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Background and Aims: Recent trends in mortality with gallstone disease remain scarce in the United States. Yet multiple changes in clinical management, such as rates of endoscopy, cholecystectomy, and cholecystostomy, and insurance access at the state level, may have occurred. Thus, we evaluated recent secular trends of mortality with gallstone disease in New Jersey., Methods: We performed a retrospective, cohort study of mortality from 2009 to 2018 using the National Center for Health Statistics, Restricted Mortality Files. The primary outcome was any death with an International Classifications of Disease, 10th Revision, Clinical Modification diagnosis code of gallstone disease in New Jersey. Simple linear regression was used to model trends of incidence of death., Results: 1580 deaths with diagnosed gallstone disease (dGD) occurred from 2009 to 2018. The annual trend of incidence of death was flat over 10 years. The incidence of death with dGD relative to all death changed only from 0.21% to 0.20% over 10 years. These findings were consistent also in 18 of 20 subgroup combinations, although the trend of death with dGD in Latinos 65 years or older increased [slope estimate 0.93, 95% confidence limit 0.42-1.43, P = .003]., Conclusion: The rate of death with dGD showed little change over the recent 10 years in New Jersey. This needs to be reproduced in other states and nationally. A closer examination of the changes in clinical care and insurance access is needed to help understand why they did not result in a positive change in this avoidable cause of death., Competing Interests: Conflicts of Interest: He has no other disclosures or potential conflicts of interest. Email: peckgr@rwjms.rutgers.edu. The remaining authors disclose no conflicts.

Whether patients undergo the more morbid and costly emergent rather than an elective type of surgery, may depend on many factors. Since tertiary prevention (preventing poor outcomes from emergency surgery) carries a much higher mortality than secondary prevention (preventing emergency surgery) or primary prevention (preventing the disease requiring surgery), the overall United States mortality might be reduced significantly, if emergency surgery could be avoided via high-quality primary prevention and non-surgical therapy or increasing elective surgery at the expense of emergency procedures, e.g., secondary prevention. The practice and study of acute care surgery then has the potential to broaden from a focus on the patient in the hospital emergency and operating rooms to the patient who no longer requires either, whose disease is treated or prevented in his/her/their community., Competing Interests: 1.Gregory L. Peck, DO, MPH, FACS participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He is currently supported by the NIH National Center for Advancing Translational Sciences’ (NCATS) Rutgers Clinical Translational Science KL2 Career Development Award (5 KL2 TR 3018-3). He has no potential conflict of interest. 2.Shawna V. Hudson, PhD participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. She has reviewed the manuscript, believe it represents valid work, and approves it for submission. She does not have direct support for this work and has no potential conflict of interest. 3.Jason A. Roy, PhD participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest. 4.Vicente H. Gracias, MD, FACS participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest. 5.Brian L. Strom, MD, MPH participated sufficiently in the intellectual content and writing of the manuscript to take public responsibility for it. He has reviewed the manuscript, believe it represents valid work, and approves it for submission. He does not have direct support for this work and has no potential conflict of interest.

Objectives: Globally congenital heart disease mortality is declining, yet the proportion of infant deaths attributable to heart disease rises in Colombia and other middle-sociodemographic countries. We aimed to assess the accessibility of paediatric cardiac surgery (PCS) to children <18 years of age in 2016 in the South American country of Colombia., Methods: In Bogotá, Colombia, a multi-national team used cross-sectional and retrospective cohort study designs to adapt and evaluate 4 health system indicators at the national level: first, the population with timely geographic access to an institution providing PCS; second, the number of paediatric cardiac surgeons; third, this specialized procedure volume and its national distribution; and fourth, the 30-day perioperative mortality rate after PCS in Colombia., Results: Geospatial mapping approximates 64% (n = 9 894 356) of the under-18 Colombian population lives within 2-h drivetime of an institution providing PCS. Twenty-eight cardiovascular surgeons report performing PCS, 82% (n = 23) with formal training. In 2016, 1281 PCS procedures were registered, 90% of whom were performed in 6 of the country's 32 departments. National non-risk-adjusted all-cause 30-day perioperative mortality rate after PCS was 2.73% (n = 35)., Conclusions: Colombia's paediatric population had variable access to cardiac surgery in 2016, largely dependent upon geography. While the country may have the capacity to provide timely, high-quality care to those who need it, our study enables future comparative analyses to measure the impact of health system interventions facilitating healthcare equity for the underserved populations across Colombia and the Latin American region., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: In response to the staggering global burden of conditions requiring emergency and essential surgery, the development of international surgical system strengthening (SSS) is fundamental to achieving universal, timely, quality, and affordable surgical care. Opportunity exists in identifying optimal collaborative processes that both promote global surgery research and SSS, and include medical students. This study explores an education model to engage students in academic global surgery and SSS via institutional support for longitudinal research., Objectives: We set out to design a program to align global health education and longitudinal health systems research by creating an education model to engage medical students in academic global surgery and SSS., Program Design and Implementation: In 2015, medical schools in the United States and Colombia initiated a collaborative partnership for academic global surgery research and SSS. This included development of two longitudinal academic tracks in global health medical education and academic global surgery, which we differentiated by level of institutional resourcing. Herein is a retrospective evaluation of the first two years of this program by using commonly recognized academic output metrics., Main Achievements: In the first two years of the program, there were 76 total applicants to the two longitudinal tracks. Six of the 16 (37.5%) accepted students selected global surgery faculty as mentors (Acute Care Surgery faculty participating in SSS with Colombia). These global surgery students subsequently spent 24 total working weeks abroad over the two-year period participating in culminating research experiences in SSS. As a quantitative measure of the program's success, the students collectively produced a total of twenty scholarly pieces in the form of accepted posters, abstracts, podium presentations, and manuscripts in partnership with Colombian research mentors., Policy Implications: The establishment of scholarly global health education and research tracks has afforded our medical students an active role in international SSS through participation in academic global surgery research. We propose that these complementary programs can serve as a model for disseminated education and training of the future global systems-aware surgeon workforce with bidirectional growth in south and north regions with traditionally under-resourced SSS training programs., (© 2021. The Author(s).)

Purpose: Belize has one of the highest cervical cancer burdens among Latin American and Caribbean countries, despite the implementation of national policies to increase access to prevention and treatment services. This study evaluates the policies, infrastructure, and workforce of the cervical cancer management system in Belize to inform capacity building efforts., Methods: In 2018, health facility assessments were conducted across all six districts of Belize at the national pathology facility and 12 public facilities identified as critical to cervical cancer control. Human and infrastructure resource availability and existing policies related to cervical cancer screening and treatment services were assessed through a structured instrument., Results: The public cervical cancer screening workforce in Belize consists of 75 primary care nurses and physicians-one per 1,076 screening-eligible women, with 44% conducting rural outreach. All districts have at least one screening facility, but 50% perform screening services only once per week. Colposcopy and loop electrical excision procedures are available in three and four districts, respectively; radical hysterectomy and chemotherapy are available in two districts; and radiation therapy is unavailable. Of essential pathology equipment, 38.5% were present and functional, 23% were present but nonfunctional, and 38.5% were unavailable. Additionally, 35% of supplies were unavailable at the time of assessment, and 75% were unavailable at least once in the 12 months before assessment., Conclusion: Public-sector cervical cancer management services differ among districts of Belize, with tertiary service availability concentrated in the largest district. Screening, outreach, and pathology are limited mostly by resource availability. This study characterizes the current capacity of services in Belize and pinpoints health system components for future investment and capacity-building efforts., Competing Interests: Shane S. NeibartEmployment: Hibiscus BioVenturesStock and Other Ownership Interests: NexImmune Mark H. EinsteinLeadership: ASCCPConsulting or Advisory Role: Papivax, Merck, Asierus, PDS BiotechnologiesResearch Funding: J&J, Pfizer, Invoio, AstraZeneca, PDS Biotechnologies, Becton DickinsonUncompensated Relationships: National Cancer Institute, World Health OrganizationNo other potential conflicts of interest were reported.

Introduction: Interfacility transfers may reflect a time delay of definitive surgical care, but few studies have examined the prevalence of interfacility transfers in the urban low- and middle-income (LMIC) setting. The aim of this study was to determine the number of interfacility transfers required for surgical and obstetric conditions in an urban MIC setting to better understand access to definitive surgical care among LMIC patients., Methods: A retrospective analysis of public interfacility transfer records was conducted from April 2015 to April 2016 in Cali, Colombia. Data were obtained from the single municipal ambulance agency providing publicly funded ambulance transfers in the city. Interfacility transfers were defined as any patient transfer between two healthcare facilities. We identified the number of transfers for patients with surgical conditions and categorized transfers based on patient ICD-9-CM codes. We compared surgical transfers from public vs. private healthcare facilities by condition type (surgical, obstetric, nonsurgical), transferring physician specialty, and transfer acuity (code blue, emergent, urgent and nonurgent) using logistic regression., Results: 31,659 patient transports occurred over the 13-month study period. 22250 (70.2%) of all transfers were interfacility transfers and 7777 (35%) of transfers were for patients with surgical conditions with an additional 2,244 (10.3%) for obstetric conditions. 49% (8660/17675) of interfacility transfers from public hospitals were for surgical and obstetric conditions vs 32% (1466/4580) for private facilities (P<0.001). The most common surgical conditions requiring interfacility transfer were fractures (1,227, 5.4%), appendicitis (913, 4.1%), wounds (871, 3.9%), abdominal pain (818, 3.6%), trauma (652, 2.9%), and acute abdomen (271, 1.2%)., Conclusion: Surgical and obstetric conditions account for nearly half of all urban interfacility ambulance transfers. The most common reasons for transfer are basic surgical conditions with public healthcare facilities transferring a greater proportion of patient with surgical conditions than private facilities. Timely access to an initial healthcare facility may not be a reliable surrogate of definitive surgical care given the substantial need for interfacility transfers., Competing Interests: The authors have declared that no competing interests exist.

Background: Surgical, anaesthetic, and obstetric (SAO) health-care system strengthening is needed to address the emergency and essential surgical care that approximately 5 billion individuals lack globally. To our knowledge, a complete, non-modelled national situational analysis based on the Lancet Commission on Global Surgery surgical indicators has not been done. We aimed to undertake a complete situation analysis of SAO system preparedness, service delivery, and financial risk protection using the core surgical indicators proposed by the Commission in Colombia, an upper-middle-income country., Methods: Data to inform the six core surgical system indicators were abstracted from the Colombian national health information system and the most recent national health survey done in 2007. Geographical access to a Bellwether hospital (defined as a hospital capable of providing essential and emergency surgery) within 2 h was assessed by determining 2 h drive time boundaries around Bellwether facilities and the population within and outside these boundaries. Physical 2 h access to a Bellwether was determined by the presence of a motor vehicle suitable for individual transportation. The Department Administrativo Nacional de Estadística population projection for 2016 and 2018 was used to calculate the SAO provider density. Total operative volume was calculated for 2016 and expressed nationally per 100 000 population. The total number of postoperative deaths that occurred within 30 days of a procedure was divided by the total operative volume to calculate the all-cause, non-risk-adjusted postoperative mortality. The proportion of the population subject to impoverishing costs was calculated by subtracting the baseline number of impoverished individuals from those who fell below the poverty line once out-of-pocket payments were accounted for. Individuals who incurred out-of-pocket payments that were more than 10% of their annual household income were considered to have experienced catastrophic expenditure. Using GIS mapping, SAO system preparedness, service delivery, and cost protection were also contextualised by socioeconomic status., Findings: In 2016, at least 7·1 million people (15·1% of the population) in Colombia did not have geographical access to SAO services within a 2 h driving distance. SAO provider density falls short of the Commission's minimum target of 20 providers per 100 000 population, at an estimated density of 13·7 essential SAO health-care providers per 100 000 population in 2018. Lower socioeconomic status of a municipality, as indicated by proportion of people enrolled in the subsidised insurance regime, was associated with a smaller proportion of the population in the municipality being within 2 h of a Bellwether facility, and the most socioeconomically disadvantaged municipalities often had no SAO providers. Furthermore, Colombian providers appear to be working at or beyond capacity, doing 2690-3090 procedures per 100 000 population annually, but they have maintained a relatively low median postoperative mortality of 0·74% (IQR 0·48-0·84). Finally, out-of-pocket expenses for indirect health-care costs were a key barrier to accessing surgical care, prompting 3·1 million (6·4% of the population) individuals to become impoverished and 9·5 million (19·4% of the population) individuals to incur catastrophic expenditures in 2007., Interpretation: We did a non-modelled, indicator-based situation analysis of the Colombian SAO system, finding that it has not yet met, but is working towards achieving, the targets set by the Lancet Commission on Global Surgery. The observed interdependence of these indicators and correlation with socioeconomic status are consistent with well recognised factors and outcomes of social, health, and health-care inequity. The internal consistency observed in Colombia's situation analysis validates the use of the indicators and has now informed development of an early national SAO plan in Colombia, to set a data-informed stage for implementation and evaluation of timely, safe, and affordable SAO health care, within the National Public Health Decennial Plan, which is due in 2022., Funding: Zoll Medical., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The revised version of the article corrected Figure 2. This change appears in the revised online PDF copy of this article.

The Pigmented Lesion Assay (PLA, sensitivity 91-95%, specificity 69-91%, negative predictive value ?99%) is a commercially available, non-invasive gene expression test that helps dermatologists guide pigmented lesion management decisions and rule out melanoma. Earlier studies have demonstrated high clinical utility and no missed melanomas in a 3-6-month follow-up period. We undertook the current investigations to provide 12-month follow-up data on PLA(-) tests, and to further confirm utility. A 12-month chart review follow-up of 734 pigmented lesions that had negative PLA results from 5 US dermatology centers was performed. Thirteen of these lesions (1.8%) were biopsied in the follow-up period and submitted for histopathologic review. None of the lesions biopsied had a histopathologic diagnosis of melanoma. The test's utility was studied further in a registry (N=1575, 40 US dermatology offices, 62 participating providers), which demonstrated that 99.9% of PLA(-) lesions were clinically monitored, thereby avoiding a surgical procedure, and 96.5% of all PLA(+) lesions were appropriately biopsied, most commonly with a tangential shave. This long-term follow-up study confirms the PLA's high negative predictive value and high utility in helping guide the management of pigmented lesions to avoid unnecessary surgical procedures.

In 2015, the Lancet Commission on Global Surgery (LCoGS) working groups developed a National Surgical, Obstetric, and Anesthesia Plan (NSOAP) framework to guide national surgical system development globally predicated on six data points (indicators) which can assess surgical systems. Zambia as well as other subSaharan Africa (SSA) countries have forged ahead in designing and implementing interventions based on LCoGS indicators collected to inform NSOAP. Concurrently, the Zambian team and others have recognized the need for rigorous scientific inquiry to assess and iteratively improve upon the NSOAP process and outputs. Based on the Zambian experience, as well as that of ours in Colombia, we have identified "core principles" through convergent works which inform a scientific framework through which NSOAP can be evaluated. We propose that when contextualized, participatory action research (PAR) and dissemination and implementation science are methodologies upon which a robust framework can be developed to achieving objective and iterative NSOAP evaluation, and ultimately universal health coverage as envisioned by the World Health Organization (WHO)., (© 2018 The Author(s); Published by Kerman University of Medical Sciences. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

The American College of Academic International Medicine (ACAIM) represents a group of clinicians who seek to promote clinical, educational, and scientific collaboration in the area of Academic International Medicine (AIM) to address health care disparities and improve patient care and outcomes globally. Significant health care delivery and quality gaps persist between high-income countries (HICs) and low-and-middle-income countries (LMICs). International Medical Programs (IMPs) are an important mechanism for addressing these inequalities. IMPs are international partnerships that primarily use education and training-based interventions to build sustainable clinical capacity. Within this overall context, a comprehensive framework for IMPs (CFIMPs) is needed to assist HICs and LMICs navigate the development of IMPs. The aim of this consensus statement is to highlight best practices and engage the global community in ACAIM's mission. Through this work, we highlight key aspects of IMPs including: (1) the structure; (2) core principles for successful and ethical development; (3) information technology; (4) medical education and training; (5) research and scientific investigation; and (6) program durability. The ultimate goal of current initiatives is to create a foundation upon which ACAIM and other organizations can begin to formalize a truly global network of clinical education/training and care delivery sites, with long-term sustainability as the primary pillar of international inter-institutional collaborations., Competing Interests: There are no conflicts of interest.

The growth of academic international medicine (AIM) as a distinct field of expertise resulted in increasing participation by individual and institutional actors from both high-income and low-and-middle-income countries. This trend resulted in the gradual evolution of international medical programs (IMPs). With the growing number of students, residents, and educators who gravitate toward nontraditional forms of academic contribution, the need arose for a system of formalized metrics and quantitative assessment of AIM- and IMP-related efforts. Within this emerging paradigm, an institution's "return on investment" from faculty involvement in AIM and participation in IMPs can be measured by establishing equivalency between international work and various established academic activities that lead to greater institutional visibility and reputational impact. The goal of this consensus statement is to provide a basic framework for quantitative assessment and standardized metrics of professional effort attributable to active faculty engagement in AIM and participation in IMPs. Implicit to the current work is the understanding that the proposed system should be flexible and adaptable to the dynamically evolving landscape of AIM - an increasingly important subset of general academic medical activities., Competing Interests: There are no conflicts of interest.

Adverse effects associated with the long-term low-dose regimens of retinoids used in cancer chemoprevention studies are not well described. In order to examine the clinical and laboratory adverse effects of 3 years of intervention with isotretinoin (10 mg/day) and to assess potential risk factors for developing these, we collected adverse effect data on patients participating in a randomized, placebo-controlled trial designed to evaluate the effectiveness of isotretinoin in preventing the subsequent occurrence of new basal cell carcinoma. Our results showed a significantly higher incidence of adverse mucocutaneous effects and serum triglyceride elevations in the isotretinoin group (P < 0.001). Associated risk factors included male gender, very fair skin, and elevated pretreatment triglyceride levels. The toxicity observed, although less severe and less frequent, was similar to that seen with higher doses and should be weighed with adverse skeletal effects when considering long-term treatment of patients with moderate cancer risk.

The influence of vitamin A on differentiating epithelia was examined in explants of skin from 14-day chick embryos exposed to retinoic acid (RA) in low, moderate, and high doses. The changes observed in RA-treated cultures are both dose- and time-dependent and are reversible when explants are transferred to control medium. The periderm sloughs prematurely and horizontal stratification is lost. Keratinization is inhibited and fewer desmosomes and tonofilaments are seen. Surface epidermal cells develop microvilli, bulge upwards, and detach. Golgi elements, rough endoplasmic reticulum, and polyribosomes are unusually prominent. Mucin granules form and gland-like structures develop with intercellular canaliculi characterized by tight junctions, brush borders, and dense secretory contents. On the basis of present evidence there are several possible mechanisms by which RA could alter epidermal differentiation. RA-induced gaps in the basal lamina allow direct contact between epidermal basal cells and fibroblasts and collagen fibers which could result in inappropriate dermal signals reaching the epidermis. In younger embryos the entire epidermis, including the mitotically inactive surface cells, appears to respond to RA, and this could imply an epigenetic modulation of cell phenotype. Finally, after the formation of a stratum corneum in older embryos only the relatively undifferentiated basal layer shows a metaplastic response, indicating that RA could be acting directly on the genome.

Since etretinate, an aromatic retinoid useful in the treatment of psoriasis and other skin disorders is lipid-soluble, it may be poorly absorbed in the absence of a fat load. We therefore studied serum concentrations of etretinate and its major metabolite (Ro 10-1670) after the controlled administration of etretinate. After an overnight fast, 6 Darier's disease and 4 psoriatic patients received a 1 mg/kg morning dose of etretinate with water or 1 pint of whole milk (fat load). There was a 260% increase (p less than 0.0005) in the mean of each patient's increase in the baseline-corrected peak serum concentration of etretinate after administration with milk (115 +/- 15 micrograms/dl) compared to after administration with water (32 +/- 4 micrograms/dl). Over a 24-h period there was an overall 296 +/- 26% (p less than 0.0005) increase in serum etretinate after administration with milk compared to water in 5 patients with Darier's disease. In contrast to the serum etretinate, there was a 17% mean decrease (p less than 0.025) in the corrected peak serum concentration of Ro 10-1670 in all 10 patients after administration of etretinate with milk compared to water. The net result of these alterations is that the mean corrected serum concentration of etretinate is higher than Ro 10-1670 at all time points measured after milk administration. In contrast, after administration of etretinate with water the major retinoid in the serum is Ro 10-1670. Establishing the clinical significance of these alterations may require controlled clinical trials.

Spontaneously transformed mouse fibroblasts (Balb/c 3T12-3 cells) displayed an increased adhesion when cultured in the presence of 10(-6) M all-trans retinol and acquired morphological characteristics of the normal phenotype. Thus it was of interest to investigate the metabolism of [15-(14)C]retinol in this system. Within 24 hours of culture, approximately 4.25% of the [(14)C]retinol was taken up by the cells. The hydrocarbon [(14)C]anhydroretinol was a major metabolic product and was identified by gas-liquid chromatography and by its typical ultraviolet absorption spectrum with maxima at 386, 364, and 346 nm. At 24 and 40 hours anhydroretinol represented 27% and 55%, respectively, of the total nonpolar metabolites or approximately 16% and 30% of the total radioactive products. Formalin-fixed fibroblasts or cultured intestinal mucosal cells did not convert retinol into anhydroretinol. A more polar product with a UV absorption maximum at 310 nm was also found. The time course of the synthesis of this product by 3T12 cells suggested a precursor-product relationship with anhydroretinol. A microsomal preparation from 3T12 cells was also active in synthesizing [(14)C]anhydroretinol and [(14)C]metabolite-310 from [(14)C]retinol. Moreover incubation of metabolite-310 with the 3T12 microsomes yielded anhydroretinol (40% conversion in 30 minutes), suggesting that metabolite-310 is an intermediate in the synthesis of anhydroretinol by these cells. Anhydroretinol appears to be an end product of the metabolism of retinol in 3T12-3 cells, as suggested by the finding that over 90% of [(14)C]anhydroretinol incubated for 30 hours with 3T12-3 cells was recovered unaltered, without the formation of detectable retroretinol, retinol, or retinoic acid.-Bhat, P. V., L. M. De Luca, S. Adamo, I. Akalovsky, C. S. Silverman-Jones, and G. L. Peck. Retinoid metabolism in spontaneously transformed mouse fibroblasts (Balb/c 3T12-3 cells): enzymatic conversion of retinol to anhydroretinol.

The adrenal secretion of androgens were examined in 9 women (ages 19-39 yr) with postadolescent idiopathic acne and compared to age and sex-matched normal controls. Plasma dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), androstenedione (delta 4-delta), cortisol, 17-hydroxyprogesterone, 11-deoxycortisol, and testosterone were measured by radioimmunoassay in the basal state and during a 48 hr ACTH infusion. The mean plasma and time-integrated plasma levels of the 3 adrenal androgens in patients with acne were 15-25% higher than normal controls, but the groups were not significantly different (p greater than .05). The plasma testosterone values, on the other hand, were similar in both groups. In addition, cortisol, 11-deoxycortisol and 17-hydroxyprogesterone basal plasma values and responses to ACTH in patients with acne were similar to the normal control values. These findings suggest that adrenal androgen secretion is at most mildly elevated in patients with idiopathic acne and is unlikely to be the sole cause of acne since many patients without acne have similar hormone levels. Increased sensitivity of the sebaceous gland to androgens or increased local metabolism of androgen hormones in the skin to potent androgen metabolites may offer alternative mechanisms for the pathogenesis of this disorder.

The sera of 21 patients with psoriasis were examined for the presence of IgA-containing circulating immune complexes (CIC) using the Raji IgA radioimmunoassay. In addition, the Raji IgG radioimmunoassay and 125I-Clq binding assay were used to detect IgG- and IgM-containing CIC. Twenty-five patients with other hyperkeratotic skin disorders were studied as controls. Patients were studied before institution of systemic therapy with etretinate (20 patients) or 13-cis-retinoic acid (1 patient). In addition, sera of 15 of the patients treated with etretinate were studied before, during, and after therapy. The extent of pretreatment disease involvement as well as response to therapy were evaluated in a blinded fashion. Fourteen of 21 (67%) patients with psoriasis had evidence of IgA-containing CIC at some time during the course of their disease, as compared to only 1 of 25 patients with other hyperkeratotic skin disorders. In contrast, only 2 of 19 (11%) had evidence of IgG-containing CIC using the Raji IgG assay, and only 1 of 19 (5%) had evidence of IgG- or IgM-containing CIC using the 125I-Clq binding assay. A positive correlation was found between the extent of pretreatment disease involvement and the level of IgA-containing CIC by linear regression analysis (p = 0.01). There was, however, no correlation between clinical improvement and the presence or level of IgA-containing CIC in 15 patients followed during therapy. Sucrose density gradient analysis of the IgA-containing CIC found in 2 of these patients demonstrated IgA-containing CIC in the 9S to 13S region. The finding of IgA-containing CIC in a significant number of patients with psoriasis and the relative absence of IgG- or IgM-containing CIC suggest that IgA-containing CIC may play a role in psoriasis. The lack of correlation with clinical improvement, however, suggests these IgA-containing CIC are not directly related to the cutaneous manifestations of psoriasis, but may be important in the modification of immune or inflammatory responses in these patients.