27-Hydroxycholesterol acts on estrogen receptor α expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior.

Oxysterols are metabolites of cholesterol that regulate cholesterol homeostasis. Among these, the most abundant oxysterol is 27-hydroxycholesterol (27HC), which can cross the blood-brain barrier. Because 27HC functions as an endogenous selective estrogen receptor modulator, we hypothesize that 27HC binds to the estrogen receptor α (ERα) in the brain to regulate energy balance. Supporting this view, we found that delivering 27HC to the brain reduced food intake and activated proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (POMCARH) in an ERα-dependent manner. In addition, we observed that inhibiting brain ERα, deleting ERα in POMC neurons, or chemogenetic inhibition of POMCARH neurons blocked the anorexigenic effects of 27HC. Mechanistically, we further revealed that 27HC stimulates POMCARH neurons by inhibiting the small conductance of the calcium-activated potassium (SK) channel. Together, our findings suggest that 27HC, through its interaction with ERα and modulation of the SK channel, inhibits food intake as a negative feedback mechanism against a surge in circulating cholesterol.

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.

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.

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.

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.

First use of intraventricular nicardipine in a pediatric patient with vasospasm secondary to meningitis: illustrative case.

BACKGROUND: Cerebral vasospasm is commonly associated with adult aneurysmal subarachnoid hemorrhage but can develop in children. The standard vasospasm treatment includes induced hypertension, avoidance of hypovolemia, systemic use of the calcium channel blocker (CCB) nimodipine, and cerebral angiography for intraarterial therapy. Emerging treatments in adults, such as intraventricular CCB administration, have not been investigated in children. This study demonstrates the successful use of an intraventricular CCB in a pediatric patient with refractory vasospasm secondary to meningitis. OBSERVATIONS: A 12-year-old female presented with Streptococcus pneumoniae meningitis and ventriculitis with refractory symptomatic cerebral vasospasm. She received a 5-day course of intrathecal nicardipine through an existing external ventricular drain. Her clinical status, transcranial Doppler studies, and radiography improved. Treatment was well tolerated. LESSONS: Pediatric vasospasm is uncommon and potentially devastating. The management of vasospasm in adults occurs frequently. Principles of this management are adapted to pediatric care given the rarity of vasospasm in children. The use of intraventricular nicardipine has been reported in the care of adults with level 3 evidence. It has not been adequately reported in children with refractory vasospasm. Here, the first use of intraventricular nicardipine in treating pediatric cerebral vasospasm in the setting of meningitis is described and highlighted.

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.

A comparison of the WHO 2004 and WHO 2017 thyroid tumor classifications.

INTRODUCTION: The category of borderline malignancy or unknown malignant potential was added to the WHO's 2017 classification of thyroid tumours. A new histological variety of papillary tumours and Hurthle cell tumours was given as a separate entity. The classification has also adopted the Turin criteria for histological diagnosis of poorly differentiated cancer (PDC). SETTINGS AND DESIGN: Descriptive study. METHODS AND MATERIAL: From July 2018 to June 2022, 200 thyroid neoplasm patients at a tertiary care facility in western Maharashtra were participated in the prospective research over a period of 4 years. STATISTICAL ANALYSIS USED: The descriptive statistics were used to analyse the collected data. AIM: This study was undertaken to compare the old (2004) and new (2016) WHO classifications and their importance in the treatment of thyroid malignancies. RESULTS: Out of 200 cases, the age range of 31 to 40 years had the greatest number of cases. The ratio of females to males was 5:1. In our study, according to the WHO 2004 classification, malignant tumours comprised 57.5% of the cases, while benign tumours 42.5% of the cases. When tumours were subcategorized, the most frequent benign tumour was follicular adenoma (43.5%) and malignant tumour was papillary thyroid carcinoma (37%). Malignant tumours made up 47.5% of the cases when the tumours were reclassified using the revised WHO 2017 classification, followed by borderline tumours with 27.5% of the cases and benign tumours with 25% of the cases. The most frequent borderline tumour was NIFTP (Noninvasive follicular thyroid neoplasm with papillary-like nuclear features) (17.5%), the most prevalent malignant tumour was papillary carcinoma (including its variant) (32%), and the most frequent benign tumour was follicular adenoma (27%). CONCLUSION: We concluded that the inclusion of the Boderline Category in the new WHO classification significantly improved thyroid cancer management. WHO 2017 classification prevents under diagnosis (in the case of benign tumors) and over diagnosis (in the case of malignant tumors).

Estrogen signaling in the dorsal raphe regulates binge-like drinking in mice.

Estrogens promote binge alcohol drinking and contribute to sex differences in alcohol use disorder. However, the mechanisms are largely unknown. This study aims to test if estrogens act on 5-hydroxytryptamine neurons in the dorsal raphe nucleus (5-HTDRN) to promote binge drinking. We found that female mice drank more alcohol than male mice in chronic drinking in the dark (DID) tests. This sex difference was associated with distinct alterations in mRNA expression of estrogen receptor α (ERα) and 5-HT-related genes in the DRN, suggesting a potential role of estrogen/ERs/5-HT signaling. In supporting this view, 5-HTDRN neurons from naïve male mice had lower baseline firing activity but higher sensitivity to alcohol-induced excitation compared to 5-HTDRN neurons from naïve female mice. Notably, this higher sensitivity was blunted by 17ß-estradiol treatment in males, indicating an estrogen-dependent mechanism. We further showed that both ERα and ERß are expressed in 5-HTDRN neurons, whereas ERα agonist depolarizes and ERß agonist hyperpolarizes 5-HTDRN neurons. Notably, both treatments blocked the stimulatory effects of alcohol on 5-HTDRN neurons in males, even though they have antagonistic effects on the activity dynamics. These results suggest that ERs' inhibitory effects on ethanol-induced burst firing of 5-HTDRN neurons may contribute to higher levels of binge drinking in females. Consistently, chemogenetic activation of ERα- or ERß-expressing neurons in the DRN reduced binge alcohol drinking. These results support a model in which estrogens act on ERα/ß to prevent alcohol-induced activation of 5-HTDRN neurons, which in return leads to higher binge alcohol drinking.

Socioeconomic status is associated with pediatric adenotonsillectomy outcomes: A single institution study.

OBJECTIVE: Our institution serves a diverse patient population across a large metropolitan city. Literature has shown pediatric otolaryngology patients with lower socioeconomic status (SES) have higher rates of sleep-disordered breathing, delays in treatment time, and greater risks of complications post-tonsillectomy. This study aims to examine the effects of SES on adenotonsillectomy outcomes performed at our institution. STUDY DESIGN: A retrospective chart review including 1560 pediatric patients (ages 0-18) who underwent adenotonsillectomy between January 2015 and December 2020. SETTING: Large metropolitan hospital, level 1 trauma center. METHODS: Outcome variables included postoperative hospital admission, phone calls, 30-day follow-up, and persistent obstructive sleep apnea (OSA). Descriptive statistics using Wilcoxon Signed Rank Tests and univariate and multivariate logistic regression modeling were used to determine statistically significant covariates at α = 0.05. RESULTS: The cohort included Non-Hispanic White (n = 488, 31 %), Non-Hispanic Black (n = 801, 51 %), Hispanic (n = 210, 13 %), and other (n = 61, 4 %) groups. Using multivariate regression, privately insured patients were less likely to have moderate-to-severe OSA before surgery (0.65 95 % CI 0.45, 0.93 p = 0.017) and be admitted postoperatively (0.73, 0.55-0.96, p < 0.01), while more likely to have postoperative follow-up phone calls (1.57, 1.19-2.09, p < 0.01) and visits (1.53, 1.22-1.92, p < 0.01). Increased income was associated with decreased rehospitalizations within three months of surgery (0.98, 0.97-1.00, p < 0.01). CONCLUSION: This study suggests SES significantly affects adenotonsillectomy outcomes. Further studies are warranted to provide better care for all pediatric patients.

Socioeconomic Disparities Affecting the Presentation and Outcomes in Pediatric Subdural Empyema Patients.

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.

Cervical corpectomy in a pediatric patient with chondrodysplasia punctata and C5 dysplasia with spinal cord compression: illustrative case.

BACKGROUND: Chondrodysplasia punctata (CDP) describes skeletal dysplasia secondary to a variety of genetic underpinnings characterized by cartilaginous stippling from abnormal calcium deposition during endochondral bone formation. Approximately 20%-38% of patients with CDP have cervical spine abnormalities, resulting in stenosis and cord compression. However, approaches to management differ among patients. OBSERVATIONS: The authors present an 18-year-old male with a known history of CDP and cervical kyphosis with worsening paresthesias and increased spasticity. Imaging confirmed dysplastic C4 and C5 vertebra with focal kyphosis, bony retropulsion, spinal cord compression, and myelomalacia. To treat the stenosis and deformity, the patient underwent C4 and C5 vertebrectomies with C3 to C6 anterior fusion with resolution of symptoms. LESSONS: Despite many CDP patients having cervical deformities with spinal cord compression and associated neurological symptoms, there is a paucity of data on surgical management and outcomes. There are only scattered reports, and most authors recommend initial conservative management because of the high risk of operative morbidity and mortality secondary to comorbidities. When surgery is performed, long-term follow-up is recommended because of the high rates of progression of deformity, requiring subsequent operations. The authors hope that their experience adds to the literature describing the surgical management of cervical deformities in these patients.

From Gut to Glucose: A Comprehensive Review on Functional Foods and Dietary Interventions for Diabetes Management.

BACKGROUND: In the realm of diabetes research, considerable attention has been directed toward elucidating the intricate interplay between the gastrointestinal tract and glucose regulation. The gastrointestinal tract, once exclusively considered for its role in digestion and nutrient assimilation, is presently acknowledged as a multifaceted ecosystem with regulatory supremacy over metabolic homeostasis and glucose metabolism. Recent studies indicate that alterations in the composition and functionality of the gut microbiota could potentially influence the regulation of glucose levels and glucose homeostasis in the body. Dysbiosis, characterized by perturbations in the equilibrium of gut microbial constituents, has been irrevocably linked to an augmented risk of diabetes mellitus (DM). Moreover, research has revealed the potential influence of the gut microbiota on important factors, like inflammation and insulin sensitivity, which are key contributors to the onset and progression of diabetes. The key protagonists implicated in the regulation of glucose encompass the gut bacteria, gut barrier integrity, and the gut-brain axis. A viable approach to enhance glycemic control while concurrently mitigating the burden of comorbidities associated with diabetes resides in the strategic manipulation of the gut environment through adapted dietary practices. OBJECTIVE: This review aimed to provide a deep understanding of the complex relationship between gut health, glucose metabolism, and diabetes treatment. CONCLUSION: This study has presented an exhaustive overview of dietary therapies and functional foods that have undergone extensive research to explore their potential advantages in the management of diabetes. It looks into the role of gut health in glucose regulation, discusses the impact of different dietary elements on the course of diabetes, and evaluates how well functional foods can help with glycemic control. Furthermore, it investigates the mechanistic aspects of these therapies, including their influence on insulin sensitivity, ß-cell activity, and inflammation. It deliberates on the limitations and potential prospects associated with integrating functional foods into personalized approaches to diabetes care.

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.

A Comparison of Conventional Pap Smear and Liquid-Based Cytology for Cervical Cancer Screening.

Objectives: Early diagnosis and treatment of preinvasive lesions have made cervical cytology one of the most effective methods of cancer screening in industrialized nations, which have seen a sharp decline in the incidence and death of invasive cancer. The aim of this study is to compare liquid-based cytology (LBC) and conventional Pap on cervical smears. Materials and Methods: From July 2018 to June 2022, 600 patients were included in this cross-sectional study, which was done at the Pathology Department of a Tertiary Care Facility in Western Maharashtra. Results: Of the 600 patients, 570 (95%) had good conventional Pap smear (CPS), whereas 30 (5%) had poor ones. Five hundred and ninety-two (98.6%) LBC smears were satisfactory, whereas 8 (1.4%) were unsatisfactory. Endocervical cells were seen in 294 (49%) CPS, whereas 360 (60%) LBC smears showed endocervical cells. The morphology of inflammatory cells was similar in both techniques. Hemorrhagic background was seen in 212 (35%) CPS and 76 (12.6%) LBC smears. Only two samples showed diathetic background, which was seen on both CPS and smear. Out of the satisfactory smears in the case of CPS, 512 (85%) cases were reported as negative for intraepithelial lesion or malignancy (NILM), whereas 58 (9.7%) cases were reported as epithelial cell abnormality. In LBC smears, 526 (87.3%) were reported as NILM, whereas 66 (11%) were reported as epithelial cell abnormality. Organisms were detected in 208 (34%) CPS and 162 (27%) LBC smears. Screening time was 5 ± 1 min for CPS, whereas it was 3 ± 1 min for LBC smear. Conclusion: Mortality will be decreased using LBC on a bigger scale in nations where many smears can be made and screened in a short amount of time, with the provision of doing human papillomavirus-based testing on the remaining sample.

Personalizing Surveillance in Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) encompasses a spectrum of heterogeneous diseases originating in the oral cavity, pharynx, and larynx. Within the United States, head and neck cancer (HNC) accounts for 66,470 new cases, or 3% of all malignancies, annually.1 The incidence of HNC is rising, largely driven by increases in oropharyngeal cancer.2-4 Recent molecular and clinical advancements, particularly with regard to molecular and tumor biology, reflect the heterogeneity of the subsites contained within the head and neck. Despite this, existing guidelines for post-treatment surveillance remain broad without much consideration given to different anatomic subsites and etiologic factors (such as human papillomavirus [HPV] status or tobacco exposure).5 Surveillance incorporating the physical examination, imaging, and emerging molecular biomarkers is an essential part of care for patients treated for HNC and allows for the detection of locoregional recurrence, distant metastases, and second primary malignancies aiming for better functional and survival outcomes. Additionally, it allows for evaluation and management of post-treatment complications.

Use of intraoperative topical antibiotics to reduce intrathecal baclofen pump surgical site infections: a single institution's experience over 24 years.

OBJECTIVE: Patients requiring intrathecal baclofen (ITB) therapy are at high risk for surgical site infections (SSIs) given their poor functional status. After years of a nominal infection rate, there was an inexplicable increase in ITB pump infections at the authors' institution and multiple investigations offered no solution. Use of intraoperative topical antibiotics is well-documented in the orthopedic literature and was considered for ITB pump insertion. In this study, the authors investigated whether intraoperative vancomycin and tobramycin powder at the ITB pump site could reduce SSIs. METHODS: Operative and infection data were collected and analyzed retrospectively to determine the efficacy of this change. Patients were stratified into three cohorts (1998-2009, 2010-2012, and 2013-2021) to better understand the trends before and after implementation of intraoperative topical antibiotics. Each cohort had similar demographics. RESULTS: One hundred fifty-four patients underwent 272 ITB pump procedures between 1998 and 2021 (131 in 1998-2009, 49 in 2010-2012, and 92 in 2013-2021) for cerebral palsy (69.5%), spastic quadriparesis due to traumatic brain injury (7.1%), anoxic brain injury (6.5%), and other causes (16.9%). Infection rates were reduced from a high of 32% in 2010-2011 to 3.8% over the last 2.5 years (p = 0.0094). There were no adverse effects from the use of topical antibiotics. CONCLUSIONS: In the setting of an intractable rise in ITB pump infections, the addition of intraoperative topical antibiotics significantly reduced postoperative infections in a high-risk population. One could appreciate a significant drop each year in the rate of infections after the institution of intraoperative topical antibiotics. The reduction in SSIs significantly improved the long-term outcomes for these patients.

Moisture sorption by polymeric excipients commonly used in amorphous solid dispersions and its effect on glass transition temperature: III. Methacrylic acid-methyl methacrylate and related copolymers (Eudragit®).

Moisture sorption by polymeric carriers used in amorphous solid dispersion (ASD) plays a critical role in the physical stability of the dispersed drug as it can increase molecular mobility of drug in ASD by decreasing the glass transition temperatures (Tg) of the drug-polymer system, leading to drug crystallization. The present report describes Part III of a systematic investigation of moisture sorption by different polymers used in ASDs, where the results for four chemically different methacrylic acid-methyl methacrylate and related copolymers, namely, Eudragit® EPO, Eudragit® L100-55, Eudragit® L100, and Eudragit® S100, as the function of relative humidity (RH) are presented. Effects of moisture sorption on Tg of the polymers were also determined. Among the polymers, Eudragit® EPO is the least hygroscopic, having absorbed, for example, 1.3% w/w moisture at 25 °C/60% RH, while the three other polymers absorbed 4.7-7.5% w/w moisture at the same condition. The moisture sorption was relatively lower at 40 °C than that at 25 °C. The apparent Tg of polymers decreased with the increase in moisture content; however, Tg values remained higher than the usual storage temperature of ASD (25 °C) even at high RH, indicating that the effect of moisture sorption on the physical stability of ASD could be minimal when these polymers are used in ASDs.

Surveillance imaging and early surgical intervention for improved CNS tumor outcomes in children with Li-Fraumeni syndrome: Children's National Hospital experience and literature review.

OBJECTIVE: Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome caused by germline mutations in the TP53 gene. CNS tumors are the fourth most common tumor type in LFS, and recent screening guidelines demonstrate that early tumor detection is associated with improved long-term survival. However, there is a paucity of data regarding surgical intervention when lesions are identified in asymptomatic patients on surveillance imaging. The authors investigated this through their cohort and literature review. METHODS: The cohort consisted of children seen in the Pediatric Cancer Genetics Program at Children's National Hospital between August 2012 and August 2021. The authors also include a PubMed (MEDLINE) literature search of articles from 2006 to 2021 related to surveillance and CNS tumors in patients with LFS. Studies in which CNS tumors were not identified or detailed patient information was not provided were excluded. Patients from the selected articles and the authors' cohort were added for further analysis. RESULTS: Between August 2012 and August 2021, 10 children with LFS and CNS tumors were assessed at Children's National Hospital: 4 who were known carriers of the TP53 mutation had CNS lesions found on surveillance imaging, whereas 6 presented with symptomatic CNS lesions and were either known or subsequently found to have germline TP53 mutations. The literature search identified 148 articles, 7 of which were included in this review. Patients from the literature and the present cohort were added for a total of 56 CNS lesions. A majority of the low-grade CNS lesions (22/24, 92%) were found on surveillance protocols in asymptomatic patients, whereas the majority of the high-grade lesions (22/26, 85%) presented in symptomatic patients who were not undergoing routine surveillance or as the initial diagnosis of LFS. The authors noted a significant survival advantage in pediatric patients with low-grade lesions, with an overall survival of 100% at 30 months. Minor limitations of the study include patient sample size and limitations in the patient cohort due to this being a retrospective rather than a prospective study. CONCLUSIONS: Data presented in this study support surveillance protocols in LFS and demonstrate the importance of dedicated CNS imaging and early surgical intervention when lesions are identified. Systematic review registration no.: CRD42022372610 (www.crd.york.ac.uk/prospero).

Utility of prolonged prophylactic systemic antibiotics for wound drains in posterior spine surgery: a systematic review and meta-analysis.

OBJECTIVE: Closed suction drains, often used after posterior spinal surgery, pose a potential risk of infection. To combat this risk, many surgeons opt for a prolonged prophylactic antibiotic regimen. Since 2015, several studies have shown that prolonged prophylactic systemic antibiotics (PPSA) for drains provides no additional benefit in reducing surgical site infection (SSI) rates. However, most of these studies lacked sufficient power to make reliable conclusions. To date, there has been no meta-analysis conducted to further investigate this issue. The aim of this study was to investigate whether a regimen of PPSA reduces the incidence of deep SSIs in adult patients with closed suction drains following posterior spinal surgeries. METHODS: The protocol of the current systematic review was registered with PROSPERO. A systematic review of the literature in PubMed (Medline), Europe PMC, Embase, and Cochrane Review databases was conducted for all relevant literature with the keywords "spine," "antibiotics," "surgical site infection," "prophylaxis," and "drain." Retrospective and prospective studies investigating the effectiveness of PPSA in patients 18 years or older who underwent posterior cervical or thoracolumbar surgery and had postoperative wound drains were included. The primary outcome was the odds ratio for deep SSI based on the intervention (PPSA vs non-PPSA). The secondary outcomes were the rates of superficial and overall SSIs. RESULTS: From a total of 2558 titles identified from the search, 7 studies were chosen for final analysis. Three were randomized controlled trials (RCTs), and 4 were retrospective reviews. A total of 2446 patients were analyzed; 1149 received a PPSA regimen and 1297 received a non-PPSA regimen. Deep SSIs occurred in 45 patients (3.9%) and 46 patients (3.5%) in the PPSA and non-PPSA groups, respectively. The odds ratio for deep SSIs in the PPSA group compared with the non-PPSA group was 1.10 (95% CI 0.69-1.74), which was not statistically significant. Additionally, there were no differences in the rates of superficial and overall SSIs. There was a trend toward increased infections with multidrug-resistant bacteria (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus) in the PPSA group; however, it was not possible to perform a durable statistical analysis because of the small number of reported organisms in the selected publications. CONCLUSIONS: This meta-analysis demonstrates that there is no reduction in rate of deep, superficial, and overall SSIs with prolonged prophylactic antibiotics after posterior spinal surgery involving the use of closed suction drains.