Skin in the game: a review of single-cell and spatial transcriptomics in dermatological research.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) are two emerging research technologies that uniquely characterize gene expression microenvironments on a cellular or subcellular level. The skin, a clinically accessible tissue composed of diverse, essential cell populations, serves as an ideal target for these high-resolution investigative approaches. Using these tools, researchers are assembling a compendium of data and discoveries in healthy skin as well as a range of dermatologic pathophysiologies, including atopic dermatitis, psoriasis, and cutaneous malignancies. The ongoing advancement of single-cell approaches, coupled with anticipated decreases in cost with increased adoption, will reshape dermatologic research, profoundly influencing disease characterization, prognosis, and ultimately clinical practice.

Endoaortic balloon occlusion versus transthoracic cross-clamp for totally endoscopic robotic mitral valve surgery: a retrospective cohort study.

Endoaortic balloon occlusion (EABO) and transthoracic cross-clamping have been shown to have comparable safety profiles for aortic occlusion in minimally invasive mitral valve surgery (MIMVS). However, few studies have focused exclusively on the totally endoscopic robotic approach. We sought to compare outcomes for patients undergoing totally endoscopic robotic mitral valve surgery with aortic occlusion via EABO and transthoracic clamping after a period where EABO was unavailable required us to use the transthoracic clamp. Retrospective review identified 113 patients who underwent robotic mitral valve surgery at our facility between 2019 and 2021 with EABO (n = 71) or transthoracic clamping (n = 42). Relevant data were extracted and compared. Preoperative characteristics were similar other than a higher rate of coronary artery disease [EABO: 69.0% (49/71) vs clamp: 45.2% (19/42), p = .02] and chronic lung disease [EABO: 38.0% (27/71) vs clamp: 9.5% (4/42), p < .01] in the EABO group. Median percutaneous cardiopulmonary bypass time, operative time, and cross-clamp time were comparable. Similar rates of postoperative bleeding complications were observed, and no aortic complications were observed. One patient in each group underwent conversion to an open approach. 30-day mortality and readmission rates were comparable. EABO and transthoracic clamp were associated with similar bleeding and aortic outcomes, and mortality and readmission rates were comparable at thirty days postoperatively. Our findings support the comparable safety of the two techniques, which is well documented in studies encompassing all MIMVS techniques, within the specific context of the totally endoscopic robotic approach.

Feasibility of Robotic Mitral Valve Repair Using Barbed Nonabsorbable Sutures: A Preliminary Single-Center Experience.

OBJECTIVE: Barbed nonabsorbable sutures have been widely adopted for tissue closure in noncardiac robotic surgery to improve intraoperative efficiency. Here, we examine the profile in robotic mitral valve repair (rMVR), which utilized barbed nonabsorbable sutures. To our knowledge, this is the first report to describe clinical outcomes for rMVR with barbed nonabsorbable sutures. METHODS: A retrospective review identified 90 patients who underwent rMVR using barbed nonabsorbable sutures at our center between 2019 and 2021. The primary outcome measure was dehiscence, while other relevant outcomes included 30-day readmission and 30-day mortality. RESULTS: In addition to fixation of the mitral annuloplasty band, barbed nonabsorbable sutures were employed commonly in concomitant pericardiectomy closure (100.0%, 90 of 90), atriotomy closure (100.0%, 90 of 90), and left atrial appendage closure (if eligible; 98.8%, 83 of 84). One patient who underwent mitral valve annuloplasty using only barbed nonabsorbable suture required reoperation for annuloplasty ring dehiscence. Immediate postoperative ring dehiscence was not observed in any patients after the routine reinforcement of barbed nonabsorbable sutures with everting pledgeted polyester sutures, and no additional patients required reoperation for suture-related complications. Clinical signs of dehiscence were not observed after pericardiectomy, atriotomy, or left atrial appendage closure with barbed nonabsorbable sutures. The 30-day readmission rate was 3.3% (3 of 90), and 30-day mortality was 0% (0 of 90). CONCLUSIONS: These data suggest the initial feasibility of barbed nonabsorbable sutures in robotic cardiac surgery, specifically within rMVR. Further research is necessary to explore the long-term safety and efficacy profile of such approach.

A New Frontier: No Working Port for Robotic Mitral Valve Repair.

A 61-year-old male presented via referral for mitral regurgitation and was deemed an appropriate robotic surgery candidate for complex mitral valve repair with the maze procedure and patent foramen ovale and left atrial appendage closures, using all percutaneous cannulation. We report upon the first case in the literature that describes the use of only 4 robotic ports, with no working port used.

Feasibility of Postoperative Day One or Day Two Discharge After Robotic Cardiac Surgery.

INTRODUCTION: The robotic platform reduces the invasiveness of cardiac surgical procedures, thus facilitating earlier discharge in select patients. We sought to evaluate the characteristics, perioperative management, and early outcomes of patients who underwent postoperative day 1 or 2 (POD1-2) discharge after robotic cardiac surgery at our institution. METHODS: Retrospective review of 169 patients who underwent robotic cardiac surgery at our facility between 2019 and 2021 identified 57 patients discharged early on POD1 (n = 19) or POD2 (n = 38) and 112 patients who underwent standard discharge (POD3 or later). Relevant data were extracted and compared. RESULTS: In the early discharge group, median patient age was 62 [IQR: 55, 66] (IQR = interquartile range) years, and 70.2% (40/57) were male. Median Society of Thoracic Surgeons predictive risk of mortality score was 0.36 [IQR: 0.25, 0.56] %. The most common procedures performed were mitral valve repair [66.6%, (38/57)], atrial mass resection [10.5% (6/57)], and coronary artery bypass grafting [10.5% (6/57)]. The only significant differences between the POD1 and POD2 groups were shorter operative time, higher rate of in-operating room extubation, and shorter ICU length of stay in the POD1 group. Lower in-hospital morbidity and comparable 30-day mortality and readmission rates were observed between the early and standard discharge groups. CONCLUSIONS: POD1-2 discharge after various robotic cardiac operations afforded lower morbidity and similar 30-day readmission and mortality rates compared to discharge on POD3 or later. Our findings support the feasibility of POD1-2 discharge after robotic cardiac surgery for patients with low preoperative risk, an uncomplicated postoperative course, and appropriate postoperative management protocols.

The Impact of Preoperative Symptom Duration on Patient Outcomes After Posterior Cervical Decompression and Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To determine if decreased preoperative symptom duration is associated with greater clinical improvement in function and myelopathic symptoms after posterior cervical decompression and fusion (PCDF). METHODS: All patients over age 18 who underwent primary PCDF for cervical myelopathy or myeloradiculopathy at a single institution between 2014 and 2020 were retrospectively identified. Patient demographics, surgical characteristics, duration of symptoms, and preoperative and postoperative patient reported outcomes measures (PROMs) including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), Visual Analogue Scale (VAS) Neck, VAS Arm, and SF-12 were collected. Univariate and multivariate analyses were performed to compare change in PROMs and minimum clinically important difference achievement (%MCID) between symptom duration groups (< 6 months, 6 months-2 years, > 2 years). RESULTS: Preoperative symptom duration groups differed significantly by sex and smoking status. Patients with < 6 months of preoperative symptoms improved significantly in all PROMs. Patients with 6 months-2 years of preoperative symptoms did not improve significantly in mJOA, Physical Component Scores (PCS), or NDI. Patients with > 2 years of symptoms failed to demonstrate significant improvement in mJOA, NDI, or Mental Component Scores (MCS). Univariate analysis demonstrated significantly decreased improvement in mJOA with longer symptom durations. Increased preoperative symptom duration trended toward decreased %MCID for mJOA and MCS. Regression analysis demonstrated that preoperative symptom duration of > 2 years relative to < 6 months predicted decreased improvement in mJOA and NDI and decreased MCID achievement for mJOA and MCS. CONCLUSION: Increased duration of preoperative symptoms (> 2 years) before undergoing PCDF was associated with decreased postoperative improvement in myelopathic symptoms.

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.

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.

An alternate approach: Percutaneous axillary cannulation for minimally invasive cardiac surgery.

BACKGROUND: Percutaneous axillary artery cannulation for cardiopulmonary bypass (CPB) offers a novel alternate approach to mechanical circulatory support for patients with contraindications to femoral perfusion. To our knowledge, this has not yet been reported in minimally invasive cardiac surgery (MICS). AIM: We aim to highlight our experience using percutaneous axillary artery cannulation to safely facilitate CPB for minimally invasive cardiac surgery MICS. METHODS: Four patients who underwent robotic cardiac surgery utilizing the axillary artery for percutaneous cannulation between November 2019 and August 2021 at a single center were identified and included in the analysis. Preoperative, intraoperative, and postoperative data were collected and analyzed to support this case series. RESULTS: There were no perioperative hematomas, brachial plexus injuries, or neurovascular injuries. Within 30-days postoperatively there was no mortality, vessel injury, stroke, new onset atrial fibrillation, or other life-threatening bleeding. CONCLUSION: Percutaneous cannulation of the axillary artery is a novel and promising CPB modality for robotic cardiac surgery in patients with extensive peripheral and aortic atherosclerotic disease.

Routine endoscopic robotic cardiac tumor resection using an 8-mm working port and percutaneous cannulation.

OBJECTIVE: Prior studies have demonstrated robotic excision of cardiac tumors as a safe and effective treatment option. The procedure is performed with five incisions: three robotic arm ports, one atrial retractor port, and one working port. We report our unique initial experience in robotic tumor removal. To our knowledge, this is one of the first reports demonstrating cardiac myxoma and fibroelastoma removal with use of exclusively 8-mm ports. METHODS: All data for robotic cardiac tumor resection at our institution from June 2019 to December 2021 were retrospectively collected; 18 cases were included, including 13 cardiac myxomas and five fibroelastomas. Baseline demographics, intraoperative characteristics, and surgical outcomes were recorded. Descriptive statistics were calculated; continuous variables were reported as median [interquartile range], and categorical variables were reported as percentages. RESULTS: Median patient age was 64 [55, 70] years old. The cohort consisted of primarily female (67%) and white (83%) patients. Median body mass index was 26.3 [23.0, 31.5] kg/m2 . 11% of patients were current tobacco users and 50% had hypertension. All patients underwent myxoma or fibroelastoma removal with the use of five 8-mm robotic ports. Each patient underwent percutaneous cannulation via the femoral arteries. Aortic occlusion was achieved via an endoaortic balloon (67%) or transthoracic cross-clamp (33%). Cross-clamp time was 30 [26, 41] minutes. Concomitant procedures performed during myxoma removal included patent foramen ovale closure (28%), mitral valve repair (8%), left atrial appendage closure (8%), Cox-maze procedure (6%), and coronary artery bypass grafting (6%). All cardiac tumors were packaged with use of the endo-bag and subsequently removed through the working port. Maximal myxoma and fibroelastoma diameters were 2.5 [1.7, 3.5] and 0.6 [0.4, 0.7] cm, respectively. Procedural cardiopulmonary bypass time was 77 [65, 84] minutes. No intraoperative mortality, reoperation for bleeding, or postoperative cardiac issues were recorded. One in-hospital mortality occurred as the result of a thrombotic event in the context of a hypercoagulable state unrelated to the patient's operation. No other mortalities were observed at 30 days. Hospital length of stay was 4.5 [3.0, 7.8] days. CONCLUSIONS: In our study, the robotic platform facilitated safe and effective cardiac tumor excision. Our results highlight the efficacy of 8-mm port sizing and the concurrent use of other minimally invasive techniques, including percutaneous cannulation, in this patient population. In general, patients prefer the least invasive treatment option available. Our findings emphasize the importance of training cardiac surgeons to perform robotic procedures using the least invasive means possible to provide patients with various options for their treatment.

Cessation of Routine Jejunostomy Tube Placement at Time of Minimally Invasive Ivor Lewis Esophagectomy and Impact on Body Mass Index.

Jejunostomy tubes are frequently placed at time of esophagectomy. The purpose of this study is to evaluate cessation of routine j-tube placement on postoperative body mass index (BMI), return to the emergency room, and time until adjuvant therapy. We performed a retrospective review of an institutional database for consecutive patients undergoing minimally invasive Ivor Lewis Esophagectomy from 2014-2021 (after January 2019, routine j-tube placement was abandoned). Data was analyzed using Pearson's Chi-squared tests and Student's t test with 2-sided significance level of P < 0.05. In total,179 patients were included, 95 underwent j-tube placement and 84 did not. Cohorts had comparable baseline BMI's (no j-tube: 30.48 vs j-tube: 28.64, P = 0.06) and anastomotic leak rates (2.4% vs 4.2%, P = 0.5). Patients with no jejunostomy tubes were more likely to receive total parenteral nutrition (14.3% vs 5.3%, P < 0.05), but were no more likely to require total parenteral nutrition at discharge and had comparable durations of TPN requirement (7 days vs 12 days, P = 0.53). There was no difference in mean BMI reduction at 2 weeks (2.54 vs 2.09, P = 0.49) and 3-6 months postoperatively (6.11 vs 4.45 P = 0.15). There was no difference in return to the emergency room (8.3% vs 8.4%, P = 0.98) or readmissions (13.1% vs 11.6%, P = 0.76). There was a no difference in mean time to adjuvant therapy (83.5 days vs 72.6 days, P = 0.67). At esophagectomy centers with low anastomotic leak rates, cessation of routine j-tube placement at time of minimally esophagectomy can be undertaken without increasing risk of readmission, time until initiation of adjuvant therapy, or significantly impacting postoperative BMI loss.

Instrumentation Across the Cervicothoracic Junction Does Not Improve Patient-reported Outcomes in Multilevel Posterior Cervical Decompression and Fusion.

STUDY DESIGN: This was a retrospective cohort. OBJECTIVE: The objective of this study was to determine if instrumentation across the cervicothoracic junction (CTJ) in elective multilevel posterior cervical decompression and fusion (PCF) is associated with improved patient-reported outcome measures (PROMs). SUMMARY OF BACKGROUND DATA: Fusion across the CTJ may result in lower revision rates at the expense of prolonged operative duration. However, it is unclear whether constructs crossing the CTJ affect PROMs. MATERIALS AND METHODS: Standard Query Language (SQL) identified patients with PROMs who underwent elective multilevel PCF (≥3 levels) at our institution. Patients were grouped based on anatomic construct: crossing the CTJ (crossed) versus not crossing the CTJ (noncrossed). Subgroup analysis compared constructs stopping at C7 or T1. Independent t tests and χ 2 tests were utilized for continuous and categorical data, respectively. Regression analysis controlled for baseline demographics. The α was set at 0.05. RESULTS: Of the 160 patients included, the crossed group (92, 57.5%) had significantly more levels fused (5.27 vs. 3.71, P <0.001), longer operative duration (196 vs. 161 min, P =0.003), greater estimated blood loss (242 vs. 160 mL, P =0.021), and a decreased revision rate (1.09% vs. 10.3%, P =0.011). Neither crossing the CTJ (vs. noncrossed) nor constructs spanning C3-T1 (vs. C3-C7) were independent predictors of ∆PROMs (change in preoperative minus postoperative patient-reported outcomes) on regression analysis. However, C3-C7 constructs had a greater revision rate than C3-T1 constructs (15.6% vs. 1.96%, P =0.030). CONCLUSION: Crossing the CTJ in patients undergoing elective multilevel PCF was not an independent predictor of improvement in PROMs at 1 year, but they experienced lower revision rates. LEVEL OF EVIDENCE: Level III.

Use of Percutaneous Cannulation in Robotic Mitral Valve Surgery.

Minimally invasive cardiac surgery (MICS) has evolved in its practice over the past several years. Percutaneous cannulation is a technique that can be used during MICS to facilitate cardiopulmonary bypass. This manuscript describes the stepwise approach to percutaneous cannulation and decannulation in robotic mitral valve surgery.

Neurons survive simultaneous injury to axons and dendrites and regrow both types of processes in vivo.

Neurons extend dendrites and axons to receive and send signals. If either type of process is removed, the cell cannot function. Rather than undergoing cell death, some neurons can regrow axons and dendrites. Axon and dendrite regeneration have been examined separately and require sensing the injury and reinitiating the correct growth program. Whether neurons in vivo can sense and respond to simultaneous axon and dendrite injury with polarized regeneration has not been explored. To investigate the outcome of simultaneous axon and dendrite damage, we used a Drosophila model system in which neuronal polarity, axon regeneration, and dendrite regeneration have been characterized. After removal of the axon and all but one dendrite, the remaining dendrite was converted to a process that had a long unbranched region that extended over long distances and a region where shorter branched processes were added. These observations suggested axons and dendrites could regrow at the same time. To further test the capacity of neurons to implement polarized regeneration after axon and dendrite damage, we removed all neurites from mature neurons. In this case a long unbranched neurite and short branched neurites were regrown from the stripped cell body. Moreover, the long neurite had axonal plus-end-out microtubule polarity and the shorter neurites had mixed polarity consistent with dendrite identity. The long process also accumulated endoplasmic reticulum at its tip like regenerating axons. We conclude that neurons in vivo can respond to simultaneous axon and dendrite injury by initiating growth of a new axon and new dendrites.