Making sense of artificial intelligence and large language models-including ChatGPT-in pediatric hematology/oncology.

ChatGPT and other artificial intelligence (AI) systems have captivated the attention of healthcare providers and researchers for their potential to improve care processes and outcomes. While these technologies hold promise to automate processes, increase efficiency, and reduce cognitive burden, their use also carries risks. In this commentary, we review basic concepts of AI, outline some of the capabilities and limitations of currently available tools, discuss current and future applications in pediatric hematology/oncology, and provide an evaluation and implementation framework that can be used by pediatric hematologist/oncologists considering the use of AI in clinical practice.

Exploring the impact of anterior chest wall scars from implantable venous ports in adolescent survivors of cancer.

BACKGROUND: In children with cancer, port-a-caths (ports) are commonly placed in the right anterior chest wall, leaving a visible scar when removed. The psychological impact of port scars on survivors is unknown. It is unclear whether alternative sites should be considered. We assessed the impact of port scars on pediatric cancer survivors to determine whether a change in location is indicated. METHODS: We performed a cross-sectional single-center study of pediatric cancer survivors aged 13-18 years. A questionnaire explored participants' perceptions of their port scars. Four additional validated tools were used: Fitzpatrick scale, Patient and Observer Scar Assessment Scale (POSAS), Children's Dermatology Life Quality Index, and a Distress Thermometer. RESULTS: Among 100 participants (median age 15.8 years [13-18], median duration since treatment 8 years [1.5-14.8]), 75 'never/occasionally' thought about their port scars, 85 were not bothered by its location and 87 would not have preferred another site. Eleven participants were highly impacted by their scars: six thought about their scar 'everyday/all the time', four were highly bothered by its location, and nine would have preferred a different location. There was an association between the desire for different scar location and how much the location bothered participants (p < 0.0001), female sex (p = 0.03) and Patient POSAS score (p = 0.04). CONCLUSION: A port scar on the anterior chest wall was not a major concern for the majority of this cohort. A minority of participants were highly impacted by the scar and its location. Advance identification of those likely to be impacted by their scars may not be possible.

Prevalence and Clinical Correlations of Somatostatin Receptor-2 (SSTR2) Expression in Neuroblastoma.

Alternative radiolabeled, targeted agents are being investigated for children with relapsed neuroblastoma (NB) who do not respond to I-metaiodobenzylguanidine (MIBG) therapy. (DOTA-Tyr)-octreotate targets somatostatin receptors (SSTRs), particularly SSTR2, which are expressed on NB cells. We investigated SSTR2 expression in NB tumors (36 high-risk [HR]; 33 non-HR patients) and correlated SSTR2 levels with clinical features, norepinephrine transporter (NET) expression, and MIBG avidity. SSTR2 and NET immunohistochemistry scores (0 to 3) were calculated on biopsies using digital image analysis based on staining intensity and distribution. Clinical data were correlated with SSTR2 expression. Median SSTR2 score for 69 patients was 1.31 (0.26 to 2.55). Non-HR NB was associated with a higher SSTR2 score (P=0.032). The SSTR2 expression did not correlate with age, International Neuroblastoma Staging System (INSS) stage, MYCN amplification and histology. Higher SSTR2 scores were observed in MIBG-avid versus MIBG-nonavid NB. SSTR2 score was not significantly associated with NET score (r=-0.062, P=0.62). Twenty-six patients who relapsed or progressed had a median SSTR2 score of 1.33 (0.26 to 2.55). Patients with NB including relapsed or progressive disease showed SSTR2 expression at diagnosis, suggesting they could be candidates for radiolabeled-DOTA-conjugated peptide imaging or therapy.

Characteristics and management of ganglioneuroma and ganglioneuroblastoma-intermixed in children and adolescents.

BACKGROUND: Ganglioneuromas (GNs) usually demonstrate favorable histological and clinical features. Surgery is often performed due to clinical symptoms and/or theoretical concerns that GN may transform into neuroblastoma (NB); however, several studies have identified significant GN-surgical morbidities. OBJECTIVES: We compared the natural history, biological and clinical features of GN and ganglioneuroblastoma-intermixed (GNB-I) managed by surgery or observation to inform management and surveillance. PROCEDURES: This retrospective study includes patients (n = 67) with histological diagnosis of GN (50/67) and GNB-I (17/67) at the Hospital for Sick Children between 1990 and 2014. Clinical, pathological features, tumor dimensions, and management were recorded. RESULTS: Median age and maximal tumor diameter were 6 years (1.3-17.8) and 6.3 cm (1.4-16.9), respectively. Of the 67 patients, 46 (69%) had upfront surgery and 21 (31%) were observed. Of the 21 observed patients 4 later underwent resection. There were post-operative complications in 15 of the 50 (30%) surgical patients. The presence of imaging-defined risk factors correlated with complications (P = 0.005). Observed patients were older (median 8.4 vs. 5.3 years) and diagnosed more recently. Median growth was 0.3 cm/year and 6 of 21 had progressive disease (PD). At median follow-up of 2.2 years (0.2-14.3), all patients were alive and for those with evaluable imaging there were 27 complete and 10 partial responses, 19 stable and 6 PD. Pathology classification changed at resection for three cases, but no GN was reclassified to NB. CONCLUSIONS: GN and GNB-I have a slow growth rate and resection can be associated with significant morbidity. Watch and wait approaches should be considered for some GN and GNB-I.

Pleasure, sex, prohibition, intellectual disability, and dangerous ideas.

The sexual lives of people with intellectual disability continue to be the subject of prohibition and restriction by disability sectors. Without access to sex education and the concomitant sex literacy, people with intellectual disability are denied the essential conversation about sex, sexual expression, and pleasure. The authors explore the history of sexual repression of people with intellectual disability, and the culture of sexual disempowerment. This propositional paper offers a sense of hope about sex facilitation and sex education for people with intellectual disability which can afford them a full life.

Stereotactic breast biopsies: Radiological-pathological concordance in a South African referral unit.

Background: Stereotactic breast biopsies have become the gold standard for tissue diagnosis in non-palpable, sonographically occult breast abnormalities seen on mammogram. Only limited data exist in South Africa on the correlation between imaging findings and stereotactic biopsy histology. Objectives: To describe the mammographic findings and histological diagnosis in patients who underwent stereotactic breast biopsy at a referral hospital. In addition, to evaluate the proportion of malignancy in each Breast Imaging Reporting and Data System (BI-RADS) category. Method: A retrospective review of stereotactic breast biopsies was performed. Imaging characteristics (including BI-RADS category) and histological diagnosis were recorded. Using histopathology, cases were classified as benign, high-risk or malignant. Results: A total of 131 biopsies, from 123 patients, were included in the study. Most biopsies were performed on asymptomatic patients (79.3%, 104/131). The majority were categorised as BI-RADS 4 and demonstrated calcifications. Histology revealed a malignant diagnosis in 40 (30.5%) patients, a high-risk lesion in 8 (6.1%) patients and a benign diagnosis in 83 (63.4%) patients. There was a stepwise increase in the proportion of malignancy from BI-RADS category 3 to 5. When compared with surgical histology, the stereotactic biopsies demonstrated an overall ductal carcinoma in situ (DCIS) underestimation rate of 10.3%. Conclusion: Despite resource restrictions, stereotactic breast biopsies performed in a South African context produce radiological-pathological concordance in keeping with BI-RADS guidelines, as well as with local and international studies.

Perspective Toward Machine Learning Implementation in Pediatric Medicine: Mixed Methods Study.

BACKGROUND: Given the costs of machine learning implementation, a systematic approach to prioritizing which models to implement into clinical practice may be valuable. OBJECTIVE: The primary objective was to determine the health care attributes respondents at 2 pediatric institutions rate as important when prioritizing machine learning model implementation. The secondary objective was to describe their perspectives on implementation using a qualitative approach. METHODS: In this mixed methods study, we distributed a survey to health system leaders, physicians, and data scientists at 2 pediatric institutions. We asked respondents to rank the following 5 attributes in terms of implementation usefulness: the clinical problem was common, the clinical problem caused substantial morbidity and mortality, risk stratification led to different actions that could reasonably improve patient outcomes, reducing physician workload, and saving money. Important attributes were those ranked as first or second most important. Individual qualitative interviews were conducted with a subsample of respondents. RESULTS: Among 613 eligible respondents, 275 (44.9%) responded. Qualitative interviews were conducted with 17 respondents. The most common important attributes were risk stratification leading to different actions (205/275, 74.5%) and clinical problem causing substantial morbidity or mortality (177/275, 64.4%). The attributes considered least important were reducing physician workload and saving money. Qualitative interviews consistently prioritized implementations that improved patient outcomes. CONCLUSIONS: Respondents prioritized machine learning model implementation where risk stratification would lead to different actions and clinical problems that caused substantial morbidity and mortality. Implementations that improved patient outcomes were prioritized. These results can help provide a framework for machine learning model implementation.

Review: The Role of Radiolabeled DOTA-Conjugated Peptides for Imaging and Treatment of Childhood Neuroblastoma.

BACKGROUND: Childhood neuroblastoma is a heterogenous disease with varied clinical presentation and biology requiring different approaches to investigation and management. Metaiodobenzylguanidine (MIBG) is an essential component of metastatic staging for neuroblastoma and has been used as a treatment strategy for relapsed and refractory neuroblastoma. However, as 10% of children with neuroblastoma will have 123I-MIBG non-avid imaging and up to 60% with relapsed and refractory neuroblastoma will require further treatment with 131I-MIBG, alternative radioisotopes have been investigated for imaging and treatment. Neuroblastoma tumors express mostly somatostatin receptor- 2 (SSTR2) that can be targeted by somatostatin analogues including DOTA-conjugated peptides e.g. DOTATATE, DOTATOC. OBJECTIVES: This review summarizes the rationale, utility and experience of DOTA-conjugated peptides in imaging and treatment of childhood neuroblastoma. RESULTS AND CONCLUSIONS: Radiolabeled DOTA-peptides are used routinely in adults to image neuroendocrine tumors and have potential to be used to image and treat neuroblastoma. 68Ga-DOTATATE PET/CT has been shown to have better sensitivity, quicker clearance and administration times, reduced radiation exposure and limited toxicity compared to 123I-MIBG. Therapeutic studies of peptide receptor radionuclides e.g. 177Lu-DOTATATE in patients with relapsed neuroblastoma have used 68Ga- DOTATATE PET/CT to determine eligibility for therapy. Further studies would need to investigate appropriate indications, timings, scoring and clinical significance of radiolabeled DOTA-peptide conjugated PET/CT imaging in childhood neuroblastoma.

Single Session Low Frequency Left Dorsolateral Prefrontal Transcranial Magnetic Stimulation Changes Neurometabolite Relationships in Healthy Humans.

Background: Dorsolateral prefrontal cortex (DLPFC) low frequency repetitive transcranial magnetic stimulation (LF-rTMS) has shown promise as a treatment and investigative tool in the medical and research communities. Researchers have made significant progress elucidating DLPFC LF-rTMS effects-primarily in individuals with psychiatric disorders. However, more efforts investigating underlying molecular changes and establishing links to functional and behavioral outcomes in healthy humans are needed. Objective: We aimed to quantify neuromolecular changes and relate these to functional changes following a single session of DLPFC LF-rTMS in healthy participants. Methods: Eleven participants received sham-controlled neuronavigated 1 Hz rTMS to the region most activated by a 7-letter Sternberg working memory task (SWMT) within the left DLPFC. We quantified SWMT performance, functional magnetic resonance activation and proton Magnetic resonance spectroscopy (MRS) neurometabolite measure changes before and after stimulation. Results: A single LF-rTMS session was not sufficient to change DLPFC neurometabolite levels and these changes did not correlate with DLPFC activation changes. Real rTMS, however, significantly altered neurometabolite correlations (compared to sham rTMS), both with baseline levels and between the metabolites themselves. Additionally, real rTMS was associated with diminished reaction time (RT) performance improvements and increased activation within the motor, somatosensory and lateral occipital cortices. Conclusion: These results show that a single session of LF-rTMS is sufficient to influence metabolite relationships and causes widespread activation in healthy humans. Investigating correlational relationships may provide insight into mechanisms underlying LF-rTMS.

Correlation of Somatostatin Receptor-2 Expression with Gallium-68-DOTA-TATE Uptake in Neuroblastoma Xenograft Models.

Peptide-receptor imaging and therapy with radiolabeled somatostatin analogs such as 68Ga-DOTA-TATE and 177Lu-DOTA-TATE have become an effective treatment option for SSTR-positive neuroendocrine tumors. The purpose of this study was to evaluate the correlation of somatostatin receptor-2 (SSTR2) expression with 68Ga-DOTA-TATE uptake and 177Lu-DOTA-TATE therapy in neuroblastoma (NB) xenograft models. We demonstrated variable SSTR2 expression profiles in eight NB cell lines. From micro-PET imaging and autoradiography, a higher uptake of 68Ga-DOTA-TATE was observed in SSTR2 high-expressing NB xenografts (CHLA-15) compared to SSTR2 low-expressing NB xenografts (SK-N-BE(2)). Combined autoradiography-immunohistochemistry revealed histological colocalization of SSTR2 and 68Ga-DOTA-TATE uptake in CHLA-15 tumors. With a low dose of 177Lu-DOTA-TATE (20 MBq/animal), tumor growth inhibition was achieved in the CHLA-15 high SSTR2 expressing xenograft model. Although, in vitro, NB cells showed variable expression levels of norepinephrine transporter (NET), a molecular target for 131I-MIBG therapy, low 123I-MIBG uptake was observed in all selected NB xenografts. In conclusion, SSTR2 expression levels are associated with 68Ga-DOTA-TATE uptake and antitumor efficacy of 177Lu-DOTA-TATE. 68Ga-DOTA-TATE PET is superior to 123I-MIBG SPECT imaging in detecting NB tumors in our model. Radiolabeled DOTA-TATE can be used as an agent for NB tumor imaging to potentially discriminate tumors eligible for 177Lu-DOTA-TATE therapy.