Simulation-Based Analysis of Trial Design in Regional Anesthesia.

Background: In regional anesthesia, the efficacy of novel blocks is typically evaluated using randomized controlled trials (RCTs), the findings of which are aggregated in systematic reviews and meta-analyses. Systematic review authors frequently point out the small sample size of RCTs as limiting conclusions from this literature. We sought to determine via statistical simulation if small sample size could be an expected property of RCTs focusing on novel blocks with typical effect sizes. Methods: We simulated the conduct of a series of RCTs comparing a novel block versus placebo on a single continuous outcome measure. Simulation analysis inputs were obtained from a systematic bibliographic search of meta-analyses. Primary outcomes were the predicted number of large trials (empirically defined as N ≥ 256) and total patient enrollment. Results: Simulation analysis predicted that a novel block would be tested in 16 RCTs enrolling a median of 970 patients (interquartile range (IQR) across 1000 simulations: 806, 1269), with no large trials. Among possible modifications to trial design, decreasing the statistical significance threshold from p < 0.05 to p < 0.005 was most effective at increasing the total number of patients represented in the final meta-analysis, but was associated with early termination of the trial sequence due to futility in block vs. block comparisons. Conclusion: Small sample size of regional anesthesia RCTs comparing novel block to placebo is a rational outcome of trial design. Feasibly large trials are unlikely to change conclusions regarding block vs. placebo comparisons.

Malignant mixed mullerian tumors: a SEER database review of rurality and treatment modalities on disease outcome.

Introduction: Malignant Mixed Mullerian Tumors (MMMT) are rare and poorly understood sarcomas with limited research on risk factors, pathogenesis, and optimal treatments. This study aimed to address this knowledge gap and explore the impact of community size, patient characteristics, disease characteristics, and treatment modalities on MMMT outcomes. Methods: Using the Surveillance, Epidemiology, and End Results database (SEER), the largest SEER cohort to date of 3,352 MMMT patients was analyzed for demographic factors, treatment modalities, and histologic characteristics. Data was processed, including the removal of incomplete entries, and analyzed in Python 3.1 using packages scikit-learn, lifelines, and torch; log-rank analysis and Cox proportional hazards models were used to evaluate a number of demographic characteristics and disease characteristics for significance in regard to survival. Results: Our study found adjuvant radiotherapy and chemotherapy significantly improved survival, with modest benefits from neoadjuvant chemotherapy. Our findings also suggest age at diagnosis, disease grade, and suburban versus rural geographic locations may play key roles in patient prognosis. On multivariable analysis both disease Grade and surgical treatment were significant factors. Discussion: MMMTs remain challenging, but appropriate treatment appears to enhance survival. The present findings suggest opportunities for improved outcomes and treatment strategies for patients with MMMTs.

Squamous cell carcinoma of the bladder: Demographics and outcomes associated with surgery and radiotherapy.

BACKGROUND AND OBJECTIVES: Squamous cell carcinoma of the bladder (SCCB) is a rare disease composing 2%-5% of all bladder cancers with no consensus regarding treatment. The present study aims to analyze the outcomes of established treatments, namely chemotherapy, radiation, and surgery, to guide clinical decision-making for patients with non-schistosomal SCCB. METHODS: Patients with bladder SCC diagnosed between 2000 and 2018 were reviewed utilizing data from the Surveillance, Epidemiology, and End Results Registry (SEER) program. RESULTS: A total of 5653 patients with SCCB were identified; median survival was 13 months and was significantly decreased in patients treated with chemotherapy or radiation (median survival of 9 or 12 months, respectively). Patients treated with both surgery and radiotherapy saw a decreased 5 year overall survival (OS) of 14%, compared to 35% for those treated with surgery alone (p < 0.01). Furthermore, patients treated with surgery, chemotherapy, and radiotherapy saw a decreased 5 year OS of 20%, compared with 25% for those that received surgery and chemotherapy only (p < 0.01). Finally, surgical intervention provided an increased 5 year OS for patients with locoregional disease only; those with distant disease saw no increase in 5 year OS (p < 0.01). CONCLUSIONS: Based on this study's analysis, radical surgery may be the most effective treatment for this disease.

A SEER database retrospective cohort of 547 patients with penile non-squamous cell carcinoma: demographics, clinical characteristics, and outcomes.

Introduction: Little research has investigated the prevalence and distribution of the diverse pathologies of non-squamous cell carcinoma (non-SCC) of the penis. Although rare in clinical practice, these cancers have become a focus of greater importance among patients, clinicians, and researchers, particularly in developing countries. The principal objective of this study was to analyze the major types of penile non-SCC, elucidate common treatment pathways, and highlight outcomes including 5-year survival. Materials/methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried between 2000 and 2018 to identify a retrospective cohort of patients with penile non-SCC. Demographic information, cancer characteristics, diagnostic methods, treatments administered, and survival were investigated. Results: A total of 547 cases of penile non-SCC were included in the analysis. The most prevalent non-SCC cancers included epithelial neoplasms, not otherwise specified (NOS) (15.4%), unspecified neoplasms (15.2%), basal cell neoplasms (13.9%), blood vessel tumors (13.0%), nevi and melanomas (11.7%), and ductal and lobular neoplasms (9.9%). Over half (56.7%) of patients elected to undergo surgical intervention. Patients rarely received systemic therapy (3.8%) or radiation (4.0%). Five-year survival was 35.5%. Patients who underwent surgery had greater annual survival for 0-10 years compared to those who did not have surgery. Significant differences in survival were found between patients who had regional, localized, and distant metastases (p < 0.05). A significant difference in survival was found for patients married at diagnosis versus those who were unmarried at diagnosis (p < 0.05). Lower survival rates were observed for patients older than 70 years. Discussion: Although less prevalent than SCC, penile non-SCC encompasses a diverse set of neoplasms. Patients in this cohort had a high utilization of surgical management leading to superior outcomes compared to those not receiving surgery. Radiation is an uncommonly pursued treatment pathway. Patient demographics and socioeconomic variables such as marital status may be valuable when investigating cancer outcomes. This updated database analysis can help inform diagnosis, management, and clinical outcomes for this rare group of malignancies.

First application of GammaTile cesium-131 brachytherapy with maximal safe resection of a glioma in a patient with limited scleroderma.

The purpose of this report is to present the first documented application of GammaTile to an intra-cranial tumor of a patient with a symptomatic radiosensitive connective tissue disorder, a case where there were significant concerns with standard oncologic strategies. We hypothesized that GammaTile® (GT Medical Technologies, Tempe, Arizona, USA) would also be advantageous in the application of intra-cranial tumors in patients with conditions of increased radiosensitivity. We generated a standard external beam radiation therapy (EBRT) plan consisting of an overall 1.5 cm expansion to 59.4 Gy in 1.8 Gy fractions. Also, we developed a CyberKnife (Accuray, Sunnyvale, CA, USA) plan with a 5 mm expansion on the surgical cavity prescribed to 60 Gy in 30 fractions, to make an EBRT comparison using the same prescription volume as GammaTile. We report the first published application of GammaTile® brachytherapy to an intra-cranial malignancy in a patient with limited scleroderma. The dose delivered by GammaTile was compared to the dose that would be delivered with both typical volumes and small volumes of EBRT. The maximum dose delivered to the scar and scalp by GammaTile was reduced to half of that from other external beam techniques (~25 Gy vs. ~55 Gy). MRI imaging at 6 months and 12 months post-resection demonstrated no evidence of disease recurrence nor radiation necrosis. At the 12-month follow-up visit, the surgical scar was well-healed with no skin changes to the surrounding scalp. Dosimetrically and clinically, this report highlights the successful application of GammaTile to an intra-cranial tumor bed in a patient with scleroderma.

Novel combination of GammaTile cesium-131 brachytherapy with 5-aminolevulinic acid fluorescence-guided resection in the re-irradiation of pediatric recurrent high-grade glioma: illustrative case.

BACKGROUND: Herein, the authors describe the successful utilization of 5-aminolevulinic acid (5-ALA) and the first case of GammaTile cesium-131 therapy in a pediatric patient with recurrent high-grade glioma. 5-ALA was utilized to optimize gross-total resection prior to GammaTile implantation. After conversion to an equivalent dose in 2-Gy fractions (EQD2), a composite was made of the GammaTile dose with the initial external beam radiotherapy. Two hypothetical plans consisting of a standard hypofractionated strategy for glioma reirradiation and a CyberKnife plan using GammaTile's planning target volume were developed and likewise underwent EQD2 conversion and composite plan generation with the initial radiotherapy. OBSERVATIONS: 5-ALA was useful in achieving gross-total resection with no acute toxicity from the surgery or GammaTile irradiation. When compared with the hypothetical composite doses, GammaTile's composite, axium point dose (D0.03cc) to the brainstem was 32.9 Gy less than the hypofractionated and the CyberKnife composite plans at 38.7 Gy and 40.2 Gy, respectively. The right hippocampus demonstrated a substantially reduced composite plan dose with GammaTile with a D0.03cc of 62.4 Gy versus 71.7 and 80.7 Gy for the hypofractionated and CyberKnife composite plans, respectively. LESSONS: Utilization of 5-ALA and GammaTile therapy yielded clinically superior tumor debulking and effective radiotherapy dose localization with sparing of organs at risk, respectively.

Children's Special Health Care Needs and Caregivers' Well-Being During the COVID-19 Pandemic.

BACKGROUND: Caregivers of children with special health care needs (SHCN) report worse self-rated health when compared with caregivers of children without SHCN and have experienced significant stress during the COVID-19 pandemic. We sought to determine whether COVID-19 pandemic-era declines in well-being among caregivers of children with SHCN were steeper than among caregivers of children without SHCN. METHODS: We used 2020 to 2021 (pandemic-era, n = 89,560) and 2018 to 2019 (pre-pandemic, n = 57,927) data from the National Survey of Children's Health. Caregiver-reported physical and mental health outcomes were analyzed using multivariable ordinal logistic regression. RESULTS: The pandemic era was associated with 26% higher odds of reporting worse mental health among caregivers of children with SHCN (95% confidence interval [CI]: +16%, +38%), and 20% higher odds of reporting worse mental health among caregivers of children without SHCN (95% CI: +15%, +26%). The magnitudes of these changes were not significantly different from one another (P = .341). CONCLUSIONS: Although caregivers of children with SHCN faced significant burdens and increased stress during the pandemic, decline in self-rated mental health among this group was similar to the trend seen among caregivers of children without SHCN.

Surgical management of a type A aortic dissection in a pregnant patient.

Despite emphasis for emergent surgical treatment of Stanford type A aortic dissections, pregnant patients that are clinically stable may safely receive a staged approach instead, with delivery followed by delayed dissection repair.

Fasciotomy on a female patient with acquired factor VIII: A case report and literature review of management.

Key Clinical Message: Acquired factor VIII inhibitors can be a rare cause of extensive intramuscular bleeding requiring fasciotomy. The subsequent postoperative period requires close monitoring due to high risk of fatal blood loss. Abstract: Acquired factor VIII inhibitors are a rare cause of often extensive bleeding and subsequently large hematomas. This disorder's overall mortality can reach 38%, largely due to immunosuppression and subsequent infections or an underlying cause such as malignancy. The patient in this case study presented with a hematoma and extensive ecchymosis of the hand and forearm, which continued to progress, precipitating compartment syndrome of the hand and forearm and ultimately requiring fasciotomy. The combination of factors led to significant blood loss in the postoperative period requiring major fluid resuscitation and intensive care unit (ICU) level care. Due to this disorder's rarity and overall mortality, we present this case report with a literature review for management of acquired hemophilia in the setting of urgent fasciotomy.

Airway management and quadratus lumborum block for inguinal hernia repair in context of chromosome 4q deletion: A case report.

Key Clinical Message: Chromosome 4q Deletion Syndrome (4QDS) is a rare chromosomal deletion that presents with various congenital defects that could affect anesthetic management. We present a patient with known 4QDS who underwent successful general anesthetic induction, tracheal intubation, and subsequently, bilateral quadratus lumborum nerve blocks, during laparoscopic inguinal hernia repair surgery. Abstract: Chromosome 4q deletion syndrome (4QDS) is a rare chromosomal deletion with the potential for congenital defects that could affect the anesthetic management of affected patients, specifically with inconsistent reports of possible laryngeal narrowing which could precipitate intubation difficulties. We present a report of a patient with known 4QDS who underwent successful general anesthetic induction and tracheal intubation, followed by subsequent bilateral quadratus lumborum nerve blocks, in the context of laparoscopic inguinal hernia repair surgery. Given the inconsistent presentation of patients with 4QDS reported in the literature, steps were taken to exercise sufficient caution concerning the overall management of this patient per the most recent guidelines for pediatric patients.

Impact of Race on Outcomes of Advanced Stage Non-Small Cell Lung Cancer Patients Receiving Immunotherapy.

BACKGROUND: The impact of race in advanced stage non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) is conflicting. Our study sought to examine racial disparities in time to treatment initiation (TTI), overall survival (OS), and progression-free survival (PFS) using a population that was almost equally black and white. METHODS: This was a retrospective cohort study of stage IV NSCLC patients > 18 years receiving immunotherapy at our center between 2014 and 2021. Kaplan-Meier curves and the multivariate Cox proportional hazards model determined the predictors of OS and PFS. Analyses were undertaken using IBM PSAW (SPSS v.28). RESULTS: Out of 194 patients who met the inclusion criteria, 42.3% were black (n = 82). In the multivariate analysis, there was no difference in PFS (HR: 0.96; 95% CI: 0.66,1.40; p = 0.846) or OS (HR: 0.99; 95% CI: 0.66, 1.48; p = 0.966). No difference in treatment selection was observed between white and black patients (p = 0.363), nor was there a difference observed in median time to overall treatment initiation (p = 0.201). CONCLUSIONS: No difference was observed in OS and PFS in black and white patients. Black patients' reception of timelier immunotherapy was an unanticipated finding. Future studies are necessary to better understand how race impacts patient outcomes.

Severe Thrombocytopenia in a 30-Year-Old African American Male With Newly Diagnosed Sarcoidosis: A Case Report.

Sarcoidosis is a multisystem inflammatory disorder characterized by the formation of non-caseating granulomas. Hematological manifestations such as thrombocytopenia are unusual presentations of the disease. Various theories have been proposed for the development of thrombocytopenia in patients with sarcoidosis such as decreased production in bone marrow caused by granuloma formation, hypersplenism, and immune thrombocytopenia (ITP). We present a case of a 30-year-old African American male with ITP secondary to sarcoidosis who presented with a sudden onset of buccal mucosa and mucocutaneous bleeding and was found to have severe thrombocytopenia with values reaching as low as 1000/uL without prior history of easy bruising or bleeding. Overall, our patient had dyspnea, mucocutaneous bleeding, and was found to have mediastinal and hilar adenopathy, isolated thrombocytopenia, no splenomegaly, and non-necrotizing granulomas in the lymph nodes. The patient received platelet transfusions without initial response and received intravenous immunoglobulin (IVIG), romiplostim, and steroids with subsequent improvement in the platelet count after sufficient administration of a treatment regimen of approximately one week. Confounding factors that resulted in diagnostic uncertainty of our patient presentation included travel history with prophylactic antimalarial medications, doxycycline usage, only slightly elevated Angiotensin-Converting Enzyme (ACE) levels, and imaging features concerning metastatic disease vs. lymphoma. The clinical diversity of sarcoidosis often leads to diagnostic uncertainty and treatment delays due to its resemblance to other more common disorders. This is a novel case report of the earliest temporal presentation of severe thrombocytopenia and sarcoidosis in an African American male reported in the literature.

Dexmedetomidine and Propofol at End of Life in Pediatric Oncology: Trends in Palliative Sedation Therapy.

Context: Palliative sedation therapy (PST) can address suffering at the end of life (EOL) in children with cancer; yet, little is known about PST in this population. Objectives: We sought to describe the characteristics of pediatric oncology patients requiring PST at the EOL. Methods: A retrospective review was completed for pediatric oncology patients who required PST at a United States academic institution over 10 years, including demographics, disease characteristics, EOL characteristics, and medications for PST and symptom management. Results: PST was utilized in 3% of patients at the EOL. Of 24 study participants receiving PST, 83% (n = 20), 12.5% (n = 3), and 4.2% (n = 1) received dexmedetomidine, propofol, or both, respectively. The most frequent diagnosis for patients receiving PST was acute myelogenous leukemia (20.8%, n = 5). All patients were followed up by the palliative care team, and two-thirds (66.6%, n = 16) were also followed up by the pain management service; 79% (n = 19) were enrolled in hospice, and 98.5% (n = 23) had a Physician Orders for Scope of Treatment in place. Pain was the most common refractory symptom leading to PST initiation (33.3%, n = 8), followed by neuroagitation and dyspnea. PST was initiated a median of 2.5 days before death. A third of deaths occurred in the intensive care unit (33.3%, n = 8). Conclusions: PST was rare in this study; dexmedetomidine was used as first-line treatment for PST in patients at the EOL with refractory symptoms. Its place in PST protocols in pediatric oncology should be validated with prospective studies. Our study suggests the potential value of collaboration between palliative care and pain specialists in the context of PST.

Patient-Reported Sexual Function, Bladder Function and Quality of Life for Patients with Low Rectal Cancers with or without a Permanent Ostomy.

BACKGROUND: Despite the increasing utilization of sphincter and/or organ-preservation treatment strategies, many patients with low-lying rectal cancers require abdominoperineal resection (APR), leading to permanent ostomy. Here, we aimed to characterize overall, sexual-, and bladder-related patient-reported quality of life (QOL) for individuals with low rectal cancers. We additionally aimed to explore potential differences in patient-reported outcomes between patients with and without a permanent ostomy. METHODS: We distributed a comprehensive survey consisting of various patient-reported outcome measures, including the FACT-G7 survey, ICIQ MLUTS/FLUTS, IIEF-5/FSFI, and a specific questionnaire for ostomy patients. Descriptive statistics and univariate comparisons were used to compared demographics, treatments, and QOL scores between patients with and without a permanent ostomy. RESULTS: Of the 204 patients contacted, 124 (60.8%) returned completed surveys; 22 (18%) of these had a permanent ostomy at the time of survey completion. There were 25 patients with low rectal tumors (≤5 cm from the anal verge) who did not have an ostomy at the time of survey completion, of whom 13 (52%) were managed with a non-operative approach. FACTG7 scores were numerically lower (median 20.5 vs. 22, p = 0.12) for individuals with an ostomy. Sexual function measures IIEF and FSFI were also lower (worse) for individuals with ostomies, but the results were not significantly different. MLUTS and FLUTS scores were both higher in individuals with ostomies (median 11 vs. 5, p = 0.06 and median 17 vs. 5.5, p = 0.01, respectively), suggesting worse urinary function. Patient-reported ostomy-specific challenges included gastrointestinal concerns (e.g., gas, odor, diarrhea) that may affect social activities and personal relationships. CONCLUSIONS: Despite a limited sample size, this study provides patient-centered, patient-derived data regarding long-term QOL in validated measures following treatment of low rectal cancers. Ostomies may have multidimensional negative impacts on QOL, and these findings warrant continued investigation in a prospective setting. These results may be used to inform shared decision making for individuals with low rectal cancers in both the settings of organ preservation and permanent ostomy.

Compassionate de-escalation of life-sustaining treatments in pediatric oncology: An opportunity for palliative care and intensive care collaboration.

Context: Approximately 40%-60% of deaths in the pediatric intensive care unit (PICU) are in the context of de-escalation of life-sustaining treatments (LSTs), including compassionate extubation, withdrawal of vasopressors, or other LSTs. Suffering at the end of life (EOL) is often undertreated and underrecognized. Pain and poor quality of life are common concerns amongst parents and providers at a child's EOL. Integration of palliative care (PC) may decrease suffering and improve symptom management in many clinical situations; however, few studies have described medical management and symptom burden in children with cancer in the pediatric intensive care unit (PICU) undergoing de-escalation of LSTs. Methods: A retrospective chart review was completed for deceased pediatric oncology patients who experienced compassionate extubation and/or withdrawal of vasopressor support at EOL in the PICU. Demographics, EOL characteristics, and medication use for symptom management were abstracted. Descriptive analyses were applied. Results: Charts of 43 patients treated over a 10-year period were reviewed. Most patients (69.8%) were white males who had undergone hematopoietic stem cell transplantation and experienced compassionate extubation (67.4%) and/or withdrawal of vasopressor support (44.2%). The majority (88.3%) had a physician order for scope of treatment (POST - DNaR) in place an average of 13.9 days before death. PC was consulted for all but one patient; however, in 18.6% of cases, consultations occurred on the day of death. During EOL, many patients received medications to treat or prevent respiratory distress, pain, and agitation/anxiety. Sedative medications were utilized, specifically propofol (14%), dexmedetomidine (12%), or both (44%), often with opioids and benzodiazepines. Conclusions: Pediatric oncology patients undergoing de-escalation of LSTs experience symptoms of pain, anxiety, and respiratory distress during EOL. Dexmedetomidine and propofol may help prevent and/or relieve suffering during compassionate de-escalation of LSTs. Further efforts to optimize institutional policies, education, and collaborations between pediatric intensivists and PC teams are needed.

Children's unmet need for mental health care within and outside metropolitan areas.

BACKGROUND: Rural communities experience a lack of pediatric mental health providers. It is unclear if this leads to greater unmet needs for specialty mental health services among rural children. METHODS: Data from the 2016-2019 National Survey of Children's Health were used to identify children aged 6-17 years with a mental health condition. Caregiver-reported need and receipt of specialty mental health care for their child (met need, unmet need, or no need) was compared according to residence in a Metropolitan Statistical Area (MSA). RESULTS: The analysis included 13,021 children (14% living outside MSAs). Unmet need for mental health services was reported for 9% of children, with no difference by rural-urban residence (p = 0.940). Multivariable analysis confirmed this finding and identified urban children as less likely to have no need for mental health services, compared to rural children (relative risk ratio of no need vs. met need: 0.79; 95% confidence interval: 0.65, 0.95; p = 0.015). CONCLUSION: Children with mental health conditions living in rural areas (outside MSAs) did not have higher rates of unmet needs for specialty mental health services, but they had lower rates of any caregiver-reported needs for such services. Further work is needed to examine caregivers' demand for pediatric specialty mental health services.

Top Ten Tips Palliative Care Clinicians Should Know About Caring for Muslims.

Islam is the fastest-growing religion across the world and in the United States. Adherents of Islam are known as Muslims. Globally, Muslims comprise the second largest religious group with 1.8 billion people, or 24% of the world's population, and range in racial and ethnic diversity.1 As this population continues to grow, palliative care clinicians will invariably care for a Muslim patient therefore making it important to have a basic understanding of values, traditions, and beliefs held by them. This article outlines 10 basic principles held by many Muslim patients and their families that can allow for palliative care to be delivered in a culturally inclusive way. This article should serve as a point of initiation for further exploration of their needs as it is not a comprehensive guide.