Atezolizumab for Advanced Alveolar Soft Part Sarcoma.

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported. METHODS: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action. RESULTS: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1. CONCLUSIONS: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.).

Vincristine Side Effects With Concomitant Fluconazole Use During Induction Chemotherapy in Pediatric Acute Lymphoblastic Leukemia.

As a mainstay of treatment for acute lymphoblastic leukemia (ALL), vincristine's side effect profile is well known. Parallel administration of the antifungal fluconazole has been shown to interfere with the metabolism of vincristine, potentially resulting in increased side effects. We conducted a retrospective chart review to determine whether concomitant administration of vincristine and fluconazole during pediatric ALL induction therapy impacted the frequency of vincristine side effects, namely, hyponatremia and peripheral neuropathy. We also evaluated whether the incidence of opportunistic fungal infections was impacted by fluconazole prophylaxis. Medical charts of all pediatric ALL patients treated with induction chemotherapy at Children's Hospital and Medical Center in Omaha, NE, from 2013 to 2021 were retrospectively reviewed. Fluconazole prophylaxis did not significantly impact the rate of fungal infections. We found no correlation between fluconazole use and increased incidence of hyponatremia or peripheral neuropathy, which supports the safety of fungal prophylaxis with fluconazole during pediatric ALL induction therapy.

Pediatric Chronic Myelogenous Leukemia in T-lineage Blast Crisis: A Reminder in Relevance.

Pediatric Philadelphia chromosome positive (Ph+) acute T-cell lymphoblastic leukemia can mimic chronic myelogenous leukemia (CML) in T-lineage blast crisis (BC). Differentiating the 2 is critical in guiding therapy as most children with de novo Ph+ acute T-cell lymphoblastic leukemia are treated with chemotherapy and tyrosine kinase inhibitors, whereas T-lineage BC of CML can include hematopoietic stem cell transplantation. We present a unique case of CML in T-lineage BC. The patient was treated with induction chemotherapy plus imatinib followed by matched unrelated donor hematopoietic stem cell transplantation. She is currently off all medications and in complete disease remission.

Interdisciplinary care of children with trisomy 13 and 18.

Children with trisomy 13 and 18 (previously deemed "incompatible with life") are living longer, warranting a comprehensive overview of their unique comorbidities and complex care needs. This Review Article provides a summation of the recent literature, informed by the study team's Interdisciplinary Trisomy Translational Program consisting of representatives from: cardiology, cardiothoracic surgery, neonatology, otolaryngology, intensive care, neurology, social work, chaplaincy, nursing, and palliative care. Medical interventions are discussed in the context of decisional-paradigms and whole-family considerations. The communication format, educational endeavors, and lessons learned from the study team's interdisciplinary care processes are shared with recognition of the potential for replication and implementation in other care settings.

Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Advancements in technology that enhance our understanding of the biology of the disease, risk-adapted therapy, and enhanced supportive care have contributed to improved survival rates. However, additional clinical management is needed to improve outcomes for patients classified as high risk at presentation (eg, T-ALL, infant ALL) and who experience relapse. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for pediatric ALL provide recommendations on the workup, diagnostic evaluation, and treatment of the disease, including guidance on supportive care, hematopoietic stem cell transplantation, and pharmacogenomics. This portion of the NCCN Guidelines focuses on the frontline and relapsed/refractory management of pediatric ALL.

A Review of Apps for Calming, Relaxation, and Mindfulness Interventions for Pediatric Palliative Care Patients.

Patients and families increasingly use mobile apps as a relaxation and distraction intervention for children with complex, chronic medical conditions in the waiting room setting or during inpatient hospitalizations; and yet, there is limited data on app quality assessment or review of these apps for level of engagement, functionality, aesthetics, or applicability for palliative pediatric patients. The pediatric palliative care study team searched smartphone application platforms for apps relevant to calming, relaxation, and mindfulness for pediatric and adolescent patients. Apps were reviewed using a systematic data extraction tool. Validated Mobile Application Rating Scale (MARS) scores were determined by two blinded reviewers. Apps were then characterized by infant, child, adolescent, and adult caregiver group categories. Reviewer discussion resulted in consensus. Sixteen of the 22 apps identified were included in the final analysis. The apps operated on either iOS or Android platforms. All were available in English with four available in Spanish. Apps featured a relaxation approach (12/16), soothing images (8/16), and breathing techniques (8/16). Mood and sleep patterns were the main symptoms targeted by apps. Provision of mobile apps resource summary has the potential to foster pediatric palliative care providers' knowledge of app functionality and applicability as part of ongoing patient care.

Physician approaches to drug shortages: Results of a national survey of pediatric hematologist/oncologists.

AIM: To evaluate personnel involved in scarce drug prioritization and distribution and the criteria used to inform drug distribution during times of shortage among pediatric hematologists/oncologists. METHODS: Using the American Society of Pediatric Hematology/Oncology (ASPHO) membership list, a 20 question survey of pediatric hematologists/oncologists was conducted via email to evaluate personnel involved in scarce drug prioritization and distribution and criteria used to inform scarce drug distribution. RESULTS: Nearly 65% of the 191 study respondents had patients directly affected by drug shortages. Most physicians find out about shortages from the pharmacist (n = 179, 98%) or other doctors (n = 75, 41%). One third of respondents do not know if there is a program or policy for handling drug shortages at their institution. The pharmacist was the most commonly cited decision maker for shortage drug distribution (n = 128, 70%), followed by physicians (n = 109, 60%). One fourth of respondents did not know who makes decisions about shortage drug distribution at their institution. The highest priority criterion among respondents was use of the shortage drug for curative, rather than palliative intent and lowest priority criterion was order of arrival or first-come first-served. CONCLUSION: Despite pediatric hematology/oncology physicians and patients being heavily impacted by drug shortages, institutional processes for handling shortages are lacking. There is significant disparity between how decisions for distribution of shortage drugs are currently made and how study respondents felt those decisions should be made. An institution-based, and more importantly, a societal approach to drug shortages is necessary to reconcile these disparities.

An ethical framework for responding to drug shortages in pediatric oncology.

The frequency of drug shortages has increased considerably over the last decade. Important ethical issues arise whenever the supply of an effective drug is insufficient to meet demand. Using the ethical principles of beneficence, non-maleficence, and justice, institutions can guide prioritization of drug distribution before a shortage occurs to avoid unfair and unethical distribution of resources. This analysis will give a historical context for drug shortages, identify, and explore the central ethical concerns raised by drug shortages, and propose an ethical framework for addressing them in the context of pediatric oncology.

Liver transplant for congenital factor VII deficiency.

Congenital factor VII (FVII) deficiency is a rare, autosomal recessive bleeding disorder with a spectrum of phenotypes ranging from asymptomatic to life-threatening intra-cranial hemorrhage (ICH). Orthotopic liver transplantation has been described for definitive treatment in a few patients with severe manifestations. We report a patient with congenital FVII deficiency and recurrent ICH, despite twice-weekly prophylaxis with recombinant activated FVII. At 17 months of age, he underwent an orthotopic liver transplant. He is now 1-year post-transplant, on maintenance immunosuppression with no hemorrhage or other complications.

Improving pediatric hematology/oncology care in the emergency department.

PURPOSE: Pediatric hematology/oncology patients frequently use the emergency department (ED) for prompt care during potentially life-threatening events, such as sepsis and bleeding. One challenge of these visits is the unavailability of appropriate patient-specific medical information. Lack of information may result in ineffective ED visits for these patients with complex conditions. METHODS: A cross-sectional survey to determine ways to improve the care of pediatric hematology/oncology patients in the ED setting was conducted among parents at two affiliated pediatric hematology/oncology clinics. ED physicians in the catchment area of the clinic completed a separate survey. RESULTS: All physicians surveyed were confident in caring for pediatric patients in the ED; however, fewer were confident in caring for pediatric hematology/oncology patients. Physicians and parents reported that the patient's written medical history (physicians, 30%; parents, 33%), medication list (physicians, 28%; parents, 24%), on-call pediatric hematologist/oncologist contact information (physicians, 34%; parents, 31%), and needle size and gauge to access the patient's port (physicians, 8%; parents, 12%) would be valuable information to have when presenting to the ED. CONCLUSION: Parents were satisfied with ED care, but both physician and parent respondents thought additional information would be valuable to have available at the visit to help facilitate effective care.

Impact of cytomegalovirus (CMV) reactivation after umbilical cord blood transplantation.

This study investigated the impact of pretransplant cytomegalovirus (CMV) serostatus and posttransplant CMV reactivation and disease on umbilical cord blood transplant (UCBT) outcomes. Between 1994 and 2007, 332 patients with hematologic malignancies underwent UCBT and 54% were CMV seropositive. Pretransplant recipient CMV serostatus had no impact on acute or chronic graft-versus-host disease (aGVHD, cGVHD), relapse, disease-free survival (DFS), or overall survival (OS). There was a trend toward greater day 100 treatment-related mortality (TRM) in CMV-seropositive recipients (P=.07). CMV reactivation occurred in 51% (92/180) of patients with no difference in myeloablative (MA) versus reduced-intensity conditioning (RIC) recipients (P=.33). Similarly, reactivation was not influenced by the number of UCB units transplanted, the degree of HLA disparity, the CD34(+) or CD3(+) cell dose, or donor killer cell immunoglobulin-like receptor (KIR) gene haplotype. Rapid lymphocyte recovery was associated with CMV reactivation (P=.02). CMV reactivation was not associated with aGVHD (P=.97) or cGVHD (P=.65), nor did it impact TRM (P=.88), relapse (P=.62), or survival (P=.78). CMV disease occurred in 13.8% of the CMV-seropositive patients, resulting in higher TRM (P=.01) and lower OS (P=.02). Thus, although recipient CMV serostatus and CMV reactivation have little demonstrable impact on UCB transplant outcomes, the development of CMV disease remains a risk, associated with inferior outcomes.

Cutaneous leishmaniasis with boggy induration and simultaneous mucosal disease.

A woman had cutaneous, mucosal, and possible visceral leishmaniasis simultaneously. Many of her cutaneous lesions consisted of boggy indurations rather than customary papules, nodules, or ulcers. This unusual case was finally cured after four courses of miltefosine, one course of antimony, and two courses of Ambisome.

Training the clinical eye and mind: using the arts to develop medical students' observational and pattern recognition skills.

INTRODUCTION: Observation, including identification of key pieces of data, pattern recognition, and interpretation of significance and meaning, is a key element in medical decision making. Clinical observation is taught primarily through preceptor modelling during the all-important clinical years. No single method exists for communicating these skills, and medical educators have periodically experimented with using arts-based training to hone observational acuity. The purpose of this qualitative study was to better understand the similarities and differences between arts-based and clinical teaching approaches to convey observation and pattern recognition skills. METHOD: A total of 38 Year 3 students participated in either small group training with clinical photographs and paper cases (group 1), or small group training using art plus dance (group 2), both consisting of 3 2-hour sessions over a 6-month period. FINDINGS: Students in both conditions found value in the training they received and, by both self- and instructor-report, appeared to hone observation skills and improve pattern recognition. The clinically based condition appeared to have been particularly successful in conveying pattern recognition concepts to students, probably because patterns presented in this condition had specific correspondence with actual clinical situations, whereas patterns in art could not be generalised so easily to patients. In the arts-based conditions, students also developed skills in emotional recognition, cultivation of empathy, identification of story and narrative, and awareness of multiple perspectives. CONCLUSION: The interventions studied were naturally complementary and, taken together, can bring greater texture to the process of teaching clinical medicine by helping us see a more complete 'picture' of the patient.

Pectoralis major myocutaneous flap vs revascularized free tissue transfer: complications, gastrostomy tube dependence, and hospitalization.

OBJECTIVE: To evaluate the factors related to surgical complications, rate of gastrostomy tube (G-tube) dependence, and hospitalization in patients undergoing reconstruction with a pectoralis myocutaneous flap vs a soft-tissue revascularized flap. DESIGN: Quasi-experimental case series with a historic control group. POPULATION: A total of 179 patients (138 men and 41 women) with a mean (SD) age of 58 (14) years treated between January 1, 1986, and December 31, 1995, with a pectoralis flap (108 patients) or a revascularized free flap (71 patients). METHODS: Inclusion criteria were first or second extirpation, reconstruction with soft-tissue flap, or defect including the upper aerodigestive tract. Exclusion criteria were secondary reconstruction, or reconstruction for salvage of a complication. RESULTS: Although the major complication rate was not significantly different according to reconstructive approach, hypopharyngeal defects had a significantly higher major complication rate of 30% (6/20) compared with 8% (13/159) for other defect sites (P<.003). The minor complication rate was higher in the pectoralis group, at 57% (62/108), than in the revascularized flap group, at 21% (15/71) (P<.001). G-tube dependence was higher in the pectoralis group at 42% (40/96), in contrast to the revascularized flap group at 16% (10/63) (P<.001). G-tube dependence was 25% higher in patients who underwent salvage surgery after radiation (42% [30/72]) than in patients treated with postoperative radiation (17% [12/69]) (P<.004). Revascularized flaps helped ameliorate the effects of radiation before surgery; 56% (23/41) of the patients who received pectoralis flaps were G-tube dependent, while the rate of G-tube dependence in the revascularized flap group was 23% (7/31) (P<.004). Hospitalization was longer in the pectoralis group (14 days) than the revascularized flap group (12 days) (P<.006). CONCLUSION: Patients who undergo reconstruction with a pectoralis flap have significantly higher minor complication rates, a higher rate of G-tube dependence, and longer hospitalization than patients who undergo reconstruction with a soft-tissue revascularized flap.