[Soft tissue infections]. / Wekedeleninfecties.

Soft tissue infections are common, but can be difficult to diagnose and manage. In this article, the classification of soft tissue infections is discussed, as well as the diagnostic possibilities and treatment options. Furthermore, the management of recurrent infections and necrotizing soft tissue infections are discussed. The added value of compression therapy is reviewed in more detail.

Equipoise: an important ethical consideration when contemplating participation in a randomised controlled trial of hyperbaric oxygen treatment in necrotising soft tissue infections.

A proposal for a large, multi-centre, randomised controlled trial investigating the role of hyperbaric oxygen treatment (HBOT) in necrotising soft tissue infections (NSTI) has led to much discussion locally and internationally about whether participation is ethical for a centre where stakeholders already consider HBOT standard practice. This article systematically addresses the concept of clinical equipoise specific to the role of HBOT in NSTI, and presents a series of considerations to be taken into account by key stakeholders at potential participating sites.

Reported outcome measures in necrotising soft tissue infections: a systematic review.

Introduction: There are inconsistencies in outcome reporting for patients with necrotising soft tissue infections (NSTI). The aim of this study was to evaluate reported outcome measures in NSTI literature that could inform a core outcome set (COS) such as could be used in a study of hyperbaric oxygen in this indication. Methods: A systematic review of all NSTI literature identified from Cochrane, Ovid MEDLINE and Scopus databases as well as grey literature sources OpenGrey and the New York Academy of Medicine databases which met inclusion criteria and were published between 2010 and 2020 was performed. Studies were included if they reported on > 5 cases and presented clinical endpoints, patient related outcomes, or resource utilisation in NSTI patients. Studies did not have to include intervention. Two independent researchers then extracted reported outcome measures. Similar outcomes were grouped and classified into domains to produce a structured inventory. An attempt was made to identify trends in outcome measures over time and by study design. Results: Three hundred and seventy-five studies were identified and included a total of 311 outcome measures. Forty eight percent (150/311) of outcome measures were reported by two or more studies. The four most frequently reported outcome measures were mortality without time specified, length of hospital stay, amputation performed, and number of debridements, reported in 298 (79.5%), 260 (69.3%), 156 (41.6%) and 151 (40.3%) studies respectively. Mortality outcomes were reported in 23 different ways. Randomised controlled trials (RCTs) were more likely to report 28-day mortality or 90-day mortality. The second most frequent amputation related outcome was level of amputation, reported in 7.5% (28/375) of studies. The most commonly reported patient-centred outcome was the SF-36 which was reported in 1.6% (6/375) of all studies and in 2/10 RCTs. Conclusions: There was wide variance in outcome measures in NSTI studies, further highlighting the need for a COS.

Contemporary national outcomes of hyperbaric oxygen therapy in necrotizing soft tissue infections.

BACKGROUND: The role of hyperbaric oxygen therapy (HBOT) in necrotizing soft tissue infections (NSTI) is mainly based on small retrospective studies. A previous study using the 1998-2009 National Inpatient Sample (NIS) found HBOT to be associated with decreased mortality in NSTI. Given the argument of advancements in critical care, we aimed to investigate the continued role of HBOT in NSTI. METHODS: The 2012-2020 National Inpatient Sample (NIS) was queried for NSTI admissions who received surgery. 60,481 patients between 2012-2020 were included, 600 (<1%) underwent HBOT. Primary outcome was in-hospital mortality. Secondary outcomes included amputation, hospital length of stay, and costs. A multivariate model was constructed to account for baseline differences in groups. RESULTS: Age, gender, and comorbidities were similar between the two groups. On bivariate comparison, the HBOT group had lower mortality rate (<2% vs 5.9%, p<0.001) and lower amputation rate (11.8% vs 18.3%, p<0.001) however, longer lengths of stay (16.9 days vs 14.6 days, p<0.001) and higher costs ($54,000 vs $46,000, p<0.001). After multivariate analysis, HBOT was associated with decreased mortality (Adjusted Odds Ratio (AOR) 0.22, 95% CI 0.09-0.53, P<0.001) and lower risk of amputation (AOR 0.73, 95% CI 0.55-0.96, P = 0.03). HBO was associated with longer stays by 1.6 days (95% CI 0.4-2.7 days) and increased costs by $7,800 (95% CI $2,200-$13,300), they also had significantly lower risks of non-home discharges (AOR 0.79, 95%CI 0.65-0.96). CONCLUSIONS: After correction for differences, HBOT was associated with decreased mortality, amputations, and non-home discharges in NSTI with the tradeoff of increase to costs and length of stay.

[Pediatric necrotizing soft-tissue infections]. / Infections cutanées nécrosantes de l'enfant.

PEDIATRIC NECROTIZING SOFT-TISSUE INFECTIONS. Necrotizing soft-tissue infections (NSTI) include necrotizing forms of fasciitis, myositis, and cellulitis. In children, these are extremely rare conditions with an estimated annual incidence of less than 0.1/100,000 patients aged 0-18 years in France. Nevertheless, the evolution can be very serious (6% mortality, higher than the mortality observed in paediatric intensive care units [PICU]), whereas the initial local symptoms are poor and can be falsely reassuring. The monitoring of a skin infection must be close in order not to ignore the evolution towards a NSTI. In this case, prompt transfer to a PICU with all the necessary technical facilities and used to the management of these rare conditions must be done. Early initiation of antibiotic treatment and aggressive haemodynamic resuscitation according to the latest Surviving Sepsis Campaign guidelines should be a priority. The paediatric surgeon should be called upon as soon as clinical suspicion arises and participate in the frequent clinical reassessment to determine the optimal time to perform the surgical treatment.

INFECTIONS CUTANÉES NÉCROSANTES DE L'ENFANT. Les infections cutanées nécrosantes comprennent les dermo- hypodermites bactériennes nécrosantes (DHBN) et les fasciites nécrosantes (FN). Chez l'enfant, ce sont des pathologies extrêmement rares, avec une incidence annuelle en France estimée inférieure à 0,1/100 000 patients âgés de 0 à 18 ans. Néanmoins, leur évolution peut être gravissime (mortalité de 6 %, supérieure à la mortalité observée habituellement dans les unités de réanimation pédiatrique [URP]) alors que la symptomatologie locale initiale est pauvre et peut faussement rassurer. La surveillance d'une infection cutanée doit être rapprochée afin de ne pas méconnaître l'évolution vers une DHBN-FN. Dans ce cas, une orientation vers une URP disposant de l'ensemble du plateau technique nécessaire, et surtout habituée à gérer ces situations cliniques, est justifié. L'initiation précoce du traitement antibiotique et la prise en charge hémodynamique agressive en suivant les dernières recommandations de la Surviving Sepsis Campaign doivent être une priorité. Le chirurgien pédiatrique doit être appelé dès la suspicion clinique et participer à la réévaluation pluriquotidienne afin de déterminer le moment optimal pour réaliser le traitement chirurgical.

Lemierre-like syndrome after soft tissue infection due to methicillin-resistant Staphylococcus aureus: A case report and literature review.

RATIONALE: Lemierre-like syndrome (LLS) is characterized by bacteremia, septic thrombophlebitis of the internal jugular vein, and metastatic abscesses. In contrast to classic Lemierre syndrome, sources of infection are not related to oropharyngeal infections, as are frequent soft tissue infections. In recent years, Staphylococcus aureus has been identified as an emergent pathogen that causes this syndrome. The mortality rate of LLS caused by this pathogen is approximately 16%. Timely diagnosis, antibiotic treatment, and infection control are the cornerstones to treat LLS. Anticoagulant therapy as adjuvant treatment remains controversial. PATIENT CONCERNS: A 31-year-old woman from California, United States (US), was admitted to the emergency room with a history of 2 days of fever and severe throbbing pain in the left cervical region. Thorax and neck CT tomography revealed confluent cavities suggestive of septic embolism in the lungs and a filiform thrombus in the lumen of the left internal jugular vein, with moderate swelling of the soft and muscular tissues. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the blood culture. DIAGNOSIS: The thrombus in the internal jugular vein associated with cellulitis in the neck and multiple cavitary lesions in the lungs support the diagnosis of LLS caused by MRSA with septic embolization. INTERVENTIONS: During treatment, the patient received vancomycin IV for 25 days and returned to the US with linezolid orally. In addition, assisted video-thoracoscopy and bilateral mini-thoracotomy with pleural decortication were performed for infectious source control, where 1700cc of purulent pleural fluid was drained. OUTCOMES: The patient was discharged with optimal evolution. LESSONS: LLS should be suspected in patients with skin and soft tissue infections who develop thrombosis or metastatic infections. MRSA infections should be considered in patients from areas where this pathogen is prevalent.

Negative Pressure Wound Therapy With and Without Instillation in Necrotizing Soft Tissue Infections.

Background: Necrotizing soft tissue infections (NSTIs) are rare but deadly infections that require early and often extensive surgical debridement. After debridement, patients frequently have substantial morbidity because of large, open wounds. Hypothesis: Negative pressure wound therapy with instillation (NPWTi) results in higher wound closure rates compared with traditional negative pressure wound therapy (NPWT) or wet to dry dressings (moist wound care dressing). Patients and Methods: A prospectively maintained Acute and Critical Care Surgery database spanning 2008-2018 was queried for patients with a diagnosis of necrotizing fasciitis, Fournier gangrene, or gas gangrene. Data were collected on patient comorbidities, operative management, and clinical outcomes. Patients were stratified by use of moist wound care dressing, traditional NPWT, or NPWTi. Data were analyzed using analysis of variance (ANOVA), χ2, and logistic regression. Results: During the 10-year study period, patients were treated for NSTI; 173 were managed with moist wound care dressing, 150 with NPWT, and 48 with NPWTi. Patients were similar in terms of demographics, body mass index (BMI), diabetes mellitus, and smoking rates. Overall, complication rates were not substantially different, but mortality was higher in the moist wound care dressing group (16.2% vs. 10.7% NPWT vs. 2.1% NPWTi; p = 0.02). In the moist wound care dressing group, 81.5% of patients had an open wound at discharge compared with 52.7% of the NPWT group and only 14.6% of the NPWTi group (p < 0.001). On multivariable regression, NPWTi was associated with closure rates five times higher than the NPWT group (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.40-11.61; p < 0.001) after controlling for smoking status, intravenous drug use, number of operations, and involvement of the most common region of the body. Conclusions: Negative pressure wound therapy with instillation is associated with higher rates of wound closure without increasing complication rates in patients with NSTI compared with traditional NPWT or moist wound care dressing. Although prospective studies are needed, this indicates the potential to improve patient quality of life through reduced pain and outpatient home health needs.

Necrotizing fasciitis: an update on epidemiology, diagnostic methods, and treatment.

PURPOSE OF REVIEW: The aim of this review is to discuss the latest evidence of epidemiology, diagnostic methods, and treatment of necrotizing soft tissue infections (NSTIs) with a particular focus on necrotizing fasciitis (NF). RECENT FINDINGS: NSTIs have been historically referred to as NF but encompass a broader range of infections, with variable rates ranging from 0.86 to 32.64 per 100 000 person-years, influenced by factors such as climate and seasonal variations. They have diverse microbiological profiles categorized into different types based on the involved pathogens, including polymicrobial or monomicrobial infections caused by organisms such as group A streptococcus (GAS), Staphylococcus aureus , some Gram-negative pathogens, and filamentous fungi following trauma and natural disasters. Diagnosis relies on clinical symptoms and signs, laboratory markers, and imaging. However, the gold standard for diagnosis remains intraoperative tissue culture. Treatment involves repeated surgical debridement of necrotic tissues in addition to intravenous antibiotics. Adjuvant therapies with intravenous immunoglobulin (IVIG) and hyperbaric oxygen therapy (HBOT) might have a role. Soft tissue reconstruction may be necessary following surgery. SUMMARY: Prompt diagnosis and proper medical and surgical management of NSTI will improve outcomes.

Characterization of patients with odontogenic necrotizing soft tissue infections in the head and neck area. A retrospective analysis.

OBJECTIVE: Necrotizing soft-tissue infection (NSTI) in the head and neck area may develop from odontogenic infections. The aim of this study was to characterize patients with NSTI in the head and neck with odontogenic origin in a well-defined prospectively collected cohort. MATERIAL AND METHODS: Patients with NSTI in the head and neck, hospitalized between 2013 and 2017 at Copenhagen University Hospital and registered in the Scandinavian INFECT database were included. Medical records of identified patients and from the INFECT database were screened for a defined set of data including the primary focus of infection, comorbidities, predisposing factors, clinical and radiographic diagnostics, course of treatment, and treatment outcome. RESULTS: Thirty-five patients with NSTI in the head and neck area were included in the study. A total of 54% had odontogenic origin, primarily from mandibular molars, and 94% had radiographic signs of infectious oral conditions. Overall, comorbidities were reported in 51% with cardiovascular disease being the most prevalent. In 20%, no comorbidities or predisposing conditions could be identified. The overall 30-day mortality rate was 9%. CONCLUSIONS: More than half of NSTI cases in the head and neck region had an odontogenic origin, and special attention should be paid to infections related to mandibular molars.

Bacterial Skin and Soft Tissue Infections in Older Adults.

This article focuses on bacterial infections that commonly affect geriatric patients. The elderly population is at a higher risk of contracting bacterial infections due to weakened immune systems and comorbidities. The article explores the cause, pathogenesis, clinical manifestations, and treatment options of these infections. Additionally, antibiotic resistance is a growing concern in the treatment of bacterial infections. The article highlights the importance of preventing these infections through proper hygiene and wound care. This article aims to provide an understanding of bacterial infections in geriatric patients and inform health-care providers on the most effective ways to manage and prevent these infections.

Key pathways and genes that are altered during treatment with hyperbaric oxygen in patients with sepsis due to necrotizing soft tissue infection (HBOmic study).

BACKGROUND: For decades, the basic treatment strategies of necrotizing soft tissue infections (NSTI) have remained unchanged, primarily relying on aggressive surgical removal of infected tissue, broad-spectrum antibiotics, and supportive intensive care. One treatment strategy that has been proposed as an adjunctive measure to improve patient outcomes is hyperbaric oxygen (HBO2) treatment. HBO2 treatment has been linked to several immune modulatory effects; however, investigating these effects is complicated due to the disease's acute life-threatening nature, metabolic and cell homeostasis dependent variability in treatment effects, and heterogeneity with respect to both patient characteristics and involved pathogens. To embrace this complexity, we aimed to explore the underlying biological mechanisms of HBO2 treatment in patients with NSTI on the gene expression level. METHODS: We conducted an observational cohort study on prospective collected data, including 85 patients admitted to the intensive care unit (ICU) for NSTI. All patients were treated with one or two HBO2 treatments and had one blood sample taken before and after the intervention. Total RNAs from blood samples were extracted and mRNA purified with rRNA depletion, followed by whole-transcriptome RNA sequencing with a targeted sequencing depth of 20 million reads. A model for differentially expressed genes (DEGs) was fitted, and the functional aspects of the obtained set of genes was predicted with GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of genes and Genomes) enrichment analyses. All analyses were corrected for multiple testing with FDR. RESULTS: After sequential steps of quality control, a final of 160 biological replicates were included in the present study. We found 394 protein coding genes that were significantly DEGs between the two conditions with FDR < 0.01, of which 205 were upregulated and 189 were downregulated. The enrichment analysis of these DEGs revealed 20 GO terms in biological processes and 12 KEGG pathways that were significantly overrepresented in the upregulated DEGs, of which the term; "adaptive immune response" (GO:0002250) (FDR = 9.88E-13) and "T cell receptor signaling pathway" (hsa04660) (FDR = 1.20E-07) were the most significant. Among the downregulated DEGs two biological processes were significantly enriched, of which the GO term "apoptotic process" (GO:0006915) was the most significant (FDR = 0.001), followed by "Positive regulation of T helper 1 cell cytokine production" (GO:2000556), and "NF-kappa B signaling pathway" (hsa04064) was the only KEGG pathway that was significantly overrepresented (FDR = 0.001). CONCLUSIONS: When one or two sessions of HBO2 treatment were administered to patients with a dysregulated immune response and systemic inflammation due to NSTI, the important genes that were regulated during the intervention were involved in activation of T helper cells and downregulation of the disease-induced highly inflammatory pathway NF-κB, which was associated with a decrease in the mRNA level of pro-inflammatory factors. TRIAL REGISTRATION: Biological material was collected during the INFECT study, registered at ClinicalTrials.gov (NCT01790698).

Quality of Life After Intensive Care Unit Admittance for Necrotizing Soft Tissue Infections Is Deemed Acceptable for Patients.

Background: Because mortality and amputation rates are declining for necrotizing soft tissue infections (NSTIs), this study aimed to assesses the self-reported one-year quality of life (QoL) of severely ill patients with NSTI who survived beyond the intensive care unit (ICU). Patients and Methods: A retrospective cohort study of patients with NSTI admitted to the ICU between 2010 and 2019 was conducted. A year after ICU discharge, QoL was assessed using the three-level EuroQol five-dimensions (EQ-5D-3L) questionnaire, Impact of Event Scale-Revised (IES-R) questionnaires, and pain scales. Furthermore, willingness to undergo ICU admission again if needed was reviewed. Results: Twenty-nine (of 38) patients with NSTI survived their hospitalization (76%). During the one-year follow-up, three patients died (8%; one-year survival 68%). Nineteen patients filled out the questionnaires (73%). The median EQ-5D-3L index score was 0.775 (interquartile range [IQR], 0.687-0.843). The domains reported most to cause impairment were "usual activity" and "pain/discomfort." Patients had a median pain score of five (of 10; IQR, 1-6) and two patients (15%; of 13) scored "clinical concern for PTSD.". Eighty-five percent of the patients would undergo the ICU treatment again if needed. Conclusions: The one-year QoL of ICU-admitted patients with NSTI varies widely, however, the overall QoL and one-year survival was similar to other ICU patients who underwent acute surgery and the QoL was slightly lower than the general ICU population. Most patients experience problems with daily activity and pain, but this does not mean that patients with NSTI automatically had poor self-reported quality of life or unwillingness to undergo ICU treatment again if needed.

Necrotizing Soft-Tissue Infections: A Case-Based Review.

GENERAL PURPOSE: To review the assessment and management of necrotizing fasciitis. TARGET AUDIENCE: This continuing-education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Identify the etiologic pathogens for necrotizing fasciitis.2. Summarize assessment guidelines for patients who present with signs of necrotizing fasciitis.3. Explain recommended treatment protocols for patients who have necrotizing fasciitis.

Necrotizing fasciitis is a rapidly progressive soft-tissue infection with tissue necrosis and a high mortality rate. This case-based review provides an overview of an approach to the diagnosis and management of necrotizing fasciitis for clinicians.

A prospective study on skin and soft tissue infections: a fact-finding mission from a tertiary centre in north India.

OBJECTIVE: Despite the high prevalence and poor outcome of skin and soft tissue infections (SSTIs), very few studies from India have dealt with the subject. We planned a prospective study of inpatients with SSTIs to study the aetiology, clinical presentation (severity) and outcome of patients with SSTIs in our facility. METHOD: Patients with SSTIs involving >5% body surface area (BSA) and/or systemic signs were admitted to the surgery department of a teaching tertiary level hospital in Delhi, India, and were clinically classified into cellulitis, necrotising soft tissue infections (NSTIs), pyomyositis, and abscess. Demographic and clinical variables such as: age; sex; occupation; history of trauma/insect or animal bites; duration of illness; presenting symptoms and signs; comorbid conditions; predisposing factors such as lymphoedema or venous disease; hospital course; treatment instituted; complications; hospital outcome; presence of crepitus, bullae, gangrene, muscle necrosis and compartment syndrome were recorded. The chief outcome parameters were death and length of hospital stay; others, such as abscess drainage, the need for plastic surgical procedures and amputations were also noted. RESULTS: Out of 250 patients enrolled in the study, 145 (58%) had NSTIs, 64 (26%) had abscesses, 15 (6%) had cellulitis and 26 (10%) had pyomyositis. Mortality was observed with NSTIs (27/145, 19%) and with pyomyositis (3/26, 11.5%). Factors affecting mortality by univariate analysis in the NSTI group were: abnormal pulse; hypotension; tachypnea; bullae; increased blood urea and serum creatinine; inotrope or ventilator support (all with p<0.001); local tenderness, gangrene, dialysis support and BSA (9.33±6.44 versus 5.12±3.62; p<0.05 for the last four). No factor was found to be significant on multivariate analysis. Variables associated with hospital stay >12 days were immunocompromise, pus discharge, ulceration or gangrene, and after interventions such as blood transfusion, drainage or skin grafting. CONCLUSION: High prevalence of NSTI and pyomyositis with high mortality was observed in our SSTI patients, often in immunocompetent young individuals. Epidemiological studies focused on virulent strains of Staphylococcus aureus may be required to identify the cause, since Staphylococcal toxins have been implicated in other infections.

Diabetic Soft Tissue Infections.

Diabetes is a systemic illness that can cause a broad range of physiologic effects. Infection rates and wound healing are both affected through multiple mechanisms. Other physiologic changes increase risk for wounds as well as complex soft tissue infections ranging from simple cellulitis to necrotizing soft tissue infections. Clinicians and surgeons need to have a low index of suspicion for severe infection in a patient presenting with diabetes, and even more so in patients with uncontrolled diabetes.

Severe necrotizing soft tissue infections-Is wound microbiology a prognostic factor for clinical outcome?

Necrotizing soft tissue infections (NSTIs) represent similar pathophysiological features, but the clinical course might range from subacute to a rapidly progressive, fulminant sepsis. Initial wound microbiology is the base for the Guiliano classification. The timeline of microbiological colonization has not been described during the clinical course. The role of the different microbiological pathogens on the outcome and mortality is unclear. One hundred eighty patients were included with septic inflammation response syndrome on admission. Initial wound microbiology and the changes in wound microbiology were analysed during the clinical course and correlated with outcome and risk indicators. Overall mortality was 35%. Higher age, a high Charlson Comorbidity Index or ASA score and truncal infections were highly prognostic for a lethal outcome. Microbiological findings revealed significant differences in the persistence of bacteria during the course of disease. Streptococci were only detectable within the first 5 days, whereas other bacteria persisted over a longer period of time. Initial microbiological findings correlated with better prognosis when no causative agent was identified and for gram-negative rods. Varying survival rates were observed for different Streptococci, Staphylococci, Enterococci and other bacteria. The highest odds ratio for a lethal outcome was observed for Enterococci and fungi. Microbiological colonization changes during the clinical course of NSTIs and some microbiologic pathogens are predictive for worsening the outcome and survival. Streptococcus pyogenes is only detectable in the very early phase of NSTI and after 6 days not anymore detectable. Later Enterococci and fungi showed the highest odds ratios for a lethal outcome. Enterococci bacteria and fungi have yet not been considered of clinical relevance in NSTI or even as indicator for worsening the outcome.

Severe and complicated soft tissue infections: a single-centre case series.

OBJECTIVE: To assess the demographic and clinical characteristics, laboratory findings, and economic burden of patients with a diagnosis of complicated skin and soft tissue infection (cSSTI). METHOD: The demographic and clinical characteristics, laboratory findings, surgical interventions, cost of treatment, and outcome of patients diagnosed with cSSTIs between January 2017 and December 2019 were retrospectively analysed. RESULTS: A total of 24 patients with cSSTIs were included in the study. The median age was 53 (22-85) years, and 14 (58%) were female. The most common comorbidity was diabetes (54%). On admission, 75% of patients presented with sepsis, and 70% had a high-grade Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score. The causative microorganism was isolated from 21 (87%) patients, and the multidrug resistance rate of Gram-negative bacteria was 50%. The median number of debridements was 3 (1-12). In all, 11 patients were followed up in the intensive care unit, and the mortality rate was 29%. The presence of confusion (p=0.025), causative Gram-negative microorganisms (p=0.009), hyponatraemia (p=0.034), the need for intensive care (p=0.001), anti-meticillin-resistant Staphylococcus aureus antibiotics (p=0.023) and the rate of antibiotic changes during treatment (p=0.019) were significantly higher in the non-survival patient group. Hyponatraemia was a significant independent risk factor for mortality (p=0.048). The median cost of per-patient treatment was $9453 USD in the non-surviving and $1536 in the surviving group. CONCLUSION: It is important to know possible factors and local resistance rates at the beginning of empirical antibacterial and surgical treatment. The presence of hyponatraemia, sepsis and a high LRINEC score can be considered to be the mortality predictors.