Citations

Purpose of review The purpose of this review is to analyze and consolidate recently published literature to provide updated guidelines on the diagnosis and management of nontuberculous mycobacterial lymphadenitis (NTM LAD) in the pediatric population and to suggest areas of further research. Recent findings Diagnosis of NTM LAD relies on a detailed clinical history, physical examination, laboratory tests, and imaging techniques. Treatment strategies vary widely, with a shift towards complete surgical excision being observed due to its higher cure rate, improved aesthetic outcomes, and lower recurrence rates. However, patient-specific factors must be considered. The role of genetic factors, such as Mendelian susceptibility to mycobacterial disease (MSMD), is being increasingly recognized and could lead to targeted therapies. Summary Despite strides in the understanding and management of NTM LAD, substantial gaps remain in key areas such as the role of diagnostic imaging, optimal treatment parameters, postoperative care, and surveillance strategies. In this article, we explain our approach to NTM using the most relevant evidence-based medicine while offering directions for future work.

Abstract Background: Reliable non-invasive biomarkers for human papillomavirus (HPV) associated oropharyngeal squamous cell carcinoma (OPX) are lacking. We performed a discovery and validation study of methylated DNA markers (MDMs) for detection of OPX. In addition, we sought to evaluate the MDM profiles in saliva gargle samples from normal controls (nSAL). Methods: Formalin fixed paraffin embedded OPX and gender-balanced normal oropharyngeal tissue (NOP) were pathologically reviewed and punched for DNA extraction and sequenced using reduced representation bisulfite sequencing (RRBS). A tiling algorithm was used to define candidate MDMs. Highest ranked (e.g., area under the receiver operating characteristic curve (AUC), fold-change, p-value) candidate MDMs were validated by qMSP in independent OPX and NOP samples. nSAL DNA was used to assess MDM background signal. Discrimination between OPX tissue, NOP, and nSAL was assessed using AUC with corresponding 95% confidence intervals. HPV was confirmed with p16 staining or DNA in situ hybridization. Results: RRBS discovery assessed 18 OPX, 18 NOP, and 18 normal WBC samples. 234 MDM candidates from approximately 3 × 106 CpGs at >10X coverage were identified. 36 MDMs were selected for validation in independent patient samples which included 32 OPX, 36 NOP, and 35 nSAL specimens. OPX patients were older (median 51; IQR 45-54 years) than NOP patients (median 29; IQR 24-42). 69 and 61% of OPX and NOP patients were female, respectively. The majority of OPX patients were Stage I (n=27, 84%). We observed excellent discrimination between OPX and NOP in the validation set; the median AUC across 36 MDMs was 0.90 (IQR 0.87-0.95). The 10 highest performing markers (PARP15, EPDR1, SHROOM1, EMBP1.rs, IFFO1, MAX.chr19.118, ZNF763, ITGB4, FAM19A2, and MT1IP) exhibited AUCs ranging from 0.95-0.99. Strong discrimination was also observed between OPX and nSAL (Median AUC=0.97; IQR=0.93-0.99). All 10 of the highest-performing markers in tissue exhibited AUCs of at least 0.97 for discriminating OPX versus nSAL. Median fold change between NOP and nSAL across all MDMs was 1.9 (IQR 1.4-3.8), demonstrating low background signal in nSAL. Conclusions: We found strong discrimination in a panel of 36 MDMs between OPX case and control tissue as well as between OPX case tissue and normal saliva. The low background signal observed in normal saliva makes this media a strong candidate for non-invasive detection of OPX. Further studies are in development to assess the utility of measuring these MDMs in both case and control saliva and blood for detecting OPX non-invasively. Citation Format: Benjamin R. Gochanour, David M. Routman, Kathleen R. Bartemes, William R. Taylor, Douglas W. Mahoney, Rondell P. Graham, Xiaoming Cao, Calise K. Berger, Sara S. Then, Karen A. Doering, Kelli N. Burger, Patrick H. Foote, John B. Kisiel, Kathryn M. Van Abel. Discovery and validation of methylated DNA markers of human papillomavirus associated oropharyngeal squamous cell carcinoma [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PO-039.

Prognosis is generally poor for patients with pancreatic ductal adenocarcinoma. However, patients with germline BRCA1 or BRCA2 mutations (gBRCAm) may benefit from first-line platinum-based chemotherapy and maintenance therapy with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib following at least 16 weeks of first-line platinum-based chemotherapy without disease progression. Germline breast cancer gene (BRCA) testing is therefore important to ensure that patients receive the most effective treatment. In addition, testing for other DNA damage response gene mutations beyond gBRCAm may also guide treatment decisions. However, clinical pathways for genetic testing are often suboptimal, leading to delays in treatment initiation or missed opportunities for personalized therapy. Barriers to testing include low rates of referral and uptake, delays to referral and slow result turnaround times, cost, and biopsy and assay limitations if somatic testing is performed, leading to the requirement for subsequent dedicated germline testing. Low rates of referral may result from lack of awareness among physicians of the clinical value of testing, coupled with low confidence in interpreting test results and poor availability of genetic counseling services. Among patients, barriers to uptake may include similar lack of awareness of the clinical value of testing, anxiety regarding the implications of test results, lack of insurance coverage, fear of negative insurance implications, and socioeconomic factors. Potential solutions include innovative approaches to testing pathways, including ‘mainstreaming’ of testing in which BRCA tests are routinely arranged by the treating oncologist, with the involvement of genetic counselors if a patient is found to have a gBRCAm. More recently, the utility of multigene panel analyses has also been explored. Access to genetic counseling may also be improved through initiatives such as having a genetic counseling appointment for all new patient visits and telemedicine approaches, including the use of telephone consultations or DVD-assisted counseling. Educational programs will also be beneficial, and cost effectiveness is likely to improve as the number of targeted treatments increases and when the earlier detection of tumors in family members following cascade testing is considered.

Introduction: The safety of conversional bariatric procedures after sleeve gastrectomy (SG) for weight recurrence (WR) or inadequate weight loss (IWL) is debated due to limited evidence. Conversion options include Roux-en-Y gastric bypass (RYGB), single anastomosis duodeno-ileal bypass (SADI), and biliopancreatic diversion with duodenal switch (BPD-DS). We aimed to compare serious complications and mortality rates between these procedures within 30 days. Methods: Using the 2020 and 2021 MBSAQIP databases, we identified patients who underwent a conversion from SG to RYGB, SADI, or BPD-DS. We performed a multivariable logistic regression to assess predictors of 30-day complications and mortality. Results: Among 7388 patients (77.6% RYGB, 8.7% SADI, 13.7% BPD-DS), those undergoing SADI and BPD-DS had higher preoperative body mass index. Conversion reasons included WR (63.0%) and IWL (37.0%). SADI and BPD-DS patients had longer operative times (p < 0.001) and higher leak rates (p = 0.001). Serious complications, reoperations, readmissions, and 30-day mortality were similar across groups. Conversion procedure type was not an independent predictor of complications. Conclusion: RYGB was the most performed conversional procedure after SG. The study indicated a similar safety profile for revisional RYGB, SADI, and BPD-DS, with comparable 30-day complications and mortality rates. However, SADI and BPD-DS patients had longer operative time and higher leak rates.

AbstractBackgroundOutcomes for children with relapsed/refractory (R/R) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are poor, and new therapies are needed. Pevonedistat is an inhibitor of the NEDD‐8 activating enzyme, a key regulator of the ubiquitin proteasome system that is responsible for protein turnover, with protein degradation regulating cell growth and survival.ProcedureWe evaluated the feasibility, toxicity, and pharmacokinetics (PK) of pevonedistat (20 mg/m2 days 1, 3, 5) in combination with azacitidine, fludarabine, cytarabine (aza‐FLA) in children with R/R AML and MDS (NCT03813147). Twelve patients were enrolled, median age was 13 years (range 1–21). Median number of prior chemotherapeutic regimens was two (range one to five), and two (25%) patients had prior hematopoietic cell transplantation. Diagnoses were AML NOS (n = 10, 83%), acute monocytic leukemia (n = 1), and therapy‐related AML (n = 1).ResultsOverall, three of 12 (25%) patients experienced DLTs. The day 1 mean ± SD (n = 12) Cmax, VSS, T1/2, and CL were 223 ± 91 ng/mL, 104 ± 53.8 L/m2, 4.3 ± 1.2 hours, and 23.2 ± 6.9 L/h/m2, respectively. T1/2, VSS, and Cmax, but not CL, were significantly different between age groups. The overall response rate was 25%, with n = 3 patients achieving a complete remission with incomplete hematologic recovery (CRi).ConclusionsPevonedistat 20 mg/m2 combined with Aza‐FLA was tolerable in children with R/R AML with similar toxicity profile to other intensive AML regimens. However, within the confines of a phase 1 study, we did not observe that the pevonedistat + Aza‐FLA combination demonstrated significant anti‐leukemic activity.

AbstractIntroductionPalliative care is a critical component of pediatric oncology care. Embedded pediatric palliative care (PPC) is relatively new in pediatric hematology/oncology (PHO) and may improve access, utilization, and quality of PPC. In June 2020, the Mayo Clinic PPC service transitioned from an afternoon, physically independent clinic to an all‐day clinic embedded within PHO.MethodsRetrospective chart review was used to quantify consultation rates from PHO to PPC in 12‐month study periods before and after establishment of an embedded clinic. Changes in descriptive statistics and consult patterns were calculated. Study periods were compared using either chi‐square or Fisher's exact tests for categorical variables and Wilcox rank sum tests for continuous variables.ResultsThere was an 89% increase in consultations from PHO to PPC after initiation of an embedded clinic (n = 20 vs. n = 38 per 12 months). The absolute number of completed outpatient consults increased from three (15% of visits) pre‐embedment to fourteen (37%) post‐embedment (p = .082). The median number of days from first oncology visit to PPC assessment was unchanged after embedment (36 vs. 47 days, p = .98). Consults for solid tumors increased from 22% (n = 4) pre‐embedment to 60% (n = 18) post‐embedment (p < .05). Consults for symptom management increased from 60% (n = 12) to 87% (n = 33) (p < .05).ConclusionsEmbedment of PPC into a PHO workspace was associated with an increased number of total consults, outpatient consults, solid tumor consults, and consults for symptom management. Our “partial‐PPO” model allowed for provision of PPC in the outpatient oncology setting in a clinic where there is not enough volume to support a full‐time oncology‐focused clinician team.

Purpose To evaluate long‐term patient‐reported outcomes and achievement rates of patient acceptable symptomatic state (PASS) in young athletes undergoing hip arthroscopy, and to report long‐term sports continuance and reoperation. Methods Inclusion criteria consisted of age <24 years at surgery, femoroacetabular impingement undergoing primary hip arthroscopy with labral repair, and participation in sport with intent to return to sport after surgery. The enrollment period was from April 2009 to June 2014. Modified Harris Hip Scores (mHHS), Hip Outcome Score (HOS), HOS Activities of Daily Living (HOS‐ADL), and HOS Sport (HOS‐Sport) were collected preoperatively, 2 years’ postoperatively, and final follow‐up. Patients were evaluated for PASS achievement, reoperation, and sports participation. Results Forty‐two hips in 37 patients (11 male, 26 female, age: 17.7 ± 2.1 years, range 13.6‐23.0, body mass index 22.8 ± 2.9, range 17.6‐33.7) met inclusion criteria and were followed for 10.0 ± 1.3 years (range 8.5‐13.0) postoperatively. Mean mHHS, HOS‐ADL and HOS‐Sports outcome scores at minimum 8.5 years were 82.2 ± 12.9, 89.6 ± 10.9, and 81.8 ± 16.4, respectively, with significant ( P < .001) postoperative improvements. Thirty survey respondents (83%) met PASS for mHHS, 27 (75%) for HOS‐ADL, and 24 (67%) for HOS‐Sports. At minimum 8.5‐year follow‐up, only 9 of 37 (24%) cited their hip as the reason for stopping sport. Of the remaining patients, 17 of 28 (61%), continued playing their initial sport. There was no difference in patient‐reported outcomes between patients who endorsed sports continuance and patients who did not report sports continuance and did not cite their hip as a reason ( P ≥ .229). At final follow‐up, 4 hips (10%) had undergone subsequent surgical intervention at a mean of 4.8 ± 3.3 years (range 1.0‐8.4) postoperatively. Conclusions Durable mid‐term outcomes and satisfactory PASS achievement rates are observed in young amateur athletes undergoing primary hip arthroscopy. At minimum 8.5‐year follow up, approximately 1 in 4 patients discontinue their sports due to hip related reasons. Level of Evidence Level IV, case‐series.

Purpose To develop a machine learning model capable of identifying subscapularis tears before surgery based on imaging and physical examination findings. Methods Between 2010 and 2020, 202 consecutive shoulders underwent arthroscopic rotator cuff repair by a single surgeon. Patient demographics, physical examination findings (including range of motion, weakness with internal rotation, lift/push‐off test, belly press test, and bear hug test), and imaging (including direct and indirect signs of tearing, biceps status, fatty atrophy, cystic changes, and other similar findings) were included for model creation. Results Sixty percent of the shoulders had partial or full thickness tears of the subscapularis verified during surgery (83% of these were upper third). Using only preoperative imaging‐related parameters, the XGBoost model demonstrated excellent performance at predicting subscapularis tears (c‐statistic, 0.84; accuracy, 0.85; F1 score, 0.87). The top 5 features included direct signs related to the presence of tearing as evidenced on magnetic resonance imaging (MRI) (changes in tendon morphology and signal), as well as the quality of the MRI and biceps pathology. Conclusions In this study, machine learning was successful in predicting subscapularis tears by MRI alone in 85% of patients, and this accuracy did not decrease by isolating the model to the top features. The top five features included direct signs related to the presence of tearing as evidenced on MRI (changes in tendon morphology and signal), as well as the quality of the MRI and biceps pathology. Last, in advanced modeling, the addition of physical examination or patient characteristics did not make a significant difference in the predictive ability of this model. Level of Evidence Level III, diagnostic case‐control study.