Current Applications of VR/AR (Virtual Reality/Augmented Reality) in Pediatric Neurosurgery.

Neurosurgical procedures are some of the most complex procedures in medicine and since the advent of the field, planning, performing, and learning them has challenged the neurosurgeon. Virtual reality (VR) and augmented reality (AR) are making these challenges more manageable. VR refers to a virtual digital environment that can be experienced usually through use of stereoscopic glasses and controllers. AR, on the other hand, fuses the natural environment with virtual images, such as superimposing a preoperative MRI image on to the surgical field [1]. They initially were used primarily as neuronavigational tools but soon their potential in other areas of surgery, such as planning, education, and assessment, was noted and explored. Through this chapter, we outline the history and evolution of these two technologies over the past few decades, describe the current state of the technology and its uses, and postulate future directions for research and implementation.

The role of focused ultrasound for pediatric brain tumors: current insights and future implications on treatment strategies.

INTRODUCTION: Focused ultrasound (FUS) is an innovative and emerging technology for the treatment of adult and pediatric brain tumors and illustrates the intersection of various specialized fields, including neurosurgery, neuro-oncology, radiation oncology, and biomedical engineering. OBJECTIVE: The authors provide a comprehensive overview of the application and implications of FUS in treating pediatric brain tumors, with a special focus on pediatric low-grade gliomas (pLGGs) and the evolving landscape of this technology and its clinical utility. METHODS: The fundamental principles of FUS include its ability to induce thermal ablation or enhance drug delivery through transient blood-brain barrier (BBB) disruption, emphasizing the adaptability of high-intensity focused ultrasound (HIFU) and low-intensity focused ultrasound (LIFU) applications. RESULTS: Several ongoing clinical trials explore the potential of FUS in offering alternative therapeutic strategies for pathologies where conventional treatments fall short, specifically centrally-located benign CNS tumors and diffuse intrinsic pontine glioma (DIPG). A case illustration involving the use of HIFU for pilocytic astrocytoma is presented. CONCLUSION: Discussions regarding future applications of FUS for the treatment of gliomas include improved drug delivery, immunomodulation, radiosensitization, and other technological advancements.

MR-guided focused ultrasound in pediatric neurosurgery: current insights, technical challenges, and lessons learned from 45 treatments at Children's National Hospital.

OBJECTIVE: MR-guided focused ultrasound (MRgFUS) is an evolving technology with numerous present and potential applications in pediatric neurosurgery. The aim of this study was to describe the use of MRgFUS, technical challenges, complications, and lessons learned at a single children's hospital. METHODS: A retrospective analysis was performed of a prospectively collected database of all pediatric patients undergoing investigational use of MRgFUS for treatment of various neurosurgical pathologies at Children's National Hospital. Treatment details, clinical workflow, and standard operating procedures are described. Patient demographics, procedure duration, and complications were obtained through a chart review of anesthesia and operative reports. RESULTS: In total, 45 MRgFUS procedures were performed on 14 patients for treatment of diffuse intrinsic pontine glioma (n = 12), low-grade glioma (n = 1), or secondary dystonia (n = 1) between January 2022 and April 2024. The mean age at treatment was 9 (range 5-22) years, and 64% of the patients were male. With increased experience, the total anesthesia time, sonication time, and change in core body temperature during treatment all significantly decreased. Complications affected 4.4% of patients, including 1 case of scalp edema and 1 patient with a postprocedure epidural hematoma. Device malfunction requiring abortion of the procedure occurred in 1 case (2.2%). Technical challenges related to transducer malfunction and sonication errors occurred in 6.7% and 11.1% of cases, respectively, all overcome by subsequent user modifications. CONCLUSIONS: The authors describe the largest series on MRgFUS technical aspects in pediatric neurosurgery at a single institution, comprising 45 total treatments. This study emphasizes potential technical challenges and provides valuable insights into the nuances of its application in pediatric patients.

Evolution of Surgical Management of Pineal Region Tumors in the Pediatric Population: A 17-Year Experience at a Single Institution.

INTRODUCTION: Pineal region tumors have historically been challenging to treat. Advances in surgical techniques have led to significant changes in care and outcomes for these patients, and this is well demonstrated by our single institution's experience over a 17-year-period in which the evolution of diagnosis, treatment, and outcomes of pineal tumors in pediatric patients will be outlined. METHODS: We retrospectively collected data on all pediatric patients with pineal region lesions treated with surgery at Children's National Hospital (CNH) from 2005 to 2021. Variables analyzed included presenting symptoms, presence of hydrocephalus, diagnostic and surgical approach, pathology, and adverse events, among others. IRB approval was obtained (IRB: STUDY00000009), and consent was waived due to minimal risk to patients included. RESULTS: A total of 43 pediatric patients with pineal region tumors were treated during a 17-year period. Most tumors in our series were germinomas (n = 13, 29.5%) followed by pineoblastomas (n = 10, 22.7%). Twenty seven of the 43 patients (62.8%) in our series received a biopsy to establish diagnosis, and 44.4% went on to have surgery for resection. The most common open approach was posterior interhemispheric (PIH, transcallosal) - used for 59.3% of the patients. Gross total resection was achieved in 50%; recurrence occurred in 20.9% and mortality in 11% over a median follow-up of 47 months. Endoscopic third ventriculostomy (ETV) was employed to treat hydrocephalus in 26 of the 38 patients (68.4%) and was significantly more likely to be performed from 2011 to 2021. Most (73%) of the patients who received an ETV also underwent a concurrent endoscopic biopsy. No difference was found in recurrence rate or mortality in patients who underwent resection compared to those who did not, but complications were more frequent with resection. There was disagreement between frozen and final pathology in 18.4% of biopsies. CONCLUSION: This series describes the evolution of surgical approaches and outcomes over a 17-year-period at a single institution. Complication rates were higher with open resection, reinforcing the safety of pursuing endoscopic biopsy as an initial approach. The most significant changes occurred in the preferential use of ETVs over ventriculoperitoneal shunts. Though there has been a significant evolution in our understanding of and treatment for these tumors, in our series, the outcomes for these patients have not significantly changed over that time.

Medulloblastomas, CNS embryonal tumors, and cerebellar mutism syndrome: advances in care and future directions.

Central nervous system (CNS) embryonal tumors, commonly found in pediatric patients, represent a heterogeneous mix of lesions with an overall poor (though improving) prognosis. Medulloblastomas are by far the most frequently encountered and most widely studied subtype, though others include atypical teratoid/rhabdoid tumors (AT/RTs), embryonal tumor with multilayered rosettes (ETMRs), and CNS neuroblastomas, FOX-R2 activated. The classification, diagnosis, and treatment of these lesions have evolved drastically over the years as their molecular underpinnings have been elucidated. We describe the most recent 2021 WHO Classification system, discuss current understanding of the genetic basis, and demonstrate current thinking in treatment for these highly complex tumors. Since surgical resection continues to remain a mainstay of treatment, preventing and managing surgical complications, especially cerebellar mutism syndrome (CMS), is paramount. We describe the current theories for the etiology of CMS and two centers' experience in mitigating its risks. As our surgical toolbox continues to evolve along with our understanding of these tumors, we hope future patients can benefit from both improved overall survival and quality of life.

The clinical significance of adenomatous polyposis coli (APC) and catenin Beta 1 (CTNNB1) genetic aberrations in patients with melanoma.

BACKGROUND: Melanoma-intrinsic activated ß-catenin pathway, the product of the catenin beta 1 (CTNNB1) gene, has been associated with low/absent tumor-infiltrating lymphocytes, accelerated tumor growth, metastases development, and resistance to anti-PD-L1/anti-CTLA-4 agents in mouse melanoma models. Little is known about the association between the adenomatous polyposis coli (APC) and CTNNB1 gene mutations in stage IV melanoma with immunotherapy response and overall survival (OS). METHODS: We examined the prognostic significance of somatic APC/CTNNB1 mutations in the Cancer Genome Atlas Project for Skin Cutaneous Melanoma (TCGA-SKCM) database. We assessed APC/CTNNB1 mutations as predictors of response to immunotherapies in a clinicopathologically annotated metastatic patient cohort from three US melanoma centers. RESULTS: In the TCGA-SKCM patient cohort (n = 434) presence of a somatic APC/CTNNB1 mutation was associated with a worse outcome only in stage IV melanoma (n = 82, median OS of APC/CTNNB1 mutants vs. wild-type was 8.15 vs. 22.8 months; log-rank hazard ratio 4.20, p = 0.011). APC/CTNNB1 mutation did not significantly affect lymphocyte distribution and density. In the 3-melanoma institution cohort, tumor tissues underwent targeted panel sequencing using two standards of care assays. We identified 55 patients with stage IV melanoma and APC/CTNNB1 genetic aberrations (mut) and 169 patients without (wt). At a median follow-up of more than 25 months for both groups, mut compared with wt patients had slightly more frequent (44% vs. 39%) and earlier (66% vs. 45% within six months from original diagnosis of stage IV melanoma) development of brain metastases. Nevertheless, time-to-development of brain metastases was not significantly different between the two groups. Fortunately, mut patients had similar clinical benefits from PD-1 inhibitor-based treatments compared to wt patients (median OS 26.1 months vs. 29.9 months, respectively, log-rank p = 0.23). Less frequent mutations in the NF1, RAC1, and PTEN genes were seen in the mut compared with wt patients from the 3-melanoma institution cohort. Analysis of brain melanoma tumor tissues from a separate craniotomy patient cohort (n = 55) showed that melanoma-specific, activated ß-catenin (i.e., nuclear localization) was infrequent (n = 3, 6%) and not prognostic in established brain metastases. CONCLUSIONS: APC/CTNNB1 mutations are associated with a worse outcome in stage IV melanoma and early brain metastases independent of tumor-infiltrating lymphocyte density. However, PD1 inhibitor-based treatments provide comparable benefits to both mut and wt patients with stage IV melanoma.

Nortriptyline Hydrochloride Solubility-pH Profiles in a Saline Phosphate Buffer: Drug-Phosphate Complexes and Multiple pHmax Domains with a Gibbs Phase Rule "Soft" Constraints.

The solubility of a model basic drug, nortriptyline (Nor), was investigated as a function of pH in phosphate and/or a chloride-containing aqueous suspension using experimental practices recommended in the previously published "white paper" (Avdeef et al., 2016). The pH-Ramp Shake-Flask (pH-RSF) method, introduced in our earlier work (Markovic et al., 2019), was applied. An improved and more detailed experimental design of the Nor solubility measurement allowed us to exploit the full capacity of the pH-RSF method. Complex equilibria in the aqueous phase (cationic and anionic complex formation between Nor and the phosphate) and solid-phase transformations (Nor free base, 1:1 Nor hydrochloride salt, 1:1 and 1:2 Nor phosphate salts) were characterized by a detailed analysis of the solubility measurements using the computer program pDISOL-X. The solid phases were characterized by thermogravimetric analysis, differential scanning calorimetry, powder X-ray diffraction, and elemental analyses. The results of the present investigation illustrate the influence of competing counterions, such as buffering agents, complexing agents, salt coformers, tonicity adjusters, and so forth, on the aqueous solubility of drugs and interconversion of salts. Careful attention given to these factors can be helpful in the formulation of drug products.

" the availability of contraceptives is everywhere.": coordinated and integrated public family planning service delivery in Rwanda.

BACKGROUND: Contraceptive use in Rwanda tripled since 2005. This study aims to understand the role of coordinated and integrated public family planning service delivery in achieving this increase in contraceptive use in Rwanda. METHODS: This qualitative study in 2018 included eight focus group discussions with family planning providers and 32 in-depth interviews with experienced family planning users. RESULTS: Results indicate a well-coordinated public family planning service delivery system with community health workers and nurses filling different and complementary roles in meeting family planning client needs at the local level. In addition, integration of family planning into other maternal and child health services is the norm. CONCLUSIONS: The coordination and integration of family planning across both providers and services may help explain the rapid increase in Rwanda's contraceptive use and has potential applications for enhancing family planning service delivery in other settings.

Family planning use increased from 17 to 53% in Rwanda in between 2005 and 2015. The purpose of this study is to understand the roles of two types of family planning workers in providing family planning services, how those providers work together to achieve the goal to provide public services, and how the Rwandan health system includes family planning services in a variety of other types of health services. To achieve the study purpose, 32 women with experience using modern methods of contraception were interviewed. In addition, 88 providers participated in eight group discussions to discuss these topics. The results from the interviews and group discussions showed that family planning services are easy to access for Rwandans­due to two types of family planning providers filling different roles to assist Rwandans start and keep using family planning methods. Family planning services are included in services for pregnant, delivering, and postpartum mothers­as well as services for infants and children. These are all times when those adults using the services would also be in need of family planning services. The family planning service delivery team approach­as well as including family planning services in mother's and children's health services likely helps explain the increase in family planning use in Rwanda. Other nations might learn from Rwanda's service delivery approach to family planning to also increase access to family planning for their citizens.

"She is courageous because she does not care what people think about her ": attitudes toward adolescent contraception use among Rwandan family planning providers and adult female modern contraceptive users.

INTRODUCTION: In Rwanda, only 20% of sexually active unmarried young women use family planning as compared to 64% of married women. Adolescence is an important time of growth and development that often includes the initiation of sexual activity. Sexually active adolescents need support in accessing contraceptive services to prevent negative health outcomes. In sub-Saharan Africa, the adolescent population represents a large share of the total population and that proportion is predicted to expand over time. Adolescent contraceptive needs have largely been unmet, and with growing numbers, there is increased potential for negative health sequelae. Due to the low use of contraception by adolescents in Rwanda, and the growing population of adolescents, this study aims to explore the perspectives of family planning providers and adult modern contraceptive users on adolescent contraceptive use. Inclusion of adult community members in the study is a unique contribution, as research on adolescent contraceptive use in sub-Saharan Africa relies primarily on perspectives from adolescents and family planning providers. METHODS: This qualitative study in 2018 utilized 32 in-depth interviews with modern contraceptive users and eight focus group discussions with family planning providers. Respondents were from Musanze and Nyamasheke districts in Rwanda, the districts with the highest and lowest modern contraceptive use among married women, respectively. Coding was conducted in Atlas.ti. RESULTS: Stigma regarding premarital sex results in barriers to adolescent access to contraceptive services. Family planning providers do provide services to adolescents; however, they often recommend secondary abstinence, offer a limited method selection, and accentuate risks associated with sexual activity and contraceptive use. Providers support adolescent clients by emphasizing the need for privacy, confidentiality, and expedient services, particularly through youth corners, which are spaces within health facilities designed to meet youth needs specifically. Modern contraceptive-using adult female community members advocate for youth access to contraception, however mothers have mixed comfort discussing sexual health with their own youth. CONCLUSION: To destigmatize premarital sexual activity, government efforts to initiate communication about this topic must occur at national and community levels with the goal of continued conversation within the family. The government should also train family planning providers and all health personnel interacting with youth on adolescent-friendly health services. Dialogue between community members and family planning providers about adolescent access to contraceptive services could also reduce barriers for adolescents due to community members' generally supportive views on adolescent contraceptive use. Efforts to engage adolescent caregivers in how to talk to youth about sex could also contribute to expanded use.

In Rwanda, youth who are having sex use family planning less than married women. This study involved asking family planning providers and adults what they think about youth using family planning. Data for this study was collected in 2018, and included 32 interviews with adult family planning users and eight group discussions with family planning providers in two areas of Rwanda. The findings show that Rwandans believe youth should not have sex before they are married. Family planning providers do provide youth with services; however, they often push stopping sexual activity, offer a smaller selection of family planning methods, and exaggerate risks associated with sex and family planning use. Family planning providers support youth by honoring their need for privacy, keeping their secrets, and providing fast services so fewer people see them at the clinic. Providers like to help adolescents in youth corners, which are special spaces within health facilities just for youth. Importantly, adult women who use family planning want youth in their community to be able to use family planning, too. In order to respond to the issues raised, the Rwandan government can start conversations in villages and more broadly about the need for youth to have access to family planning. The government should also teach family planning providers and anyone who comes into contact with youth to offer helpful and friendly services. Setting up spaces for adults to talk with family planning providers about youth access to family planning could also contribute to fewer barriers to services for adolescents.

Redirecting Nonurgent Patients From the Pediatric Emergency Department to Their Pediatrician Office for a Same-Day Visit-A Quality Improvement Initiative.

OBJECTIVES: Providing high-quality care in the appropriate setting to optimize value is a worthy goal of an efficient health system. Consequences of managing nonurgent complaints in the emergency department (ED) have been described including inefficiency, loss of the primary care-patient relationship, and delayed care for other ED patients. The purpose of this initiative was to redirect nonurgent patients arriving in the ED to their primary care office for a same-day visit, and the SMART AIM was to increase redirected patients from 0% of those eligible to 30% in a 12-month period. METHODS: The setting was a pediatric ED (PED) and primary care office of a tertiary care pediatric medical system. The initiative utilized the electronic health record to identify and mediate the redirection of patients to the patient's primary care office after ED triage. The primary measurement was the percentage of eligible patients redirected. Additional measures included health benefits during the primary care visit (vaccines, well-visits) and a balancing measure of patients returned to the PED. RESULTS: The SMART AIM of >30% redirection was achieved and sustained with a final redirection rate of 46%. In total, 216 of 518 eligible patients were redirected, with zero untoward outcomes. The encounter time for redirected patients was similar for those who remained in the PED, and additional health benefits were appreciated for redirected patients. CONCLUSIONS: This initiative redirected nonurgent patients efficiently from a PED setting to their primary care office. The process is beneficial to patients and families and supports the patient-centered medical home. The balancing measure of no harm done to patients who accepted redirect reinforced the reliability of PED triage. The benefits achieved through the project highlight the value of the primary care-patient relationship and the continued need to improve access for patients and families.

Family planning providers and contraceptive users in Rwanda employ strategies to prevent discontinuation.

BACKGROUND: In Rwanda, nearly a third of contraceptive users discontinue within the first year of use. Family planning programs often focus more on recruitment of new users as opposed to maintaining use among current users. A focus on sustaining users and minimizing discontinuation is imperative for long-term family planning program success. This study explores the efforts providers and contraceptive users in Rwanda employ to prevent one of the greatest challenges to family planning programs: contraceptive discontinuation. METHODS: This was a qualitative study conducted in Rwanda between February and July 2018. It included eight focus group discussions with 88 family planning providers and 32 in-depth interviews with experienced modern contraceptive users. Data were collected in two districts with the highest (Musanze) and lowest (Nyamasheke) rates of contraceptive use. Data were analyzed using thematic content approach. RESULTS: Family planning providers in this study used the following strategies to prevent discontinuation: counseling new users on the potential for side effects and switching, reminding clients about appointments for resupply, as well as supporting dissatisfied users by providing counseling, medicine for side effects, and discussing options for switching methods. Users, on the other hand, employed the following strategies to prevent discontinuation: having an understanding that experiences of side effects vary by individuals, supporting peers to sustain use, persisting with use despite experiences of side effects, and switching methods. CONCLUSIONS: The strategies used by family planning providers and users in Rwanda to prevent discontinuation suggest the possibility of long-term sustained use of contraception in the country. Harnessing and supporting such strategies could contribute to sustaining or improving further contraceptive use in the country.

" the way we welcome them is how we will lead them to love family planning.": family planning providers in Rwanda foster compassionate relationships with clients despite workplace challenges.

BACKGROUND: Rwanda has markedly increased the nation's contraceptive use in a short period of time, tripling contraceptive prevalence in just 5 years between 2005 and 2010. An integral aspect of family planning programs is the interactions between family planning providers and clients. This study aims to understand the client-provider relationship in the Rwandan family planning program and to also examine barriers to those relationships. METHODS: This qualitative study in Rwanda utilized convenience sampling to include eight focus group discussions with family planning providers, both family planning nurses and community health workers, as well as in-depth interviews with 32 experienced modern contraceptive users. Study participants were drawn from the two districts in Rwanda with the highest and lowest modern contraceptive rates, Musanze and Nyamasheke, respectively Data analysis was guided by the thematic content approach, Atlas.ti 8 was utilized for coding the transcripts and collating the coding results, and Microsoft Excel for analyzing the data within code. RESULTS: Data analysis revealed that, despite workplace related challenges - including inadequate staffing, training, and resources, relationships between providers and clients are strong. Family planning providers work hard to understand, learn from, and support clients in their initiation and sustained use of contraceptives. CONCLUSION: Given the existing context of purposeful efforts on the part of family planning providers to build relationships with their clients, if the current level of government support for family planning service provision is enhanced, Rwanda will likely sustain many current users of contraception and engage even more Rwandans in contraceptive services in the future.

An examination of the barriers to and benefits from collaborative couple contraceptive use in Rwanda.

BACKGROUND: Supportive male involvement is strongly correlated with contraceptive use. In Rwanda, where the contraceptive prevalence rate among married women increased from 17 to 52% from 2005 to 2010, and stagnated at 53% in 2015, understanding the role of male partners in collaborative couple contraceptive use can help inform programs designed to further increase the use of contraception in Rwanda. METHODS: This study utilized qualitative methods in 2018, specifically 32 in-depth interviewers with mostly current users of modern contraceptive methods and eight focus group discussions with family planning providers-both family planning nurses and community health workers (CHWs). Respondents were from Musanze and Nyamasheke Districts, the districts with the highest and lowest modern contraceptive use, respectively, to explore the role of couple collaboration in family planning use in Rwanda. Data were analyzed using the thematic content approach in Atlas.ti (8). RESULTS: Findings demonstrate that some men are opposed to use of male methods of contraception, and some are opposed to any contraceptive use, which can lead to covert use. Women and providers prefer collaborative couple contraceptive use-as a result, providers advocate for and encourage male partner participation in contraceptive use. Women are most often burdened with seeking out information, initiating discussions, and sharing information discovered about contraceptive use with partners. Decision-making about contraceptive use, once discussed, can be collaborative and motivated by financial considerations. When couple contraceptive use is collaborative, benefits range from marital harmony to husband's support of sustained use through reminders about appointments, joint counseling, and support in managing side effects. CONCLUSION: Family planning providers at the community and clinic levels encourage collaborative contraceptive use among couples and some Rwandan couples communicate well about family planning use. Despite the positives, women are expected to source family planning information, share that information with their male partners, seek out family planning services, and use family planning. If more Rwandan male partners accepted use, used male methods of contraception, and participated even more in the work it takes to use family planning, the potential for sustained, and even enhanced, contraceptive use in Rwanda could be realized.

Enhancing Next-Generation Sequencing-Guided Cancer Care Through Cognitive Computing.

BACKGROUND: Using next-generation sequencing (NGS) to guide cancer therapy has created challenges in analyzing and reporting large volumes of genomic data to patients and caregivers. Specifically, providing current, accurate information on newly approved therapies and open clinical trials requires considerable manual curation performed mainly by human "molecular tumor boards" (MTBs). The purpose of this study was to determine the utility of cognitive computing as performed by Watson for Genomics (WfG) compared with a human MTB. MATERIALS AND METHODS: One thousand eighteen patient cases that previously underwent targeted exon sequencing at the University of North Carolina (UNC) and subsequent analysis by the UNCseq informatics pipeline and the UNC MTB between November 7, 2011, and May 12, 2015, were analyzed with WfG, a cognitive computing technology for genomic analysis. RESULTS: Using a WfG-curated actionable gene list, we identified additional genomic events of potential significance (not discovered by traditional MTB curation) in 323 (32%) patients. The majority of these additional genomic events were considered actionable based upon their ability to qualify patients for biomarker-selected clinical trials. Indeed, the opening of a relevant clinical trial within 1 month prior to WfG analysis provided the rationale for identification of a new actionable event in nearly a quarter of the 323 patients. This automated analysis took <3 minutes per case. CONCLUSION: These results demonstrate that the interpretation and actionability of somatic NGS results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing could potentially improve patient care by providing a rapid, comprehensive approach for data analysis and consideration of up-to-date availability of clinical trials. IMPLICATIONS FOR PRACTICE: The results of this study demonstrate that the interpretation and actionability of somatic next-generation sequencing results are evolving too rapidly to rely solely on human curation. Molecular tumor boards empowered by cognitive computing can significantly improve patient care by providing a fast, cost-effective, and comprehensive approach for data analysis in the delivery of precision medicine. Patients and physicians who are considering enrollment in clinical trials may benefit from the support of such tools applied to genomic data.

LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases.

PURPOSE: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. PATIENTS AND METHODS: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. RESULTS: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2-5). OS was 12.2 mos (95% CI 0.6-20.2). Grade 3-4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. CONCLUSION: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. CLINICAL TRIAL: (NCT01305941).

Planar xanthomas secondary to post-transplantation cholangiopathy in a 16-month-old boy.

Planar xanthomas in children represent rare dermatologic findings associated with abnormalities in lipid metabolism. While planar xanthomas in Alagille's syndrome have been well described in the literature, there have been no cases reported of eruptive xanthomas in pediatric liver transplant patients. Herein we report a case of a 16-month-old boy status post-liver transplantation who presents with planar xanthomas secondary to cholangiopathy. A brief review of xanthomas and the related literature is also provided.

Esophageal contractions in type 3 achalasia esophagus: simultaneous or peristaltic?

Absence of peristalsis and impaired relaxation of lower esophageal sphincter are the hallmarks of achalasia esophagus. Based on the pressurization patterns, achalasia has been subdivided into three subtypes. The goal of our study was to evaluate the esophageal contraction pattern and bolus clearance in type 3 achalasia esophagus. High-resolution manometry (HRM) recordings of all patients diagnosed with achalasia esophagus in our center between the years 2011 and 2013 were reviewed. Recordings of 36 patients with type 3 achalasia were analyzed for the characteristics of swallow-induced "simultaneous esophageal contraction." The HRM impedance recordings of 14 additional patients with type 3 achalasia were analyzed for bolus clearance from the impedance recording. Finally, the HRM impedance along with intraluminal ultrasound imaging was conducted in six patients to further characterize the simultaneous esophageal contractions. Among 187 achalasia patients, 30 were type 1, 121 type 2, and 36 type 3. A total of 434 swallows evaluated in type 3 achalasia patients revealed that 95% of the swallow-induced contractions met criteria for simultaneous esophageal contraction, based on the onset of contraction. Interestingly, the peak and termination of the majority of simultaneous esophageal contractions were sequential. The HRM impedance revealed that 94% of the "simultaneous contractions" were associated with complete bolus clearance. Ultrasound image analysis revealed that baseline muscle thickness of patients in type 3 achalasia is larger than normal but the pattern of axial shortening is similar to that in normal subjects. The majority of esophageal contractions in type 3 achalasia are not true simultaneous contractions because the peak and termination of contraction are sequential and they are associated with complete bolus clearance.

Circular and longitudinal muscles shortening indicates sliding patterns during peristalsis and transient lower esophageal sphincter relaxation.

Esophageal axial shortening is caused by longitudinal muscle (LM) contraction, but circular muscle (CM) may also contribute to axial shortening because of its spiral morphology. The goal of our study was to show patterns of contraction of CM and LM layers during peristalsis and transient lower esophageal sphincter (LES) relaxation (TLESR). In rats, esophageal and LES morphology was assessed by histology and immunohistochemistry, and function with the use of piezo-electric crystals and manometry. Electrical stimulation of the vagus nerve was used to induce esophageal contractions. In 18 healthy subjects, manometry and high frequency intraluminal ultrasound imaging during swallow-induced esophageal contractions and TLESR were evaluated. CM and LM thicknesses were measured (40 swallows and 30 TLESRs) as markers of axial shortening, before and at peak contraction, as well as during TLESRs. Animal studies revealed muscular connections between the LM and CM layers of the LES but not in the esophagus. During vagal stimulated esophageal contraction there was relative movement between the LM and CM. Human studies show that LM-to-CM (LM/CM) thickness ratio at baseline was 1. At the peak of swallow-induced contraction LM/CM ratio decreased significantly (<1), whereas the reverse was the case during TLESR (>2). The pattern of contraction of CM and LM suggests sliding of the two muscles. Furthermore, the sliding patterns are in the opposite direction during peristalsis and TLESR.

Histomorphologic analysis of ovarian tumors according to the New 2020 WHO classification of female genital tumors.

INTRODUCTION: In terms of female genital tract-related cancers, ovarian tumors account for 3% of all tumors. On the basis of gross, radiological, and clinical features alone, ovarian neoplasms cannot be diagnosed. Therefore, a clear histological diagnosis is necessary before beginning a permanent course of therapy. SETTINGS AND DESIGN: Cross-sectional analytical study. MATERIAL AND METHODS: In this ambispective study, a total of 480 patients with ovarian tumors were included from January 2015 to July 2022 at a tertiary care center in western Maharashtra. STATISTICAL ANALYSIS USED: Descriptive statistics-percentages, mean, and Chi-square test (to calculate P value) were used to analyze the collected data. AIM: To determine clinical presentation, age distribution and incidence of various morphological and histological variants of ovarian tumors. RESULTS: Out of 480, 250 cases (52%) in 41-50 years of age, followed by 154 cases (32%) in 21-30 years of age. Our study showed 301 cases of benign, 42 cases of borderline, and 137 cases of malignant neoplasms of ovary out of 480 cases studied. Out of 480 cases, 244 cases (50.83%) were cystic, 138 cases (28.75%) were solid, and 98 cases (20.42%) were mixed (cystic/solid). Out of 480 cases, 326 cases (67.91%) were surface epithelial ovarian neoplasms. In this research, most frequent ovarian neoplasms were serous tumors in 216 cases (45%) followed by mucinous tumors in 78 cases (16.25%). In 96% cases, clinical diagnosis matched with histopathological diagnosis. CONCLUSION: In our research, benign ovarian neoplasms were most frequent. Serous tumors were the most frequent type of surface epithelial neoplasms followed by mucinous tumors. Peak incidence was seen in fifth decade. Higher risk of malignancy was seen in nulliparity or low parity and early menarche not associated with risk of malignancy. Cystic morphology more common in benign neoplasms and complex or solid morphology showed greatest increase in incidence of malignancy. Latest WHO classification has important impact on prognosis and therapy of the patient.

Urothelial Carcinoma With Bone Metastasis Mimicking Sciatica: A Common Neoplasm With an Uncommon Presentation.

Bone metastasis in urothelial cancer is underreported and not well-researched. A case of urothelial carcinoma (UC) with bone metastasis presenting as musculoskeletal pain is reported. The patient presented with persistent lower back pain associated with right lower extremity pain, numbness, and tingling. Initially, a diagnosis of sciatica was suspected, but the patient did not respond to treatment. An MRI spine was done, which revealed a bright signal mass in the vertebral body suspicious for a metastatic lesion, left hydroureteronephrosis, and a nonspecific cystic focus in the right iliacus muscle. Subsequent imaging revealed an irregular soft tissue mass at the left posterolateral bladder base, resulting in apparent obstruction of the left ureter, highly suggestive of neoplasm, along with numerous lytic bone lesions in the pelvic girdle with associated soft tissue masses, consistent with metastatic disease. The patient underwent an interventional radiology biopsy of the right iliac soft tissue mass to evaluate the lytic bony lesions, which revealed metastatic carcinoma, consistent with UC. A prompt referral was made for urology and oncology consultations. The patient underwent left percutaneous nephrostomy placement for obstruction, but he was not a candidate for any systemic therapy because of his poor performance status, and hospice was recommended as his metastatic disease was not curable and the goal of any kind of treatment was palliative. The optimal treatment for UC with bone metastasis remains divergent, and the management options should be determined as part of a shared decision-making process. This case highlights the importance of having a high suspicion of neoplastic pathology in patients presenting with musculoskeletal pain, like back pain, and not responding to treatment. This should alert the physicians to the potential for serious disease processes.