Gangrene

Last updated
Gangrene
Other namesGangrenous necrosis
GangreneFoot.JPG
Dry gangrene affecting the toes as a result of peripheral artery disease
Specialty Infectious disease, surgery, podiatry
Symptoms Change in skin color to red or black, numbness, pain, skin breakdown, coolness [1]
Complications Sepsis, amputation [1] [2]
Types Dry, wet, gas, internal, necrotizing fasciitis [3]
Risk factors Diabetes, peripheral arterial disease, smoking, major trauma, alcoholism, plague, HIV/AIDS, frostbite, Raynaud's syndrome [3] [4]
Diagnostic method Based on symptom, With medical imaging used to identify the underlying cause.
TreatmentDepends on underlying cause [5]
Prognosis Variable
FrequencyUnknown [2]

Gangrene is a type of tissue death caused by a lack of blood supply. [4] Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. [1] The feet and hands are most commonly affected. [1] If the gangrene is caused by an infectious agent, it may present with a fever or sepsis. [1]

Contents

Risk factors include diabetes, peripheral arterial disease, smoking, major trauma, alcoholism, HIV/AIDS, frostbite, influenza, dengue fever, malaria, chickenpox, plague, hypernatremia, radiation injuries, meningococcal disease, Group B streptococcal infection and Raynaud's syndrome. [3] [4] It can be classified as dry gangrene, wet gangrene, gas gangrene, internal gangrene, and necrotizing fasciitis. [3] The diagnosis of gangrene is based on symptoms and supported by tests such as medical imaging. [6]

Treatment may involve surgery to remove the dead tissue, antibiotics to treat any infection, and efforts to address the underlying cause. [5] Surgical efforts may include debridement, amputation, or the use of maggot therapy. [5] Efforts to treat the underlying cause may include bypass surgery or angioplasty. [5] In certain cases, hyperbaric oxygen therapy may be useful. [5] How commonly the condition occurs is unknown. [2]

Signs and symptoms

An illustration showing four different stages of gangrene, including one (Fig. 4 top right) caused by an obstacle to the return of the venous blood due to heart disease. Plate II Mortification (gangrene), Robert Carswell 1830s Wellcome L0074380.jpg
An illustration showing four different stages of gangrene, including one (Fig. 4 top right) caused by an obstacle to the return of the venous blood due to heart disease.

Symptoms may include a change in skin color to red or black, numbness, pain, skin breakdown, and coolness. [1] The feet and hands are most commonly involved. [1]

Causes

Gangrene is caused by a critically insufficient blood supply (e.g., peripheral vascular disease) or infection. [3] [7] [8] It is associated with diabetes [9] and long-term tobacco smoking. [4] [3]

Dry gangrene

Dry gangrene is a form of coagulative necrosis that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. It is not a disease itself, but a symptom of other diseases. [10] The term dry is used only when referring to a limb or to the gut (in other locations, this same type of necrosis is called an infarction, such as myocardial infarction). [11] Dry gangrene is often due to peripheral artery disease, but can be due to acute limb ischemia. As a result, people with atherosclerosis, high cholesterol, diabetes and smokers commonly have dry gangrene. [12] The limited oxygen in the ischemic limb limits putrefaction and bacteria fail to survive. The affected part is dry, shrunken, and dark reddish-black. The line of separation usually brings about complete separation, with eventual falling off of the gangrenous tissue if it is not removed surgically, a process called autoamputation. [12]

Dry gangrene is the result of chronic ischemia without infection. If ischemia is detected early, when ischemic wounds rather than gangrene are present, the process can be treated by revascularization (via vascular bypass or angioplasty). [13] However, once gangrene has developed, the affected tissues are not salvageable. [14] Because dry gangrene is not accompanied by infection, it is not as emergent as gas gangrene or wet gangrene, both of which have a risk of sepsis. Over time, dry gangrene may develop into wet gangrene if an infection develops in the dead tissues. [15]

Diabetes mellitus is a risk factor for peripheral vascular disease, thus for dry gangrene, but also a risk factor for wet gangrene, particularly in patients with poorly controlled blood sugar levels, as elevated serum glucose creates a favorable environment for bacterial infection. [16]

Wet gangrene

Wet gangrene of the foot. Wet gangrene of the foot.jpg
Wet gangrene of the foot.

Wet, or infected, gangrene is characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. In wet gangrene, the tissue is infected by saprogenic microorganisms ( Clostridium perfringens or Bacillus fusiformis , for example), which cause tissue to swell and emit a foul odor. Wet gangrene usually develops rapidly due to blockage of venous (mainly) or arterial blood flow. [12] The affected part is saturated with stagnant blood, which promotes the rapid growth of bacteria. The toxic products formed by bacteria are absorbed, causing systemic manifestation of sepsis and finally death. The affected part is edematous, soft, putrid, rotten, and dark.[ citation needed ]

Because of the high mortality associated with infected gangrene (about 80% without treatment and 20% with treatment), an emergency salvage amputation, such as a guillotine amputation, is often needed to limit systemic effects of the infection. [17] Such an amputation can be converted to a formal amputation, such as a below- or above-knee amputation. [17]

Gas gangrene

Gas gangrene is a bacterial infection that produces gas within tissues. It can be caused by Clostridium , most commonly alpha toxin-producing C. perfringens, or various nonclostridial species. [8] [18] Infection spreads rapidly as the gases produced by the bacteria expand and infiltrate healthy tissue in the vicinity. Because of its ability to quickly spread to surrounding tissues, gas gangrene should be treated as a medical emergency.

Gas gangrene is caused by bacterial exotoxin-producing clostridial species, which are mostly found in soil, and other anaerobes such as Bacteroides and anaerobic streptococci. These environmental bacteria may enter the muscle through a wound and subsequently proliferate in necrotic tissue and secrete powerful toxins that destroy nearby tissue, generating gas at the same time. A gas composition of 5.9% hydrogen, 3.4% carbon dioxide, 74.5% nitrogen, and 16.1% oxygen was reported in one clinical case. [19]

Gas gangrene can cause necrosis, gas production, and sepsis. Progression to toxemia and shock is often very rapid. [20]

Other types

Treatment

Treatment varies based on the severity and type of gangrene. [12]

Lifestyle

Exercises such as walking and massage therapy may be tried. [12]

Medication

Medications may include pain management, medications that promote circulation in the circulatory system and antibiotics. Since gangrene is associated with periodic pain caused by too little blood flow, pain management is important so patients can continue doing exercises that promote circulation. Pain management medications can include opioids and opioid-like analgesics. Since gangrene is a result of ischemia, circulatory system management is important. These medications can include antiplatelet drug, anticoagulant, and fibrinolytics. As infection is often associated with gangrene, antibiotics are often a critical component of its treatment. The life-threatening nature of gangrene requires treatment with intravenous antibiotics in an inpatient setting. [12] Antibiotics alone are not effective because they may not penetrate infected tissues sufficiently. [25]

Surgery

Surgical removal of all dead tissue, however, is the mainstay of treatment for gangrene. Often, gangrene is associated with underlying infection, thus the gangrenous tissue must be debrided to hinder the spread of the associated infection. The extent of surgical debridement needed depends on the extent of the gangrene and may be limited to the removal of a finger, toe, or ear, but in severe cases may involve a limb amputation. [12]

Dead tissue alone does not require debridement, and in some cases, such as dry gangrene, the affected part falls off (autoamputates), making surgical removal unnecessary. Waiting for autoamputation, however, may cause health complications as well as decreased quality of life. [12]

After the gangrene is treated with debridement and antibiotics, the underlying cause can be treated. In the case of gangrene due to critical limb ischemia, revascularization can be performed to treat the underlying peripheral underlateral artery disease.[ citation needed ]

Ischemic disease of the legs is the most common reason for amputations. In about a quarter of these cases, the other side requires amputation in the next three years. [26]

Angioplasty should be considered if severe blockage in lower leg vessels (tibial and peroneal artery) leads to gangrene. [27]

Other

Hyperbaric oxygen therapy treatment is used to treat gas gangrene. It increases pressure and oxygen content to allow blood to carry more oxygen to inhibit anaerobic organism growth and reproduction. [28]

Regenerative medical treatments and stem-cell therapies have successfully altered gangrene and ulcer prognosis.[ citation needed ]

History

Confederate Army Private Milton E. Wallen lies in bed with a gangrenous amputated arm Milton Wallen, CWMI098C, National Museum of Health and Medicine (373561781).jpg
Confederate Army Private Milton E. Wallen lies in bed with a gangrenous amputated arm

As early as 1028, flies and maggots were commonly used to treat chronic wounds or ulcers to prevent or arrest necrotic spread, [29] as some species of maggots consume only dead flesh, leaving nearby living tissue unaffected. This practice largely died out after the introduction of antibiotics to the range of treatments for wounds. In recent times, however, maggot therapy has regained some credibility and is sometimes employed with great efficacy in cases of chronic tissue necrosis. [30] [31] [32]

The French Baroque composer Jean-Baptiste Lully contracted gangrene in January 1687 when, while conducting a performance of his Te Deum , he stabbed his own toe with his pointed staff (which was used as a baton). The disease spread to his leg, but the composer refused to have his toe amputated, which eventually led to his death in March of that year. [33]

French King Louis XIV died of gangrene in his leg on 1 September 1715, four days prior to his 77th birthday. [34]

Sebald Justinus Brugmans, Professor at Leyden University, from 1795 on Director of the Medical Bureau of the Batavian Republic, and inspector-general of the French Imperial Military Health-Service in 1811, became a leading expert in the fight against hospital-gangrene and its prevention. He wrote a treatise on gangrene in 1814 in which he meticulously analyzed and explained the causes of this dreadful disease, which he was convinced was contagious. He completed his entry with a thorough evaluation of all possible and well experienced sanitary regulations. His work was very well received and was instrumental in convincing most later authors that gangrene was a contagious disease. [35] [36]

John M. Trombold wrote: "Middleton Goldsmith, a surgeon in the Union Army during the American Civil War, meticulously studied hospital gangrene and developed a revolutionary treatment regimen. The cumulative Civil War hospital gangrene mortality was 45%. Goldsmith's method, which he applied to over 330 cases, yielded a mortality under 3%." [37] Goldsmith advocated the use of debridement and topical and injected bromide solutions on infected wounds to reduce the incidence and virulence of "poisoned miasma". Copies of his book [38] were issued to Union surgeons to encourage the use of his methods. [39]

Etymology

The etymology of gangrene derives from the Latin word gangraena and from the Greek gangraina (γάγγραινα), which means "putrefaction of tissues". [40]

Related Research Articles

<span class="mw-page-title-main">Necrosis</span> Unprogrammed cell death caused by external cell injury

Necrosis is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is often regarded as one of the founders of modern pathology. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated digestion of cell components. In contrast, apoptosis is a naturally occurring programmed and targeted cause of cellular death. While apoptosis often provides beneficial effects to the organism, necrosis is almost always detrimental and can be fatal.

<span class="mw-page-title-main">Ulcer (dermatology)</span> Type of cutaneous condition

An ulcer is a sore on the skin or a mucous membrane, accompanied by the disintegration of tissue. Ulcers can result in complete loss of the epidermis and often portions of the dermis and even subcutaneous fat. Ulcers are most common on the skin of the lower extremities and in the gastrointestinal tract. An ulcer that appears on the skin is often visible as an inflamed tissue with an area of reddened skin. A skin ulcer is often visible in the event of exposure to heat or cold, irritation, or a problem with blood circulation.

<span class="mw-page-title-main">Necrotizing fasciitis</span> Infection that results in the death of the bodys soft tissue

Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.

<span class="mw-page-title-main">Peripheral artery disease</span> Medical condition

Peripheral artery disease (PAD) is a vascular disorder abnormal narrowing of arteries other than those that supply the heart or brain. PAD can happen in any blood vessel, but it is more common in the legs than the arms.

<span class="mw-page-title-main">Osteomyelitis</span> Infection of the bones

Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the feet, spine, and hips are most commonly involved in adults.

<span class="mw-page-title-main">Cellulitis</span> Bacterial infection of the inner layers of the skin called the dermis

Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of the area of redness are generally not sharp and the skin may be swollen. While the redness often turns white when pressure is applied, this is not always the case. The area of infection is usually painful. Lymphatic vessels may occasionally be involved, and the person may have a fever and feel tired.

In medical and surgical therapy, revascularization is the restoration of perfusion to a body part or organ that has had ischemia. It is typically accomplished by surgical means. Vascular bypass and angioplasty are the two primary means of revascularization.

<span class="mw-page-title-main">Maggot therapy</span> Wound care by maggot therapy

Maggot therapy is a type of biotherapy involving the introduction of live, disinfected maggots into non-healing skin and soft-tissue wounds of a human or other animal for the purpose of cleaning out the necrotic (dead) tissue within a wound (debridement), and disinfection.

<span class="mw-page-title-main">Gas gangrene</span> Human bacterial infection

Gas gangrene is a bacterial infection that produces tissue gas in gangrene. This deadly form of gangrene usually is caused by Clostridium perfringens bacteria. About 1,000 cases of gas gangrene are reported yearly in the United States.

A chronic wound is a wound that does not heal in an orderly set of stages and in a predictable amount of time the way most wounds do; wounds that do not heal within three months are often considered chronic. Chronic wounds seem to be detained in one or more of the phases of wound healing. For example, chronic wounds often remain in the inflammatory stage for too long. To overcome that stage and jump-start the healing process, a number of factors need to be addressed such as bacterial burden, necrotic tissue, and moisture balance of the whole wound. In acute wounds, there is a precise balance between production and degradation of molecules such as collagen; in chronic wounds this balance is lost and degradation plays too large a role.

<span class="mw-page-title-main">Lymphangitis</span> Medical condition

Lymphangitis is an inflammation or an infection of the lymphatic channels that occurs as a result of infection at a site distal to the channel. It may present as long red streaks spreading away from the site of infection. It is a possible medical emergency as involvement of the lymphatic system allows for an infection to spread rapidly. The most common cause of lymphangitis in humans is bacteria, in which case sepsis and death could result within hours if left untreated. The most commonly involved bacteria include Streptococcus pyogenes and hemolytic streptococci. In some cases, it can be caused by viruses such as mononucleosis or cytomegalovirus, as well as specific conditions such as tuberculosis or syphilis, and the fungus Sporothrix schenckii. Lymphangitis is sometimes mistakenly called "blood poisoning". In reality, "blood poisoning" is synonymous with sepsis.

<span class="mw-page-title-main">Fournier gangrene</span> Medical condition

Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia or perineum. It commonly occurs in older men, but it can also occur in women and children. It is more likely to occur in people with diabetes or alcoholism or those who are immunocompromised.

An open fracture, also called a compound fracture, is a type of bone fracture that has an open wound in the skin near the fractured bone. The skin wound is usually caused by the bone breaking through the surface of the skin. An open fracture can be life threatening or limb-threatening due to the risk of a deep infection and/or bleeding. Open fractures are often caused by high energy trauma such as road traffic accidents and are associated with a high degree of damage to the bone and nearby soft tissue. Other potential complications include nerve damage or impaired bone healing, including malunion or nonunion. The severity of open fractures can vary. For diagnosing and classifying open fractures, Gustilo-Anderson open fracture classification is the most commonly used method. This classification system can also be used to guide treatment, and to predict clinical outcomes. Advanced trauma life support is the first line of action in dealing with open fractures and to rule out other life-threatening condition in cases of trauma. The person is also administered antibiotics for at least 24 hours to reduce the risk of an infection.

<i>Clostridium septicum</i> Species of bacterium

Clostridium septicum is a gram positive, spore forming, obligate anaerobic bacterium.

<span class="mw-page-title-main">Arterial insufficiency ulcer</span> Medical condition

Arterial insufficiency ulcers are mostly located on the lateral surface of the ankle or the distal digits. They are commonly caused by peripheral artery disease (PAD).

Proteases are in use, or have been proposed or tried, for a number of purposes related to medicine or surgery. Some preparations involving protease have undergone successful clinical trials and have regulatory authorization; and some further ones have shown apparently useful effects in experimental medical studies. Proteases have also been used by proponents of alternative therapies, or identified in materials of traditional or folk medicine. A serine protease of human origin, activated protein C, was produced in recombinant form and marketed as Drotrecogin alfa and licensed for intensive-care treatment of severe sepsis. It was voluntarily withdrawn by the manufacturer in 2011 after being shown to be ineffective.

<i>Clostridium tertium</i> Species of bacterium

Clostridium tertium is an anaerobic, motile, gram-positive bacterium. Although it can be considered an uncommon pathogen in humans, there has been substantial evidence of septic episodes in human beings. C. tertium is easily decolorized in Gram-stained smears and can be mistaken for a Gram-negative organism. However, C.tertium does not grow on selective media for Gram-negative organisms.

<span class="mw-page-title-main">Diabetic foot ulcer</span> Medical condition

Diabetic foot ulcer is a breakdown of the skin and sometimes deeper tissues of the foot that leads to sore formation. It may occur due to a variety of mechanisms. It is thought to occur due to abnormal pressure or mechanical stress chronically applied to the foot, usually with concomitant predisposing conditions such as peripheral sensory neuropathy, peripheral motor neuropathy, autonomic neuropathy or peripheral arterial disease. It is a major complication of diabetes mellitus, and it is a type of diabetic foot disease. Secondary complications to the ulcer, such as infection of the skin or subcutaneous tissue, bone infection, gangrene or sepsis are possible, often leading to amputation.

Chronic limb threatening ischemia (CLTI), also known as critical limb ischemia (CLI), is an advanced stage of peripheral artery disease (PAD). It is defined as ischemic rest pain, arterial insufficiency ulcers, and gangrene. The latter two conditions are jointly referred to as tissue loss, reflecting the development of surface damage to the limb tissue due to the most severe stage of ischemia. Compared to the other manifestation of PAD, intermittent claudication, CLI has a negative prognosis within a year after the initial diagnosis, with 1-year amputation rates of approximately 12% and mortality of 50% at 5 years and 70% at 10 years.

<span class="mw-page-title-main">Diabetic foot infection</span> Medical condition

Diabetic foot infection is any infection of the foot in a diabetic person. The most frequent cause of hospitalization for diabetic patients is due to foot infections. Symptoms may include pus from a wound, redness, swelling, pain, warmth, tachycardia, or tachypnea. Complications can include infection of the bone, tissue death, amputation, or sepsis. They are common and occur equally frequently in males and females. Older people are more commonly affected.

References

  1. 1 2 3 4 5 6 7 "Gangrene Symptoms". NHS. 13 October 2015. Retrieved 12 December 2017.
  2. 1 2 3 "Gangrene". patient.info. 12 March 2014. Retrieved 12 December 2017.
  3. 1 2 3 4 5 6 "Gangrene Causes". NHS. 13 October 2015. Retrieved 12 December 2017.
  4. 1 2 3 4 "Gangrene". NHS. 13 October 2015. Retrieved 12 December 2017.
  5. 1 2 3 4 5 "Gangrene Treatment". NHS. Retrieved 12 December 2017.
  6. ↑ "Gangrene Diagnosis". NHS. 13 October 2015. Retrieved 12 December 2017.
  7. ↑ Gardner, AW; Afaq, A (November–December 2008). "Management of lower extremity peripheral arterial disease". Journal of Cardiopulmonary Rehabilitation and Prevention. 28 (6): 349–57. doi:10.1097/HCR.0b013e31818c3b96. PMC   2743684 . PMID   19008688.
  8. 1 2 Yang, Z; Hu, J; Qu, Y; Sun, F; Leng, X; Li, H; Zhan, S (3 December 2015). "Interventions for treating gas gangrene". The Cochrane Database of Systematic Reviews. 2015 (12): CD010577. doi:10.1002/14651858.CD010577.pub2. PMC   8652263 . PMID   26631369.
  9. ↑ Korzon-Burakowska, A; Dziemidok, P (December 2011). "Diabetic foot-the need for comprehensive multidisciplinary approach". Annals of Agricultural and Environmental Medicine. 18 (2): 314–17. PMID   22216805.
  10. ↑ Smith, Tyler (2015). Gangrene Management: Today and Tomorrow. Hayle Medical. ISBN   978-1632412232.[ page needed ]
  11. ↑ Cross, Simon (2018). Underwood's Pathology: A Clinical Approach (7th ed.). Elsevier Health Sciences. p. 124. ISBN   9780702072109 . Retrieved 8 April 2020.
  12. 1 2 3 4 5 6 7 8 Al Wahbi, Abdullah (2018-06-01). "Autoamputation of diabetic toe with dry gangrene: a myth or a fact?". Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 11: 255–264. doi: 10.2147/DMSO.S164199 . ISSN   1178-7007. PMC   5987754 . PMID   29910628.
  13. ↑ Aiello A, Anichini R, Brocco E, Caravaggi C, Chiavetta A, Cioni R, Da Ros R, De Feo ME, Ferraresi R, Florio F, Gargiulo M, Galzerano G, Gandini R, Giurato L, Graziani L, Mancini L, Manzi M, Modugno P, Setacci C, Uccioli L (2014). "Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE)". Nutr Metab Cardiovasc Dis. 24 (4): 355–69. doi: 10.1016/j.numecd.2013.12.007 . PMID   24486336.
  14. ↑ Gerhard-Herman, MD; Gornik, HL; Barrett, C; Barshes, NR; Corriere, MA; Drachman, DE; Fleisher, LA; Fowkes, FG; Hamburg, NM; Kinlay, S; Lookstein, R; Misra, S; Mureebe, L; Olin, JW; Patel, RA; Regensteiner, JG; Schanzer, A; Shishehbor, MH; Stewart, KJ; Treat-Jacobson, D; Walsh, ME (2017). "2016 AHA/ACC Guideline on the Management of Patients With Lower Extremity Peripheral Artery Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines". Circulation. 135 (12): e726–79. doi:10.1161/CIR.0000000000000471. PMC   5477786 . PMID   27840333.
  15. ↑ Nather, Aziz (2013). The diabetic foot. World Scientific. ISBN   978-9814417006.
  16. ↑ Vayvada, H; Demirdover, C; Menderes, A; Karaca, C (August 2013). "Necrotising fasciitis in the central part of the body: diagnosis, management and review of the literature". International Wound Journal. 10 (4): 466–72. doi:10.1111/j.1742-481x.2012.01006.x. PMC   7950796 . PMID   22694053. S2CID   5693425.
  17. 1 2 Tisi, PV; Than, MM (8 April 2014). "Type of incision for below knee amputation". The Cochrane Database of Systematic Reviews. 4 (4): CD003749. doi:10.1002/14651858.CD003749.pub3. PMC   7154343 . PMID   24715679.
  18. ↑ Sakurai, J.; Nagahama, M.; Oda, M. (November 2004). "Clostridium perfringens alpha-toxin: characterization and mode of action". Journal of Biochemistry . 136 (5): 569–74. doi:10.1093/jb/mvh161. PMID   15632295. S2CID   12940936.
  19. ↑ Chi CH, Chen KW, Huang JJ, Chuang YC, Wu MH (December 1995). "Gas composition in Clostridium septicum gas gangrene". Journal of the Formosan Medical Association. 94 (12): 757–59. PMID   8541740.
  20. ↑ "Gas Gangrene". The Lecturio Medical Concept Library. Retrieved 22 July 2021.
  21. ↑ "For Clinicians: Type II Necrotizing Fasciitis | CDC". www.cdc.gov. 2019-02-21. Retrieved 2019-08-05.
  22. ↑ Sivapathasundharam, B.; Rajendran, Arya (30 June 2012). Shafer's Textbook of Oral Pathology. Elsevier Health Sciences. p. 333. ISBN   978-81-312-3800-4.
  23. ↑ Levenson, RB; Singh, AK; Novelline, RA (March–April 2008). "Fournier gangrene: role of imaging". Radiographics. 28 (2): 519–28. doi:10.1148/rg.282075048. PMID   18349455. S2CID   2930176.
  24. ↑ Warkentin, TE (August 2010). "Agents for the treatment of heparin-induced thrombocytopenia". Hematology/Oncology Clinics of North America. 24 (4): 755–75. doi:10.1016/j.hoc.2010.05.009. PMID   20659659.
  25. ↑ Lipsky BA (December 1999). "Evidence-based antibiotic therapy of diabetic foot infections". FEMS Immunol. Med. Microbiol. 26 (3–4): 267–76. doi: 10.1016/s0928-8244(99)00143-1 . PMID   10575138.
  26. ↑ Amputations of the Lower Extremity at eMedicine
  27. ↑ "Angioplasty and stent placement – peripheral arteries" . Retrieved July 24, 2013.
  28. ↑ Liu R, Li L, Yang M, Boden G, Yang G (2013). "Systematic review of the effectiveness of hyperbaric oxygenation therapy in the management of chronic diabetic foot ulcers". Mayo Clin. Proc. 88 (2): 166–75. doi:10.1016/j.mayocp.2012.10.021. PMID   23374620.
  29. ↑ Shi, Eric; Shofler, David (2014). "Maggot debridement therapy: A systematic review". British Journal of Community Nursing. 19: S6–S13. doi:10.12968/bjcn.2014.19.Sup12.S6. PMID   25478859.
  30. ↑ "Product Classification: Maggots, Medical". fda.gov. US: Food and Drug Administration.
  31. ↑ "FDA CDRH 510(k) summary" (PDF).
  32. ↑ Sun, Xinjuan; Jiang, Kechun; Chen, Jingan; et al. (2014). "A systematic review of maggot debridement therapy for chronically infected wounds and ulcers". International Journal of Infectious Diseases . 25: 32–7. doi: 10.1016/j.ijid.2014.03.1397 . PMID   24841930.
  33. ↑ "Music Trivia – The Death of Lully". The Musician's Lounge. Utah Symphony Orchestra. August 2010. Retrieved March 7, 2017.
  34. ↑ Laurenson, John (21 November 2015). "The strange death of Louis XIV". The Spectator. Retrieved 12 March 2017.
  35. ↑ Teun van Heiningen, "Sebald Justinus Brugmans' strijd tegen de hospitaalversterving", Leiden University, URN:NBN:NL:UI:10-1-112565
  36. ↑ Brugmans, Sebald Justinus (May 24, 1814). "Verhandeling ter beantwoording der vrage: Kan de gesteldheid en zamenstelling van den dampkring, welke onmiddelijk tot de Hospitaal-versterving (Gangraena NosocomialisZ) aanleiding geeft, door Natuur- of Scheikundige middelen worden ontdekt?". J. van der Heij – via Google Books.
  37. ↑ Trombold JM (2011). "Gangrene therapy and antisepsis before lister: the civil war contributions of Middleton Goldsmith of Louisville". Am Surg. 77 (9): 1138–43. doi: 10.1177/000313481107700924 . PMID   21944621. S2CID   26732207.
  38. ↑ A report on hospital gangrene, erysipelas and pyaemia. 1863
  39. ↑ Watson, Dr. Scott. "Hospital Gangrene During The Civil War – Civil War Medicine" . Retrieved 2014-04-15.
  40. ↑ Liddell & Scott's Lexicon, Oxford University Press, 1963 edition
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.