Native human and mouse skin infection models to study Candida auris-host interactions.

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant fungal pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need and present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology and immunofluorescence analysis of ex vivo skin biopsies of human adult and fetal, as well as mouse origin infected with C. auris via distinct routes. We demonstrate that an intact skin barrier efficiently protects from C. auris penetration and invasion. Although C. auris readily grows on native human skin, it can reach deeper layers only upon physical disruption of the barrier by needling or through otherwise damaged skin. By contrast, a barrier disruption is not necessary for C. auris penetration of native mouse skin. Importantly, we show that C. auris undergoes morphogenetic changes upon skin penetration, as it acquires pseudohyphal growth phenotypes in deeper human and mouse dermis. Taken together, this new human and mouse skin model toolset yields new insights into C. auris colonization, adhesion, growth and invasion properties of native versus damaged human skin. The results form a crucial basis for future studies on skin immune defense to colonizing pathogens, and offer new options for testing the action and efficacy of topical antimicrobial compound formulations.

Chronic kidney disease and cardiovascular disease reduce survival rates after burn injury: A retrospective study over 20 years.

BACKGROUND: The Abbreviated Burn Severity Index and comparable scores are used to assess the probability of survival in burned patients. These scores may be useful during the initial management of the patient and in addition to the clinical evaluation. As current models do not include the influence of chronic diseases, we evaluated the impact of comorbidities on survival probability, aiming to improve the existing scoring systems and survival probability accuracy further. METHODS: In this retrospective single-center study, patient data from a center for Severe Burn Injury were collected. Over a period of 20 years (2000-2019), a total of 1,193 patients were recorded. The influence of comorbidities (chronic kidney disease, diabetes mellitus type II, and cardiovascular diseases) on the survival probability was analyzed using regression models. These analyses were stratified for sex and period. RESULTS: Pre-existing chronic kidney disease, as well as pre-existing cardiovascular disease, had a significant influence on the survival of patients. For chronic kidney disease, the influence was stronger in men than in women. Women were more likely to survive a burn injury with a history of chronic renal insufficiency. An improved Abbreviated Burn Severity Index model, which assigns an additional point for chronic kidney disease, best-described survival probability in our patient cohort. CONCLUSION: Cardiovascular disease and chronic kidney disease both have an impact on the survival probability of severely burned patients, but this impact is more severe for chronic kidney disease. An additional Abbreviated Burn Severity Index point for chronic kidney disease would be a proposed adaptation to predict the outcome of burn patients better.

Skin Bank Establishment in Treatment of Severe Burn Injuries: Overview and Experience with Skin Allografts at the Vienna Burn Center.

Depending on their extent, burn injuries require different treatment strategies. In cases of severe large-area trauma, the availability of vital skin for autografting is limited. Donor skin allografts are a well-established but rarely standardized option for temporary wound coverage. Ten patients were eligible for inclusion in this retrospective study. Overall, 202 donor skin grafts obtained from the in-house skin bank were applied in the Department of Plastic and Reconstructive and Aesthetic Surgery, Medical University of Vienna. Between 2017 and 2022, we analysed the results in patient treatment, the selection of skin donors, tissue procurement, tissue processing and storage of allografts, as well as the condition and morphology of the allografts before application. The average Abbreviated Burn Severity Index (ABSI) was 8.5 (range, 5-12), and the mean affected total body surface area (TBSA) was 46.1% (range, 20-80%). In total, allograft application was performed 14 times. In two cases, a total of eight allografts were removed due to local infection, accounting for 3.96% of skin grafts. Six patients survived the acute phase of treatment. Scanning electron microscope images and histology showed no signs of scaffold decomposition and intact tissue layers of the allografts. The skin banking program and the application of skin allografts at the Vienna Burn Center can be considered successful. In severe burn injuries, skin allografts provide time by serving as sufficient wound coverage after early necrosectomy. Having an in-house skin banking program at a dedicated burn centre is particularly advantageous since issues of availability and distribution can be minimized. Skin allografts provide a reliable treatment option in patients with extensive burn injuries.

Impact of the COVID-19 pandemic on the epidemiology of severe burns : A single center study from a specialized burn center in Vienna.

INTRODUCTION: Currently, very little detailed information on the epidemiological distribution and specificities of severely burned patients during the coronavirus disease 2019 (COVID-19) pandemic is available. This retrospective study aims to describe and compare this specific patient population based on 114 patients who were treated between March 2019 and March 2021 at the Center for Severe Burn Injuries at the Medical University of Vienna. METHODS: To answer the research questions, a retrospective cohort study has been conducted over a period of 24 months, starting in March 2019 and ending in March 2021. To evaluate the epidemiological differences, the patients were divided into 2 observation periods of 12 months each. RESULTS: In the period from 12 March 2020 to 11 March 2021, a total of 62 patients were admitted to the Center for Severe Burn Injuries. In comparison, only 52 patients were admitted in the same period of the previous year, which corresponds to an increase of 19.2%. In addition, it was noted that during the 2019-2020 observation period, 27% of patients were female and 73% male, whereas during the pandemic the gender distribution was 42% female and only 58% male. During the pre-pandemic observational period, 13 out of 52 patients admitted died (25%), whereas during the pandemic, 17 out of 62 patients succumbed to their injuries (27%). CONCLUSION: Although the severity of the COVID-19 pandemic seems to be decreasing, especially due to the increasing availability of vaccines, there is a need for more data on the impact of the crisis on severely burned patients. In contrast to the current literature, we have seen a greater number of inpatient admissions to the Center for Severe Burn Injuries, as well as significant differences in gender distribution. Our data also suggest that the circumstances of the pandemic have no influence on the likelihood of survival for patients with severe burns.

Disturbances in microbial skin recolonization and cutaneous immune response following allogeneic stem cell transfer.

The composition of the gut microbiome influences the clinical course after allogeneic hematopoietic stem cell transplantation (HSCT), but little is known about the relevance of skin microorganisms. In a single-center, observational study, we recruited a cohort of 50 patients before undergoing conditioning treatment and took both stool and skin samples up to one year after HSCT. We could confirm intestinal dysbiosis following HSCT and report that the skin microbiome is likewise perturbed in HSCT-recipients. Overall bacterial colonization of the skin was decreased after conditioning. Particularly patients that developed acute skin graft-versus-host disease (aGVHD) presented with an overabundance of Staphylococcus spp. In addition, a loss in alpha diversity was indicative of aGVHD development already before disease onset and correlated with disease severity. Further, co-localization of CD45+ leukocytes and staphylococci was observed in the skin of aGVHD patients even before disease development and paralleled with upregulated genes required for antigen-presentation in mononuclear phagocytes. Overall, our data reveal disturbances of the skin microbiome as well as cutaneous immune response in HSCT recipients with changes associated with cutaneous aGVHD.

Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells.

Skin is an active immune organ where professional antigen-presenting cells such as epidermal Langerhans cells (LCs) link innate and adaptive immune responses. While Reticulon 1A (RTN1A) was recently identified in LCs and dendritic cells in cutaneous and lymphoid tissues of humans and mice, its function is still unclear. Here, we studied the involvement of this protein in cytoskeletal remodeling and immune responses toward pathogens by stimulation of Toll-like receptors (TLRs) in resident LCs (rLCs) and emigrated LCs (eLCs) in human epidermis ex vivo and in a transgenic THP-1 RTN1A+ cell line. Hampering RTN1A functionality through an inhibitory antibody induced significant dendrite retraction of rLCs and inhibited their emigration. Similarly, expression of RTN1A in THP-1 cells significantly altered their morphology, enhanced aggregation potential, and inhibited the Ca2+ flux. Differentiated THP-1 RTN1A+ macrophages exhibited long cell protrusions and a larger cell body size in comparison to wild-type cells. Further, stimulation of epidermal sheets with bacterial lipoproteins (TLR1/2 and TLR2 agonists) and single-stranded RNA (TLR7 agonist) resulted in the formation of substantial clusters of rLCs and a significant decrease of RTN1A expression in eLCs. Together, our data indicate involvement of RTN1A in dendrite dynamics and structural plasticity of primary LCs. Moreover, we discovered a relation between activation of TLRs, clustering of LCs, and downregulation of RTN1A within the epidermis, thus indicating an important role of RTN1A in LC residency and maintaining tissue homeostasis.

Tick feeding modulates the human skin immune landscape to facilitate tick-borne pathogen transmission.

During cutaneous tick attachment, the feeding cavity becomes a site of transmission for tick salivary compounds and tick-borne pathogens. However, the immunological consequences of tick feeding for human skin remain unclear. Here, we assessed human skin and blood samples upon tick bite and developed a human skin explant model mimicking Ixodes ricinus bites and tick-borne pathogen infection. Following tick attachment, we observed rapidly occurring patterns of immunomodulation, including increases in neutrophils and cutaneous B and T cells. T cells upregulated tissue residency markers, while lymphocytic cytokine production was impaired. In early stages of Borrelia burgdorferi model infections, we detected strain-specific immune responses and close spatial relationships between macrophages and spirochetes. Preincubation of spirochetes with tick salivary gland extracts hampered accumulation of immune cells and increased spirochete loads. Collectively, we showed that tick feeding exerts profound changes on the skin immune network that interfere with the primary response against tick-borne pathogens.

Intensive care in an older population: Influence of age, comorbidities and sex in 304 plastic and reconstructive surgical patients older than 75 years.

AIM: An aging population will lead to an increasing demand for critical care resources. Hence, we evaluated the potential influence of age, comorbidities and sex in plastic and reconstructive patients ≥75 years that were admitted to the intensive care unit (ICU). METHODS: We included 304 patients who required intensive care between 2000 and 2019. Besides patient demographics, medical case characteristics were statistically evaluated. RESULTS: In this study, 184 patients were female (61%) (120 male), the median age was 81.8 years (25th and 75th percentiles: 77.4-87.2) with a range of 75.0-98.9 years. The median length of stay in the ICU was 12 days (25th and 75th percentiles: 3-28) with a range of 0-382 days. The reasons for admission were burn injury (n = 230, 76%), necrotizing fasciitis (n = 34, 11%), non-combustion-related traumas (n = 22, 7%) and postoperative observation after plastic surgery procedures (n = 18, 6%). In total, 108 patients (36%), who were significantly older (P = 0.005) and had a significantly shorter stay (P < 0.001) compared with the surviving cohort, died during their stay in the ICU. Our multivariable logistic regression model revealed that age (odds ratio: 1.05 [1.01, 1.09]; P = 0.017) and number of operations (odds ratio: 0.75 [0.60, 0.96]; P = 0.023) were significant predictors for death in the ICU. DISCUSSION: Age plays a critical role in determining fatal outcome of old patients requiring intensive care. In contrast, sex and number of comorbidities shows no significant influence. Geriatr Gerontol Int 2022; 22: 597-602.

Effects of metformin on human bone-derived mesenchymal stromal cell-breast cancer cell line interactions.

Metformin is used to treat patients with type 2 diabetes mellitus and was found to lower the incidence of cancer. Bone metastasis is a common impairment associated with advanced breast cancer. The present study investigated the effects of metformin on human bone-derived mesenchymal stromal cells (BM-MSC)-breast cancer cell line interactions. BM-MSCs grown from box chisels were tested for growth-stimulating and migration-controlling activity on four breast cancer cell lines either untreated or after pretreatment with metformin. Growth stimulation was tested in MTT tests and migration in scratch assays. Furthermore, the expression of adipokines of BM-MSCs in response to metformin was assessed using Western blot arrays. Compared to breast cancer cell lines (3.6 ± 1.4% reduction of proliferation), 500 µM metformin significantly inhibited the proliferation of BM-MSC lines (mean 12.3 ± 2.2 reduction). Pretreatment of BM-MSCs with metformin showed variable effects of the resulting conditioned media (CM) on breast cancer cell lines depending on the specific BM-MSC-cancer line combination. Metformin significantly reduced the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in response to CM of drug-pretreated BM-MSCs. Assessment of metformin-induced alterations in the expression of adipokines by BM-MSC CM indicated increased osteogenic signaling and possibly impairment of metastasis. In conclusion, the anticancer activities of metformin are the result of a range of direct and indirect mechanisms that lower tumor proliferation and progression. A lower metformin-induced protumor activity of BM-MSCs in the bone microenvironment seem to contribute to the positive effects of the drug in selected breast cancer patients.

The molecular and phenotypic makeup of fetal human skin T lymphocytes.

The adult human skin contains a vast number of T cells that are essential for skin homeostasis and pathogen defense. T cells are first observed in the skin at the early stages of gestation; however, our understanding of their contribution to early immunity has been limited by their low abundance and lack of comprehensive methodologies for their assessment. Here, we describe a new workflow for isolating and expanding significant amounts of T cells from fetal human skin. Using multiparametric flow cytometry and in situ immunofluorescence, we found a large population with a naive phenotype and small populations with a memory and regulatory phenotype. Their molecular state was characterized using single-cell transcriptomics and TCR repertoire profiling. Importantly, culture of total fetal skin biopsies facilitated T cell expansion without a substantial impact on their phenotype, a major prerequisite for subsequent functional assays. Collectively, our experimental approaches and data advance the understanding of fetal skin immunity and potential use in future therapeutic interventions.

Single-cell analysis reveals innate lymphoid cell lineage infidelity in atopic dermatitis.

BACKGROUND: Although ample knowledge exists about phenotype and function of cutaneous T lymphocytes, much less is known about the lymphocytic components of the skin's innate immune system. OBJECTIVE: To better understand the biologic role of cutaneous innate lymphoid cells (ILCs), we investigated their phenotypic and molecular features under physiologic (normal human skin [NHS]) and pathologic (lesional skin of patients with atopic dermatitis [AD]) conditions. METHODS: Skin punch biopsies and reduction sheets as well as blood specimens were obtained from either patients with AD or healthy individuals. Cell and/or tissue samples were analyzed by flow cytometry, immunohistochemistry, and single-cell RNA sequencing or subjected to in vitro/ex vivo culture. RESULTS: Notwithstanding substantial quantitative differences between NHS and AD skin, we found that the vast majority of cutaneous ILCs belong to the CRTH2+ subset and reside in the upper skin layers. Single-cell RNA sequencing of cutaneous ILC-enriched cell samples confirmed the predominance of biologically heterogeneous group 2 ILCs and, for the first time, demonstrated considerable ILC lineage infidelity (coexpression of genes typical of either type 2 [GATA3 and IL13] or type 3/17 [RORC, IL22, and IL26] immunity within individual cells) in lesional AD skin, and to a much lesser extent, in NHS. Similar events were demonstrated in ILCs from skin explant cultures and in vitro expanded ILCs from the peripheral blood. CONCLUSION: These findings support the concept that instead of being a stable entity with well-defined components, the skin immune system consists of a network of highly flexible cellular players that are capable of adjusting their function to the needs and challenges of the environment.

The Three-Hour Lower Body Lift: Evolution of a Technique and Personal Experience after 155 Consecutive Cases.

BACKGROUND: Body-contouring is a surgical field in growing demand, as the number of massive weight loss patients following bariatric surgery is increasing. The purpose of this study was to provide a straightforward and time-efficient circumferential body lift technique to achieve optimal lower truncal contouring. PATIENTS AND METHODS: A total of 155 massive weight loss patients (133 women and 22 men) underwent lower body lift surgery between 2006 and 2018. The mean preoperative weight reduction and body mass indices were 56.5 ± 16.6 kg and 26.7 ± 4.7 kg/m2, respectively. The preoperative markings focused on the back and gluteal region, and the modified surgical technique are described. Additionally, improvements of intra-operative repositioning of the patient and how to deal with sterilization and dressings are elucidated. RESULTS: The average intra-operative time was 178 ± 54.6 minutes. The mean follow-up of all patients was 8.2 ± 2.4 years. The most common complications were related to wound dehiscence (n = 38) and seroma (n = 18). The mean weight of the resected tissue was 3 056 ± 1 816.5 g. CONCLUSION: The lower body lift represents an effective and safe body contouring procedure to treat massive weight loss patients with multiple regions of concern. The current study describes a modified surgical technique that reduces operating time and complications, notably. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .

Delayed antiretroviral therapy in HIV-infected individuals leads to irreversible depletion of skin- and mucosa-resident memory T cells.

People living with HIV (PLWH) are at increased risk for developing skin and mucosal malignancies despite systemic reconstitution of CD4+ T cells upon antiretroviral therapy (ART). The underlying mechanism of chronic tissue-related immunodeficiency in HIV is unclear. We found that skin CD4+ tissue-resident memory T (Trm) cells were depleted after HIV infection and replenished only upon early ART initiation. TCR clonal analysis following early ART suggested a systemic origin for reconstituting CD4+ Trm cells. Single-cell RNA sequencing in PLWH that received late ART treatment revealed a loss of CXCR3+ Trm cells and a tolerogenic skin immune environment. Human papilloma virus-induced precancerous lesion biopsies showed reduced CXCR3+ Trm cell frequencies in the mucosa in PLWH versus HIV- individuals. These results reveal an irreversible loss of CXCR3+ Trm cells confined to skin and mucosa in PLWH who received late ART treatment, which may be a precipitating factor in the development of HPV-related cancer.

A modified microvascular "Tube-in-Tube" concept for penile construction in female-to-male transsexuals: Combined radial forearm free flap with anterolateral thigh flap.

INTRODUCTION: Phalloplasty is a complex surgical task and remains a significant challenge in plastic surgery. To date, there are various techniques; however, complication rates are still not satisfactory. Here, we present our surgical approach of a modified tube-in-tube concept combining a radial forearm free flap and an anterolateral thigh flap and assess its outcome in a series of female-to-male transsexuals. PATIENTS AND METHODS: In this report, 21 female-to-male transsexual patients were included. The first surgical step includes colpectomy and elongation of the fixed part of the urethra with a full-thickness skin graft. Subsequently, a radial forearm free flap was adapted to build the inner tube which represents the neourethra. For the last step, a free anterolateral thigh flap is utilized as the outer tube of the neophallus. All patients were evaluated regarding aesthetic and functional outcomes as well as postoperative complications and revision surgeries. RESULTS: Our results showed a 100% flap survival rate with a mean follow-up of 4.4 years (range, 2.7-6). Three radial forearm free flaps and one free anterolateral thigh flap presented with partial flap necrosis. Generally, complications occurred in 11 patients (52.4%). The most common complications were related to urethral reconstruction including fistula formation (n = 8) and stenosis (n = 5). All except one patient obtained the ability to void while standing. CONCLUSION: Despite the complexity, the initial results are very promising for a single-stage phalloplasty with complete functional creation of a neophallus. Further improvements have to be implemented for reduction of postoperative complications particularly regarding urethral reconstruction. LEVEL OF EVIDENCE: IV (Therapeutic).

Nanocellulose-based wound dressing for conservative wound management in children with second-degree burns.

The initial care of burn wounds and choice of dressing are pivotal to optimally support the healing process. To ensure fast re-epithelialisation within 10-14 days and prevent complications, an optimal healing environment is essential. An innovative dressing based on nanocellulose was used for the treatment of burns in children. Children (0-16 years) with clean, partial-thickness burn wounds, 1 to 10% of the total body surface area were included. Complete re-epithelialisation was achieved within 7-17 days, with 13 patients showing re-epithelialised >95% by day 10. Satisfying results concerning time to re-epithelialisation and material handling were obtained. The possibility to leave the dressing on the wounds for 7 days showed a positive effect in the treatment of children, for whom every hospital visit may cause massive stress reactions. The nanocellulose-based dressing is a promising tool in conservative treatment of burns. Reducing the frequency of dressing changes supports a fast and undisturbed recovery; moreover, the dressing provides an optimal moist healing environment. The time to re-epithelialisation is comparable to frequently used materials, and cost reduction effect can be achieved without loss of quality. Possible pain and distress levels are kept to a minimum; therefore, flexibility and compliance of the patients and their parents are enhanced.

Effects of metformin on adipose-derived stromal cell (ADSC) - Breast cancer cell lines interaction.

AIMS: Metformin is a clinical drug administered to patients to treat type 2 diabetes mellitus that was found to be associated with a lower risk of occurrence of cancer and cancer-related death. The present study investigated the effects of metformin on human adipose-derived stromal cells (ADSC) - breast cancer cell line interactions. MAIN METHODS: ADSCs grown from lipoaspirates were tested for growth-stimulating and migration-controlling activity on breast cancer cell lines after pretreatment with metformin. Furthermore, secreted proteins of ADSCs, phosphorylation of intracellular proteins and the effect of metformin on adipocytic differentiation of ADSCs were assayed. KEY FINDINGS: Compared to breast cancer cell lines (4.0 ± 3.5% reduction of proliferation), 2 mM metformin significantly inhibited the proliferation of ADSC lines (19.2 ± 8.4% reduction of proliferation). This effect on ADSCs seems to be mediated by altered phosphorylation of GSK-3, CREB and PRAS40. Furthermore, treatment with metformin abolished the induction of differentiation of three ADSC lines to adipocytes. 1 and 2 mM metformin significantly impaired the migration of breast cancer cell lines MDA-MB-231 and MDA-MB-436 in scratch assays. SIGNIFICANCE: Metformin showed low direct inhibitory effects on breast cancer cell lines at physiological concentrations but exerted a significant retardation of the growth and the adipocytic differentiation of ADSCs. Thus, the anticancer activity of metformin in breast cancer at physiological drug concentrations seems to be mediated by an indirect mechanism that lowers the supportive activity of ADSCs.

Comparison of Energy-Based Tissue Dissection Techniques in Abdominoplasty: A Randomized, Open-Label Study Including Economic Aspects.

BACKGROUND: Abdominoplasty is one of the most common procedures in plastic surgery, and energy-based tissue dissection techniques have become the gold standard. Despite its frequency, abdominoplasty is still associated with high complication rates. OBJECTIVES: The authors compared clinical and economic data of 4 methods of energy-based tissue dissection in a randomized, open-label study. METHODS: A total of 57 patients were preoperatively randomized into 4 groups: electrocautery, Ultracision Harmonic Scalpel, argon plasma coagulation, and PEAK-Plasmablade. Demographic and operational data as well as information on the postoperative course and complications were collected. For economic analysis, quotes were obtained from the device companies or official suppliers. RESULTS: Duration of surgery, drainage quantity, and wound healing complications did not differ significantly between groups. The Ultracision method caused significantly greater blood loss compared with all other techniques (P < 0.01). PEAK and Ultracision devices entailed greater surgical costs compared with APC and electrocautery. CONCLUSIONS: All methods evaluated can be applied safely and effectively in abdominoplasty procedures. However, these data demonstrate a significantly higher blood loss for the Ultracision Harmonic Scalpel. Considering the clinical data, the higher costs of PEAK and Ultracision methods appear unjustified.

Seasonal Impact on Surgical-Site Infections in Body Contouring Surgery: A Retrospective Cohort Study of 602 Patients over a Period of 6 Years.

BACKGROUND: Postoperative surgical-site infections are severe complications following body contouring surgery. Here, the authors evaluate whether surgical-site infection rates are influenced by higher temperatures during the summer season. METHODS: We enrolled 602 patients who underwent body contouring surgery between 2009 and 2015 in a retrospective cohort study. Data collected included demographics, surgical data, and postoperative outcome. Body contouring surgery procedures included lower and upper body lift, abdominoplasty, breast reduction, mastopexy, brachioplasty, and thigh lift. Infection rates were calculated on a seasonal basis and compared using Fisher's exact test and logistic regression analysis. RESULTS: There were 136 patients (125 women and 11 men) in the warm season [June to August; with an average temperature of 67.622°F (19.79°C)] and 466 patients (438 women and 28 men) in the cold seasons group [September to May, with an average temperature of 45.45 °F (7.47°C)]. The composition of the study cohorts was comparable. The average age was 40 years and the average body mass index was 27 kg/m. From a total of 602 patients, the authors observed 33 surgical-site infections, representing a rate of 5.48 percent. A statistically significant increase of postoperative surgical-site infections could be detected during summer (10.29 percent versus 4.08 percent; p = 0.0071), representing an increase of 150 percent. In addition, a logistic regression analysis determined "season" as the strongest predictor for surgical-site infections, with a risk increase of 2.693 times in the warm season. CONCLUSIONS: Body contouring operations are elective procedures, making careful risk consideration an absolute prerequisite. The authors demonstrate a significantly increased infection risk during summer and establish a causal link between the warm season and surgical-site infection accumulation. Consequently, preoperative patient information and operative planning should be adjusted accordingly. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.