Remote telesurgery in humans: a systematic review.

BACKGROUND: Since the conception of robotic surgery, remote telesurgery has been a dream upon which incredible technological advances haven been built. Despite the considerable enthusiasm for, there have been few published studies of remote telesurgery on humans. METHODS: We performed a systematic review of the English literature (PubMed, EMbase, Inspec & Compendex and Web of Science) to report studies of remote telesurgery in humans. Keywords included telesurgery, remote surgery, long-distance surgery, and telerobotics. Subjects had to be human (live patients or cadavers). The operating surgeon had to be remote from the patient, separated by more than one kilometer. The article had to explicitly report the use of a long-distance telerobotic technique. Articles that focused on telepresence or tele-mentoring were excluded. RESULTS: The study included eight articles published from 2001 to 2020. One manuscript (1 subject) described remote surgery on a cadaver model, and the other seven were on live humans (72 subjects). Procedure types included percutaneous, endovascular, laparoscopic, and transoral. Communication methods varied, with the first report using a telephone line and the most recent studies using a 5G network. Six of the studies reported signal latency as a single value and it ranged from 28 ms to 280 ms. CONCLUSIONS: Few studies have described remote telesurgery in humans, and there is considerable variability in robotic and communication methods. Future efforts should work to improve reporting of signal latency and follow careful research methodology.

Preclinical experience with a novel single-port platform for transoral surgery.

BACKGROUND: We investigated a novel minimally invasive surgical platform for use in the oropharynx, hypopharynx, and larynx for single-port transoral surgery used in concert with standard transoral laryngeal and pharyngeal instrumentation. METHODS: The preclinical investigational device by Fortimedix Surgical B.V. (Netherlands) features two channels for manually controlled flexible articulating surgical instruments. A third central channel accepts both rigid and flexible endoscopes. The system is coupled to a standard laryngoscope for transoral access. In three cadaver models, we evaluated the surgical capabilities using wristed grasping instruments, microlaryngeal scissors, monopolar cautery, and a laser fiber sheath. Procedures were performed within the oropharynx, supraglottis, glottis, subglottis, and hypopharynx. RESULTS: Within the oropharynx, we found adequate strength, range of motion, and dexterity to perform lateral oropharyngectomy and tongue base resection. Within the larynx, visualization was achieved with a variety of instruments including a flexible, 0° and 30° rigid endoscope. The glottis, supraglottis, pyriform sinuses, post-cricoid space, and esophageal inlet were readily accessible. Visualization and manipulation of grasping, laser, and monopolar cautery instruments were also possible within the subglottis. Instrument reach and accuracy facilitated completion of a delicate micro-flap on the true vocal fold. Other procedures included vocal fold resection, cricopharyngeal myotomy, and resection of subglottic mucosa. CONCLUSIONS: From this initial proof of concept experience with this novel platform, we found a wide range of procedures within the oropharynx, larynx, and hypopharynx to be feasible. Further work is needed to evaluate its applicability to the clinical setting. The ability of this platform to be used with conventional instrumentation may provide an opportunity for complex transoral surgery to be performed in a facile manner at greatly reduced cost.

Compensatory motion scaling for time-delayed robotic surgery.

BACKGROUND: Round trip signal latency, or time delay, is an unavoidable constraint that currently stands as a major barrier to safe and efficient remote telesurgery. While there have been significant technological advancements aimed at reducing the time delay, studies evaluating methods of mitigating the negative effects of time delay are needed. Herein, we explored instrument motion scaling as a method to improve performance in time-delayed robotic surgery. METHODS: This was a robotic surgery user study using the da Vinci Research Kit system. A ring transfer task was performed under normal circumstances (no added time delay), and with 250 ms, 500 ms, and 750 ms delay. Robotic instrument motion scaling was modulated across a range of values (- 0.15, - 0.1, 0, + 0.1, + 0.15), with negative values indicating less instrument displacement for a given amount of operator movement. The primary outcomes were task completion time and total errors. Three-dimensional instrument movement was compared against different motion scales using dynamic time warping to demonstrate the effects of scaling. RESULTS: Performance declined with increasing time delay. Statistically significant increases in task time and number of errors were seen at 500 ms and 750 ms delay (p < 0.05). Total errors were positively correlated with task time on linear regression (R = 0.79, p < 0.001). Under 750 ms delay, negative instrument motion scaling improved error rates. Negative motion scaling trended toward improving task times toward those seen in non-delayed scenarios. Improvements in instrument path motion were seen with the implementation of negative motion scaling. CONCLUSIONS: Under time-delayed conditions, negative robotic instrument motion scaling yielded fewer surgical errors with slight improvement in task time. Motion scaling is a promising method of improving the safety and efficiency of time-delayed robotic surgery and warrants further investigation.

Transoral Thyroidectomy Using A Flexible Robotic System: A Preclinical Cadaver Feasibility Study.

OBJECTIVES/HYPOTHESIS: Traditionally, most thyroid surgery utilizes a curvilinear cervical incision with a resulting permanent scar. Minimally invasive and remote access thyroid surgery techniques continue to evolve. Transoral approaches through a vestibular incision have been developed at several centers throughout the world, obviating the need for a cutaneous incision and optimizing aesthetics. To date this technique has been performed using rigid endoscopes or a linear robotic platform. The goal of this study was to test the feasibility of a novel flexible robotic system to perform a transvestibular thyroidectomy in a preclinical cadaver model. STUDY DESIGN: Preclinical feasibility study. METHODS: Right and left thyroid lobectomies were successfully performed via a transvestibular approach in four cadavers. RESULTS: A single vestibular incision between bilateral mental nerves allowed entrance of the flexible robot in a subplatysmal plane in both male and female cadavers. The recurrent laryngeal nerves and parathyroids were identified and preserved. The flexible three-dimensional camera allowed excellent visualization and could be easily repositioned for optimal visualization of right and left structures. The flexible and wristed instruments enabled an atraumatic approach and allowed for precise surgical technique. CONCLUSIONS: The transoral vestibular approach to the central neck is a promising technique for thyroidectomy with optimal cosmesis and can be successfully accomplished using this novel flexible robotic system. Improvements in visualization and access offered by this system may improve application of this technique. LEVEL OF EVIDENCE: NA Laryngoscope, 129:1482-1487, 2019.

CXCR4/IgG-expressing plasma cells are associated with human gastrointestinal tissue inflammation.

BACKGROUND: We previously reported abnormalities in circulating B cells in patients with chronic granulomatous disease (CGD) and those with HIV infection. Gastrointestinal complications are common to both diseases and likely involve perturbation of immune cells, including plasma cells (PCs). IgA is the most abundant immunoglobulin in the human body, with roles in protection and maintenance of intestinal homeostasis. IgA is produced primarily by PCs residing in mucosal tissues that are also thought to circulate in the blood. OBJECTIVE: We sought to characterize and compare PCs in patients with infectious (HIV) and noninfectious (CGD and Crohn disease) diseases that have been associated with intestinal inflammation. METHODS: Phenotypic and transcriptional analyses were performed on cells isolated from the blood and colon. RESULTS: IgA-secreting CCR10-expressing PCs predominated in the guts of healthy subjects, whereas in patients with HIV, CGD, and Crohn disease, there was a significant increase in the proportion of IgG-secreting PCs. Where intestinal inflammation was present, IgG-secreting PCs expressed reduced levels of CCR10 and increased levels of CXCR4. The intensity of CXCR4 expression correlated with the frequency of IgG-expressing PCs and the frequency of CXCR4(+)/IgG(+) PCs was associated with the severity of intestinal inflammatory disease yet distinct from PCs and plasmablasts circulating in the blood. CONCLUSIONS: These findings suggest that regardless of the underlying disease, the presence of CXCR4(+)/IgG(+) PCs in the gut is a strong yet localized indicator of intestinal inflammation. Furthermore, our findings suggest that CXCR4(+)/IgG(+) PCs might play a role in immune cell homeostasis during inflammatory processes of the gut.

Short communication: Interferon/ribavirin treatment for HCV is associated with the development of hypophosphatemia in HIV/hepatitis C virus-coinfected patients.

One-third of all HIV-infected individuals in the United States are estimated to be coinfected with the hepatitis C virus (HCV). Treatment of chronic hepatitis C in patients coinfected with HIV is a complex problem associated with toxicities and drug interactions between HIV antiretrovirals and interferon and ribavirin. In recent HCV treatment studies, we observed a previously unreported development of hypophosphatemia in HIV/HCV-coinfected patients treated with interferon/ribavirin (IFN/RBV). To further investigate this observation, we retrospectively reviewed 61 HIV/HCV-coinfected patients on antiretrovirals (ARVs) during treatment with IFN/RBV as well as 154 HIV-infected patients treated with ARVs alone. We found that HIV/HCV-coinfected patients on IFN/RBV therapy were more likely to develop frequent (57% vs. 13%, IFN/RBV-treated patients vs. no IFN/RBV; χ(2)=0.001) and higher-grade hypophosphatemia (67.0% Grade 2, 33.3% Grade 3 vs. 94.7% Grade 2, 5.3% Grade 3, IFN/RBV-treated patients vs. no IFN/RBV; χ(2)<0.001) than untreated patients. In addition, we found that the new onset of hypophosphatemia after IFN/RBV treatment initiation was followed by a diminished frequency of this toxicity upon cessation of IFN/RBV, supporting the idea that a drug-drug interaction may increase the risk of this toxicity. To understand the risks of developing this toxicity, we evaluated the association between individual ARV use and hypophosphatemia incidence. Our data suggest that concomitant tenofovir (TDF) use may be a risk factor for the development of hypophosphatemia in HIV/HCV-coinfected patients treated with IFN/RBV. Although the etiology of this abnormality is likely multifactorial, clinicians should be aware of hypophosphatemia as a potential marker of renal toxicity in HIV/HCV-coinfected patients being treated with IFN/RBV regimens.

Characterization of plasmablasts in the blood of HIV-infected viremic individuals: evidence for nonspecific immune activation.

Terminal differentiation of B cells and hypergammaglobulinemia are hallmarks of B-cell hyperactivity in HIV disease. Plasmablasts are terminally differentiating B cells that circulate transiently in the blood following infection or vaccination; however, in HIV infection, they arise early and are maintained at abnormally high levels in viremic individuals. Here we show that only a small fraction of plasmablasts in the blood of viremic individuals is HIV specific. Assessment of plasmablast immunoglobulin isotype distribution revealed increased IgG(+) plasmablasts in early and most prominently during chronic HIV viremia, contrasting with a predominantly IgA(+) plasmablast profile in HIV-negative individuals or in aviremic HIV-infected individuals on treatment. Of note, IgG is the predominant immunoglobulin isotype of plasmablasts that arise transiently in the blood following parenteral immunization. Serum immunoglobulin levels were also elevated in HIV-infected viremic individuals, especially IgG, and correlated with levels of IgG(+) plasmablasts. Several soluble factors associated with immune activation were also increased in the sera of HIV-infected individuals, especially in viremic individuals, and correlated with serum immunoglobulin levels, particularly IgG. Thus, our data suggest that while plasmablasts in the blood may contribute to the HIV-specific immune response, the majority of these cells are not HIV specific and arise early, likely from indirect immune-activating effects of HIV replication, and reflect over time the effects of chronic antigenic stimulation. Such B-cell dysregulation may help explain why the antibody response is inadequate in HIV-infected individuals, even during early infection.

Effect of histone deacetylase inhibitors on HIV production in latently infected, resting CD4(+) T cells from infected individuals receiving effective antiretroviral therapy.

Persistence of the latent viral reservoir has been recognized as a major obstacle to eradicating human immunodeficiency virus (HIV) in infected individuals receiving antiretroviral therapy. It has been suggested that histone deacetylase inhibitors (HDACis) may purge HIV in the latent viral reservoir. However, the effect of HDACis on the degree and extent of HIV expression in the latent viral reservoir has not been fully delineated. Here we demonstrate that HDACis do not induce HIV production in the latent viral reservoir of aviremic individuals. Therefore, alternative therapeutic strategies may be necessary to eliminate HIV in the latent viral reservoir.

Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy.

Maintenance of HIV latency in vitro has been linked to methylation of HIV DNA. However, examinations of the degree of methylation of HIV DNA in the latently infected, resting CD4(+) T cells of infected individuals receiving antiretroviral therapy have been limited. Here, we show that methylation of the HIV 5' long terminal repeat (LTR) in the latent viral reservoir of HIV-infected aviremic individuals receiving therapy is rare, suggesting that other mechanisms are likely involved in the persistence of viral latency.