MRSA infection, re-infection and clinical outcomes in diabetic foot infections.

The aim was to investigate methicillin-resistant Staphylococcus aureus (MRSA) incidence, conversion and outcomes in diabetic foot infections (DFIs). This is a pooled patient-level analysis of combined data sets from two randomised clinical trials including 219 patients admitted to the hospital with moderate or severe DFIs. Intraoperative bone and tissue cultures identified bacterial pathogens. We identified pathogens at index infections and subsequent re-infections. We identified MRSA conversion (MSSA to MRSA) in re-infections. MRSA incidence in index infections was 10.5%, with no difference between soft tissue infections (STIs) and osteomyelitis (OM). MRSA conversion occurred in 7.7% of the re-infections in patients who initially had MSSA in their cultures. Patients with re-infection were 2.2 times more likely to have MRSA compared to the first infection (10.5% vs. 25.8%, relative risk [RR] = 2.2, p = 0.001). Patients with MRSA had longer antibiotic treatment during the 1-year follow-up, compared to other pathogens (other 49.8 ± 34.7 days, MRSA 65.3 ± 41.5 days, p = 0.04). Furthermore, there were no differences in healing, time to heal, length of stay, re-infection, amputation, re-ulceration, re-admission, surgery after discharge and amputation after discharge compared to other pathogens. The incidence of MRSA at the index was 10.5% with no difference in STI and OM. MRSA incidence was 25.8% in re-infections. The RR of having MRSA was 2.2 times higher in re-infections. Patients with MRSA used more antibiotics during the 1-year follow-up. Furthermore, there were no differences in clinical outcomes compared to other bacterial pathogens.

The infected diabetic foot: Analysis of diabetic and non-diabetic foot infections.

The aim of this study was to compare outcomes of moderate and severe foot infections in people with and without diabetes mellitus (DM). We retrospectively evaluated 382 patients (77% with DM and 23% non-DM). We collected demographic data, co-morbidities and one-year outcomes including healing, surgical interventions, number of surgeries, length of stay, re-infection and re-hospitalisation. DM patients required more surgeries (2.3 ± 2.2 vs. 1.7 ± 1.3, p = 0.01), but did not have a longer hospital length of stay during the index hospitalisation (DM 10.9 days ±9.2 vs. non-DM = 8.8 days ±5.8, p = 0.43). After the index hospitalisation, DM patients had increased rates of re-hospitalisation for any reason (63.3% vs. 35.2%, CI 1.9-5.2, OR 3.2, p < 0.01), re-infection at the index wound infection site (48% vs. 30.7%, CI 1.3-3.5, OR 2.1, p < 0.01), re-hospitalisation for a foot pathology (47.3% vs. 29.5%, CI 1.3-3.6, OR 2.1, p < 0.01), and longer times to ulcer healing (151.8 days ±108.8 vs. 108.8 ± 90.6 days, p = 0.04). Patients with DM admitted to hospital with foot infections have worse clinical outcomes during the index hospitalisation and are more likely to have re-infection and re-admission to hospital in the next year.

The infected diabetic foot: Modulation of traditional biomarkers for osteomyelitis diagnosis in the setting of diabetic foot infection and renal impairment.

The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM-NSRI), and patients with diabetes and SRI (DM-SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM-NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM-SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM-NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM-SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient-specific factors when interpreting ESR results in the context of OM diagnosis.

Cone-beam-computed tomography evaluation of mandibular nutrient canals in patients with periodontal diseases.

Background and Aim: The aim of this study was to evaluate radiographically the prevalence of mandibular nutrient canals (NCs) in patients with/without periodontal bone loss with aging and to correlate the number of NCs with the severity of bone loss using cone-beam-computed tomography (CBCT). Patients and Methods: CBCT examinations of 208 patients were evaluated retrospectively of all patients, 114 had periodontal bone loss, whereas 94 patients were control subjects. Alveolar bone loss investigations were performed according to the Progressive Rate Index. Results: NCs were observed in 55% of the control group and 86% of the periodontitis patients. NCs were more prevalent in the elderly age group with periodontal bone loss. In the study group, the NCs were statistically more frequent than in the control subjects (P > 0.05). Conclusion: Statistical analysis showed a significant difference between the age groups and the prevalence of NCs increased in patients with periodontal alveolar bone loss with aging (P < 0.05).

Comparison of BMIPP-SPECT/CT to 18FDG-PET/CT for Imaging Brown or Browning Fat in a Preclinical Model.

Obesity is a leading cause of preventable death and morbidity. To elucidate the mechanisms connecting metabolically active brown adipose tissue (BAT) and metabolic health may provide insights into methods of treatment for obesity-related conditions. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is traditionally used to image human BAT activity. However, the primary energy source of BAT is derived from intracellular fatty acids and not glucose. Beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) is a fatty acid analogue amenable to in vivo imaging by single photon emission computed tomography/CT (SPECT/CT) when radiolabeled with iodine isotopes. In this study, we compare the use of 18FDG-PET/CT and 125I-BMIPP-SPECT/CT for fat imaging to ascertain whether BMIPP is a more robust candidate for the non-invasive evaluation of metabolically active adipose depots. Interscapular BAT, inguinal white adipose tissue (iWAT), and gonadal white adipose tissue (gWAT) uptake of 18FDG and 125I-BMIPP was quantified in mice following treatment with the BAT-stimulating drug CL-316,243 or saline vehicle control. After CL-316,243 treatment, uptake of both radiotracers increased in BAT and iWAT. The standard uptake value (SUVmean) for 18FDG and 125I-BMIPP significantly correlated in these depots, although uptake of 125I-BMIPP in BAT and iWAT more closely mimicked the fold-change in metabolic rate as measured by an extracellular flux analyzer. Herein, we find that imaging BAT with the radioiodinated fatty acid analogue BMIPP yields more physiologically relevant data than 18FDG-PET/CT, and its conventional use may be a pivotal tool for evaluating BAT in both mice and humans.

Radiological Evaluation of the Recesses on the Posterior Wall of the Nasopharynx with Cone-beam Computed Tomography.

BACKGROUND: The posterior wall of the nasopharynx is composed of loose connective tissue that includes many important anatomical structures. Various structures, such as the opening of the Eustachian tube (ET), the Rosenmüller fossa (RF), and the pharyngeal bursa (PB) are found here. AIM: To evaluate the nasopharynx posterior wall anatomic structures, including the Eustachian tube, Rosenmüller fossa, and pharyngeal bursa with cone-beam computed tomography. MATERIALS AND METHODS: The depth, width, and length of the Eustachian tube, Rosenmüller fossa, and pharyngeal bursa were measured in 150 patients using axial-sagittal cone-beam computed tomography. The Eustachian tube and Rosenmüller fossa distance to the midsagittal plane, the coronal region passing through the posterior end of the nasal septum, the superior-inferior extremity of the recesses, and the nasal floor plane distance were measured. The relationship between Rosenmüller fossa types and other parameters were evaluated. RESULTS: The incidence of right Rosenmüller fossa types 1, 2, and 3 were 16%, 18%, and 66%, respectively, and that of the left Rosenmüller fossa types 1, 2, and 3 were 16%, 19.3%, and 64.7%, respectively. The mean pharyngeal bursa width, length, and depth were 10.8, 5.7, and 4.0 mm, respectively; those of the Eustachian tube were 5.6, 7.1, and 7.3 m, respectively; those of the right Rosenmüller fossa were 4.0, 12.4, and 10.5 mm, respectively; and those of the left Rosenmüller fossa were 3.8, 12.5, and 10.9 mm, respectively. CONCLUSIONS: The posterior wall of the nasopharynx contains several important anatomical structures. Evaluation of these using cone-beam computed tomography has many clinical and radiological advantages. To understand and interpret the coincidental findings in CBCT, dental radiologists should have access to more detailed information concerning the anatomy of the nasopharynx.

Publication trends in micro-CT endodontic research: a bibliometric analysis over a 25-year period.

AIM: To conduct a bibliographic analysis of the research studies published in Endodontics using micro-computed tomography (micro-CT) as an analytical tool over a 25-year period. METHODOLOGY: The Web of Science electronic database was accessed, and an advanced search using strict criteria was undertaken from January 1995 to June 2020 for studies in the field of Endodontics that used micro-CT as an analytical tool. A further search was conducted between January and August of 2020 for a combination of specific terms and descriptors. For each selected article, the following parameters were recorded: field of the study, analysed specimen, publication title and year, authorship, journal of publication, institution and country of origin, collaborating institutions and countries, and number of citations. The acquired data were analysed using descriptive statistics and graphical mappings. RESULTS: The screening process identified 877 relevant articles that were classified into 30 thematic categories. The main fields of research were root canal preparation (23.8%), root canal anatomy (17.4%), canal filling (9.2%) and root canal retreatment (7.0%). The most productive half-decade comprised the period of 2015-2019 (n = 513; 58.5%), with the highest number of articles published in 2019 (n = 146; 16.6%). The authors who lead the list as first authors were G De-Deus, A Keles, F Paqué, MA Versiani and Y Gu, respectively, whilst Versiani was the most productive (n = 51). The leading countries regarding the number of studies were Brazil, China and Turkey with 236, 130 and 65 publications, respectively. The University of São Paulo (n = 90; 10.3%) followed by Wuhan University (n = 37; 4.2%) and the University of Zurich (n = 18; 2.1%) were the prominent contributors by producing the largest number of articles, whilst the University of Zurich was the most-cited institution. The selected studies were published in 140 scientific journals, but the Journal of Endodontics and International Endodontic Journal accounted for almost 50% of the publications. CONCLUSION: This bibliometric analysis portrayed an original and comprehensive view on the progress and trends of the use of micro-CT technology in endodontic research, and enabled a deep understanding of the development process in this field over the last 25 years.

The effect of type 2 diabetes mellitus on changes in the fractal dimension of periapical lesion in teeth after root canal treatment: a fractal analysis study.

AIM: This single-centre retrospective case-control study evaluated fractal dimension (FD) changes in radiographs of periapical lesions using a fractal analysis in healthy individuals and type 2 diabetes mellitus (DM) patients following root canal treatment. METHODOLOGY: The study data consisted of two groups: the DM group which contained a total of 46 mandibular molar teeth in 37 patients with no systemic disease other than type 2 DM, and the control group which contained a total of 52 mandibular molar teeth in 41 patients without systemic disease. Periapical radiographs were obtained prior to root canal treatment and 1 year post-treatment. Fractal analysis was performed by selecting a region of interest on the periapical radiographs. For both groups, the FD changes in lesion area were calculated and compared. In addition, periapical status was evaluated using the periapical index (PAI) scores on periapical radiographs for both groups. Data were analysed using dependent-sample t-test, independent-sample t-test, Wilcoxon signed-rank test and Mann-Whitney U-test. RESULTS: In both groups, FD values were increased significantly 1 year post-treatment as compared with those prior to treatment (P < 0.05). The time-dependent increase in FD was significantly greater in the control group (P < 0.05). Time-dependent increases in FD did not differ between genders (P > 0.05). There was a significant decrease in PAI scores in both type 2 DM and control groups depending on time (P < 0.05). No significant difference was found between the groups in terms of time-related decreases in PAI scores (P > 0.05). CONCLUSION: An increase in the FD of the periapical lesion area was observed 1 year after root canal treatment. DM had a negative effect on FD increase.

Pathophysiology and Molecular Imaging of Diabetic Foot Infections.

Diabetic foot infection is the leading cause of non-traumatic lower limb amputations worldwide. In addition, diabetes mellitus and sequela of the disease are increasing in prevalence. In 2017, 9.4% of Americans were diagnosed with diabetes mellitus (DM). The growing pervasiveness and financial implications of diabetic foot infection (DFI) indicate an acute need for improved clinical assessment and treatment. Complex pathophysiology and suboptimal specificity of current non-invasive imaging modalities have made diagnosis and treatment response challenging. Current anatomical and molecular clinical imaging strategies have mainly targeted the host's immune responses rather than the unique metabolism of the invading microorganism. Advances in imaging have the potential to reduce the impact of these problems and improve the assessment of DFI, particularly in distinguishing infection of soft tissue alone from osteomyelitis (OM). This review presents a summary of the known pathophysiology of DFI, the molecular basis of current and emerging diagnostic imaging techniques, and the mechanistic links of these imaging techniques to the pathophysiology of diabetic foot infections.

Gray value measurement for the evaluation of local alveolar bone density around impacted maxillary canine teeth using cone beam computed tomography.

BACKGROUND: To investigate whether any relationship between local alveolar bone density and maxillary canine impaction using gray values from cone beam computed tomography. MATERIAL AND METHODS: The cone beam computed tomography images of 151 patients were retrospectively evaluated. Maxillary canine was defined as an impacted tooth when root formation was complete and the patient's age older than 13 or the other side of the maxillary canine has completely erupted. Similarly, complete eruption was defined as the tooth in its expected occlusion and position. Using the cone beam computed tomography software, the region of interest which was 5 mm2 in area, was placed in the trabecular bone on cross sectional cone beam computed tomography images and the gray value measurements were recorded. After measuring the gray values of all the teeth, the images were grouped according to the field of view size. Comparison of the gray values of impacted and non-impacted teeth was made between images with the same field of view size. RESULTS: A total of 151 patients, 101 (66.9%) female and 50 (33.1%) male, were included in the study. The mean age of the patients was 24.94 ±13.9. In images with a 40X40 field of view, the gray values of the impacted canine teeth were higher than the gray values of the non-impacted ones and statistically significant difference was found between them (p=0.003). However no statistically significant difference was found between the gray values of impacted and non-impacted canine teeth in 60x60 and 100x50 field of view (p=0.197, p=0.170, respectively). CONCLUSIONS: We suggest using the smallest field of view size when evaluating bone density using gray values from cone beam computed tomography images and we support the idea that the local increased bone density may influence on impaction.

The Infected Diabetic Foot: Re-evaluating the Infectious Diseases Society of America Diabetic Foot Infection Classification.

BACKGROUND: We provide evidence to revise the Infectious Diseases Society of America (IDSA) diabetic foot infection classification by adding a separate tier for osteomyelitis and evaluating if moderate and severe infection criteria improve the classification's ability to direct therapy and determine outcomes. METHODS: We retrospectively evaluated 294 patients with moderate and severe infections. Osteomyelitis was confirmed by bone culture or histopathology. Soft tissue infection (STI) was based on negative bone culture, magnetic resonance imaging, or single-photon emission computed tomography. We stratified STI and osteomyelitis using IDSA criteria for moderate and severe infections and compared outcomes and complications. RESULTS: Osteomyelitis patients had greater antibiotic duration (32.5 ± 46.8 vs 63.8 ± 55.1 days; P < .01), surgery frequency (55.5% vs 99.4%; P < .01), number of surgeries (2.1 ± 1.3 vs 3.3 ± 2.3; P < .01), amputations (26.3% vs 83.4%; P < .01), reinfection (38.0% vs 56.7%; P < .01), and length of stay (14.5 ± 14.9 vs 22.6 ± 19.0 days; P < .01). There were no differences in moderate and severe STI outcomes except for infection readmissions (46.2% vs 25.0%; P = .02), and acute kidney injury (31.2% vs 50.0%; P = .03). There were no differences in moderate and severe osteomyelitis except the number of surgeries (2.8 ± 2.1 vs 4.1 ± 2.5; P < .01) and length of stay (18.6 ± 17.5 vs 28.2 ± 17.7; P < .01). CONCLUSIONS: The IDSA classification better reflects outcomes if risk categories are stratified by STI or osteomyelitis and moderate and severe infections are not categorized separately.

Randomized clinical study to compare negative pressure wound therapy with simultaneous saline irrigation and traditional negative pressure wound therapy for complex foot infections.

The aim of this study was to compare the efficacy of different negative pressure wound therapy (NPWT) devices and NPWT with and without simultaneous irrigation in patients admitted to hospital with moderate and severe foot infections. Ninety patients were randomized in a 12-week prospective, randomized noninferiority trial to compare wound healing in patients with moderate and severe infected foot wounds treated with NPWT after surgery. Inclusion criteria included ABI > 0.5 or toe pressures >30 PVR/mmHg, >18 years of age and exclusion included active Charcot arthropathy, collagen vascular disease, HIV, and hypercoagulable state. We compared two different traditional devices, NPWT-K (KCI, VAC Ulta) and NPWT-C (Cardinal, PRO), and NPWT-I with saline irrigation (Cardinal, PRO). All patients had therapy delivered at 125 mmHg continuous pressure. In patients who received simultaneous saline irrigation (NPWT-I), the administration rate was 15 ml per hour. The primary outcome was the proportion of healed wounds in 12 weeks. Secondary outcomes included surgical wound closure, number of surgeries, length of stay, and time to wound healing. Continuous data was presented as mean ± standard deviation. Analysis of variance was used to compare continuous variables and chi-square to compare dichotomous variables with an alpha of 0.05. There were no differences in outcomes among NPWT-I, NPWT-C, and NPWT-K groups in proportion of healed wounds (63.3%, 50.0%, 46.7% p = 0.39), surgical wound closure (83.3%, 80.0%, 63.3%, p = 0.15), number of surgeries (2.0 ± 0.49, 2.4 ± 0.77, 2.4 ± 0.68, p = 0.06), length of stay (16.3 ± 15.7, 14.7 ± 7.4, 15.3 ± 10.5 days, p = 0.87), time to wound healing (46.2 ± 22.8, 40.9 ± 18.8, 45.9 ± 28.3 days, p = 0.78). We did not identify any significant differences in clinical outcomes or adverse events between patients treated with different NPWT devices or NPWT with and without irrigation.

Evaluation of artificial intelligence for detecting periapical pathosis on cone-beam computed tomography scans.

AIM: To verify the diagnostic performance of an artificial intelligence system based on the deep convolutional neural network method to detect periapical pathosis on cone-beam computed tomography (CBCT) images. METHODOLOGY: images of 153 periapical lesions obtained from 109 patients were included. The specific area of the jaw and teeth associated with the periapical lesions were then determined by a human observer. Lesion volumes were calculated using the manual segmentation methods using Fujifilm-Synapse 3D software (Fujifilm Medical Systems, Tokyo, Japan). The neural network was then used to determine (i) whether the lesion could be detected; (ii) if the lesion was detected, where it was localized (maxilla, mandible or specific tooth); and (iii) lesion volume. Manual segmentation and artificial intelligence (AI) (Diagnocat Inc., San Francisco, CA, USA) methods were compared using Wilcoxon signed rank test and Bland-Altman analysis. RESULTS: The deep convolutional neural network system was successful in detecting teeth and numbering specific teeth. Only one tooth was incorrectly identified. The AI system was able to detect 142 of a total of 153 periapical lesions. The reliability of correctly detecting a periapical lesion was 92.8%. The deep convolutional neural network volumetric measurements of the lesions were similar to those with manual segmentation. There was no significant difference between the two measurement methods (P > 0.05). CONCLUSIONS: Volume measurements performed by humans and by AI systems were comparable to each other. AI systems based on deep learning methods can be useful for detecting periapical pathosis on CBCT images for clinical application.

Clinical Outcomes of Foot Infections in Patients Without Diabetes.

The aim of this study was to report clinical outcomes of moderate and severe foot infections in patients without diabetes. Medical records of 88 nondiabetic patients with foot infections treated at a safety net hospital were retrospectively reviewed. Patients were grouped by the presence of soft-tissue infection (STI) or osteomyelitis (OM). The diagnosis of OM was determined by positive bone culture or histopathology. STIs were defined by negative bone biopsy or negative imaging with magnetic resonance imaging or computed tomography/dual-modality radiolabeled white blood cell single-photon emission computed tomography. Patient outcomes were recorded ≤1 year after admission. Eighty-eight nondiabetic patients admitted to our institution for moderate or severe foot infections were included, 45 OM and 43 STI. No differences were noted in patient characteristics except that OM patients had a higher prevalence of neuropathy (66.7% versus 39.5%, p = .02). OM patients required surgery more often (97.8% versus 67.4%, p < .01), a greater number of surgeries (2.0 ± 1.2 versus 1.4 ± 1.3, p = .02), and more amputations (75.6% versus 11.6%, p < .01) than STI patients. OM patients had a higher proportion of wounds that healed (82.2% versus 62.8%, p = .04). There were no significant differences in reinfection (35.6% versus 25.6%, p = .36), foot-related readmission to hospital (35.6% versus 23.3%, p = .25), or total duration of antibiotics (13.9 ± 10.2 versus 13.5 ± 12.9, p = .87) between OM and STI patients. In conclusion, OM patients required more surgeries and amputations than patients with STIs; however, they had similar rates of reinfection and readmission within a year after the index hospitalization.

Translation of Quantitative Imaging Biomarkers into Clinical Chest CT.

Quantitative imaging has been proposed as the next frontier in radiology as part of an effort to improve patient care through precision medicine. In 2007, the Radiological Society of North America launched the Quantitative Imaging Biomarkers Alliance (QIBA), an initiative aimed at improving the value and practicality of quantitative imaging biomarkers by reducing variability across devices, sites, patients, and time. Chest CT occupies a strategic position in this initiative because it is one of the most frequently used imaging modalities, anatomically encompassing the leading causes of mortality worldwide. To date, QIBA has worked on profiles focused on the accurate, reproducible, and meaningful use of volumetric measurements of lung lesions in chest CT. However, other quantitative methods are on the verge of translation from research grounds into clinical practice, including (a) assessment of parenchymal and airway changes in patients with chronic obstructive pulmonary disease, (b) analysis of perfusion with dual-energy CT biomarkers, and (c) opportunistic screening for coronary atherosclerosis and low bone mass by using chest CT examinations performed for other indications. The rationale for and the key facts related to the application of these quantitative imaging biomarkers in cardiothoracic chest CT are presented. ©RSNA, 2019 See discussion on this article by Buckler (pp 977-980).

Comparison of Various Hematopoietic Stem Cell Mobilization Regimens in Patients with Lymphoma and Myeloma.

BACKGROUND: The aim of this study was to evaluate the efficacy of cyclophosphamide-based (CB) and platinum-based (PB) chemotherapy regimens for hematopoietic stem cell mobilization in patients with Multiple Myeloma (MM), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) and the less well-known IEV (iphosphamide, epirubicin, etoposide) regimen in terms of stem cell harvesting competence, factors affecting stem cell com-petence, and toxicity. METHODS: A retrospective evaluation was made of 203 patients (94 MM, 37 HL, and 72 NHL) with peripheral blood stem cell mobilization in different chemotherapy regimens between 2000 and 2010 at the Department of He-matology, Faculty of Medicine, Akdeniz University. RESULTS: There were no differences between CB or PB mobilization regimens and IEV chemotherapy schema in terms of sufficiency of peripheral stem cell harvest, which was predefined as the collected number of peripheral stem cells ≥ 3 x 106/kg for single hematopoietic stem cell transplantation (HSCT) and ≥ 5 x 106/kg for tandem HSCT. There were also no significant differences between low dose cyclophosphamide, high dose cyclophosphami-de, and HCVAD (cyclophosphamide, vincristine, dexamethasone, methotrexate, cytosine arabinoside [ARA-C]) among the subgroups of cyclophosphamide-based regimens. The number of peripheral blood stem cells collected using ESHAP (ethoposide, methylprednisolone, ARA-C, cisplatin), a platin-based regimen, was significantly higher than the other platin-based regimens including DHAP (dexamethasone, ARA-C, cisplatin), ICE (iphosphamide, carboplatin, ethopocide), and EDAP (etoposide, dexamethasone, ARA-C, cisplatin). The toxicity profiles of CB, PB, and IEV chemotherapies were similar. To determine the independent predictors of the efficacy of the stem cell harvest procedure and collected stem cell count, age, diagnosis, duration of disease, number of treatment sequences before mobilization, and number of rescue regimens were included into multiple logistic regression analysis. However, no correlations were determined. CONCLUSIONS: The results of this study provide information on the effectiveness of different stem cell mobilization regimens. Although no significant difference was determined between the three major chemotherapy regimens, the ESHAP regimen appears to be the preferred treatment regimen for stem cell mobilization in selected lymphomas.

What are the Optimal Cutoff Values for ESR and CRP to Diagnose Osteomyelitis in Patients with Diabetes-related Foot Infections?

BACKGROUND: Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined. QUESTIONS/PURPOSES: (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection? METHODS: The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations. RESULTS: An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67-80) and specificity of 56% (95% CI, 48-63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41-57) and specificity of 80% (95% CI, 74-86). If the ESR is < 30 mm/h, the likelihood of osteomyelitis is low. However, if ESR is > 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered. CONCLUSIONS: While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging. LEVEL OF EVIDENCE: Level III, diagnostic study.

Effects of alpha-lipoic acid therapy on experimentally induced apical periodontitis: a biochemical, histopathological and micro-CT analysis.

AIM: To investigate the possible therapeutic effects of alpha-lipoic acid (ALA) in a model of chronic apical periodontitis in rats by analysing biochemical, histopathological and micro-CT parameters. METHODOLOGY: The study was approved by the Animal Ethics Committee of the Near East University. Thirty-two Wistar rats were divided into four groups of eight rats each: Control Group; ALA Group; AP Group; AP + ALA Group. In the AP and AP + ALA groups, the pulp chambers of the mandibular first molars were surgically exposed and were left open to the oral environment for 4-weeks to allow the establishment of periapical lesions. The rats in the Control and AP groups were treated intraperitoneally with saline solution (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). The rats in the ALA and AP + ALA groups were treated intraperitoneally with ALA (with a daily dose of 100 mg kg-1 , for 28 days after periapical lesion induction). After decapitation, the trunk blood was collected for the assessment of biochemical parameters. The mandibles were surgically removed and dissected for histopathologic analysis and further scanned with micro-CT. Groups of data were compared with a two-way analysis of variance (two-way anova) followed by Sidak's multiple comparison tests. Values of P < 0.05 were regarded as significant. RESULTS: TNF-α, IL-1ß, MMP-1, MMP-2 levels were significantly lower in AP + ALA group compared with AP group (P < 0.05). There was a significant difference between the AP and AP + ALA groups according to assessment of the inflammatory scores (P < 0.05). The periapical inflammatory infiltrates were significantly more severe (P < 0.05) in the AP group. The AP + ALA group exhibited lower values both in terms of surface area and volume of resorption cavities than the AP group and this difference was significant (P < 0.05). CONCLUSION: alpha-lipoic acid treatment provided therapeutic effects on the inhibition of periapical bone loss.

Imaging Metabolically Active Fat: A Literature Review and Mechanistic Insights.

Currently, obesity is one of the leading causes death in the world. Shortly before 2000, researchers began describing metabolically active adipose tissue on cancer-surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in adult humans. This tissue generates heat through mitochondrial uncoupling and functions similar to classical brown and beige adipose tissue in mice. Despite extensive research, human brown/beige fat's role in resistance to obesity in humans has not yet been fully delineated. FDG uptake is the de facto gold standard imaging technique when studying brown adipose tissue, although it has not been rigorously compared to other techniques. We, therefore, present a concise review of established and emerging methods to image brown adipose tissue activity in humans. Reviewed modalities include anatomic imaging with CT and magnetic resonance imaging (MRI); molecular imaging with FDG, fatty acids, and acetate; and emerging techniques. FDG-PET/CT is the most commonly used modality because of its widespread use in cancer imaging, but there are mechanistic reasons to believe other radiotracers may be more sensitive and accurate at detecting brown adipose tissue activity. Radiation-free modalities may help the longitudinal study of brown adipose tissue activity in the future.

Are We Misdiagnosing Diabetic Foot Osteomyelitis? Is the Gold Standard Gold?

To compare the incidence of osteomyelitis based on different operational definitions using the gold standard of bone biopsy, we prospectively enrolled 35 consecutive patients who met the criteria of ≥21 years of age and a moderate or severe infection based on the Infectious Diseases Society of America classification. Bone samples were obtained from all patients by percutaneous bone biopsy or intraoperative culture if the patient required surgery. Bone samples were analyzed for conventional culture, histology, and 16S ribosomal RNA genetic sequencing. We evaluated 5 definitions for osteomyelitis: 1) traditional culture, 2) histology, 3) genetic sequencing, 4) traditional culture and histology, and 5) genetic sequencing and histology. There was variability in the incidence of osteomyelitis based on the diagnostic criteria. Traditional cultures identified more cases of osteomyelitis than histology (68.6% versus 45.7%, p = .06, odds ratio [OR] 2.59, 95% confidence interval [CI] 0.98 to 6.87), but the difference was not significant. In every case that histology reported osteomyelitis, bone culture was positive using traditional culture or genetic sequencing. The 16S ribosomal RNA testing identified significantly more cases of osteomyelitis compared with histology (82.9% versus 45.7%, p = .002, OR 5.74, 95% CI 1.91 to 17.28) and compared with traditional cultures but not significantly (82.9% versus 68.6%, p = .17, OR 2.22, 95% CI 0.71 to 6.87). When both histology and traditional culture (68.6%) or histology and genetic sequencing cultures (82.9%) were used to define osteomyelitis, the incidence of osteomyelitis did not change. There is variability in the incidence of osteomyelitis based on how the gold standard of bone biopsy is defined in diabetic foot infections.