Return of genetic research results in 21,532 individuals with autism.

PURPOSE: The aim of this study is to identify likely pathogenic (LP) and pathogenic (P) genetic results for autism that can be returned to participants in SPARK (SPARKforAutism.org): a large recontactable cohort of people with autism in the United States. We also describe the process to return these clinically confirmed genetic findings. METHODS: We present results from microarray genotyping and exome sequencing (ES) of 21,532 individuals with autism and 17,785 of their parents. We returned LP and P (American College of Medical genetics (ACMG) criteria) copy number variants (CNVs), chromosomal aneuploidies, and variants in genes with strong evidence of association with autism and intellectual disability. RESULTS: We identified 1903 'returnable' LP/P variants in 1861 individuals with autism (8.6%). 89.5% of these variants were not known to participants. The diagnostic genetic result was returned to 589 participants (53% of those contacted). Features associated with a higher probability of having a returnable result include cognitive and medically complex features, being female, being White (versus non-White) and being diagnosed more than 20 years ago. We also find results among autistics across the spectrum, as well as in transmitting parents with neuropsychiatric features but no autism diagnosis. CONCLUSION: SPARK offers an opportunity to assess returnable results among autistic people who have not been ascertained clinically. SPARK also provides practical experience returning genetic results for a behavioral condition at a large scale.

Illusory Responses across the Lewy Body Disease Spectrum.

OBJECTIVE: This study was undertaken to study pareidolias, or perceived meaningful objects in a meaningless stimulus, in patients across the Lewy body (LB) disease spectrum, where most do not report hallucinations or delusions. METHODS: We studied illusory responses on the Noise Pareidolia Task in 300 participants (38 cognitively impaired LB, 65 cognitively unimpaired LB, 51 Alzheimer disease spectrum [AD-s], 146 controls). Pairwise between-group comparisons examined how diagnosis impacts the number of illusory responses. Ordinal regression analysis compared the number of illusory responses across diagnosis groups, adjusting for age, sex, and education. Analyses were repeated after removing participants with reported hallucinations or delusions. RESULTS: Cognitively impaired LB participants were 12.3, 4.9, and 4.6 times more likely than control, cognitively unimpaired LB, and AD-s participants, respectively, to endorse illusory responses. After adjusting for age, sex, and education, the probability of endorsing 1 or more illusory responses was 61% in the cognitively impaired LB group, compared to 26% in AD-s, 25% in cognitively unimpaired LB, and 12% in control participants. All results were similar after repeated analysis only in participants without hallucinations or delusions. In LB without hallucinations or delusions, 52% with mild cognitive impairment and 66.7% with dementia endorsed at least 1 illusory response. INTERPRETATION: We found illusory responses are common in cognitively impaired LB patients, including those without any reported psychosis. Our data suggest that, prior to the onset of hallucinations and delusions, the Noise Pareidolia Task can easily be used to screen for unobtrusive pareidolias in all LB patients. ANN NEUROL 2023;93:702-714.

Malignant myopericytoma: Case report and review of the literature.

A 29-year-old male presented with a two-week history of a tender lesion on his right thigh. The lesion was a 1.5 cm erythematous nodule with overlying hemorrhagic crust. Histopathologic examination of a biopsy specimen revealed a highly cellular neoplasm with irregular vesicular nuclei, prominent nucleoli, and scattered mitotic figures. The cells within the lesion were rounded, ovoid and spindle shaped cells with perivascular growth. The architecture and staining pattern of the lesion were most consistent with a diagnosis of malignant myopericytoma, an exceedingly rare malignancy.

Changes in serum prealbumin as a marker for nitrogen balance in surgical oncology patients.

BACKGROUND: Serum prealbumin has long been used as a marker of nutritional status. However, prealbumin is a negative acute phase reactant influenced by several non-nutritional-related factors including surgery, infection, and cancer. An increasing prealbumin has been correlated with a positive nitrogen balance in general surgery patients receiving parenteral nutrition (PN) with 88% specificity and 70% sensitivity. To date, no trial has evaluated the effect of concurrent cancer and surgery on the value of prealbumin in predicting nitrogen balance. METHODS: This study is a concurrent retrospective design of post-operative patients (≥ 19 years of age) identified by the nutrition support service who received PN for ≥ 5 days, had a baseline and follow-up serum prealbumin and C-reactive Protein (CRP) measured, as well as a 24-h urinary urea nitrogen (UUN) performed between days 5-10 of PN. Exclusion criteria include anuric renal failure, Child-Pugh Class C liver failure, pregnancy, and corticosteroid use. Prealbumin was correlated to nitrogen balance, measuring sensitivity, specificity, and negative and positive predictive values. Information was collected regarding patient demographics and presence or absence of metastatic cancer. RESULTS: Thirty patients were identified and evaluated for this study from December 1st, 2010 to July 15th, 2011. Patients included in the study had a mean age of 57 years old (range 20-82), 53% male, with a mean weight of 84 kg (range 42-140) and body mass index (BMI) of 29 kg/m2 (range 14.9-56.8). The mean daily caloric dose of PN per actual body weight was 21 kcal/kg (range 10-34) and the mean daily protein dose was 1.4 g/kg (range 1-2). Forty seven percent of patients were obese (BMI > 30 kg/m2) and were prescribed high-protein hypocaloric PN. The most common indication for PN was post-operative ileus (23/30 patients). 24-h urine collection for UUN was performed on average of day 8 after PN initiation (range 5-10 days). Nitrogen balance as calculated from 24-h UUN was positive in 17/30 patients. A positive prealbumin change of greater than 2.8 mg/dL was found to have a statistically significant association with positive nitrogen balance (p = 0.02). At the cut off level of positive 2.8 mg/dL, the likelihood of a positive nitrogen balance had a sensitivity of 82% (95% confidence interval (CI) 64-100%); specificity of 62% (95% CI 35-88%); positive predictive value of 74% (95% CI 54-93%); negative predictive value of 73% (95% CI 46-99%). No absolute value for prealbumin level (e.g., > 20  mg/dL) was found to be a significant predictor of positive nitrogen balance. CRP levels at initiation of PN were significantly elevated with a mean level of 147 mg/dL. CONCLUSION: These results indicate a positive change in serum prealbumin (> 2.8 mg/dL) has sufficient sensitivity (82%) to predict positive changes in nitrogen balance in the surgical oncology population. However, the low specificity (62%) makes it less useful in predicting a negative nitrogen balance. Absolute prealbumin levels were greatly affected by inflammation, as evidenced by CRP levels, and single values were not useful in predicting positive nitrogen balance. CLINICAL RELEVANCY: Positive changes in serum prealbumin levels have previously been associated with a positive nitrogen balance (NB) in surgical patients receiving parenteral nutrition (PN); however, it is unclear if this is true in oncologic surgery patients. This study highlights how changing levels of serum prealbumin and C-reactive protein correlates to NB for cancer patients in the post-operative period requiring PN. Changes in prealbumin levels from baseline showed sufficient sensitivity, but not specificity to utilize routinely for predicting NB in this population.

Tau PET imaging with 18F-PI-2620 in aging and neurodegenerative diseases.

PURPOSE: In vivo measurement of the spatial distribution of neurofibrillary tangle pathology is critical for early diagnosis and disease monitoring of Alzheimer's disease (AD). METHODS: Forty-nine participants were scanned with 18F-PI-2620 PET to examine the distribution of this novel PET ligand throughout the course of AD: 36 older healthy controls (HC) (age range 61 to 86), 11 beta-amyloid+ (Aß+) participants with cognitive impairment (CI; clinical diagnosis of either mild cognitive impairment or AD dementia, age range 57 to 86), and 2 participants with semantic variant primary progressive aphasia (svPPA, age 66 and 78). Group differences in brain regions relevant in AD (medial temporal lobe, posterior cingulate cortex, and lateral parietal cortex) were examined using standardized uptake value ratios (SUVRs) normalized to the inferior gray matter of the cerebellum. RESULTS: SUVRs in target regions were relatively stable 60 to 90 min post-injection, with the exception of very high binders who continued to show increases over time. Robust elevations in 18F-PI-2620 were observed between HC and Aß+ CI across all AD regions. Within the HC group, older age was associated with subtle elevations in target regions. Mildly elevated focal uptake was observed in the anterior temporal pole in one svPPA patient. CONCLUSION: Preliminary results suggest strong differences in the medial temporal lobe and cortical regions known to be impacted in AD using 18F-PI-2620 in patients along the AD trajectory. This work confirms that 18F-PI-2620 holds promise as a tool to visualize tau aggregations in AD.

Changes in Sexual Behavior Related to the COVID-19 Stay-at-Home Orders Among Young Black Men Who Have Sex With Women in New Orleans, LA.

BACKGROUND: COVID-19 stay-at-home orders enacted in New Orleans, LA on March 16, 2020, may have caused changes in the way young men interacted with sex partners. METHODS: An online substudy was conducted (May 21, 2020 to June 9, 2020) among Black men who have sex with women, 18 years and older, and who had previously enrolled in the parent study Check It (May 17, 2017 to March 6, 2020) to assess changes in sexual behavior during the stay-at-home orders. RESULTS: Among 111 participants, from enrollment in Check It to during stay-at-home orders, recent vaginal sex declined from 96.4% to 47.8% (P < 0.0001), reports of multiple female sex partners declined from 45.0% to 14.4% (P < 0.0001), and sexual abstinence increased from 3.6% to 38.7% (P < 0.0001). Among those who did have vaginal sex, condomless sex rates did not change between enrollment in Check It and the substudy (64.5% vs 67.9%, P = 0.68). During stay-at-home orders oral sex, virtual sex, and pornography viewing were 40.5%, 42.3%, and 76.6%, respectively. Some (17.1%) acquired a new sex partner during stay-at-home orders, and 44.1% left their home to meet a partner for sex. Only 27.9% had seen information about safe sex during the pandemic. Income was diminished for 62.2% and 23.4% moved away from New Orleans when stay-at-home orders were enacted. CONCLUSIONS: Although there was an overall reduction in physical sex, half of participants reported physical sex, with many leaving their home to have sex during stay-at-home orders and many not using condoms. Others adopted sexual abstinence, increased virtual sex, and/or pornography viewing, which may have protected them from both sexually transmitted infections and COVID-19.

Fine-mapping analysis of a chromosome 2 region linked to resistance to Mycobacterium tuberculosis infection in Uganda reveals potential regulatory variants.

Tuberculosis (TB) is a major public health burden worldwide, and more effective treatment is sorely needed. Consequently, uncovering causes of resistance to Mycobacterium tuberculosis (Mtb) infection is of special importance for vaccine design. Resistance to Mtb infection can be defined by a persistently negative tuberculin skin test (PTST-) despite living in close and sustained exposure to an active TB case. While susceptibility to Mtb is, in part, genetically determined, relatively little work has been done to uncover genetic factors underlying resistance to Mtb infection. We examined a region on chromosome 2q previously implicated in our genomewide linkage scan by a targeted, high-density association scan for genetic variants enhancing PTST- in two independent Ugandan TB household cohorts (n = 747 and 471). We found association with SNPs in neighboring genes ZEB2 and GTDC1 (peak meta p = 1.9 × 10-5) supported by both samples. Bioinformatic analysis suggests these variants may affect PTST- by regulating the histone deacetylase (HDAC) pathway, supporting previous results from transcriptomic analyses. An apparent protective effect of PTST- against body-mass wasting suggests a link between resistance to Mtb infection and healthy body composition. Our results provide insight into how humans may escape latent Mtb infection despite heavy exposure.

Estimating cumulative pathway effects on risk for age-related macular degeneration using mixed linear models.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the elderly in developed countries and typically affects more than 10% of individuals over age 80. AMD has a large genetic component, with heritability estimated to be between 45% and 70%. Numerous variants have been identified and implicate various molecular mechanisms and pathways for AMD pathogenesis but those variants only explain a portion of AMD's heritability. The goal of our study was to estimate the cumulative genetic contribution of common variants on AMD risk for multiple pathways related to the etiology of AMD, including angiogenesis, antioxidant activity, apoptotic signaling, complement activation, inflammatory response, response to nicotine, oxidative phosphorylation, and the tricarboxylic acid cycle. While these mechanisms have been associated with AMD in literature, the overall extent of the contribution to AMD risk for each is unknown. METHODS: In a case-control dataset with 1,813 individuals genotyped for over 600,000 SNPs we used Genome-wide Complex Trait Analysis (GCTA) to estimate the proportion of AMD risk explained by SNPs in genes associated with each pathway. SNPs within a 50 kb region flanking each gene were also assessed, as well as more distant, putatively regulatory SNPs, based on DNaseI hypersensitivity data from ocular tissue in the ENCODE project. RESULTS: We found that 19 previously associated AMD risk SNPs contributed to 13.3% of the risk for AMD in our dataset, while the remaining genotyped SNPs contributed to 36.7% of AMD risk. Adjusting for the 19 risk SNPs, the complement activation and inflammatory response pathways still explained a statistically significant proportion of additional risk for AMD (9.8% and 17.9%, respectively), with other pathways showing no significant effects (0.3% - 4.4%). DISCUSSION: Our results show that SNPs associated with complement activation and inflammation significantly contribute to AMD risk, separately from the risk explained by the 19 known risk SNPs. We found that SNPs within 50 kb regions flanking genes explained additional risk beyond genic SNPs, suggesting a potential regulatory role, but that more distant SNPs explained less than 0.5% additional risk for each pathway. CONCLUSIONS: From these analyses we find that the impact of complement SNPs on risk for AMD extends beyond the established genome-wide significant SNPs.

AidData's Geospatial Global Chinese Development Finance Dataset.

AidData's Global Chinese Development Finance Dataset (Version 3.0) provides detailed information about more than 20,000 development projects across 165 low- and middle-income countries financed by 791 official sector Chinese donors and lenders from 2000 to 2021. In this study, we introduce a methodology for identifying the geospatial features of these projects. Our application of the methodology has resulted in the Geospatial Global Chinese Development Finance Dataset (Version 3.0), which captures the geospatial features of 9,405 projects across 148 low- and middle-income countries supported by Chinese grant and loan commitments worth more than USD 830 billion. The dataset provides details for 6,266 projects containing spatial definitions of roads, railways, power plants, transmission lines, buildings, and other precisely geocoded features. It identifies approximate and administrative-level locations for 3,139 additional projects. The methodology, dataset, and the code used to construct the dataset have been made publicly available to facilitate replication and future applications.

Biochemical Safety of SBRT to Multiple Intrahepatic Lesions for Hepatocellular Carcinoma.

Background: We aim to better characterize stereotactic body radiation therapy (SBRT)-related hepatic biochemical toxicity in patients with multiple intrahepatic lesions from hepatocellular carcinoma (HCC). Methods: We conducted a retrospective analysis of patients with HCC who underwent SBRT for 2 or more synchronous or metachronous liver lesions. We collected patient characteristics and dosimetric data (mean liver dose [MLD], cumulative effective volume [Veff], cumulative volume of liver receiving 15 Gy [V15Gy], and cumulative planning target volume [PTV]) along with liver-related toxicity (measured by albumin-bilirubin [ALBI] and Child-Pugh [CP] scores). A linear mixed-effects model was used to assess the effect of multi-target SBRT on changes in ALBI. Results: There were 25 patients and 56 lesions with median follow-up of 29 months. Eleven patients had synchronous lesions, and 14 had recurrent lesions treated with separate SBRT courses. Among those receiving multiple SBRT courses, there were 7 lesions with overlap of V15Gy (median V15Gy overlap: 35 mL, range: 0.5-388 mL). There was no association between cumulative MLD, Veff, V15Gy, or PTV and change in ALBI. Four of 25 patients experienced non-classic radiation-induced liver disease (RILD), due to an increase of CP score by ≥2 points 3 to 6 months after SBRT. Sixteen of 25 patients experienced an increase in ALBI grade by 1 or more points 3 to 6 months after SBRT. Comparing the groups that received SBRT in a single course versus multiple courses revealed no statistically significant differences in liver toxicity. Conclusion: Liver SBRT for multiple lesions in a single or in separate courses is feasible and with acceptable risk of hepatotoxicity. Prospective studies with a larger cohort are needed to better characterize safety in this population.

Long-Term Survival of Patients With Cancer, Sepsis, and Vasopressor Requirements Based on Lactate Levels.

A prospective cohort study was conducted to evaluate the 1-year survival of cancer patients with sepsis and vasopressor requirements. Eligible patients were admitted a Comprehensive Cancer Center's ICU and were compared based on their admission lactate levels. Of the 132 included patients, 87 (66%) had high lactate (HL; > 2.0 mmol/L), and 45 (34%) had normal lactate (NL; ≤ 2.0 mmol/L). The 1-year survival rates of the two groups were similar (HL 16% vs. NL 18%; p = 0.0921). After adjustment for ICU baseline characteristics, HL was not significantly associated with a 1-year survival (Hazards ratio, 1.39; 95% CI, 0.94-2.05). Critically ill cancer patients with sepsis and vasopressor requirements, regardless of the lactate level, had 1-year survival of less than 20%. Large multicenter cancer registries would enable to confirm our findings and better understand the long-term trajectories of sepsis in this vulnerable population.

Outcomes of surgical resection and intraoperative electron radiotherapy for patients with para-aortic recurrences of gastrointestinal and gynecologic malignancies.

BACKGROUND: Para-aortic lymph node (PALN) metastases from primary pelvic malignancies are often treated with resection, but recurrence is common. We report toxicity and oncologic outcomes for patients with PALN metastases from gastrointestinal and gynecologic malignancies treated with resection and intraoperative electron radiotherapy (IORT). METHODS: We retrospectively identified patients with recurrent PALN metastases who underwent resection with IORT. All patients were included in the local recurrence (LR) and toxicity analyses. Only patients with primary colorectal tumors were included in the survival analysis. RESULTS: There were 26 patients with a median follow up of 10.4 months. The rate of para-aortic local control (LC) was 77% (20/26 patients) and the rate of any cancer recurrence was 58% (15/26 patients). Median time from surgery and IORT to any recurrence was 7 months. The LR rate for those with positive/close margins was 58% (7/12 patients) versus 7% (1/14 patients) for those with negative margins (p = 0.009). 15% (4/26 patients) developed surgical wound and/or infectious complications, 8% (2/26 patients) developed lower extremity edema, 8% (2/26 patients) experienced diarrhea, and 19% (5/26 patients) developed an acute kidney injury. There were no reported nerve injuries, bowel perforations, or bowel obstructions. For patients with primary colorectal tumors (n = 19), the median survival (OS) was 23 months. CONCLUSIONS: We report favorable LC and acceptable toxicity for patients receiving surgical resection and IORT for a population that has historically poor outcomes. Our data show disease control rates similar to literature comparisons for patients with strong risk factors for LR, such as positive/close margins.

A Diagnostic Dilemma: Atypical Systemic Pyoderma Gangrenosum.

Pyoderma gangrenosum (PG) is a rare neutrophilic dermatosis that classically presents with chronic ulcerations with raised, violaceous, and undermined borders commonly found on the lower extremities. Less common presentations include tender nodules, pustules, or bullae that may occur on other sites of the body. In rarer circumstances, PG can lead to a systemic inflammatory response syndrome with extensive pulmonary infiltrates but ultimately cause and etiology of the disease are still uncertain. Unfortunately, there is no laboratory test or histopathologic finding that is specific to PG, which makes the diagnosis even more elusive.

Prospective Characterization of Circulating Tumor Cell Kinetics in Patients With Oligometastatic Disease Receiving Definitive Intent Radiation Therapy.

PURPOSE: There are currently no predictive molecular biomarkers to identify patients with oligometastatic disease (OMD) who will benefit from definitive-intent radiation therapy (RT). We prospectively characterized circulating tumor cell (CTC) kinetics in patients with OMD undergoing definitive-intent RT. METHODS: This prospective correlative biomarker study included patients with any solid malignancy ≤5 metastatic sites in ≤3 anatomic organ systems undergoing definitive-intent RT to all disease sites. Circulating tumor cells (CTCs) were captured and enumerated using a biomimetic cell rolling and nanotechnology-based assay functionalized with antibodies against epithelial cell adhesion molecule, against human epidermal growth factor receptor 2, and against epidermal growth factor receptor before and during RT and at follow-up visits up to 2 years post-RT. RESULTS: We enrolled 43 patients with a median follow-up of 14.3 months. The pretreatment CTC level (cells captured/mL) was not associated with the number of disease sites (median one metastatic site/patient, range 1-5) or metastasis location (bone, brain, visceral) on Wilcoxon signed-rank test, P > .05. Post-RT, 56% of patients received systemic therapy, and 72% of patients experienced subsequent local or systemic progression. For 90% of patients, a CTC level <15 within 130 days post-RT corresponded to a durable control of irradiated lesions. Patients with a favorable versus an unfavorable clearance profile experienced significantly longer progression-free survival after RT (median 13 v 4 months, log-rank test, P = .0011). On logistic regression, CTC level >15 at a given time point was associated with clinical disease progression within the subsequent 6 months (odds ratio 3.31, P = .007). In 26% of patients with disease progression, a CTC level >15 preceded radiographic or clinical progression. CONCLUSION: CTCs may serve as a biomarker for disease control in OMD and may predict disease progression before standard assessments for patients receiving diverse cancer-directed therapies.

Factors associated with radiation necrosis and intracranial control in patients treated with immune checkpoint inhibitors and stereotactic radiotherapy.

BACKGROUND AND PURPOSE: Emerging data suggest immune checkpoint inhibitors (ICI) and stereotactic radiosurgery (SRS) or radiotherapy (SRT) may work synergistically, potentially increasing both efficacy and toxicity. This manuscript characterizes factors associated with intracranial control and radiation necrosis in this group. MATERIALS AND METHODS: All patients had non-small cell lung cancer, renal cell carcinoma, or melanoma and were treated from 2013 to 2021 at two institutions with ICI and SRS/SRT. Univariate and multivariate analysis were used to analyze factors associated with local failure (LF) and grade 2+ (G2 + ) radiation necrosis. RESULTS: There were 179 patients with 549 metastases. The median follow up from SRS/SRT was 14.7 months and the median tumor size was 7 mm (46 tumors ≥ 20 mm). Rates of LF and G2 + radiation necrosis per metastasis were 5.8% (32/549) and 6.9% (38/549), respectively. LF rates for ICI +/- 1 month from time of radiation versus not were 3% (8/264) and 8% (24/285) (p = 0.01), respectively. G2 + radiation necrosis rates for PD-L1 ≥ 50% versus < 50% were 17% (11/65) and 3% (5/203) (p=<0.001), respectively. PD-L1 ≥ 50% remained significantly associated with G2 + radiation necrosis on multivariate analysis (p = 0.03). Rates of intracranial failure were 54% (80/147) and 17% (4/23) (p = 0.001) for those without and with G2 + radiation necrosis, respectively. CONCLUSIONS: PD-L1 expression (≥50%) may be associated with higher rates of G2 + radiation necrosis, and there may be improved intracranial control following the development of radiation necrosis. Administration of ICIs with SRS/SRT is overall safe, and there may be some local control benefit to delivering these concurrently.

Treatment of Localized Amyloid Light Chain Amyloidosis With External Beam Radiation Therapy.

PURPOSE: Localized amyloidosis is a condition characterized by deposits of fibrillary proteins confined to a single organ. The most common subtype is amyloid light chain amyloidosis, which is caused by secretion of amyloidogenic light chain by a monoclonal population of plasma cells. We present a review and discussion of the literature in the context of a case presentation of localized amyloid light chain amyloidosis of the nasopharynx treated with radiation alone. METHODS AND MATERIALS: We reviewed literature relevant to this topic from 1970 to the present. Relevant studies, reports, and articles were summarized in table form. RESULTS: Surgical resection has historically been the primary therapeutic modality for these patients, with radiation being reserved for recurrent lesions or for those unfit for surgery. Although the data are limited to small retrospective series, radiation has been shown to provide good control with mild toxicity that is as good as or better than surgery. Doses range from 20 to 45 Gy, conventionally fractionated. There is no known risk of progression to systemic disease without local therapy. CONCLUSIONS: We recommend local therapy for symptomatic patients after systemic disease has been excluded. We generally recommend radiation in the setting of recurrent lesions, unacceptable toxicity with surgery, poor surgical candidates, and as the initial modality in select patients (elderly individuals with bothersome but nonobstructive lesions).

Transarterial Chemoembolization with LC Bead LUMI followed by Stereotactic Body Radiation Therapy in Treatment of Hepatocellular Carcinoma.

PURPOSE: Transarterial chemoembolization (TACE) in combination with stereotactic body radiation therapy (SBRT) is a promising therapy for patients with hepatocellular carcinoma (HCC). A radiopaque drug-eluting embolic bead used during TACE, called LC Bead LUMI (Boston Scientific), was developed to allow improved visualization during TACE. The purpose of this case series is to assess the visibility of LUMI after TACE and discuss its potential use as an alignment tool for SBRT. METHODS: Fourteen patients with HCC (median age 69) received TACE using LUMI immediately followed by SBRT to 50 Gy in 5 fractions (13 patients) or 40 Gy in 5 fractions (1). Computed tomography (CT) simulation and cone beam CT (CBCT) images taken before each fraction were compared with immediate post-TACE imaging. Success of the LUMI bead opacification was graded from excellent to poor visualization. Patients were followed to assess target lesion response, disease control, survival, and the long-term visibility of LUMI beads. RESULTS: CBCT immediately after TACE with LUMI displayed excellent tumor visibility for 6 of 13 patients (46.2%), moderate tumor visibility for 4 patients (30.8%), and poor tumor visibility for 3 patients (23.1%). When comparing CBCTs used for SBRT image verification to post-TACE CBCT, 53.8% remained unchanged and 46.2% deteriorated from excellent to moderate or moderate to poor, but none deteriorated from excellent to poor visualization. Median follow-up was 13 months (range 2-35). On average, LUMI beads were visible on noncontrast CT up to 20 months after SBRT. CONCLUSIONS: LC Bead LUMI has the ability to provide liver tumor demarcation on noncontrast and cone beam CT weeks to months following TACE. It can serve as an alignment tool and could improve the therapeutic ratio in liver SBRT by allowing for tumor margin reduction with a potential decrease in the risk of toxicity when treating HCC in facilities without magnetic resonance imaging-linear accelerator.

Dosimetric and Clinical Factors Associated With Breast Reconstruction Complications in Patients Receiving Postmastectomy Radiation.

PURPOSE: Approximately 30% of women who receive postmastectomy radiation therapy in the setting of breast reconstruction suffer from reconstruction complications. This study aims to assess clinical and dosimetric factors associated with the risk of reconstruction complications after postmastectomy radiation therapy, with the ultimate goal of identifying a dosimetric constraint that can be used clinically to limit this risk. METHODS AND MATERIALS: We retrospectively identified 41 patients who underwent a modified radical or total mastectomy, followed by immediate or delayed reconstruction (autologous or implant-based) and radiation at a single institution between 2014 and 2020. Reconstruction complications were defined as a flap or implant failure, necrosis, capsular contracture, cellulitis/infection, implant rupture, implant malposition, leakage/rupture, unplanned operation, and hematoma/seroma. Clinical and dosimetric variables associated with complications were assessed with univariate analyses. RESULTS: Twelve patients (29%) suffered reconstruction complications, which led to a flap or implant failure in 5 patients. The median time to complication after reconstruction was 8 months. Thirty-two percent of patients with immediate and 20% with delayed reconstruction suffered a complication, respectively. There were no local failures. Smoking (P = .02), use of bolus (P = .03), and the percentage of the chest wall/reconstructed breast target volume that received ≥107% of the prescribed radiation dose (V107) > 11% (P = .03) were associated with increased complication rates. The complication rates were 42% when V107 > 11% versus 12% when V107 < 11%; 58% in smokers versus 17% in nonsmokers; and 42% with versus 7% without bolus. CONCLUSIONS: Plan heterogeneity appears to be associated with the risk of reconstruction complications. Pending further validation, V107 < 11% may serve as a reasonable guide to limit this risk. Further consideration should be given to the selective use of bolus in this setting and optimization of clinical factors, such as smoking cessation.

Confirming Pathogenicity of the F386L PSEN1 Variant in a South Asian Family With Early-Onset Alzheimer Disease.

OBJECTIVES: The F386L PSEN1 variant has been reported in 1 Japanese family with limited clinical information. We aimed to prove that F386L is pathogenic by demonstrating that it segregates with early-onset Alzheimer disease (AD). METHODS: Eight individuals in a South Asian family provided DNA for genetic testing and underwent a neurologic examination. RESULTS: The female proband was diagnosed with AD at age 45 years and died at age 49 years. She had a CSF biomarker profile consistent with AD, and her florbetaben PET scan was amyloid positive with high uptake in the striatum. Her MRI showed no prominent white matter disease. Her affected relatives had an age at onset range of 38-57 years and had imaging and biomarker profiles similar to hers. DISCUSSION: The results presented here, in conjunction with the prior report, confirm the pathogenicity of F386L. Furthermore, our study highlights the importance of studying families from underrepresented populations to identify or confirm the pathogenicity of rare variants that may be specific to certain genetic ancestries.