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1.  Paraspinal Abscess Communicated with Epidural Abscess after Extra-Articular Facet Joint Injection 
Yonsei Medical Journal  2007;48(4):711-714.
Facet joint injection is considered to be a safe procedure. There have been some reported cases of facet joint pyogenic infection and also 3 cases of facet joint infection spreading to paraspinal muscle and epidural space due to intra-articular injections. To the author's knowledge, paraspinal and epidural abscesses after facet joint injection without facet joint pyogenic infection have not been reported. Here we report a case in which extra-articular facet joint injection resulted in paraspinal and epidural abscesses without facet joint infection. A 50-year-old man presenting with acute back pain and fever was admitted to the hospital. He had the history of diabetes mellitus and had undergone the extra-articular facet joint injection due to a facet joint syndrome diagnosis at a private clinic 5 days earlier. Physical examination showed tenderness over the paraspinal region. Magnetic resonance image (MRI) demonstrated the paraspinal abscess around the fourth and fifth spinous processes with an additional epidural abscess compressing the thecal sac. The facet joints were preserved. The laboratory results showed a white blood cell count of 14.9 × 109 per liter, an erythrocyte sedimentation rate of 52mm/hour, and 10.88mg/dL of C-reactive protein. Laminectomy and drainage were performed. The pus was found in the paraspinal muscles, which was communicated with the epidural space through a hole in the ligamentum flavum. Cultures grew Staphylococcus aureus. Paraspinal abscess communicated with epidural abscess is a rare complication of extra-articular facet joint injection demonstrating an abscess formation after an invasive procedure near the spine is highly possible.
doi:10.3349/ymj.2007.48.4.711
PMCID: PMC2628056  PMID: 17722247
Complication; infection; injection; facet joint
2.  Sternoclavicular joint septic arthritis following paraspinal muscle abscess and septic lumbar spondylodiscitis with epidural abscess in a patient with diabetes: a case report 
Background
Septic arthritis of the sternoclavicular joint (SCJ) is extremely rare, and usually appears to result from hematogenous spread. Predisposing factors include immunocompromising diseases such as diabetes.
Case presentation
A 61-year-old man with poorly controlled diabetes mellitus presented to our emergency department with low back pain, high fever, and a painful mass over his left SCJ. He had received two epidural blocks over the past 2 weeks for severe back and leg pain secondary to lumbar disc herniation. He did not complain of weakness or sensory changes of his lower limbs, and his bladder and bowel function were normal. He had no history of shoulder injection, subclavian vein catheterization, intravenous drug abuse, or focal infection including tooth decay. CT showed an abscess of the left SCJ, with extension into the mediastinum and sternocleidomastoid muscle, and left paraspinal muscle swelling at the level of L2. MRI showed spondylodiscitis of L3-L4 with a contiguous extradural abscess. Staphylococcus aureus was isolated from cultures of aspirated pus from his SCJ, and from his urine and blood. The SCJ abscess was incised and drained, and appropriate intravenous antibiotic therapy was administered. Two weeks after admission, the purulent discharge from the left SCJ had completely stopped, and the wound showed improvement. He was transferred to another ward for treatment of the ongoing back pain.
Conclusion
Diabetic patients with S. aureus bacteremia may be at risk of severe musculoskeletal infections via hematogenous spread.
doi:10.1186/1471-227X-12-7
PMCID: PMC3447652  PMID: 22702399
Sternoclavicular joint; Septic arthritis; Spondylitis; Epidural abscess; Epidural anesthesia; Staphylococcus aureus
3.  Isolated septic facet joint arthritis as a rare cause of acute and chronic low back pain – a case report and literature review 
Polish Journal of Radiology  2012;77(4):72-76.
Summary
Background:
The most common cause of low back pain is degenerative disease of the intervertebral disc and other structures of the lumbar spine. However, in some cases other less frequent causes of such pain can be seen, for example septic facet joint arthritis. Until now, only 40 cases of such inflammatory changes within the spine have been reported in the literature. The disease is probably underestimated due to improper diagnostic pathway.
Case Report:
The authors describe a case of a 53-year-old woman who was repeatedly hospitalized during a five-month period because of an acute, severe low back pain, with sphincter dysfunction, partially resembling sciatic symptoms. Physical examinations revealed also focal tenderness in the area of the lumbar spine. Inflammatory markers (ESR – erythrocyte sedimentation rate, CRP – C-reactive protein) were elevated. Conservative analgetic treatment brought only partial and temporary relief of the pain and symptoms. The final accurate diagnosis of isolated septic facet joint arthritis at the level of L5/S1 was established after several months from the onset of the first symptoms, after performing various imaging examinations, including bone scintigraphy as well as CT and MRI of the lumbosacral spine. The patient fully recovered after antibiotic therapy and surgery, which was proven in several follow-up examinations showing no relevant pathology of the lumbar spine. The authors broadly describe the etiology and clinical symptoms of the septic facet joint arthritis as well as the significant role of imaging methods, especially MRI, in diagnostic process. The authors also discuss currently available treatment options, both conservative and surgical.
Conclusions:
The diagnostic procedure of septic facet joint arthritis requires several steps to be taken. Establishing a correct diagnosis may be difficult, that is why it is important to remember about rare causes of low back pain and to perform detailed physical examination, laboratory tests and choose appropriate imaging techniques.
PMCID: PMC3529718  PMID: 23269942
low back pain; diagnostics; facet joint arthritis
4.  Septic arthritis of the temporomandibular joint: Case reports and review of the literature 
The Journal of emergency medicine  2013;45(5):674-678.
Background
Septic arthritis of the temporomandibular (TM) joint is rare, but it is associated with high risk for significant morbidity.
Objective
We reviewed the available literature regarding the presentation, evaluation, treatment, and clinical course of TM joint septic arthritis, focusing on elements relevant to emergency medicine physicians.
Case Reports
In the first case, a healthy 6-year-old boy presented with fever and trismus; computed tomography with contrast revealed a TM joint effusion. After empiric intravenous antibiotics, intraoperative arthrocentesis of the TM joint returned one milliliter of flocculent fluid, which was cultured and grew pan-sensitive Streptococcus pyogenes. He was discharge home with amoxicillin/clavulanate and experienced complete resolution of his symptoms. In the second case, more than three weeks after extraction of her third molars, an 18-year-old woman presented with facial pain, swelling, and trismus and was found to have a loculated abscess involving the left masseteric and pterygomandibular spaces with extension to the left deep temporal region and the skull base. She experienced a complicated postoperative course and required multiple procedures and intravenous antibiotics for growth of multiple bacteria. More than a month later underwent TM joint arthrotomy for TM joint septic arthritis, and she was found to have acute osteomyelitis. She continued to require multiple treatment modalities; twenty months after her initial presentation, she underwent left total TM joint arthroplasty for fibrous ankylosis of the TM joint.
Conclusion
Septic arthritis of the TM joint may be caused by hematogenous spread of distant infection or local spread of deep masticator space infections. Patients may present with TM joint septic arthritis acutely or sub-acutely. Septic arthritis of the TM joint should be considered in the differential diagnosis of patients who present with trismus and pain or fever.
doi:10.1016/j.jemermed.2013.01.034
PMCID: PMC4074402  PMID: 23896057
septic arthritis; temporomandibular joint; emergency department (ED); pediatric; adult; trismus
5.  Septic arthritis of unilateral lumbar facet joint with contiguous abscess, without prior intervention 
BMJ Case Reports  2012;2012:bcr0920114849.
A 40-year-old female patient presented with persistent severe back pain radiating to the right leg, abdominal pain and constipation. Other clinical symptoms included nausea, vomiting and high-grade fever. Clinical examination showed generalised abdominal and lower back tenderness. There was no sensory loss or motor weakness in lower limbs, however investigations showed raised inflammatory markers. Radiographs of the lumbar spine and hip joint were normal. MRI revealed a septic arthritis of the right L3/4 facet joint, associated with a large abscess extending anteriorly to the right paraspinal muscles and posteriorly into the right posterolateral aspect of the epidural space in the central spinal canal, with moderate compression of the dural sac. Unlike any other reported similar case, this septic arthritis developed without prior medical intervention. The patient was treated successfully with ultrasound guided drainage of the facet joint/abscess and antibiotics.
doi:10.1136/bcr.09.2011.4849
PMCID: PMC3339176  PMID: 22602829
6.  Escherichia coli – Marauding masquerading microbe 
Background
Escherichia coli is a rare cause of monoarticular septic arthritis, but is an even rarer cause of polyarticular septic arthritis.
Case description
We report an unusual case of polyarticular septic arthritis with an atypical presentation caused by E. coli, the source of which was a left pyelonephritis. Our patient developed E coli sepsis resulting in polyarticular septic arthritis (PASA) in the absence of typical risk factors except for pre-existing osteoarthritis. The joints involved were the hip, ankle, sternoclavicular and L5/S1 joints. Of interest, ankle pain was not reported or evident until correlated with nuclear medicine scans. Furthermore, sternoclavicular joint involvement presented as left shoulder pain, resulting in an initial misdiagnosis of left shoulder septic arthritis. The patient was treated with surgical washout and antibiotic therapy. He was subsequently discharged from rehabilitation having returned to his baseline level of mobility. Future consideration will be given to total hip arthroplasty.
Literature review
There are no reported cases of E. coli PASA involving more than three joints in the absence of any recognized risk factors for septic arthritis.
Purpose and clinical relevance
Asymptomatic involvement of joints can occur in polyarticular septic arthritis and should be considered in all cases of monoarticular septic arthritis (MASA). We believe that clinical suspicion is the key to early and comprehensive diagnosis of polyarticular septic arthritis particularly when presenting in an atypical fashion with an atypical pathogen. Strong consideration should be given to performing nuclear imaging in cases of monoarticular septic arthritis where polyarticular involvement cannot be definitively ruled out.
doi:10.1016/j.jcot.2013.10.001
PMCID: PMC3880952
Escherichia coli sepsis; Polyarticular septic arthritis; Septic arthritis; Nuclear medicine imaging; Bone-Gallium scan
7.  Salmonella enteridis Septic Arthritis: A Report of Two Cases 
Introduction. Nontyphoidal salmonellosis causes significant morbidity, is transmitted via fecal-oral route, and is a worldwide cause of gastroenteritis, bacteremia, and local infections. Salmonella is a less common etiologic factor for septic arthritis compared with other gram-negative bacteria. Cases. We present two septic arthritis cases with Salmonella enteridis as a confirmed pathogen and also discuss the predisposing factors and treatment. Discussion. Septic arthritis is an orthopedic emergency. The gold standard treatment of septic arthritis is joint debridement, antibiotic therapy according to the culture results, and physiotherapy, which should start in the early postoperative period to prevent limitation of motion. Salmonella is an atypical agent for septic arthritis. It must be particularly kept in mind as an etiologic factor for the acute arthritis of a patient with sickle cell anemia and systemic lupus erythematosus. Clinicians should be cautious that the white blood cell count in synovial fluid can be under 50.000/mm3 in immune compromised individuals with septic arthritis. The inflammatory response can be deficient, or the microorganism may be atypical. Conclusion. Atypical bacteria such as Salmonella species in immune compromised patients can cause joint infections. Therefore, Salmonella species must always be kept in mind for the differential diagnosis of septic arthritis in a clinically relevant setting.
doi:10.1155/2013/642805
PMCID: PMC3819818  PMID: 24251049
8.  Arthritis of the sternoclavicular joint masquerading as rupture of the cervical oesophagus: a case report 
Introduction
Sternoclavicular septic arthritis is a rare condition and accounts only for 1% of cases of septic arthritis in the general population. The most common risk factors are intravenous drug use, central-line infection, distant-site infection, immunosuppression, trauma and diabetes mellitus. This is a report of an unusual case where this type of arthritis was masquerading as rupture of the cervical oesophagus.
Case presentation
A 63-year-old man presented complaining of right neck pain and dysphagia following a bout of violent coughing. Physical examination revealed cellulitis extending from the right sternoclidomastoid region to the anterior upper chest. Computed tomography showed inflammatory changes behind the right sternoclavicular joint with mediastinitis and ipsilateral pleural effusion. These findings raised the suspicion of spontaneous rupture of the cervical oesophagus. Management involved jejunal feeding along with broad-spectrum antibiotics. The inflammation, however, relapsed after discontinuation of the antibiotics and this time, computed tomography pointed to a diagnosis of arthritis of the sternoclavicular joint. The patient responded completely to a 6-week course of oral penicillin, flucloxacillin and metronidazole.
Conclusion
Sternoclavicular arthritis is a rare condition that has been associated with a variety of predisposing factors. It may, however, occur in otherwise completely healthy individuals and should be included in the differential diagnosis of other inflammatory conditions of the neck and upper chest.
doi:10.1186/1752-1947-3-40
PMCID: PMC2639601  PMID: 19178739
9.  The characteristics of bony ankylosis of the facet joint of the upper cervical spine in rheumatoid arthritis patients 
European Spine Journal  2009;18(8):1130-1134.
This study investigated the bony ankylosis of the upper cervical spine facet joints in patients with a cervical spine involvement due to rheumatoid arthritis (RA) using computed tomography (CT) and then examined the characteristics of the patients showing such ankylosis. Forty-six consecutive patients who underwent surgical treatment for RA involving the cervical spine were reviewed. The radiographic diagnoses included atlanto-axial subluxation in 30 cases, vertical subluxation (VS) in 10 cases, VS + subaxial subluxation in 3 cases and cervical spondylotic myelopathy in 3 cases. The patients were classified into two groups, those developing bony ankylosis or not and then the differences in the patient characteristics between the two groups was investigated. Furthermore, cervical spine disorders and surgeries were also evaluated in patients who demonstrated such bony ankylosis. The CT reconstruction image demonstrated bony ankylosis in 12 patients (group BA), and the remaining 34 cases (group NB) showed no bony ankylosis. The level at which bony ankylosis occurred was atlanto-occipital joint (AOJ) in eight cases, atlanto-axial joint (AAJ) in two cases and AOJ, AAJ in two cases. No differences were observed between the two groups (age P > 0.54, gender P > 0.39, duration of RA P > 0.72). There was a significant difference between two groups in the patients showing obvious neurological impairment (P = 0.017). In BA group, arthrodesis or decompression was adapted for a caudal region of bony ankylosis. In conclusion, bony ankylosis of the facet joint of the upper cervical spine was detected in 12 of 46 RA patients with involvement of the cervical spine who thus required surgery. These findings showed that the patients demonstrating such ankylosis showed severe cervical myelopathy. In addition, we suggest that the occurrence of bony ankylosis was a risk factor for instability of AAJ, and subaxial instability or stenosis.
doi:10.1007/s00586-009-1023-8
PMCID: PMC2899501  PMID: 19424730
Atlanto-axial subluxation; Vertical subluxation; Bony ankylosis; Rheumatoid arthritis
10.  Arthroscopic Lavage and Debridement for Osteoarthritis of the Knee 
Executive Summary
Objective
The purpose of this review was to determine the effectiveness and adverse effects of arthroscopic lavage and debridement, with or without lavage, in the treatment of symptoms of osteoarthritis (OA) of the knee, and to conduct an economic analysis if evidence for effectiveness can be established.
Questions Asked
Does arthroscopic lavage improve motor function and pain associated with OA of the knee?
Does arthroscopic debridement improve motor function and pain associated with OA of the knee?
If evidence for effectiveness can be established, what is the duration of effect?
What are the adverse effects of these procedures?
What are the economic considerations if evidence for effectiveness can be established?
Clinical Need
Osteoarthritis, the most common rheumatologic musculoskeletal disorder, affects about 10% of the Canadian adult population. Although the natural history of OA is not known, it is a degenerative condition that affects the bone cartilage in the joint. It can be diagnosed at earlier ages, particularly within the sports injuries population, though the prevalence of non-injury-related OA increases with increasing age and varies with gender, with women being twice as likely as men to be diagnosed with this condition. Thus, with an aging population, the impact of OA on the health care system is expected to be considerable.
Treatments for OA of the knee include conservative or nonpharmacological therapy, like physiotherapy, weight management and exercise; and more generally, intra-articular injections, arthroscopic surgery and knee replacement surgery. Whereas knee replacement surgery is considered an end-of-line intervention, the less invasive surgical procedures of lavage or debridement may be recommended for earlier and more severe disease. Both arthroscopic lavage and debridement are generally indicated in patients with knee joint pain, with or without mechanical problems, that are refractory to medical therapy. The clinical utility of these procedures is unclear, hence, the assessment of their effectiveness in this review.
Lavage and Debridement
Arthroscopic lavage involves the visually guided introduction of saline solution into the knee joint and removal of fluid, with the intent of extracting any excess fluids and loose bodies that may be in the knee joint. Debridement, in comparison, may include the introduction of saline into the joint, in addition to the smoothening of bone surface without any further intervention (less invasive forms of debridement), or the addition of more invasive procedures such as abrasion, partial or full meniscectomy, synovectomy, or osteotomy (referred to as debridement in combination with meniscectomy or other procedures). The focus of this health technology assessment is on the effectiveness of lavage, and debridement (with or without meniscal tear resection).
Review Strategy
The Medical Advisory Secretariat followed its standard procedures and searched these electronic databases: Ovid MEDLINE, EMBASE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and The International Network of Agencies for Health Technology Assessment.
The keywords searched were: arthroscopy, debridement, lavage, wound irrigation, or curettage; arthritis, rheumatoid, osteoarthritis; osteoarthritis, knee; knee or knee joint.
Time frame: Only 2 previous health technology assessments were identified, one of which was an update of the other, and included 3 of 4 randomized controlled trials (RCTs) from the first report. Therefore, the search period for inclusion of studies in this assessment was January 1, 1995 to April 24, 2005.
Excluded were: case reports, comments, editorials, and letters. Identified were 335 references, including previously published health technology assessments, and 5 articles located through a manual search of references from published articles and health technology assessments. These were examined against the criteria, as described below, which resulted in the inclusion of 1 health technology assessment and its corresponding update, and 4 articles (2 RCTs and 2 level 4 studies) for arthroscopic lavage and 8 papers (2 RCTs and 6 level 4 studies) for arthroscopic debridement.
Inclusion Criteria
English-language articles from PubMed, EMBASE, Cochrane Systematic Reviews, and health technology assessments from January 1, 1995 onward
Studies on OA of the knee with a focus on the outcomes of motor function and pain
Studies of arthroscopic procedures only
Studies in which meniscal tear resection/meniscectomy (partial or full) has been conducted in conjunction with lavage or debridement.
Exclusion Criteria
Studies that focus on inflammatory OA, joint tuberculosis, septic joints, psoriatic joints (e.g., psoriatic knee joint synovitis), synovitis, chondropathy of the knee and gonarthrosis (which includes varotic gonarthrosis)
Studies that focus on rheumatoid arthritis
Studies that focus on meniscal tears from an acute injury (e.g., sports injury)
Studies that are based on lavage or debridement for microfracture of the knee
Studies in which other surgical procedures (e.g., high tibial osteotomy, synovectomy, have been conducted in addition to lavage/debridement)
Studies based on malalignment of the knee (e.g., varus/valgus arthritic conditions).
Studies that compare lavage to lavage plus drug therapy
Studies on procedures that are not arthroscopic (i.e., visually guided) (e.g., nonarthroscopic lavage)
Studies of OA in children.
Intervention
Arthroscopic lavage or debridement, with or without meniscectomy, for the treatment of motor function symptoms and pain associated with OA of the knee.
Comparators
Studies in which there was a comparison group of either diseased or healthy subjects or one in which subjects were their own control were included. Comparisons to other treatments included placebo (or sham) arthroscopy. Sham arthroscopy involved making small incisions and manipulating the knee, without the insertion of instruments.
Summary of Findings
In early OA of the knee with pain refractory to medical treatment, there is level 1b evidence that:
Arthroscopic lavage gives rise to a statistically significant, but not clinically meaningful effect in improving pain (WOMAC pain and VAS pain) up to 12 months following surgery. The effect on joint function (WOMAC function) and the primary outcome (WOMAC aggregate) was neither statistically nor clinically significant.
In moderate or severe OA of the knee with pain refractory to medical treatment, there is:
Level 1b evidence that the effect on pain and function of arthroscopic lavage (10 L saline) and debridement (with 10 L saline lavage) is not statistically significant up to 24 months following surgery.
Level 2 evidence that arthroscopic debridement (with 3 L saline lavage) is effective in the control of pain in severe OA of the medial femoral condyle for up to 5 years.
For debridement in combination with meniscectomy, there is level 4 evidence that the procedure, as appropriate, might be effective in earlier stages, unicompartmental disease, shorter symptom duration, sudden onset of mechanical symptoms, and preoperative full range of motion. However, as these findings are derived from very poor quality evidence, the identification of subsets of patients that may benefit from this procedure requires further testing.
In patients with pain due to a meniscal tear, of the medial compartment in particular, repair of the meniscus results in better pain control at 2 years following surgery than if the pain is attributable to other causes. There is insufficient evidence to comment on the effectiveness of lateral meniscus repair on pain control.
Conclusions
Arthroscopic debridement of the knee has thus far only been found to be effective for medial compartmental OA. All other indications should be reviewed with a view to reducing arthroscopic debridement as an effective therapy.
Arthroscopic lavage of the knee is not indicated for any stage of OA.
There is very poor quality evidence on the effectiveness of debridement with partial meniscectomy in the case of meniscal tears in OA of the knee.
PMCID: PMC3382413  PMID: 23074463
11.  Septic Arthritis in Adults with Sickle Cell Disease Often is Associated with Osteomyelitis or Osteonecrosis 
Background
Septic arthritis is a known complication of sickle cell disease (SCD) in children, and the association with osteomyelitis and osteonecrosis has been described. However, it is unclear whether this association applies to adults.
Questions/Purposes
We therefore asked whether septic arthritis is a frequent complication in adults with SCD and whether it also is associated with osteomyelitis or osteonecrosis.
Methods
We retrospectively reviewed the charts of 2000 consecutive adult patients diagnosed with SCD and recorded symptoms, select findings during physical examination, laboratory data, and select radiographic CT, and MRI observations.
Results
Fifty-nine of the 2000 patients (3%) had septic arthritis, 56 of the 59 patients had hemoglobin SS. Thirty-six of the 59 infections (61%) were in the hip. The most frequent findings were pain, swelling, fever greater than 38.2°C (71% of cases), a leukocyte count exceeding 15,000/mm3 (range, 7900–32,300/mm3), a Westergren sedimentation rate greater than 24 mm/hour, and C-reactive protein exceeding 20 mg/L. Cultures were positive in 96% of the joint aspirates. Staphylococcus and Gram-negative infection predominated; no patients had Salmonella joint infections. Preexisting factors of bacterial arthritis included osteonecrosis (29 patients) and osteomyelitis (37 cases) in childhood. Diabetes, rheumatoid arthritis, glucocorticoids, and immunoparesis related to medical treatment by hydroxyurea were associated comorbidities. CT and MRI confirmed the diagnosis of associated osteonecrosis or osteomyelitis and allowed joint aspiration and detection of soft tissue abscess.
Conclusions
The incidence of septic arthritis in adults with SCD is low, but often is associated with osteomyelitis or osteonecrosis.
Level of Evidence
Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
doi:10.1007/s11999-009-1149-3
PMCID: PMC2865595  PMID: 19885711
12.  Glenohumeral tuberculous arthritis complicated with beta haemolytic streptococcus: An extraordinary rare association: A case report 
INTRODUCTION
Septic arthritis of the glenohumeral joint is a rare entity and its diagnosis is difficult with a superadded infection in the presence of underlying tuberculosis. We report the first case of group B beta haemolytic streptococcal glenohumeral arthritis with underlying tuberculosis.
CASE PRESENTATION
A 40 year old lady previously diagnosed to have poliomyelitis, rheumatoid arthritis, hepatitis C, and diabetes mellitus for the last 10 years, presented to the emergency room with diabetic ketoacidosis. Two weeks prior to presentation she developed fever along with pain and swelling in left shoulder with uncontrolled blood sugars. Local examination of the shoulder revealed global swelling with significant restricted range of motion. MRI showed a large multiloculated collection around the left shoulder joint extending into the axilla, and proximal arm. Urgent arthrotomy performed and about 120 ml thick pus was drained. The patient was started on clindamicin and antituberculous chemotherapy and her symptoms dramatically improved.
DISCUSSION
Bone and joint involvement accounts for approximately 2% of all reported cases of tuberculosis (TB), and it accounts for approximately 10% of the extra pulmonary cases of TB. Tuberculosis of the shoulder joint constitutes 1–10.5% of skeletal tuberculosis. Classical symptoms of fever, night sweats, and weight loss may be absent, and a concurrent pulmonary focus may not be evident in most cases.
CONCLUSION
Despite acute presentation of septic arthritis, in areas endemic for tuberculosis and particularly in an immunocompromised patient, workup for tuberculosis should be part of the routine evaluation.
doi:10.1016/j.ijscr.2011.09.008
PMCID: PMC3312055  PMID: 22382034
Glenohumeral tuberculous arthritis; Beta haemolytic streptococcus; Septic arthritis
13.  Is hybrid imaging (SPECT/CT) a useful adjunct in the management of suspected facet joints arthropathy? 
International Orthopaedics  2013;37(5):865-870.
Purpose
The purpose of this study was to assess the value of SPECT/CT imaging in patients with chronic spinal pain.
Methods
This was a retrospective consecutive study. Patients with chronic neck or back pain from outpatient spinal clinics with clinical features raising the possibility of a facetogenic pain generator and non-conclusive MRI/CT findings were included. Imaging was performed on a dual-headed, hybrid SPECT/CT γ-camera with a low-dose CT transmission scan acquired after the SPECT study. SPECT/CT studies were viewed in the coronal, axial, and sagittal planes and in 3-dimensional mode. Descriptive statistical analysis was performed.
Results
Seventy-two patients were included (37 females, 35 males, mean age of 53.9 years). There were 25 cervical spine scans and 49 lumbar spine scans. In the cervical spine group, 13 (52 %) patients had scintigraphically active cervical facet joint arthropathy and ten (36 %) had other pathology identified. Two thirds of patients diagnosed with facet joint arthropathy received steroid guided injections following their scans. In the lumbar spine group 34 (69.4 %) patients had scintigraphically active lumbar facet joint arthropathy and eight had other pathology identified. Twenty patients (58.8 %) diagnosed with facet joint arthropathy subsequently received steroid guided injections.
Conclusions
Hybrid SPECT/CT imaging identified potential pain generators in 92 % of cervical spine scans and 86 % of lumbar spine scans. The scan precisely localised SPECT positive facet joint targets in 65 % of the referral population and a clinical decision to inject was made in 60 % of these cases.
doi:10.1007/s00264-013-1811-y
PMCID: PMC3631481  PMID: 23412368
14.  Acute Septic Arthritis 
Clinical Microbiology Reviews  2002;15(4):527-544.
Acute septic arthritis may develop as a result of hematogenous seeding, direct introduction, or extension from a contiguous focus of infection. The pathogenesis of acute septic arthritis is multifactorial and depends on the interaction of the host immune response and the adherence factors, toxins, and immunoavoidance strategies of the invading pathogen. Neisseria gonorrhoeae and Staphylococcus aureus are used in discussing the host-pathogen interaction in the pathogenesis of acute septic arthritis. While diagnosis rests on isolation of the bacterial species from synovial fluid samples, patient history, clinical presentation, laboratory findings, and imaging studies are also important. Acute nongonococcal septic arthritis is a medical emergency that can lead to significant morbidity and mortality. Therefore, prompt recognition, rapid and aggressive antimicrobial therapy, and surgical treatment are critical to ensuring a good prognosis. Even with prompt diagnosis and treatment, high mortality and morbidity rates still occur. In contrast, gonococcal arthritis is often successfully treated with antimicrobial therapy alone and demonstrates a very low rate of complications and an excellent prognosis for full return of normal joint function. In the case of prosthetic joint infections, the hardware must be eventually removed by a two-stage revision in order to cure the infection.
doi:10.1128/CMR.15.4.527-544.2002
PMCID: PMC126863  PMID: 12364368
15.  The Epidemiology and Clinical Spectrum of Melioidosis: 540 Cases from the 20 Year Darwin Prospective Study 
Background
Over 20 years, from October 1989, the Darwin prospective melioidosis study has documented 540 cases from tropical Australia, providing new insights into epidemiology and the clinical spectrum.
Principal Findings
The principal presentation was pneumonia in 278 (51%), genitourinary infection in 76 (14%), skin infection in 68 (13%), bacteremia without evident focus in 59 (11%), septic arthritis/osteomyelitis in 20 (4%) and neurological melioidosis in 14 (3%). 298 (55%) were bacteremic and 116 (21%) developed septic shock (58 fatal). Internal organ abscesses and secondary foci in lungs and/or joints were common. Prostatic abscesses occurred in 76 (20% of 372 males). 96 (18%) had occupational exposure to Burkholderia pseudomallei. 118 (22%) had a specific recreational or occupational incident considered the likely infecting event. 436 (81%) presented during the monsoonal wet season. The higher proportion with pneumonia in December to February supports the hypothesis of infection by inhalation during severe weather events. Recurrent melioidosis occurred in 29, mostly attributed to poor adherence to therapy. Mortality decreased from 30% in the first 5 years to 9% in the last five years (p<0.001). Risk factors for melioidosis included diabetes (39%), hazardous alcohol use (39%), chronic lung disease (26%) and chronic renal disease (12%). There was no identifiable risk factor in 20%. Of the 77 fatal cases (14%), 75 had at least one risk factor; the other 2 were elderly. On multivariate analysis of risk factors, age, location and season, the only independent predictors of mortality were the presence of at least one risk factor (OR 9.4; 95% CI 2.3–39) and age ≥50 years (OR 2.0; 95% CI 1.2–2.3).
Conclusions
Melioidosis should be seen as an opportunistic infection that is unlikely to kill a healthy person, provided infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care.
Author Summary
Melioidosis is an occupationally and recreationally acquired infection important in Southeast Asia and northern Australia. Recently cases have been reported from more diverse locations globally. The responsible bacterium, Burkholderia pseudomallei, is considered a potential biothreat agent. Risk factors predisposing to melioidosis are well recognised, most notably diabetes. The Darwin prospective melioidosis study has identified 540 cases of melioidosis over 20 years and analysis of the epidemiology and clinical findings provides important new insights into this disease. Risk factors identified in addition to diabetes, hazardous alcohol use and chronic renal disease include chronic lung disease, malignancies, rheumatic heart disease, cardiac failure and age ≥50 years. Half of patients presented with pneumonia and septic shock was common (21%). The decrease in mortality from 30% in the first 5 years of the study to 9% in the last five years is attributed to earlier diagnosis and improvements in intensive care management. Of the 77 fatal cases (14%), all had known risk factors for melioidosis. This supports the most important conclusion of the study, which is that melioidosis is very unlikely to kill a healthy person, provided the infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care where required.
doi:10.1371/journal.pntd.0000900
PMCID: PMC2994918  PMID: 21152057
16.  Percutaneous transpedicular discectomy and drainage in pyogenic spondylodiscitis 
European Spine Journal  2004;13(8):707-713.
The natural history of uncomplicated hematogenous pyogenic spondylodiscitis is self-limiting healing. However, a variable degree of bone destruction frequently occurs, predisposing the spine to painful kyphosis. Delayed treatment may result in serious neurologic complications. Early debridement of these infections by percutaneous transpedicular discectomy can accelerate the natural process of healing and prevent progression to bone destruction and epidural abscess. The purpose of this manuscript is to present our technique of percutaneous transpedicular discectomy (PTD), to revisit this minimally invasive surgical technique with stricter patient selection, and to exclude cases of extensive vertebral body destruction with kyphosis and neurocompression by epidural abscess, infected disc herniation, and foraminal stenosis. In a previously published report of 28 unselected patients with primary hematogenous pyogenic spondylodiscitis, the immediate relief of pain after PTD was 75%, and in the longterm follow-up, the success rate was 68%. Applying stricter patient selection criteria in a second series of six patients (five with primary hematogenous spondylodiscitis and one with secondary postlaminectomydiscectomy spondylodiscitis), all patients with primary hematogenous spondylodiskitis (5/5) experienced immediate relief of pain that remained sustained at 12–18 months follow-up. This procedure was not very effective, however, in the patient who suffered from postlaminectomy infection. This lack of response was attributed to postlaminectomydiscitis instability. The immediate success rate after surgery for unselected patients in this combined series of 34 patients was 76%. This technique can be impressively effective and the results sustained when applied in the early stages of uncomplicated spondylodiscitis and contraindicated in the presence of instability, kyphosis from bone destruction, and neurological deficit. The special point of this procedure is a minimally invasive technique with high diagnostic and therapeutic effectiveness.
doi:10.1007/s00586-004-0699-z
PMCID: PMC3454057  PMID: 15197626
Percutaneous transpedicular discectomy; Primary hematogenous pyogenic spondylodiscitis
17.  64-year-old male with septic arthritis of the pubic symphysis 
Clinics and Practice  2011;1(3):e76.
Septic arthritis of the pubic symphysis is a rare disease. Typical clinical features include fever, pubic or groin pain, pain with hip motion, and painful or waddling gait. Identified predisposing factors to develop an infection in pubic joint include female incontinence surgery or postpartum period; sports, especially soccer; pelvic malignancy; and intravenous drug abuse. The most often identified microorganisms were Staphylococcus aureus and Pseudomonas aeruginosa. Osteomyelitis complicates the majority of cases, and about half of the patients require surgical debridement along with a prolonged antibiotic treatment. We report a case of Streptococcus anginosus septic arthritis of the pubic symphysis. The patient did not have any of the above risk factors.
doi:10.4081/cp.2011.e76
PMCID: PMC3981387  PMID: 24765337
septic arthritis of the pubic symphysis; Streptococcus anginosus.
18.  Endoscopic Facet Debridement for the treatment of facet arthritic pain - a novel new technique 
Study design: Retrospective, observational, open label.
Objective: We investigated the efficacy of facet debridement for the treatment of facet joint pain.
Summary of background data: Facet joint disease, often due to degenerative arthritis, is common cause of chronic back pain. In patients that don't respond to conservative measures, nerve ablation may provide significant improvement. Due to the ability of peripheral nerves to regenerate, ablative techniques of the dorsal nerve roots often provide only temporary relief. In theory, ablation of the nerve end plates in the facet joint capsule should prevent reinnervation.
Methods: All patients treated with endoscopic facet debridement at our clinic from 2003-2007 with at least 3 years follow-up were included in the analysis. Primary outcome measure was percent change in facet-related pain as measured by Visual Analog Scale (VAS) score at final follow-up visit.
Results: A total of 174 people (77 women, 97 men; mean age 64, range 22-89) were included. Location of facet pain was cervical in 45, thoracic in 15, and lumbar in 114 patients. At final follow-up, 77%, 73%, and 68% of patients with cervical, thoracic, or lumbar disease, respectively, showed at least 50% improvement in pain. Mean operating time per joint was 17 minutes (range, 10-42). Mean blood loss was 40 ml (range, 10-100). Complications included suture failure in two patients, requiring reclosure of the incision. No infection or nerve damage beyond what was intended occurred.
Conclusions: Our results demonstrate a comparable efficacy of endoscopic facet debridement compared to radiofrequency ablation of the dorsal nerve branch, with durable results. Large scale, randomized trials are warranted to further evaluate the relative efficacy of this surgical treatment in patients with facet joint disease.
PMCID: PMC2880840  PMID: 20567612
vertebral arthritis; facet syndrome; back pain; minimally invasive; nerve ablation
19.  Artificial Cervical Disc Arthroplasty (ACDA): tips and tricks 
Journal of Injury and Violence Research  2012;4(3 Suppl 1): Paper No. 36.
Abstract:
Background:
Anterior cervical discectomy and fusion (ACDF) is currently treatment of choice for managing medical therapy refractory cervical degenerative disc disease. Numerous studies have demonstrated the effectiveness of ACDF; patients generally experience rapid recoveries, and dramatic improvement in their pain and quality of life. However, as several studies reported symptomatic adjacent segment disease attributed to fusions’ altered kinematics, cervical disc arthroplasty emerged as a new motion-sparing alternative to fusion. Fusion at one level increases motion at adjacent levels along with increased intradiscal pressures. This phenomenon can result in symptomatic adjacent level degeneration, which can necessitate reoperation at these levels. The era of cervical arthroplasty began in Europe in the late 1990s. In recent years, artificial cervical disc arthroplasty (ACDA) has been increasingly used by spine surgeons for degenerative cervical disc disease. There have been several reports of safety, efficacy and indications of ACDA.
Cervical arthroplasty offers several theoretical advantages over anterior cervical discectomy and fusion (ACDF) in the treatment of selected patients with medically refractory cervical radiculopathy. Preserving motion at the operated level, cervical TDR has the potential to decrease the occurrence of adjacent segment degeneration.
There are a few studies on the efficacy and effectiveness of ACDA compared to cervical fusion. However, the true scenery of cervical arthroplasty yet to be identified.
Objective:
This study is intended to define patients' characteristics and outcomes of ACDA by a single surgeon in Iran.
Methods:
This retrospective study was performed in two general Hospitals in Tehran, Iran from 2005 To 2010. All patients were operated by one senior neurospine surgeon. One hundred fifty three patients were operated in this period. All patients signed the informed consent form prior to surgery. All patients presented with cervical discopathy who had myelopathy or radiculopathy and failed conservative management, undergoing cervical disc arthroplasty by ACDA were included, consecutively. Patients were followed for at least 2 years.
Exclusion criteria was age greater than 60 years, non compliance with the study protocol, osteoporosis, infection, congenital or post traumatic deformity, malignancy metabolic bone disease, and narrow cervical canal (less than 12 mm). Heterotopic ossification and adjacent segment degenerative changes were assessed at 2 years follow up by means of neutral and dynamic xrays and CT/MRI if clinically indicated. Neck and upper extremity pain were assessed before the procedure and in the first post-operative visit and 3 months later by means of visual analogue scale.
A standard approach was performed to the anterior cervical spine. Patients were positioned supine while holding neck in neutral position. A combination of sharp and blunt dissection was performed to expose longus coli musculature and anterior cervical vertebrae. Trachea and esophagus were retracted medially and carotid artery and jugular vein laterally. After a thorough discectomy, the intersomatic space is distracted in a parallel way by a vertebral distracter. Followed by Caspar distractor is applied to provide a working channel into posterior disc space. In this stage, any remnant disc materials as well as osteophytes are removed and foraminal decompression is done. Posterior longitudinal ligament (PLL) opening and removal, although discouraged by some, is done next. In order to define the size of the prosthesis, multiple trials are tested. It is important not to exceed the height of the healthy adjacent disc to avoid facet joint overdistraction. An specific insertor is applied to plant the prosthesis in disc space. Control X-rays are advised to check the precise positioning of the implant.
Results:
one hundred-fifty three patients including 87 females and 66 males were included. The mean age was 41 for females and 42 for males. Affected level was C5-C6 in 81 cases, C6-C7 in 72 cases and C4-C5 in 10 cases. The most common applied ACDA was DiscoCerv which was inserted in 127 cases followed by prodisc-c in three patients and Baguera in thirty three psatients.Ten cases had two levels involvement. Both neck and upper extremity pain improved significantly in early and late post op assessments compared to pre-op. There was only one operative complication of quadriparesis which might be attributed to the iatrogenic cervical spinal trauma.
Conclusions:
Cervical disc arthroplasty has been advocated to address drawbacks of fusion including loss of motion segment and adjacent level degeneration; our study along with several other reports provide considerable evidence in this regard. Cervical disc arthroplasty is a safe and effective alternative for fusion in cervical degenerative disc disease.
Keywords:
Cervical degenerative disc disease, Artificial cervical disc arthroplasty, Safety, Efficacy
PMCID: PMC3571562
20.  Generalized infection following facet joint injection -A case report- 
Korean Journal of Anesthesiology  2010;58(4):401-404.
Facet joints have been shown to be a source of chronic low back pain, and it is generally accepted in clinical practice that diagnostic and therapeutic facet joint injections are the most reliable technique for the treatment of facet joint pain, which is considered to be an easy and safe procedure. Serious complications and side effects are uncommon after facet joint injection. However, infectious complications including septic arthritis, epidural abscess, meningitis and endocarditis have been reported following facet joint injections. We report here the first case of death following lumbar facet joint injection due to generalized infection.
doi:10.4097/kjae.2010.58.4.401
PMCID: PMC2876864  PMID: 20508800
Abscess; Facet joint; Infection; Low back pain
21.  Bilateral sternoclavicular joint septic arthritis secondary to indwelling central venous catheter: a case report 
Introduction
Septic arthritis of the sternoclavicular joint is rare, comprising approximately 0.5% to 1% of all joint infections. Predisposing causes include immunocompromising diseases such as diabetes, HIV infection, renal failure and intravenous drug abuse.
Case presentation
We report a rare case of bilateral sternoclavicular joint septic arthritis in an elderly patient secondary to an indwelling right subclavian vein catheter. The insidious nature of the presentation is highlighted. We also review the literature regarding the epidemiology, investigation and methods of treatment of the condition.
Conclusion
SCJ infections are rare, and require a high degree of clinical suspicion. Vague symptoms of neck and shoulder pain may cloud the initial diagnosis, as was the case in our patient. Surgical intervention is often required; however, our patient avoided major intervention and settled with parenteral antibiotics and washout of the joint.
doi:10.1186/1752-1947-2-131
PMCID: PMC2390578  PMID: 18445257
22.  Troublesome Tuberculosis: A Case Report on Multi-focal Tuberculous Osteomyelitis in An Immunocompetent Patient 
Bone and joint tuberculosis is a chronic debilitating condition that leads to progressive damage and even deformity of joints. It may affect one or multiple sites. It could present in a myriad of ways which may result in an incorrect diagnosis being made. Common misdiagnoses include seronegative inflammatory arthritis, septic arthritis, malignancy, osteoporotic fractures and mechanical type back pain. It was initially only diagnosed in patients with previous active tuberculosis or latent tuberculosis. However, in recent years, it has also been reported in patients without a history of previous tuberculosis infection. Making a diagnosis of bone and joint tuberculosis is challenging. As the symptoms are not always typical, a delay in initiating anti-tuberculosis treatment is not uncommon in clinical practice. Systemic features are not always present in multi-drug resistant tuberculosis of joints which makes the diagnosis even more challenging. Multi-drug resistant tuberculosis is an increasingly common problem. It is not only limited to immunocompromised patients, but also found in immunocompetent patients. Multifocal tuberculous osteomyelitis is an uncommon condition and may involve any bone such as the skull, ribs, long bones, spine and phalanx. Tuberculous pyomyositis and tuberculous tenosynovitis may also be the presenting features of multifocal tuberculosis. Identification of mycobacterium tuberculosis in synovial fluid and biopsy, tissue culture, tissue fluid cytology and tissue polymerase chain reaction are crucial investigations in these cases. As the presentation of extra pulmonary tuberculosis can be very variable, it is important to maintain a high index of suspicion. The diagnosis and therefore treatment may be expedited using a clinically directed multidisciplinary approach.
Keywords
Bone and joint tuberculosis; Multi focal tuberculous osteomyelitis; Extra-pulmonary tuberculosis; Multi-drug resistant tuberculosis; Latent tuberculosis
doi:10.4021/jocmr758e
PMCID: PMC3279507  PMID: 22383933
23.  Infectious sacroiliitis caused by Staphylococcus aureus following acupuncture: a case report 
Acupuncture in Medicine  2013;32(1):77-80.
Determination of the origin of infectious sacroiliitis (ISI), a rare form of septic arthritis, is often time consuming and clinically difficult owing to its various presentations, which include joint, skin and urinary tract infections. This report describes the diagnosis, determination of infectious origin and treatment of a case of ISI attributed to the use of acupuncture for the treatment of lower back pain. We report on a 61-year-old man who developed right hip pain and fever 3 days after undergoing acupuncture over the right buttock region for the treatment of lower back pain. Blood culture showed infection with methicillin-susceptible Staphylococcus aureus and MRI disclosed the presence of an inflamed area over the right iliac bone and the right portion of the sacrum. The patient was cured after a 4-week course of antimicrobial treatment. Clinicians should take a history of acupuncture use when evaluating patients presenting with fever of unknown origin and/or bacteraemia and consider the possibility of ISI when evaluating patients with hip pain and infectious signs after acupuncture or other possible causes of infection. This indicates the importance of performing clinically clean procedures to prevent septic complications when treating patients with acupuncture.
doi:10.1136/acupmed-2013-010457
PMCID: PMC4151478  PMID: 24135310
Acupuncture; Infectious Diseases; Microbiology; Therapeutics
24.  Spinal Epidural Abscess with Pyogenic Arthritis of Facet Joint Treated with Antibiotic-Bone Cement Beads - A Case Report - 
Asian Spine Journal  2007;1(1):61-64.
Most epidural abscesses are a secondary lesion of pyogenic spondylodiscitis. An epidural abscess associated with pyogenic arthritis of the facet joint is quite rare. To the best of our knowledge, there is no report of the use of antibiotic-cement beads in the surgical treatment of an epidural abscess. This paper reports a 63-year-old male who sustained a 1-week history of radiating pain to both lower extremities combined with lower back pain. MRI revealed space-occupying lesions, which were located in both sides of the anterior epidural space of L4, and CT scans showed irregular widening and bony erosion of the facet joints of L4-5. A staphylococcal infection was identified after a posterior decompression and an open drainage. Antibiotic- bone cement beads were used as a local controller of the infection and as a spacer or an indicator for the second operation. An intravenous injection of anti-staphylococcal antibiotics resolved the back pain and radicular pain and normalized the laboratory findings. We point out not only the association of an epidural abscess with facet joint infection, but also the possible indication of antibiotic-bone cement beads in the treatment of epidural abscesses.
doi:10.4184/asj.2007.1.1.61
PMCID: PMC2857502  PMID: 20411156
Epidural abscess; Facet joint infection; Lumbar spine; Antibiotic-bone cement bead
25.  Evidence-based Diagnostics: Adult Septic Arthritis 
Background
Acutely swollen or painful joints are common complaints in the emergency department (ED). Septic arthritis in adults is a challenging diagnosis, but prompt differentiation of a bacterial etiology is crucial to minimize morbidity and mortality.
Objectives
The objective was to perform a systematic review describing the diagnostic characteristics of history, physical examination, and bedside laboratory tests for nongonococcal septic arthritis. A secondary objective was to quantify test and treatment thresholds using derived estimates of sensitivity and specificity, as well as best-evidence diagnostic and treatment risks and anticipated benefits from appropriate therapy.
Methods
Two electronic search engines (PUBMED and EMBASE) were used in conjunction with a selected bibliography and scientific abstract hand search. Inclusion criteria included adult trials of patients presenting with monoarticular complaints if they reported sufficient detail to reconstruct partial or complete 2 × 2 contingency tables for experimental diagnostic test characteristics using an acceptable criterion standard. Evidence was rated by two investigators using the Quality Assessment Tool for Diagnostic Accuracy Studies (QUADAS). When more than one similarly designed trial existed for a diagnostic test, meta-analysis was conducted using a random effects model. Interval likelihood ratios (LRs) were computed when possible. To illustrate one method to quantify theoretical points in the probability of disease whereby clinicians might cease testing altogether and either withhold treatment (test threshold) or initiate definitive therapy in lieu of further diagnostics (treatment threshold), an interactive spreadsheet was designed and sample calculations were provided based on research estimates of diagnostic accuracy, diagnostic risk, and therapeutic risk/benefits.
Results
The prevalence of nongonococcal septic arthritis in ED patients with a single acutely painful joint is approximately 27% (95% confidence interval [CI] = 17% to 38%). With the exception of joint surgery (positive likelihood ratio [+LR] = 6.9) or skin infection overlying a prosthetic joint (+LR = 15.0), history, physical examination, and serum tests do not significantly alter posttest probability. Serum inflammatory markers such as white blood cell (WBC) counts, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) are not useful acutely. The interval LR for synovial white blood cell (sWBC) counts of 0 × 109–25 × 109/ L was 0.33; for 25 × 109–50 × 109/L, 1.06; for 50 × 109–100 × 109/L, 3.59; and exceeding 100 × 109/L, infinity. Synovial lactate may be useful to rule in or rule out the diagnosis of septic arthritis with a +LR ranging from 2.4 to infinity, and negative likelihood ratio (−LR) ranging from 0 to 0.46. Rapid polymerase chain reaction (PCR) of synovial fluid may identify the causative organism within 3 hours. Based on 56% sensitivity and 90% specificity for sWBC counts of >50 × 109/L in conjunction with best-evidence estimates for diagnosis-related risk and treatment-related risk/benefit, the arthrocentesis test threshold is 5%, with a treatment threshold of 39%.
Conclusions
Recent joint surgery or cellulitis overlying a prosthetic hip or knee were the only findings on history or physical examination that significantly alter the probability of nongonococcal septic arthritis. Extreme values of sWBC (>50 × 109/L) can increase, but not decrease, the probability of septic arthritis. Future ED-based diagnostic trials are needed to evaluate the role of clinical gestalt and the efficacy of nontraditional synovial markers such as lactate.
doi:10.1111/j.1553-2712.2011.01121.x
PMCID: PMC3229263  PMID: 21843213

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