Immunosequencing Applications in Cutaneous T-Cell Lymphoma

Immunosequencing has emerged as a newer clinical test for assessment of T-cell clonality in the blood and skin of cutaneous T-cell lymphoma (CTCL) patients. Utilization of immunosequencing, also known as high-throughput sequencing of the T-cell receptor (HTS-TCR), enables identification and quantification of the precise genetic signature of dominant T-cell clones. Although immunosequencing is more sensitive than commonly used methods such as polymerase chain reaction (PCR) paired with capillary electrophoresis or flow cytometry, it remains underutilized for CTCL management. Nonetheless, incorporation of HTS-TCR in clinical practice offers distinct advantages compared to other molecular analyses that may improve diagnostic evaluation, prognostication, and disease monitoring in CTCL. The objective of this comprehensive review is to provide a thorough explanation of the application of immunosequencing in the context of CTCL. We describe the significance of T-cell clonality and the methods used to detect it, including a detailed comparison between PCR paired with capillary electrophoresis and HTS-TCR. The utilization of immunosequencing in the blood and skin of CTCL patients is discussed in depth, specifically outlining how HTS-TCR can assist in diagnosing CTCL, predicting outcomes, and tracking disease progression. Finally, we address the potential applications of immunosequencing in clinical management and research as well as the novel challenges it presents

Sub-percent Photometry: Faint DA White Dwarf Spectophotometric Standards for Astrophysical Observatories

We have established a network of 19 faint (16.5 mag $< V <$19 mag) northern and equatorial DA white dwarfs as spectrophotometric standards for present and future wide-field observatories. Our analysis infers SED models for the stars that are tied to the three CALSPEC primary standards. Our SED models are consistent with panchromatic Hubble Space Telescope ($HST$) photometry to better than 1%. The excellent agreement between observations and models validates the use of non-local-thermodynamic-equilibrium (NLTE) DA white dwarf atmospheres extinguished by interstellar dust as accurate spectrophotometric references. Our standards are accessible from both hemispheres and suitable for ground and space-based observatories covering the ultraviolet to the near infrared. The high-precision of these faint sources make our network of standards ideally suited for any experiment that has very stringent requirements on flux calibration, such as studies of dark energy using the Large Synoptic Survey Telescope (LSST) and the Wide-Field Infrared Survey Telescope ($WFIRST$).Comment: 46 pages, 23 figures, 8 tables, accepted for publication in ApJ

Utility of T-Cell Immunosequencing in Distinguishing Mycosis Fungoides Progression From Treatment Related Cutaneous Adverse Events

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events

Utility of T-cell immunosequencing in distinguishing mycosis fungoides progression from treatment related cutaneous adverse events

Cutaneous adverse events of both topical and systemic drugs in patients with mycosis fungoides (MF) present a diagnostic challenge as it is often difficult to distinguish drug associated rash from disease progression in the skin. Mogamulizumab and mechlorethamine gel are approved treatments for MF, both of which can cause treatment related cutaneous adverse events. It can often be challenging to distinguish mogamulizumab associated rash (MAR) and mechlorethamine gel associated hypersensitivity dermatitis from MF progression both clinically and histologically. High-throughput sequencing (HTS) of the T-cell receptor (TCR), also known as immunosequencing, can be used to assess T-cell clonality to support a diagnosis of MF. After identification of the malignant TCR clone at baseline, immunosequencing can track the established malignant TCR sequence and its frequency over time with high sensitivity. As a result, immunosequencing clone tracking can aid in distinguishing disease progression from treatment side effects. Here, we present a case series to demonstrate how monitoring of the malignant T-cell frequency by immunosequencing can aid in diagnosis of mogamulizumab and mechlorethamine gel cutaneous adverse events

Robotically Assisted Mitral Valve Repair—Port-Only Totally Endoscopic Approach

Robotic mitral valve repair (MVR) is an emerging option to treat degenerative valve disease. Compared to open thoracotomy, robotic mitral valve surgery has been shown to afford decreased postoperative length of stay with comparable rates of mortality and morbidity. Among the variety of techniques for robotic MVR, the totally endoscopic approach remains the least invasive method to date. In this report, we describe our technique for totally endoscopic robotically-assisted MVR. In particular, we seek to highlight the use of several unique techniques in MVR. Percutaneous cannulation with use of the endoballoon is employed for cardiopulmonary bypass (CPB), thus avoiding traditional aortic cross-clamping. Moreover, intercostal nerve cryoanesthesia is performed from T3–T9 to reduce post-operative pain and aid in reducing opioid management. Barbed, nonabsorbable sutures are used throughout the procedure (for left atrial appendage closure, mitral valve annuloplasty band placement, left atrial closure, pericardial re-approximation), eliminating the need for knot-tying at several steps. We also detail the installation of two sets of neochords for mitral regurgitation and the fastening of the mitral annuloplasty band. Finally, we would like to highlight the small size of each port used in the case (eight millimeters maximum diameter). Taken together, these features of the robotic platform make it notable for its minimally invasive approach to MVR