High-Resolution Ultrasound-Guided Perforator Mapping and Characterization by the Microsurgeon in Lower Limb Reconstruction.

BACKGROUND: Preoperative ultrasound (US)-guided perforator mapping has immensely simplified perforator flap planning. It may be executed by the microsurgeon. Device settings and selection of ultrasound modes are of utmost significance for detection of low-flow microvessels. The following study evaluates different US modes. METHODS: A prospective complete data acquisition was performed from July 2018 to June 2019 in a subset of patients who underwent US-guided flap planning. Multifrequency linear transducers were used applying five US modes. Brightness (B)-mode, color flow (CF), power Doppler (PD), pulse wave (PW), and B-flow modes were evaluated regarding applicability by microsurgeons. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were chosen to evaluate flow characteristics. US results were correlated to intraoperative findings. RESULTS: A total number of eight patients (six males and two females) undergoing anterolateral thigh (ALT) or superficial circumflex iliac artery perforator (SCIP) flap surgery received an extensive standardized US-guided perforator characterization. Qualitative evaluation was performed in B-mode, color-coded duplex sonography (CCDS), PD, and B-flow mode. Quantitative assessment was executed using PW-mode and CCDS measuring the microvessels' diameter (mm) and flow characteristics (PSV, EDV, and RI). CCDS provided a mean diameter of 1.93 mm (range: 1.2-2.8 ± 0.51), a mean systolic peak of 16.9 cm/s (range: 9.9-33.4 ± 7.79), and mean RI of 0.71 (range: 0.55-0.87 ± 0.09) for lower limb perforators. All perforators located with US were verified by intraoperative findings. An optimized, time-effective US mapping algorithm was derived. Qualitative parameters may be evaluated with B-mode, CF, or B-flow. Smallest microvessels may be assessed in PD-mode. Lowering pulse-repetition frequency (PRF)/scale is mandatory to image low-flow microvessels as perforators. Quantitative information may be obtained using PW-mode and the distance-measuring tool in CF-mode. Image and video materials are provided. CONCLUSION: CCDS proved to be a powerful tool for preoperative perforator characterization when using a structured approach and mapping algorithm. Different techniques may be applied for specific visualizations and performed by the microsurgeon.

Feasibility study of preoperative microvessel evaluation and characterization in perforator flaps using various modes of color-coded duplex sonography (CCDS).

BACKGROUND: Color-coded duplex sonography (CCDS) is useful for perforator flap design showing the highest sensitivity in identifying microvessels. This prospective study evaluates the feasibility of different ultrasound (US) modes applied by the microsurgeon in daily practice suggesting quantifiable reference values. METHODS: Twenty-four patients aged between 17 and 68 years (mean 43.3 ± 14.2 years) with 18 anterolateral thigh (ALT) and 6 superficial circumflex iliac artery (SCIP) flaps were included. Indications were traumatic (n = 12), infectious (n = 6), ischemic (n = 4), or tumor-associated defects (n = 2). Different US modes were evaluated regarding applicability using multifrequency linear probes (5-15 MHz). Vessels diameter, peak systolic velocity (PSV), end diastolic velocity (EDV), and resistance index (RI) were measured. Preoperative results were correlated to intraoperative findings. RESULTS: In the examined patient group with 24 perforator flaps a 100% correlation was seen when comparing perforators detected with CCDS/PD with intraoperative findings using optimized US settings. Sensitivity, PPV, and accuracy of CCDS were 100% respectively. Mean PSV of 16.99 ± 6.07 cm/s, mean EDV of 5.01 ± 1.84 cm/s and RI of 0.7 ± 0.07 were measured in microvessels (PW-mode). CCDS proved to be superior compared to PD in correct diameter assessment showing a mean diameter of 1.65 ± 0.45 mm, compared to PD-mode 1.31 ± 0.24 mm. Mean PSV and EDV were higher in ALT than in SCIP flaps, RI was slightly higher in SCIP flaps (p > .05). There were no significant differences in size of different flaps' perforators (p > .05). CONCLUSION: CCDS represents a highly valuable tool in the daily practice of free flap reconstructions using optimized low flow US settings and multifrequency linear probes.

Pedicled ALT-flap for soft tissue reconstruction in the trochanteric area.

BACKGROUND: Coverage of soft tissue defects following surgery at the trochanteric area is challenging. Revision surgery in case of compromised wound healing may lead to soft tissue defects requiring reconstruction with pedicled or free flaps. Previous access to the hip joint may jeopardize neurovascular structures relevant to the flap. OBJECTIVE: In this study, we evaluated if the use of a pedicled anterior lateral thigh (ALT) flap is a valuable option for soft tissue reconstruction. METHODS: In this retrospective study, seven patients were included. Defect etiology was tumor resection in one case, screw osteosynthesis in another case and total hip arthroplasty in three cases. All patients underwent reconstruction by proximal pedicled anterior lateral thigh (ALT) flap. RESULTS: Pedicled ALT flap was a safe procedure in all cases. One patient showed delayed wound healing with need for additional surgery. No further complications were observed. CONCLUSIONS: Pedicled ALT flap transfer represents a reliable option for soft tissue coverage in the trochanteric area after primary surgery such as hip arthroplasty, osteosynthesis or tumor resection.

Pure Wisdom or Potemkin Villages? A Comparison of ChatGPT 3.5 and ChatGPT 4 on USMLE Step 3 Style Questions: Quantitative Analysis.

BACKGROUND: The United States Medical Licensing Examination (USMLE) has been critical in medical education since 1992, testing various aspects of a medical student's knowledge and skills through different steps, based on their training level. Artificial intelligence (AI) tools, including chatbots like ChatGPT, are emerging technologies with potential applications in medicine. However, comprehensive studies analyzing ChatGPT's performance on USMLE Step 3 in large-scale scenarios and comparing different versions of ChatGPT are limited. OBJECTIVE: This paper aimed to analyze ChatGPT's performance on USMLE Step 3 practice test questions to better elucidate the strengths and weaknesses of AI use in medical education and deduce evidence-based strategies to counteract AI cheating. METHODS: A total of 2069 USMLE Step 3 practice questions were extracted from the AMBOSS study platform. After including 229 image-based questions, a total of 1840 text-based questions were further categorized and entered into ChatGPT 3.5, while a subset of 229 questions were entered into ChatGPT 4. Responses were recorded, and the accuracy of ChatGPT answers as well as its performance in different test question categories and for different difficulty levels were compared between both versions. RESULTS: Overall, ChatGPT 4 demonstrated a statistically significant superior performance compared to ChatGPT 3.5, achieving an accuracy of 84.7% (194/229) and 56.9% (1047/1840), respectively. A noteworthy correlation was observed between the length of test questions and the performance of ChatGPT 3.5 (ρ=-0.069; P=.003), which was absent in ChatGPT 4 (P=.87). Additionally, the difficulty of test questions, as categorized by AMBOSS hammer ratings, showed a statistically significant correlation with performance for both ChatGPT versions, with ρ=-0.289 for ChatGPT 3.5 and ρ=-0.344 for ChatGPT 4. ChatGPT 4 surpassed ChatGPT 3.5 in all levels of test question difficulty, except for the 2 highest difficulty tiers (4 and 5 hammers), where statistical significance was not reached. CONCLUSIONS: In this study, ChatGPT 4 demonstrated remarkable proficiency in taking the USMLE Step 3, with an accuracy rate of 84.7% (194/229), outshining ChatGPT 3.5 with an accuracy rate of 56.9% (1047/1840). Although ChatGPT 4 performed exceptionally, it encountered difficulties in questions requiring the application of theoretical concepts, particularly in cardiology and neurology. These insights are pivotal for the development of examination strategies that are resilient to AI and underline the promising role of AI in the realm of medical education and diagnostics.

Diagnosing lagophthalmos using artificial intelligence.

Lagophthalmos is the incomplete closure of the eyelids posing the risk of corneal ulceration and blindness. Lagophthalmos is a common symptom of various pathologies. We aimed to program a convolutional neural network to automatize lagophthalmos diagnosis. From June 2019 to May 2021, prospective data acquisition was performed on 30 patients seen at the Department of Plastic, Hand, and Reconstructive Surgery at the University Hospital Regensburg, Germany (IRB reference number: 20-2081-101). In addition, comparative data were gathered from 10 healthy patients as the control group. The training set comprised 826 images, while the validation and testing sets consisted of 91 patient images each. Validation accuracy was 97.8% over the span of 64 epochs. The model was trained for 17.3 min. For training and validation, an average loss of 0.304 and 0.358 and a final loss of 0.276 and 0.157 were noted. The testing accuracy was observed to be 93.41% with a loss of 0.221. This study proposes a novel application for rapid and reliable lagophthalmos diagnosis. Our CNN-based approach combines effective anti-overfitting strategies, short training times, and high accuracy levels. Ultimately, this tool carries high translational potential to facilitate the physician's workflow and improve overall lagophthalmos patient care.

Iliac Bone Corridors to Host the Transiliac Internal Fixator-An Experimental CT Based Analysis.

BACKGROUND: The transiliac internal fixator (TIFI) is a novel minimally invasive surgical procedure to stabilize posterior pelvic ring fractures. Two bone corridors with different lengths, widths, and angulations are suitable to host screws in the posterior iliac wing. While the length and the width have been described previously, the angulation has not been determined yet. METHODS: We created a computer tomography-based 3D-model of 40 patients (20 women, 20 men). The possible bone corridors to host the ilium screws for the TIFIcc (cranio-caudal) and the TIFIdv (dorso-ventral) procedure were identified. After reaching the optimal position, the angles in relation to the sagittal and axial plane were measured. The anterior pelvic plane was chosen as the reference plane. RESULTS: The mean angle of the TIFIcc screws related to the axial plane was 63.4° (±1.8°) and to the sagittal plane was 12.3° (±1.5°). The mean angle of the TIFIdv screws related to the axial plane was 16.1° (±1.2°) and to the sagittal plane was 20.1° (±2.0°). In each group, a high constancy was apparent irrespective of the age or physical dimension of the patient, although a significant gender-dependent difference was observed". CONCLUSIONS: Due to a high inter-individual constancy in length, width, and angulation, bone corridors in the posterior iliac wing are reliable to host screws for posterior pelvic ring fixation irrespective of each individual patient's anatomy.

Microanatomy of the Frontal Branch of the Facial Nerve: The Role of Nerve Caliber and Axonal Capacity.

BACKGROUND: A commonly seen issue in facial palsy patients is brow ptosis caused by paralysis of the frontalis muscle powered by the frontal branch of the facial nerve. Predominantly, static methods are used for correction. Functional restoration concepts include the transfer of the deep temporal branch of the trigeminal nerve and cross-facial nerve grafts. Both techniques can neurotize the original mimic muscles in early cases or power muscle transplants in late cases. Because axonal capacity is particularly important in cross-facial nerve graft procedures, the authors investigated the microanatomical features of the frontal branch to provide the basis for its potential use and to ease intraoperative donor nerve selection. METHODS: Nerve biopsy specimens from 106 fresh-frozen cadaver facial halves were obtained. Histologic processing and digitalization were followed by nerve morphometric analysis and semiautomated axon quantification. RESULTS: The frontal branch showed a median of three fascicles (n = 100; range, one to nine fascicles). A mean axonal capacity of 1191 ± 668 axons (range, 186 to 3539 axons; n = 88) and an average cross-sectional diameter of 1.01 ± 0.26 mm (range, 0.43 to 1.74 mm; n = 67) were noted. In the linear regression model, diameter and axonal capacity demonstrated a positive relation (n = 57; r2 = 0.32; p < 0.001). Based on that equation, a nerve measuring 1 mm is expected to carry 1339 axons. CONCLUSION: The authors' analysis on the microanatomy of the frontal branch could promote clinical use of cross-facial nerve graft procedures in frontalis muscle neurotization and free muscle transplantations.

A prospective randomised, open-labeled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma.

BACKGROUND: The potential anti-cancer effects of mammalian target of rapamycin (mTOR) inhibitors are being intensively studied. To date, however, few randomised clinical trials (RCT) have been performed to demonstrate anti-neoplastic effects in the pure oncology setting, and at present, no oncology endpoint-directed RCT has been reported in the high-malignancy risk population of immunosuppressed transplant recipients. Interestingly, since mTOR inhibitors have both immunosuppressive and anti-cancer effects, they have the potential to simultaneously protect against immunologic graft loss and tumour development. Therefore, we designed a prospective RCT to determine if the mTOR inhibitor sirolimus can improve hepatocellular carcinoma (HCC)-free patient survival in liver transplant (LT) recipients with a pre-transplant diagnosis of HCC. METHODS/DESIGN: The study is an open-labelled, randomised, RCT comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing LT for HCC. Patients with a histologically confirmed HCC diagnosis are randomised into 2 groups within 4-6 weeks after LT; one arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol and the second arm is maintained on a centre-specific mTOR-inhibitor-free immunosuppressive protocol for the first 4-6 weeks, at which time sirolimus is initiated. A 21/2 -year recruitment phase is planned with a 5-year follow-up, testing HCC-free survival as the primary endpoint. Our hypothesis is that sirolimus use in the second arm of the study will improve HCC-free survival. The study is a non-commercial investigator-initiated trial (IIT) sponsored by the University Hospital Regensburg and is endorsed by the European Liver and Intestine Transplant Association; 13 countries within Europe, Canada and Australia are participating. DISCUSSION: If our hypothesis is correct that mTOR inhibition can reduce HCC tumour growth while simultaneously providing immunosuppression to protect the liver allograft from rejection, patients should experience less post-transplant problems with HCC recurrence, and therefore could expect a longer and better quality of life. A positive outcome will likely change the standard of posttransplant immunosuppressive care for LT patients with HCC. TRIAL REGISTER: Trial registered at http://www.clinicaltrials.gov: NCT00355862(EudraCT Number: 2005-005362-36).

Histological and SEM Assessment of Blood Stasis in Kidney Blood Vessels after Repeated Intra-Arterial Application of Radiographic Contrast Media.

BACKGROUND: After application of iodinated contrast media (CM), a pronounced deterioration of the microcirculation in skin and myocardium was reported. Clinically, the repeated application of CM, especially, led to an increase of the renal resistance index (RRI). With respect to the transiency of the RRI increase, it is reasonable to assume that the deterioration of blood flow could be due to transient blood stasis caused by reversible morphologic cell alterations due to osmotic discrepancies between CM and human blood. Therefore, the hypothesis was investigated whether CM are able to induce in vivo such blood stasis and cell deformations in the renal vasculature of well-hydrated pigs. METHODS: The in vivo study was performed as a prospective randomized examination to compare the effects of two different CM in 16 pigs (German Landrace). Pigs were randomized to receive either Iodixanol (n = 8), or Iopromide (n = 8). Each animal received 10 injections separated by 5-min intervals via the suprarenal aorta at a rate of 10 mL/s according to the usual procedure during a cardiac catheter examination. Finally, the kidneys were explanted and processed for histology (H & E staining and fibrin staining according to Weigert) as well as for scanning electron microscopy (SEM) with regards to morphologic correlates explaining the changes in the microcirculation. RESULTS: In each of the predefined four categories of vascular diameters, blood stasis were found, but clearly more often after application of Iopromide than after application of Iodixanol (p < 0.001). In addition, Iopromide induced more blood stasis in all of the examined kidney regions compared to Iodixanol (p = 0.0001). There were no obstructive events in the middle cortex following the application of Iodixanol. Except for the region around a puncture channel of a placed-in catheter probe, no fibrin was detected in Weigert's fibrin-stained samples, neither around the histologically assessed thrombi nor in vessels with blood stasis. Complementary SEM analyses revealed in a few cases only a slight generation of fibrin and thrombi and deformations, such as echinocyte and "box-like" deformations. CONCLUSIONS: According to previous in vitro studies, pathological erythrocyte deformations, such as echinocyte and box-like formation of erythrocytes, were observed also in vivo. In addition, blood stasis and/or thrombi could be detected in histological samples from explanted kidneys from young pigs after repeated in vivo administration of CM. In only a few cases, mural platelet aggregates within minimal fibrin meshes occurred only after the application of Iopromide.

Transcutaneous pO2 imaging during tourniquet-induced forearm ischemia using planar optical oxygen sensors.

BACKGROUND: Oxygen-dependent quenching of luminescence using transparent planar sensor foils was shown to overcome the limitations of the polarographic electrode technique in an animal model. This method was then transferred to a clinical setting to measure the transcutaneous pO(2) (p(tc)O(2)). METHODS: In six healthy subjects, a cuff on the upper arm was occluded up to 20 mmHg above systolic pressure and released after 8 min. P(tc)O(2) was measured at the lower arm every 30 s before, during, and up to 20 min after cuff occlusion (40 degrees C applied skin temperature) using luminescence lifetime imaging (LLI) of platinum(II)-octaethyl-porphyrin immobilized in a polystyrene matrix. For validation, the polarographic Clark electrode technique was applied in close proximity, and measurements were conducted simultaneously. RESULTS: P(tc)O(2) measurements before (70.8+/-19.1 vs. 66.2+/-7.7 mmHg) and at the end of ischemic (2.7+/-1.2 vs. 3.6+/-1.7 mmHg) and reperfusion phases (72.2+/-3.6 vs. 68.4+/-8.9 mmHg) did not differ significantly using the Clark electrode vs. LLI. At both the initial ischemic and the reperfusion phases, the Clark electrode measured a faster decrease or increase, respectively, in p(tc)O(2) because of the oxygen consumption occurring in this method. CONCLUSION: The presented method provides accurate and reproducible p(tc)O(2) values under changing microcirculatory conditions. The lack of oxygen consumption during measurement allows both a more realistic estimation of p(tc)O(2) than compared with the gold standard and permanent use in regions with critical oxygen supply.

Effect of iodinated contrast media on renal perfusion: A randomized comparison study in pigs using quantitative contrast-enhanced ultrasound (CEUS).

The administration of iodinated contrast media (CM) can cause microcirculatory disorder leading to acute renal dysfunction. In a prospective, randomized investigation two CM (Iodixanol vs Iopromide) were compared in 16 pigs. Each animal received 10 intra-aortal injections (5 ml Iodixanol or 4.32 ml Iopromide). Microcirculation was assessed using contrast-enhanced ultrasound (CEUS) directly on the kidney surface using time-to-peak (TTP) and blood-volume-analysis. Macroscopic observations were documented. Post mortem residual CM distribution in the kidneys was detected using X-ray. TTP was significantly prolonged over the descending vasa recta of the Iopromide group. This coincided with a visible marble-like pattern on the kidney surface occurring in 30 out of 80 Iopromide-injections but in 4 out of 80 Iodixanol-injections (p = 0.007). The blood volume over the entire kidney did not change after Iodixanol-application, but decreased by about 6.1% after Iopromide-application. The regional blood volume in the renal cortex showed a tendency to decrease by about 13.5% (p = 0.094) after Iodixanol-application, and clearly decreased by about 31.7% (p = 0.022) after Iopromide-application. The study revealed a consistent influence of repeated injections of two different CM on the kidney perfusion using three different imaging methods (CEUS analysis, macroscopic observation and X-ray analysis).

Flap design and perfusion are keys of success: Axial fasciocutaneous posterior thigh flaps for deep small pelvic defect reconstruction.

BACKGROUND AND OBJECTIVES: Radical excisions of the rectum often result in large perineal and intrapelvic defects. Compromised wound healing can delay adjuvant therapies and limit the patient's prognosis. With current treatment, integrity of the abdominal wall may be maintained. The defect geometry is unique and requires extensive volume for reconstruction. This study describes the surgical technique and reports clinical outcomes of fasciocutaneous posterior thigh flaps as preliminary data for this indication. METHODS: Thirteen posterior thigh flaps were used in eleven patients between 2013-2015. Patients were prospectively followed-up for the pursposes of this case series. Flap dimensions and volume were measured in two representative cases. The surgical technique is described in detail. RESULTS: Dead space occlusion was achieved in 100% of cases. No intestinal herniation was detected. Vaginal wall defects were concurrently reconstructed in two patients. Total flap volume was calculated as 315-360 cm3. The fasciocutaneous flaps were easy to harvest, versatile to manipulate and did not result in significant function deficits. CONCLUSIONS: In contrast to classic Vertical Rectus Abdominis Muscle (VRAM) flaps, the posterior thigh flaps preserve abdominal wall function and should be considered as a reliable alternative option in reconstruction of intrapelvic defects including neighboring organs. Future studies of larger patient series should be executed to verify our findings and determine the optimal point in time for reconstruction.

Sirolimus Use in Liver Transplant Recipients With Hepatocellular Carcinoma: A Randomized, Multicenter, Open-Label Phase 3 Trial.

BACKGROUND: We investigated whether sirolimus-based immunosuppression improves outcomes in liver transplantation (LTx) candidates with hepatocellular carcinoma (HCC). METHODS: In a prospective-randomized open-label international trial, 525 LTx recipients with HCC initially receiving mammalian target of rapamycin inhibitor-free immunosuppression were randomized 4 to 6 weeks after transplantation into a group on mammalian target of rapamycin inhibitor-free immunosuppression (group A: 264 patients) or a group incorporating sirolimus (group B: 261). The primary endpoint was recurrence-free survival (RFS); intention-to-treat (ITT) analysis was conducted after 8 years. Overall survival (OS) was a secondary endpoint. RESULTS: Recurrence-free survival was 64.5% in group A and 70.2% in group B at study end, this difference was not significant (P = 0.28; hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62; 1.15). In a planned analysis of RFS rates at yearly intervals, group B showed better outcomes 3 years after transplantation (HR, 0.7; 95% CI, 0.48-1.00). Similarly, OS (P = 0.21; HR, 0.81; 95% CI, 0.58-1.13) was not statistically better in group B at study end, but yearly analyses showed improvement out to 5 years (HR, 0.7; 95% CI, 0.49-1.00). Interestingly, subgroup (Milan Criteria-based) analyses revealed that low-risk, rather than high-risk, patients benefited most from sirolimus; furthermore, younger recipients (age ≤60) also benefited, as well sirolimus monotherapy patients. Serious adverse event numbers were alike in groups A (860) and B (874). CONCLUSIONS: Sirolimus in LTx recipients with HCC does not improve long-term RFS beyond 5 years. However, a RFS and OS benefit is evident in the first 3 to 5 years, especially in low-risk patients. This trial provides the first high-level evidence base for selecting immunosuppression in LTx recipients with HCC.

Recommendations for contrast enhanced ultrasound (CEUS) in free tissue transplant monitoring.

Complications rates after free flap transplantation still amount up to 5% . Consequently a reliable monitoring system is of high importance in plastic and reconstructive surgery. The following guidelines provide an overview of the current opportunities for free flap planning and monitoring with ultrasound and in particular with contrast enhanced ultrasound.