Free Flap Reconstruction of Sternal Defects after Cardiac Surgery: An Algorithmic Approach for Dealing with Sparse Recipient Vessels.

Background: Sparsity of recipient vessels poses a challenge for microsurgical free flap reconstruction of sternal defects following deep sternal wound infection after cardiac surgery. Methods: From January 2013, a standardized algorithm for dealing with sparse recipient vessels was strictly followed. In this retrospective study including 75 patients, we compared operative details, surgical complications, and reconstructive outcomes of patients treated according to this algorithm (group A: January 2013-May 2021; n = 46) with a historical control group (group B: January 2000-December 2012, n = 29). Results: The left internal mammary artery had been harvested for arterial bypass grafting in 40 of 46 cases (87%) in group A and in all cases in group B. The right internal mammary artery (RIMA) and right internal mammary vein (RIMV) were the first choice as recipient vessels. In case of unsuitability of the RIMV, a right cephalic vein (CV) turndown was used for venous outflow. If both RIMA and RIMV proved insufficient, a single-stage arterio-venous loop (AVL) between the CV and subclavian artery (CV-SA AVL), CV and thoracoacromial artery (CV-TA AVL), or subclavian artery and subclavian vein (SA-SV AVL) was established. The algorithmic approach significantly reduced partial flap necrosis [group A: n = 3 (7%) versus group b: n = 7 (24%); P = 0.04], and overall operation time [group A: 360 ±â€…88 min versus group B: 415 ±â€…80 min; P = 0.01]. Conclusions: Standardized approaches improve clinical outcomes in microsurgical free flap sternal reconstruction after cardiac surgery.

[Scars from Nonsuicidal Self-Injury - What Plastic Surgery Can Do]. / Narben aus nichtsuizidalem selbstverletzendem Verhalten ­ therapeutische Möglichkeiten der plastischen Chirurgie.

Scars from Nonsuicidal Self-Injury - What Plastic Surgery Can Do Abstract. Objective: Nonsuicidal self-injury (NSSI) can induce characteristic scar patterns indicating the origin of these scars. This frequently results in the stigmatization of the involved patients with far-reaching consequences for their daily routine and quality of life. Despite patients being highly interested in scar correction, the potential of surgical therapy to alleviate NSSI-prone behavior and its help in destigmatizing surgical corrections and esthetic improvements in these situations are not well-known. Method: Over a period of 5 years, we analyzed 600 patients requesting NSSI scar treatment in our outpatient clinic. We collected data on the motivation for a scar correction, on the maturity of the scars, the involved body parts, and potential prior scar treatments as well as the amount, localization, and type of performed surgical procedures in our institution. Results: Stigmatization (57 %) and limitations in choice of clothing (18 %) were the most frequent reasons given for scar correction. We performed 358 dermabrasions and 55 serial excisions on these patients, nine combinations of both, and 13 other procedures. Conclusions: Plastic surgery offers multiple possibilities to reduce the stigmatization of patients with NSSI scars, who should thus be informed early about their choices.

Relevance of the Scaphoid Shift Test for the Investigation of Scapholunate Ligament Injuries.

Background: Although it is part of the common clinical examination of scapholunate ligament pathologies, there are only little data on the diagnostic value of the scaphoid shift test. The aim of this study was to evaluate the scaphoid shift test in a large cohort of patients. Materials and Methods: We retrospectively analysed 447 patients who underwent the scaphoid shift test and wrist arthroscopy because of various suspected injuries of the wrist, correlating the results of clinical examination with data obtained during the wrist arthroscopy. Sensitivity, specificity, and positive and negative predictive values were calculated and evaluated. Results: The sensitivity of the scaphoid shift test was low (0.50) when examining the whole cohort. In a subgroup of patients specifically referred for suspected scapholunate ligament injury, the sensitivity was higher (0.61), but the specificity was low (0.62). In detecting more serious lesions (Geissler 3 + 4), the scaphoid shift test demonstrated higher sensitivity (0.66). Conclusions: An isolated scaphoid shift test may only be of limited value in the diagnosis of scapholunate ligament lesions and should, therefore, be viewed as a useful tool for a preliminary assessment, but a negative test should not prevent the surgeon from indicating a more extensive diagnostic workup.

Zur medizinischen Indikation bei ästhetisch-plastischen Operationen.

The concept of indication is used in many ways in medicine and in the healthcare industry. In connection with "medical" and/or "physician-based", it is often used to describe the path that a doctor and a patient take - after weighing up all available information - to describe a common treatment goal and to define measures derived from that goal. From today's perspective, however, there is a third factor that plays a role: the healthcare industry, here in particular in the form of health insurance (both statutory health insurance and private health insurance), but more recently also in the form of financial administration. Plastic surgery is faced with the dilemma that, although there is a medically proven indication in many cases, neither the payers nor the financial courts or offices are willing to follow the medical assessment and reject the indication (usually without justification). This article offers support in defining an indication for aesthetic plastic surgery.

[Non-suicidal self-injurious Behaviour: Insights into a littleknown Patient Population in Plastic Surgery]. / Nicht-suizidales selbstverletzendes Verhalten ­ Einblicke in ein wenig bekanntes plastisch-chirurgisches Patient*innenkollektiv.

BACKGROUND: Despite its high prevalence in adolescents and young adults, non-suicidal self-injury (NSSI) is poorly known and understood in areas other than psychiatry. Due to this lack of knowledge, affected patients often face a lack of understanding as well as rejection and discrimination when seeking help from medical professionals. This not only hampers a lasting improvement of NSSI and the development of a trustful physician-patient relationship but may also lead to traumatisation of affected patients. Based on our patients' data, this article aims to inform interested plastic surgeons about NSSI and thus to support the treatment of affected patients. PATIENTS AND METHODS: 600 patients with scars from NSSI presenting to our outpatient clinic for the first time during the past five years were enrolled in this study. Extensive data collected during the first contact was analysed and compared with the current literature. RESULTS: 95 % of the patients were female; 5 % were male. On average, patients presented 8.4 years after the last NSSI event and with a mean age of 26 years. NSSI scars were most often located on the left forearm (48 %), followed by both forearms (40 %), the left upper arm (20 %), both upper arms (15 %) and both thighs (14 %). In 57 % of patients, scars were only present on one side. A mean of 380 cm2 of the body surface was affected by NSSI scars. 47 % of patients reported having at least one additional diagnosis, with thyroid dysfunction and depression being the most common. 21 % of patients had ongoing psychiatric or psychological therapy at the time of their first consultation in our clinic. CONCLUSION: Our data provides first insight into a large population of NSSI patients seeking treatment options for their NSSI-associated scars in a plastic surgery outpatient clinic. Most patients were female with scars located on their forearms. A mean of more than 8 years had passed between their last NSSI and their first presentation to our clinic. Our findings offer a data-based approach to a group of patients with a disease pattern that is largely misunderstood in surgical disciplines and needs more attention, especially in the light of its high prevalence and life-long consequences.

Comparison of venous couplers versus hand-sewn technique in 4577 cases of DIEP-flap breast reconstructions - A multicenter study.

INTRODUCTION: Venous anastomosis remains to be a challenging step in microsurgical tissue transfer and venous complications constitute to a common reason for free flap failure. While several studies have compared mechanical vs. hand-sewn venous anastomoses, there is no large-series study comparing the type of anastomosis exclusively in DIEP flap breast reconstructions. PATIENTS AND METHODS: Between 2011 and 2019, 3926 female patients underwent 4577 free DIEP-flap breast reconstructions in 22 different breast cancer centers. Patient data was collected via an online database, files were screened and cases were divided into a hand- (HA) and a coupler-anastomosis (CA) group. Complications were accounted for and the two groups were then compared. RESULTS: Mean ischemia time was significantly shorter in the CA group (46.88 ± 26.17 vs. 55.48 ± 24.70 min; p < .001), whereas mean operative time was comparable (316 ± 134.01 vs. 320.77 ± 120.29 minutes; p = .294). We found no significant difference between both groups regarding the rate of partial (CA: 1.0% vs. HA: 1.3%) and total flap loss (CA: 2.2% vs. HA: 1.8%). However, revision rates were significantly higher in the CA group (CA: 10.5% vs. HA: 7.9%; p = .003), with higher numbers of arterial (2.3 vs. 0.9%; p < .001) and venous thromboses (3.4 vs. 1.8%; p = .001) accounting for this finding. CONCLUSIONS: All taken into account, our findings do support the feasibility of venous coupler anastomoses in principle, however the inflationary use of coupler devices should be evaluated critically.

Donor Defect Morbidity of Intrinsic Flaps in the Posttraumatized Hand.

INTRODUCTION: There are many types of intrinsic flaps to cover wound defects on the hand, which have been well described in scientific literature. However, the donor sites are often neglected in such studies. Therefore, we aimed to evaluate donor site morbidity for homodigital island flaps, cross-finger flaps, Foucher's pedicle flaps, and flaps of the dorsal metacarpal artery system (DMCA). MATERIALS AND METHODS: A total of 106 intrinsic flap procedures were performed on 106 patients (16 women, 90 men). The donor sites were retrospectively followed up after an average of 3.4 years by a questionnaire, a Disability of the Arm, Shoulder and Hand score, and clinical examination. Donor sites of different flap types were compared for aesthetic outcome, trophic level, and sensation, including 2-point discrimination, temperature, sharp/dull discrimination, the Semmes-Weinstein monofilament test, pain (visual analog scale), and functionality. RESULTS: In general, primarily closed donor sites showed more favorable results than did grafted donor sites. Satisfaction among patients regarding aesthetics of the donor site was highest in patients who had received homodigital island flaps. Grip strength and pain at the operated hand were very heterogeneous and rather influenced by the primary trauma than the type of flap. Homodigital island flap donor sites demonstrated the best results for 2-point discrimination and sharp/dull discrimination, and those for DMCA flaps in the Semes-Weinstein test. CONCLUSIONS: Overall, intrinsic flaps demonstrated low donor site morbidity with reliable coverage of the defects. Of these, the DMCA (especially after primary closure) and homodigital island flaps seemed to produce the best donor site results.

[Immunosuppressive effect of mitomycin C-treated peripheral mononuclear blood cells (MICs) in vascularised composite allotransplantation]. / Immunsuppressive Wirkung von Mitomycin-C-behandelten mononukleären Zellen des peripheren Blutes (MICs) in der Vaskularisierten Composite Allotransplantation.

BACKGROUND: Vascularized Composite Allotransplantation (VCA) enables the restoration of complex tissue defects. Since the first successful hand and face transplants were performed, clinical and experimental research has consistently improved immunosuppressive therapies. The incubation of peripheral blood mononuclear cells (PBMCs) with mitomycin C (MMC) results in immunomodulatory cells (MICs). In previous studies, the systemic application of MICs on the day of allogeneic hind limb transplantation led to a significant immunosuppression in rats. The aim of this study is to further investigate the optimal point in time of MIC application in a complex VCA model. MATERIAL AND METHODS: In six groups, 60 allogeneic hind limb transplantations were performed. Fully mismatched rats were used as hind limb donors [Lewis (LEW)] and recipients [Brown-Norway (BN)]. Group A received donor-derived MICs seven days preoperatively. Group B received no immunosuppression; group C received untreated PBMCs seven days prior to transplantation. Animals in group D received cell culture media, whereas group E was treated with a standard immunosuppression consisting of tacrolimus and prednisolone. In group F, syngeneic hind limb transplantations (BN→BN) were performed. Transplant rejection was assessed clinically and histologically. RESULTS: Group A showed a significantly earlier onset of allograft rejection after 3.5 ± 0.2 days (p < 0.01) when compared with control groups B, C and D (5.5 ± 0.7, 5.3 ± 0.7 und 5.7 ± 0.5). Groups E and F showedno allograft rejection. CONCLUSION: This study shows that the time of application determines the immunomodulatory effects of MICs. Whereas the systemic application of MICs on the day of transplantation led to a significant immunosuppression in previous studies, this study demonstrates that preoperative injections of MICs lead to an acceleration of allotransplant rejection. Follow-up studies are necessary to investigate further modifications of application time as well as dose-effect relations and cell characteristics of these potential immunosuppressive cells.

Modulation of Nitric Oxide Bioavailability Attenuates Ischemia-Reperfusion Injury in Type II Diabetes.

BACKGROUND: Diabetes mellitus increases the susceptibility of free tissue transplantations to ischemia-reperfusion injury. The aim of this study was to enhance nitric oxide (NO) bioavailability through exogenous NO synthase and the substrate L-arginine to attenuate ischemia reperfusion-induced alterations in a type 2 diabetes rodent model. MATERIAL AND METHODS: Sixty-four Wistar rats were divided into 8 experimental groups. Type 2 diabetes was established over 3 months with a combination of a high-fat diet and streptozotocin. A vascular pedicle isolated rat skin flap model that underwent 3 h of ischemia was used. At 30 min before ischemia, normal saline, endothelial NOSs (eNOSs), inducible NOSs, neuronal NOSs (1 and 2 IU), and L-arginine (50 mg/kg body weight) were administered by intravenous infusion alone or in combination. Ischemia-reperfusion-induced alterations were measured 5 days after the operation. RESULTS: The three isoforms of NOS significantly increased the flap vitality rate (VR) between 20% and 28% as compared to the control group (3%). Sole L-arginine administration increased the VR to 33%. The combination of L-arginine with NOS resulted in a further increase in flap VRs (39%-50%). Best results were achieved with the combination of eNOS and L-arginine (50%). An increase in enzyme dosage led to decreased VRs in all NOS isoforms alone and even in combination with L-arginine. CONCLUSION: Modulation of NO bioavailability through the exogenous application of NOSs and L-arginine significantly attenuated ischemia-reperfusion-induced alterations in a type 2 diabetic skin flap rat model. The combination of enzyme and substrate result in the highest VRs. Higher enzyme dosage seems to be less effective. This pharmacological preconditioning could be an easy and effective interventional strategy to support the conversion of L-arginine to NO in ischemic and in type 2 diabetic conditions.

In vivo cardiac pacemaker function of differentiated human mesenchymal stem cells from adipose tissue transplanted into porcine hearts.

BACKGROUND: Mesenchymal stem cells (MSC) modified by gene transfer to express cardiac pacemaker channels such as HCN2 or HCN4 were shown to elicit pacemaker function after intracardiac transplantation in experimental animal models. Human MSC derived from adipose tissue (haMSC) differentiate into cells with pacemaker properties in vitro, but little is known about their behavior after intracardiac transplantation. AIM: To investigate whether haMSC elicit biological pacemaker function in vivo after transplantation into pig hearts. METHODS: haMSC under native conditions (nhaMSC) or after pre-conditioning by medium differentiation (dhaMSC) (n = 6 pigs each, 5 × 106 cells/animal) were injected into the porcine left ventricular free wall. Animals receiving PBS injection served as controls (n = 6). Four weeks later, total atrioventricular (AV)-block was induced by radiofrequency catheter ablation, and electronic pacemaker devices were implanted for backup stimulation and heart rate monitoring. Ventricular rate and rhythm of pigs were evaluated during a follow-up of 15 d post ablation by 12-lead-ECG with heart rate assessment, 24-h continuous rate monitoring recorded by electronic pacemaker, assessment of escape recovery time, and pharmacological challenge to address catecholaminergic rate response. Finally, hearts were analyzed by histological and immunohistochemical investigations. RESULTS: In vivo transplantation of dhaMSC into the left ventricular free wall of pigs elicited spontaneous and regular rhythms that were pace-mapped to ventricular injection sites (mean heart rate 72.2 ± 3.6 bpm; n = 6) after experimental total AV block. Ventricular rhythms were stably detected over a 15-d period and were sensitive to catecholaminergic stimulation (mean maximum heart rate 131.0 ± 6.2 bpm; n = 6; P < 0.001). Pigs, which received nhaMSC or PBS presented significantly lower ventricular rates (mean heart rates 47.2 ± 2.5 bpm and 37.4 ± 3.2 bpm, respectively; n = 6 each; P < 0.001) and exhibited little sensitivity towards catecholaminergic stimulation (mean maximum heart rates 76.4 ± 3.1 bpm and 60.5 ± 3.1 bpm, respectively; n = 6 each; P < 0.05). Histological and immunohistochemical evaluation of hearts treated with dhaMSC revealed local clusters of transplanted cells at the injection sites that lacked macrophage or lymphocyte infiltrations or tumor formation. Intense fluorescence signals at these sites indicated membrane expression of HCN4 and other pacemaker-specific proteins involved in cardiac automaticity and impulse propagation. CONCLUSION: dhaMSC transplanted into pig left ventricles sustainably induced rate-responsive ventricular pacemaker activity after in vivo engraftment for four weeks. The data suggest that pre-conditioned MSC may further differentiate along a pacemaker-related lineage after myocardial integration and may establish superior pacemaker properties in vivo.

[Complex microsurgical reconstructions: relevant billing in an outdated CPT system]. / Komplexe mikrochirurgische Rekonstruktionen und ihre gebührenrechtliche Abbildung im antiquierten Vergütungssystem der GOÄ.

The German equivalent of the USA CPT Code dates in his surgical parts back to 1996. This implies that modern surgical procedures cannot be adequately coded.This article discusses the codes that are frequently challenged by insurance companies and justifies their application with relevant judicial decisions.

Pharmaceutical Preconditioning With Nitric Oxide Synthase and L-Arginine in Ischemic Tissues.

BACKGROUND: Nitric oxide (NO) is a multifunctional signaling molecule involved in regulating vascular tone and tissue oxygenation. It is also an important cytoprotective agent against ischemia-reperfusion injury (IRI). Enhancing NO bioavailability via exogenous NO synthases (NOSs) and L-arginine promotes conversation to NO, circumventing the problem of nonfunctioning NOSs under hypoxic and acidic conditions. In this study, the authors evaluated the therapeutic efficacy of neuronal, inducible, and endothelial NOS and L-arginine on reperfusion-induced skin flap alterations. METHODS: The vascular pedicle isolated rat skin flap model was used and underwent 3 hours of ischemia. At 30 minutes before ischemia, normal saline, endothelial-, inducible-, and neuronal NOSs (1/2 IU) and L-arginine (100 mg/kg body weight) were administered by means of intravenous infusion. The IRI-induced alterations were measured 5 days after the operation. RESULTS: The 3 isoforms of NOS increased the flap vitality rate (VR) from 10% to 23% compared with the control group. L-Arginine treatment also increased the VR by approximately 15%. The combination of L-arginine with NOS resulted in even higher flap VRs. The best results could be achieved with the combination of endothelial NOS (2 IU) and L-arginine. CONCLUSIONS: Modulation of NO bioavailability via exogenous application of NOSs and L-arginine significantly improved VRs in a skin flap rat model. This pharmacologic preconditioning has the potential to attenuate IRI-induced alterations in skin flaps.

[Quality assurance in breast reconstruction - Establishment of a prospective national online registry for microsurgical breast reconstructions]. / Qualitätssicherung in der Brustrekonstruktion ­ Etablierung eines prospektiven nationalen Onlineregisters für mikrochirurgische Brustrekonstruktionen.

BACKGROUND: The loss of a breast, and thus of the female body shape, is often extremely traumatising for women affected. Although free flap grafts have become the gold standard in reconstructive breast surgery, it has not been possible to date to unequivocally document their superiority over conventional alternative techniques. To date, there are no data on the care situation in Germany. Neither the number of reconstructions nor the proportion of the individual techniques is known. A prospective online registry has been set up in order to systematically collect and transparently present the structure and quality of care. The long-term goals are to record the existing quality of care, improve deficits and to certify centres with the appropriate expertise to establish a high level of care nationwide. METHODS: For this purpose, the German Society of Plastic, Reconstructive and Aesthetic Surgeons (DGPRÄC) has set up an internet-based database in which treatment data are recorded anonymously. As part of a certification process, auditors checked structure quality, compliance with specifications, and the stringency of the data entered in comparison with the hospital's internal documentation. If the evaluation is positive, the DGPRÄC quality seal is awarded. RESULTS: Since its introduction in 2012, the database has provided validated information. Initially, only a few departments were prepared to present their results transparently. However, the number has grown steadily in recent years. As a result, the quality recording assumed a pioneering function nationwide and can now be used as a reliable source of information by patients and doctors. The DGPRÄC website features a map of the centres, which are colour-coded according to their respective qualifications. It is thus possible to find a qualified plastic surgeon with comprehensive expertise in acceptable proximity to every oncological breast centre. CONCLUSION: The database provides an overview of the quality of the various surgical techniques and thus the possibility of serious self monitoring and scientific analysis. The systematic collection of data has contributed to strengthening the position of plastic surgery in the field of reconstructive breast surgery. However, the financial and personnel resources required to establish the database were clearly underestimated.

Inducible Nitric Oxide Synthase and L-Arginine Optimizes Nitric Oxide Bioavailability in Ischemic Tissues Under Diabetes Mellitus Type 1.

BACKGROUND: The mechanisms influencing the balance of nitric oxide (NO) bioavailability in tissues are negatively affected under diabetic and also under ischemic conditions. Free tissue transplantation for diabetic patients has to deal with both ischemic and diabetic circumstances, which lead to a significantly decrease in providing NO, thus increasing ischemia-reperfusion injury. In previous studies, we could prove that enhancing NO bioavailability leads to attenuated ischemia-reperfusion injury macrocirculatory and microcirculatory alterations in healthy and also in diabetes type 2 rats. This study is evaluating the role of inducible nitric oxide synthase in different dosages and L-arginine under diabetes type 1 conditions. METHODS: Diabetic type 1 conditions were established via streptozotocin over a period of 4 weeks and verified via blood sugar, insulin, and C-peptide levels. Vascular pedicle isolated rat skin flap model that underwent 3 hours of ischemia was used. At 30 minutes before ischemia, normal saline, inducible nitric oxide synthase (NOS) (1/2 IE), and L-arginine (50 mg/kg body weight) were administered systemically. Ischemia/reperfusion (I/R)-induced alterations were measured 5 days after the operation. RESULTS: The inducible NOS (iNOS) attenuated I/R-induced alterations under diabetic type 1 conditions significantly with vitality rates of 16.1% compared with control group (5.5%). Best results could be achieved with the combination of iNOS (1 IE) and L-arginine displaying vitality rates of 43%. Increased dosage of inducible nitric oxide (2 IE) led to decreased vitality rates (22.2%/27.4% without/with L-arginine). CONCLUSIONS: Supporting the mechanisms of NO bioavailability via exogenous application of iNOS and L-arginine significantly attenuated I/R-induced alterations in a skin flap rat model. This pharmacologic preconditioning could be an easy and effective interventional strategy to uphold conversation of L-arginine to NO even on ischemic and type 1 diabetic conditions.

Pacemaker cell characteristics of differentiated and HCN4-transduced human mesenchymal stem cells.

AIMS: Cell-based biological pacemakers aim to overcome limitations and side effects of electronic pacemaker devices. We here developed and tested different approaches to achieve nodal-type differentiation using human adipose- and bone marrow-derived mesenchymal stem cells (haMSC, hbMSC). MAIN METHODS: haMSC and hbMSC were differentiated using customized protocols. Quantitative RT-PCR was applied for transcriptional pacemaker-gene profiling. Protein membrane expression was analyzed by immunocytochemistry. Pacemaker current (If) was studied in haMSC with and without lentiviral HCN4-transduction using patch clamp recordings. Functional characteristics were evaluated by co-culturing with neonatal rat ventricular myocytes (NRVM). KEY FINDINGS: Culture media-based differentiation for two weeks generated cells with abundant transcription of ion channel genes (Cav1.2, NCX1), transcription factors (TBX3, TBX18, SHOX2) and connexins (Cx31.9 and Cx45) characteristic for cardiac pacemaker tissue, but lack adequate HCN transcription. haMSC-derived cells revealed transcript levels, which were closer related to sinoatrial nodal cells than hbMSC-derived cells. To substitute for the lack of If, we performed lentiviral HCN4-transduction of haMSC resulting in stable If. Co-culturing with NRVM demonstrated that differentiated haMSC expressing HCN4 showed earlier onset of spontaneous contractions and higher beating regularity, synchrony and rate compared to co-cultures with non-HCN4-transduced haMSC or HCN4-transduced, non-differentiated haMSC. Confocal imaging indicated increased membrane expression of cardiac gap junctional proteins in differentiated haMSC. SIGNIFICANCE: By differentiation haMSC, rather than hbMSC attain properties favorable for cardiac pacemaking. In combination with lentiviral HCN4-transduction, a cellular phenotype was generated that sustainably controls and stabilizes rate in co-culture with NRVM.

Rodent models of diet-induced type 2 diabetes mellitus: A literature review and selection guide.

Several research teams have focused on finding the "ideal" animal model that reflects the pathophysiological changes and closely simulates the metabolic characteristics of patients with type 2 diabetes. However, the multitude of studies on this topic has resulted in large variations, making the models difficult to compare, as the measured parameters vary significantly. Additionally, selecting the appropriate animal model for a new study has become more difficult due to the increasing number of background variables. This article gives a detailed overview of the literature, covering the entire range of animal models and model characteristics, and most importantly, provides guidance for selecting the most suitable model for specific research goals in the future.