Management of ruptured ovarian teratoma mimicking advanced ovarian cancer.

•Chronic chemical peritonitis caused by spontaneous rupture of a mature cystic teratoma may result in prolonged hospitalization and respiratory decline and can mimic a gynecologic malignancy.•Earlier surgical intervention for mature teratoma may prevent morbidity.•Inclusion of a gynecologic oncologist is advised for management discussions and/or surgical back-up.•Complex benign gynecologic surgeries may have some benefit for gynecologic oncologic trainees, which can be used for later oncologic cases.

Vulvar Cancer, Version 3.2024, NCCN Clinical Practice Guidelines in Oncology.

Vulvar cancer is annually diagnosed in an estimated 6,470 individuals and the vast majority are histologically squamous cell carcinomas. Vulvar cancer accounts for 5% to 8% of gynecologic malignancies. Known risk factors for vulvar cancer include increasing age, infection with human papillomavirus, cigarette smoking, inflammatory conditions affecting the vulva, and immunodeficiency. Most vulvar neoplasias are diagnosed at early stages. Rarer histologies exist and include melanoma, extramammary Paget's disease, Bartholin gland adenocarcinoma, verrucous carcinoma, basal cell carcinoma, and sarcoma. This manuscript discusses recommendations outlined in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for treatments, surveillance, systemic therapy options, and gynecologic survivorship.

Circulating Tumor DNA (ctDNA) and Its Role in Gynecologic Malignancies.

OPINION STATEMENT: Circulating tumor DNA (ctDNA) refers to small fragments of DNA released into the bloodstream by cancer cells. It is obtained through "liquid biopsy;" which most commonly refers to plasma or blood samples, but can be obtained from a number of bodily fluids including ascitic fluid, saliva, and even urine and stool. ctDNA is detected via polymerase chain reaction (PCR) or next-generation sequencing (NGS). The DNA from these samples is analyzed for the detection of point mutations, copy-number alterations, gene fusion, and DNA methylation. These results have the potential for use in cancer diagnosis, determining prognosis, targeting gene-specific therapies, and monitoring for/predicting disease recurrence and response to treatment. ctDNA offers an alternative to tissue biopsy; it is less invasive and can be monitored serially over time without multiple procedures. Moreover it may have the ability to detect disease recurrence or predict behavior in a way that solid tissue biopsies, tumor marker surveillance, and imaging cannot. Recent explosion in interest in ctDNA shows promising developments for widespread adoption of these techniques in cancer care. However, the use of ctDNA in diagnosis and treatment of gynecologic malignancies is currently limited, compared to adoption in other solid-organ tumors such as breast and colorectal cancers. Compared to other cancer types, there appear to be fewer comprehensive studies and clinical validations specifically focusing on the use of ctDNA in gynecologic cancers. More research is needed in this area to advance the potential for use of ctDNA in ovarian, endometrial, and cervical cancers before this can be routinely adopted to improve care for patients with gynecologic malignancies.

Perspectives of gynecologic oncology fellowship training and preparedness for practice.

We aimed to examine the preparedness of recent gynecologic oncology fellowship graduates for independent practice.We conducted a web-based survey study using REDCap targeting Society of Gynecologic Oncology (SGO) members who graduated gynecologic oncology fellowship within the last six years. The survey included 52 items assessing fellowship training experiences, level of comfort in performing core gynecologic oncology surgical procedures and administering cancer-directed therapies. Questions also addressed factors driving participants' selection of fellowship programs, educational experience, research and preparedness for independent practice. A total of 296 participants were invited to complete the survey. Response rate was 42% with n = 124 completed surveys included for analysis. The highest ranked factor for fellowship selection was fit with program 36% (n = 45). Upon completing fellowship, most were uncomfortable performing ureteral conduit formation 84% (n = 103), ureteroneocystostomy 77% (n = 94), exenteration 68% (n = 83), splenectomy 67% (n = 83) and lower anterior resection 41% (n = 51). Most were comfortable managing intraoperative complications 85% (n = 104) and standard cancer staging procedures (range: 61%-99%). Majority were comfortable providing cancer directed therapies with chemotherapy 99% (n = 123), immunotherapy 84% (n = 104), and poly ADP-ribose polymerase (PARP) inhibitors 97% (n = 120). Upon completing fellowship, 77% (n = 95) report having mentorship that met their expectations during fellowship and 94% (n = 116) felt they were ready for independent practice. Majority of fellowship graduates were prepared for independent practice and felt comfortable performing routine surgical procedures and cancer directed treatment. However, most are not comfortable with ultra-radical gynecologic oncology procedures. Maximizing surgical opportunities during fellowship training and acquiring early career mentorship may help.

NCCN Guidelines® Insights: Cervical Cancer, Version 1.2024.

The NCCN Guidelines for Cervical Cancer provide recommendations for all aspects of management for cervical cancer, including the diagnostic workup, staging, pathology, and treatment. The guidelines also include details on histopathologic classification of cervical cancer regarding diagnostic features, molecular profiles, and clinical outcomes. The treatment landscape of advanced cervical cancer is evolving constantly. These NCCN Guidelines Insights provide a summary of recent updates regarding the systemic therapy recommendations for recurrent or metastatic disease.

Targeting RAS-ERK pathway alterations with MEK inhibitors to improve chemosensitivity in high grade serous ovarian cancers.

OBJECTIVE: Assess if MEK inhibitor blockade of RAS-ERK pathway adaptive response in high grade serous ovarian cancers (HGSOC) improves platinum sensitivity. METHODS: Three HGSOC cell lines and three patient derived organoid (PDOs) samples from ascites of platinum resistant HGSOC patients were collected. Cell lines and PDOs were exposed to carboplatin and MEK inhibitors cobimetinib or trametinib. Cytotoxic effects of MEK inhibitors alone or combined with carboplatin were established. Western blots demonstrated RAS-ERK pathway blockage after MEK inhibitor treatment. RNA sequencing assessed gene expression after MEK inhibitor treatment. Cell line NF1 gene knockdown was performed with corresponding chemosensitivity levels. RESULTS: High carboplatin IC50 levels indicated platinum resistance in cell lines and PDOs. Cobimetinib induced cytotoxicity in cell lines and PDOs, while trametinib was less effective. Western blot confirmed MEK-ERK pathway blockage at minimal concentrations of MEK inhibitors in cell lines and PDOs. Phosphorylated-ERK levels of untreated cells indicated higher levels of RAS-ERK pathway activation in OVSAHO and OVCAR7 compared to OVCAR3. OVSAHO harbors a NF1 mutation and had highest levels of RAS-ERK activation. Cotreatment with carboplatin and MEK inhibitors showed varying synergistic cytotoxic effects at different combinations. Synergistic effect was most prominent in the OVSAHO carboplatin and cobimetinib combination. RNA sequencing identified downregulation of c-MYC and FOXM1 gene expression after MEK inhibitor treatment. NF1 gene knockdown showed an acquired increased IC50 compared to parental cells. CONCLUSION: MEK inhibitors block RAS-ERK pathways in platinum resistant HGSOC cells and PDOs. MEK inhibitors with carboplatin have select synergistic effects which may indicate a strategy to improve platinum sensitivity.

Primary clear cell carcinoma of the vulva: A case report.

Clear cell carcinoma (CCC) of the vulva is extremely rare. We report a case of a 54-year-old woman who presented with a 5 cm mass of the mons pubis. She underwent needle biopsy demonstrating CCC. She then underwent radical vulvectomy with bilateral inguinofemoral lymph node dissection. Surgical pathology revealed CCC of the vulva with lymphovascular space invasion (LVSI) and metastatic carcinoma in 1/7 inguinal lymph nodes. The patient has a history of endometriosis, raising suspicion that her CCC could have arisen from endometriosis in the mons. She completed adjuvant treatment with cisplatin and concurrent external beam radiation therapy with radiographic evidence of complete response. However, short-interval imaging demonstrated multi-focal recurrence, which was confirmed with supraclavicular lymph node biopsy. She then completed 8 cycles carboplatin, paclitaxel, and biosimilar bevacizumab-bvzr with favorable response on imaging. She was continued on bevacizumab maintenance. She was later started on pembroluzimab for disease progression based on new mediastinal adenopathy and worsening retroperitoneal lymphadenopathy. She received eight cycles of pembrolizumab with ongoing disease progression before enrolling in hospice and discontinuing cancer-directed treatment. As described in the related literature which we summarize here, the majority of reported cases of vulvar CCC arise from endometriosis implants at the site of prior episiotomy or from the Bartholin's gland. This patient had clinical history of endometriosis; prior tissue sampling was not performed to support the diagnosis. Given the absence of data regarding this rare type of primary vulvar cancer, treatment of this patient's disease was based on existing data specific to squamous cell carcinoma of the vulva and extrapolated from treatment guidelines for CCC of the ovary and endometrium. Continued research is needed on this rare form of vulvar carcinoma to determine the risk factors, prognostic factors, and treatment recommendations specific to this disease.

Gestational choriocarcinoma.

Gestational choriocarcinoma accounts for 5% of gestational trophoblastic neoplasms. Approximately 50%, 25%, and 25% of gestational choriocarcinoma occur after molar pregnancies, term pregnancies, and other gestational events, respectively. The FIGO scoring system categorizes patients into low (score 0 to 6) and high risk (score 7 or more) choriocarcinoma. Single-agent and multi-agent chemotherapy are used in low- and high-risk patients, respectively. Chemotherapy for localized disease has a goal of eradication of disease without surgery and is associated with favorable prognosis and fertility preservation. Most patients with gestational choriocarcinoma are cured with chemotherapy; however, some (<5.0%) will die as a result of multi-drug resistance, underscoring the need for novel approaches in this group of patients. Although there are limited data due to its rarity, the treatment response with immunotherapy is high, ranging between 50-70%. Novel combinations of immune checkpoint inhibitors with targeted therapies (including VEGFR-2 inhibitors) are under evaluation. PD-L1 inhibitors are considered a potential important opportunity for chemo-resistant patients, and to replace or de-escalate chemotherapy to avoid or minimize chemotherapy toxicity. In this review, the Rare Tumor Working Group and the European Organization for Research and Treatment of Cancer evaluated the current landscape and further perspective in the management of patients diagnosed with gestational choriocarcinoma.

Platelet count and risk of severe illness in hospitalised children with Influenza-Like illness.

AIM: To examine the clinical significance of thrombocytosis (platelets > 500 × 109 /L) in admitted children with an influenza-like illness. METHODS: We performed a database analysis consisting of patients evaluated at our medical centers with an influenza-like illness between 2009 and 2013. We included paediatric patients and examined the association between platelet count, respiratory viral infections, and admission outcomes (hospital length of stay and admission to the paediatric intensive care unit) using regression models adjusting for multiple variables. RESULTS: A total of 5171 children were included in the study cohort (median age 0.8 years; interquartile range, 0.2-1.8; 58% male). Younger age, and not the type of viral infection, was associated with a high platelet count (p < 0.001). Elevated platelet count independently predicted admission outcomes (p ≤ 0.05). The presence of thrombocytosis was associated with an increased risk for a prolonged length of stay (odds ratio = 1.2; 95% Confidence interval = 1.1 to 1.4; p = 0.003) and admission to the paediatric intensive care unit (odds ratio = 1.5; 95% Confidence interval = 1.1 to 2.0; p = 0.002). CONCLUSION: In children admitted with an influenza-like illness, a high platelet count is an independent predictor of admission outcomes. Platelet count may be used to improve risk assessment and management decisions in these paediatric patients.

Health Disparities in Ovarian Cancer: Report From the Ovarian Cancer Evidence Review Conference.

Health disparity, defined by the Centers for Disease Control and Prevention (CDC) as "preventable differences in the burden of disease, injury, violence, or opportunities to achieve optimal health that are experienced by socially disadvantaged populations," is seen across multiple diseases. We conducted an evidence review of health disparities and inequities and their mitigation strategies related to ovarian cancer as part of a CDC-sponsored project to develop educational materials for clinicians on the prevention and early diagnosis of gynecologic cancers. Our review found profound disparities in outcomes such as survival, treatment, and stage at diagnosis by factors such as race and ethnicity, insurance, socioeconomic status, and geographic location. We found little direct evidence on mitigation strategies. Studies support equivalent response to equivalent treatment between groups, suggesting that adherence to National Comprehensive Cancer Network guidelines can at least partially mitigate some of the differences.

Executive Summary of the Ovarian Cancer Evidence Review Conference.

The Centers for Disease Control and Prevention awarded funding to the American College of Obstetricians and Gynecologists to develop educational materials for clinicians on gynecologic cancers. The American College of Obstetricians and Gynecologists convened a panel of experts in evidence review from the Society for Academic Specialists in General Obstetrics and Gynecology and content experts from the Society of Gynecologic Oncology to review relevant literature, best practices, and existing practice guidelines as a first step toward developing evidence-based educational materials for women's health care clinicians about ovarian cancer. Panel members conducted structured literature reviews, which were then reviewed by other panel members and discussed at a virtual meeting of stakeholder professional and patient advocacy organizations in February 2022. This article is the executive summary of the relevant literature and existing recommendations to guide clinicians in the prevention, early diagnosis, and special considerations of ovarian cancer. Substantive knowledge gaps are noted and summarized to provide guidance for future research.

Survival After Declining Pediatric Tracheostomy Placement.

OBJECTIVE: To determine survival among critically ill children when caregivers decline tracheostomy placement. STUDY DESIGN: Retrospective cohort. METHODS: All children (<18 years) obtaining a pre-tracheostomy consultation at a tertiary children's hospital between 2016 and 2021 were included. Comorbidities and mortality were compared between children of caregivers that declined or agreed to tracheostomy. RESULTS: Tracheostomy was declined for 58 children but was placed for 203 children. After consultation, mortality was 52% (30/58) when declining and 21% (42/230) when agreeing to tracheostomy (p < 0.001) at a mean of 10.7 months (standard deviation [SD]: 16) and 18.1 months (SD: 17.1), respectively (p = 0.07). For those declining, 31% (18/58) died during the hospitalization within a mean of 1.2 months (SD: 1.4) while 21% (12/58) died at a mean of 23.6 months (SD: 17.5) after discharge. Among children of caregivers declining tracheostomy, older age (odds ratio [OR]: 0.85, 95% confidence interval [CI]: 0.74-0.97, p = 0.01) and chronic lung disease (OR: 0.18, 95% CI: 0.04-0.82, P = .03) were associated with lower odds of mortality but sepsis (OR: 9.62, 95% CI: 1.161-57.43, p = 0.01) and intubation (OR: 4.98, 95% CI: 1.24-20.08, p = 0.02) were associated with higher odds of mortality. Median survival after declining tracheostomy was 31.9 months (interquartile range [IQR]: 2.0-50.7) and declining placement was associated with increased mortality risk (hazard ratio [HR]: 4.04, 95% CI: 2.49-6.55, p < 0.001). CONCLUSION: When caregivers declined tracheostomy placement, less than half of critically ill children in this cohort survived with younger age, sepsis, and intubation associated with higher mortality. This information offers valuable insight for families weighing decisions pertaining to pediatric tracheostomy placement. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3602-3607, 2023.

Pediatric respiratory admissions and related viral infections during the COVID-19 pandemic.

INTRODUCTION: The COVID-19 pandemic has affected the incidence of respiratory viral infections. Our aim was to assess changes in pediatric admissions due to respiratory diseases and associated respiratory viral infections. METHODS: An observational study including all respiratory admissions to the pediatric departments from January 2015 to August 2021. We compared respiratory admission percentage, respiratory viral panel results and clinical characteristics of these admissions between two study periods, January 2015 to February 2020 (pre-COVID-19 era) and March 2020 to August 2021 (COVID-19 era). RESULTS: A total of 8774 respiratory admissions were included, 7157 pre-COVID-19 era and 1617 COVID-19 era. Relative to all pediatric admissions, there was a 17% decrease in respiratory admission percentage during the COVID-19 era (p < 0.001) and a 31% and 22% decreased in the admission percentages due to bronchiolitis (p < 0.001) and pneumonia (p < 0.001), respectively. However, admission percentages for asthma, wheezing illness, complicated pneumonia, and stridor remained the same. There was a significant decrease in the detection of a respiratory viral pathogen associated with these respiratory admissions (p < 0.001). This was related to a significant decrease in the detection of respiratory syncytial virus (RSV) (37% vs. 27%, p < 0.001) and influenza (5% vs. 0.3%, p < 0.001), but not other respiratory viruses. An alteration in the circulation pattern of most respiratory viruses, was observed. CONCLUSIONS: During the COVID-19 pandemic, a decrease in the prevalence of RSV and influenza was associated with a significant decrease in admissions for bronchiolitis and pediatric pneumonia. This may allow us to estimate the significance of preventive measures for RSV and influenza on pediatric respiratory admissions.

Uterine Neoplasms, Version 1.2023, NCCN Clinical Practice Guidelines in Oncology.

Adenocarcinoma of the endometrium (also known as endometrial cancer, or more broadly as uterine cancer or carcinoma of the uterine corpus) is the most common malignancy of the female genital tract in the United States. It is estimated that 65,950 new uterine cancer cases will have occurred in 2022, with 12,550 deaths resulting from the disease. Endometrial carcinoma includes pure endometrioid cancer and carcinomas with high-risk endometrial histology (including uterine serous carcinoma, clear cell carcinoma, carcinosarcoma [also known as malignant mixed Müllerian tumor], and undifferentiated/dedifferentiated carcinoma). Stromal or mesenchymal sarcomas are uncommon subtypes accounting for approximately 3% of all uterine cancers. This selection from the NCCN Guidelines for Uterine Neoplasms focuses on the diagnosis, staging, and management of pure endometrioid carcinoma. The complete version of the NCCN Guidelines for Uterine Neoplasms is available online at NCCN.org.

Peripheral Blood Biomarkers for Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Systematic Review.

BACKGROUND: Biomarkers have been proposed as tools to aid in the identification and prognostication of interstitial lung disease (ILD) in rheumatoid arthritis (RA). We performed a systematic review of studies evaluating peripheral blood biomarkers and their association with RA-ILD and its prognosis. METHODS: Medline, Embase, the Cochrane Library, and Scopus were queried for relevant studies, with the final search update on July 12, 2021. We included studies evaluating peripheral blood biomarkers for the identification and/or prognostication of RA-ILD, extracting the performance of individual biomarkers for identifying RA-ILD, and predicting prognosis. Modified versions of the Quality Assessment of Diagnostic Accuracy Studies 2 and the Quality in Prognosis Studies tools were used for quality assessment. RESULTS: Seventy studies met eligibility criteria. Study and patient characteristics, analytical methods, strength and consistency of associations, and study quality were heterogeneous. A total of 92 biomarkers were positively associated and 12 were negatively associated with RA-ILD among patients with RA in one or more report. Only a small number of biomarkers were evaluated in multiple cohorts using adjusted analyses. Biomarkers most strongly associated with RA-ILD overlapped with those identified for idiopathic pulmonary fibrosis. Few prognostic biomarkers of RA-ILD were identified. CONCLUSION: Several peripheral blood biomarkers are associated with the presence of RA-ILD, but few have been assessed in multivariable models, have been externally validated, have discriminated RA-ILD from other lung disease, or have prognosticated the disease course. High-quality studies investigating and validating peripheral biomarkers in RA-ILD are needed before they can be employed in clinical care.

Caregiver quality of life after pediatric tracheostomy.

OBJECTIVE: To determine the impact of a child with a tracheostomy on caregiver quality of life. METHODS: A repeated cross-sectional analysis included families with tracheostomy-dependent children between 2019 and 2021. Caregivers were surveyed using the PedsQL™ Family Impact Module with assessments at tracheostomy placement and during ambulatory office visits. RESULTS: Two-hundred and fifty-five surveys were performed with 66 at tracheostomy placement (26%) and 189 at follow-up visits (74%). Compared to families with healthy children, total scores at placement (77.2 vs. 87.6, P < .001) and follow-up visits (78.9 vs. 87.6, P < .001) were significantly lower among pediatric tracheostomy families. Caregivers were likely to report significant improvement in emotional functioning (6.2 points; 95% CI: 0.5-12, P = .03) and worry (9 points, 95% CI: 2.1-15.9, P = .01) over time. Demographic variables demonstrated no confounding or interactive effects. CONCLUSIONS: The presence of a tracheostomy is associated with lower caregiver quality of life scores in the short- and long-term compared to caregivers of healthy children. Providers should be sensitive to these challenges and provide appropriate support for families of tracheostomy-dependent children.

Multisystem inflammatory syndrome in children associated with COVID-19 presenting as cervical inflammation.

AIM: The major clinical manifestations multisystem inflammatory syndrome in children (MIS-C) are fever, gastrointestinal and cardiac. The aim of this study was to describe MIS-C in a series of patients who presented primarily with cervical manifestations. METHODS: We retrospectively reviewed medical records of all patients who met the Centers for Disease Control and Prevention and World Health Organization MIS-C diagnostic criteria treated at Hadassah-Hebrew University Medical Center between April 2020 and September 2021. RESULTS: Of 37 children diagnosed with MIS-C (median age: 10.2 years, range 1.5-18 years, 20 male) five, 13.5% (median age: 14.4 years, range 9.2-17.5 years) presented with cervical symptoms mimicking neck infections. One was hospitalised with a working diagnosis of retropharyngeal abscess, and four with acute cervical lymphadenitis that did not respond to early antibiotic treatment. All developed full MIS-C phenotype. CONCLUSION: MIS-C may present as cervical inflammation. An ill-appearing child with symptoms and/or signs of cervical inflammation should be evaluated for clinical and laboratory features of MIS-C, thereby facilitating prompt treatment of this potentially fatal disorder.

Accidental Tracheostomy Decannulations in Children-A Prospective Cohort Study of Inpatients.

OBJECTIVES: To determine the incidence of tracheostomy accidental decannulations (AD) among pediatric inpatients and identify risks for these events. STUDY DESIGN: Prospective cohort. METHODS: All tracheostomy patients (≤18 years) admitted at a tertiary children's hospital between August 2018 and April 2021 were included. AD were recorded and patient harm was classified as no harm/minor, moderate, or severe. Monthly AD incidence was described as events per 1000 tracheostomy-days. RESULTS: One-hundred seventeen AD occurred among 67 children with 33% (22/67) experiencing multiple events (median: 2.5 events, range: 2-10). Mean age at AD was 4.7 years (SD: 4.4). AD resulted from patient movement (32%, 37/117), performing tracheostomy care (27%, 31/117), repositioning or transporting (15%, 17/117), or unclear reasons (27%, 32/117). A parent or guardian was involved in 28% (33/117) of events. Nearly all AD resulted in no more than minor harm (84%, 98/117) but moderate (12%, 14/117) and severe (4%, 5/117) events did occur. There were no deaths. Tracheostomy care or repositioning were frequently responsible in acute versus subacute events (48% vs. 26%, p = 0.04). Mean monthly AD incidence was 4.7 events per 1000 tracheostomy-days (95% CI: 3.7-5.8) and after implementation of safety initiatives, the mean rate decreased from 5.9 events (95% CI: 4.2-7.7) to 3.7 events (95% CI: 2.5-5.0) per 1000 tracheostomy-days (p = 0.04). CONCLUSIONS: AD in children occur at nearly 5 events per 1000 tracheostomy-days and often result in minimal harm. Quality initiatives targeting patient movement, provider education, and tracheostomy care might reduce the frequency of these complications. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:963-969, 2023.

Mortality Among Children with a Tracheostomy.

OBJECTIVES: To characterize the cause of death among children with a tracheostomy. STUDY DESIGN: Prospective cohort. METHODS: All pediatric patients (<18 years) who had a tracheostomy placed at a tertiary care institution between 2015 and 2020 were included. The location and cause of death were recorded along with patient demographics and age. RESULTS: A total of 271 tracheostomies were placed with 46 mortalities reviewed for a mortality rate of 16.8%. Mean age at placement was 1.7 years (SD: 3.4) and mean age at death was 2.9 years (SD: 3.5). Most tracheostomies were placed for respiratory failure (N = 33, 72%). The mean time to death after tracheostomy was 1.2 years (SD: 1.2) and 28% (N = 13) occurred during the same admission as placement. Mean time to death after hospital discharge was 1.3 years (SD: 1.3). Etiology of death was respiratory failure (33%, N = 15), cardiopulmonary arrest (15%, N = 7), unknown (43%, N = 20), or secondary to a tracheostomy-related complication for 9% (N = 4). Location of death was in intensive care units for 41% (N = 19) and 30% died at home (N = 14). Comfort care measures were taken for 37% (N = 17). Severe neurological disability (HR: 4.06, p = 0.003, 95% CI: 1.59-10.34) and congenital heart disease (HR: 2.36, p = 0.009, 95% CI: 1.24-4.48) correlated with time to death on Cox proportional hazard modeling. CONCLUSIONS: Nearly one-third of children with a tracheostomy who expire will do so during the same admission as tracheostomy placement. Although progression of underlying disease will lead to most deaths, 9% will be a result of a tracheostomy-related complication, which represents a meaningful target for quality improvement initiatives. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:403-409, 2023.

Neurological complications following pediatric allogeneic hematopoietic stem cell transplantation: Risk factors and outcome.

Background: Allogeneic hematopoietic stem cell transplantation (HSCT) is an efficient treatment for numerous malignant and nonmalignant conditions affecting children. This procedure can result in infectious and noninfectious neurological complications (NCs). Objective: The objective of the study is to examine the incidence, risk factors, and outcomes of NCs in pediatric patients following allogeneic HSCT. Methods: We performed a retrospective study of 746 children who underwent 943 allogeneic HSCTs in two large pediatric hospitals in Israel from January 2000 to December 2019. Results: Of the pediatric patients 107 (14.3%) experienced 150 NCs. The median follow-up was 55 months. Noninfectious NCs were more common than infectious NCs (81.3% vs. 18.7%). Factors significantly associated with type of NC (infectious vs. noninfectious) were underlying disease (immunodeficiency vs. malignant and metabolic/hematologic disease) (p-value = 0.000), and use of immunosuppressive agent, either Campath or ATG (p-value = 0.041). Factors with a significant impact on developing neurological sequelae post-NC were number of HSCT >1 (p-value = 0.028), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.003), and infectious type of NC (p-value = 0.046). The overall survival rate of whole NC-cohort was 44%; one-third of all mortality cases were attributed to the NC. The strongest prognostic factors associated with mortality were older age at HSCT (p-value = 0.000), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.004), and the existence of neurological sequelae (p-value = 0.000). Abnormal central nervous system imaging (p-value = 0.013), the use of alemtuzumab as an immunosuppressive agent (p-value = 0.019), and neurological sequelae (p-value = 0.000) had statistically significant effects on neurological cause of death. Conclusion: Infectious and noninfectious NCs are a significant cause of morbidity and mortality following allogeneic HSCT in children. Further research is required to better understand the risk factors for different NCs and their outcomes regarding sequelae and survival.