Fertility-sparing uterine displacement for pelvic malignancies: surgical options and radiotherapy dosimetry on a human cadaver.

BACKGROUND: Radio(chemo)therapy is often required in pelvic malignancies (cancer of the anus, rectum, cervix). Direct irradiation adversely affects ovarian and endometrial function, compromising the fertility of women. While ovarian transposition is an established method to move the ovaries away from the radiation field, surgical procedures to displace the uterus are investigational. This study demonstrates the surgical options for uterine displacement in relation to the radiation dose received.  METHODS: The uterine displacement techniques were carried out sequentially in a human female cadaver to demonstrate each procedure step by step and assess the uterine positions with dosimetric CT scans in a hybrid operating room. Two treatment plans (anal and rectal cancer) were simulated on each of the four dosimetric scans (1. anatomical position, 2. uterine suspension of the round ligaments to the abdominal wall 3. ventrofixation of the uterine fundus at the umbilical level, 4. uterine transposition). Treatments were planned on Eclipse® System (Varian Medical Systems®,USA) using Volumetric Modulated Arc Therapy. Data about maximum (Dmax) and mean (Dmean) radiation dose received and the volume receiving 14 Gy (V14Gy) were collected. RESULTS: All procedures were completed without technical complications. In the rectal cancer simulation with delivery of 50 Gy to the tumor, Dmax, Dmean and V14Gy to the uterus were respectively 52,8 Gy, 34,3 Gy and 30,5cc (1), 31,8 Gy, 20,2 Gy and 22.0cc (2), 24,4 Gy, 6,8 Gy and 5,5cc (3), 1,8 Gy, 0,6 Gy and 0,0cc (4). For anal cancer, delivering 64 Gy to the tumor respectively 46,7 Gy, 34,8 Gy and 31,3cc (1), 34,3 Gy, 20,0 Gy and 21,5cc (2), 21,8 Gy, 5,9 Gy and 2,6cc (3), 1,4 Gy, 0,7 Gy and 0,0cc (4). CONCLUSIONS: The feasibility of several uterine displacement procedures was safely demonstrated. Increasing distance to the radiation field requires more complex surgical interventions to minimize radiation exposure. Surgical strategy needs to be tailored to the multidisciplinary treatment plan, and uterine transposition is the most technically complex with the least dose received.

Obesity paradox: is a high body mass index positively influencing survival outcomes in gynecological cancers? A systematic review and meta-analysis.

OBJECTIVE: Obesity represents an exponentially growing preventable disease leading to different health complications, particularly when associated with cancer. In recent years, however, an 'obesity paradox' has been hypothesized where obese individuals affected by cancer counterintuitively show better survival rates. The aim of this systematic review and meta-analysis is to assess whether the prognosis in gynecological malignancies is positively influenced by obesity. METHODS: This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting the impact of a body mass index (BMI) of >30 kg/m2 compared with <30 kg/m2 in patients with gynecological cancers listed in PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for quality assessment of the selected articles. RESULTS: Twenty-one studies were identified for the meta-analysis, including 14 108 patients with cervical, ovarian, or endometrial cancer. There was no benefit in 5-year overall survival for obese patients compared with non-obese patients (OR 1.2, 95% CI 1.00 to 1.44, p=0.05; I2=71%). When pooling for cancer sub-groups, there were no statistically significant differences in 5-year overall survival in patients with cervical cancer and 5-year overall survival and progression-free survival in patients with ovarian cancer. For obese women diagnosed with endometrial cancer, a significant decrease of 44% in 5-year overall survival (p=0.01) was found, with no significant difference in 5-year disease-free survival (p=0.78). CONCLUSION: According to the results of the present meta-analysis, a BMI of ≥30 kg/m2 does not have a positive prognostic effect on survival compared with a BMI of <30 kg/m2 in women diagnosed with gynecological cancers. The existence of the 'obesity paradox' in other fields, however, suggests the importance of further investigations with prospective studies.

Ultrasound-guided robotic surgical procedures: a systematic review.

INTRODUCTION: Ultrasound has been nicknamed "the surgeon's stethoscope". The advantages of laparoscopic ultrasound beyond a substitute for the sense of touch are considerable, especially for robotic surgery. Being able to see through parenchyma and into vascular structures enables to avoid unnecessary dissection by providing a thorough assessment at every stage without the need for contrast media or ionising radiation. The limitations of restricted angulation and access within the abdominal cavity during laparoscopy can be overcome by robotic handling of miniaturised ultrasound probes and the use of various and specific frequencies will meet tissue- and organ-specific characteristics. The aim of this systematic review was to assess the reported applications of intraoperative ultrasound-guided robotic surgery and to outline future perspectives. METHODS: The study adhered to the PRISMA guidelines. PubMed, Google Scholar, ScienceDirect and ClinicalTrials.gov were searched up to October 2023. Manuscripts reporting data on ultrasound-guided robotic procedures were included in the qualitative analysis. RESULTS: 20 studies met the inclusion criteria. The majority (53%) were related to the field of general surgery during liver, pancreas, spleen, gallbladder/bile duct, vascular and rectal surgery. This was followed by other fields of oncological surgery (42%) including urology, lung surgery, and retroperitoneal lymphadenectomy for metastases. Among the studies, ten (53%) focused on locating tumoral lesions and defining resection margins, four (15%) were designed to test the feasibility of robotic ultrasound-guided surgery, while two (10.5%) aimed to compare robotic and laparoscopic ultrasound probes. Additionally two studies (10.5%) evaluated the robotic drop-in probe one (5%) assessed the hepatic tissue consistency and another one (5%) aimed to visualize the blood flow in the splenic artery. CONCLUSION: The advantages of robotic instrumentation, including ergonomics, dexterity, and precision of movements, are of relevance for robotic intraoperative ultrasound (RIOUS). The present systematic review demonstrates the virtue of RIOUS to support surgeons and potentially reduce minimally invasive procedure times.

Initial experience of robotically assisted endometriosis surgery with a novel robotic system: first case series in a tertiary care center.

Endometriosis is a benign disease requiring surgery if medical treatment can not achieve symptom control. Laparoscopy remains the gold standard and robotic assistance can be beneficial in complex cases. Robot-assisted radical endometriosis excision using the Hugo™ RAS system is a novel approach. The aim of this study is to describe its setting and outcomes in a series of patients in a robotic surgery center. Endometriosis patients who consecutively underwent robot-assisted surgery with the Hugo™ RAS system (Medtronic, USA) were retrospectively enrolled. Disease-specific symptoms before and after surgery, endometriosis stage, as well as perioperative and intraoperative variables including system setup were collected. Early post-operative complications (< 30 days) and follow-up (up to 3 months) were reported. All procedures were completed robotically. Port placement followed the "bridge" configuration with a "compact" docking. The median operative time was 186.5 min (IQR 174-220), the median estimated blood loss 50 ml (IQR 0-100). An intraoperative complication occurred in one patient (6.6%), a bladder laceration with postoperative antibiotic treatment. The median lenght of hospital stay (LOS) was 3 days (IQR 3-4). Surgery achieved a statistically significant decrease in symptoms: mean dysmenorrhea (9.50 ± 0.83 versus 1.7 ± 2.26; p = 0.001), dyschezia (4.27 ± 3.61 versus 2.40 ± 2.92; p = 0.026), dysuria (2.73 ± 3.39 versus 1.87 ± 2.41; p = 0.358), dyspareunia (6.53 ± 3.15 versus 2.93 ± 2.89; p = 0.002) and chronic pelvic pain (8.8 ± 1.20 versus 3.20 ± 2.39; p = 0.001). The integration of this platform in the described configuration was safe with regular perioperative outcomes and significant improvement in symptoms. Prospective comparative studies with a larger cohort and longer follow-up are needed to assess potential advantages over the current gold standard.

Endoscopic ultrasound-guided perivascular pancreatic radiofrequency ablation using a hydroxyethyl starch solution prior to pancreatectomy.

Background and study aims Pancreatic surgery remains complex, particularly for borderline resectable and locally advanced tumors. Vascular invasion compromises resectability, and vascular resection entails increased morbidity and mortality. Following a feasibility and safety demonstration of augmented endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) using hydroxyethyl starch (HES) in porcine pancreatic parenchyma, the present study assesses whether this approach (EUS-sugar-RFA) in the pancreatic perivascular space is safe and creates a controllable margin of necrosis to enable a vessel-sparing resection. Methods EUS-sugar-RFA in the pancreatic parenchyma adjacent to the splenic artery and vein was performed in a live animal model. Following different survival periods (0-4 days) in the interventional group (n = 3), open pancreatectomy was carried out. The control group (n = 4) included open pancreatectomies in two pigs with non-treated pancreases and in two with pancreatic RFA alone on the same day. Results All procedures were completed successfully, without intraoperative or postoperative complications. Survival periods were uncomplicated. Histopathological examination showed local necrosis and inflammatory reaction at the ablation sites. Vascular wall integrity was preserved in all specimens. The untreated pancreatic zones in the interventional group were no different from the normal pancreases in the control group. Conclusions Preoperative perivascular augmented RFA using HES was safe, and in the pancreatic animal model, the best timeframe was within 24 hours before pancreatic surgery. This technique might improve resectability in selected borderline and locally advanced pancreatic cancers.

CholecTriplet2022: Show me a tool and tell me the triplet - An endoscopic vision challenge for surgical action triplet detection.

Formalizing surgical activities as triplets of the used instruments, actions performed, and target anatomies is becoming a gold standard approach for surgical activity modeling. The benefit is that this formalization helps to obtain a more detailed understanding of tool-tissue interaction which can be used to develop better Artificial Intelligence assistance for image-guided surgery. Earlier efforts and the CholecTriplet challenge introduced in 2021 have put together techniques aimed at recognizing these triplets from surgical footage. Estimating also the spatial locations of the triplets would offer a more precise intraoperative context-aware decision support for computer-assisted intervention. This paper presents the CholecTriplet2022 challenge, which extends surgical action triplet modeling from recognition to detection. It includes weakly-supervised bounding box localization of every visible surgical instrument (or tool), as the key actors, and the modeling of each tool-activity in the form of triplet. The paper describes a baseline method and 10 new deep learning algorithms presented at the challenge to solve the task. It also provides thorough methodological comparisons of the methods, an in-depth analysis of the obtained results across multiple metrics, visual and procedural challenges; their significance, and useful insights for future research directions and applications in surgery.

Use of fluorescence imaging and indocyanine green during thyroid and parathyroid surgery: Results of an intercontinental, multidisciplinary Delphi survey.

BACKGROUND: In recent years, fluorescence imaging-relying both on parathyroid gland autofluorescence under near-infrared light and angiography using the fluorescent dye indocyanine green-has been used to reduce risk of iatrogenic parathyroid injury during thyroid and parathyroid resections, but no published guidelines exist regarding its use. In this study, orchestrated by the International Society for Fluorescence Guided Surgery, areas of consensus and nonconsensus were examined among international experts to facilitate future drafting of such guidelines. METHODS: A 2-round, online Delphi survey was conducted of 10 international experts in fluorescence imaging use during endocrine surgery, asking them to vote on 75 statements divided into 5 modules: 1 = patient preparation and contraindications to fluorescence imaging (n = 11 statements); 2 = technical logistics (n = 16); 3 = indications (n = 21); 4 = potential advantages and disadvantages of fluorescence imaging (n = 20); and 5 = training and research (n = 7). Several methodological steps were taken to minimize voter bias. RESULTS: Overall, parathyroid autofluorescence was considered better than indocyanine green angiography for localizing parathyroid glands, whereas indocyanine green angiography was deemed superior assessing parathyroid perfusion. Additional surgical scenarios where indocyanine green angiography was thought to facilitate surgery are (1) when >1 parathyroid gland requires resection; (2) during redo surgeries, (3) facilitating parathyroid autoimplantation; and (4) for the predissection visualization of abnormal glands. Both parathyroid autofluorescence and indocyanine green angiography can be used during the same procedure and employing the same imaging equipment. However, further research is needed to optimize the dose and timing of indocyanine green administration. CONCLUSION: Though further research remains necessary, using fluorescence imaging appears to have uses during thyroid and parathyroid surgery.

Robotically assisted augmented reality system for identification of targeted lymph nodes in laparoscopic gynecological surgery: a first step toward the identification of sentinel node : Augmented reality in gynecological surgery.

BACKGROUND: To prove feasibility of multimodal and temporal fusion of laparoscopic images with preoperative computed tomography scans for a real-time in vivo-targeted lymph node (TLN) detection during minimally invasive pelvic lymphadenectomy and to validate and enable such guidance for safe and accurate sentinel lymph node dissection, including anatomical landmarks in an experimental model. METHODS: A measurement campaign determined the most accurate tracking system (UR5-Cobot versus NDI Polaris). The subsequent interventions on two pigs consisted of an identification of artificial TLN and anatomical landmarks without and with augmented reality (AR) assistance. The AR overlay on target structures was quantitatively evaluated. The clinical relevance of our system was assessed via a questionnaire completed by experienced and trainee surgeons. RESULTS: An AR-based robotic assistance system that performed real-time multimodal and temporal fusion of laparoscopic images with preoperative medical images was developed and tested. It enabled the detection of TLN and their surrounding anatomical structures during pelvic lymphadenectomy. Accuracy of the CT overlay was > 90%, with overflow rates < 6%. When comparing AR to direct vision, we found that scores were significatively higher in AR for all target structures. AR aided both experienced surgeons and trainees, whether it was for TLN, ureter, or vessel identification. CONCLUSION: This computer-assisted system was reliable, safe, and accurate, and the present achievements represent a first step toward a clinical study.

Rendezvous: Attention mechanisms for the recognition of surgical action triplets in endoscopic videos.

Out of all existing frameworks for surgical workflow analysis in endoscopic videos, action triplet recognition stands out as the only one aiming to provide truly fine-grained and comprehensive information on surgical activities. This information, presented as 〈instrument, verb, target〉 combinations, is highly challenging to be accurately identified. Triplet components can be difficult to recognize individually; in this task, it requires not only performing recognition simultaneously for all three triplet components, but also correctly establishing the data association between them. To achieve this task, we introduce our new model, the Rendezvous (RDV), which recognizes triplets directly from surgical videos by leveraging attention at two different levels. We first introduce a new form of spatial attention to capture individual action triplet components in a scene; called Class Activation Guided Attention Mechanism (CAGAM). This technique focuses on the recognition of verbs and targets using activations resulting from instruments. To solve the association problem, our RDV model adds a new form of semantic attention inspired by Transformer networks; called Multi-Head of Mixed Attention (MHMA). This technique uses several cross and self attentions to effectively capture relationships between instruments, verbs, and targets. We also introduce CholecT50 - a dataset of 50 endoscopic videos in which every frame has been annotated with labels from 100 triplet classes. Our proposed RDV model significantly improves the triplet prediction mAP by over 9% compared to the state-of-the-art methods on this dataset.

Visual Haptic Feedback for Training of Robotic Suturing.

Current surgical robotic systems are teleoperated and do not have force feedback. Considerable practice is required to learn how to use visual input such as tissue deformation upon contact as a substitute for tactile sense. Thus, unnecessarily high forces are observed in novices, prior to specific robotic training, and visual force feedback studies demonstrated reduction of applied forces. Simulation exercises with realistic suturing tasks can provide training outside the operating room. This paper presents contributions to realistic interactive suture simulation for training of suturing and knot-tying tasks commonly used in robotically-assisted surgery. To improve the realism of the simulation, we developed a global coordinate wire model with a new constraint development for the elongation. We demonstrated that a continuous modeling of the contacts avoids instabilities during knot tightening. Visual cues are additionally provided, based on the computation of mechanical forces or constraints, to support learning how to dose the forces. The results are integrated into a powerful system-agnostic simulator, and the comparison with equivalent tasks performed with the da Vinci Xi system confirms its realism.

Evaluation of an Innovative Care Pathway in the Diagnostic and Therapeutic Management of Hepatobiliary and Pancreatic Pathologies: "One-Day Diagnosis".

"One-Day Diagnosis" (1DD) for hepatobiliary and pancreatic (HBP) diseases is an innovative care pathway that combines, on the same day, surgical consultation, medical imaging, anesthesia, diagnosis announcement, and therapeutic support consultations. The objective was to evaluate the length of the 1DD care pathway compared to a conventional one. The prospective "1DD care pathway" arm included 330 consecutive patients (January 2017−April 2019) vs. 152 (November 2014−November 2015) in the retrospective "conventional" one. In the 1DD group, diagnosis was made on the same day in 83% of consultations vs. 68.4% (p = 0.0005). Although there was no difference in overall time to diagnosis, diagnostic and therapeutic management was faster in the 1DD group (1 day vs. 15 days, p < 0.0004). In addition, 77% of patients who benefited from 1DD were very satisfied with their treatment overall. The mean cost of the 1DD consultation was EUR 176.8 +/− 149 (range: 50−546). The median cost of the overall program was similar (EUR 584 vs. EUR 563, p = 0.67). As an organizational innovation, the 1DD for HBP pathologies is a promising care pathway that optimizes diagnostic and therapeutic management, without creating medical overconsumption or additional costs. Given patient satisfaction, this model should be generalized to optimize cancer care by adapting it to the constraints of different healthcare structures.

Fluorescence Image-Guided Surgery for Thyroid Cancer: Utility for Preventing Hypoparathyroidism.

Background: Hypoparathyroidism is one of the most frequent complications of thyroid surgery, especially when associated with lymph node dissection in cases of thyroid cancer. Fluorescence-guided surgery is an emerging tool that appears to help reduce the rate of this complication. The present review aims to highlight the utility of fluorescence imaging in preserving parathyroid glands during thyroid cancer surgery. Methods: We performed a systematic review of the literature according to PRISMA guidelines to identify published studies on fluorescence-guided thyroid surgery with a particular focus on thyroid cancer. Articles were selected and analyzed per indication and type of surgery, autofluorescence or exogenous dye usage, and outcomes. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess the methodological quality of the included articles. Results: Twenty-five studies met the inclusion criteria, with three studies exclusively assessing patients with thyroid cancer. The remaining studies assessed mixed cohorts with thyroid cancer and other thyroid or parathyroid diseases. The majority of the papers support the potential benefit of fluorescence imaging in preserving parathyroid glands in thyroid surgery. Conclusions: Fluorescence-guided surgery is useful in the prevention of post-thyroidectomy hypoparathyroidism via enhanced early identification, visualization, and preservation of the parathyroid glands. These aspects are notably beneficial in cases of associated lymphadenectomy for thyroid cancer.

Computer-assisted quantification and visualization of bowel perfusion using fluorescence-based enhanced reality in left-sided colonic resections.

BACKGROUND: Fluorescence-based enhanced reality (FLER) is a computer-based quantification method of fluorescence angiographies to evaluate bowel perfusion. The aim of this prospective trial was to assess the clinical feasibility and to correlate FLER with metabolic markers of perfusion, during colorectal resections. METHODS: FLER analysis and visualization was performed in 22 patients (diverticulitis n = 17; colorectal cancer n = 5) intra- and extra-abdominally during distal and proximal resection, respectively. The fluorescence signal of indocyanine green (0.2 mg/kg) was captured using a near-infrared camera and computed to create a virtual color-coded cartography. This was overlaid onto the bowel (enhanced reality). It helped to identify regions of interest (ROIs) where samples were subsequently obtained. Resections were performed strictly guided according to clinical decision. On the surgical specimen, samplings were made at different ROIs to measure intestinal lactates (mmol/L) and mitochondria efficiency as acceptor control ratio (ACR). RESULTS: The native (unquantified) fluorescent signal diffused to obvious ischemic areas during the distal appreciation. Proximally, a lower diffusion of ICG was observed. Five anastomotic complications occurred. The expected values of local capillary lactates were correlated with the measured values both proximally (3.62 ± 2.48 expected vs. 3.17 ± 2.8 actual; rho 0.89; p = 0.0006) and distally (4.5 ± 3 expected vs. 4 ± 2.5 actual; rho 0.73; p = 0.0021). FLER values correlated with ACR at the proximal site (rho 0.76; p = 0.04) and at the ischemic zone (rho 0.71; p = 0.01). In complicated cases, lactates at the proximal resection site were higher (5.8 ± 4.5) as opposed to uncomplicated cases (2.45 ± 1.5; p = 0.008). ACR was reduced proximally in complicated (1.3 ± 0.18) vs. uncomplicated cases (1.68 ± 0.3; p = 0.023). CONCLUSIONS: FLER allows to image the quantified fluorescence signal in augmented reality and provides a reproducible estimation of bowel perfusion (NCT02626091).

Near-infrared fluorescent coatings of medical devices for image-guided surgery.

Rapidly expanding field of image-guided surgery needs new materials for near-infrared imaging with deep tissue penetration. Here, we introduce near-infrared coating of equipment (NICE) for image-guided surgery based on a series of lipophilic cyanine-7.5 dyes with bulky hydrophobic counterions and a biocompatible polymer, poly(methyl methacrylate). The NICE material exhibits superior brightness (15-20-fold higher) and photostability compared to fluorescent coatings based on commonly used indocyanine green (ICG). It can be deposited on different surfaces and devices, such as steel and gold fiducials, silicone and PVC catheters, polymeric surgical sutures and gauzes. Such coated medical devices show excellent stability in air and buffer for ≥150 days. Accelerated ageing revealed their shelf-life of ≥3 years. They are also stable in serum-containing media, whereas ICG-based coating shows rapid dye leakage. NICE is compatible with standard sterilization protocols based on ethylene oxide and vapor. Moreover, our coating material is biocompatible, where cultured cells spread effectively without signs of cytotoxicity. Ex vivo studies suggest that NICE on fiducials can be visualized as deep as 0.5 cm, and NICE on catheters enables their visualization inside ureters and esophagus. Finally, NICE on different medical devices has been validated for image-guided surgery in porcine and human cadaver models. Thus, the developed NIR coating material emerges as a powerful tool for a variety of medical applications.

Robotics in flexible endoscopy: current status and future prospects.

PURPOSE OF REVIEW: Advanced endoscopy procedures are technically challenging and require extensive training. Recent technological advances made in computer science and robotics have the potential to enhance the performance of complex intraluminal and transluminal interventions and potentially optimize precision and safety. This review covers the different technologies used for robot-assisted interventions in the gastrointestinal tract, organized according to their clinical availability, and focusing on flexible endoscopy-based systems. RECENT FINDINGS: In the curvilinear gastrointestinal anatomy, robotic technology can enhance flexible endoscopes to augment effectiveness, safety, and therapeutic capabilities, particularly for complex intraluminal and transluminal interventions. Increased visual angles, increased degrees of freedom of instrumentation, optimized navigation, and locomotion, which may lead to a reduced physician learning curve and workload, are promising achievements with the promise to ultimately replace conventional endoscopy techniques for screening and therapeutic endoscopy. SUMMARY: The majority of these devices are not commercially available yet. The best clinical applications are also currently being researched. Nonetheless, robotic assistance may encourage surgeons to use flexible endoscopes to administer surgical therapies and increase interest among gastroenterologists in advanced therapies. Robotics may be a means to overcome the technical obstacles of incisionless natural orifice procedures and favor an increased adoption of complex endoscopic procedures such as third-space therapies.

Acute abdomen in patients with SARS-CoV-2 infection or co-infection.

PURPOSE: Patients with an acute abdomen require emergency surgery. SARS-CoV-2 infection can affect multiple organ systems, including the digestive tract. Little is known about the consequences of COVID-19 infection in emergency surgical patients. METHODS: Perioperative data for COVID-19 patients undergoing emergency surgery from March 1, 2020, to May 23, 2020 were collected prospectively (NCT04323644). RESULTS: During this period, 215 patients underwent surgery, including 127 patients in an emergency setting, of whom 13 (10.2%) had COVID-19. Two scenarios were identified: (a) patients who were admitted to a hospital for an acute surgical condition with a concomitant diagnosis of COVID-19, and (b) patients with severe COVID-19 developing acute abdominal pathologies during their hospital stay. When compared with those in group B, patients in group A globally recovered better, with a lower mortality rate (14.3% vs. 33.3%), lower ARDS rate (28.5% vs. 50.0%), less rates of preoperative invasive ventilation (14.3% vs. 50.0%) and postoperative invasive ventilation (28.5% vs. 100.0%), and a shorter duration of invasive ventilation. No causality between SARS-CoV-2 infection and gastrointestinal affliction was found. CONCLUSION: Our observations underline that mild co-infection with COVID-19 did not result in more complications for emergency abdominal surgery. Howe, an acute abdomen during severe COVID-19 infection was part of an unfavorable prognosis.