Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy.

Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8+ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8+ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT.

Molecular determinants and signaling effects of PKA RIα phase separation.

Spatiotemporal regulation of intracellular signaling molecules, such as the 3',5'-cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA), ensures proper cellular function. Liquid-liquid phase separation (LLPS) of the ubiquitous PKA regulatory subunit RIα promotes cAMP compartmentation and signaling specificity. However, the molecular determinants of RIα LLPS remain unclear. Here, we reveal that two separate dimerization interfaces, combined with the cAMP-induced unleashing of the PKA catalytic subunit (PKA-C) from the pseudosubstrate inhibitory sequence, drive RIα condensate formation in the cytosol of mammalian cells, which is antagonized by docking to A-kinase anchoring proteins. Strikingly, we find that the RIα pseudosubstrate region is critically involved in forming a non-canonical R:C complex, which recruits active PKA-C to RIα condensates to maintain low basal PKA activity in the cytosol. Our results suggest that RIα LLPS not only facilitates cAMP compartmentation but also spatially restrains active PKA-C, thus highlighting the functional versatility of biomolecular condensates in driving signaling specificity.

A phase 1 trial of 8-chloro-adenosine in relapsed/refractory acute myeloid leukemia: An evaluation of safety and pharmacokinetics.

BACKGROUND: This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 8-chloro-adenosine (8-Cl-Ado) in patients with relapsed/refractory acute myeloid leukemia (AML). METHODS: 8-Cl-Ado was administered daily for 5 days; the starting dose was 100 mg/m2 , the highest dose tested was 800 mg/m2 . The end points were toxicity, disease response, and PK/PD measurements. RESULTS: The predominant nonhematologic toxicity was cardiac with grade ≥3 toxicity. Plasma PK in all patients suggested heterogeneity among patients, yet, some dose-dependency for the accumulation of 8-Cl-Ado. Two 8-Cl-Ado metabolites accumulated at similar levels to 8-Cl-Ado. Cellular PK in eight patients indicated accumulation of 8-Cl-ATP, which was associated with AML blast cytoreduction in peripheral blood. The authors determined the RP2D of 8-Cl-Ado to be 400 mg/m2 . CONCLUSIONS: Given the cardiac adverse events observed, patients require monitoring for arrhythmias and QT interval during infusion. Although peripheral blood cytoreduction was observed, responses were transient, suggesting combination strategies will be required.

Elongation of intercostal nerve cutaneous branches for breast and nipple neurotization during breast reconstruction after mastectomy for breast cancer: case-control study.

BACKGROUND: To restore sensation after breast reconstruction, a modified surgical approach was employed by identifying the cut fourth intercostal lateral cutaneous branch, elongating it with intercostal nerve grafts, and coapting it to the innervating nerve of the flap or by using direct neurotization of the spared nipple/skin. METHODS: This was a retrospective case-control study including 56 patients who underwent breast neurotization surgery. Breast operations included immediate reconstruction after nipple-sparing mastectomy (36 patients), skin-sparing mastectomy (8 patients), and delayed reconstruction with nipple preservation (7 patients) or without nipple preservation (5 patients). Patients who underwent breast reconstruction without neurotization were included as the non-neurotization negative control group. The contralateral normal breasts were included as positive controls. RESULTS: The mean(s.d.) monofilament test values were 0.07(0.10) g for the positive control breasts and 179.13(143.31) g for the breasts operated on in the non-neurotization group. Breasts that underwent neurotization had significantly better sensation after surgery, with a mean(s.d.) value of 35.61(92.63) g (P < 0.001). The mean(s.d.) sensory return after neurotization was gradual; 138.17(143.65) g in the first 6 months, 59.55(116.46) g at 7-12 months, 14.54(62.27) g at 13-18 months, and 0.37(0.50) g at 19-24 months after surgery. Two patients had accidental rupture of the pleura, which was repaired uneventfully. One patient underwent re-exploration due to a lack of improvement 1.5 years after neurotization. CONCLUSION: Using the lateral cutaneous branch of the intercostal nerve as the innervating stump and elongating it with intercostal nerve grafts is a suitable technique to restore sensation after mastectomy. This method effectively innervates reconstructed breasts and spares the nipple/skin with minimal morbidity.

Implementation of Bedaquiline, Pretomanid, and Linezolid in the United States: Experience Using a Novel All-Oral Treatment Regimen for Treatment of Rifampin-Resistant or Rifampin-Intolerant Tuberculosis Disease.

BACKGROUND: Rifampin-resistant tuberculosis is a leading cause of morbidity worldwide; only one-third of persons start treatment, and outcomes are often inadequate. Several trials demonstrate 90% efficacy using an all-oral, 6-month regimen of bedaquiline, pretomanid, and linezolid (BPaL), but significant toxicity occurred using 1200-mg linezolid. After US Food and Drug Administration approval in 2019, some US clinicians rapidly implemented BPaL using an initial 600-mg linezolid dose adjusted by serum drug concentrations and clinical monitoring. METHODS: Data from US patients treated with BPaL between 14 October 2019 and 30 April 2022 were compiled and analyzed by the BPaL Implementation Group (BIG), including baseline examination and laboratory, electrocardiographic, and clinical monitoring throughout treatment and follow-up. Linezolid dosing and clinical management was provider driven, and most patients had linezolid adjusted by therapeutic drug monitoring. RESULTS: Of 70 patients starting BPaL, 2 changed to rifampin-based therapy, 68 (97.1%) completed BPaL, and 2 of the 68 (2.9%) experienced relapse after completion. Using an initial 600-mg linezolid dose daily adjusted by therapeutic drug monitoring and careful clinical and laboratory monitoring for adverse effects, supportive care, and expert consultation throughout BPaL treatment, 3 patients (4.4%) with hematologic toxicity and 4 (5.9%) with neurotoxicity required a change in linezolid dose or frequency. The median BPaL duration was 6 months. CONCLUSIONS: BPaL has transformed treatment for rifampin-resistant or intolerant tuberculosis. In this cohort, effective treatment required less than half the duration recommended in 2019 US guidelines for drug-resistant tuberculosis. Use of individualized linezolid dosing and monitoring likely enhanced safety and treatment completion. The BIG cohort demonstrates that early implementation of new tuberculosis treatments in the United States is feasible.

Exposure to behavioral regularities in everyday life predicts infants' acquisition of mental state vocabulary.

There are two broad views of children's theory of mind. The mentalist view is that it emerges in infancy and is possibly innate. The minimalist view is that it emerges more gradually in childhood and is heavily dependent on learning. According to minimalism, children initially understand behaviors rather than mental states, and they are assisted in doing so by recognizing repeating patterns in behavior. The regularities in behavior allow them to predict future behaviors, succeed on theory-of-mind tasks, acquire mental state words, and eventually, understand the mental states underlying behavior. The present study provided the first clear evidence for the plausibility of this view by fitting head cameras to 54 infants aged 6 to 25 months, and recording their view of the world in their daily lives. At 6 and 12 months, infants viewed an average of 146.5 repeated behaviors per hour, a rate consistent with approximately 560,000 repetitions in their first year, and with repetitions correlating with children's acquisition of mental state words, even after controlling for their general vocabulary and a range of variables indexing social interaction. We also recorded infants' view of people searching or searching for and retrieving objects. These were 92 times less common and did not correlate with mental state vocabulary. Overall, the findings indicate that repeated behaviors provide a rich source of information for children that would readily allow them to recognize patterns in behavior and help them acquire mental state words, providing the first clear evidence for this claim of minimalism. RESEARCH HIGHLIGHTS: Six- to 25-month-olds wore head cameras to record home life from infants' point-of-view and help adjudicate between nativist and minimalist views of theory-of-mind (ToM). Nativists say ToM is too early developing to enable learning, whereas minimalists say infants learn to predict behaviors from behavior patterns in environment. Consistent with minimalism, infants had an incredibly rich exposure (146.5/h, >560,000 in first year) to repeated behaviors (e.g., drinking from a cup repeatedly). Consistent with minimalism, more repeated behaviors correlated with infants' mental state vocabulary, even after controlling for gender, age, searches witnessed and non-mental state vocabulary.

The Preferred Reconstructive Choice for a Lower Third Tibial Exposure Defect: An Online Survey of 356 Microsurgeons.

BACKGROUND: One of the most challenging yet common areas in reconstructive surgery is the closure of defects in the lower leg. Surgeons can choose from several reconstructive options including local and free flaps. The aim of this study was to understand the reconstructive strategy for lower leg defects of different microsurgeons around the world by harnessing the power of social media and online questionnaires. METHODS: A case of a patient with an exposed plate over distal tibial fracture was presented via an online questionnaire distributed on various social media platforms. A total of 369 international microsurgeons replied with their preferred treatment choice. The data were analyzed according to geographic area, microsurgical training, seniority, and subspecialty. RESULTS: Among all the respondents (n = 369), 64% would have opted for a free flap reconstruction, while the remaining 36% would have opted for a local/pedicle flap. In the group that would have opted for a free flap, 63% would reconstruct the defect using a free fasciocutaneous flap, while the remaining 37% would have used a free muscle flap. In the local flap group, 60% would have used a local perforator while 30% would have chosen a conventional local flap. While North American and European microsurgeons had a clear preference toward free flaps, Asian, Middle Eastern, African, and South American surgeons were evenly divided between local and free flaps. CONCLUSION: In this study, we provide a current global overview of the reconstructive strategies for a lower limb with skin defect and bone or prosthesis exposure. We hope that this will be able to help global microsurgeons and patients worldwide.

Heterotopic Digital Replantation in Mutilating Hand Injuries: An Algorithmic Approach Based on 53 Cases and Literature Review.

BACKGROUND: Reconstruction of the mutilated hand is one of the most difficult challenges for hand microsurgeons. When multiple digits are amputated, orthotopic digital replantation of the available remnants may not adequately restore the hand function. In such cases, heterotopic digital replantation may provide a more functional reconstruction. METHODS: Between 1997 and 2018, 53 patients with mutilating hand injuries were treated with heterotopic digital replantation at our institution. A retrospective chart review was conducted to determine the details of the injury, indications for heterotopic digital replantation, and functional outcomes. RESULTS: In total, 173 digits were amputated from 53 patients (one patient suffered from bilateral hand injuries, so totally 54 hands). Sixty-eight digits underwent heterotopic digital replantation, 30 digits had orthotopic digital replantation, and 75 stumps were terminalized. The survival rate of digits treated by heterotopic digital replantation and orthotopic digital replantation was 83.8% (57/68) and 86.7% (26/30), respectively (p = 1). Tripod grip was achieved in 83.3% (45/54) of patients following replantation and optional secondary reconstructive surgeries. CONCLUSION: Heterotopic digital replantation is a practical and reliable method for achieving optimal hand function following mutilating hand injuries. The basic principles are to restore a functional thumb in the first instance, followed by at least two adjacent fingers against which the thumb can oppose. This method is particularly indicated when orthotopic digital replantation of the available amputated parts would yield a suboptimal result.

Double Fascicular Transfer Using Partially Injured Donor Nerves: Is It Powerful Enough to Restore Elbow Flexion in Acute Brachial Plexus Injuries?

BACKGROUND: Loss of elbow flexion is a common sequela of acute brachial plexus injuries (BPIs). The Mackinnon/Oberlin-II double fascicular transfer (DFT) is a widely used method to restore this function in acute C5-6 or C5-7 injuries. This study attempted to evaluate if this technique can be applied reliably for cases involving C8 and/or T1 injuries. METHODS: Adult patients with acute BPIs who underwent the Mackinnon/Oberlin-II DFT in our center between 2008 and 2018 were retrospectively identified. Group I (n = 37) included patients with only C5-6 or C5-7 injury, while group II (n = 32) patients presented C5-8 ± T1 injuries. The demographic data, pre- and postoperative neurologic evaluations, electrodiagnostic studies, and grip strength assessment were collected. RESULTS: A total of 69 patients met the inclusion criteria. Preoperatively, the patients in group II presented poorer nerve conduction and electromyography in both the median and the ulnar nerves and the supply muscles. The percentage of M3 achievement in both groups was 91.9 versus 87.5% and M4 was 73.0 and 71.9%, respectively, which both were not statically significant but the achievement of group II was slower than the group I, 1 to 2 months slower, respectively. Both groups had 57.57 and 46.0% of the postoperative grip power compared with the healthy side, the result of shoulder abduction was not different (p = 0.480). CONCLUSION: With careful preoperative evaluation, early intervention, appropriate intraoperative functional fascicle selection, and aggressive postoperative rehabilitation, indications for the Mackinnon/Oberlin-II DFT technique can safely include acute C5-8 injuries and even partial T1 acute BPIs.

Carbodiimide-Driven Dimerization and Self-Assembly of Artificial, Ribose-Based Amphiphiles.

The aqueous self-assembly of amphiphiles into aggregates such as micelles and vesicles has been widely investigated over the past decades with applications ranging from materials science to drug delivery. The combination of characteristic properties of nucleic acids and amphiphiles is of substantial interest to mimic biological self-organization and compartmentalization. Herein, we present ribose- and ribonucleotide-based amphiphiles and investigate their self-assembly as well as their fundamental reactivity. We found that various types of aggregates are formed, ranging in size from nanometers to micrometers and all amphiphiles exhibit aggregation-induced emission (AIE) in solution as well as in the solid state. We also observed that the addition of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) leads to rapid and selective dimerization of the amphiphiles into pyrophosphates, which decreases the critical aggregation concentration (CAC) by a factor of 25 when compared to the monomers. Since the propensity for amphiphile dimerization is correlated with their tendency to self-assemble, our results may be relevant for the formation of rudimentary compartments under prebiotic conditions.

Genetic Regulation of Atherosclerosis-Relevant Phenotypes in Human Vascular Smooth Muscle Cells.

RATIONALE: Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. Recent genome-wide association studies revealed 163 loci associated with CAD. However, the precise molecular mechanisms by which the majority of these loci increase CAD risk are not known. Vascular smooth muscle cells (VSMCs) are critical in the development of CAD. They can play either beneficial or detrimental roles in lesion pathogenesis, depending on the nature of their phenotypic changes. OBJECTIVE: To identify genetic variants associated with atherosclerosis-relevant phenotypes in VSMCs. METHODS AND RESULTS: We quantified 12 atherosclerosis-relevant phenotypes related to calcification, proliferation, and migration in VSMCs isolated from 151 multiethnic heart transplant donors. After genotyping and imputation, we performed association mapping using 6.3 million genetic variants. We demonstrated significant variations in calcification, proliferation, and migration. These phenotypes were not correlated with each other. We performed genome-wide association studies for 12 atherosclerosis-relevant phenotypes and identified 4 genome-wide significant loci associated with at least one VSMC phenotype. We overlapped the previously identified CAD loci with our data set and found nominally significant associations at 79 loci. One of them was the chromosome 1q41 locus, which harbors MIA3. The G allele of the lead risk single nucleotide polymorphism (SNP) rs67180937 was associated with lower VSMC MIA3 expression and lower proliferation. Lentivirus-mediated silencing of MIA3 (melanoma inhibitory activity protein 3) in VSMCs resulted in lower proliferation, consistent with human genetics findings. Furthermore, we observed a significant reduction of MIA3 protein in VSMCs in thin fibrous caps of late-stage atherosclerotic plaques compared to early fibroatheroma with thick and protective fibrous caps in mice and humans. CONCLUSIONS: Our data demonstrate that genetic variants have significant influences on VSMC function relevant to the development of atherosclerosis. Furthermore, high MIA3 expression may promote atheroprotective VSMC phenotypic transitions, including increased proliferation, which is essential in the formation or maintenance of a protective fibrous cap.

International Microsurgery Club Webinar Series-Bridging the Knowledge Gap during the COVID-19 Pandemic.

BACKGROUND: The impact of the coronavirus disease 2019 (COVID-19) outbreak shut down most conferences. To minimalize the influence, virtual meetings sprang up subsequently. International Microsurgery Club (IMC), as one of the largest professionals-only online microsurgery education groups worldwide, began to host regular weekend webinars during the pandemic to fill the knowledge gap. This study aims to discuss how webinars have fundamentally changed the way knowledge is delivered and exchanged. METHODS: From February 29, 2020 to March 14, 2021, 103 IMC webinars were reviewed and analyzed in detail to determine the use, benefit, and effect. A comparison between webinars hosted by the different societies was made as well. A questionnaire survey focusing on attendees' behavior, attitude, and using habit about webinars was also made. RESULTS: As for the 103 IMC webinar events, the peak participants were 112.3 people in average. The members requesting to join IMC abruptly increased during the pandemic, and the group activity increased dramatically. From the questionnaire (n = 68), the satisfaction level was high (8.88 ± 1.18/10). The respondents were most satisfied with the good quality of the speakers (73.5%). Not only hosts our webinar series but IMC also serves as the platform that welcomes webinars from other societies to share their information. In September 2020, International Microsurgery Webinar League was established via the significant webinar hosts, with more than 300 recorded webinar talks connected successfully. CONCLUSION: As the knowledge revolution driven by COVID-19 will continue, IMC will keep playing an essential role in exploring new and emerging opportunities to improve knowledge dissemination worldwide beyond the space-time boundary.

Tuberculosis-Associated Hospitalizations and Deaths after COVID-19 Shelter-In-Place, San Francisco, California, USA.

A mandated shelter-in-place and other restrictions associated with the coronavirus disease pandemic precipitated a decline in tuberculosis diagnoses in San Francisco, California, USA. Several months into the pandemic, severe illness resulting in hospitalization or death increased compared with prepandemic levels, warranting heightened vigilance for tuberculosis in at-risk populations.

All-Conjugated Polymer Core-Shell and Core-Shell-Shell Particles with Tunable Emission Profiles and White Light Emission.

Future applications of conjugated polymer particles (CPP) in medicine, organic photonics, and optoelectronics greatly depend on high performance and precisely adjustable optical properties of the particles. To meet these criteria, current particle systems often combine conjugated polymers with inorganic particles in core-shell geometries, extending the possible optical characteristics of CPP. However, current conjugated polymer particles are restricted to a single polymer phase composed of a distinct polymer or a polymer blend. Here, a synthetic toolbox is presented that enables the synthesis of monodisperse core-shell and core-shell-shell particles, which consist entirely of conjugated polymers but of different types in the core and the shells. Seeded and fed-batch dispersion polymerizations based on Suzuki-Miyaura-type cross-coupling are investigated. The different approaches allow accurate control over the created interface between the conjugated polymer phases and thus also over the energy transfer phenomena between them. This approach opens up completely new synthetic freedom for fine tuning of the optical properties of CPP, enabling, for example, the synthesis of individual white light-emitting particles.

Establishment and Evaluation of a Large Contact-Tracing and Case Investigation Virtual Training Academy.

During the COVID-19 pandemic, the Virtual Training Academy (VTA) was established to rapidly develop a contact-tracing workforce for California. Through June 2021, more than 10 000 trainees enrolled in a contact-tracing or case investigation course at the VTA. To evaluate program effectiveness, we analyzed trainee pre- and postassessment results using the Wilcoxon signed-rank test. There was a statistically significant (P < .001) improvement in knowledge and self-perceived skills after course completion, indicating success in training a competent contact-tracing workforce. (Am J Public Health. 2021;111(11):1934-1938. https://doi.org/10.2105/AJPH.2021.306468).

Competitive binding of antagonistic peptides fine-tunes stomatal patterning.

During development, cells interpret complex and often conflicting signals to make optimal decisions. Plant stomata, the cellular interface between a plant and the atmosphere, develop according to positional cues, which include a family of secreted peptides called epidermal patterning factors (EPFs). How these signalling peptides orchestrate pattern formation at a molecular level remains unclear. Here we report in Arabidopsis that Stomagen (also called EPF-LIKE9) peptide, which promotes stomatal development, requires ERECTA (ER)-family receptor kinases and interferes with the inhibition of stomatal development by the EPIDERMAL PATTERNING FACTOR 2 (EPF2)-ER module. Both EPF2 and Stomagen directly bind to ER and its co-receptor TOO MANY MOUTHS. Stomagen peptide competitively replaced EPF2 binding to ER. Furthermore, application of EPF2, but not Stomagen, elicited rapid phosphorylation of downstream signalling components in vivo. Our findings demonstrate how a plant receptor agonist and antagonist define inhibitory and inductive cues to fine-tune tissue patterning on the plant epidermis.

Holistic reconstruction of mandible defect, lower lip and chin sensation, and smile reanimation in an advanced gum cancer patient: A case report.

Facial deformity, facial paralysis, and sensory loss are inevitable after some head and neck tumor resection and reconstruction, especially in high stage cancer. To overcome these obstacles, we present a case of T4a gum cancer patient (41-year-old) who received holistic reconstruction of the mandible defect via an osteo-peroneal-artery-perforator combined flap for defect coverage and cross-mental nerve graft for lower lip and chin sensation at the primary stage, followed by ipsilateral facial nerve (lower trunk) innervated gracilis functioning free muscle transplantation for facial reanimation and correction of the sunken face 3 years later. After 4.5 years of follow-up, the patient was satisfied with his appearance, and obtained a spontaneous and symmetrical smile without sensory deficit. This experience showed a possible solution to the reconstruction for complicated head and neck cancer patients.

Reversal of thoracic sympathectomy through robot-assisted microsurgical sympathetic trunk reconstruction with sural nerve graft and additional end-to-side coaptation of the intercostal nerves: A case report.

Thoracic sympathectomy to treat palmar hyperhidrosis (PH) has widely been performed. Many patients regret the surgery due to compensatory hyperhidrosis (CH), gustatory hyperhidrosis, arrhythmia, hypertension, gastrointestinal disturbances, and emotional distress. Robotic applications in microsurgery are very limited. We report the technique and long-term patient-reported outcomes of bilateral robot-assisted microsurgical sympathetic trunk reconstruction with a sural nerve graft in an interdisciplinary setting. A 59-year-old female suffered from severe adverse effects after endoscopic thoracic sympathectomy (ETS) for PH 25 years ago. She reported CH over the whole trunk, gustatory hyperhidrosis, excessive dry hands, and emotional distress. An interdisciplinary surgical team performed a bilateral sympathetic trunk reversal reconstruction with an interpositional sural nerve graft per side by a da Vinci® Robot. The nerve graft was microsurgically coapted using 9-0 sutures end-to-end to the sympathetic trunk stumps and side-to-end to the intercostal nerves T2-T4. At 24, 33 and 42 months, palmar dryness and emotional distress were strongly reduced. A highly specialized interdisciplinary setting may provide a precise, safe, and efficient treatment for ETS sequelae. A clinical study is initiated to validate this new therapy.

Robotic-Assisted Peripheral Nerve Surgery: A Systematic Review.

BACKGROUND: Robotic-assisted techniques are a tremendous revolution in modern surgery, and the advantages and indications were well discussed in different specialties. However, the use of robotic technique in plastic and reconstructive surgery is still very limited, especially in the field of peripheral nerve reconstruction. This study aims to identify current clinical applications for peripheral nerve reconstruction, and to evaluate the advantages and disadvantages to establish potential uses in the future. METHODS: A review was conducted in the literatures from PubMed focusing on currently published robotic peripheral nerve intervention techniques. Eligible studies included related animal model, cadaveric and human studies. Reviews on robotic microsurgical technique unrelated to peripheral nerve intervention and non-English articles were excluded. The differences of wound assessment and nerve management between robotic-assisted and conventional approach were compared. RESULTS: Total 19 studies including preclinical experimental researches and clinical reports were listed and classified into brachial plexus reconstruction, peripheral nerve tumors management, peripheral nerve decompression or repair, peripheral nerve harvesting, and sympathetic trunk reconstruction. There were three animal studies, four cadaveric studies, eight clinical series, and four studies demonstrating clinical, animal, or cadaveric studies simultaneously. In total 53 clinical cases, only 20 (37.7%) cases were successfully approached with minimal invasive and intervened robotically; 17 (32.1%) cases underwent conventional approach and the nerves were intervened robotically; 12 (22.6%) cases converted to open approach but still intervened the nerve by robot; and 4 (7.5%) cases failed to approach robotically and converted to open surgery entirely. CONCLUSION: Robotic-assisted surgery is still in the early stage in peripheral nerve surgery. We believe the use of the robotic system in this field will develop to become popular in the future, especially in the fields that need cooperation with other specialties to provide the solutions for challenging circumstances.