Infantile spasms (West syndrome): update and resources for pediatricians and providers to share with parents

Background Infantile spasms (IS; West syndrome) is a severe form of encephalopathy that typically affects infants younger than 2 years old. Pediatricians, pediatric neurologists, and other pediatric health care providers are all potentially key early contacts for families who have an infant with IS. The objective of this article is to assist pediatric health care providers in the detection of the disease and in the counseling and guidance of families who have an infant with IS. Methods Treatment guidelines, consensus reports, and original research studies are reviewed to provide an update regarding the diagnosis and treatment of infants with IS. Web sites were searched for educational and supportive resource content relevant to providers and families of patients with IS. Results Early detection of IS and pediatrician referral to a pediatric neurologist for further evaluation and initiation of treatment may improve prognosis. Family education and the establishment of a multidisciplinary continuum of care are important components of care for the majority of patients with IS. The focus of the continuum of care varies across diagnosis, initiation of treatment, and short- and long-term needs. Several on-line educational and supportive resources for families and caregivers of patients with IS were identified. Conclusions Given the possibility of poor developmental outcomes in IS, including the emergence of other seizure disorders and cognitive and developmental problems, early recognition, referral, and treatment of IS are important for optimal patient outcomes. Dissemination of and access to educational and supportive resources for families and caregivers across the lifespan of the child with IS is an urgent need. Pediatric health care providers are well positioned to address these needs

The TechEdSat-N Series: A Collaborative Technology Development Platform in the Nano-Satellite Form Factor

The TechEdSat-1 (TES-1) was the first U.S. CubeSat to be deployed from the ISS (International Space Station). This permitted the initiation of a flight series that has recently de-orbited the 6th nano-satellite with subsequent numbers 7-10 under development. The nano-satellites range from 1U (1 unit) to 6U (TechEdSat-8) but have the critical ISS Safety design features standardized in order to focus on the particular experiment objectives. Incremental experimental development has included unique communication subsystems such as command/control of the nanosatellite through email commands -as well as a recent record for Wifi transmission. Also, the thermophysics of controlled drag devices (Exo-Brake) has been developed which will prelude sample return and planetary exploration applications. The successful "rapid incremental experiment" approach has also been incorporated into collaborations with academia, permitting professors/student interns to be exposed to the rigors of space mission hardware design and execution. The TechEdSat-8, a linear 6U configuration, allows for 5 different groups to contribute an "experiment, sensor, or sub-system" through a well-defined common interface. Lastly, the flying laboratory concept is helpful in developing future interplanetary nano-satellite subsystems which will advance exploration goals by allowing rapid demonstration/validation first in LEO (Low Earth Orbit)

Reducing nasal morbidity after skull base reconstruction with the nasoseptal flap: Free middle turbinate mucosal grafts

The nasoseptal flap provides hearty, vascularized tissue for reconstruction of Expanded Endonasal Approaches (EEA); however, it produces donor site morbidity due to exposed cartilage. Mucosalization of the septum requires 12 weeks, multiple debridements, and frequent saline rinses. This study addresses the reduction of nasal morbidity by grafting middle turbinate mucosa onto the exposed septum

A Multidisciplinary Breast Cancer Brain Metastases Clinic: The University of North Carolina Experience

Breast cancer brain metastasis (BCBM) confers a poor prognosis and is unusual in requiring multidisciplinary care in the metastatic setting. The University of North Carolina at Chapel Hill (UNC-CH) has created a BCBM clinic to provide medical and radiation oncology, neurosurgical, and supportive services to this complex patient population. We describe organization and design of the clinic as well as characteristics, treatments, and outcomes of the patients seen in its first 3 years

Weight gain in hormone receptor-positive (HR+) early-stage breast cancer: is it menopausal status or something else?

Purpose: This study investigates weight trajectories in pre- versus postmenopausal breast cancer (BC) survivors diagnosed with hormone receptor-positive tumors, with a specific focus on discerning menopausal status and type of endocrine treatment (ET) as risk factors for weight gain during ET. Methods: We conducted a retrospective review of electronic medical records. Descriptive statistics and Chi-squared and t tests were used to compare pre- and postmenopausal women. Chi-squared tests and ANOVA were used for within-group associations between patient characteristics and weight trajectories. Log-binomial regression models were used to estimate relative risk for weight gain. Results: The final sample was 32% premenopausal (n = 140) and 68% postmenopausal (n = 298). Relative risk (RR) for weight gain during ET was highest in women who were premenopausal (RR = 1.29, 1.03–1.52) and had Stage 3 BC (RR = 2.12, 1.59–2.82), mastectomy (RR = 1.49, 1.19–1.88), axillary node dissection (RR = 1.39, 1.11–1.73), and chemotherapy (RR = 1.80, 1.37–2.36). For each kg of weight gained between BC diagnosis and start of ET, and for each additional year of age, RR of gaining weight during ET decreased (RR = 0.98, 0.97–0.99, and RR = 0.99, 0.98–0.99, respectively). Menopausal status and type of ET were not significant predictors of weight gain. In multivariable analysis, only weight loss between BC diagnosis and start of ET was significant. Conclusion: The association of weight loss prior to ET and subsequent substantial weight gain during ET warrants further investigation

De Novo Mutations in SIK1 Cause a Spectrum of Developmental Epilepsies

Developmental epilepsies are age-dependent seizure disorders for which genetic causes have been increasingly identified. Here we report six unrelated individuals with mutations in salt-inducible kinase 1 (SIK1) in a series of 101 persons with early myoclonic encephalopathy, Ohtahara syndrome, and infantile spasms. Individuals with SIK1 mutations had short survival in cases with neonatal epilepsy onset, and an autism plus developmental syndrome after infantile spasms in others. All six mutations occurred outside the kinase domain of SIK1 and each of the mutants displayed autophosphorylation and kinase activity toward HDAC5. Three mutations generated truncated forms of SIK1 that were resistant to degradation and also showed changes in sub-cellular localization compared to wild-type SIK1. We also report the human neuropathologic examination of SIK1-related developmental epilepsy, with normal neuronal morphology and lamination but abnormal SIK1 protein cellular localization. Therefore, these results expand the genetic etiologies of developmental epilepsies by demonstrating SIK1 mutations as a cause of severe developmental epilepsy

Segment Anything Model (SAM) for Digital Pathology: Assess Zero-shot Segmentation on Whole Slide Imaging

The segment anything model (SAM) was released as a foundation model for image segmentation. The promptable segmentation model was trained by over 1 billion masks on 11M licensed and privacy-respecting images. The model supports zero-shot image segmentation with various segmentation prompts (e.g., points, boxes, masks). It makes the SAM attractive for medical image analysis, especially for digital pathology where the training data are rare. In this study, we evaluate the zero-shot segmentation performance of SAM model on representative segmentation tasks on whole slide imaging (WSI), including (1) tumor segmentation, (2) non-tumor tissue segmentation, (3) cell nuclei segmentation. Core Results: The results suggest that the zero-shot SAM model achieves remarkable segmentation performance for large connected objects. However, it does not consistently achieve satisfying performance for dense instance object segmentation, even with 20 prompts (clicks/boxes) on each image. We also summarized the identified limitations for digital pathology: (1) image resolution, (2) multiple scales, (3) prompt selection, and (4) model fine-tuning. In the future, the few-shot fine-tuning with images from downstream pathological segmentation tasks might help the model to achieve better performance in dense object segmentation

Obesity, comorbidities, and treatment selection in Black and White women with early breast cancer

Background: This study investigates obesity and comorbidity in Black and White women with early breast cancer (stages I-III) and their potential impact on treatment decisions for patients with hormone receptor–positive (HR+)/human epidermal growth factor receptor 2–negative (HER2–) tumors. Methods: In this retrospective chart review, comparisons of frequencies for Black and White patients were calculated with the Fisher exact test. Log binomial regression was used to estimate prevalence ratios (PRs) with 95% confidence intervals for total and individual comorbidities, and multivariable modeling was used to estimate PRs adjusted for age and body mass index (BMI). Results: In a sample of 548 patients, 26% were Black, and 74% were White. Sixty-two percent of Black patients and 32% of White patients were obese (BMI ≥ 30 kg/m2; P <.0001). Seventy-five percent of Black patients and 87% of White patients had HR+ tumors (P =.001). Significant intergroup differences were seen for 2 or more total comorbidities (62% of Blacks vs 47% of Whites; P =.001), 2 or more obesity-related comorbidities (33% vs 10%; P <.0001), hypertension (60% vs 32%; P <.0001), diabetes mellitus (23% vs 6%; P <;.0001), hypercholesterolemia or hyperlipidemia (28% vs 18%; P =.02), and hypothyroidism (4% vs 11%; P =.012). In women with HR+/HER2– tumors, there were no intergroup differences in treatment decisions regarding the type of surgery, chemotherapy regimen, radiation, or endocrine treatment despite significant differences in the prevalence of obesity and comorbidities. Conclusions: This study documents significant disparities between Black and White women with early breast cancer with regard to high rates of obesity, overall comorbidities, and obesity-related comorbidities, and it highlights the prevalence of competing risks that may complicate outcomes in breast cancer

Weight changes in postmenopausal breast cancer survivors over 2 years of endocrine therapy: a retrospective chart review

Purpose: Obesity and weight gain after breast cancer (BC) diagnosis can affect cancer outcomes. This study explores the question of weight change during the first 2 years of endocrine treatment (ET) to identify the independent effects of BC diagnosis and treatment on post-diagnosis weight trajectories in early-stage postmenopausal BC survivors. Methods: The study design is a retrospective chart review. Chi square tests and ANOVA were used to compare patients who gained >2 kg, lost >2 kg, or had stable weight. Log-binomial regression models were used to evaluate associations between patient characteristics and weight trajectories. Results: The final sample is N = 300, with mean age at BC diagnosis of 65 years and 76% white. After 2 years of ET, 39% of study participants had gained >2 kg, 27% had lost >2 kg, and 34% had stable weight. Relative risks (RR) for weight gain were as follows: age at diagnosis = 0.98 (0.96, 0.99), being married = 1.48 (1.04, 2.12), weight change between BC diagnosis and start of ET = 0.98 (0.97, 0.99), Stage II = 1.42 (1.01, 2.01) or Stage III = 1.99 (1.41, 2.82), PR negative = 0.70 (0.51, 0.96), HER2 positive = 1.51 (1.07, 2.13), mastectomy = 1.49 (1.12, 1.98), axillary node dissection = 1.67 (1.27, 2.20), adjuvant chemotherapy = 1.49 (1.02, 2.19), and neoadjuvant chemotherapy = 2.29 (1.67, 3.14). Type of ET (tamoxifen or aromatase inhibitor) was not significant. Conclusions: In our sample of postmenopausal early-stage BC survivors, a majority had stable or lost weight during the first 2 years of ET. Higher disease complexity and associated treatment posed higher RR for weight gain

Weight trajectories in women receiving systemic adjuvant therapy for breast cancer

Background: Weight gain after breast cancer (BC) diagnosis is a well-known phenomenon; however, it is not a universal phenomenon and identification of patients at highest risk for weight gain is needed. This study investigates weight trajectories in early BC patients at 2 years post-primary treatment, examining potential contributing factors such as age, race, and receipt of chemotherapy, anti-HER-2 therapy, and endocrine treatment (ET). Methods: A single institution cohort of newly diagnosed women age 21 and older with early breast cancer patients (Stage 0–3) were identified by retrospective chart review (diagnosis year 1995 to 2016). Log-binomial regression models for net weight changes at 2 years post-primary treatment including patient demographic, clinical, and treatment characteristics. Results: The final sample of 625 patients included 29% who were non-White and 37% who were pre-menopausal at diagnosis. Body mass index (BMI) at diagnosis was calculated and found to be normal in 33% (BMI 18 to 2 kg, 34% had stable weight ± 2 kg, and 35% had gained > 2 kg. Factors associated with > 2 kg weight gain were menopausal status (pre-menopausal HR 1.65, 95% CI 1.34–2.04, p <.0001), receiving any chemotherapy (HR 1.36, 95% CI 1.04–1.77), and anthracycline-based chemotherapy followed by ET (HR 1.60, CI 1.01–2.45). Anti-HER-2 therapy and transition from pre- to post-menopausal during the 2-year study period were not significant factors in weight gain. In multivariate analysis, menopausal status remained the only significant variable related to weight gain when adjusted for treatment. For all treatment combinations, pre-menopausal women had significantly more weight gain. Conclusions and relevance: Weight gain, weight loss, and stable weight in women with early breast cancer vary greatly by treatment plan. However, pre-menopausal patients have the highest risk for weight gain