History Of Tobacco Use Research Articles

Factors Associated With the Development of a Confirmed Fracture-Related Infection.

To identify factors associated with the development of fracture-related infection (FRI) in patients who have undergone operative fixation of their fracture. Retrospective study. Academic medical center. Patients with peripheral extremity long-bone fractures and shoulder and pelvic girdle fractures who underwent operative repair. This included patients who had undergone fixation inside and outside of our institution. Chi-square, Fisher exact testing, analysis of variance (ANOVA), and t tests were used for analysis of data, as appropriate. Binomial logistic regression analysis was performed to determine risk factors of FRI. Demographics, fracture location, injury mechanism, open wound status, and wound complication type. One hundred ninety-three patients comprised the FRI cohort. Of those with confirmed signs of FRI, 36 (18.7%) had wound breakdown to bone or implant, 120 (62.1%) had a sinus track, and 170 patients (88.1%) had the confirmed presence of microorganisms in deep tissue samples obtained during operative intervention. Factors associated with development of an FRI were as follows: higher BMI; being of Black and Hispanic race; higher American Society of Anesthesiologists class; history of tobacco, alcohol, and drug use; and fractures of the lower extremity (foot, tibia, and femur/pelvis). The results of binary logistic regression demonstrated that treatment at an urban level I trauma center and drug use positively predicted the development of FRI. Our results demonstrate that higher BMI; being of Black or Hispanic race; higher American Society of Anesthesiologists; history of tobacco, alcohol, and drug use; and fractures of the foot, tibia, and femur/pelvis are all factors associated with development of FRI. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Opportunities to Improve Tobacco Control for State Agency Employees.

The aim of the study is to explore tobacco-related knowledge and perceptions at Washington State (WA) agencies. The study used a cross-sectional employee survey and qualitative focus groups with managers/supervisors. We produced descriptive statistics to examine differences in awareness and perceptions of tobacco-control efforts among employees and conducted a rapid thematic analysis of focus group data. Of employees, only 18% with a history of tobacco use had used their agency's cessation benefits. Employees who did not use tobacco and who had higher education had more favorable attitudes toward tobacco-control efforts. In the focus groups, manager/supervisors described limited tobacco cessation promotion at their agency, barriers to tobacco control implementation, and concerns about the perceived effectiveness of additional tobacco-control efforts. State agencies should increase promotion of tobacco control policies and programs to increase awareness and reduce disparities in tobacco use.

Continued tobacco use among tobacco-related head and neck cancer patients seeking care in a tertiary care facility, South India

IntroductionContinued tobacco use in cancer patients leads to decreased treatment efficacy and safety, decreased survival, decreased quality of life, and an increased risk of cancer recurrence and primary tumours at other sites. ObjectiveTo determine the prevalence of continued tobacco usage during the first 6 months of diagnosis among tobacco-related head and neck cancer patients seeking care from a tertiary care centre and the factors associated with it. MethodsA facility-based cohort study was conducted at a tertiary care centre in Puducherry, India. Newly diagnosed head and neck cancer patients aged > 18 years with a history of tobacco use were interviewed to gather information on their socio-demographic, clinical characteristics, and tobacco usage. All participants were interviewed again at the 3rd month and at the 6th month during their follow-up visit. The data were entered in EpiData v3.1 and analysed using STATA v14. Multivariable logistic regression analysis was done with continued tobacco use as the dependent variable and variables that were found significantly associated with continued tobacco use in univariate analysis. ResultsOut of 220 study participants at baseline, 157(71 %; 95 % CI: 65.1–77.1) were using tobacco at the time of diagnosis. Out of these 157 participants, 80(50.9 %; 95 % CI; 43.1–58.7) continued to use tobacco at the 3rd month, 63(40.1 %: 95 % CI: 32.6–47.9) continued to use tobacco at the 6th month. The characteristics significantly associated with continued tobacco use are age (less than 39 years and more than 70 years), primary school education, nuclear family, and living alone, smoking tobacco, and increased duration of tobacco use. ConclusionTwo-fifths of head and neck cancer patients with a history of tobacco use continued to use tobacco at the 6th month after diagnosis of cancer. Awareness of effects of tobacco use and the benefits of tobacco cessation needs to be created among cancer patients.

Risk factors for the development of triple-negative breast cancer versus non-triple-negative breast cancer: a case-control study.

The risk factors for breast cancer have been defined in several studies but there is deficient data for specific subtypes. We report here the pathological characteristics of a breast cancer cohort and risk factors for patients with triple-negative disease. In this case-control study, a prospective breast cancer cohort was evaluated for demographic, reproductive, obesity-related and other risk factors using a validated questionnaire. Tumors were characterized for routine pathological characteristics and immunohistochemical markers of basal-like breast cancer. Patients with triple-negative breast cancer (TNBC) constituted cases and those with non-TNBC were controls. Odds ratios (OR) were calculated for each risk factor and independent associations were tested in an unconditional logistic regression analysis. Between 2011 and 2014, 1146 patients were recruited, of whom 912 [TNBC 266 (29.1%), non-TNBC 646 (70.9%)] with sufficient pathology material were analysed. Reproductive factors of parity, breastfeeding, age-at-menarche, age at first full-term pregnancy and oral contraceptive use were not significantly associated with TNBC. Higher body mass index (BMI > 24.9 vs ≤ 24.9, OR 0.89, 95%CI 0.63-1.24, p = 0.49) was not significantly associated while lesser waist circumference (> 80cm vs ≤ 80cm, OR 0.64, 95%CI 0.45-0.9, p = 0.012) and lower waist-to-hip ratio were significantly associated (> 0.85 vs ≤ 0.85, OR 0.72, 95%CI 0.51-1.0, p = 0.056), with TNBC. History of tobacco use was not significantly associated while lower socio-economic status was borderline associated with TNBC (socio-economic category > 5 versus ≤ 5, OR 0.73, 95%CI 0.50-1.06, p = 0.106). No factor was significant after adjustment for covariates. Central obesity seems to be preferentially associated with non-TNBC, and lower socio-economic status with TNBC in India, while most other conventional risk factors of breast cancer show no significant association with TNBC versus non-TNBC.

Bisphosphonate Use May be Associated With an Increased Risk of Periprosthetic Hip Fracture

BackgroundOsteoporosis is common among patients undergoing primary total hip arthroplasty (THA). This study aimed to evaluate the effect of bisphosphonate treatment on osteoporotic patients undergoing primary THA. MethodsUsing a national database, 30,137 patients who had osteoporosis before primary elective THA were identified during 2010 to 2020. Patients undergoing nonelective THA and those using corticosteroids or other medications for osteoporosis were excluded. Bisphosphonate users and bisphosphonate naïve patients were matched 1:1 based on age, sex, Elixhauser comorbidity index, and a history of obesity, rheumatoid arthritis, tobacco use, and alcohol abuse. Kaplan–Meier and multivariate analyses were used to compare 2-year outcomes between groups. ResultsAmong matched cohorts of 9,844 patients undergoing primary THA, bisphosphonate use was associated with a significantly higher 2-year rate of periprosthetic fracture (odds ratio 1.29, 95% confidence interval 1.04 to 1.61, P = .022). There was a trend toward increased risk of any revision with bisphosphonate use (odds ratio 1.19, confidence interval 1.00 to 1.41, P = .056). Rates of infection, aseptic loosening, dislocation, and mortality were not statistically different between bisphosphonate users and bisphosphonate-naïve patients. ConclusionIn osteoporotic patients, bisphosphonate use before primary THA is an independent risk factor for periprosthetic fracture. Additional longer-term data are needed to determine the underlying mechanism for this association and identify preventative measures.

Diabetes mellitus, its prevalence, awareness, and control in Panama: Data from ENSPA 2019, a national cross-sectional study.

Diabetes mellitus (DM) represents an important global burden of disease. In Panama, DM was investigated in 1 study utilizing questionnaires and in another using biomarkers, but at subnational level. Using data from a recent cross-sectional country-wide population-based study that included biomarkers, we estimated the prevalence of DM, its awareness, and control; evaluating possible risk factors. We used data from 4400 participants aged 18 years or older from the National Health Study of Panama (ENSPA) study conducted in 2019 at a national level. Weighted prevalence and 95% confidence intervals for DM, awareness, and control were estimated by sociodemographic factors, family history of DM, tobacco and alcohol use, nutritional status, and hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression models to assess the possible risk factors associated with DM prevalence and awareness. We generated OR estimates by pooling ENSPA data with a previous regional study, prevalence of cardiovascular risk factors. The prevalence of DM was estimated to be 12.4% (10.9%-14.05%). In both men and women, age, family history of diabetes (OR in men: 4.0 ([2.4-6.7]; OR in women 3.5 [2.5-4.8]), and obesity (OR in men: 2.6 [1.4-5.1]; OR in women: 2.0 [0.9-4.5]) were associated with DM. Diagnosed and controlled hypertension was associated with DM only in women (OR: 2.1 [1.2-3.6]). DM awareness was estimated to be 62.6% (56.3%-68.9%). In both men and women, DM awareness was associated with age and a family history of diabetes (OR in men: 6.6 [2.4-18.4]; OR in women 1.9 ([1.1-3.6]). In women, having secondary education (OR: 1.9 [0.9-3.9]) and being diagnosed with uncontrolled hypertension (OR: 3.3 [1.2-9.5]) was also associated to DM awareness. Men in the ENSPA study were less likely to be aware of DM than those in the prevalence of cardiovascular risk factors (OR: 0.2 [0.0-0.7]). Less than half of the individuals diagnosed with DM had their condition controlled (39.6% [31.4%-47.8%]). This study revealed that the prevalence, awareness, and control of DM were similar to recent estimates reported in other Latin American countries. It also provides a baseline regarding DM and associated risk factors in Panama at a country-level knowledge that is essential for health policy development and useful in clinical practice.

PREVALENCE AND RISK FACTORS OF HELICOBACTER PYLORI INFECTION AMONG INDIVIDUALS WITH TOBACCO CONSUMPTION HABITS IN DISTRICT PESHAWAR: A CROSS-SECTIONAL STUDY

This cross-sectional study aimed to determine the prevalence of Helicobacter pylori infection and its association with tobacco consumption (smoking and snuff use) in Peshawar, Pakistan. 150 blood samples were collected from H. pylori suspected patients in tertiary care hospitals. Demographic data, tobacco consumption habits, and potential risk factors were gathered through a questionnaire. The prevalence of H. pylori among smokers and snuff users was 42%. All participants had a history of tobacco use, with 59% being smokers and 41% being snuff users. Most participants (81%) had not been tested for H. pylori before. Eight risk factors associated with H. pylori infection were investigated, including family history, stomach ulcers or gastritis, consumption of spicy or heavily seasoned food, poor hygiene practices, low socioeconomic status, history of antibiotic use, close contact with infected individuals, and consumption of contaminated food or water. Participants' opinions and beliefs about these risk factors varied. The study demonstrated significant associations between H. pylori antigen detection and smoking, snuff use, overcrowding, and various risk factors such as family history, dietary habits, hygiene practices, socioeconomic status, antibiotic use and exposure to contaminated water or food. The study emphasizes the need for further research to understand these risk factors and their impact on H. pylori infection.

Trends in the Prevalence of Hepatitis C Infection During Pregnancy and Maternal-Infant Outcomes in the US, 1998 to 2018

Injection drug use is the primary risk factor for hepatitis C virus (HCV) infection in adults. More than one-third of newly reported HCV cases occur in women, particularly among persons aged 20 to 39 years. However, nationally representative data on HCV during pregnancy are limited. To estimate the temporal trend of HCV-positive pregnancies during the opioid epidemic and identify HCV-associated maternal and perinatal outcomes. A cross-sectional study was performed with data from the US, from calendar year 1998 through 2018. Data analysis was conducted from November 14, 2021, to May 14, 2023. Participants included women during in-hospital childbirth or spontaneous abortion in the National Inpatient Sample of the Healthcare Cost and Utilization Project. Maternal HCV infection. The main outcome was the temporal trend, measured as change in the annual prevalence, in the prevalence of HCV positivity among pregnant women since the start of the opioid epidemic in the late 1990s. Secondary outcomes were the associations shown as relative odds between maternal HCV infection and maternal and perinatal adverse events. During the study period, more than 70 million hospital admissions resulted in childbirth or spontaneous abortion. Among them, 137 259 (0.20%; 95% CI, 0.19%-0.21%) involved mothers with HCV; these individuals were more often White (77.4%; 95% CI, 76.1%-78.6%), low-income (40.0%; 95% CI, 38.6%-41.5%), and likely to have histories of tobacco (41.7%; 95% CI, 40.6%-42.9%), alcohol (1.8%; 95% CI, 1.6%-2.0%), and opioid (28.9%; 95% CI, 27.3%-30.6%) use compared with HCV-negative mothers. The median age of women with HCV was 28.0 (IQR, 24.3-32.2) years, and the median age of HCV-negative women was 27.2 (IQR, 22.7-31.8) years. The prevalence of HCV-positive pregnancies increased 16-fold during the study period, reaching 5.3 (95% CI, 4.9-5.7) cases per 1000 pregnancies in 2018. Age-specific prevalence increases ranged from 3-fold (age, 41-50 years) to 31-fold (age, 21-30 years). Higher odds of cesarean delivery, preterm labor, poor fetal growth, or fetal distress were associated with HCV-positivity during pregnancy. However, no significant differences were observed in gestational diabetes, preeclampsia, eclampsia, or stillbirths. In this cross-sectional study, the prevalence of HCV-positive pregnancies increased markedly, and maternal HCV infection was associated with increased risks for adverse perinatal outcomes. These data may support recent recommendations for universal HCV screening with each pregnancy.

Efficacy of an expanded preoperative survey during perioperative care to identify illicit substance use in teenagers and adolescents.

As illicit substance use can present several perioperative concerns, effective means to identify such practices are necessary to ensure patient safety. Identification of illicit substance use in pediatric patients may be problematic as screening may rely on parental reporting. The current study compares answers regarding use of illicit substances between a survey completed by the patient and the preoperative survey completed by parents or guardians. The study included patients presenting for surgery at Nationwide Children's Hospital, ranging in age from 12 to 21 years. After consent, patients completed a survey of six drop-down questions using an iPad. The six questions involved the patient's history of alcohol, tobacco, marijuana, vaping, and opioid use. The results were compared to the answers obtained from the parents during a preoperative phone call. The study cohort included surveys from 250 patients with a median age of 16 years. Survey data showed a statistically higher reporting of substance use or abuse from the patient study survey in comparison to the routine parental preoperative survey. Alcohol report rates were highest with 69 (27.6%) patients reporting use compared to only 5 parental reports (2%). There was a similar discrepancy in reported rates of vaping use (40 patient reports, 16.0% vs. 11 parental reports, 4.4%) and illicit substance use including marijuana (52 patient reports, 20.8% vs. 11 parental reports, 4.4%). Reported rates of tobacco use were lowest among the survey responses with 12 patient reports (4.8%) and 5 parental reports (2.0%). Identifying illicit substance and tobacco use via a phone survey of parents is inaccurate and does not allow for proper identification of use of these substances in patients ≤21 years of age presenting for surgery. An anonymous 2-min survey completed by the patient more correctly identifies these issues.

Females Are More Likely Than Males to Fill an Opioid Prescription in the Year After Anterior Cruciate Ligament Reconstruction

To report rates of preoperative and postoperative opioid use between male and female patients and to identify risk factors for extended opioid use following anterior cruciate ligament reconstruction (ACLR). Patients undergoing ACLR between 2011 and 2018 were identified from the PearlDiver database. The opioid refill rates for males vs females were compared at monthly intervals for 1 year after ACLR. Patients who filled an opioid prescription <3 months before surgery were classified as opioid users, while those who had never filled one were classified as nonopioid users. Of 106,995 ACLR patients, 37,890 (35.4%) were opioid users <3 months before surgery, and 37,554 (35.1%) had never filled an opioid prescription. Of the preoperative opioid users, 20,413 (53.9%) were female and 17,477 (46.1%) were male (P < .001). Postoperatively, females were at higher risk of filling an opioid prescription at each monthly interval, except for the first month after surgery. The refill rate for opioid users was also higher than that for nonopioid users at each monthly interval after ACLR. In addition to patient sex, a preoperative diagnosis of anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use increased a patient's risk of filling an opioid prescription postoperatively. This study demonstrated that females are significantly more likely to be opioid users than males prior to ACLR and are more likely to continue to refill an opioid prescription in the year following surgery. Multiple risk factors were associated with prolonged postoperative opioid utilization, including female sex, anxiety/depression, low back pain, myalgia, a history of drug dependence, alcohol abuse, and tobacco use. Level III, retrospective cohort study.

Analysis of postoperative complications related to cannabis and tobacco usage in patients undergoing mandible facial fracture surgeries

Cannabis is the third most used controlled substance in the world. Despite its widespread use, minimal research investigates cannabis usage in patients undergoing facial fracture surgeries. This study aimed to evaluate patterns of postoperative complications related to cannabis and tobacco usage after mandible fracture surgeries. PearlDiver™, a commercially available healthcare database, was used to identify patients endorsing the use of cannabis, tobacco, or both who underwent mandible fracture surgeries for cross-sectional analysis. The study population was categorized into groups using the Classification of Diseases, 9th revision (ICD-9), ICD-10, and Current Procedural Terminology (CPT) codes. A chi-square analysis was performed to assess the influence of cannabis and tobacco use on postoperative complications. A total of 8288 patients met the inclusion criteria, with 72 patients with cannabis-only usage, 914 patients with cannabis and tobacco usage, 3236 patients with tobacco-only usage, and 4066 in the control group. For patients using only cannabis, there was not an increased risk of developing postoperative complications compared with the control population. Patients with concurrent cannabis and tobacco usage and those with tobacco-only usage had an increased risk of surgical site infection, facial nonunion, facial abscess, debridement, and malocclusion after surgical repair of mandibular facial fracture. Patients with tobacco-only as well as cannabis and tobacco usage had an increased risk of all postoperative complications, except malocclusion, compared with cannabis-only. Based on the results of this study, it is recommended that healthcare providers consider a patient's history of tobacco use when planning and performing surgical treatment for traumatic mandible fractures.

Leveraging natural language processing to identify eligible lung cancer screening patients with the electronic health record

ObjectiveTo develop and validate an approach that identifies patients eligible for lung cancer screening (LCS) by combining structured and unstructured smoking data from the electronic health record (EHR). MethodsWe identified patients aged 50–80 years who had at least one encounter in a primary care clinic at Vanderbilt University Medical Center (VUMC) between 2019 and 2022. We fine-tuned an existing natural language processing (NLP) tool to extract quantitative smoking information using clinical notes collected from VUMC. Then, we developed an approach to identify patients who are eligible for LCS by combining smoking information from structured data and clinical narratives. We compared this method with two approaches to identify LCS eligibility only using smoking information from structured EHR. We used 50 patients with a documented history of tobacco use for comparison and validation. Results102,475 patients were included. The NLP-based approach achieved an F1-score of 0.909, and accuracy of 0.96. The baseline approach could identify 5,887 patients. Compared to the baseline approach, the number of identified patients using all structured data and the NLP-based algorithm was 7,194 (22.2 %) and 10,231 (73.8 %), respectively. The NLP-based approach identified 589 Black/African Americans, a significant increase of 119 %. ConclusionWe present a feasible NLP-based approach to identify LCS eligible patients. It provides a technical basis for the development of clinical decision support tools to potentially improve the utilization of LCS and diminish healthcare disparities.

Early Complications after Prepectoral Tissue Expander Placement in Breast Reconstruction with and without Acellular Dermal Matrix.

Prepectoral breast reconstruction has become popularized with the concurrent use of acellular dermal matrix (ADM). The authors sought to compare 3-month postoperative complication rates and explantation rates for first-stage, tissue-expander-based, prepectoral breast reconstruction with and without the use of ADM. A single-institution retrospective chart review was performed to identify consecutive patients undergoing prepectoral tissue-expander-based breast reconstruction from August of 2020 to January of 2022. Chi-square tests were used to compare demographic categorical variables, and multiple variable regression models were used to identify variables associated with 3-month postoperative outcomes. The authors enrolled 124 consecutive patients. Fifty-five patients (98 breasts) were included in the no-ADM cohort and 69 patients (98 breasts) were included in the ADM cohort. There were no statistically significant differences between the ADM and no-ADM cohorts with regard to 90-day postoperative outcomes. On multivariable analysis, there were no independent associations between seroma, hematoma, wound dehiscence, mastectomy skin flap necrosis, infection, unplanned return to the operating room, or explantation in the ADM and no-ADM groups after controlling for age, body mass index, history of diabetes, tobacco use, neoadjuvant chemotherapy, and postoperative radiotherapy. The authors' results reveal no significant differences in odds of postoperative complications, unplanned return to the operating room, or explantation between the ADM and no-ADM cohorts. More studies are needed to evaluate the safety of prepectoral, tissue expander placement without ADM. Therapeutic, III.

Risk factors for reamputation in patients with diabetic foot: A case-control study

BackgroundReamputation as a complication of diabetic foot ulcers presents a high economic burden and represents a therapeutic failure. It is paramount to identify as early as possible patients in whom a minor amputation may not be the best option. The purpose of this investigation was to do a case-controlled study to determine risk factors associated with re-amputation in patients with DFU (diabetic foot ulcers) at two University Hospitals. MethodsMulticentric, observational, retrospective, case-control study from clinical records of 2 university hospitals. Our study included 420 patients, with 171 cases (re-amputations), and 249 controls. We performed a multivariate logistic regression analysis and time-to-event survival analysis to identify re-amputation risk factors. ResultsStatistically significant risk factors were artery history of tobacco use (p = 0.001); male sex (p = 0.048); arterial occlusion in Doppler ultrasound (p = 0.001); percentage of stenosis in arterial ultrasound>50 % (p = 0.053); requirement of vascular intervention (p = 0.01); and microvascular involvement in photoplethysmography (p = 0.033). The most parsimonious regression model suggests that history of tobacco use, male sex, arterial occlusion in ultrasound, and percentage of stenosis in arterial ultrasound>50 % remained statistically significant. The survival analysis identified earlier amputations in patients with larger occlusion in arterial ultrasound, high leukocyte count, and elevated ESR. ConclusionDirect and surrogate outcomes in patients with diabetic foot ulcers identify vascular involvement as an important risk factor for reamputation. Level of evidenceIII

The final analysis of a phase I/II study of nivolumab, ipilimumab combined with nintedanib in advanced non-small cell lung cancer.

9102 Background: Nintedanib (NT) is an oral triple kinase inhibitor that is active against NSCLC and inhibits the activity of the immunosuppressive cancer associated fibroblasts in the tumor microenvironment (TME). Targeting the TME with NT may represent an important synergistic approach in improving immunotherapy (IO) outcomes for NSCLC. We initiated a phase Ib/II trial to evaluate the combination of NT, nivolumab (N) and ipilimumab (I) in advanced (a)NSCLC. Based on the phase IB (dose escalation) results, the combination of N (3mg/kg/2w), I (1mg/kg/6w) and NT (150mg once daily) was declared as the recommended phase 2 dose (RP2D). Here we present the final analysis of the regimen in treatment naïve (TN), and IO pretreated (IP) aNSCLC. Methods: This is a single institution, non- randomized, parallel assignment phase I/II clinical trial of aNSCLC pts. Eligible pts were TN (Arm A) or with disease progression following IO (Arm B) with planned sample size of 40/arm. Enrollment into phase II was by the Bayesian two-stage design method with the primary objective of determining the overall response rate (ORR) in the intent to treat population. Key secondary objectives were overall survival (OS) and progression-free survival (PFS). Descriptive statistics were used to summarize demographic and safety data. The Kaplan- Meier method with log-rank test (5% level of significance, 95% CI and 2-sided test) was used for survival analysis. Results: 22 and 29 pts received the N+I+NT at the RP2D in Arm A and B, respectively. The median age was 67 [42;92] with 53% (27/51) females, 84% (42/51) Caucasian, ECOG 1 in 88% (45/51), and a current/prior history of tobacco use in 88% (45/51) pts. Adenocarcinoma histology was common (64%, 33/51) with PD-L1 ≥1% in 52% (22/42) pts. As of Oct 24, 2022, 18 and 26 pts were evaluable for response in Arm A and B, respectively. Clinical efficacy was observed in the TN and IP cohorts (Table). The most common treatment-related adverse events (TRAEs) were similar in both cohorts. TRAE of any grade in Arm A were nausea (8, 36%), diarrhea (8, 36%), fatigue (7, 32%), and in Arm B were nausea (10, 34%), fatigue (9, 31%), anorexia (8,27%). Conclusions: The combination of nivolumab, ipilimumab and nintedanib had a manageable toxicity profile and demonstrated promising antitumor activity in both TN and IP aNSCLC patients. Clinical trial information: NCT03377023 . [Table: see text]

Presence of hyperdiploidy and history of tobacco use in African American patients with SMM.

8062 Background: Smoldering multiple myeloma (SMM) has a clinically variable course in progression to active myeloma (MM). Accurate risk stratification is essential in identifying which patients may benefit from early therapeutic intervention. Current models do not account for the potential impact of race on risk of progression to SMM. Here, we seek to identify independent risk factors for progression in African American (AA) versus white patients in a real-world single institutional database of SMM patients. Methods: We retrospectively identified 224 patients (pts) with untreated SMM from 2007 to 2021 treated at our institution. Patient demographics and disease characteristics were obtained from our IRB-approved myeloma database. TTP was defined as the time from diagnosis of SMM to diagnosis of active MM, estimated by Kaplan-Meier and compared by log-rank test. Univariate analyses were performed using Cox proportional hazard models for TTP. Results: A total of 224 pts (AA 35%, white 47%, other/unknown 17%) were identified with median age 62y (range 32-82). Median follow-up was 4.3y in Whites and 5y in AA pts. Notable characteristics include M/F 45%/54%, IgG/IgA/FLC 76%/17%/6%, 30% current/past smoker (median 15 pack-years), 12% alcohol use (≥10 drinks/wk), 45% with BMI &gt; 30. Multiple cytogenetic abnormalities were defined as presence of ≥2 of the following: t(4;14), t(14;16), gain(1q21), del(1p), del(13), or del(17p). The median TTP (mTTP) was 6.8 [95% CI (3.7, 8.2)] years in whites and 5.6 [95% CI (4.6, 11.8)] years in AA. On univariate analysis, M-spike &gt; 1.5, involved K/L ratio &gt; 12, and bone marrow PC &gt; 20% were associated with increased risk of progression for both AA and whites (all p &lt; 0.05). As expected, gain of 1q21 was associated with increased risk of progression for both groups, though more pronounced in AA (HR 2.94, p = 0.025) versus whites (HR 2.33, p = 0.013). Hyperdiploidy was associated with shorter mTTP in AA (HR 3.03, p = 0.004) compared to whites (HR 1.39, p = 0.3). Multiple cytogenetic abnormalities was associated with shorter mTTP in whites (HR 2.63, p = 0.004) but was not statistically significant in AA (HR 2.63, p = 0.104). Interestingly, tobacco use was associated with shorter mTTP in Blacks (HR 2.94, p = 0.005) but not in whites (HR 0.96, p = 0.85). Conclusions: Understanding the potential impact of racial background on progression from SMM to MM is critical in the appropriate management of all patients with SMM. In this database, with a large proportion of AA patients, hyperdiploidy and +1q portend high risk of progression in AA patients. Further study is needed to better classify these potential differences to ensure risk stratification models are applicable to all patients.

Amplification of wild-type RET and clinical response to selpercatinib for non–small-cell lung cancer (NSCLC).

9123 Background: RET rearrangements and RET kinase domain mutations represent targetable genomic alterations in various cancer types. However, the frequency and characteristics of RET amplification in cancer and its potential role as a targetable oncogenic driver are not well-characterized. Methods: In a pan-cancer cohort of patients at the Dana-Farber Cancer Institute (DFCI) whose tumors underwent next-generation sequencing (NGS), we evaluated the frequency of wild-type (wt) RET amplification (defined as ≥6 copies) in the absence of RET rearrangements or activating mutations. We validated our findings using merged data from the TCGA, GENIE, and China Pan-Cancer datasets. Results: The frequency of wt RET amplification across all cancers was 0.08% (28/34,463) in the DFCI cohort and 0.16% (145/91,466) in the validation cohort. In NSCLC, the frequency of RET amplification was 0.10% (5/4773) in the DFCI cohort and 0.13% (15/11,622) in the validation cohort. Other cancer types with RET amplification included hepatobiliary cancer, prostate cancer, and breast cancer, among others. For 22 RET-amplified cases with available copy number data , the median RET gene copy number was 7 (range 6-36). Among 20 RET-amplified NSCLCs, 10 had no other known driver mutations, and 10 had concurrent driver mutations (including MET exon 14 skipping, MET amplification, KRAS G12C/S/D, EGFR L858R, EGFR exon 20 insertion, and EGFR exon 19 deletion). In cases with available smoking status, 5 out of 6 patients with RET-amplified NSCLC had a history of tobacco use. A 69-year-old man with unresectable stage III NSCLC had disease recurrence after chemoradiation and durvalumab. Both the initial and recurrent biopsy samples showed focal high-level RET amplification (22 and 28 copies, respectively); genomic and RNA sequencing showed no other driver mutations or RET rearrangements. He experienced partial response to the selective RET inhibitor selpercatinib with decrease of both intracranial and systemic tumor burden. Conclusions: Amplification of wt RET represents a novel, targetable, rare molecular subset of NSCLC and other cancers.

Molecular characterization of resistance to immune checkpoint inhibitor and chemotherapy treatment in advanced non-small cell lung cancer.

9034 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer and a leading cause of cancer death. Standard of care (SOC) treatment for advanced NSCLC patients include immune checkpoint inhibitors (ICI) and/or chemotherapy (CT). However, the majority of patients do not respond to SOC therapy. Mechanisms of resistance and how they differ across treatments are not fully understood. We characterized molecular markers of resistance for advanced NSCLC patients with ICI monotherapy, CT, or combination ICI-CT. Methods: Advanced stage III or IV NSCLC patients with adenocarcinoma histology who received at least 21 days of ICI monotherapy, CT, or combination ICI-CT were identified from a de-identified, multimodal real-world database from Tempus Labs, Inc. All patients had a tissue biopsy taken within 100 days prior to the specified therapy start and all samples underwent next generation sequencing with the Tempus xT assays (DNA-seq of 596-648 genes at 500x coverage and whole transcriptome RNA-seq). Resistance to therapy was defined as having time to next treatment &lt; 90 days, or disease progression or death within 120 days of therapy initiation. We characterized the clinical and molecular characteristics of patients and compared differential expression of genes by resistance status for each cohort. Results: A total of 365 patients were included in the study (ICI = 121, CT = 122, ICI-CT = 122). Across cohorts, 30% of patients were identified as having resistance to treatment (ICI = 35%, CT = 23%, ICI-CT = 32%). 53% of patients were &gt; 65 years (median [range] = 67 [25- 88]), and 53% were males. Most patients were white (63%) and had a history of tobacco use (85% current or former smoker). At the time of biopsy, most patients were diagnosed with metastatic NSCLC (Stage IV = 73%) and had received no previous lines of therapy (92%). The alteration frequencies of known NSCLC oncogenic driver mutations including TP53 (65%), KRAS (42%), STK11 (14%), KEAP1 (11%), and EGFR (9%) were broadly consistent with previous characterizations of NSCLC. Validated biomarkers of response to ICI treatment such as Tumor Mutation Burden, IFN-γ signaling, PD-1, and PD-L1 expression were negatively associated with resistance to ICI treatment. Across the ICI, ICI-CT, and CT cohorts, 253, 153, and 178 genes, respectively, were significantly upregulated (FDR &lt; 0.05, LogFC &gt; 1) in patients with resistance to treatment. Of the 550 distinct genes correlated to resistance across treatments, 95% were unique to each cohort, and only 32 genes (5%) were shared across more than one treatment cohort. Conclusions: Distinct molecular characteristics were associated with resistance to ICI and/or CT treatment. This suggests that mechanisms of resistance to ICI monotherapy, ICI-CT, or CT could be separate and unique. Further research can provide valuable insights for novel therapies or combinations.

OC-028 USING THE VACUUM ASSISTED “FRENCH FRY” TECHNIQUE (FFT) FOR WOUND CLOSURE IN CONTAMINATED OPEN ABDOMINAL WALL RECONSTRUCTION (AWR)

Abstract Introduction In some settings, it is not appropriate to close wounds primarily, such as when patients are felt to be at high risk for wound infection. FFT is a useful method of wound closure in these patients following open AWR. Methods A consecutive series of patients were closed with FFT following AWR from 2019–2022. The FFT includes cutting a vacuum-assisted closure (VAC) sponge into 1×1×8cm segments that are partially placed through an otherwise closed wound. A skin VAC is placed over the wound and external portion of the FFs. Patient characteristics, operative details, and postoperative outcomes were collected. Standard descriptive statistics were reported. Results Wound closure was performed with FFT in 15 patients. Patients were 63.8±13.1 years old, mean BMI was 31.1±6.5 kg/m2, and there was history of tobacco use in 40.0% of patients, diabetes in 46.7%, and prior failed hernia repair in 11(73.3%). Almost all had CDC wound class of 3 or 4(13, 86.7%) wounds, and hernia defect size was 144[8, 310]cm2. Biologic mesh was placed in 9(60.0%), and no mesh was used in 6(40.0%). Wound complication risk based on the CeDAR risk score was 59.5±15.1%. There were 2(13.3%) 30-day readmissions, including 1(6.7%) for a wound infection that was reopened at the bedside. There were no other wound complications. Conclusions FFT is an alternative method of wound closure for significantly at-risk wounds in patients undergoing AWR. The present study describes FFT use in high-risk, complex patients with only 1 of 15 patients having a postoperative wound complication.

Effects of chewing tobacco on corneal endothelium in patients with diabetes mellitus.

To determine the impact of tobacco chewing on corneal endothelial structure in patients with diabetes mellitus (DM). Corneal endothelial parameters (endothelial cell count, ECD; coefficient of variation, CV; hexagonality, Hex, and central corneal thickness, CCT) were analysed in 1234 eyes of 1234 patients using non-contact specular microscopy (EM 4000 Tomey Nishi-Ku, Nagoya, Aichi, Japan). The study group (with a present history of tobacco chewing) comprising of 948 subjects, with 473 having DM was compared with age and gender-matched control group comprising of 286 subjects (139 having DM) with no history of tobacco use in any form. Tobacco chewers had a significantly reduced ECD (P = 0.024) and Hex (P = 0.009) as compared with non-chewers. Similar results were noted in ECD (P = 0.004) and Hex (P = 0.005) in patients with DM. Tobacco chewers had a significantly decreased ECD values among males, HbA1C ≤ 7.5% and duration of DM ≤ 20 years, and significantly decreased Hex among those with >50 years of age, females, and duration of DM > 20 years. The CV and CCT values were comparable between the study and the control groups. Tobacco chewers showed a significant association of ECD with age, HbA1C, and duration of DM; CV with HbA1C; Hex with age and duration of DM; and CCT with gender, age, HbA1C and duration of DM. Tobacco chewing may negatively impact corneal health, especially confounded by additional factors like age and DM. These factors must be accounted for in the pre-operative evaluation of such patients prior to any intra-ocular surgery.