Twenty-first Century Trends in the Global Epidemiology of Pediatric-Onset Inflammatory Bowel Disease: Systematic Review.

BACKGROUND & AIMS: The incidence of inflammatory bowel disease (IBD) is increasing internationally, particularly in nations with historically low rates. Previous reports of the epidemiology of pediatric-onset IBD identified a paucity of data. We systematically reviewed the global trends in incidence and prevalence of IBD diagnosed in individuals <21 years old over the first 2 decades of the 21st century. METHODS: We systematically reviewed studies indexed in MEDLINE, EMBASE, Airiti Library, and SciELO from January 2010 to February 2020 to identify population-based studies reporting the incidence and/or prevalence of IBD, Crohn's disease, ulcerative colitis, and/or IBD-unclassified. Data from studies published before 2000 were derived from a previously published systematic review. We described the geographic distribution and trends in children of all ages and limiting to very early onset (VEO) IBD. RESULTS: A total of 131 studies from 48 countries were included. The incidence and prevalence of pediatric-onset IBD is highest in Northern Europe and North America and lowest in Southern Europe, Asia, and the Middle East. Among studies evaluating trends over time, most (31 of 37, 84%) studies reported significant increases in incidence and all (7 of 7) reported significant increases in prevalence. Data on the incidence and prevalence of VEO-IBD are limited to countries with historically high rates of IBD. Time trends in the incidence of VEO-IBD were visually heterogeneous. CONCLUSIONS: Rates of pediatric-onset IBD continue to rise around the world and data are emerging from regions where it was not previously reported; however, there remains a paucity of data on VEO-IBD and on pediatric IBD from developing and recently developed countries.

OnabotulinumtoxinA Injections for the Treatment of Myofascial Pelvic Pain: 12-Year Experience at a Tertiary Care Academic Center.

OBJECTIVE: The aim of this study was to highlight the safety of OnabotulinumtoxinA (BTA) injections, with or without concurrent pudendal nerve block, in treating women with myofascial pelvic pain (MFPP). DESIGN: This was a retrospective cohort study. SETTING: The review was conducted in a tertiary care academic center. Participants/Materials: We conducted a chart review of patients who were diagnosed with MFPP and treated with BTA with or without pudendal nerve block between January 2010 and February 2022. METHODS: BTA was injected transvaginally into the pelvic floor muscle group. The primary outcomes were adverse events after BTA injections, and the secondary outcome was the effect of concomitant pudendal nerve block at the time of BTA injections. RESULTS: The cohort included 182 patients; 103 (56.6%) received BTA injections with pudendal nerve block, and 79 (43.4%) received BTA alone. There were no significant demographic differences between the two groups. Post-treatment complications of BTA administration included worsening of pelvic pain (11.5%), constipation (6.6%), urinary tract infection (2.7%), urinary retention (3.8%), and fecal incontinence (2.7%). No statistical difference was noted in the number of phone calls, patient-initiated electronic messages, emergency room visits, or clinic visits for both groups within 30 days post-treatment. The mean number of total injections was 1.6 in the BTA-only group and 1.7 in the BTA with pudendal block group (p = 0.421). Median time to re-intervention with a second BTA injection was 6.0 months; 5.6 months in the BTA with pudendal block group; and 6.8 months in the BTA-only group, p = 0.46. There were 63 re-intervention events after BTA injections. LIMITATIONS: Limitations of our study include the retrospective design making it vulnerable to missing or incomplete data available for review. CONCLUSION: OnabotulinumtoxinA is beneficial in treating women with MFPP; with a duration of therapeutic effect of approximately 6 months. The use of a concurrent pudendal nerve block did not impact clinical outcomes.

Ventriculo-inferior-venacaval shunt salvage via endovascular surgery.

INTRODUCTION: Hydrocephalus treatment can be very challenging. While some hydrocephalic patients can be treated endoscopically, many will require ventricular shunting. Frequent shunt issues over a lifetime is not uncommon. Although most shunt malfunctions are of the ventricular catheter or valve, distal failures occur as well. A subset of patients will accumulate non-functioning distal drainage sites. CASE DESCRIPTION: We present a 27-year-old male with developmental delay who was shunted perinatally for hydrocephalus from intraventricular hemorrhage of prematurity. After failure of the peritoneum, pleura, superior vena cava (SVC), gallbladder, and endoscopy, an inferior vena cava (IVC) shunt was placed minimally-invasively via the common femoral vein. We believe this is only the eighth reported ventriculo-inferior-venacaval shunt. IVC occlusion years later was successfully treated with endovascular angioplasty and stenting followed by anticoagulation. To our knowledge, a ventriculo-inferior-venacaval shunt salvaged by endovascular surgery has not been previously described in the literature. CONCLUSION: After failure of the peritoneum, pleura, SVC, gallbladder, and endoscopy, IVC shunt placement is an option. Subsequent IVC occlusion can be rescued by endovascular angioplasty and stenting. Anticoagulation after stenting (and potentially after initial IVC placement) is advised.

Internet search results correlate with seasonal variation of sarcoidosis.

BACKGROUND: The etiology and pathophysiology of sarcoidosis remains unclear, with epidemiologic studies limited by its relatively low prevalence. The internet has prompted patients to seek information about medical diagnoses online; Google Trends provides access to an anonymized version of this data, which has a new role in epidemiology. We hypothesize that there is seasonal variation in the relative search interest of sarcoidosis, which would suggest seasonal variation in the incidence of sarcoidosis. METHODS: Google Trends was used to assess the relative search volume from 2010 to 2020 for "sarcoidosis" and "sarcoid" in 7 countries. ANOVA with multiple comparisons was performed to compare the mean relative search volume by month and by season for each country, with a p-value less than 0.05 indicating statistical significance. RESULTS: Our analysis revealed a significant seasonal variation in search popularity in 4 of the 7 countries and in the Northern Hemispheric countries combined. Direct comparison showed search terms to be more popular in spring, specifically March & April, than in the winter. Southern Hemisphere data was not statistically significant but showed a trend towards a nadir in December and a peak in September and October. CONCLUSIONS: Overall, these findings suggest seasonal variation with a possible peak in spring and nadir in winter. This supports the hypothesis that sarcoidosis has seasonal variation and is more commonly diagnosed in spring, but more evidence is needed to support this, as well as investigation into the pathophysiology of sarcoidosis to explain this phenomenon.

Impact of Legislation on Opioid Prescribing following Hysterectomy and Hysteroscopy in Arizona and Florida.

OBJECTIVES: This study aimed to determine the oral morphine equivalents (OMEs) prescribed and refill rates following hysterectomy and hysteroscopy in the setting of opioid prescribing practice changes in 2 states. DESIGN: This is a retrospective cohort analysis consisting of 2,916 patients undergoing hysterectomy or hysteroscopy between July 2016 and September 2019 at 2 affiliated academic hospitals in states that underwent legislative changes in opioid prescribing in 2018. METHODS: Participants were identified using the Current Procedural Terminology procedure codes in Arizona and Florida. Hysterectomy was chosen as the most invasive gynecologic procedure, while hysteroscopy was chosen as the least invasive. Medical records were abstracted to find opioid prescriptions from 90 days before surgery to 30 days after discharge. Patients with opioid use between 90 and 7 days before surgery were excluded. Prescriptions were converted to OMEs and were calculated per quarter year. Statistical analysis included Wilcoxon rank sum t tests for OMEs and χ2 t tests for refill rates. Interrupted time-series analysis was used to determine significant change in OMEs before and after legislative change. Statistical analysis was performed using SAS version 9.4 (SAS Institute, Cary, NC, USA). RESULTS: In Arizona, 1,067 hysterectomies were performed; 459 (43%) vaginal, 561 (52.6%) laparoscopic/robotic, and 47 (4.4%) abdominal. There were 530 hysteroscopies. Overall median OMEs decreased from 225 prior to July 2018 to 75 after July 2018 (p < 0.0001). The opioid refill rate remained unchanged at 7.4% (p = 0.966). In Florida, there were 769 hysterectomies; 241 (31.3%) vaginal, 476 (61.9%) laparoscopic/robotic, and 52 (6.8%) abdominal. There were 549 hysteroscopies. Overall median OMEs decreased from 150 prior to July 2018 to 0 after July 2018 (p < 0.0001). The opioid refill rate was similar (7.8% before July 2018 and 7.3% after July 2018; p = 0.739). LIMITATIONS: Limitations include involvement of a single hospital institution with a total of 10 fellowship-trained surgeons and biases inherent to retrospective study design. CONCLUSIONS: Legislative and provider-led changes coincided with decreases in opioid prescribing after 2018 in both states without increasing rates of refills and showed actual data reflected in the medical record. Gynecologists must actively participate in safe prescribing practices to decrease opioid dependence and misuse.

Attacked and Shaken by a Dog: A Cause of Traumatic Brain and Carotid Injury in an Infant.

BACKGROUND: Posttraumatic carotid artery dissection (PTCAD) is a common injury in motor vehicle accidents and other extension and rotation injuries, but rarely developed from being shaken vigorously. CASE DESCRIPTION: A 7-day-old infant presented to our facility after being attacked by a large dog. Initial examination revealed multiple puncture wounds and lacerations with visible dura. Head CT demonstrated subarachnoid, intraparenchymal, and epidural hemorrhages as well as left hemispheric loss of gray-white differentiation. Thus, the patient presented similarly to shaken baby syndrome (SBS). The patient was taken emergently to the operating room for hematoma evacuation and dural repair. Postoperatively, worsened left hemispheric ischemia was noted and an MRA demonstrated a Grade IV left ICA dissection. No intervention, including anticoagulation, was sought as the stroke was determined to be complete with irreversible damage. Hospital course was complicated by worsening exam, seizures, and a retinal hemorrhage. At 2 years follow-up, the patient still has notable delays but is progressing slowly through milestones. CONCLUSION: Large animal attacks are a rare cause of PTCAD but may be due to the mechanism of shaking during the attack. We propose either CTA or MRA be considered as part of the initial workup in cases where an infant is attacked by a dog or other large animals, preventing delay of treatment.

Treating overactive bladder with percutaneous tibial nerve stimulation.

ABSTRACT: Overactive bladder can affect patients at any age; however, it is more common in women over age 40 years. Many treatments are available, including behavioral interventions, antimuscarinics, beta-3 agonists, and botulinum toxin injection. This article describes a patient who was successfully treated with percutaneous tibial nerve stimulation after traditional treatment failed.

Hyperthermic intraperitoneal chemotherapy for treating ovarian cancer.

ABSTRACT: Hyperthermic intraperitoneal chemotherapy (HIPEC) has been used for decades as a treatment for disseminated abdominal malignancies, including pseudomyxoma peritonei and peritoneal mesothelioma. HIPEC had been used to treat recurrent ovarian cancer only when curative options were lacking, but new data indicate that it may be suitable as a primary treatment for patients with late-stage epithelial ovarian cancer, increasing the recurrence-free time interval and improving quality of life. However, treatment can be challenging because of patient trauma from surgery, combined with the toxicity and high temperature of the chemotherapeutic agents. This article reviews HIPEC and its targeted intraoperative and postoperative management.

New options for managing fecal incontinence in women.

Fecal incontinence often is underreported and can be associated with both social embarrassment and isolation. As patients often do not proactively discuss their symptoms, healthcare providers should screen for this distressing condition. The cause of fecal incontinence often is multifactorial, so no single therapy can guarantee perfect, risk-free outcomes. This article reviews the limited therapies for managing fecal incontinence, including a minimally invasive vaginal control device that may offer hope for managing fecal incontinence in women.

What is the role of dehydroepiandrosterone in gynecologic practice?

In small clinical trials, dehydroepiandrosterone (DHEA) has been found to relieve symptoms associated with postmenopausal conditions and infertility in women. DHEA may provide a cost-effective alternative to typical hormone therapies. Because of a lack of long-term and large-scale studies, only intravaginal DHEA supplementation is approved and recommended for treatment. Further investigation of DHEA supplementation is needed and encouraged to determine its safety and effectiveness.

An introductory review of post-resection chemotherapeutics for primary brain tumors.

The treatment of central nervous system (CNS) tumors is complicated by high rates of recurrence and treatment resistance that contribute to high morbidity and mortality (Nat Rev Neurol. 2022;18:221-36. doi: 10.1038/s41582-022-00621-0). One of the challenges of treating these tumors is the limited permeability of the blood brain barrier (BBB). Early pharmacologic treatments worked to overcome the BBB by targeting vulnerabilities in the tumor cell replication process directly through alkylating agents like temozolomide. However, as advancements have been made options have expanded to include immunologic targets through the use of monoclonal antibodies. In the future, treatment will likely continue to focus on the use of immunotherapies, as well as emerging technology like the use of low-intensity focused ultrasound (LIFU). Ultimately, this paper serves as an introductory overview of current therapeutic options for post-resection primary brain tumors, as well as a look towards future work and emerging treatment options.

The Richmond Acute Subdural Hematoma Score: A Validated Grading Scale to Predict Postoperative Mortality.

BACKGROUND: Traumatic acute subdural hematomas (aSDHs) are common, life-threatening injuries often requiring emergency surgery. OBJECTIVE: To develop and validate the Richmond acute subdural hematoma (RASH) score to stratify patients by risk of mortality after aSDH evacuation. METHODS: The 2016 National Trauma Data Bank (NTDB) was queried to identify adult patients with traumatic aSDHs who underwent craniectomy or craniotomy within 4 h of arrival to an emergency department. Multivariate logistic regression modeling identified risk factors independently associated with mortality. The RASH score was developed based on a factor's strength and level of association with mortality. The model was validated using the 2017 NTDB and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2516 cases met study criteria. The patients were 69.3% male with a mean age of 55.7 yr and overall mortality rate of 36.4%. Factors associated with mortality included age between 61 and 79 yr (odds ratio [OR] = 2.3, P < .001), age ≥80 yr (OR = 6.3, P < .001), loss of consciousness (OR = 2.3, P < .001), Glasgow Coma Scale score of ≤8 (OR = 2.6, P < .001), unilateral (OR = 2.8, P < .001) or bilateral (OR = 3.9, P < .001) unresponsive pupils, and midline shift >5 mm (OR = 1.7, P < .001). Using these risk factors, the RASH score predicted progressively increasing mortality ranging from 0% to 94% for scores of 0 to 8, respectively (AUC = 0.72). Application of the RASH score to 3091 cases from 2017 resulted in similar accuracy (AUC = 0.74). CONCLUSION: The RASH score is a simple and validated grading scale that uses easily accessible preoperative factors to predict estimated mortality rates in patients with traumatic aSDHs who undergo surgical evacuation.

Graft dural closure is associated with a reduction in CSF leak and hydrocephalus in pediatric patients undergoing posterior fossa brain tumor resection.

OBJECTIVE: The authors aimed to evaluate clinical, radiological, and surgical factors associated with posterior fossa tumor resection (PFTR)-related outcomes, including postoperative complications related to dural augmentation (CSF leak and wound infection), persistent hydrocephalus ultimately requiring permanent CSF diversion after PFTR, and 90-day readmission rate. METHODS: Pediatric patients (0-17 years old) undergoing PFTR between 2000 and 2016 at Monroe Carell Jr. Children's Hospital of Vanderbilt University were retrospectively reviewed. Descriptive statistics included the Wilcoxon signed-rank test to compare means that were nonnormally distributed and the chi-square test for categorical variables. Variables that were nominally associated (p < 0.05) with each outcome by univariate analysis were included as covariates in multivariate linear regression models. Statistical significance was set a priori at p < 0.05. RESULTS: The cohort consisted of 186 patients with a median age at surgery of 6.62 years (range 3.37-11.78 years), 55% male, 83% Caucasian, and average length of follow-up of 3.87 ± 0.25 years. By multivariate logistic regression, the variables primary dural closure (PDC; odds ratio [OR] 8.33, 95% confidence interval [CI] 1.07-100, p = 0.04), pseudomeningocele (OR 7.43, 95% CI 2.23-23.76, p = 0.0007), and hydrocephalus ultimately requiring permanent CSF diversion within 90 days of PFTR (OR 9.25, 95% CI 2.74-31.2, p = 0.0003) were independently associated with CSF leak. PDC versus graft dural closure (GDC; 35% vs 7%, OR 5.88, 95% CI 2.94-50.0, p = 0.03) and hydrocephalus ultimately requiring permanent CSF diversion (OR 3.30, 95% CI 1.07-10.19, p = 0.0007) were associated with wound infection requiring surgical debridement. By multivariate logistic regression, GDC versus PDC (23% vs 37%, OR 0.13, 95% CI 0.02-0.87, p = 0.04) was associated with persistent hydrocephalus ultimately requiring permanent CSF diversion, whereas pre- or post-PFTR ventricular size, placement of peri- or intraoperative extraventricular drain (EVD), and radiation therapy were not. Furthermore, the addition of perioperative EVD placement and dural closure method to a previously validated predictive model of post-PFTR hydrocephalus improved its performance from area under the receiver operating characteristic curve of 0.69 to 0.74. Lastly, the authors found that autologous (vs synthetic) grafts may be protective against persistent hydrocephalus (p = 0.02), but not CSF leak, pseudomeningocele, or wound infection. CONCLUSIONS: These results suggest that GDC, independent of potential confounding factors, may be protective against CSF leak, wound infection, and hydrocephalus in patients undergoing PFTR. Additional studies are warranted to further evaluate clinical and surgical factors impacting PFTR-associated complications.

Predictors of endoscopic third ventriculostomy ostomy status in patients who experience failure of endoscopic third ventriculostomy with choroid plexus cauterization.

OBJECTIVE: At failure of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC), the ETV ostomy may be found to be closed or open. Failure with a closed ostomy may indicate a population that could benefit from evolving techniques to keep the ostomy open and may be candidates for repeat ETV, whereas failure with an open ostomy may be due to persistently abnormal CSF dynamics. This study seeks to identify clinical and radiographic predictors of ostomy status at the time of ETV/CPC failure. METHODS: The authors conducted a multicenter, retrospective cohort study on all pediatric patients with hydrocephalus who failed initial ETV/CPC treatment between January 2013 and October 2016. Failure was defined as the need for repeat ETV or ventriculoperitoneal (VP) shunt placement. Clinical and radiographic data were collected, and ETV ostomy status was determined endoscopically at the subsequent hydrocephalus procedure. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank-sum test, t-test, and Pearson chi-square test where appropriate, as well as multivariate logistic regression. RESULTS: Of 72 ETV/CPC failures, 28 patients (39%) had open-ostomy failure and 44 (61%) had closed-ostomy failure. Patients with open-ostomy failure were older (median 5.1 weeks corrected age for gestation [interquartile range (IQR) 0.9-15.9 weeks]) than patients with closed-ostomy failure (median 0.2 weeks [IQR -1.3 to 4.5 weeks]), a significant difference by univariate and multivariate regression. Etiologies of hydrocephalus included intraventricular hemorrhage of prematurity (32%), myelomeningocele (29%), congenital communicating (11%), aqueductal stenosis (11%), cyst/tumor (4%), and other causes (12%). A wider baseline third ventricle was associated with open-ostomy failure (median 15.0 mm [IQR 10.3-18.5 mm]) compared to closed-ostomy failure (median 11.7 mm [IQR 8.9-16.5 mm], p = 0.048). Finally, at the time of failure, patients with closed-ostomy failure had enlargement of their ventricles (frontal and occipital horn ratio [FOHR], failure vs baseline, median 0.06 [IQR 0.00-0.11]), while patients with open-ostomy failure had no change in ventricle size (median 0.01 [IQR -0.04 to 0.05], p = 0.018). Previous CSF temporizing procedures, intraoperative bleeding, and time to failure were not associated with ostomy status at ETV/CPC failure. CONCLUSIONS: Older corrected age for gestation, larger baseline third ventricle width, and no change in FOHR were associated with open-ostomy ETV/CPC failure. Future studies are warranted to further define and confirm features that may be predictive of ostomy status at the time of ETV/CPC failure.

Investigating the effects of subconcussion on functional connectivity using mass-univariate and multivariate approaches.

There are concerns about the effects of subconcussive head impacts in sport, but the effects of subconcussion on brain connectivity are not well understood. We hypothesized that college football players experience changes in brain functional connectivity not found in athletes competing in lower impact sports or healthy controls. These changes may be spatially heterogeneous across participants, requiring analysis methods that go beyond mass-univariate approaches commonly used in functional MRI (fMRI). To test this hypothesis, we analyzed resting-state fMRI data from college football (n = 15), soccer (n = 12), and lacrosse players (n = 16), and controls (n = 29) collected at preseason and postseason time points. Regional homogeneity (ReHo) and degree centrality (DC) were calculated as measures of local and long-range functional connectivity, respectively. Standard voxel-wise analysis and paired support vector machine (SVM) classification studied subconcussion's effects on local and global functional connectivity. Voxel-wise analyses yielded minimal findings, but SVM classification had high accuracy for college football's ReHo (87%, p = 0.009) and no other group. The findings suggest subconcussion results in spatially heterogeneous changes in local functional connectivity that may only be detectible with multivariate analyses. To determine if voxel-wise and SVM analyses had similar spatial patterns, region-average t-statistic and SVM weight values were compared using a measure of ranking distance. T-statistic and SVM weight rankings exhibited significantly low ranking distance values for all groups and metrics, demonstrating that the analyses converged on a similar underlying effect. Overall, this research suggests that subconcussion in football may produce local functional connectivity changes similar to concussion.

Streptophyte Terrestrialization in Light of Plastid Evolution.

Key steps in evolution are often singularities. The emergence of land plants is one such case and it is not immediately apparent why. A recent analysis found that the zygnematophycean algae represent the closest relative to embryophytes. Intriguingly, many exaptations thought essential to conquer land are common among various streptophytes, but zygnematophycean algae share with land plants the transfer of a few plastid genes to the nucleus. Considering the contribution of the chloroplast to terrestrialization highlights potentially novel exaptations that currently remain unexplored. We discuss how the streptophyte chloroplast evolved into what we refer to as the embryoplast, and argue this was as important for terrestrialization by freshwater algae as the host cell-associated exaptations that are usually focused upon.