Clinical features and outcomes of advanced HER2+ esophageal/GEJ cancer with brain metastasis.

BACKGROUND: Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood. METHODS: We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated. RESULTS: We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM. CONCLUSION: HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation.

Downsampled depth encoding for enhanced 3D range geometry compression.

The use of three-dimensional (3D) range geometry is expanding across a variety of disciplines ranging from medicine to the visual arts. A large amount of information is available in 3D range geometry, causing some applications to be limited in their ability to effectively store or transmit captured data. To help alleviate this constraint, a variety of 3D range data compression techniques have been proposed. One method, multiwavelength depth (MWD) encoding, smoothly encodes 3D range geometry into the three color channels of a 2D RGB image. To the best of our knowledge, we present a novel compression enhancement to further reduce file sizes that employs image downsampling, MWD encoding, and lossless (e.g., PNG) or lossy (e.g., JPEG) compression. Image upsampling is used to return downsampled encodings to their original resolution from which the 3D information is then decoded. The proposed method is robust to various scales of downsampling and levels of lossy compression. For example, when this method was applied with 50% downsampling and JPEG 85 to an encoding of a 3D face scan, a compression ratio of 68.85:1 versus the raw data was achieved with a global RMS reconstruction accuracy of 98.77%. Experimental results demonstrate that the proposed method can provide substantial file size savings at minimal reduction in overall reconstruction accuracy.

Flowthrough Omental Flap for Vascularized Lymph Node Transplant of the Lower Extremity.

SUMMARY: Vascularized lymph node transplantation is a surgical approach for the treatment of chronic lymphedema. However, there is no clinical standard for flap placement nor vascular anastomoses. The authors propose a novel flowthrough configuration for an omental vascularized lymph node transplant in the popliteal space. To prepare the popliteal space for an omental free flap, the medial popliteal fat pad and medial head of the gastrocnemius muscle were debulked. Venous anastomoses were completed with vein couplers, joining the right gastroepiploic vein to the medial sural venae comitantes and the left gastroepiploic vein to the lesser saphenous vein. Arterial anastomoses were hand sewn, joining the right gastroepiploic artery to the proximal medial sural artery and the left gastroepiploic artery to the distal medial sural artery, to create the flowthrough configuration. A retrospective review of patients who underwent this procedure at a single institution was performed. Six patients with chronic lymphedema of the lower extremity underwent vascularized lymph node transplantation from June of 2019 to November of 2020. Five patients underwent at least 3 months of postoperative surveillance, with no postoperative complications reported. In this technique contribution, the authors describe a novel flowthrough configuration for an omental free flap to the popliteal space. The popliteal space offers an aesthetically favorable recipient location when appropriately prepared. The medial sural vessels are ideal recipient vessels for the flowthrough omental flap. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Foveated 3D range geometry compression via loss-tolerant variable precision depth encoding.

The capacity of three-dimensional (3D) range geometry acquisition methods to capture high-precision scans at high frame rates increases every year. These improvements have influenced a broadening range of disciplines to implement 3D range geometry capture systems, including telepresence, medicine, the visual arts, and many others. However, its increased popularity, precision, and capture rates have caused mounting pressure on the storage and transmission of 3D range geometry, thus straining their capacities. Compression techniques seek to alleviate this pressure by offering reduced file sizes, while maintaining the levels of precision needed for particular applications. Several such compression methods use sinusoidal modulation approaches to encode floating-point 3D data into conventional 2D red, green, and blue (RGB) images. In some applications, such as telepresence, high precision may only be required in a particular region within a depth scan, thus allowing less important data to be compressed more aggressively. This paper proposes a feature-driven compression method that provides a way to encode regions of interest at higher levels of precision while encoding the remaining data less precisely to reduce file sizes. This method supports both lossless and lossy compression, enabling even greater file-size savings. For example, in the case of a depth scan of a bust, an algorithmically extracted bounding box of the face was used to create a foveated encoding distribution so that the facial region was encoded at higher precisions. When using JPEG 80, the RMS reconstruction error of this novel, to the best of our knowledge, encoding was 0.56 mm in the region of interest, compared to a globally fixed higher precision encoding where the error was 0.54 mm in the same region. However, the proposed encoding achieved a 26% reduction in overall compressed file size compared to the fixed, higher-precision encoding.

An integrated high temperature environmental cell for atom probe tomography studies of gas-surface reactions: instrumentation and results.

An integrated environmental cell has been designed and developed for the latest generation of Atom Probe Tomography LEAP™ instruments, allowing controlled exposure of samples to gases at high temperatures. Following treatment, samples can be transferred through the LEAP vacuum system for subsequent APT analysis, which provides detailed information on changes to chemical microstructures following the reactions with near-atomic resolution. A full description of the cell is presented, along with some sample results on the oxidation of aluminum and two platinum-group alloys, demonstrating the capability of combining exposure/characterization functionality in a single instrument.

An integrated genomic analysis of lung cancer reveals loss of DUSP4 in EGFR-mutant tumors.

To address the biological heterogeneity of lung cancer, we studied 199 lung adenocarcinomas by integrating genome-wide data on copy number alterations and gene expression with full annotation for major known somatic mutations in this cancer. This showed non-random patterns of copy number alterations significantly linked to EGFR and KRAS mutation status and to distinct clinical outcomes, and led to the discovery of a striking association of EGFR mutations with underexpression of DUSP4, a gene within a broad region of frequent single-copy loss on 8p. DUSP4 is involved in negative feedback control of EGFR signaling, and we provide functional validation for its role as a growth suppressor in EGFR-mutant lung adenocarcinoma. DUSP4 loss also associates with p16/CDKN2A deletion and defines a distinct clinical subset of lung cancer patients. Another novel observation is that of a reciprocal relationship between EGFR and LKB1 mutations. These results highlight the power of integrated genomics to identify candidate driver genes within recurrent broad regions of copy number alteration and to delineate distinct oncogenetic pathways in genetically complex common epithelial cancers.

A comparison of drug interaction software programs: applicability to the emergency department.

STUDY OBJECTIVE: To compare the features of available drug interaction software programs in terms of general applicability to an emergency department setting. DESIGN: Prospective evaluation of drug interaction software programs based on presence or absence of a variety of performance features. SETTING: University and community hospital EDs. PARTICIPANTS: Eight commercially available drug interaction software programs. RESULTS: Programs were evaluated according to designated performance and data base features. Tabulated results were compiled for purposes of comparison. CONCLUSION: Although no computer program tested completely met the specific needs of a busy ED, many programs have features with at least some general applicability.

Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer.

To determine the potential efficacy of the CA 125 assay as one component of a strategy for early detection of ovarian malignancy, serum CA 125 levels were determined in 1082 women 40 years of age or older in Stockholm. Initial serum CA 125 levels exceeded 35 U/ml in 36 women (3.3%) and 65 U/ml in 11 women (1.0%), placing the exact 95% upper confidence limits on false positive rates for a single screen at 4.3 and 1.7%, respectively. Follow-up CA 125 levels were obtained for those women with initially elevated levels and a group of age-matched controls. Mean CA 125 levels declined significantly for women with initially elevated levels (P = 0.0014). Interindividual variation and variation within individual subjects over the entire follow-up period were 52 and 35%, respectively. Of the 36 subjects with initially elevated serum CA 125 levels, only 2 showed a doubling of these levels; in only 1 of these 2 was this increase sustained. Intensive clinical follow-up with pelvic examination and ultrasonography, with investigators blinded to CA 125 results, led to the diagnosis of Stage III ovarian cancer in the latter individual. Diagnosis was made 21 months after the initially elevated serum CA 125 measurement and 15 months after the first measured doubling of that level. Because no other malignancies were identified at entry or during the follow-up period (median 560 days) in the women with elevated CA 125 levels, the specificity of the assay over that time period would have been 99.9% using the doubling of an initially elevated value as the criterion for determining positivity and 100% using as the criterion a sustained increase in level for those with initially elevated levels that doubled. These results support the continued investigation of longitudinally collected CA 125 levels to identify individuals at high risk for ovarian malignancy.

Serum CA 125 levels in a group of nonhospitalized women: relevance for the early detection of ovarian cancer.

Serum samples were collected from 915 nonhospitalized Roman Catholic nuns with a median age of 55 years (range 19-94 years). Using an immunoradiometric assay, serum CA 125 levels ranged from 0-574 U/mL with a median of 10.5 and mean of 14.3 U/mL. Thirty-six women (3.9%) had serum levels greater than 35 U/mL, and only seven (0.76%) had serum CA 125 levels above 65 U/mL. In only 14 (2.4%) of 586 women aged 50 or older were CA 125 levels above 35 U/mL, and in only three (0.51%) of this group did levels exceed 65 U/mL. Among the seven women with levels above 65 U/ML, five were found to have benign or malignant neoplasms or other masses at the time of entry into the study or during the follow-up interval (mean 311 +/- 103 days). Moreover, in six of seven members of this "false positive" group, some disorder was diagnosed during the study period that might have elevated the CA 125 level. No correlation was found between serum CA 125 levels and a variety of nonmalignant disorders or a variety of concurrent medications. The apparent specificity of the CA 125 assay in this study population suggests that, if used in conjunction with other tests to discriminate ovarian carcinoma from disorders that could elevate serum CA 125 levels, this assay might be a potential component of a strategy aimed at the early detection of ovarian cancer.

Molecular cloning and expression of hipA, a gene of Escherichia coli K-12 that affects frequency of persistence after inhibition of murein synthesis.

The hipA gene at 33.8 min on the Escherichia coli chromosome controls the frequency of persistence upon inhibition of murein synthesis; for strains bearing hipA+ the frequency is 10(-6), and for hipA- strains the frequency is 10(-2). hip+ has been cloned by selection for a kanamycin resistance determinant at 33.9 min. hipA+ is dominant over hipA- in both recA+ and recA- backgrounds. The smallest DNA insert which contains hipA+, as determined by the ability of the plasmids to complement hipA- strains, is 1,885 base pairs. Both orientations of hipA+ are obtained when the cloning site of vector is remote from strong promoters; both orientations complement hipA-, and both encode a unique peptide of 50,000 Mr. The probable direction of transcription has been deduced from the pattern of peptides encoded by plasmids from which either end of the insert and adjacent vector sequences have been deleted. This information and the recovery of only one orientation of hipA+ when the cloning site is close to a strong promoter suggest that a high level of expression of the gene is not tolerated by E. coli.