Lower Socioeconomic Status Predicts Greater Obstacles to Care: Using Outpatient Cholecystectomy as a Model Cohort.

BACKGROUND: Patients with low socioeconomic status (SES) are disadvantaged in terms of access to health care. A novel metric for SES is the Distressed Communities Index (DCI). This study evaluates the effect of DCI on hospital choice and distance traveled for surgery. METHODS: A Florida database was queried for patients with symptomatic cholelithiasis or chronic cholecystitis who underwent an outpatient cholecystectomy between 2016 and 2019. Patients' DCI was compared with hospital ratings, comorbidities, Charlson Comorbidity Index, and distance traveled for surgery. Stepwise logistic regression was used to determine which factors most influenced distance traveled for surgery. RESULTS: There were 54,649 cases-81 open, 52,488 laparoscopic, and 2,080 robotic. There was no difference between surgical approach and patient's DCI group (p = 0.12). Rural patients traveled the farthest for surgery (avg 21.29 miles); urban patients traveled the least (avg 5.84 miles). Patients from distressed areas more often had surgery at one- or two-star hospitals than prosperous patients (61% vs 36.3%). Regression indicated distressed or at-risk areas predicted further travel for rural/small-town patients, while higher hospital ratings predicted further travel for suburban/urban patients. DISCUSSION: Compared to prosperous areas, patients from distressed areas have surgery at lower-rated hospitals, travel further if they live in rural/small-town areas, but travel less if they live in suburban areas. We postulate that farther travel in rural areas may be explained by a lack of health care resources in poor, rural areas, while traveling less in suburban areas may be explained by personal lack of resources for patients with low SES.

Chemokine receptor hetero-oligomers regulate monocyte chemotaxis.

It is known that stress influences immune cell function. The underlying molecular mechanisms are unclear. We recently reported that many chemokine receptors (CRs) heteromerize with α1-adrenoceptors (α1-ARs) through which CRs are regulated. Here, we show that arginine vasopressin receptor 1A (AVPR1A) heteromerizes with all human CRs, except chemokine (C-X-C motif) receptor (CXCR)1, in recombinant systems and that such heteromers are detectable in THP-1 cells and human monocytes. We demonstrate that ligand-free AVPR1A differentially regulates the efficacy of CR partners to mediate chemotaxis and that AVPR1A ligands disrupt AVPR1A:CR heteromers, which enhances chemokine (C-C motif) receptor (CCR)1-mediated chemotaxis and inhibits CCR2-, CCR8-, and CXCR4-mediated chemotaxis. Using bioluminescence resonance energy transfer to monitor G protein activation and CRISPR/Cas9 gene-edited THP-1 cells lacking AVPR1A or α1B-AR, we show that CRs that share the propensity to heteromerize with α1B/D-ARs and AVPR1A exist and function within interdependent hetero-oligomeric complexes through which the efficacy of CRs to mediate chemotaxis is controlled. Our findings suggest that hetero-oligomers composed of CRs, α1B/D-ARs, and AVPR1A may enable stress hormones to regulate immune cell trafficking.

Adjuvant and Neo-Adjuvant Anti-Obesity Medications and Bariatric Surgery: A Scoping Review.

PURPOSE OF REVIEW: To comprehensively summarize the current body of literature on the topic of adjuvant and neoadjuvant pharmacotherapy used in combination with bariatric surgery. RECENT FINDINGS: Anti-obesity medications (AOMs) have been used since the mid-1900s; however, their use in combination with bariatric surgery is a newer area of research that is rapidly growing. Pharmacotherapy may be used before (neoadjuvant) or after (adjuvant) bariatric surgery. Recent literature suggests that adjuvant AOMs may address weight regain and inadequate weight loss following bariatric surgery. Research on neoadjuvant AOM used to optimize weight loss before bariatric surgery is more limited. A literature review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Thirty-four studies were included after screening and exclusion of irrelevant records. Included studies were as follows: seven prospective studies on adjuvant AOM use, 23 retrospective studies on adjuvant AOM use, one prospective study on adjuvant and neoadjuvant AOM use, one retrospective study on adjuvant or neoadjuvant AOM use, one prospective study on neoadjuvant AOM use, and one case series on neoadjuvant AOM use. In the following scoping review, each of these studies is discussed with the goal of presenting a complete synthesis of the current body of literature on AOM use in combination with bariatric surgery.

Evaluating the use of adjuvant and neoadjuvant terminology in bariatric surgery: a scoping review.

BACKGROUND: Weight regain and inadequate weight loss are common after bariatric surgery. Literature is emerging regarding the use of pharmacotherapy with bariatric surgery as a potential solution to these adverse effects. Pharmacotherapy may be used before (neoadjuvant) or after (adjuvant) bariatric surgery, although this terminology has not been standardized. As a rapidly growing area of research, there is opportunity to standardize terminology for future ease of research, data synthesis, and communication. This review aimed to comprehensively evaluate the use of the terms "adjuvant" and "neoadjuvant" to describe pharmacotherapy used in combination with bariatric surgery and propose standardized terminology for future research. METHODS: Literature search was conducted systematically and in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they were published after 1999; were randomized controlled trials, prospective/retrospective cohort studies, or case series; and used human subjects that were adults at least 18 years of age. The use of the terms "neoadjuvant" and "adjuvant" was analyzed over time. RESULTS: Thirty-four publications were included. Thirty-two (94.1%) studied the use of adjuvant pharmacotherapy after bariatric surgery. Four (11.8%) studied the use of pharmacotherapy before bariatric surgery, and 1 used the term "neoadjuvant" to describe medications used before bariatric surgery. Eight publications used the term "adjuvant" to describe medications used after bariatric surgery. CONCLUSION: Standardized terminology is needed to ease future understanding, evidence synthesis, and dissemination of work. We propose that the terms "neoadjuvant" and "adjuvant" become the standard terminology to describe pharmacotherapy use before and after bariatric surgery, respectively.

Corrigendum to "Association of state-level factors with rate of firearm-related deaths" [Surg. Open Sci. vol. 14 (2023) 114-119].

[This corrects the article DOI: 10.1016/j.sopen.2023.07.011.].

Association of state-level factors with rate of firearm-related deaths.

Background: Over 48,000 people died by firearm in the United States in 2021. Firearm violence has many inciting factors, but the full breadth of associations has not been characterized. We explored several state-level factors including factors not previously studied or insufficiently studied, to determine their association with state firearm-related death rates. Methods: Several state-level factors, including firearm open carry (OC) and concealed carry (CC) laws, state rank, partisan lean, urbanization, poverty rate, anger index, and proportion of college-educated adults, were assessed for association with total firearm-related death rates (TFDR). Secondary outcomes were firearm homicide (FHR) and firearm suicide rates (FSR). Exploratory data analysis with correlation plots and ANOVA was performed. Univariable and multivariable linear regression on the rate of firearm-related deaths was also performed. Results: All 50 states were included. TFDR and FSR were higher in permitless OC and permitless CC states. FHR did not differ based on OC or CC category. Open carry and CC were eliminated in all three regression models due to a lack of significance. Significant factors for each model were: 1) TFDR - partisan lean, urbanization, poverty rate, and state ranking; 2) FHR - poverty rate; 3) FSR - partisan lean and urbanization. Conclusions: Neither open nor concealed carry is associated with firearm-related death rates when socioeconomic factors are concurrently considered. Factors associated with firearm homicide and suicide differ and will likely require separate interventions to reduce firearm-related deaths. Key message: Neither open carry nor concealed carry law are associated with total firearm-related death rate, but poverty rate, urbanization, partisan lean, and state ranking are associated. When analyzing firearm homicide and suicide rates separately, poverty rate is strongly associated with firearm homicide rate, while urbanization and partisan lean are associated with firearm suicide rate.

Effects of chemokine (C-C motif) receptor 2 and 3 antagonists in rat models of hemorrhagic shock.

Systemic concentrations of chemokine CCL2, an agonist at chemokine receptors CCR2/3/5, have been associated with hemodynamic instability after traumatic-hemorrhagic shock. We reported previously that the CCR2 antagonist INCB3284 prevents cardiovascular collapse and reduces fluid requirements after 30min of hemorrhagic shock (HS), whereas the CCR5 antagonist Maraviroc was ineffective. The effects of CCR3 blockade after HS are unknown and information on the therapeutic potential of INCB3284 after longer periods of HS and in HS models in the absence of fluid resuscitation (FR) is lacking. The aims of the present study were to assess the effects of CCR3 blockade with SB328437 and to further define the therapeutic efficacy of INCB3284. In series 1-3, Sprague-Dawley rats were hemorrhaged to a mean arterial blood pressure (MAP) of 30mmHg, followed by FR to MAP of 60mmHg or systolic blood pressure of 90mmHg. Series 1: 30min HS and FR until t = 90min. SB328437 at t = 30min dose-dependently reduced fluid requirements by >60%. Series 2: 60min HS and FR until t = 300min. INCB3284 and SB328437 at t = 60min reduced fluid requirements by more than 65% (p<0.05 vs. vehicle) and 25% (p>0.05 vs. vehicle), respectively, until t = 220min. Thereafter, all animals developed a steep increase in fluid requirements. Median survival time was 290min with SB328437 and >300min after vehicle and INCB3284 treatment (p<0.05). Series 3: HS/FR as in series 2. INCB3284 at t = 60min and t = 200min reduced fluid requirements by 75% until t = 300min (p<0.05 vs. vehicle). Mortality was 70% with vehicle and zero with INCB3284 treatment (p<0.05). Series 4: INCB3284 and SB328437 did not affect survival time in a lethal HS model without FR. Our findings further support the assumption that blockade of the major CCL2 receptor CCR2 is a promising approach to improve FR after HS and document that the dosing of INCB3284 can be optimized.

α1-adrenoceptor ligands inhibit chemokine receptor heteromerization partners of α1B/D-adrenoceptors via interference with heteromer formation.

We reported previously that α1-adrenoceptor (α1-AR) ligands inhibit chemokine receptor (CR) heteromerization partners of α1B/D-AR. The underlying mechanisms are unknown and in vivo evidence for such effects is missing. Utilizing CCR2 and α1B-AR as prototypical partners, we observed in recombinant systems and THP-1 cells that α1B-AR enhanced whereas its absence inhibited Gαi signaling of CCR2. Phenylephrine and phentolamine reduced the CCR2:α1B-AR heteromerization propensity and inhibited Gαi signaling of CCR2. Phenylephrine cross-recruited ß-arrestin-2 to CCR2, and reduced expression of α1B/D-AR, CR partners (CCR1/2, CXCR4) and corresponding heteromers. Phentolamine reduced CR:α1B/D-AR heteromers without affecting ß-arrestin-2 recruitment or receptor expression. Phenylephrine/phentolamine prevented leukocyte infiltration mediated via CR heteromerization partners in a murine air pouch model. Our findings document that α1-AR ligands inhibit leukocyte migration mediated by CR heteromerization partners in vivo and suggest interference with α1B-AR:CR heteromerization as a mechanism by which CR partners are inhibited. These findings provide new insights into the pharmacology of GPCR heteromers and indicate that an agonist and antagonist at one GPCR can act as antagonists at heteromerization partners of their target receptors.

Brugada Syndrome: The Role of Risk Stratification in Selecting Patients for Implantable Cardioverter-defibrillator Placement.

Brugada syndrome (BS) is an inherited cardiac ion channelopathy that is a rare, but treatable, cause of sudden cardiac death (SCD). There are many studies that explore the management of symptomatic BS, but few trials have been conducted regarding management of asymptomatic Brugada patients. Asymptomatic BS patients are shown to be at increased risk (0.5%-1.5%) for SCD compared to the general population and account for nearly 20% of deaths from SCD in patients with structurally normal hearts. Treatment for asymptomatic BS patients is often debated with the current guidelines allowing for management decisions to be made on a case-by-case basis. Therapies include either anti-arrhythmic medications, implantable cardioverter-defibrillator (ICD) placement, or no active treatment. This review intended to assess whether ICD placement benefits asymptomatic BS patients and what criteria may be useful in selecting patients for ICD placement. Results showed that ICD placement can reduce mortality in select asymptomatic patients. There were certain risk factors that increased the likelihood that an asymptomatic patient would experience SCD and thus benefit from an ICD. These factors include an electrocardiogram(ECG) demonstrating spontaneous type 1 Brugada Syndrome and inducibility of ventricular tachyarrhythmias during electrophysiological study. Other variables including gender, family history of SCD, and the presence of SCN5A mutation were not predictive of arrhythmic events. Moreover, many patients can suffer complications from ICDs that can affect the quality of life including inappropriate shocks, device malfunction, infection, mental health problems, and difficulties with replacements. Guidelines for quantifying the risk of SCD relative to the risks associated with ICD placement are still poorly defined. These complications and risk factors should be taken into consideration in the context of a patient-centered discussion regarding ICD placement in asymptomatic patients.

Learning efficiency: The influence of cue salience during spatial navigation.

In three experiments, male Wistar rats were trained to find a hidden platform in the Morris water maze using two cues for five or ten days. Experiments 1 and 2 investigated two factors of cue salience; proximity to the goal and brightness. Results from Experiment 1 showed that rats tested with a bright distal cue were significantly better at locating the platform than rats tested with the proximal cue after five- and ten-day training with both cues. In Experiment 2, the position of the cues was reversed. Rats tested with a brighter proximal cue outperformed those tested with a distal cue. Findings from Experiments 1 and 2 suggest that brightness acquired more control over rats' behaviour than proximity to the goal. Animals in Experiment 3 were trained with equally bright proximal and distal cues. Unexpectedly, probe tests revealed that rats tested with the farther cue were more accurate than those tested with the proximal cue, but only after extended training. Possible explanations for this result are discussed with reference to errors in directional information estimation and cue assignment, cue elevation and the use of the pool wall as a navigational aid. Taken together, findings point towards the use of an elemental learning strategy involving the more salient of the two cues which emerged earlier when the relative saliences of the cues differed considerably.