors. Molecular dynamics simulations showed that the pentyl chain of THC could adopts an I-shape conformation, filling an intracellular cavity between Phe3.36 and Trp6.48 for initial agonist-induced receptor activation, in CB1R but not in CB2R. This cavity opens to the five-carbon chain of THC by the conformational change of the γ-branched, flexible, Leu6.51 side chain of CB1R, which is not feasible by the ß-branched, mode rigid, Val6.51 side chain of CB2R. In agreement with our computational results, THC could not decrease the forskolin-induced cAMP levels in cells expressing mutant CB1RL6.51V receptor but could activate the mutant CB2RV6.51L receptor as efficiently as wild-type CB1R. Additionally, JWH-133, a full CB2R agonist, contains a branched dimethyl moiety in the ligand chain that bridges Phe3.36 and Val6.51 for receptor activation. In this case, the substitution of Val6.51 to Leu in CB2R makes JWH-133 unable to activate CB2RV6.51L. In conclusion, our combined computational and experimental results have shown that the amino acid at position 6.51 is a key additional player in the initial mechanism of activation of GPCRs that recognize signaling molecules derived from lipid species.

Cannabidiol at Nanomolar Concentrations Negatively Affects Signaling through the Adenosine A2A Receptor.

Cannabidiol (CBD) is a phytocannabinoid with potential as a therapy for a variety of diseases. CBD may act via cannabinoid receptors but also via other G-protein-coupled receptors (GPCRs), including the adenosine A2A receptor. Homogenous binding and signaling assays in Chinese hamster ovary (CHO) cells expressing the human version of the A2A receptor were performed to address the effect of CBD on receptor functionality. CBD was not able to compete for the binding of a SCH 442416 derivative labeled with a red emitting fluorescent probe that is a selective antagonist that binds to the orthosteric site of the receptor. However, CBD reduced the effect of the selective A2A receptor agonist, CGS 21680, on Gs-coupling and on the activation of the mitogen activated kinase signaling pathway. It is suggested that CBD is a negative allosteric modulator of the A2A receptor.

Regulation of Expression of Cannabinoid CB2 and Serotonin 5HT1A Receptor Complexes by Cannabinoids in Animal Models of Hypoxia and in Oxygen/Glucose-Deprived Neurons.

Background: Cannabidiol (CBD) is a phytocannabinoid with potential in one of the most prevalent syndromes occurring at birth, the hypoxia of the neonate. CBD targets a variety of proteins, cannabinoid CB2 and serotonin 5HT1A receptors included. These two receptors may interact to form heteromers (CB2-5HT1A-Hets) that are also a target of CBD. Aims: We aimed to assess whether the expression and function of CB2-5HT1A-Hets is affected by CBD in animal models of hypoxia of the neonate and in glucose- and oxygen-deprived neurons. Methods: We developed a quantitation of signal transduction events in a heterologous system and in glucose/oxygen-deprived neurons. The expression of receptors was assessed by immuno-cyto and -histochemistry and, also, by using the only existing technique to visualize CB2-5HT1A-Hets fixed cultured cells and tissue sections (in situ proximity ligation PLA assay). Results: CBD and cannabigerol, which were used for comparative purposes, affected the structure of the heteromer, but in a qualitatively different way; CBD but not CBG increased the affinity of the CB2 and 5HT1A receptor-receptor interaction. Both cannabinoids regulated the effects of CB2 and 5HT1A receptor agonists. CBD was able to revert the upregulation of heteromers occurring when neurons were deprived of oxygen and glucose. CBD significantly reduced the increased expression of the CB2-5HT1A-Het in glucose/oxygen-deprived neurons. Importantly, in brain sections of a hypoxia/ischemia animal model, administration of CBD led to a significant reduction in the expression of CB2-5HT1A-Hets. Conclusions: Benefits of CBD in the hypoxia of the neonate are mediated by acting on CB2-5HT1A-Hets and by reducing the aberrant expression of the receptor-receptor complex in hypoxic-ischemic conditions. These results reinforce the potential of CBD for the therapy of the hypoxia of the neonate.

Similarities and differences upon binding of naturally occurring Δ9-tetrahydrocannabinol-derivatives to cannabinoid CB1 and CB2 receptors.

We have here assessed, using Δ9-tetrahydrocannabinol (Δ9-THC) for comparison, the effect of Δ9-tetrahydrocannabinolic acid (Δ9-THCA) and of Δ9-tetrahydrocannabivarin (Δ9-THCV) that is mediated by human versions of CB1, CB2, and CB1-CB2 receptor functional units, expressed in a heterologous system. Binding to the CB1 and CB2 receptors was addressed in living cells by means of a homogeneous assay. A biphasic competition curve for the binding to the CB2 receptor, was obtained for Δ9-THCV in cells expressing the two receptors. Signaling studies included cAMP level determination, activation of the mitogen-activated protein kinase pathway and ß-arrestin recruitment were performed. The signaling triggered by Δ9-THCA and Δ9-THCV via individual receptors or receptor heteromers disclosed differential bias, i.e. the bias observed using a given phytocannabinoid depended on the receptor (CB1, CB2 or CB1-CB2) and on the compound used as reference to calculate the bias factor (Δ9-THC, a selective agonist or a non-selective agonist). These results are consistent with different binding modes leading to differential functional selectivity depending on the agonist structure, and the state (monomeric or heteromeric) of the cannabinoid receptor. In addition, on studying Gi-coupling we showed that Δ9-THCV and Δ9-THCA and Δ9-THCV were able to revert the effect of a selective CB2 receptor agonist, but only Δ9-THCV, and not Δ9-THCA, reverted the effect of arachidonyl-2'-chloroethylamide (ACEA 100 nM) a selective agonist of the CB1 receptor. Overall, these results indicate that cannabinoids may have a variety of binding modes that results in qualitatively different effects depending on the signaling pathway that is engaged upon cannabinoid receptor activation.

Pharmacological potential of varinic-, minor-, and acidic phytocannabinoids.

While natural Δ9-tetrahidrocannabinol (Δ9THC), cannabidiol (CBD), and their therapeutic potential have been extensively researched, some cannabinoids have been less extensively investigated. The present article compiles data from the literature that highlight the health benefits and therapeutic potential of lesser known phytocannabinoids, which we have divided into varinic, acidic, and "minor" (i.e., cannabinoids that are not present in high quantities in common varieties of Cannabis sativa L). A growing interest in these compounds, which are enriched in some cannabis varieties, has already resulted in enough preclinical information to show that they are promising therapeutic agents for a variety of diseases. Every phytocannabinoid has a "preferential" mechanism of action, and often targets the cannabinoid receptors, CB1 and/or CB2. The recent resolution of the structure of cannabinoid receptors demonstrates the atypical nature of cannabinoid binding, and that different binding modes depend on the agonist or partial agonist/inverse agonist, which allows for differential signaling, even acting on the same cannabinoid receptor. In addition, other players and multiple signaling pathways may be targeted/engaged by phytocannabinoids, thereby expanding the mechanistic possibilities for therapeutic use.

Pharmacological data of cannabidiol- and cannabigerol-type phytocannabinoids acting on cannabinoid CB1, CB2 and CB1/CB2 heteromer receptors.

BACKGROUND: Recent approved medicines whose active principles are Δ9Tetrahidrocannabinol (Δ9-THC) and/or cannabidiol (CBD) open novel perspectives for other phytocannabinoids also present in Cannabis sativa L. varieties. Furthermore, solid data on the potential benefits of acidic and varinic phytocannabinoids in a variety of diseases are already available. Mode of action of cannabigerol (CBG), cannabidiolic acid (CBDA), cannabigerolic acid (CBGA), cannabidivarin (CBDV) and cannabigerivarin (CBGV) is, to the very least, partial. HYPOTHESIS/PURPOSE: Cannabinoid CB1 or CB2 receptors, which belong to the G-protein-coupled receptor (GPCR) family, are important mediators of the action of those cannabinoids. Pure CBG, CBDA, CBGA, CBDV and CBGV from Cannabis sativa L. are differentially acting on CB1 or CB2 cannabinoid receptors. STUDY DESIGN: Determination of the affinity of phytocannabinoids for cannabinoid receptors and functional assessment of effects promoted by these compounds when interacting with cannabinoid receptors. METHODS: A heterologous system expressing the human versions of CB1 and/or CB2 receptors was used. Binding to membranes was measured using radioligands and binding to living cells using a homogenous time resolved fluorescence resonance energy transfer (HTRF) assay. Four different functional outputs were assayed: determination of cAMP levels and of extracellular-signal-related-kinase phosphorylation, label-free dynamic mass redistribution (DMR) and ß-arrestin recruitment. RESULTS: Affinity of cannabinoids depend on the ligand of reference and may be different in membranes and in living cells. All tested phytocannabinoids have agonist-like behavior but behaved as inverse-agonists in the presence of selective receptor agonists. CBGV displayed enhanced potency in many of the functional outputs. However, the most interesting result was a biased signaling that correlated with differential affinity, i.e. the overall results suggest that the binding mode of each ligand leads to specific receptor conformations underlying biased signaling outputs. CONCLUSION: Results here reported and the recent elucidation of the three-dimensional structure of CB1 and CB2 receptors help understanding the mechanism of action that might be protective and the molecular drug-receptor interactions underlying biased signaling.

Effect of Resistance Exercise Plus Cholecalciferol on Nutritional Status Indicators in Adults With Stage 4 Chronic Kidney Disease.

OBJECTIVE: Decreased serum concentrations of 25-hydroxyvitamin D (25(OH)D) affect people with chronic kidney disease (CKD); lower concentrations of 25(OH)D have been associated with decrease in nutritional status indicators. On the other hand, muscle resistance exercise has improved the nutritional status of patients with CKD.The aim of this study was to evaluate the effect of resistance exercise and dietary supplementation with cholecalciferol on nutritional status indicators in adults with stage 4 CKD. METHODS: Patients with an estimated glomerular filtration rate between 15 and 29 mL/min/1.73 m2 in an open-label clinical trial were followed for 12 weeks. The intervention group received exercise resistance training sessions three times per week with oral cholecalciferol supplementation each day. The control group only received standard medical care. The outcomes were anthropometric measurements, handgrip strength, and bioelectrical impedance analysis. RESULTS: Thirty-nine patients of a median age of 48 (36-52) years had an estimated glomerular filtration rate of 21.8 ± 6.5 mL/min/1.73 m2. A total of 57.5% of the patients were women. In 41% of the patients, the etiology of CKD was diabetes. After 12 weeks, in the intervention group, the adherence to the resistance training was 77%, and the adherence to the supplementation with cholecalciferol was 96.2%. Significant improvements in 25(OH)D serum concentrations and in handgrip strength were detected in the intervention group (P < .05). In the control group, a decrease in 25(OH)D serum concentrations and a loss in handgrip strength were observed, although the difference was not statistically significant. Anthropometrics and biochemical and dietary indicators, but not bioelectrical impedance data, exhibited changes. CONCLUSION: Supplementation with cholecalciferol improves serum concentrations of 25(OH)D and, when combined with resistance exercise, improved muscle function as measured by handgrip strength in a study of patients with CKD not on dialysis.

Potentiation of cannabinoid signaling in microglia by adenosine A2A receptor antagonists.

Neuroprotective M2-skewed microglia appear as promising to alter the course of neurodegenerative diseases and G protein-coupled receptors (GPCRs) are potential targets to achieve such microglial polarization. A common feature of adenosine A2A (A2A R) and cannabinoid CB2 (CB2 R) GPCRs in microglia is that their expression is upregulated in Alzheimer's disease (AD). On the one hand, CB2 R seems a target for neuroprotection, delaying neurodegenerative processes like those associated to AD or Parkinson's diseases. A2A R antagonists reduce amyloid burden and improve cognitive performance and memory in AD animal models. We here show a close interrelationship between these two receptors in microglia; they are able to physically interact and affect the signaling of each other, likely due to conformational changes within the A2A -CB2 receptor heteromer (A2A -CB2 Het). Particularly relevant is the upregulation of A2A -CB2 Het expression in samples from the APPSw ,Ind AD transgenic mice model. The most relevant finding, confirmed in both heterologous cells and in primary cultures of microglia, was that blockade of A2A receptors results in increased CB2 R-mediated signaling. This heteromer-specific feature suggests that A2A R antagonists would potentiate, via microglia, the neuroprotective action of endocannabinoids with implications for AD therapy.

Two Cases of Neisseria meningitidis Proctitis in HIV-Positive Men Who Have Sex with Men.

We report 2 cases from Spain of infectious proctitis caused by Neisseria meningitidis in HIV-positive men who have sex with men. Genetic characterization of the isolates showed that they are unusual strains not found in other more frequent meningococcal locations. This finding suggests an association between specific strains and anogenital tract colonization.

Untargeted analysis to monitor metabolic changes of garlic along heat treatment by LC-QTOF MS/MS.

Black garlic is increasing its popularity in cuisine around the world; however, scant information exists on the composition of this processed product. In this study, polar compounds in fresh garlic and in samples taken at different times during the heat treatment process to obtain black garlic have been characterized by liquid chromatography coupled to tandem mass spectrometry in high resolution mode. Ninety-five compounds (mainly amino acids and metabolites, organosulfur compounds, and saccharides and derivatives) were tentatively identified in all the analysed samples and classified as a function of the family they belong to. Statistical analysis of the results allowed establishing that the major changes in garlic occur during the first days of treatment, and they mainly affect to the three representative families. The main pathways involved in the synthesis of the compounds affected by heat treatment, and their evolution during the process were studied.

Composition of fatty acids in virgin olive oils from cross breeding segregating populations by gas chromatography separation with flame ionization detection.

BACKGROUND: Recent technological advances to improve the quality of virgin olive oil (VOO) have been focused on olive breeding programs by selecting outstanding cultivars and target progenies. Fatty acid (FA) composition, with special emphasis on oleic acid (C18:1) and palmitic acid (C16:0), is one of the most critical quality factors to be evaluated in VOO. For this reason, the profile of FAs is frequently used as a decision tool in olive breeding programs. RESULTS: A method based on gas chromatography with flame ionization detection (GC-FID) was used to study the influence of genotype on the concentration of ten of the most important FAs in VOOs from target crosses Arbequina × Arbosana, Picual × Koroneiki and Sikitita × Arbosana and their corresponding genitors Arbequina, Arbosana, Koroneiki, Picual and Sikitita. For this purpose, a targeted approach was selected for determination of esterified FAs (EFAs) and non-esterified FAs (NEFAs) in a dual analysis by the same chromatographic method. A Pearson analysis revealed correlations between pairs of FAs, which allowed detecting metabolic connections through desaturation and elongation enzymes. An ANOVA test (with P < 0.01) led to identification of C16:0 EFA, C16:1 EFA and C18:1 EFA and also C16:1 NEFA and C18:0 NEFA as the FAs more influenced by cross breeding. Statistical analysis was carried out by unsupervised analysis using principal component analysis (PCA) and cluster analysis (CA) to look for variability sources. CONCLUSION: Crosses with a common genitor (Arbequina × Arbosana and Sikitita × Arbosana) were partially overlapped in the PCAs using the profile of FAs. The CA results revealed clear differences between Sikitita × Arbosana and Picual × Koroneiki crosses in the composition of the most significant FAs, while Arbequina × Arbosana was not properly discriminated from the other crosses.

Correlates of measured prehypertension and hypertension in Latina women living along the US-Mexico border, 2007-2009.

INTRODUCTION: Although Latinos have lower hypertension rates than non-Latino whites and African Americans, they have a higher prevalence of undiagnosed and uncontrolled hypertension. Research on predictors of hypertension has mostly focused on intrapersonal factors with no studies assessing the combined influence of intrapersonal, interpersonal, and environmental factors. The purpose of this study was to assess a broad range of correlates including intrapersonal, interpersonal, and environmental factors on measured blood pressure category (nonhypertensive, prehypertensive, and hypertensive) in a sample of Latina women residing in San Diego, California. METHODS: This cross-sectional study used baseline data from the San Diego Prevention Research Center's Familias Sanas y Activas program, a promotora-led physical activity intervention. The sample was 331 Latinas who self-selected into this program. Backward conditional logistic regression analysis was conducted to determine the strongest correlates of measured blood pressure category. RESULTS: Logistic regression analysis suggested that the strongest correlates of prehypertension were soda consumption (odds ratio [OR] = 1.34, [1.00-1.80], P ≤ .05) and age (OR = 1.03, [1.00-1.05], P ≤ .05). The strongest correlates of hypertension were soda consumption (OR = 1.92, [1.20-3.07], P ≤ .01), age (OR = 1.09, [1.05-1.13], P ≤ .001), and measured body mass index (OR = 1.13, [1.05-1.22], P ≤ .001). All analyses controlled for age and education. No interpersonal or environmental correlates were significantly associated with blood pressure category. CONCLUSION: Future research should aim to further understand the role of soda consumption on risk for hypertension in this population. Furthermore, interventions aimed at preventing hypertension may want to focus on intrapersonal level factors.

High-resolution mass spectrometry to evaluate the influence of cross-breeding segregating populations on the phenolic profile of virgin olive oils.

BACKGROUND: The growing demand for high-quality virgin olive oils (VOOs) has increased the interest in olive breeding programs. Cross-breeding is considered, within these programs, the best strategy to generate new cultivars as an attempt to improve the present cultivars. In this research, the phenolic profile of VOOs from target crosses (Arbequina × Arbosana, Picual × Koroneiki and Sikitita × Arbosana) and their corresponding genitors (Arbequina, Arbosana, Koroneiki, Picual and Sikitita) has been evaluated using a targeted metabolomics approach. RESULTS: The phenolic profiles were obtained by liquid chromatographic-hybrid quadrupole time-of-flight mass spectrometric targeted analysis of 37 phenols or compounds involved in the main pathways for their biosynthesis. Statistical multivariate analysis by principal component analysis was applied to study the influence of genotype on phenol composition. Phenolic compounds with the highest contribution to explain the observed variability associated to genotype were identified through fold change algorithms (cut-off > 2.0) and t-test analysis. CONCLUSION: A total of nine phenols (viz. quercetin, ligstroside aglycon (p-HPEA-EA), demethyl oleuropein aglycon, oleuropein aglycon (3,4-DHPEA-EA), hydroxypinoresinol, hydroxytyrosol and phenolic acids such as p-coumaric acid, ferulic acid and protocatechuic acid) contributed to explain the observed variability with 99% confidence (P<0.01).

Pharmacokinetics and oral bioavailability of cannabidiol in horses after intravenous and oral administration with oil and micellar formulations.

BACKGROUND: Intravenous pharmacokinetics and oral bioavailability of cannabidiol (CBD) with different formulations have not been investigated in horses and may represent a starting point for clinical studies. OBJECTIVES: To describe pharmacokinetics after intravenous and oral administrations with oil and micellar formulations and simulate different treatments. STUDY DESIGN: Single intravenous experiment and two-way randomised oral experiments, Latin-square design. METHODS: Eight healthy horses received intravenous CBD at 1.00 mg/kg dose, oral CBD in sesame oil and in micellar formulation, both at 10.00 mg/kg. Concentrations were measured using LC-MS/MS and fitted by nonlinear mixed effect modelling. Parameters obtained were used to simulate single and multiple treatments at steady state. RESULTS: Intravenous and oral concentrations were simultaneously fitted using a three-compartment model. Final estimates indicate that CBD has a volume of distribution of 36 L/kg associated with a systemic clearance of 1.46 L/h/kg and half-lives ranged between 24 and 34 h. Oral bioavailability was close to 14% for both oral administrations. Simulated dose regimen of CBD every 12 and 24 h predicted similar percentages to reach effective plasma concentration with both oral formulation at 10.00 mg/kg. MAIN LIMITATIONS: A small horse population was used (8 horses per trial). CONCLUSIONS AND CLINICAL IMPORTANCE: Oral bioavailability was low at the doses studied but fell within the range described for horse and other species. CBD had a high steady-state volume of distribution, a high clearance and long half-lives. No adverse reactions were detected at any dose or route. The micellar formulation showed a faster absorption and higher concentration peak, while the oil formulation presented lower levels, but more maintained over time. Simulations predicted that both could be useful in multiple oral dose treatments. These results indicated that CBD could be of interest, but further studies are needed to evaluate its clinical use in horses.

Neuroprotective Effect of a Pharmaceutical Extract of Cannabis with High Content on CBD Against Rotenone in Primary Cerebellar Granule Cell Cultures and the Relevance of Formulations.

Introduction: Preclinical research supports the benefits of pharmaceutical cannabis-based extracts for treating different medical conditions (e.g., epilepsy); however, their neuroprotective potential has not been widely investigated. Materials and Methods: Using primary cultures of cerebellar granule cells, we evaluated the neuroprotective activity of Epifractan (EPI), a cannabis-based medicinal extract containing a high level of cannabidiol (CBD), components like terpenoids and flavonoids, trace levels of Δ9-tetrahydrocannabinol, and the acid form of CBD. We determined the ability of EPI to counteract the rotenone-induced neurotoxicity by analyzing cell viability and morphology of neurons and astrocytes by immunocytochemical assays. The effect of EPI was compared with XALEX, a plant-derived and highly purified CBD formulation (XAL), and pure CBD crystals (CBD). Results: The results revealed that EPI induced a significant reduction in the rotenone-induced neurotoxicity in a wide range of concentrations without causing neurotoxicity per se. EPI showed a similar effect to XAL suggesting that no additive or synergistic interactions between individual substances present in EPI occurred. In contrast, CBD did show a different profile to EPI and XAL because a neurotoxic effect per se was observed at higher concentrations assayed. Medium-chain triglyceride oil used in EPI formulation could explain this difference. Conclusion: Our data support a neuroprotective effect of EPI that may provide neuroprotection in different neurodegenerative processes. The results highlight the role of CBD as the active component of EPI but also support the need for an appropriate formulation to dilute pharmaceutical cannabis-based products that could be critical to avoid neurotoxicity at very high doses.

Telephonic Follow-up and the Risk of Death in Ambulatory Patients with COVID-19.

BACKGROUND: Primary care level close monitoring of mild COVID-19 patients has shown to provide a risk reduction in hospitalization and death. We aimed to compare the risk of all-cause death among COVID-19 ambulatory patients who received and did not receive telephonic follow-up in primary health care settings. METHODS: A secondary database analysis, 2-group comparative study, was conducted with data from the medical information systems of the Mexican Institute of Social Security. A total of 1,498,808 ambulatory patients aged 20 years old and over and with laboratory confirmed SARS-CoV-2 by PCR or rapid antigen test were analyzed. Of them, 535,898 (35.8%) where followed by telephonic calls. The cases were attended from October 14, 2020, to April 10, 2022. Death incidence was evaluated. To assess the association between death and telephonic follow-up we calculated risk ratio using a multivariate logistic model. RESULTS: Case fatality rate was 1.29% in the patients who received telephonic follow-up and 2.95% in the cases who did not receive phone calls. Medical history of chronic kidney disease, COPD, cardiovascular disease, tobacco consumption and diabetes were associated with increased risk of death. In the multivariate model, telephonic follow-up was associated with lower risk of all-cause death, with an adjusted risk ratio of 0.61 (95% confidence interval from 0.59, 0.64). CONCLUSION: Our data suggest that telephonic follow-up is associated with a risk of death reduction in adult outpatients with mild COVID-19, in the context of a multimodal strategy in the primary health care settings.

Effect of temperature in the degradation of cannabinoids: From a brief residence in the gas chromatography inlet port to a longer period in thermal treatments.

The substantial increase in legalization and subsequent regulation of cannabis has intensified the control and analytical monitoring of cannabis products to assure sample quality and control the cannabinoid content of the crop. In this sense, the restriction on cultivating legal cannabis plants has been limited to 0.2-0.3% of Δ9-THC content, depending on the host country's laws. Thereby, cannabis flowers containing more than this limit are considered illicit drug-type cultivations and require the obtention of specific permits to work with them. The official method established by the European Commission set the gas chromatography/flame ionization detector (GC-FID) as the proper instrument to analyze the delta-9 tetrahydrocannabinol (Δ9-THC) content. In the present work, the potential drawbacks associated with the utilization of the official method for the evaluation of the Δ9-THC content have been described. Thus, the effect of the GC injector port temperature in the degradation of cannabinoids was evaluated, observing the degradation of CBD by 20%, generating Δ9-THC and CBN as by-products. Likewise, 17.2% of Δ9-THC was degraded, producing CBN as a by-product. Therefore, despite the brief residence of cannabinoids in the GC inlet, the effect of temperature is noteworthy and must be considered. Derivatization of cannabinoids should be a mandatory step to prevent the thermal degradation of cannabinoids, assuring the accuracy of the results. Furthermore, the evaluation of cannabinoid degradation thermally treated for longer periods of time was carried out. The kinetic degradation of CBD was evaluated in this way, observing a degradation of 0.22 µg/L per second. At the same time, the kinetics of the appearance of Δ9-THC demonstrates the intermediate nature of this cannabinoid, being degraded at 0.03 s-1 µM-1. The degradation of CBD also produced CBN and CBE as by-products.

Assessment of performance characteristics of COVID-19 ICD-10-CM diagnosis code U07.1 using SARS-CoV-2 nucleic acid amplification test results.

The Food and Drug Administration's Biologics Effectiveness and Safety Initiative conducts active surveillance to protect public health during the coronavirus disease 2019 (COVID-19) pandemic. This study evaluated performance of International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code U07.1 in identifying COVID-19 cases in claims compared with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid amplification test results in linked electronic health records (EHRs). Care episodes in three populations were defined using COVID-19-related diagnoses (population 1), SARS-CoV-2 nucleic acid amplification test procedures (population 2), and all-cause hospitalizations (population 3) in two linked claims-EHR databases: IBM® MarketScan® Explorys® Claims-EMR Data Set (commercial) and OneFlorida Data Trust linked Medicaid-EHR. Positive and negative predictive values were calculated. Respectively, populations 1, 2, and 3 included 26,686, 26,095, and 2,564 episodes (commercial) and 29,117, 23,412, and 9,629 episodes (Florida Medicaid). The positive predictive value was >80% and the negative predictive value was >95% in each population, with the highest positive predictive value in population 3 (commercial: 91.9%; Medicaid: 93.1%). Findings did not vary substantially by patient age. Positive predictive values in populations 1 and 2 fluctuated during April-June 2020. They then stabilized in the commercial but not the Medicaid population. Negative predictive values were consistent over time in all populations and databases. Our findings indicate that U07.1 has high performance in identifying COVID-19 cases and noncases in claims databases. Performance may vary across populations and periods.

A Multimodal Strategy to Reduce the Risk of Hospitalization/death in Ambulatory Patients with COVID-19.

BACKGROUND: Different interventions have been implemented worldwide for the house-hold monitoring of patients with mild COVID-19 to reduce the burden of healthcare systems and guarantee quality of care. Telephone follow up and treatment kits have not been evaluated in the context of a national-wide primary care program. AIM OF THE STUDY: To compare the risk of hospitalization and death for COVID-19 between ambulatory patients who received and those who did not receive a treatment kit and telephone follow-up in a developing country METHODS: A two-group comparative analysis was conducted using data from the medical information systems of the Mexican Institute of Social Security. We included a total of 28,048 laboratory-confirmed SARS-CoV-2 patients: 7,898 (28.2%) received a medical kit and 20,150 (71.8%) did not. The incidence rates of hospitalization and death combined were calculated. To identify significant associations between hospitalization or death and treatment medical kits, we calculated the risk ratios using a multivariate logistic model. RESULTS: The incidence of hospitalization was 6.14% in patients who received a kit and 11.71% in those who did not. Male sex, age, and a medical history of obesity, hypertension, diabetes, immunosuppression, or kidney disease were associated with increased risk of hospitalization or death. The risk rates were reduced in patients who received a medical kit or telephone follow-up. In the multivariate model, receiving a medical kit was associated with a lower risk of hospitalization or death from COVID-19: adjusted risk ratio 0.41 (95% confidence interval 0.36-0.47). CONCLUSION: Use of a multimodal strategy may reduce the risk of hospitalization and death in adult outpatients with mild COVID-19.