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Competing Interests: The authors declare no conflicts of interest.

Background: The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA)., Methods: Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN-), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker., Results: Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN- group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN- group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration., Conclusions: This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The incidence of malignant melanoma has been rising steadily over the past decades and Merkel cell carcinoma is a highly aggressive neuroendocrine skin tumor with a high mortality rate. Sentinel lymph node (SLN) biopsy is a recommended prognostic tool in primary cutaneous malignant melanomas of intermediate thickness and in all clinically node-negative Merkel cell carcinomas. The gold standard method for identification of SLNs is lymphoscintigraphy, which involves radioactive tracers. Indocyanine green-based near-infrared fluorescence imaging (NIRFI) has been also used for intraoperative SLN identification. We aim to evaluate the diagnostic sensitivity of the VisionSense VS3 NIRFI device for SNL identification. This device uses stereoscopic 3D high definition for both fluorescence and visible light imaging. Our hypothesis is that SLNs may be identified transcutaneously using fluorescent dye injections and NIRFI; therefore, obviating the need for lymphoscintigraphy in the future. METHODS AND ANALYSIS:: lymph node identification in skin malignancy using indocyanine green transcutaneously is a prospective diagnostic sensitivity study conducted at the Department of Plastic and Hand Surgery at the University Hospital Berne, Inselspital, Switzerland. The study aims at recruiting 93 patients (start date September 2017) to compare the accuracy of VisionSense VS3 camera at identifying SLNs transcutaneously with the current gold standard, lymphoscintigraphy. Moreover, a secondary objective is to determine if anatomical location of the SLN and patient factors (eg, body mass index, age) have an impact on the ability of VisionSense to detect SLNs when compared with the same gold standard., Trial Registration Number: ClinicalTrials.gov NCT03545334.

The effect of early mobilization on the healing of nerve repair was studied in a canine model. Median and ulnar nerves in the left wrist of 16 adult mongrel dogs were transected and immediately repaired. No motion of the repaired forelimb was allowed in the immobilized group (n = 10), while controlled passive motion between 30 and 90 degrees of wrist flexion was begun on the first postoperative day for 10 minutes twice daily in the mobilized group (n = 6). The pattern of revascularization and collagen formation at neurorrhaphy was examined by transillumination of India ink-injected specimen and by conventional histologic sections. Revascularization of nerve repair was found to occur by ingrowth of capillaries from proximal and distal nerve ends, which typically crossed the neurorrhaphy by 3 weeks in the immobilized group. Following early mobilization, there was a persistent "hypovascular zone" at the nerve repair site for up to 6 weeks. In addition, more scar tissue was generated by early motion according to gross observation and quantitative collagen analysis. Early mobilization, therefore, seems to impede nerve regeneration by delaying revascularization and enhancing scar formation.

Septal deviations interfere with nasal airflow and contribute to deformities in the external appearance of the nose. An aesthetically and functionally satisfactory correction of severe septal deformities or "crippled" septal plates often requires a temporary intraoperative removal of the septal cartilage for appropriate remodeling. This article describes refinements to the previously described technique of extracorporal septoplasty; these refinements have proven useful and have made the procedure safer in the hands of less experienced surgeons. The refinements simplify the straightening methods for the explanted septal plate, achieving a stable and median fixation of the replanted septum while maintaining a satisfactory contour of the nasal dorsum. A milling cutter is used to straighten the irregularities of the explanted septal plate and to thin broadly based anterior nasal spines. When necessary, microplates are added to stabilize the osteotomized and medialized anterior nasal spine. The final positioning of the replanted septal plate is greatly enhanced by a rein stitch, transosseous sutures, and multiple quilt stitches. Additionally, direct fixation of the replanted septum to the edges of the upper lateral cartilages further improves the stability of the reconstruction. Finally, particular care should be taken to avoid residual irregularities of the nasal dorsum; it they occur, these irregularities can be covered with a thin cartilaginous splint or a layer of dehydrated fascia lata or autologous temporal fascia. A total of 436 patients who underwent rhinoseptoplasties at the authors' department during a 1-year period were reviewed. Of these patients, 108 presented with severe septal deviations and underwent an extracorporal septoplasty using the refined techniques described herein. Despite the complexity of the procedure, the patients' satisfaction rates were high, independent of the operating surgeon.

The use of surgical lasers has been shown to decrease adhesion formation as compared with scalpel control groups in various surgical procedures. The potential benefits of laser technology have not been assessed in the treatment of adherent tendons. The current study was designed to first develop a reliable and reproducible model for consistent adhesion formation following flexor tendon trauma. The second goal was to compare the effects of laser tenolysis procedures on tendon gliding with those of traditional scalpel tenolysis. In phase I, the adhesion-induction model utilized bilateral standardized crush- abrasion injuries to the hind limb digital flexor tendons of New Zealand White rabbits. Following 4 weeks of immobilization, the animals were sacrificed, and peritendoneal adhesions were assessed biomechanically. A significantly higher maximal force was required to extract the adherent tendons from the foot as compared with nontraumatized control tendons. In phase II, six groups of animals underwent the same standardized tendon trauma. Four weeks later the rabbits were randomly assigned to undergo either CO2 laser or holmium:YAG laser tenolysis on one foot. Scalpel lysis was used on the contralateral foot and served as an intraindividual control. Biomechanical assessment was performed at 1, 2, and 4 weeks following tenolysis. Significantly less force was required to extract the treated tendons at 1 and 2 weeks following holmium:YAG laser tenolysis when compared with scalpel or CO2 laser tenolysis. After 4 weeks, differences between holmium:YAG and CO2 laser and scalpel treatment were no longer significant. Extracted tendons were pulled apart to failure, and no difference in breaking strength was noted between groups. We conclude that holmium:YAG laser tenolysis results in easier tendon gliding as compared with scalpel or CO2 laser tenolysis at early time points. Laser tenolysis does not affect intrinsic tendon strength.

With increasing life span of patients with CF, more women with CF are becoming pregnant and others are seeking information about the risks involved during pregnancy and delivery. A striking limitation of the available information is the lack of large prospective studies of pregnant patients with CF matched for age and disease severity compared with their non-pregnant cohorts. A study investigating the effect of pregnancy on morbidity and mortality is being completed by the Cystic Fibrosis Foundation. We recommend that all women with CF be offered contraceptive measures and counseling on the maternal and fetal risks of pregnancy, including the genetic risks for the child. The issue of who will raise the child in the event of subsequent morbidity or maternal mortality should ideally be prospectively discussed.

The effect of delay procedures on the survival of large arterialized venous flaps was studied in a rabbit ear model. Both ears of 25 New Zealand White rabbits (n = 50) were randomized into three operative groups receiving (1) no delay, (2) limited delay, or (3) extensive delay. Two weeks later the ear flap was completely divided, and arterialization of the flap venous tree was achieved by anastomosing the central artery of the ear to the anterior branch of the flap central vein. Survival area of 10 flaps in each group was assessed at 14 days. Flap vasculature was assessed in 10 additional ears in the nondelayed and extensively delayed groups by standardized vascular injections with radiopaque silicon rubber immediately, 6 hours, 24 hours, and 2 weeks after arterialization. Delay procedures significantly increased (p = 0.001, unpaired two-tailed Student's t test) survival of arterialized venous flaps in this model. Whereas all flaps in the non-delayed group underwent total necrosis, the mean viable surface area of the flaps was 67.9 percent in the limited delay group and 94.0 percent in the extensively delayed group. Lastly, angiographic studies suggest that delay procedures prior to arterialization of the venous tree enhance perfusion of the arterial tree by increasing venoarterial communications.

This investigation compared the variation of the biomechanical properties of canine and porcine craniofacial bones in homotypical (same site in opposite sides of an animal) and heterotypical (same site in different animals) sites. Biomechanical analysis is a reliable method to assess bone healing, because fracture repair correlates closely with the changes in biomechanical properties. Paired bone fragments were harvested in nine dogs and nine minipigs from each side of the skull from three different sites-the frontal bone, the supraorbital rim, and the zygomatic arch- and submitted to torque to failure. Maximum torque, stiffness, and toughness were recorded and comparative analysis performed. A normal range of variation between paired craniofacial bones in two useful animal models is provided. The results showed that the variability between homotypic left and right sides was not significant, whereas the variability between heterotypic sites in separate animals was. Maximum torque was the most reliable of the three parameters considered, because the data fell over a much narrower range. We conclude that the use of the contralateral side is a valid control in experimental procedures that may alter the biomechanical properties of one side.

This study examined the feasibility of achieving bone fixation of the upper facial skeleton using n-butyl-2-cyanoacrylate. We compared the fixation obtained with this adhesive to that obtained with plates and screws in an animal model. The stability of fixation of both osteotomies and onlay grafts was studied in six minipigs. Three osteotomies were performed on each side of the skull. Additionally, a parietal split-thickness autograft was fixated to the nasal bone as an onlay. Plates and screws were used on the right and adhesive on the left. The animals were killed at 6 weeks, and both sides were compared biomechanically and histologically. Clinical assessment showed stability of all fragments. No statistical difference was found in the comparison of the maximum torque to failure between analogous plated and glued sides. Radiographic cephalometry revealed no significant displacement of the fragments. Histologic analysis demonstrated bony union. In this study, n-butyl-2-cyanoacrylate was as effective as plates and screws in the fixation of surgically created osteotomies of the upper facial skeleton.

We investigated left ventricular (LV) early diastolic filling in 10 normal conscious dogs that had been previously instrumented to measure LV and left atrial (LA) pressures and three orthogonal LV internal dimensions. LV volume was calculated as a general ellipsoid. The pressure within a passive structure increases as it is filled. If myocardial relaxation is rapid enough to substantially aid LV diastolic filling, it may overcome this effect and cause LV pressure to fall despite an increase in volume. Thus, we defined the amount of LV filling that occurred while LV pressure was falling as relaxation filling, which is a measure of the importance of LV relaxation during early diastolic filling. The time constant of relaxation (T) was derived from the exponential fall of LV pressure during isovolumic relaxation. While LV pressure was falling early in diastole (the relaxation filling period), all three LV diameters increased. Autonomic blockade with hexamethonium (5 mg/kg) and atropine (0.1 mg/kg) reduced relaxation filling from 21 +/- 6% (mean +/- SD) to 12 +/- 3% of the stroke volume (p less than 0.01). The mean LA pressure also was significantly decreased (from 12 +/- 2 to 10 +/- 5 mm Hg, p less than 0.05), while the duration of the relaxation filling period and T were unchanged. Positive inotropic stimulation with dobutamine (10 micrograms/kg/min) shortened T without changing LA pressure. The maximum LA-LV pressure gradient, dV/dtmax, and relaxation filling all increased. Augmented preload produced by dextran infusion (500 ml/10 min) caused an increase in LA pressure (from 11 +/- 3 to 21 +/- 8 mm Hg, p less than 0.05) without altering T. This also increased the maximum LA-LV pressure gradient, dV/dtmax, and relaxation filling. Augmented afterload produced by methoxamine (10 mg/3 min i.v.) significantly increased LA pressure (from 9 +/- 4 to 15 +/- 10 mm Hg, p less than 0.05) and lengthened T (from 35 +/- 4 to 50 +/- 7 msec, p less than 0.05) and the duration of relaxation filling (from 36 +/- 5 to 44 +/- 9 msec, p less than 0.01) without altering the maximum LA-LV pressure gradient, dV/dtmax, or LV relaxation filling. Incremental changes in heart rate induced by atrial pacing (from 100-180 beats/min) resulted in progressive decreases in the time constant of LV relaxation and the duration of relaxation filling. The LA pressure was also decreased. There was no corresponding increase in the amount of active LV filling until the heart rate reached 180 beats/min. During all these interventions, T correlated with the duration of LV relaxation filling (r = 0.99. p less than 0.05). The amount of relaxation filling and dV/dtmax both correlated with the maximum LA-LV pressure gradient.(ABSTRACT TRUNCATED AT 400 WORDS)

Although the measurement of transmural pressure is important, calculation of transmural pressure is complicated by the difficulties in measuring pericardial pressure. Recently, flat balloons have been proposed to measure pericardial pressure. Over a wide range of volumes, right ventricular diastolic pressure and pericardial balloon pressure were similar in diastole, suggesting that the right ventricle is unstressed at physiologic volumes and that right atrial pressure can be used to estimate pericardial pressure. To evaluate these concepts and to assess indirectly the accuracy of measuring pericardial pressure using flat balloons, six canine hearts were examined postmortem. The pericardium was removed and the hearts were submerged in cold cardioplegic solution. Balloons were inserted into the right and left ventricles, and right and left ventricular pressure-volume curves were obtained. Right ventricular transmural pressures of 2.6 +/- 0.5, 3.9 +/- 0.9, 5.9 +/- 1.4, and 8.9 +/- 2.4 mm Hg were required to distend the right ventricle to 10, 20, 30, and 40 ml, respectively. For the left ventricle, transmural pressures of 3.4 +/- 0.7, 5.4 +/- 1.2, 8.6 +/- 2.1, and 14.1 +/- 3.8 mm Hg were recorded at volumes of 10, 20, 30, and 40 ml, respectively. Although the right ventricular transmural pressures were less than the left ventricular transmural pressures over the physiologic range, right ventricular transmural pressures were always positive and increased with increments in ventricular volume. Thus the right ventricle is not unstressed over the entire range of physiologic volumes, suggesting that pericardial balloon pressures may overestimate pericardial pressure and that right atrial pressure cannot be used to estimate pericardial pressure.

To help determine if coronary angiography can predict the site of a future coronary occlusion that will produce a myocardial infarction, the coronary angiograms of 42 consecutive patients who had undergone coronary angiography both before and up to a month after suffering an acute myocardial infarction were evaluated. Twenty-nine patients had a newly occluded coronary artery. Twenty-five of these 29 patients had at least one artery with a greater than 50% stenosis on the initial angiogram. However, in 19 of 29 (66%) patients, the artery that subsequently occluded had less than a 50% stenosis on the first angiogram, and in 28 of 29 (97%), the stenosis was less than 70%. In every patient, at least some irregularity of the coronary wall was present on the first angiogram at the site of the subsequent coronary obstruction. In only 10 of the 29 (34%) did the infarction occur due to occlusion of the artery that previously contained the most severe stenosis. Furthermore, no correlation existed between the severity of the initial coronary stenosis and the time from the first catheterization until the infarction (r2 = 0.0005, p = NS). These data suggest that assessment of the angiographic severity of coronary stenosis may be inadequate to accurately predict the time or location of a subsequent coronary occlusion that will produce a myocardial infarction.