ctDNA transiting into urine is ultrashort and facilitates noninvasive liquid biopsy of HPV+ oropharyngeal cancer.

BACKGROUNDTransrenal cell-free tumor DNA (TR-ctDNA), which transits from the bloodstream into urine, has the potential to enable noninvasive cancer detection for a wide variety of nonurologic cancer types.MethodsUsing whole-genome sequencing, we discovered that urine TR-ctDNA fragments across multiple cancer types are predominantly ultrashort (<50 bp) and, therefore, likely to be missed by conventional ctDNA assays. We developed an ultrashort droplet digital PCR assay to detect TR-ctDNA originating from HPV-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) and confirmed that assaying ultrashort DNA is critical for sensitive cancer detection from urine samples.ResultsTR-ctDNA was concordant with plasma ctDNA for cancer detection in patients with HPV+ OPSCC. As proof of concept for using urine TR-ctDNA for posttreatment surveillance, in a small longitudinal case series, TR-ctDNA showed promise for noninvasive detection of recurrence of HPV+ OPSCC.ConclusionOur data indicate that focusing on ultrashort fragments of TR-ctDNA will be important for realizing the full potential of urine-based cancer diagnostics. This has implications for urine-based detection of a wide variety of cancer types and for facilitating access to care through at-home specimen collections.FundingNIH grants R33 CA229023, R21 CA225493; NIH/National Cancer Institute grants U01 CA183848, R01 CA184153, and P30CA046592; American Cancer Society RSG-18-062-01-TBG; American Cancer Society Mission Boost grant MBGI-22-056-01-MBG; and the A. Alfred Taubman Medical Research Institute.

Characterization of T-/natural killer cell lymphoproliferative neoplasms associated with systemic, chronic, active Epstein-Barr virus in adults: A report of 5 cases in a Western population.

OBJECTIVES: Because of its low frequency in adult populations and clinical and laboratory overlap with hemophagocytic lymphohistiocytosis and other T-cell lymphomas, T-cell/natural killer (NK) cell systemic, chronic, active Epstein-Barr virus (EBV) (T/NK sCAEBV) infection remains underdiagnosed, preventing critical, prompt therapeutic interventions. METHODS: We report a 5-case series that included 2 adult patients with T/NK sCAEBV and 3 additional adult patients with T/NK lymphomas with concomitant systemic EBV infection to review these entities' overlapping diagnostic and clinical features. RESULTS: Approximately 95% of the world population has been infected with EBV during their lifetime, and infection is usually asymptomatic, with symptomatic cases eventually resolving spontaneously. A small subset of immunocompetent patients develops CAEBV, a life-threatening complication resulting from EBV-infected T-cell or NK cell neoplastic lymphocytes. The sites of end-organ damage in T/NK sCAEBV demonstrate pathologic findings such as reactive lymphoid proliferations, making the diagnosis difficult to establish, with the only curative option being an allogeneic hematopoietic stem cell transplant. CONCLUSIONS: This diagnosis is most prevalent in Asia, with few cases reported in Western countries. Adult age is an independent risk factor for poor outcomes, and most cases are diagnosed in pediatric populations.

Novel In-Training Evaluation Report in an Internal Medicine Residency Program: Improving the Quality of the Narrative Assessment.

OBJECTIVE: To determine whether incorporating our novel in-training evaluation report (ITER), which prompts each resident to list at least three self-identified learning goals, improved the quality of narrative assessments as measured by the Narrative Evaluation Quality Instrument (NEQI). METHODS: A total of 1468 narrative assessments from a single institution from 2017 to 2021 were deidentified, compiled, and sorted into the pre-intervention form arm and post-intervention form arm. Due to limitations in our residency management suite, incorporating learning goals required switching from an electronic form to a hand-deliver form. Comments were graded by two research personnel utilizing the NEQI's scale of 0-12, with 12 representing the maximum quality for a comment. The outcome of the study was the mean difference in NEQI score between the electronic pre-intervention period and paper post-intervention period. RESULTS: The mean NEQI score for the pre-intervention period was 2.43 ± 3.34, and the mean NEQI score for the post-intervention period was 3.31 ± 1.71, with a mean difference of 0.88 (p < 0.001). In the pre-intervention period, 46% of evaluations were submitted without a narrative assessment (scored as a zero) while 1% of post-intervention period evaluations had no narrative assessment. Internal consistency reliability, as measured by Ebel's intraclass correlation coefficient (ICC), showed high agreement between the two raters (ICC = 0.92). CONCLUSIONS: Our findings suggest that implementing a timely, hand-delivered paper ITER that incorporates resident learning goals can lead to overall higher-quality narrative assessments.

T-Cell Prolymphocytic Leukemia: Diagnosis, Pathogenesis, and Treatment.

T-cell prolymphocytic leukemia (T-PLL) is a rare and aggressive neoplasm of mature T-cells. Most patients with T-PLL present with lymphocytosis, anemia, thrombocytopenia, and hepatosplenomegaly. Correct identification of T-PLL is essential because treatment for this disease is distinct from that of other T-cell neoplasms. In 2019, the T-PLL International Study Group (TPLL-ISG) established criteria for the diagnosis, staging, and assessment of response to treatment of T-PLL with the goal of harmonizing research efforts and supporting clinical decision-making. T-PLL pathogenesis is commonly driven by T-cell leukemia 1 (TCL1) overexpression and ATM loss, genetic alterations that are incorporated into the TPLL-ISG diagnostic criteria. The cooperativity between TCL1 family members and ATM is seemingly unique to T-PLL across the spectrum of T-cell neoplasms. The role of the T-cell receptor, its downstream kinases, and JAK/STAT signaling are also emerging themes in disease pathogenesis and have obvious therapeutic implications. Despite improved understanding of disease pathogenesis, alemtuzumab remains the frontline therapy in the treatment of naïve patients with indications for treatment given its high response rate. Unfortunately, the responses achieved are rarely durable, and the majority of patients are not candidates for consolidation with hematopoietic stem cell transplantation. Improved understanding of T-PLL pathogenesis has unveiled novel therapeutic vulnerabilities that may change the natural history of this lymphoproliferative neoplasm and will be the focus of this concise review.

Air All in the Wrong Places: A Case of Pneumorrhachis Secondary to Chronic Vomiting.

Pneumorrhachis (PR) is a rare phenomenon in which air is present in the spinal canal. PR can be stratified into different categories based on etiology, with spontaneous PR being the least common. In this report, we describe the case of a 33-year-old male with a four-year history of emesis secondary to chronic gastroparesis who presented with pleuritic chest pain radiating to the neck. A CT scan of the chest showed pneumomediastinum, with air extending into the soft tissues of the neck and the spinal canal. A literature review found a trend between maneuvers that increase intrathoracic pressure, such as emesis or coughing, and the incidence of spontaneous pneumomediastinum, in which air may freely communicate with the epidural space of the spinal canal. Currently, there are no guidelines for the management of patients with PR. From our experience, conservative management of asymptomatic PR is an appropriate approach for these patients.

Describing the sternalis muscle: a new variant and an amended classification.

PURPOSE: With emphasis on the clinical setting, knowledge of anatomical variation decreases misdiagnoses and surgical complications. We report a previously undocumented variant of sternalis muscle and recommend an augmented classification scheme. METHODS: Dissection of the anterior thoracic wall on an 83-year-old female cadaver revealed bilateral sternalis muscles. The Snosek et al. classification system was referenced to describe the variant types. RESULTS: The right sternalis muscle has a single belly and can be classified using the Snosek et al. classification system as a simple type, right single. The left sternalis muscle presented with three muscle bellies, each having a unique pattern of superior attachments (heads). This variation is previously undocumented and requires a more detailed classification. CONCLUSIONS: We propose the addition of a new subtype of sternalis classification, as well as a modification to the Snosek et al. (Clin Anat 27:866-884, 2014) classification scheme, to include classification of different muscle bellies when multiple are present.