The Postoperative Utilization of Intensive Care Beds After Visceral Surgery Procedures.

BACKGROUND: The necessary number of intensive care beds has been under debate in recent years. This study aims to provide a descriptive analysis of postoperative intensive care for visceral surgery patients based on three indicator procedures, with particular attention to the frequency and duration of intensive care among these patients, trends in the occupancy of intensive care units, and the course during the COVID-19 pandemic. METHODS: Routine data from inpatient cases of the Helios group (24 888 cases from 71 acute care hospitals) from 01.01.2016 to 31.12.2021 were analyzed retrospectively. The indicator procedures were colorectal resection, surgery for gastric carcinoma, and left pancreatic resection. RESULTS: Routine data reveal a decline in the utilization of intensive care by these patients over the years, e.g., after colorectal resection, from 84.2% in 2016 to 63.1% in 2021. The percentage of patients requiring mechanical ventilation declined to a small extent as well (2016: 10.3%; 2021: 8.9%). In-hospital mortality remained stable in the range of 4.1% to 5.2%. The number of gastric carcinomas operated on fell from 355 in 2016 to 239 in 2021, while the number of left pancreatic resections remained stable in the range of 147 to 172 per year. CONCLUSION: In the hospitals studied, visceral surgery patients still commonly undergo intensive care postoperatively, at a rate that is declining slowly over the years. No adjustments were made for age, sex, or Elixhauser comorbidity index.

Osteosynthesis-associated infection in maxillofacial surgery by bacterial biofilms: a retrospective cohort study of 11 years.

OBJECTIVES: The aim of this retrospective cohort study was to determine risk factors for osteosynthesis-associated infections (OAI) with subsequent necessity of implant removal in oral and maxillofacial surgery. MATERIALS AND METHODS: A total of 3937 records of patients who received either orthognathic, trauma, or reconstructive jaw surgery from 2009 to 2021 were screened for osteosynthetic material removal due to infection. Treatment-intervals, volume of applied osteosynthetic material, and respective surgical procedures were also assessed. Moreover, intraoperatively harvested microbial flora was cultured and subsequently identified by MALDI TOF. Bacteria were then screened for antibiotic resistance via VITEK system or, if necessary, via agar diffusion or epsilometer test. Data was analyzed utilizing SPSS statistical software. For statistical analysis of categorical variables, chi-square tests or Fisher exact tests were used. Continuous variables were compared via non-parametric tests. The level of significance for p-values was set at < 0.05. Descriptive analysis was also performed. RESULTS: The lower jaw was more prone to OAI than the mid face region. Larger volumes of osteosynthetic material led to significantly more OAI, resulting in reconstruction plates bearing the highest risk for OAI especially when compared to small-volume mini-plates frequently applied in trauma surgery. Among OAI associated with implant volumes smaller than 1500 mm3, the detection of Streptococcus spp., Prevotella spp., Staphylococcus spp., and Veillonella spp. was significantly elevated, whereas implant volumes larger than 1500 mm3 showed a significant increase of Enterococcus faecalis, Proteus mirabilis and Pseudomonas aeruginosa. High susceptibility rates (87.7-95.7%) were documented for 2nd- and 3rd-generation cephalosporines and piperacillin/tazobactam. CONCLUSION: High material load and lower jaw reconstruction bear the greatest risks for OAI. When working with large volume osteosynthetic implants, gram-negative pathogens must be considered when choosing an appropriate antibiotic regime. Suitable antibiotics include, e.g., piperacillin/tazobactam and 3rd-generation cephalosporines. CLINICAL RELEVANCE: Osteosynthetic material utilized in reconstructive procedures of the lower jaw may be colonized with drug-resistant biofilms.

Diplodia sapinea infection reprograms foliar traits of its pine (Pinus sylvestris L.) host to death.

Infection with the necrotrophic fungus Diplodia sapinea (Fr.) Fuckel is among the economically and ecologically most devastating diseases of conifers in the northern hemisphere and is accelerated by global climate change. This study aims to characterize the changes mediated by D. sapinea infection on its pine host (Pinus sylvestris L.) that lead to the death of its needles. For this purpose, we performed an indoor infection experiment and inoculated shoot tips of pine seedlings with virulent D. sapinea. The consequences for foliar traits, including the phytohormone profile, were characterized at both the metabolite and transcriptome level. Our results showed that D. sapinea infection strongly affected foliar levels of most phytohormones and impaired a multitude of other metabolic and structural foliar traits, such as reactive oxygen species scavenging. Transcriptome analysis revealed that these changes are partially mediated via modified gene expression by fungal exposure. Diplodia sapinea appears to overcome the defense reactions of its pine host by reprogramming gene expression and post-transcriptional controls that determine essential foliar metabolic traits such as the phytohormone profile, cell wall composition and antioxidative system.

What doesn't kill you makes you differentiate.

Tissues need strategies to cope with genomic insults to maintain their integrity. In this issue of Developmental Cell, Kato et al. use in vivo fate tracing to observe selective elimination of epidermal stem cells (EpiSCs) harboring severe genomic lesions through their differentiation and compensatory expansion of surrounding intact cells.

Systemic reprogramming of phytohormone profiles and metabolic traits by virulent Diplodia infection in its pine (Pinus sylvestris L.) host.

The widespread ascomycetous fungus Diplodia pinea is a latent, necrotrophic pathogen in Pinus species causing severe damages and world-wide economic losses. However, the interactions between pine hosts and virulent D. pinea are largely not understood. In the present study, systemic defence responses were investigated in non-inoculated, asymptomatic needles and roots of D. pinea infected saplings of two P. sylvestris provenances under controlled greenhouse conditions. Here, we show that D. pinea infection induced a multitude of systemic responses of the phytohormone profiles and metabolic traits. Shared systemic responses of both pine provenances in needles and roots included increased abscisic acid and jasmonic acid levels. Exclusively in the roots of both provenances, enhanced salicylic acid and reduced indole-3-acetic acid levels, structural biomass, and elevated activities of anti-oxidative enzymes were observed. Despite these similarities, the two pine provenances investigated different significantly in the systemic responses of both, phytohormone profiles and metabolic traits in needles and roots. However, the different systemic responses did not prevent subsequent destruction of non-inoculated needles, but rather prevented damage to the roots. Our results provide a detailed view on systemic defence mechanisms of pine hosts that are of particular significance for the selection of provenances with improved defence capacity.

Cefazolin versus ampicillin/sulbactam as an empiric antibiosis in severe odontogenic neck infection descending from the lower jaw-retrospective analysis of 350 cases.

OBJECTIVES: Odontogenic infections descending from the lower jaw may lead to severe health conditions. Commonly, a biphasic treatment of surgical drainage and antibiotic therapy is conducted. The choice of the administered empiric antibiotic agent remains debatable. MATERIAL AND METHODS: Retrospectively, we analyzed 350 medical records of patients who were consecutively treated with odontogenic infections descending from the lower jaw. All patients received surgical drainage and either cefazolin or ampicillin/sulbactam as empiric antibiosis. In particular, the number of secondary operations, infectious parameters, and length of in-hospital stay were investigated. RESULTS: The most frequently infected space was the perimandibular/buccal space for both groups followed by the submandibular space. Number of revision procedures, early recurrence, and length of stay presented no significant difference between both groups (p > 0.05). Inflammatory parameters (c-reactive protein, leukocytes) similarly decreased in both groups. CONCLUSION: Cefazolin targets the majority of the pathogens detected in severe odontogenic neck infections descending from the lower jaw and reveals comparable results to AMP/S in regard to the inflammatory parameters and in-hospital stay. CLINICAL RELEVANCE: Cefazolin is a feasible empiric antibiosis for odontogenic neck infections descending from the lower jaw if surgical drainage is performed.

Murine Epidermal Ceramide Synthase 4 Is a Key Regulator of Skin Barrier Homeostasis.

Epidermal barrier dysfunction is associated with a wide range of highly prevalent inflammatory skin diseases. However, the molecular processes that drive epidermal barrier maintenance are still largely unknown. Here, using quantitative proteomics, lipidomics, and mouse genetics, we characterize epidermal barrier maintenance versus a newly established barrier and functionally identify differential ceramide synthase 4 protein expression as one key difference. We show that epidermal loss of ceramide synthase 4 first disturbs epidermal lipid metabolism and adult epidermal barrier function, ultimately resulting in chronic skin barrier disease characterized by acanthosis, hyperkeratosis, and immune cell accumulation. Importantly, prolonged barrier dysfunction induced by loss of ceramide synthase 4 induced a barrier repair response that largely recapitulates molecular programs of barrier establishment. Collectively, this study provides an unbiased temporal proteomic characterization of barrier maintenance and disturbed homeostasis and shows that lipid homeostasis is essential to maintain adult skin barrier function to prevent disease.

A tissue-specific screen of ceramide expression in aged mice identifies ceramide synthase-1 and ceramide synthase-5 as potential regulators of fiber size and strength in skeletal muscle.

Loss of skeletal muscle mass is one of the most widespread and deleterious processes in aging humans. However, the mechanistic metabolic principles remain poorly understood. In the framework of a multi-organ investigation of age-associated changes of ceramide species, a unique and distinctive change pattern of C16:0 and C18:0 ceramide species was detected in aged skeletal muscle. Consistently, the expression of CerS1 and CerS5 mRNA, encoding the ceramide synthases (CerS) with substrate preference for C16:0 and C18:0 acyl chains, respectively, was down-regulated in skeletal muscle of aged mice. Similarly, an age-dependent decline of both CerS1 and CerS5 mRNA expression was observed in skeletal muscle biopsies of humans. Moreover, CerS1 and CerS5 mRNA expression was also reduced in muscle biopsies from patients in advanced stage of chronic heart failure (CHF) suffering from muscle wasting and frailty. The possible impact of CerS1 and CerS5 on muscle function was addressed by reversed genetic analysis using CerS1Δ/Δ and CerS5Δ/Δ knockout mice. Skeletal muscle from mice deficient of either CerS1 or CerS5 showed reduced caliber sizes of both slow (type 1) and fast (type 2) muscle fibers, fiber grouping, and fiber switch to type 1 fibers. Moreover, CerS1- and CerS5-deficient mice exhibited reduced twitch and tetanus forces of musculus extensor digitorum longus. The findings of this study link CerS1 and CerS5 to histopathological changes and functional impairment of skeletal muscle in mice that might also play a functional role for the aging skeletal muscle and for age-related muscle wasting disorders in humans.

Oral recipient site infections in reconstructive surgery - impact of the graft itself and the perioperative antibiosis.

OBJECTIVES: This study was designed to assess the influence of peri/post-operative antibiotic prophylaxis (POABP) and the reconstructive graft itself on recipient sites infections in head and neck surgery. MATERIALS AND METHODS: In this retrospective cohort study, 322 consecutive patients with reconstructive surgery were investigated. The primary objective was to analyze the differences of commonly applied reconstructive grafts on the occurrence of oral recipient site infections. Moreover, differences of POABP regimes (namely: ampicillin/sulbactam, 2nd generation cephalosporins, clindamycin) and antibiotic alternatives were investigated. In addition, patients' length of in-hospital stay was analyzed in regard to reconstructive graft and POABP regime. RESULTS: The free radial forearm flap and split-thickness skin graft presented significantly less recipient site infections and shorter length of in-hospital stays (LOS) in comparison to further six reconstructive technique with pedicled tissue transfer or bone transfers. LOS was significantly shorter for patients with ampicillin/sulbactam than with 2nd generation cephalosporins as POABP. 91% of the harvested pathogens (n=193) were susceptible to the combination of 2nd and 3rd generation cephalosporins. Secondly, 92 out 113 (81%) harvested pathogens presented susceptibility to moxifloxacin. CONCLUSION: Smaller tissue transfers are less prone to infections of the recipient site and present low LOS. For an POABP regime, the combination of 2nd and 3rd generation cephalosporins presents substantial results in recipient site infections. In cases of allergy, potential pathogens show adequate susceptibility to moxifloxacin. CLINICAL RELEVANCE: A combination of 2nd and 3rd generation cephalosporins may be used to prevent recipient sites in head and neck surgery.

Microbial diversity in infections of patients with medication-related osteonecrosis of the jaw.

OBJECTIVES: A central role of infections in the treatment of MRONJ patients is widely accepted. An investigation of the MRONJ lesions' biofilms as potential pathogens seems logical. MATERIALS AND METHODS: We investigated the clinical data of our MRONJ patients who received surgery in advanced stage of the disease. Special attention was granted to the local colonizers harvested from osseous MRONJ specimens and submucosal putrid infections. RESULTS: Eleven out of 71 patients presented a spontaneous onset of the disease and for 60 out of 71 patients a trigger was detected. Breast cancer (29.6%) and prostate cancer (22.5%) were the most frequent underlying disease for prescription of an antiresorptive therapy, mostly zoledronate. Submucosal soft tissue biofilms significantly differed from biofilms harvested from the MRONJ lesions bottom, yet the most frequent bacteria were equally present in both groups: Streptococcus species (spp.), Prevotella spp., Actinomyces spp., Veillonella spp., and Parvimonas micra. The cephalosporins, cefuroxime and cefotaxime, and ß-lactam antibiotics with ß-lactamase inhibitor revealed the greatest susceptibility for the detected bacteria. CONCLUSION: The bacteria from the submucosal areas and the bottom of the infected bone presented comparable susceptibility to the common antibiotics regimes. Streptococcus spp., Prevotella spp., and Veillonella spp. present a high abundance in MRONJ lesions beside Actinomyces spp. The MRONJ lesions bottom is in many cases not infected by Actinomyces spp. CLINICAL RELEVANCE: The removal of the necrotic bone reduces the variety of bacteria found in MRONJ lesions, in particular at the bottom of the lesion.

Prevention and management of bacterial infections of the donor site of flaps raised for reconstruction in head and neck surgery.

PURPOSE: In the field of reconstructive head and neck surgery, surgical site infections (SSI) are commonly investigated for the recipient site of various reconstructive procedures. Data about SSI of the donor site of different flaps raised for reconstruction are rare. MATERIAL AND METHODS: With regard to the bacterial donor site infections, we retrospectively investigated the medical data, surgical reports and wound management protocols of 267 patients who received reconstruction of the head and neck after ablative surgery. All patients underwent reconstruction with one of the following flaps: free fasciocutaneous radial forearm flap (RFFF), free fasciocutaneous anterolateral thigh flap (ALTFF), pedicled myocutaneous latissimus dorsi flap (PLDF), pedicled myocutaneous pectoralis major flap (PPMF), free osteocutaneous fibula flap (FFF). Follow-up was conducted for 12 months. RESULTS: The lowest detection ratio (DR: number of infected sites/flaps raised from the respective donor site) was calculated for the radial forearm, 0.087. Pedicled flaps presented a moderate DR (PLDF: 0.27, PMMF:0.35). Donor sites of the leg possessed the highest DR (ALTFF:0.61, FFF: 045). Mainly gram-positive facultative anaerobic bacteria (n = 41) were detected and gram-negative bacteria (aerobe/anaerobe) were present in 27 cases. The most frequently detected bacteria were Staphylococcus spp., Viridans Streptococci, Pseudomonas aeruginosa and Escheria coli. Continuous wound management for in-hospital patients was able to prevent any local spreading or a prolonged length of in-hospital stay. CONCLUSION: Overall, gram-positive facultative anaerobic bacteria, mainly Staphylococcus spp., are the predominant bacteria detected in donor site wounds. For wound care management, an infection with gram-negative pathogens should not be neglected.

Consequences of Sphaeropsis tip blight disease for the phytohormone profile and antioxidative metabolism of its pine host.

Phytopathogenic fungi infections induce plant defence responses that mediate changes in metabolic and signalling processes with severe consequences for plant growth and development. Sphaeropsis tip blight, induced by the endophytic fungus Sphaeropsis sapinea that spreads from stem tissues to the needles, is the most widespread disease of conifer forests causing dramatic economic losses. However, metabolic consequences of this disease on bark and wood tissues of its host are largely unexplored. Here, we show that diseased host pines experience tissue dehydration in both bark and wood. Increased cytokinin and declined indole-3-acetic acid levels were observed in both tissues and increased jasmonic acid and abscisic acid levels exclusively in the wood. Increased lignin contents at the expense of holo-cellulose with declined structural biomass of the wood reflect cell wall fortification by S. sapinea infection. These changes are consistent with H2 O2 accumulation in the wood, required for lignin polymerization. Accumulation of H2 O2 was associated with more oxidized redox states of glutathione and ascorbate pools. These findings indicate that S. sapinea affects both phytohormone signalling and the antioxidative defence system in stem tissues of its pine host during the infection process.

The impact of surgical intervention and antibiotics on MRONJ stage II and III - Retrospective study.

OBJECTIVES: Metastatic bone disease and osteoporosis are the main indications for bisphosphonates and anti-resorptive agent therapy. Inhibition of bone turnover and angiogenesis are mainly responsible for the development of Medication Related Osteonecrosis of Jaws (MRONJ) as therapeutic side-effect. Yet, the role of infection for the development and recurrence of MRONJ is not fully elucidated. The aim of this retrospective study is to explore if a difference in antibiotic regimes has an impact on the surgical intervention needed to achieve a painless stable stage of the disease. Furthermore, we investigated concomitant submucosal infections in local relation to the MRONJ site. METHODS: A retrospective study (2006-2015) of 143 patients treated with MRONJ stage II and stage III in a single institutional university hospital was performed. All patients experienced at least one surgical intervention and received antibiotics. Their medical records, pathological and microbial findings were reviewed. Data was controlled for the achievement of an event free time period of at least 12 months. RESULTS: We investigated the number and kind of treatments that were performed on patients with MRONJ stage II and III to achieve a painless stable stage of the disease. The first and second healing approach differed significantly from each other (p < 0.05). In 7 (4.9%) cases up to four surgical interventions were needed to achieve oral rehabilitation. In 135 (95.1%) of all cases a segmental resection could be prevented, with extended decortication being the most applied method. Patients under perioperative ampicillin/sulbactam showed a significant reduction for a second or fourth intervention compared to the clindamycin group (p < 0.05). Results for a third intervention presented a similar difference between both groups, but were not significant (p = 0.06). Intraoperatively in 76 out of 241 (31.5%) cases presented putrid submucosal infections. The isolated bacteria were gram-negative facultative anaerobes (39.1%) and strictly anaerobic bacteria (gram-positive/38.2%, gram-negative/19.1%). Susceptibly of the cultured bacteria were significantly (p < 0.05) in favor to ampicillin/sulbactam (79.1%) compared to clindamycin (49.5%). CONCLUSION: The perioperative antibiotic regime for patients with MRONJ stage II and III undergoing surgically treatment does have an influence on the recurrence of the disease. Further investigation is needed to elucidate the role of infection in the treatment of MRONJ.

Odontogenic sinusitis maxillaris: A retrospective study of 121 cases with surgical intervention.

PURPOSE: Otolaryngologists, dentists and maxilla-facial surgeons see patients suffering from odontogenic maxillary sinusitis on a daily routine. The study was performed to investigate the different origins of the odontogenic maxillary sinusitis ranging from periodontitis to augmentative implant surgery. Furthermore, the microbial flora of purulent odontogenic maxillary sinusitis was analyzed in order to present a proper antibiotic treatment in addition to a surgical approach. MATERIALS AND METHODS: A retrospective study was performed, analyzing the clinical trials of 121 patients suffering from odontogenic maxillary sinusitis who undergone surgery. Harvested bacteria were tested for susceptibility on a routine base, surgical reports of removed foreign material or dental focus were reviewed as well as preoperative CBCT. RESULTS: Patients mean age was 56.62 (±16 SD) with a slight female gender dominance. Allergic profile to ß-lactam antibiotics had no influence on patients' length of in-hospital stay. 69 out of 121 cases of OMS occurred after dental surgery (extractions, augmentation or implant surgery). Maxillary molars were the teeth mostly hold accountable for an onset without surgery in recent history. 22.3% of the patients possessed a dislocated foreign body in the maxillary sinus. Pseudomonas aeruginosa infection was significantly associated with misplaced foreign bodies (root filling, augmentative dental material e.g. p < 0.05). We protocoled an anaerobic dominance with 45 anaerobes versus 19 aerobes. Ampicillin/Sulbactam (80%) and Piperacillin/Tazobactam (93.3%) present sufficient susceptibly rates to the harvested bacteria. Likewise showed Moxifloxacin (86.3%) equal results, whereas Clindamycin had a poor outcome with merely 50% of the tested bacteria being susceptible to Clindamycin. CONCLUSION: If OMS is diagnosed dental focus should be treated, misplaced bodies should be removed and purulent exacerbation has to be additionally treated with a calculated antibiotic therapy according to the pathogens resistance patterns.

Mistletoe infestation mediates alteration of the phytohormone profile and anti-oxidative metabolism in bark and wood of its host Pinus sylvestris.

European mistletoe (Viscum album L.) has largely infested Central European forests and causes high mortality probability particularly in dry years. However, little information is available about the consequences of mistletoe infestation for metabolic processes in bark and wood of its host, despite their important roles in infestation defense. We analyzed the tissue hydration, carbohydrate composition, phytohormone profile, reactive oxygen species and anti-oxidant levels in bark and wood of Scots pines (Pinus sylvestris L.), as dependent on mistletoe infestation. As a consequence of mistletoe infestation, host bark and wood showed impaired hydration and reduced total carbon content. In the bark, soluble sugar and lignin contents increased, apparently at the expense of holo-cellulose. Hydrogen peroxide accumulation was accompanied by increased glutathione and decreased reduced ascorbic acid levels. Mistletoe infestation mediated alteration of the phytohormone profile in bark and wood of its host. Cytokinins, jasmonic acid and abscisic acid levels increased in both tissues, whereas salicylic acid and indole-3-acetic acid, which were only detected in the bark, declined. The present results show that mistletoe infestation affects both the host's anti-oxidative defense system and the phytohormone profile after establishment of the xylem tapping haustorium. The significance of these processes for the development of the woody mistletoe stem and the haustorium is discussed.

Recent Zika Virus Isolates Induce Premature Differentiation of Neural Progenitors in Human Brain Organoids.

The recent Zika virus (ZIKV) epidemic is associated with microcephaly in newborns. Although the connection between ZIKV and neurodevelopmental defects is widely recognized, the underlying mechanisms are poorly understood. Here we show that two recently isolated strains of ZIKV, an American strain from an infected fetal brain (FB-GWUH-2016) and a closely-related Asian strain (H/PF/2013), productively infect human iPSC-derived brain organoids. Both of these strains readily target to and replicate in proliferating ventricular zone (VZ) apical progenitors. The main phenotypic effect was premature differentiation of neural progenitors associated with centrosome perturbation, even during early stages of infection, leading to progenitor depletion, disruption of the VZ, impaired neurogenesis, and cortical thinning. The infection pattern and cellular outcome differ from those seen with the extensively passaged ZIKV strain MR766. The structural changes we see after infection with these more recently isolated viral strains closely resemble those seen in ZIKV-associated microcephaly.

Keim oder kein Keim: Herausforderungen bei der Diagnose mykobakterieller Infektionen der Haut.

Kutane Mykobakteriosen sind in Deutschland selten. Dennoch ist es für eine frühzeitige Diagnose und anschließende wirksame Behandlung erforderlich, dass diese Krankheitsbilder im ärztlichen Bewusstsein verankert sind. Darüber hinaus stehen Infektionen mit Mykobakterien auf der Liste der Differentialdiagnosen vieler Hautkrankheiten. Diagnosen kutaner Mykobakteriosen beruhen auf klinischen Merkmalen und auf Laboruntersuchungen, einschließlich bakterieller Kulturen, histopathologischer Untersuchungen und PCR-basierten Verfahren. Das Wissen um Möglichkeiten und Grenzen dieser Laboruntersuchungen ist von zentraler Bedeutung, um eine angemessene klinische Entscheidung zu treffen. In diesem Beitrag diskutieren wir die aktuellen diagnostischen Möglichkeiten, die in Verdachtsfällen kutaner Mykobakteriosen zur Verfügung stehen.

Bug or no bug: challenges in diagnosing cutaneous mycobacterial infections.

Cutaneous mycobacterioses are rare in Germany. Nevertheless, early diagnosis and subsequent effective treatment requires awareness of these conditions. Moreover, mycobacterial infections are on the differential diagnosis list of many skin diseases. Diagnoses of cutaneous mycobacterioses are based on clinical features, but also on laboratory investigations, including bacterial culture, histopathology and PCR-based methods. Knowledge about the opportunities and limitations of theses laboratory tests is pivotal to reasonable clinical decision-making. In this paper, we review the current diagnostic options when suspecting a case of cutaneous mycobacterial infection.

Ceramide synthase 4 regulates stem cell homeostasis and hair follicle cycling.

Ceramides are crucial for skin barrier function, but little is known about the regulation of epidermal appendages and whether stem cell populations that control their regeneration depend on specific ceramide species. Here we demonstrate that ceramide synthase 4 (CerS4) is highly expressed in the epidermis of adult mice where it is localized in the interfollicular epidermis and defined populations within the pilosebaceous unit. Inactivation of CerS4 in mice resulted in precocious activation of hair follicle bulge stem cells while expanding the Lrig1(+) junctional zone and sebaceous glands. This was preceded first by a decrease in bone morphogenetic protein (BMP) and a subsequent increase in Wnt signaling. This imbalance in quiescent versus activating signals likely promoted a prolonged anagen-like hair follicle state after the second catagen, which exhausted stem cells over time ultimately resulting in hair loss in aged mice. K14-Cre-mediated deletion of CerS4 revealed a similar phenotype, thus suggesting an epidermis intrinsic function of CerS4 in regulating the regeneration of the pilosebaceous unit. The data indicate that CerS4-directed epidermal ceramide composition is essential to control hair follicle stem and progenitor cell behavior potentially through its regulation of BMP and Wnt signaling.