Prevalence of Small Intestinal Bacterial Overgrowth Syndrome in Patients with Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis: A Cross-Sectional Study.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is a multifactorial, wide-spectrum liver disorder. Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the number and/or type of colonic bacteria in the upper gastrointestinal tract. SIBO, through energy salvage and induction of inflammation, may be a pathophysiological factor for NAFLD development and progression. AIM/METHODS: Consecutive patients with histological, biochemical, or radiological diagnosis of any stage of NAFLD (non-alcoholic fatty liver [NAFL], non-alcoholic steatohepatitis [NASH], cirrhosis) underwent upper gastrointestinal endoscopy. Duodenal fluid (2cc) was aspirated from the 3rd-4th part of duodenum into sterile containers. SIBO was defined as ≥103 aerobic colony-forming units (CFU)/mL of duodenal aspirate and/or the presence of colonic-type bacteria. Patients without any liver disease undergoing gastroscopy due to gastroesophageal reflux disease (GERD) comprised the healthy control (HC) group. Concentrations (pg/mL) of tumor necrosis factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 were also measured in the duodenal fluid. The primary endpoint was to evaluate the prevalence of SIBO in NAFLD patients, while the comparison of SIBO prevalence among NAFLD patients and healthy controls was a secondary endpoint. RESULTS: We enrolled 125 patients (51 NAFL, 27 NASH, 17 cirrhosis, and 30 HC) aged 54 ± 11.9 years and with a weight of 88.3 ± 19.6 kg (NAFLD vs. HC 90.7 ± 19.1 vs. 80.8 ± 19.6 kg, p = 0.02). Overall, SIBO was diagnosed in 23/125 (18.4%) patients, with Gram-negative bacteria being the predominant species (19/23; 82.6%). SIBO prevalence was higher in the NAFLD cohort compared to HC (22/95; 23.2% vs. 1/30; 3.3%, p = 0.014). Patients with NASH had higher SIBO prevalence (6/27; 22.2%) compared to NAFL individuals (8/51; 15.7%), but this difference did not reach statistical significance (p = 0.11). Patients with NASH-associated cirrhosis had a higher SIBO prevalence compared to patients with NAFL (8/17; 47.1% vs. 8/51; 15.7%, p = 0.02), while SIBO prevalence between patients with NASH-associated cirrhosis and NASH was not statistically different (8/17; 47.1% vs. 6/27; 22.2%, p = 0.11). Mean concentration of TNF-α, IL-1ß, and IL-6 did not differ among the different groups. CONCLUSION: The prevalence of SIBO is significantly higher in a cohort of patients with NAFLD compared to healthy controls. Moreover, SIBO is more prevalent in patients with NASH-associated cirrhosis compared to patients with NAFL.

Effect of intravenous clarithromycin in patients with sepsis, respiratory and multiple organ dysfunction syndrome: a randomized clinical trial.

BACKGROUND: Clarithromycin may act as immune-regulating treatment in sepsis and acute respiratory dysfunction syndrome. However, clinical evidence remains inconclusive. We aimed to evaluate whether clarithromycin improves 28-day mortality among patients with sepsis, respiratory and multiple organ dysfunction syndrome. METHODS: We conducted a multicenter, randomized, clinical trial in patients with sepsis. Participants with ratio of partial oxygen pressure to fraction of inspired oxygen less than 200 and more than 3 SOFA points from systems other than the respiratory function were enrolled between December 2017 and September 2019. Patients were randomized to receive 1 gr of clarithromycin or placebo intravenously once daily for 4 consecutive days. The primary endpoint was 28-day all-cause mortality. Secondary outcomes were 90-day mortality; sepsis response (defined as at least 25% decrease in SOFA score by day 7); sepsis recurrence; and differences in peripheral blood cell populations and leukocyte transcriptomics. RESULTS: Fifty-five patients were allocated to each arm. By day 28, 27 (49.1%) patients in the clarithromycin and 25 (45.5%) in the placebo group died (risk difference 3.6% [95% confidence interval (CI) - 15.7 to 22.7]; P = 0.703, adjusted OR 1.03 [95%CI 0.35-3.06]; P = 0.959). There were no statistical differences in 90-day mortality and sepsis response. Clarithromycin was associated with lower incidence of sepsis recurrence (OR 0.21 [95%CI 0.06-0.68]; P = 0.012); significant increase in monocyte HLA-DR expression; expansion of non-classical monocytes; and upregulation of genes involved in cholesterol homeostasis. Serious and non-serious adverse events were equally distributed. CONCLUSIONS: Clarithromycin did not reduce mortality among patients with sepsis with respiratory and multiple organ dysfunction. Clarithromycin was associated with lower sepsis recurrence, possibly through a mechanism of immune restoration. Clinical trial registration clinicaltrials.gov identifier NCT03345992 registered 17 November 2017; EudraCT 2017-001056-55.

BioFire® FilmArray® Pneumonia Panel for Severe Lower Respiratory Tract Infections: Subgroup Analysis of a Randomized Clinical Trial.

INTRODUCTION: The epidemiology of severe lower respiratory tract infections (LRTI) is constantly changing. We aimed to describe it using the BioFire® FilmArray® Pneumonia plus (PNplus) Panel. METHODS: In a sub-study of the PROGRESS trial, sputum samples of 90 patients with sepsis and LRTI were retrospectively studied. The primary endpoint was the comparative detection rate of pathogens between conventional microbiology and PNplus Panel; secondary endpoints were microbiology and the association with the inflammatory host response. RESULTS: Fifty-six patients with community-acquired pneumonia without risk factors for multidrug-resistant (MDR) pathogens and another 34 patients with risk factors for MDR were studied; median pneumonia severity index (PSI) was 113 (88-135). PNplus detection rate was 72.2% compared to 10% by conventional microbiology (p < 0.001); Streptococcus pneumoniae was the most common pathogen. PSI and procalcitonin were greater among patients with bacterial pathogens than viral pathogens. Median procalcitonin was 0.49 ng/ml and 0.18 ng/ml among patients with ≥ 105 and < 105 copies/ml of detected bacteria, respectively (p = 0.004). Resistance reached 14.4%. CONCLUSION: PNplus detects severe pneumonia pathogens at a greater rate than conventional microbiology. High levels of inflammation accompany bacterial detection. TRIAL REGISTRATION: PROGRESS, ClinicalTrials.gov NCT03333304, 06/11/2017.

Host cystathionine-γ lyase derived hydrogen sulfide protects against Pseudomonas aeruginosa sepsis.

Hydrogen sulfide (H2S) has recently been recognized as a novel gaseous transmitter with several anti-inflammatory properties. The role of host- derived H2S in infections by Pseudomonas aeruginosa was investigated in clinical and mouse models. H2S concentrations and survival was assessed in septic patients with lung infection. Animal experiments using a model of severe systemic multidrug-resistant P. aeruginosa infection were performed using mice with a constitutive knock-out of cystathionine-γ lyase (Cse) gene (Cse-/-) and wild-type mice with a physiological expression (Cse+/+). Experiments were repeated in mice after a) treatment with cyclophosphamide; b) bone marrow transplantation (BMT) from a Cse+/+ donor; c) treatment with H2S synthesis inhibitor aminooxyacetic acid (ΑΟΑΑ) or propargylglycine (PAG) and d) H2S donor sodium thiosulfate (STS) or GYY3147. Bacterial loads and myeloperoxidase activity were measured in tissue samples. The expression of quorum sensing genes (QS) was determined in vivo and in vitro. Cytokine concentration was measured in serum and incubated splenocytes. Patients survivors at day 28 had significantly higher serum H2S compared to non-survivors. A cut- off point of 5.3 µΜ discriminated survivors with sensitivity 92.3%. Mortality after 28 days was 30.9% and 93.7% in patients with H2S higher and less than 5.3 µΜ (p = 7 x 10-6). In mice expression of Cse and application of STS afforded protection against infection with multidrug-resistant P. aeruginosa. Cyclophosphamide pretreatment eliminated the survival benefit of Cse+/+ mice, whereas BMT increased the survival of Cse-/- mice. Cse-/- mice had increased pathogen loads compared to Cse+/+ mice. Phagocytic activity of leukocytes from Cse-/- mice was reduced but was restored after H2S supplementation. An H2S dependent down- regulation of quorum sensing genes of P.aeruginosa could be demonstrated in vivo and in vitro. Endogenous H2S is a potential independent parameter correlating with the outcome of P. aeruginosa. H2S provides resistance to infection by MDR bacterial pathogens.

Bilateral Total Knee Arthroplasty for Charcot Arthropathy After Cauda Equine Syndrome: A Case Report.

Charcot arthropathy of the knee is a relatively rare and poorly understood condition. Diagnosis requires detailed history of the patient, radiological investigation and exclusion of other causes of arthropathy. Conservative treatment is sufficient only in early stages. In late stages, either arthrodesis or total knee arthroplasty is the treatment of choice. We report a case of a 65-year-old woman who presented with Charcot arthropathy in both knees, after a spinal fracture 35 years ago, which caused cauda equine syndrome with diminished sensation of both legs. She underwent bilateral total knee arthroplasty using hinged knee prosthesis.

Diagnostic and treatment modalities in nonunions of the femoral shaft: a review.

Nonunions of the femoral shaft represent a treatment challenge for the orthopaedic surgeon and a serious socioeconomic problem for the patient. Inadequate fracture stability, insufficient blood supply, bone loss or presence of infection are the main reasons for the development of a nonunion. Careful classification and exclusion of infection are crucial for the choice of the proper treatment alternative. Nail dynamization, primary intramedullary nailing or nail exchange, plate osteosynthesis and external fixation along with bone grafting, usage of bone substitutes and electrical stimulation can stimulate osseous union. A review of the aetiology, classification and treatment should prove helpful managing this serious complication.

Accuracy of pedicle screw placement: a systematic review of prospective in vivo studies comparing free hand, fluoroscopy guidance and navigation techniques.

INTRODUCTION: With the advances and improvement of computer-assisted surgery devices, computer-guided pedicle screws insertion has been applied to the lumbar, thoracic and cervical spine. The purpose of the present study was to perform a systematic review of all available prospective evidence regarding pedicle screw insertion techniques in the thoracic and lumbar human spine. MATERIALS AND METHODS: We considered all prospective in vivo clinical studies in the English literature that assessed the results of different pedicle screw placement techniques (free-hand technique, fluoroscopy guided, computed tomography (CT)-based navigation, fluoro-based navigation). MEDLINE, OVID, and Springer databases were used for the literature search covering the period from January 1950 until May 2010. RESULTS: 26 prospective clinical studies were eventually included in the analysis. These studies included in total 1,105 patients in which 6,617 screws were inserted. In the studies using free-hand technique, the percentage of the screws fully contained in the pedicle ranged from 69 to 94%, with the aid of fluoroscopy from 28 to 85%, using CT navigation from 89 to 100% and using fluoroscopy-based navigation from 81 to 92%. The screws positioned with free-hand technique tended to perforate the cortex medially, whereas the screws placed with CT navigation guidance seemed to perforate more often laterally. CONCLUSIONS: In conclusion, navigation does indeed exhibit higher accuracy and increased safety in pedicle screw placement than free-hand technique and use of fluoroscopy.

Kümmell's disease: pathophysiology, diagnosis, treatment and the role of nuclear medicine. Rationale according to our experience.

Kümmell's disease (KD) is a rare clinical entity and includes patients, who after a trivial trauma and an asymptomatic period, develop a progressive vertebral body collapse and a painful kyphosis. The main pathologic eliciting event still remains unclear. Vertebral body collapse can be the result of infection, malignant neoplasia or trauma. It may be difficult to distinguish among them, particularly in osteoporosis. To explain the time lag between initial trauma and vertebral collapse, the hypothesis of ischemic necrosis was suggested. Many authors considering KD as a case of mere vertebral osteonecrosis have wrongly reported cases of osteonecrosis without a spinal trauma, as KD. The fact that intravertebral vacuum cleft often coexists with vertebral osteonecrosis further added to confusion. Various imaging modalities including bone scan support the diagnosis of KD. It is described that bone single photon emission tomography (SPET) or SPET/computed tomography scintigraphy using dynamic and static, acquisition can identify the chronicity of the lesions.

Traumatic pneumorrhachis: etiology, pathomechanism, diagnosis, and treatment.

BACKGROUND CONTEXT: Traumatic pneumorrhachis (PR) is a rare entity, consisting of air within the spinal canal. It can be classified as epidural or subarachnoid, identifying the anatomical space where the air is located, and is associated with different etiologies, pathology, and treatments. PURPOSE: To conduct a systematic review of the scientific literature focused on the etiology, pathomechanism, diagnosis, and treatment of PR, and to report a case of an asymptomatic epidural type. STUDY DESIGN: International medical literature has been reviewed systematically for the term "traumatic pneumorrhachis" and appropriate related subject headings, such as traumatic intraspinal air, traumatic intraspinal pneumocele, traumatic spinal pneumatosis, traumatic spinal emphysema, traumatic aerorachia, traumatic pneumosaccus, and traumatic air myelogram. All cases that were identified were evaluated concerning their etiology, pathomechanism, and possible complications. SAMPLES: Studies that included one of the aforementioned terms in their titles. METHODS: A systematic review was performed to identify, evaluate, and summarize the literature related to the term "traumatic pneumorrhachis" and related headings. Furthermore, we report a rare case of an asymptomatic epidural PR extending to the cervical and thoracic spinal canal. We present the current data regarding the etiology, pathomechanism, diagnosis, and treatment modalities of patients with PR. RESULTS: The literature review included 37 related articles that reported 44 cases of traumatic PR. Only isolated case reports and series of no more than three cases were found. In 21 cases, the air was located in the epidural space, and in 23 cases, it was in the subarachnoid space. Most of the cases were localized to a specific spinal region. However, eight cases extending to more than one spinal region have been reported. CONCLUSIONS: Traumatic PR is an asymptomatic rare clinical entity and often is underdiagnosed. It usually resolves by itself without specific treatment. We stress the significance of this information to trauma specialists, so that they may better differentiate between epidural and subarachnoid PR. This is of great significance because subarachnoid PR is a marker of severe injury. The management of traumatic PR has to be individualized and frequently requires multidisciplinary treatment, involving head, chest, and/or abdomen intervention.

Antibiotic prophylaxis in primary hip and knee arthroplasty: comparison between cefuroxime and two specific antistaphylococcal agents.

This is a prospective randomized study comparing cefuroxime to 2 antistaphylococal agents (fusidic acid and vancomycin), for prophylaxis in total hip arthroplasty (THA) and total knee arthroplasty (TKA) in an institute, where methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) prevalence exceeds 25% of orthopedic infections. There were 3 patient groups. Group A included the patients who received cefuroxime, group B those who received fusidic acid, and group C those who received vancomycin. Patients were evaluated for the presence of superficial and/or deep infection at the surgical site. Statistical analysis did not reveal any substantial difference between the 3 groups. We do not recommend the use of specific antistaphylococcal agents for prophylactic use in primary THA and TKA, even in institution where MRSA and MRSE exceed 25% of orthopedic infections.

An unusual case of olecranon tuberculosis.

A 67-year-old woman presented with erythema and swelling over her left elbow. She felt pain during palpation of the olecranon, while the range of elbow motion was slightly reduced (02 in circle-302 in circle-1302 in circle). She had been treated conservatively elsewhere for 3 months with nonsteroidal anti-inflammatory drugs and splint immobilization. Radiographs and computed tomography showed an osteolytic area over the olecranon with cortex disruption. She underwent open biopsy of the olecranon, and the histologic features were compatible with tuberculosis. Erythrocyte sedimentation rate was elevated and she had a positive Mantoux test (14 mm). She mentioned no history of pulmonary disease and had a normal chest radiograph. She received antituberculous treatment (isoniazid, rifambin, and pyrazinamide) for 2 months without obvious improvement. She underwent surgical debridement of the olecranon while she continued antituberculous treatment for 12 months, discontinuing pyrazinamide after the third month. After the completion of antituberculous treatment, the patient was pain-free, without local signs of infection and with improved range of motion (02 in circle-202 in circle-1452 in circle). Early diagnosis and treatment of olecranon tuberculosis is of great value, and the prognosis is good when there is no spread in the elbow joint.

Functional outcome of surgical treatment for multilevel lumbar spinal stenosis.

BACKGROUND: There is no consensus regarding the best treatment of patients with multilevel lumbar stenosis. We evaluated the clinical and radiological findings in 41 patients with complex degenerative spinal stenosis of the lumbar spine who were treated surgically. METHODS: Between 1997 and 2003, 41 patients suffering from degenerative lumbar spinal stenosis were included in a prospective clinical study. The spinal stenosis was multilevel in all patients and in 13 of them there was degenerative scoliosis, in 18 there was degenerative spondylolisthesis, and in 10 there was segmental instability. Plain radiographs, MRI and/or CT myelograms were obtained preoperatively. The patients were assessed clinically with the Oswestry disability index (ODI) and visual analog scale (VAS). Surgery included wide posterior decompression and fusion using a trans-pedicular instrumentation system and bone graft. RESULTS: After a mean follow-up of 3.7 (1-6) years, the patients' clinical improvement on the ODI and VAS was statistically significant. Recurrent stenosis was not observed, and 39 of 41 patients were satisfied with the outcome. 3 patients with improvement initially had later surgery because of instability. INTERPRETATION: The above-mentioned technique gives good and long lasting clinical results, when selection of patients is done carefully and when the spinal levels that are to be decompressed are selected accurately.

Secondary intramedullary nailing after distraction osteogenesis: 30 patients followed for 2-12 years.

BACKGROUND: There is no consensus about replacement of an external fixator by reamed intramedullary nailing in fracture cases. PATIENTS AND METHODS: We evaluated the outcome in 30 patients (33 segments) of secondary intramedullary nailing during the consolidation phase after callus distraction using an external device. The main reasons for nailing were docking site nonunion (17 patients), angular deformity or fracture of the lengthened area (8 patients) or intolerance of the external device (5 patients), in 11 patients combined with a delayed distracted callus maturation. The average follow-up time was 4 (2-12) years. RESULTS: Intramedullary infection after nailing occurred in 1 case, and slight loss in callus length in 5 cases. Failure of union at the docking site with nail breakage occurred in 1 case. In the other patients, consolidation in the lengthened callus area and also union at the docking site were achieved on average 6 months after nailing. INTERPRETATION: We believe that intramedullary nailing during the consolidation phase after bone lengthening or bone transport is a treatment option for delayed callus maturation or docking site nonunion, reducing prolonged use of the external fixator.

Operative treatment of unilateral bicondylar Hoffa fractures.

A rare case of unilateral bicondylar fractures of the femoral condyles is presented. Internal fixation of the fragments was achieved by three cancellous lag screws, followed by a short period of cast immobilization and intensive physiotherapy. Full weight bearing was allowed 3 months postoperatively. Full range of motion of the knee and no presence of articular defects on femoral condyles were observed 2 years after hardware and heterotopic ossification removal.