Subcutaneous Pocket Research Articles

3D-printed scaffolds with controlled-releasing compounds for ectopic activation of dormant ovarian follicles

Throughout a woman’s reproductive life, hundreds of functioning follicles are activated for development, while thousands of dormant follicles remain in the ovaries. Dormant follicle activation in vitro is an effective clinical strategy for women with fertility needs who suffer from ovarian dysfunction. However, activating dormant follicles in vivo is still a challenge due to difficulties such as delivering stimulators to local sites. Here, we developed a compound-preloaded microporous scaffold by combining three-dimensional (3D) printing techniques with pharmacological activators to support and stimulate the activation and development of primordial follicles. The gelatin/alginate composite scaffolds exhibited exceptional mechanical properties and biological compatibility, effectively supporting the survival of ovarian granulosa cells for more than 7 days, which is essential for oocyte development. Furthermore, the ovarian tissue-scaffold complex successfully survived after transplantation under the mouse kidney capsule, demonstrating its excellent biocompatibility. After pre-mixing widely used clinical activators into the bio-ink, the scaffold had the ability to gradually release the mixture of compounds, effectively activating primordial follicles. By transplanting the ovary-scaffold complex containing activators into the mouse abdominal subcutaneous pocket, dormant follicles could be activated subcutaneously and developed into growing follicles. The number of growing follicles is approximately three times higher compared to the group without activators. In conclusion, by integrating biomaterials, activators, and 3D printing technology, we have developed 3D-printed biological scaffolds that can ectopically support primordial follicle activation and development in vivo. This novel approach could provide a promising strategy for treating ovarian insufficiency and endocrine disorders in the clinic, without the need for in situ ovarian tissue grafting.

Molybdenum temporary epicardial pacing wires: function and biodegradation

Abstract Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Wires typically begin to fail around postoperative day four and are extracted. Occasionally, TEPW cannot be mechanically removed, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW which will dissolve over time, even if postoperative removal is unsuccessful. We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 µM diameter each, length 18 cm for ex vivo, 7.5 cm for in vivo experiments) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, the polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 µg/cm2·d (n = 5) compared to uncoated electrodes with 30.3 ± 0.8 µg/cm2·d (n = 4, p < 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test the in vivo properties of Mo TEPW, we sutured them epicardially onto the anterior wall of the heart of female Wistar rats, led them out of the thorax through an intercostal space and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation and after different time periods. Mo TEPW showed similar pacing and sensing properties directly upon implantation and after 2 weeks, with only impedance and slew rate of the sensed R-wave decreasing time-dependently. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Progressive Mo degradation led to multiple fragmentation of the Mo TEPW after 6 months. The conventional steel TEPW we used as control had similar electrical properties directly after implantation, after 2 weeks and one month without signs of broken electrodes. After 6 months, all but one pair of steel electrodes were mechanically broken at their thorax exit site. Comparing urinary Mo concentration of Mo TEPW treated rats to controls, we saw similar values of 1.9 ± 1.9 µM (n = 6) vs. 0.6 ± 0.2 µM (n = 5, n.s.) after one week. In contrast, we saw a significant increase of 12.1 ± 9.7 µM (n = 5) vs. 1.0 ± 0.9 µM (n = 5, p < 0.001) after 6 months, reflecting the degradation progress. We demonstrate that Mo TEPW are a feasible option for epicardial pacing in vivo for up to 2 weeks and observed the progress of Mo degradation up to 6 months. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.Graphical AbstractIn Vivo Degradation Progress

Pharmacokinetic study of local and systemic gentamicin concentrations after subcutaneous implantation of a gentamicin-impregnated collagen sponge in dogs

This study evaluated the pharmacokinetics of commercial gentamicin-impregnated collagen sponges (GICS) applied subcutaneously in dogs. In six healthy beagles, an 11 ×6 cm subcutaneous pocket was created, a folded 10×10 cm GICS was inserted, and saline was injected to mimic a seroma. Wound fluid samples were aspirated, and the gentamicin concentration was determined. Simultaneously, blood samples were collected to evaluate the corresponding systemic gentamicin concentration. All samples were collected before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, and 168 hours after GICS placement. The local Cmax of gentamicin was reached after 0.5 hours (range, 0.5–1.0 hours) post-implantation in 5/6 dogs at a median concentration of 2053.3 µg/mL (range, 918.0–2791.9 µg/mL). Whitin 24 hours, the local concentration dropped below the MIC for Staphylococcus sp. (4 µg/mL) in 5/6 dogs. Plasma Cmax was achieved at a median of 1.2 hours post-implantation (range, 1.0–2.0 hours) and reached a median concentration of 10.3 µg/mL (range, 8.8–18.03 µg/mL). After 6 hours, the gentamicin concentration in the plasma was below 4 µg/mL in all dogs. The GICS provided a high local concentration of gentamicin in a short time with a local Cmax:MIC ratio of 513:1, largely sufficient to eliminate susceptible bacteria, including methicillin-resistant Staphylococcus pseudintermedius (MRSP) and Pseudomonas sp., in a clinical setting. The repeated administration of saline in the present study seemed to have induced a quicker gentamicin release from the GICS than described in previous studies that typically dealt with "drier" wounds.

Concentration of Marbofloxacin in equine subcutaneous tissue fluid after subcutaneous administration in encapsulated microparticles

Surgical-site infections (SSIs) at implant sites in horses are sometimes difficult to control with systemic antimicrobials. Because one of the likely reasons is insufficient antimicrobial concentrations, there is a need to increase these concentrations in and around the infected tissue. Marbofloxacin (MAR)-encapsulated microparticles (MAR-MPs) made of biodegradable poly (lactic-co-glycolic) acid are capable of sustained release in vitro. We examined the concentration of MAR in the subcutaneous tissue fluid at sites where MAR-MPs had been administered. On day 0, six 3- × 4-cm subcutaneous pockets were created in the neck of each of six Thoroughbred horses under sedation and local anesthesia. MAR-MPs containing 50 mg of MAR were added to each pocket, which was then sutured. On days 1, 2, 3, 4, and 7, subcutaneous tissue fluid from one pocket per horse was collected and analyzed by LC-MS/MS. From days 1 to 7, the median MAR concentration in the subcutaneous tissue fluid ranged from 17.7 (4.89–125.6) to 33.05 (15.1–71.6) µg/mL. The median concentrations in the subcutaneous tissue fluid exceeded the MIC90 (the minimum inhibitory concentration that would inhibit the growth of 90 % of the tested bacterial isolates) of MAR for clinical isolates reported previously. The area of swelling at the site of administration was significantly larger on days 1 to 4 than just after administration (P < 0.05). MAR-MPs could be useful for controlling SSIs that require high antimicrobial concentrations for extended periods when they are used with strategies that reduce side effects.

Unseparated Temporal Muscle and Duramater Cranioplasty Methods Following Decompressive Craniectomy: Technical Note.

Cranioplasty (CP) is used to repair cranial defects after decompressive craniectomy. During this procedure, the temporal muscle can contract or retract toward the base and adhere to the scalp flaps above and/or below the dura. Several complications including functional and cosmetic problems can occur following CP. This study presents the technical notes and outcomes of CP. This retrospective observational study collect data of CP-procedures using unseparated muscle-dura technique performed at our hospital in 2019-2022. Technical note is presented regarding the lack of separation of the temporal muscles from the dura mater. A bone flap or titanium mesh was placed above the temporal muscle layer, which was still attached to the dura mater. Functional outcomes were evaluated using OHIP-14 Questionnaire to assess mastication quality. Twenty-three patients were included in this study. Initial surgeries were mostly caused by trauma (65.2%). Most patients underwent autologous bone flap CP (52.2%), during which the bone flap was stored in either the abdominal subcutaneous pocket or cryoprecipitated. Only one patient experienced mastication problems after CP (p<0.001). Temporal hollowing remained a problem in this technique. However, dissection of the temporalis muscle to reduce temporal hollowing can cause facial nerve injuries and masticatory problems. Due to the lack of temporal muscle manipulation, our patients had minimal mastication problems. CP should be performed to improve functional and aesthetic outcomes. A CP technique with the temporal muscle unseparated from the dura mater can be selected to avoid damage to the muscle and mastication problems after surgery.

Clinical practice and outcome of S-ICD replacement: results from the multicenter rhythm detect registry

Abstract Background Subcutaneous implantable cardioverter-defibrillator (S-ICD) therapy is expanding rapidly. However, there are few data on the S-ICD replacement procedure. Objective The aim of this analysis was to describe the procedure and outcome of S-ICD replacement in clinical practice. Methods From 2013 to 2022, consecutive patients undergoing de-novo implantation of an S-ICD were enrolled at 66 Italian centers of the Rhythm Detect Registry. We analyzed consecutive patients who required S-ICD replacement. Results 319 S-ICD generators (49 Cameron, 270 Emblem) were replaced for battery depletion. All the procedures were performed in electrophysiology laboratories, by one or two expert operators. In 118 (37%) cases, the replacement was performed as outpatient procedure. The procedure was performed under local anesthesia with or without conscious sedation in 297 patients (93%). The previous S-ICD generator was in an intermuscular pocket in 195 (61%) patients, and in a subcutaneous pocket in the remaining 124 (39%). 39 (31%) generators were shifted from subcutaneous to intermuscular pocket, and their PRAETORIAN score improved from 43±20 to 34±13 (p=0.007). In most cases (308 (97%)), the defibrillation test was not performed after replacement, but the overall PRAETORIAN score was very low (37±28). The S-ICD system was successfully replaced in all patients and no complications were reported; the procedure duration was 39±16 min and was comparable in the case of generator re-implanted in the same pocket or in case of shift to a new pocket. Conclusions S-ICD replacement was safe and easy to perform, with no peri-operative complications. In clinical practice the replacement procedure is often an opportunity to optimize the position of the generator

Exploring the effect of platelet-rich plasma on vascularization and survival of follicles in xenotransplanted human ovarian tissue

Research questionDo platelet-rich plasma (PRP) products, specifically human platelet lysate (hPL) and umbilical cord plasma, enhance vascularization and follicular survival in human ovarian tissue transplanted to immunodeficient mice? DesignHuman ovarian tissue was transplanted to subcutaneous pockets in nude mice, followed by daily injections for 6 days of PRP or saline at the transplantation sites. After a grafting period of 3 and 6 days, vascularization was assessed using CD-31 quantification, and gene expression of angiogenic markers (VEGF/Vegf) together with apoptosis-related genes (BAX/BCL-2), oxidative stress markers (HMOX-1/Hmox-1) and pro-inflammatory markers (Il-1β/Il-6/Tnf-α) was quantitively analysed. Follicle density was analysed in the grafts after 4 weeks. Additionally, a pilot study was conducted exploring the suitability of ultrasound scanning for assessing survival and vascularization in ovarian tissue xenografted to mice. ResultsAlthough there was a significant increase in the CD-31 area from day 3 to day 6 post-grafting, there were no significant differences between the hPL and control groups. Gene expression analysis revealed significant down-regulation of VEGF from day 3 to day 6 for both the hPL and control groups, and significant up-regulation of BAX/BCL-2 in the hPL group compared with the controls. The follicle density showed no significant differences in the hPL group and UCP groups compared with the controls. Furthermore, ultrasound biomicroscopy provided valuable insights into graft morphology, necrotic areas and blood flow, suggesting its potential as a monitoring tool. ConclusionsDespite the angiogenic properties of PRP, this study was unable to demonstrate a significant impact of hPL on vascularization or of hPL and UCP on follicular survival in xenotransplanted human ovarian tissue.

#1387 Comprehensive evaluation of clinical consequences in diverse forms of fistula elevation procedure

Abstract Background and Aims Arteriovenous fistula (AVF) superficialization is a recommended alternative autologous vascular access (VA) in patients for whom conventional AVF creation is not possible because of insufficient forearm vessels. This procedure utilizes a deeply located vein as an outflow conduit in AVF creation and makes the vein accessible for cannulation. Tunnel transposition (TT) is employed in a standard manner as a venous superficialization technique. This is accomplished by tunneling the transected vein through a subcutaneous tunnel. However, TT is frequently associated with stenosis at the area of transposition because the transposed vein is torsed, kinked, or compressed by external tissue. Thus, TT tends to be exclusively applied to the basilic vein in the upper arm considering both the anatomic positional relation and the inherent limitations of this procedure. We recently reported that elevation transposition (ET) can serve as a practical substitute for TT (Contrib Nephrol. 2019:198:1-11). ET is a simplified minimally invasive superficialization approach in which the vein is elevated and positioned in a subcutaneous pocket immediately beneath the incision. In AVF superficialization employing ET (i.e., fistula elevation procedure [FEP]), three potential outflow veins are available in the upper arm: the cephalic, basilic, and brachial veins. This study was performed to comprehensively evaluate the clinical consequences of three valid FEP techniques to ascertain whether they are reasonable alternatives to autologous VA and which, if any, have superior performance. Method The demographic and outcome data of 111 patients who underwent the FEP from April 2016 to June 2023 were retrospectively collected and analyzed. The outcomes of the three fistula techniques were assessed and compared in terms of patency rates, requirements for VA intervention therapy (VAIVT), and complication rates. Results The mean follow-up period was 36.2 ± 20.1 (range, 1.3-80.8) months. The basilic, cephalic, and brachial vein-based FEP was performed in 63.1%, 23.4%, and 13.5% of cases, respectively. The overall cumulative primary and secondary patency rates were 76.2% and 98.2% at 1 year and 70.7% and 97.0% at 2 years, respectively. VAIVT was required in 32.4% of cases, and the patency rates at 1 and 2 years after VAIVT were 65.3% and 62.0%, respectively. There were no significant differences in these patency rates among the three FEP types. Minor complications such as lymphorrhea or epidermolysis occurred in only 4.5% of cases. Conclusion Our results suggest that the FEP provides three equivalently reliable options to accommodate the deeply located venous anatomy of the upper arm on individual-patient basis. The diversity of the FEP may contribute to avoiding prosthetic VA and central venous catheter-based dialysis, at least in part, by expanding the applicability of the autologous VA.

Bioselective and Radiopaque Zinc-Biopolymeric Complex-Based Porous Biomaterials Promote Mammalian Tissue Ingrowth In Vivo While Inhibiting Microbial Biofilm Gene Expression and Biofilm Formation.

Metal-organic complexes have shown astounding bioactive properties; however, they are rarely explored as biomaterials. Recent studies showed that carboxymethyl-chitosan (CMC) genipin-conjugated zinc biomimetic scaffolds have unique bioselective properties. The biomaterial was reported to be mammalian cell-friendly; at the same time, it was found to discourage microbial biofilm formation on its surface, which seemed to be a promising solution to addressing the problem of trauma-associated biofilm formation and development of antimicrobial resistance. However, the mechanically frail characteristics and zinc overload raise concerns and limit the potential of the said biomaterials. Hence, the present work is focused on improving the strength of the earlier scaffold formulations, testing its in vivo efficacy and reaffirming its action against biofilm-forming microbe Staphylococcus aureus. Scaling up of CMC proportion increased rigidity, and 8% CMC was found to be the ideal concentration for robust scaffold fabrication. Freeze-dried CMC scaffolds with or without genipin (GP) cross-linking were conjugated with zinc using 2 M zinc acetate solution. Characterization results indicated that the CMC-Zn scaffolds, without genipin, showed mechanical properties close to bone fillers, resist in vitro enzymatic degradation until 4 weeks, are porous in nature, and have radiopacity close to mandibular bones. Upon implantation in a subcutaneous pocket of Wistar rats, the scaffolds showed tissue in-growth with simultaneous degradation without any signs of toxicity past 28 days. Neither were there any signs of toxicity in any of the vital organs. Considering many superior properties among the other formulations, the CMC-Zn scaffolds were furthered for biofilm studies. CMC-Zn showed negligible S. aureus biofilm formation on its surface as revealed by an alamar blue-based study. RT-PCR analysis revealed that CMC-Zn downregulated the expression of pro-biofilm effector genes such as icaC and clfB. A protein docking study predicted the inhibitory mechanism of CMC-Zn. Although it binds strongly when alone, at high density, it may cause inactivation of the transmembrane upstream activators of the said genes, thereby preventing their dimerization and subsequent inactivation of the effector genes. In conclusion, zinc-conjugated carboxymethyl-chitosan scaffolds are mechanically robust, porous, yet biodegradable, harmless to the host in the long term, they are radiopaque and prevent biofilm gene expression in notorious microbes; hence, they could be a suitable candidate for bone filler applications.

Expansion of the Subcutaneous Compartment by Umbilicus Resection for Intrathecal Pump Placement: The "Karagoz-Hacivat Technique".

Intrathecal baclofen (ITB) for severe spasticity can encounter complications such as wound dehiscence and ulcers because of elevated intracompartmental pressure within the abdominal subcutaneous and subfascial pocket housing the pump. We propose an innovative technique to manage ITB wound ulcers. Resecting the umbilicus create a more spacious and less tension-prone pocket for the ITB pump. Between 2015 and 2023, we implanted ITB pumps in 65 patients. Among them, 5 patients presented with skin ulcer or dehiscence underwent surgery using the novel technique. Postoperative follow-up revealed successful wound healing, with no further wound-related complications. The proposed technique provides effective and practical solution to wound and skin complications related to ITB pump. Moreover, it may serve as a viable preemptive strategy during the initial implantation of the ITB pump in selected patients.

Early real-world implant experience with a helix-fixation ventricular leadless pacemaker.

Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release. In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated. A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5min [20.0, 35.0] and 5.7min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8V [0.5, 1.3], 9.0mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events. The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications.

Branched Channels in Porous β-Tricalcium Phosphate Scaffold Promote Vascularization.

Rapid and efficient vascularization is still considerably challenging for a porous β-tricalcium phosphate (β-TCP) scaffold to achieve. To overcome this challenge, branched channels were created in the porous β-TCP scaffold by using 3D printing and a template-casting method to facilitate the instant flow of blood supply. Human bone mesenchymal stem cells (hBMSCs) and human umbilical vein endothelial cells (HUVECs) were seeded in the channeled porous scaffolds and characterized through a double-stranded DNA (dsDNA) assay, alkaline phosphatase (ALP) assay, and cell migration. Channeled porous β-TCP scaffolds were then implanted in the subcutaneous pockets of mice. Histological staining and immunohistochemical staining on vascularization and bone-related markers were carried out on the embedded paraffin sections. Results from in vitro experiments showed that branched channels significantly promoted HUVECs' infiltration, migration, proliferation, and angiogenesis, and also promoted the proliferation and osteogenesis differentiation of hBMSCs. In vivo implantation results showed that, in the early stage after implantation, cells significantly migrated into branched channeled scaffolds. More matured blood vessels formed in the branched channeled scaffolds compared to that in nonchanneled and straight channeled scaffolds. Beside promoting vascularization, the branched channels also stimulated the infiltration of bone-related cells into the scaffolds. These results suggested that the geometric design of branched channels in the porous β-TCP scaffold promoted rapid vascularization and potentially stimulated bone cells recruitment.

Hematoma Prevention Using Tachosil (Fibrin Sealant) Patch during Insertion of Cardiovascular Implantable Electronic Devices without Suspending Antithrombotics: Three Case Reports

Patients undergoing insertion of cardiac implantable electronic devices often exhibit perioperative hemorrhagic complications. Perioperative antithrombotic management, which balances the risk of acute thrombosis and postoperative bleeding, is therefore important for these patients. In this case report, we present three cases of cardiovascular implantable electronic device (CIED) insertion. While the three patients each had different reasons for not discontinuing antithrombotic medications, they all needed CIEDs. During the CIED implantation procedures, a small incision was made on the pectoralis muscle region to obtain a small subcutaneous pocket, and Tachosil, a fibrin sealant patch, was inserted below and above the inserted device. The patients showed no pocket hematoma formation or any hemorrhagic complications. We thus concluded the application of a fibrin sealant patch could be an option for perioperative anticoagulation management without interruption of anticoagulants and antiplatelets.

Biomimetic fabrication of sr-silk fibroin co-assembly hydroxyapatite based microspheres with angiogenic and osteogenic properties for bone tissue engineering

Bone defects caused by trauma, tumor resection, or developmental abnormalities are important issues in clinical practice. The vigorous development of tissue engineering technology provides new ideas and directions for regenerating bone defects. Hydroxyapatite (HAp), a bioactive ceramic, is extensively used in bone tissue engineering because of its excellent osteoinductive performance. However, its application is challenged by its single function and conventional environment-unfriendly synthesis methods. In this study, we successfully "green" synthesized sr-silk fibroin co-assembly hydroxyapatite nanoparticles (Sr-SF-HA) using silk fibroin (SF) as a biomineralized template, thus enabling it to have angiogenic activity and achieving the combination of organic and inorganic substances. Then, the rough composite microspheres loaded with Sr-SF-HA (CS/Sr-SF-HA) through electrostatic spraying technology and freeze-drying method were prepared. The CCK-8 test and live/dead cell staining showed excellent biocompatibility of CS/Sr-SF-HA. Alkaline phosphatase (ALP) staining, alizarin red staining (ARS), immunofluorescence, western blotting, and qRT-PCR test showed that CS/Sr-SF-HA activated the expression of related genes and proteins, thus inducing the osteogenic differentiation of rBMSCs. Moreover, tube formation experiments, scratch experiments, immunofluorescence, and qRT-PCR detection indicated that CS/Sr-SF-HA have good angiogenic activity. Furthermore, in vivo studies showed that the CS/Sr-SF-HA possesses excellent biocompatibility, vascular activity, as well as ectopic osteogenic ability in the subcutaneous pocket of rats. This study indicates that the construction of CS/Sr-SF-HA with angiogenic and osteogenic properties has great potential for bone tissue engineering.

Using Auricular Cartilage-fascia Composite Tissue Free Grafting Technique to Improve Cartilage Survival Outcomes.

Auricular cartilage graft has a wide range of applications in plastic and reconstructive surgery. However, there is still a risk of absorption of the grafts over time. Intrinsic postauricular fascia (IPF) with a rich vascular network may play an important role in the nutrition and repair of auricular cartilage. This study aimed to investigate the effect of IPF on the survival viability of free auricular cartilage grafts. 24 auricular cartilages were obtained from 6 New Zealand white rabbits which were divided into the cartilage-fascia composite graft group (FC group, n=12) and the cartilage without fascia group (C group, n=12). Two groups of cartilage were implanted into each side of the subcutaneous pocket of the rabbit's dorsum. The rabbits were sacrificed after 3 months and all cartilage grafts were obtained. Macroscopic observation, histopathological staining, and biomechanical testing were performed on all specimens. There were significant differences between the 2 groups regarding proliferating chondrocytes, apoptotic chondrocytes, vascularization, and matrix collagen. Compared to the auricular cartilage grafts without fascia, the auricular cartilage-fascia composite grafts had more neovascularization, proliferative chondrocytes, and type II collagen, with a homogeneous cartilage matrix and no obvious areas of heterogeneous staining. Young's modulus and ultimate tensile strength of cartilage were reduced in both groups compared to pretransplantation, but the composite graft group was superior to the fascia-free group. Auricular cartilage-fascial composite tissue free graft could improve cartilage survival outcomes with higher viability and mechanical properties.

Autoinoculation Therapy for the Treatment of Widespread Cutaneous Warts.

Cutaneous warts are common lesions that are often unresponsive to various therapeutic modalities. To assess the role of autoinoculation therapy in the treatment of widespread cutaneous warts. This interventional study included patients with widespread skin warts who did not respond to conventional treatments. Two methods were used to perform the autoinoculation therapy. The first procedure was performed by obtaining a small piece of the wart and inoculating it into a subcutaneous pocket. The second method was developed by the investigator and was performed by inserting a needle into the center of the wart toward the nearby subcutaneous tissue, with multiple forward and backward movements in several directions around the lesion. The prospective study included 23 patients. The illness duration ranged from 3 months to 5 years. Autoinoculation interventions revealed full recovery of all warts in 20 cases (87%) within 20 to 90 days (mean: 40.7 days). Autoinoculation procedures demonstrated effectiveness, less cost, lesser pain, less invasiveness, without leaving skin scars in comparison with other conventional therapies.

The Micra Transcatheter Pacing System: past, present and the future.

Leadless permanent pacemakers represent an important innovation in cardiac device developments. Althoughtransvenous permanent pacemakers have become indispensable in managing bradyarrhythmia and saving numerous lives, the use of transvenous systems comes with notable risks tied to intravascular leads and subcutaneous pockets. This drawback has spurred the creation of leadless cardiac pacemakers. Within this analysis, we compile existing clinical literature and proceed to evaluate the efficacy and safety of the Micra Transcatheter Pacing System. We also delve into the protocols for addressing a malfunctioning or end-of-life Micra as well as device extraction. Lastly, we explore prospects in this domain, such as the emergence of entirely leadless cardiac resynchronization therapy-defibrillator devices.

PP41 Using Medicare Claims Data To Support Reimbursement Of A Novel Leadless Pacing System For The Management Of Bradycardia

IntroductionThe Micra Transcatheter Pacing System (Micra TPS) is a single-chamber transcatheter leadless pacemaker (LPM). LPMs do not require leads or a subcutaneous pocket, which represent the primary sources of device-related complications with conventional transvenous pacemakers (TVPMs). Complications such as infections and lead dislodgements cause significant patient burden, which have significant economic consequences. Running a randomized controlled trial (RCT) to estimate risk differences of infrequent events requires large sample sizes and long follow-up periods. Real-world observational data, while informative, requires an appropriate study design and statistical adjustments to control for potential biases.MethodsThe Micra Coverage with Evidence Development (CED) study was a cohort study of LPM versus TVPM based on US Medicare claims data of 16,431 patients with 2-year follow up (LPM: n=6,219; TVPM: n=10,212). Propensity score matching (PSM) was applied to account for differences in baseline characteristics. As no RCT was identified in the literature, this study was presented to the Australian payer as the primary source of clinical evidence, upon which a cost-utility analysis was conducted.ResultsAfter PSM, the CED study demonstrated significantly more complications with TVPM versus LPM with adjusted rates of 6.5 percent and 4.6 percent (p&lt;0.001). Significant differences favoring LPM (p&lt;0.01) were observed in device breakdown (1.4% vs 2.0%), dislodgment (0.4% vs 1.2%) and infection (&lt;0.1% vs 0.6%). Based on these findings, a claim of superior safety was accepted by Medical Services Advisory Committee (MSAC) to support reimbursement. In making this decision, MSAC considered that the large sample size and propensity weighting overcame some of the potential biases and the magnitude of the benefit supported cost-effectiveness relative to TVPM.ConclusionsThe lack of a sufficiently powered RCT with an extended follow-up period can mean the impact and benefits of new technologies that reduce clinically important adverse events of relative infrequency are not formally incorporated into payer decision making, particularly where RCTs are a requirement. A well-designed observational study can provide valuable, real-world evidence to support a HTA for reimbursement decisions.

A GAVeCeLT bundle for PICC-port insertion: The SIP-Port protocol.

In the last decade, a new type of brachial port has been introduced in clinical practice, the so-called "PICC-port." This is a brachial port, but inserted according to the methodologies and technologies currently adopted for the insertion of peripherally inserted central catheters (PICCs). Several studies have shown that PICC-port insertion is safe, not associated with any relevant immediate or early complication, and that the expected incidence of late complications is significantly lower if compared to "traditional" brachial ports (i.e. inserted without ultrasound guidance). Furthermore, PICC-ports yield excellent esthetic results and are associated with optimal patient compliance. This paper describes an insertion bundle-developed by GAVeCeLT, the Italian Group of Long Term Venous Access Devices, and nicknamed "SIP-Port" (Safe Insertion of PICC-Ports)-which consists of few evidence-based strategies aiming to further minimize all immediate, early, or late complications potentially associated with PICC-port insertion. Also, this insertion bundle has been developed for the purpose of defining more closely the differences between a traditional brachial port and a PICC-port. The SIP-Port bundle is currently adopted by all training courses on PICC-port insertion held by GAVeCeLT. It includes eight steps: (1) preprocedural ultrasound assessment utilizing the RaPeVA (Rapid Peripheral Venous Assessment) protocol; (2) appropriate skin antiseptic technique and maximal barrier precautions; (3) choice of appropriate vein, in terms of caliber and site; (4) clear identification of the median nerve and of the brachial artery during the venipuncture; (5) ultrasound-guided puncture and cannulation of the vein; (6) ultrasound-guided tip navigation; (7) intra-procedural assessment of tip location by intracavitary ECG or by trans-thoracic echocardiography; (8) appropriate creation and closure of the subcutaneous pocket.

18F-FDG PET/CT in left ventricular assist device infections: In-depth characterization and clinical implications

BackgroundPrevious retrospective studies suggest a good diagnostic performance of 18F-FDG-PET/CT in left ventricular assist device (LVAD) infections. Our aim was to prospectively evaluate the role of PET/CT in the characterization and impact on clinical management of LVAD infections. Methods40 patients (58[53–62] years) with suspected LVAD infection and 5 controls (69[64–71] years) underwent 18F-FDG-PET/CT. Four LVAD components were evaluated: exit site and subcutaneous driveline (peripheral), pump pocket, and outflow graft. The location with maximal uptake was considered the presumed site of infection. Infection was confirmed by positive culture (exit site or blood) and/or surgical findings. ResultsVisual uptake was present in 40 patients (100%) in the infection group vs 4 (80%) control subjects. For each individual component, presence of uptake was more frequent in the infection than in the control group. The location of maximal uptake was most frequently the pump pocket (48%) in the infection group and the peripheral components (75%) in the control group. SUVmax was higher in the infection than in the control group: SUVmax (average all components):6.9[5.1-8.5] vs 3.8[3.7-4.3], p=0.002; SUVmax (location of maximal uptake):10.6±4.0 vs 5.4±1.9, p=0.01.Pump pocket infections were more frequent in patients with bacteremia than without bacteremia (79% vs 31%, p=0.011). Pseudomonas (32%) and methicillin-susceptible Staphylococcus aureus (29%) were the most frequent pathogens and were associated with pump pocket infections, while Staphylococcus epidermis (11%) was associated with peripheral infections. PET/CT affected the clinical management of 83% of patients with infection, resulting in surgical debridement (8%), pump exchange (13%), and upgrade in the transplant listing status (10%) leading to 8% of urgent transplants. Conclusions18F-FDG-PET/CT enables the diagnosis and characterization of the extent of LVAD infections, which can significantly affect the clinical management of these patients.