Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

BACKGROUND: The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. METHODS: In this prospective community-based cohort, participants with normal kidney function were analysed (N = 5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60 mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. RESULTS: The participants' mean age was 57.2 ± 8.3 years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] µg/ng, P < 0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI < 23.0 kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI ≥ 23.0 kg/m2 and those without sarcopenia. CONCLUSIONS: A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI < 23.0 kg/m2 and sarcopenia.

Risk of Fracture in Patients with Myasthenia Gravis: A Nationwide Cohort Study in Korea.

Myasthenia gravis (MG) is an autoimmune disorder that affects the neuromuscular junctions, resulting in muscle weakness and fatigue. Muscle weakness, restricted mobility, and frequent use of corticosteroids in patients with MG may predispose them to a higher risk of fractures. However, studies on the impact of MG on bone health and the associated fracture risk are scarce. Utilizing claim database of the Korean National Health Insurance Service collected between 2002 and 2020, we compared the risk of major osteoporotic fracture between 23 118 patients with MG and 115 590 individuals as an age- and sex-matched control group using multivariable Cox proportional hazard models. Over a median follow-up duration of 5.58 years, the MG group (mean age 53.7 years; 55% women) had higher risk of major osteoporotic fracture compared to controls (incidence rate 13.59 versus 9.74 per 10 000 person-years), which remained independent of age, sex, comorbidities, drug use including anti-osteoporotic agents, and previous fracture history (adjusted hazard ratio [aHR] 1.19, p < 0.001; subdistributed HR 1.14, p < 0.001 adjusted for mortality as competing risk). Subgroup analyses showed a greater association between MG and major osteoporotic fracture risk in younger (age 50 or younger) than older individuals (aHR 1.34 vs. 1.17) and in men compared to women (aHR 1.32 vs. 1.15; p for interaction <0.05 for all). An imminent divergence of the fracture risk curve between MG and controls was observed for vertebral fracture while there was time delay for non-vertebral sites, showing site-specific association. Factors associated with higher fracture risk in patients with MG were older age, female gender, high dose glucocorticoid use (> 7.5 mg/day), immunosuppressant use, and previous history of fracture. In summary, patients with MG had higher risk of major osteoporotic fracture compared to controls, which calls further preventive actions in this patient group.

Impact of diabetes distress on glycemic control and diabetic complications in type 2 diabetes mellitus.

The effect of diabetes distress on glycemic control and its association with diabetes complications is still poorly understood. We aimed to study the clinical features of patients with high diabetes distress, focusing on changes in glycemic control and risk of diabetic complications. From the Korean National Diabetes Program data, we investigated 1862 individuals with type 2 diabetes mellitus (T2DM) who completed diabetic complication studies and the Korean version of the Problem Areas in Diabetes Survey (PAID-K). A total score of PAID-K ≥ 40 was considered indicative of high distress. Individuals with high distress (n = 589) had significantly higher levels of glycated hemoglobin than those without distress (7.4% vs. 7.1%, p < 0.001). This trend persisted throughout the 3-year follow-up period. Higher PAID-K scores were associated with younger age, female gender, longer duration of diabetes, and higher carbohydrate intake (all p < 0.05). There was a significant association between high distress and diabetic neuropathy (adjusted odds ratio, 1.63; p = 0.002), but no significant association was found with other complications, including retinopathy, albuminuria, and carotid artery plaque. In conclusion, high diabetes distress was associated with uncontrolled hyperglycemia and higher odds of having diabetic neuropathy.

Association of secondhand smoke with fracture risk in community-dwelling nonsmoking adults in Korea.

Although the detrimental effects of active smoking on bone health have been widely recognized, the impact of secondhand smoke exposure on fracture risk in non-smokers remains less understood. A total of 4843 nonsmokers aged 40-69 yr, who participated in the Korean Genome and Epidemiology Study from 2001 to 2018, were analyzed. The participants were categorized into two groups based on their exposure status to secondhand smoke: currently exposed and unexposed. The exposure group was subsequently divided into two subgroups based on the median weekly exposure time (high vs low). The incidence of new fractures was determined using self-reported questionnaires. The identified fractures were categorized according to the fracture site: overall, vertebral, hip, non-vertebral, and non-vertebral non-hip fractures. The mean age of the participants was 52.4 yr (84.1% women). Exposure to secondhand smoke was associated with an increased risk of fracture (adjusted hazard ratio [aHR]: 1.27, P = 0.028) after adjusting for multiple covariates including age, sex, BMI, household income, bone density of mid-shaft tibia, C-reactive protein, alcohol consumption, and fracture history. Secondhand smoke remained as a significant risk factor for fracture, independent of the major osteoporotic fracture probabilities estimated using a fracture risk assessment tool (aHR: 1.24, P = 0.038). The high exposure group had higher risk of fracture than that of the unexposed group (aHR: 1.33, P = 0.025), whereas the fracture risk did not differ significantly between low exposure and unexposed groups (aHR: 1.18, P = 0.253), suggesting a potential dose-response relationship. Secondhand smoke showed robust association with increased risk of non-vertebral (aHR: 1.37, P = 0.008) or non-vertebral non-hip fractures (aHR: 1.36, P = 0.013), while its association with vertebral fracture was attenuated (aHR: 1.03, P = 0.908). Secondhand smoke was associated with an elevated risk of fracture in nonsmokers, independent of clinical risk factors.

Longitudinal Analysis of SARS-CoV-2-Specific Cellular and Humoral Immune Responses and Breakthrough Infection following BNT162b2/BNT162b2/BNT162b2 and ChAdOx1/ChAdOx1/BNT162b2 Vaccination: A Prospective Cohort in Naive Healthcare Workers.

Assessing immune responses post-SARS-CoV-2 vaccination is crucial for optimizing vaccine strategies. This prospective study aims to evaluate immune responses and breakthrough infection in 235 infection-naïve healthcare workers up to 13-15 months after initial vaccination in two vaccine groups (108 BNT/BNT/BNT and 127 ChAd/ChAd/BNT). Immune responses were assessed using the interferon-gamma enzyme-linked immunospot (ELISPOT) assay, total immunoglobulin, and neutralizing activity through surrogate virus neutralization test at nine different time points. Both groups exhibited peak responses one to two months after the second or third dose, followed by gradual declines over six months. Notably, the ChAd group exhibited a gradual increase in ELISPOT results, but their antibody levels declined more rapidly after reaching peak response compared to the BNT group. Six months after the third dose, both groups had substantial cellular responses, with superior humoral responses in the BNT group (p < 0.05). As many as 55 breakthrough infection participants displayed higher neutralization activities against Omicron variants, but similar cellular responses compared to 127 infection-naïve individuals, suggesting cross-immunity. Distinct neutralization classifications (<30%, >80% inhibition) correlated with different ELISPOT results. Our study reveals diverse immune response patterns based on vaccine strategies and breakthrough infections, emphasizing the importance of understanding these dynamics for optimized vaccination decisions.

Artificial Intelligence in Gastric Cancer Imaging With Emphasis on Diagnostic Imaging and Body Morphometry.

Gastric cancer remains a significant global health concern, coercing the need for advancements in imaging techniques for ensuring accurate diagnosis and effective treatment planning. Artificial intelligence (AI) has emerged as a potent tool for gastric-cancer imaging, particularly for diagnostic imaging and body morphometry. This review article offers a comprehensive overview of the recent developments and applications of AI in gastric cancer imaging. We investigated the role of AI imaging in gastric cancer diagnosis and staging, showcasing its potential to enhance the accuracy and efficiency of these crucial aspects of patient management. Additionally, we explored the application of AI body morphometry specifically for assessing the clinical impact of gastrectomy. This aspect of AI utilization holds significant promise for understanding postoperative changes and optimizing patient outcomes. Furthermore, we examine the current state of AI techniques for the prognosis of patients with gastric cancer. These prognostic models leverage AI algorithms to predict long-term survival outcomes and assist clinicians in making informed treatment decisions. However, the implementation of AI techniques for gastric cancer imaging has several limitations. As AI continues to evolve, we hope to witness the translation of cutting-edge technologies into routine clinical practice, ultimately improving patient care and outcomes in the fight against gastric cancer.

Age-Dependent Association of Height Loss with Incident Fracture Risk in Postmenopausal Korean Women.

BACKGRUOUND: Height loss is a simple clinical measure associated with increased fracture risk. However, limited data exists on the association between height loss and fracture risk in postmenopausal Korean women. It is unknown whether this association varies with age. METHODS: Data on height loss over a 6-year period were collected from a community-based longitudinal follow-up cohort (Ansung cohort of the Korean Genome and Epidemiology Study). Incident fractures were defined based on self-reported fractures after excluding those due to severe trauma or toes/fingers. The association between incident fractures and height loss was investigated using a Cox proportional hazards model. RESULTS: During a median follow-up of 10 years after the second visit, 259/1,806 participants (median age, 64 years) experienced incident fractures. Overall, a 1 standard deviation (SD) decrease in height (1.6 cm/median 5.8 years) was associated with 9% increased risk of fracture (hazard ratio [HR], 1.09; P=0.037), which lost statistical significance after adjustment for covariates. When stratified into age groups (50-59, 60-69, 70 years or older), a 1 SD decrease in height remained a robust predictor of fracture in the 50 to 59 years age group after adjusting for covariates (adjusted hazard ratio [aHR], 1.52; P=0.003), whereas height loss was not an independent predictor of fracture in the 60 to 69 (aHR, 1.06; P=0.333) or the 70 years or older age groups (aHR, 1.05; P=0.700; P for interaction <0.05, for all). CONCLUSION: Height loss during the previous 6 years was associated with an increased 10-year fracture risk in postmenopausal women in their 50s.

Advanced non-small-cell lung cancer treated with first-line pembrolizumab plus chemotherapy: tumor response dynamics as a marker for survival.

OBJECTIVES: The study investigated tumor burden dynamics on computed tomography (CT) scans in patients with advanced non-small-cell lung cancer (NSCLC) during first-line pembrolizumab plus chemotherapy, to provide imaging markers for overall survival (OS). METHODS: The study included 133 patients treated with first-line pembrolizumab plus platinum-doublet chemotherapy. Serial CT scans during therapy were assessed for tumor burden dynamics during therapy, which were studied for the association with OS. RESULTS: There were 67 responders, with overall response rate of 50%. The tumor burden change at the best overall response ranged from - 100.0% to + 132.1% (median of - 30%). Higher response rates were associated with younger age (p < 0.001) and higher programmed cell death-1 (PD-L1) expression levels (p = 0.01). Eighty-three patients (62%) showed tumor burden below the baseline burden throughout therapy. Using an 8-week landmark analysis, OS was longer in patients with tumor burden below the baseline burden in the first 8 weeks than in those who experienced ≥ 0% increase (median OS: 26.8 vs. 7.6 months, hazard ratio (HR): 0.36, p < 0.001). Tumor burden remained below their baseline throughout therapy was associated with significantly reduced hazards of death (HR: 0.72, p = 0.03) in the extended Cox models, after adjusting for other clinical variables. Pseudoprogression was noted in only one patient (0.8%). CONCLUSIONS: Tumor burden staying below the baseline burden throughout the therapy was predictive of prolonged overall survival in patients with advanced NSCLC treated with first-line pembrolizumab plus chemotherapy, and may be used as a practical marker for therapeutic decisions in this widely used combination regimen. CLINICAL RELEVANCE STATEMENT: The analysis of tumor burden dynamics on serial CT scans in reference to the baseline burden can provide an additional objective guide for treatment decision making in patients treated with first-line pembrolizumab plus chemotherapy for their advanced NSCLC. KEY POINTS: • Tumor burden remaining below baseline burden during therapy predicted longer survival during first-line pembrolizumab plus chemotherapy. • Pseudoprogression was noted in 0.8%, demonstrating the rarity of the phenomenon. • Tumor burden dynamics may serve as an objective marker for treatment benefit to guide treatment decisions during first-line pembrolizumab plus chemotherapy.

Clinicopathologic, Genomic, and Immunophenotypic Landscape of ATM Mutations in Non-Small Cell Lung Cancer.

PURPOSE: ATM is the most commonly mutated DNA damage and repair gene in non-small cell lung cancer (NSCLC); however, limited characterization has been pursued. EXPERIMENTAL DESIGN: Clinicopathologic, genomic, and treatment data were collected for 5,172 patients with NSCLC tumors which underwent genomic profiling. ATM IHC was performed on 182 NSCLCs with ATM mutations. Multiplexed immunofluorescence was performed on a subset of 535 samples to examine tumor-infiltrating immune cell subsets. RESULTS: A total of 562 deleterious ATM mutations were identified in 9.7% of NSCLC samples. ATM-mutant (ATMMUT) NSCLC was significantly associated with female sex (P = 0.02), ever smoking status (P < 0.001), non-squamous histology (P = 0.004), and higher tumor mutational burden (DFCI, P < 0.0001; MSK, P < 0.0001) compared with ATM-wild-type (ATMWT) cases. Among 3,687 NSCLCs with comprehensive genomic profiling, co-occurring KRAS, STK11, and ARID2 oncogenic mutations were significantly enriched among ATMMUT NSCLCs (Q < 0.05), while TP53 and EGFR mutations were enriched in ATMWT NSCLCs. Among 182 ATMMUT samples with ATM IHC, tumors with nonsense, insertions/deletions, or splice site mutations were significantly more likely to display ATM loss by IHC (71.4% vs. 28.6%; P < 0.0001) compared with tumors with only predicted pathogenic missense mutations. Clinical outcomes to PD-(L)1 monotherapy (N = 1,522) and chemo-immunotherapy (N = 951) were similar between ATMMUT and ATMWT NSCLCs. Patients with concurrent ATM/TP53 mutations had significantly improved response rate and progression-free survival with PD-(L)1 monotherapy. CONCLUSIONS: Deleterious ATM mutations defined a subset of NSCLC with unique clinicopathologic, genomic, and immunophenotypic features. Our data may serve as resource to guide interpretation of specific ATM mutations in NSCLC.

Comparison of humoral and cellular immune responses between ChAd-BNT heterologous vaccination and BNT-BNT homologous vaccination following the third BNT dose: A prospective cohort study.

Introduction: The differential immune responses after two additional BNT162b2 (BNT) booster doses between ChAdOx1 nCoV-10 (ChAd)-primed and BNT-primed groups have not been elucidated. The aim of this study was to compare vaccine-induced humoral and cellular immune responses and evaluate breakthrough infection between the two vaccination strategies. Methods: In 221 healthy subjects (111 in the ChAd group), longitudinal immune responses were monitored at 3, 4, and 6 months after the 2nd dose and 1, 3, and 6 months after the 3rd dose. Humoral immunity was measured by two fully automated chemiluminescent immunoassays (Elecsys and Abbott) and a surrogate virus neutralization test (sVNT). Cellular immunity was assessed by two interferon-γ (IFN-γ) release assays (QuantiFERON SARS-CoV-2 and Covi-FERON). Results: After the 2nd dose of BNT vaccination, total antibody levels were higher in the ChAd group, but IgG antibody and sVNT results were higher in the BNT group. Following the 3rd dose vaccination, binding antibody titers were significantly elevated in both groups (ChAD-BNT; 15.4 to 17.8-fold, BNT-BNT; 22.2 to 24.6-fold), and the neutralizing capacity was increased by 1.3-fold in both cohorts. The ChAd-BNT group had lower omicron neutralization positivity than the BNT-BNT group (P = 0.001) at 6 months after the 3rd dose. Cellular responses to the spike antigen also showed 1.7 to 3.0-fold increases after the 3rd dose, which gradually declined to the levels equivalent to before the 3rd vaccination. The ChAd cohort tended to have higher IFN-γ level than the BNT cohort for 3-6 months after the 2nd and 3rd doses. The frequency of breakthrough infection was higher in the ChAd group (44.8%) than in the BNT group (28.1%) (P = 0.0219). Breakthrough infection induced increased humoral responses in both groups, and increase of cellular response was significant in the ChAd group. Discussion: Our study showed differential humoral and cellular immune responses between ChAd-BNT-BNT heterologous and BNT-BNT-BNT homologous vaccination cohorts. The occurrence of low antibody levels in the ChAd-primed cohort in the humoral immune response may be associated with an increased incidence of breakthrough infections. Further studies are needed on the benefits of enhanced cellular immunity in ChAd-primed cohorts.

Clinicopathologic and Genomic Factors Impacting Efficacy of First-Line Chemoimmunotherapy in Advanced NSCLC.

INTRODUCTION: Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized. METHODS: In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT. RESULTS: Among 1285 patients treated with CIT, a worsening performance status and increasing derived neutrophil-to-lymphocyte ratio in the blood were associated with a significantly reduced objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS). With increasing PD-L1 tumor proportion scores of less than 1%, 1% to 49%, 50% to 89%, and greater than or equal to 90%, there was a progressive improvement in ORR (32.7% versus 37.5% versus 51.6% versus 61.7%, p < 0.001), mPFS (5.0 versus 6.1 versus 6.8 versus 13.0 mo, p < 0.001), and generally mOS (12.9 versus 14.6 versus 34.7 versus 23.1 mo, p = 0.009), respectively. Of 789 NSCLCs with comprehensive genomic data, NSCLCs with a tumor mutational burden (TMB) greater than or equal to the 90th percentile had an improved ORR (53.5% versus 36.4%, p = 0.004), mPFS (10.8 versus 5.5 mo, p < 0.001), and mOS (29.2 versus 13.1 mo, p < 0.001), compared with those with a TMB less than the 90th percentile. In all-comers with nonsquamous NSCLC, the presence of an STK11, KEAP1, or SMARCA4 mutation was associated with significantly worse ORR, mPFS, and mOS to CIT (all p < 0.05); this was also observed in the KRAS-mutant subgroup of NSCLCs with co-occurring mutations in STK11, KEAP1, or SMARCA4 (all p < 0.05). In KRAS wild-type NSCLC, KEAP1 and SMARCA4 mutations were associated with a significantly shorter mPFS and mOS to CIT (all p < 0.05), but STK11 mutation status had no significant impact on mPFS (p = 0.16) or mOS (p = 0.38). CONCLUSIONS: In advanced NSCLC, better patient performance status, low derived neutrophil-to-lymphocyte ratio, increasing PD-L1 expression, a very high TMB, and STK11/KEAP1/SMARCA4 wild-type status are associated with improved clinical outcomes to first-line CIT.

Immune-Related Thyroiditis in Patients with Advanced Lung Cancer Treated with Immune Checkpoint Inhibitors: Imaging Features and Clinical Implications.

Immune checkpoint inhibitors (ICI) are widely used in advanced nonsmall cell lung cancer (NSCLC) treatment, and the immune-related adverse events involving many organs have been recognized. This article investigated the incidence and imaging characteristics of immune-related thyroiditis in NSCLC patients and correlated the findings with clinical features. A total of 534 NSCLC patients treated with ICI were included. Imaging findings indicative of thyroiditis included changes in morphology and attenuation on restaging chest CT scans and FDG uptake on PET/CT during ICI therapy. Fifty patients (9.4%) had imaging findings indicative of thyroiditis. The median time to onset was 9.5 weeks (range: 0.9-87.4 weeks). The most common finding was diffuse hypoattenuation of the gland (72%), with enlargement in 15 and atrophy in 12 patients. Heterogeneous attenuation of the gland was noted in 12 patients (24%), with enlargement in 7 and atrophy in 1 patient. Two patients (4%) showed increased FDG uptake in the gland on PET/CT without changes in the CT scan. Twenty-two patients who had both clinical and radiologic diagnoses of thyroiditis were more frequently managed with hormone replacement than those with thyroiditis without an imaging abnormality (p < 0.0001). Therefore, awareness of the imaging findings of immune-related thyroiditis may alert clinicians to the presence of clinically relevant thyroiditis.

Imaging Findings on Head Computed Tomography Scans in Victims of Intimate Partner Violence.

OBJECTIVE: The aim of the study is to analyze the imaging findings and injury patterns seen on head computed tomography (CT) examinations performed on survivors of intimate partner violence (IPV). METHODS: An institutional review board-approved retrospective analysis of 668 patients reporting IPV to our institution's violence intervention and prevention program between January 2013 and June 2018 identified 40 unique patients with radiological findings visible on head CT. All injuries visible on head CT were analyzed based on the anatomic location and injury type. Demographics, IPV screening at the time of injury, concomitant, prior, and subsequent injuries to the index head injury were also recorded. RESULTS: Our study cohort had 36 women and 4 men with a mean age at presentation of 43 ± 13 years (mean ± SD), 91 unique injuries with 57 (62.6%) isolated soft tissue injuries, 4 (3.2%) fractures, 13 (14.3%) intra-axial, and 17 (18.7%) extra-axial injuries. Soft tissue injuries and intra-axial injuries occurred most commonly in the frontal region (45.6% and 38.5%), followed by the parietal region (22.8% and 23.1%), while most extra-axial injuries were subdural hematomas (41.2%). Left-sided injuries accounted for 49% (45/91) with 29/91 right-sided (32%) and 17/91 bilateral (19%) injuries. The IPV screening occurred in 44% of injury visits (22/50). Concomitant injuries were seen in 14/50 injury visits (28%), most commonly being in the lower extremity (6/14, 42.9% [% of visits with concomitant injuries]) followed by the upper extremity (5/14, 35.7%), while 52% of visits (26/50) were preceded by prior injuries and 68% of events (34/50) were followed by subsequent injuries. CONCLUSIONS: Isolated soft tissue swelling is the most common manifestation of IPV on head CT scans with frontoparietal region being the most common site. Synchronous and metachronous injuries are frequent.

Non-Alcoholic Fatty Liver Disease with Sarcopenia and Carotid Plaque Progression Risk in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: We aimed to evaluate whether non-alcoholic fatty liver disease (NAFLD) with or without sarcopenia is associated with progression of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). METHODS: We investigated 852 T2DM patients who underwent abdominal ultrasonography, bioelectrical impedance analysis, and carotid artery ultrasonography at baseline and repeated carotid ultrasonography after 6 to 8 years. NAFLD was confirmed by abdominal ultrasonography, and sarcopenia was defined as a sex-specific skeletal muscle mass index (SMI) value <2 standard deviations below the mean for healthy young adults. SMI was calculated by dividing the sum of appendicular skeletal mass by body weight. We investigated the association between NAFLD with or without sarcopenia and the progression of carotid atherosclerosis. RESULTS: Of the 852 patients, 333 (39.1%) were classified as NAFLD without sarcopenia, 66 (7.7%) were classified as sarcopenia without NAFLD, and 123 (14.4%) had NAFLD with sarcopenia at baseline. After 6 to 8 years, patients with both NAFLD and sarcopenia had a higher risk of atherosclerosis progression (adjusted odds ratio, 2.20; P<0.009) than controls without NAFLD and sarcopenia. When a subgroup analysis was performed on only patients with NAFLD, female sex, absence of central obesity, and non-obesity were significant factors related to increased risk of plaque progression risk in sarcopenic patients. CONCLUSION: NAFLD with sarcopenia was significantly associated with the progression of carotid atherosclerosis in T2DM patients.

Interim Positron Emission Tomography During Frontline Chemoimmunotherapy for Follicular Lymphoma.

While most patients with follicular lymphoma (FL) have excellent outcomes with frontline chemoimmunotherapy (CIT), a subset of patients will experience early progression, which is associated with poor subsequent outcomes. Novel biomarkers are needed to identify high-risk patients earlier. We hypothesized that interim positron emission tomography (PET) would predict progression-free survival (PFS) in this population. We retrospectively identified 128 patients with grade 1-3A FL who had an interim PET after 2-4 cycles of frontline CIT at 2 academic centers. PET scans were analyzed using Deauville score (DS) and change in maximum standardized uptake value (ΔSUVmax). Interim PET DS was a significant predictor of PFS (P < 0.003). Patients with a DS of 3 had outcomes similar to those of patients with a DS of 4, so were categorized as PET-positive for additional analyses. Interim PET remained a strong predictor of PFS (DS 3-5, hazard ratio [HR] 2.4, P = 0.006) in a multivariable analysis and was also an early predictor of both a positive end-of-treatment PET (P < 0.001) and progression of disease within 24 months (POD24) (P = 0.006). An optimal ΔSUVmax cutoff of 75% was selected using the bootstrap method. ΔSUVmax <75% was also a significant predictor of PFS on univariable and multivariable analyses (HR 2.8, P < 0.003). In a separate cohort of 50 patients with high-grade FL, interim PET interpreted using either DS (P < 0.001) or ΔSUVmax75% (P = 0.034) was also a significant predictor of inferior PFS. In conclusion, interim PET is an independent predictor of PFS and may be useful as a tool for response-adapted treatment strategies in FL.

Minimal residual disease in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation.

Improved biomarkers are required to guide the optimal use of autologous stem cell transplantation (ASCT) in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). We hypothesized that minimal residual disease (MRD) identified using immunoglobulin high-throughput sequencing in apheresis stem cell (ASC) samples, post-ASCT peripheral blood mononuclear cell (PBMC), and plasma samples could predict relapse. We studied 159 patients with R/R DLBCL who underwent ASCT, of whom 98 had an ASC sample and 60 had post-ASCT surveillance samples. After a median post-ASCT follow-up of 60 months, the 5-year progression-free survival (PFS) was 48%. MRD was detected in of 23/98 (23%) ASC samples and was associated with very poor PFS (5-year PFS 13% vs 53%, P < .001) and inferior overall survival (52% vs 68%, P = .05). The sensitivity and specificity of ASC MRD positivity for progression and death were 36% and 93%, respectively. Positive ASC MRD remained a significant predictor of PFS in multivariable analysis (hazard ratio [HR], 3.7; P < .001). Post-ASCT surveillance MRD testing of plasma, but not PBMC samples, reliably identified patients with an impending relapse. A positive plasma MRD result was associated with inferior PFS (HR, 3.0; P = .016) in a multivariable analysis. The median lead time from MRD detection to relapse was 62 days (range, 0-518 days). In conclusion, the detection of MRD in ASC samples is associated with a very high risk of relapse, justifying alternative treatment strategies or trials of novel consolidation options in these patients. Furthermore, post-ASCT MRD monitoring may facilitate the evaluation of the early initiation of treatment at molecular relapse. This trial has been registered at www.clinicaltrials.gov as #NCT02362997.

Diagnosis and Treatment of Lung Neuroendocrine Neoplasms: Somatostatin Receptor PET Imaging and Peptide Receptor Radionuclide Therapy.

Recently, advancement of somatostatin receptor (SSTR) imaging and theragnostic approach using peptide receptor radionuclide therapy (PRRT) have changed the paradigm of diagnosis and management of neuroendocrine tumor. 68Ga-DOTATATE PET/CT can diagnose the lung carcinoids with high SSTR expression. With combination of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT, tumor heterogeneity of lung carcinoid can be identified, which may guide optimal patient selection for PRRT. PRRT may be an effective and safe treatment of advanced lung carcinoids during progression with first-line somatostatin analog therapy. This review provides updates on the diagnosis and management of lung carcinoids, focusing on SSTR imaging and PRRT.

Imaging patterns of thoracic injuries in survivors of intimate partner violence (IPV).

PURPOSE: To recognize the imaging patterns of thoracic injuries in survivors of intimate partner violence (IPV). MATERIALS AND METHODS: A retrospective radiological review of 688 patients self-reporting IPV to our institution's violence intervention and prevention program between January 2013 and June 2018 identified 30 patients with 89 thoracic injuries. Imaging and demographic data were collected. RESULTS: Thirty survivors with 89 injuries to the thorax were identified with a median age of 43.5 years (21-65 years). IPV was reported or disclosed as the direct cause of injury in 50% (15/30) of survivors, including all nine patients who sustained penetrating injuries. The most common injury type was fracture (72%, 64/89) with 52 rib, 3 sternal, 2 clavicular, and 7 vertebral fractures. There were 3 acromioclavicular dislocations. Among rib fractures, right lower anterior rib fractures (9-12 ribs) were the most common(30%, 16/52). There were 10 superficial soft tissue injuries. There were 12 deep tissue injuries which included 2 lung contusions, 2 pneumomediastinum, 7 pneumothoraces, 1 hemothorax. One third of patients had concomitant injuries of other organ systems, most commonly to the head and face, followed by extremities and one third of patients had metachronous injuries. CONCLUSION: Acute rib fractures with concomitant injuries to the head, neck, face, and extremities with an unclear mechanism of injury should prompt the radiologist to discuss the possibility of IPV with the ordering physician. ADVANCES IN KNOWLEDGE: Recognizing common injuries to the thorax will prompt the radiologists to suspect IPV and discuss it with the clinicians.

Molecular imaging in oncology: Common PET/CT radiopharmaceuticals and applications.

PET/CT is a commonly used modality in cancer imaging, as it can help in diagnosis, staging and assessment of treatment response in many cancer types. A better understanding of the tumor microenvironment and identification of multiple selective targets are promoting further investigation into different radiotracers for diagnosis and therapy. In the past few decades many radiopharmaceuticals have emerged for specific oncologic indications providing superior detection rate than some morphologic modalities. The purpose of this review is to provide an update on the most current radiopharmaceuticals used in cancer imaging including the mechanism of action, indications and pitfalls.

Update on Preoperative Parathyroid Localization in Primary Hyperparathyroidism.

Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.