Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.

In monogenic autoinflammatory diseases, mutations in genes regulating innate immune responses often lead to uncontrolled activation of inflammasome pathways or the type I interferon (IFN-I) response. We describe a mechanism of autoinflammation potentially predisposing patients to life-threatening necrotizing soft tissue inflammation. Six unrelated families are identified in which affected members present with necrotizing fasciitis or severe soft tissue inflammations. Exome sequencing reveals truncating monoallelic loss-of-function variants of nuclear factor κ light-chain enhancer of activated B cells (NFKB1) in affected patients. In patients' macrophages and in NFKB1-variant-bearing THP-1 cells, activation increases both interleukin (IL)-1ß secretion and IFN-I signaling. Truncation of NF-κB1 impairs autophagy, accompanied by the accumulation of reactive oxygen species and reduced degradation of inflammasome receptor nucleotide-binding oligomerization domain, leucine-rich repeat-containing protein 3 (NLRP3), and Toll/IL-1 receptor domain-containing adaptor protein inducing IFN-ß (TRIF), thus leading to combined excessive inflammasome and IFN-I activity. Many of the patients respond to anti-inflammatory treatment, and targeting IL-1ß and/or IFN-I signaling could represent a therapeutic approach for these patients.

Predictive Ability of LRINEC Score for Lower Extremity Amputation in Moderate to Severe Diabetic Foot Infection.

OBJECTIVE: To assess the predictive ability of the laboratory risk indicator for necrotising fasciitis (LRINEC) score for lower extremity amputation in patients with moderate to severe diabetic foot infection (DFI). STUDY DESIGN: Observational study. Place and Duration of the Study: Department of General Surgery, Combined Military Hospital, Rawalpindi, Pakistan, from June to September 2023. METHODOLOGY: Patients admitted to the surgical ward with moderate to severe DFI were included by convenience sampling. Patients with severe sepsis, unstable haemodynamics, pressure injuries, and terminal illnesses were excluded. Demographic and clinical data of patients were noted down. LRINEC score was calculated on the day of admission. Final outcome (amputation or otherwise) was recorded on the 30th day the since the day of admission. RESULTS: Two hundred patients with moderate to severe DFI were included. The median age of patients was 56 years (IQR 49-66 years). The median duration of diabetes was 11 years (IQR 4 - 18.75 years). The median LRINEC score at admission was 6 (IQR 3-9). The majority of the patients (65.5%) had some other medical comorbid besides diabetes. Patients who had amputation due to DFI at 30 days post-admission had higher LRINEC scores on admission as compared to those patients who did not have amputation (Median 8 vs. 2, p <0.001). The cut-off point of LRINEC score ≥6.5 at admission had sensitivity of 74% and specificity of 94% in predicting amputation. CONCLUSION: The LRINEC score may be used as an objective scoring system to predict the risk of amputation in patients with moderate to severe DFI in indoor clinical settings. KEY WORDS: Diabetic foot, LRINEC score, Limb loss, Necrotising fasciitis.

A case study of abdominal wall and limb necrotizing fasciitis: an extremely rare post -operative complication.

INTRODUCTION: Infectious affections are the most frequent post-operative complications, the rate have been reducing due to the administration of perioperative antibiotics and they are rarely serious. They are usually associated to pelvic collections, fistulas, urinary tract stenosis and, exceptionally, necrotizing fasciitis (FN) and pelvic organ necrosis. There is no well-codified treatment. CASE PRESENTATION: A 42-year-old female patient, was referred to our department for a stage IIIC2 adenocarcinoma of the uterine cervix. Two months after surgery, the patient presented with fever. Abdominal CT scan revealed a recto-vaginal fistula. The patient underwent a surgical evacuation of the collection and a bypass colostomy. Post-operative period was marked by the occurrence of an extensive necrosis to pelvic organs and medial left leg's thigh compartments muscles. She also presented a thrombosis of the left external iliac vein and artery. Given the septic conditions, a revascularization procedure was not feasible. A bilateral ureterostomy was required and a ligature of the left external iliac vessels. Then she received palliative treatment.she died one month after surgery because of multivisceral failure due to sepsis. CONCLUSION: Necrotizing fasciitis is extremely rare and serious condition, the diagnosis is clinical and radiological, CT scan is helpful for the. There are predisposing factors such as diabetes, neoadjuvant radiotherapy or chemotherapy. The prognosis can be improved with rapid management and appropriate medical and surgical excisions of necrotic tissue, and antibiotic therapy adapted to the suspected germs, essentially anaerobic ones.

Aeromonas hydrophila induced necrotizing fasciitis following laparoscopic cholecystectomy.

Necrotizi ng fasciit is [NF] i s a m ultifaceted disease of the muscle fascia and body tissues which demands the earliest intervention. Past reviews have documented ver y few cases of Aeromonas Hydroph ila [AH] induced N F fol lo wing abdominal surgery. AH can cause fatal NF as seen in a 72 year old female patient reported at Liaquat National Hospital &Medical College; a ter tiary care center in Karachi, Pakistan on 2nd April, 2022. She had a k nown comorbidity of hypertension and presented with the chief complaint of symptomatic gallstones for which she unde rwent Laparoscopic Cholecystectomy (LAPCHOL). She developed NF of the lower ab domen post- oper atively. Following uneventful Laparoscopic Cholecystectomy our pati ent presented to the ER two days later with severe lower abdo minal pain and overlyi ng celluliti s. Fasc io to my revealed extensive myonecrosis with necrotizing soft tissue in fe ction. Despite u ndergoing extensive surgical debr idement and broad spectr um antibi ot ic administration; the patient died in the ICU on the fifth postoperat ive day followi ng septic complications. Histopathologica l an alysis, confirmed i nflammat ion and necrosis. Culture sensitivity of the debrided tissue revealed AH. Approach should lie towards analyzing the behaviour of such microbes in high risk patients through collective case studies. This is the first clinical case showcasing such parameters e ncountered in the General Surger y Department.

[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.

[Hyperbaric oxygen therapy and eye disease: Review of the literature]. / Oxygénothérapie hyperbare et maladies oculaires : une revue de la littérature.

Hyperbaric oxygen therapy consists of breathing 100% oxygen continuously or intermittently in a chamber at a pressure equal to or greater than 1.4 absolute atmospheres. Indicated for the emergency treatment of carbon monoxide poisoning and other medical-surgical pathologies such as gas embolism or necrotizing soft-tissue infections, various studies have shown a beneficial effect of hyperbaric oxygen therapy in certain ocular pathologies, notably of microcirculatory origin, such as central retinal artery occlusion or macular edema linked to retinal vein occlusions. In addition, hyperbaric oxygen might represent an alternative treatment for ocular quinine toxicity and might also be useful as an adjuvant to surgery and antibiotics in cases of periorbital necrotizing fasciitis. On the other hand, oxygen in high concentrations has toxic ocular effects due to the production of reactive oxygen derivatives.

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.

A Cross-Sectional Analysis of Pediatric Necrotizing Soft Tissue Infection Cases and Racial Disparities From the 2016 to 2020 National Inpatient Sample.

INTRODUCTION: The incidence, treatment, and outcomes of necrotizing soft tissue infections (NSTIs) and associated racial disparities have been described in adults, but research in the pediatric population is limited. The purpose of this study is to provide a nationally representative characterization of pediatric NSTI and determine the presence of any racial disparities. METHODS: The National Inpatient Sample was analyzed from 2016 through 2020. Patients aged less than 20 y with a diagnosis of necrotizing fasciitis, Fournier's gangrene, or gas gangrene (based on International Classification of Diseases, Tenth Revision, Clinical Modification codes) were included for analysis. RESULTS: A total of 355 patients were identified. Black and Hispanic patients accounted for the most admissions in 2016 and 2018, respectively (P = 0.024). Compared to White patients, more Black patients were insured by Medicaid (P = 0.037) and were in the first zip code-based income quartile (P = 0.005). The leading infection overall was necrotizing fasciitis and most patients (81.7%) underwent a surgical procedure by the first calendar day after admission. Although the proportion of Black patients undergoing subcutaneous tissue and fascia excisions was more than that of White patients (P = 0.005), there were no significant differences by race in the time to first procedure, the total number of procedures, or number of postoperative complications. Our amputation and mortality rates were low and unreportable, but there were no differences by race. CONCLUSIONS: NSTI is rare in the pediatric population and mortality is low. Black patients are disproportionately diagnosed, but these disparities do not extend to disease treatment or outcomes.

Laparoscopic treatment of a patient with multiple organ dysfunction syndrome induced by necrotising fasciitis.

Necrotising fasciitis (NF) is an uncommon surgical emergency that threatens the life and health of patients. We report the treatment of a 76-year-old female patient with NF. The patient developed NF due to chronic poor glycaemic control, which further progressed to multiple organ dysfunction syndrome due to the severity of the hyperglycaemia. After resuscitation at the intensive care unit, surgical treatment was recommended and the patient underwent laparoscopic surgery. She had an uneventful post-operative recovery with aggressive anti-inflammatory therapy, glycaemic control and systemic nutritional support. There were no recurrences during the next 6 months of follow-up. NF should be diagnosed and treated as early as possible to gain valuable treatment time for the patient. Laparoscopic surgery is a treatment option.

Increase in Streptococcal Necrotizing Fasciitis During and After the Coronavirus Disease 2019 Pandemic.

Background: Necrotizing fasciitis (NF) is a life-threatening and rare condition. However, we report and analyze a remarkably high number of NF cases during the coronavirus disease 2019 (COVID-19) pandemic and especially in the first months after the COVID-19 pandemic. Patients and Methods: We conducted a retrospective analysis of 17 cases of NF treated in our clinic between January and May 2023. Data were collected on demographics, comorbidities, risk factors, laboratory findings, and clinical outcomes. For each individual case two risk indicating scores, the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and Laboratory and Anamnestic Risk Indicator for Necrotizing Fasciitis (LARINF) were calculated. Results: In the pandemic years 2021 and 2022 there were 21 and 30 patients with NF, respectively, treated in our clinic. Of the 17 included NF cases in this study from January until May 2023, 16 cases required intensive care unit (ICU) admission, six cases required limb amputation, and four cases resulted in death. The microbiologic examination revealed seven cases of polymicrobial infections, eight cases of monomicrobial infections primarily caused by Streptococcus pyogenes, and two cases without microbial growth. The LRINEC score showed a sensitivity of 82%, whereas the LARINF score demonstrated a sensitivity of 100% for identifying cases of NF. Conclusions: This study highlights a notable increase in NF during and after the COVID-19 pandemic, predominantly associated with Streptococcus pyogenes-induced infections. These cases demonstrate a highly aggressive nature, leading to limb amputation or death in more than half of the cases.

IDENTIFICATION OF POTENTIALLY MODIFIABLE FACTORS TO IMPROVE RECOGNITION AND OUTCOME OF NECROTIZING SOFT-TISSUE INFECTIONS.

ABSTRACT: Background : Necrotizing soft-tissue infections (NSTIs) present a surgical emergency of increasing incidence, which is often misdiagnosed and associated with substantial mortality and morbidity. A retrospective multicenter (11 hospitals) cohort study was initiated to identify the early predictors of misdiagnosis, mortality, and morbidity (skin defect size and amputation). Methods : Patients of all ages who presented with symptoms and were admitted for acute treatment of NSTIs between January 2013 and December 2017 were included. Generalized estimating equation analysis was used to identify early predictors (available before or during the first debridement surgery), with a significance level of P < 0.05. Results : The median age of the cohort (N = 216) was 59.5 (interquartile range = 23.6) years, of which 138 patients (63.9%) were male. Necrotizing soft-tissue infections most frequently originated in the legs (31.0%) and anogenital area (30.5%). More than half of the patients (n = 114, 54.3%) were initially misdiagnosed. Thirty-day mortality was 22.9%. Amputation of an extremity was performed in 26 patients (12.5%). Misdiagnosis was more likely in patients with a higher Charlson Comorbidity Index (ß = 0.20, P = 0.001), and less likely when symptoms started in the anogenital area (ß = -1.20, P = 0.003). Besides the established risk factors for mortality (septic shock and age), misdiagnosis was identified as an independent predictor of 30-day mortality (ß = 1.03, P = 0.01). The strongest predictors of the final skin defect size were septic shock (ß = 2.88, P < 0.001) and a skin-sparing approach to debridement (ß = -1.79, P = 0.002). Conclusion : Recognition of the disease is essential for the survival of patients affected by NSTI, as is adequate treatment of septic shock. The application of a skin-sparing approach to surgical debridement may decrease morbidity.

[Hand infections]. / Infections de la main.

HAND INFECTIONS. Hand and finger infections are very common. They result from the inoculation of a germ through the skin barrier. They can range from simple paronychia to extremely serious necrotizing fasciitis. Certain infections, such as those resulting from bites, have their own specific characteristics, which will determine how they are managed. While management can be medical in the early stages, it is important not to ignore the need for surgical treatment, otherwise serious complications may arise, leading to functional and aesthetic sequelae. Delays in treatment cannot be made up. Any infectious lesion can be potentially serious and must be treated in an appropriate department if there is the slightest doubt.

INFECTIONS DE LA MAIN. Les infections de la main et des doigts sont très fréquentes. Elles résultent de l'inoculation d'un germe à travers la barrière cutanée. Elles vont du simple panaris à la gravissime fasciite nécrosante. Certaines infections, comme celles faisant suite aux morsures, ont des caractéristiques propres dont dépend la prise en charge. Si elle peut être médicale au stade initial, il est important de ne pas méconnaître le moment du traitement chirurgical sous peine de voir survenir des complications graves responsables de séquelles fonctionnelles et esthétiques. Le retard à la prise en charge ne peut être rattrapé. Toute lésion infectieuse peut être potentiellement grave et, au moindre doute, doit être prise en charge dans un service adapté.

Necrotising soft tissue infections. / Nekrotiserende bløtdelsinfeksjoner.

Necrotising soft tissue infections can affect the skin, subcutaneous tissue, superficial fascia, deep fascia and musculature. The infections are severe, they spread quickly and can result in extensive tissue loss. Although rare, morbidity and mortality rates are high. Early clinical identification is crucial for the outcome, and rapid infection control through surgery and targeted antibiotic treatment is needed to save lives. Few prospective clinical trials have been conducted for the treatment of this type of infection. Specific challenges include rapid identification of the condition and the uncertain efficacy of the various treatment options. In this clinical review article, we describe clinical characteristics, diagnostics and treatment.

Emphysematous pyelonephritis with progression to necrotising fasciitis of the posterior cervical region and the retropharyngeal space.

A man in his 50s with diabetes presented with backache, left flank pain and fever. On evaluation, he was found to have emphysematous pyelonephritis of the left kidney with a paranephric abscess extending into the posterior abdominal wall and superiorly up to the posterior chest wall and inferiorly extending up to the posterior superior iliac spine. The management involved the initiation of broad-spectrum antibiotics and percutaneous drainage of the abscess. However, as he continued to worsen symptoms-wise, he underwent computed-enhanced CT of the abdomen and thorax. The imaging revealed the presence of a purulent collection in the left lumbar region with an extension along the posterior cervical region and the retropharyngeal space. He underwent a fasciotomy of the lumbar region. The occurrence of emphysematous pyelonephritis along with necrotising fasciitis is uncommon and requires early aggressive management with broad-spectrum antibiotics and adequate drainage. This emphasises the need for early reimaging if the patient does not settle with antibiotics or percutaneous drainage.