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Concept: Gangrene


The tips of mammalian digits can regenerate after amputation, like those of amphibians. It is unknown why this capacity is limited to the area associated with the nail. Here we show that nail stem cells (NSCs) reside in the proximal nail matrix and that the mechanisms governing NSC differentiation are coupled directly with their ability to orchestrate digit regeneration. Early nail progenitors undergo Wnt-dependent differentiation into the nail. After amputation, this Wnt activation is required for nail regeneration and also for attracting nerves that promote mesenchymal blastema growth, leading to the regeneration of the digit. Amputations proximal to the Wnt-active nail progenitors result in failure to regenerate the nail or digit. Nevertheless, β-catenin stabilization in the NSC region induced their regeneration. These results establish a link between NSC differentiation and digit regeneration, and suggest that NSCs may have the potential to contribute to the development of novel treatments for amputees.

Concepts: Developmental biology, Stem cell, Regeneration, Amputation, Gangrene, Toe


Pirogow’s amputation at the ankle presents a valuable alternative to lower leg amputation for patients with the corresponding indications. Although this method offers numerous advantages for the patient, such as the ability to stay mobile without the use of a prosthesis, it is rarely performed (0.1% of all lower limb amputations). The results of the operations on 20 patients were objectified 12 months after the operation using a patient questionnaire (Ankle Score), and these results were then compared to those of 20 pa-tients who underwent lower leg amputation. Using a point system the criteria pain, functional and radiological assessment, difference in leg length, and mobility without prosthesis were recorded and evaluated. 65% of those questioned who were amputated following the Pirogow method indicated an excellent or very good result, in the control group 60% of those having undergone a lower leg amputation responded similarly, indicating an excellent or very good result.In 30% in the Pirogow group in contrast to 20% after lower leg amputation postoperative complications lead to a revision-operation. In patients suffering from diabetes or restricted perfusion of the lower extremity an amputation at the level of the ankle has to be considered critically keeping the necessity of a revision-operation in mind. However, if it can be carried out successfully, the benefits of Pirogow-amputation are found in the significantly reduced difference in leg length and the increase in mobility without prosthesis.

Concepts: Cancer, Patient, Patience, Amputation, Prosthesis, Limb, Human leg, Gangrene


WHAT IS KNOWN AND OBJECTIVE: To the best of our knowledge, there has been no published study designed to identify the most appropriate duration of antibiotic therapy in lower extremity skin and skin structure infections in diabetic patients [aka “diabetic foot infections” (DFI)] post-amputation. However, recent guidelines published by the Infectious Diseases Society of America (IDSA) provide recommendations for treatment duration in these patients. Therefore, our objective is to review the literature evaluating antibiotic treatment in DFI to determine if the IDSA guidelines are reasonable. COMMENT: Evidence for the use of antibiotics after amputation comes largely from perioperative surgical prophylaxis studies evaluating the rate of infection after amputation. Three such studies were identified; 2 found a 5-day course of antibiotics post-amputation resulted in a reduction of infection rate, while 1 found no additional benefit. Comparative antibiotic studies in DFI also offers evidence for treatment duration, of which, 10 studies were identified. Five included patients who received amputations; however, only 1 reported treatment outcomes in a subset of diabetics requiring amputation. In this study, the authors concluded that antibiotic treatment is likely necessary after amputation. WHAT IS NEW AND CONCLUSION: Given the general lack of data, we recommend that post-operative treatment duration be individualized, and, until further studies are done, it seems reasonable to adhere to the recommendation provided by the 2012 IDSA DFI guidelines for a 2-5 day course of antibiotic therapy post-operatively when no residual infected tissue remains.

Concepts: Disease, Infectious disease, Bacteria, Infection, Surgery, Transmission and infection of H5N1, Antibiotic, Gangrene


BACKGROUND: Necrotizing fasciitis (NF) is a potentially lethal infection involving the skin, subcutaneous tissue, and fascia. The Laboratory Risk Indicator for Necrotizing fasciitis (LRINEC) score has been proposed as a way of using abnormal laboratory values to distinguish between severe cellulitis and necrotizing fasciitis. OBJECTIVES: The utility of the LRINEC system, including a review of current literature on this scoring system, is discussed. CASE REPORT: A case of a 37-year-old man is presented. As part of the diagnostic work-up, appropriate laboratory tests necessary to calculate a LRINEC score were obtained. Despite a LRINEC score of 0, NF was later confirmed at surgery. CONCLUSIONS: Although the LRINEC score has been proposed as a robust way of identifying patients with early NF, it failed to detect NF in the patient reported here. NF should thus remain primarily a disease of clinical suspicion, and this suspicion should trump the LRINEC score.

Concepts: Patient, Inflammations, Skin, Necrotizing fasciitis, Dermis, Gangrene


Cancrum oris is a gangrenous stomatitis arising from a periodontal infection and leading to severe soft tissue and bone destruction. The pathology involves numerous factors including local thrombosis, vascularitis, necrotizing gingivitis, immunodeficiency, Gram negative and anaerobic infection. It is usually a disease of infants and malnourished children in tropical areas often occurring after a debilitating disease like measles [3]. Burkitt lymphoma is a highly aggressive non-Hodgkin lymphoma first described by Burkitt in 1958 in African children from areas holoendemic for malaria. It is the first cancer of African child [6]. The association between Burkitt lymphoma and cancrum oris is non common. We report in the present study three cases of this association at the Academic Hospital Yalgado Ouedraogo of Ouagadougou. This association poses a problem of late diagnosis with difficulties in therapeutic management.

Concepts: AIDS, Cancer, Infectious disease, Diseases and disorders, Africa, Infection, Gangrene, Noma


Necrotizing fasciitis (NF) of odontogenic origin affecting the head and neck region is a rare but serious clinical condition, which, if diagnosed late, can lead to a fatal outcome. The early diagnosis of necrotizing fasciitis can be difficult. Delay in diagnosis leads to increase in the area of necrosis with a resulting increase in cosmetic deformity and life-threatening complication. In this study, we present two cases of elderly patients with aggressive NF affecting the neck and anterior mediastinum, which were of odontogenic origin.

Concepts: Head and neck anatomy, Head and neck, Death, Medical terms, Pneumonia, Necrotizing fasciitis, Necrosis, Gangrene


The goals of treatment for critical limb ischemia (CLI) are alleviation of ischemic rest pain, healing of arterial insufficiency ulcers, and improving quality of life, thereby preventing limb loss and CLI-related mortality. Arterial revascularization is the foundation of a contemporary approach to promote amputation-free survival. Angiosome-directed revascularization has become a popular theory of reperfusion, whereby anatomically directed arterial flow is restored straight to the wound bed. Innovations in endovascular revascularization combined with a multidisciplinary strategy of wound care accelerate progress in CLI management. This article highlights advances in CLI management, including the clinical relevance of angiosome-directed revascularization, and provides considerations for future treatment of CLI.

Concepts: Wound healing, Blood vessel, Ischemia, Reperfusion injury, Ischemic cascade, Cardiovascular system, Gangrene


Background The treatment of peripheral artery disease with percutaneous transluminal angioplasty is limited by the occurrence of vessel recoil and restenosis. Drug-coated angioplasty balloons deliver antiproliferative agents directly to the artery, potentially improving vessel patency by reducing restenosis. Methods In this single-blind, randomized trial conducted at 54 sites, we assigned, in a 2:1 ratio, 476 patients with symptomatic intermittent claudication or ischemic pain while at rest and angiographically significant atherosclerotic lesions to angioplasty with a paclitaxel-coated balloon or to standard angioplasty. The primary efficacy end point was primary patency of the target lesion at 12 months (defined as freedom from binary restenosis or from the need for target-lesion revascularization). The primary safety end point was a composite of freedom from perioperative death from any cause and freedom at 12 months from limb-related death (i.e., death from a medical complication related to a limb), amputation, and reintervention. Results The two groups were well matched at baseline; 42.9% of the patients had diabetes, and 34.7% were current smokers. At 12 months, the rate of primary patency among patients who had undergone angioplasty with the drug-coated balloon was superior to that among patients who had undergone conventional angioplasty (65.2% vs. 52.6%, P=0.02). The proportion of patients free from primary safety events was 83.9% with the drug-coated balloon and 79.0% with standard angioplasty (P=0.005 for noninferiority). There were no significant between-group differences in functional outcomes or in the rates of death, amputation, thrombosis, or reintervention. Conclusions Among patients with symptomatic femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon resulted in a rate of primary patency at 12 months that was higher than the rate with angioplasty with a standard balloon. The drug-coated balloon was noninferior to the standard balloon with respect to safety. (Funded by Lutonix-Bard; LEVANT 2 number, NCT01412541 .).

Concepts: Atherosclerosis, Cardiology, Blood vessel, Angioplasty, Vascular surgery, Gangrene, Intermittent claudication, Angiology


Very little is known about the factors that cause variation in regenerative potential within and between species. Here, we used a genetic approach to identify heritable genetic factors that explain variation in tail regenerative outgrowth. A hybrid ambystomatid salamander (Ambystoma mexicanum x A. andersoni) was crossed to an A. mexicanum and 217 offspring were induced to undergo metamorphosis and attain terrestrial adult morphology using thyroid hormone. Following metamorphosis, each salamander’s tail tip was amputated and allowed to regenerate, and then amputated a second time and allowed to regenerate. Also, DNA was isolated from all individuals and genotypes were determined for 187 molecular markers distributed throughout the genome. The area of tissue that regenerated after the first and second amputations was highly positively correlated across males and females. Males presented wider tails and regenerated more tail tissue during both episodes of regeneration. Approximately 66-68% of the variation in regenerative outgrowth was explained by tail width, while tail length and genetic sex did not explain a significant amount of variation. A small effect QTL was identified as having a sex-independent effect on tail regeneration, but this QTL was only identified for the first episode of regeneration. Several molecular markers significantly affected regenerative outgrowth during both episodes of regeneration, but the effect sizes were small (<4%) and correlated with tail width. The results show that ambysex and minor effect QTL explain variation in adult tail morphology and importantly, tail width. In turn, tail width at the amputation plane largely determines the rate of regenerative outgrowth. Because amputations in this study were made at approximately the same position of the tail, our results resolve an outstanding question in regenerative biology: regenerative outgrowth positively co-varies as a function of tail width at the amputation site.

Concepts: DNA, Genetics, Cancer, Regeneration, Amputation, Gangrene


Necrotizing fasciitis (NF) caused by flesh-eating bacteria is associated with high case fatality. In an earlier study, we reported infection of an immunocompetent individual with multiple strains of Aeromonas hydrophila (NF1-NF4), the latter three constituted a clonal group whereas NF1 was phylogenetically distinct. To understand the complex interactions of these strains in NF pathophysiology, a mouse model was used, whereby either single or mixed A. hydrophila strains were injected intramuscularly. NF2, which harbors exotoxin A (exoA) gene, was highly virulent when injected alone, but its virulence was attenuated in the presence of NF1 (exoA-minus). NF1 alone, although not lethal to animals, became highly virulent when combined with NF2, its virulence augmented by cis-exoA expression when injected alone in mice. Based on metagenomics and microbiological analyses, it was found that, in mixed infection, NF1 selectively disseminated to mouse peripheral organs, whereas the other strains (NF2, NF3, and NF4) were confined to the injection site and eventually cleared. In vitro studies showed NF2 to be more effectively phagocytized and killed by macrophages than NF1. NF1 inhibited growth of NF2 on solid media, but ExoA of NF2 augmented virulence of NF1 and the presence of NF1 facilitated clearance of NF2 from animals either by enhanced priming of host immune system or direct killing via a contact-dependent mechanism.

Concepts: HIV, Immune system, Infectious disease, Bacteria, Microbiology, Necrotizing fasciitis, Toxin, Gangrene