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1.  Sudeck's disease stage 1, or diabetic Charcot's foot stage 0? Case report and assessment of the diagnostic value of MRI 
The diagnosis of Sudeck's syndrome stage 1 (nowadays termed complex regional pain syndrome I, abbreviated CRPS I) is based on clinical features, namely swelling and pain in a limb. Plain X-ray may be normal. In the absence of pain sensitivity, e.g. in diabetic neuropathy, CRPS I of the foot can be mistaken for Charcot's foot stage 0 (so-called neuro-osteoarthropathy).
Case presentation
The case of a type-1 diabetic woman is reported, in whom CRPS I following a calcaneal fracture was mistaken for Charcot's osteoarthropathy (because of bone marrow edema displayed by conventional MR imaging). In addition, a review is presented on 6 consecutive cases with CRPS I of the foot, and on 20 cases with Charcot's foot stage 0, with particular emphasis on MR imaging findings. The number of bones per foot affected with marrow edema was similar in either condition, with a tendency towards a more patchy, diffuse distribution of bone marrow edema in CRPS I. Bone marrow edema apparently regressed more promptly in response to treatment in Charcot's foot stage 0.
Differentiation of CRPS I from Charcot's foot stage 0 remains a diagnostic dilemma in patients with pain insensitivity. Conventional MRI may be helpful, when repeated for monitoring the treatment response.
PMCID: PMC2958966  PMID: 20923545
2.  Safety and Efficacy of Mild Compression (18–25 mm Hg) Therapy in Patients with Diabetes and Lower Extremity Edema 
Patients with diabetes often present with lower extremity (LE) edema; however, because of concomitant peripheral arterial disease, compression therapy is generally avoided by providers in fear of compromising arterial circulation. This pilot study sought to assess whether diabetic socks with mild compression (18–25 mm Hg) can reduce LE edema in patients with diabetes without negatively impacting vascularity.
Eighteen subjects (9 males, 9 females) aged 61 ± 11 years with diabetes, LE edema, and a mean ankle–brachial index (ABI) of 1.10 ± 0.21 successfully completed this uncontrolled study. At baseline, subjects were fitted and instructed to wear the socks during all waking hours. Follow-up visits occurred weekly for four consecutive weeks. Edema was quantified through midfoot, ankle, and calf circumferences and cutaneous fluid measurements. Vascular status was tracked via ABI.
Repeated measures analysis of variance and least significant difference post hoc analyses were used for data analyses. Calf circumferences showed a statistically significant (p < .05) decrease of 1.3 ± 0.28 cm after just one week and remained significantly smaller than baseline throughout the study. Foot circumferences were significantly reduced at week 2 (−0.98 ± 0.35 cm) and remained significantly below baseline for the remainder of the study. The ankle also demonstrated a trend of circumference reduction but was not statistically significant. Cutaneous edema significantly reduced by week 3 (−3.1 ± 1.3 U) and remained so at week 4. Ankle–brachial index significantly increased (0.14 ± 0.049) at week 2 but was not significantly higher at weeks 3 or 4. No adverse events occurred during the study.
Mild compression therapy (18–25 mm Hg) decreased swelling in diabetes patients with LE edema without compromising vascularity.
PMCID: PMC3440039  PMID: 22768895
compression; diabetes; edema; lower extremity
3.  Determining the Etiology of Pulmonary Edema by the Edema Fluid-to-Plasma Protein Ratio 
We hypothesized that the edema fluid-to-plasma protein (EF/PL) ratio, a non-invasive measure of alveolar capillary membrane permeability, can accurately determine the etiology of acute pulmonary edema.
390 mechanically ventilated patients with acute pulmonary edema were enrolled. A clinical diagnosis of acute lung injury (ALI), cardiogenic pulmonary edema, or a mixed etiology was based on expert medical record review at the end of hospitalization. The EF/PL ratio was measured from pulmonary edema fluid and plasma samples collected at intubation.
209 patients had a clinical diagnosis of ALI, 147 had a diagnosis of cardiogenic pulmonary edema and 34 had a mixed etiology. The EF/PL ratio had an area under the receiver-operating curve of 0.84 for differentiating ALI from cardiogenic pulmonary edema. Using a predefined cutoff of 0.65, the EF/PL ratio had a sensitivity of 81% and a specificity of 81% for the diagnosis of ALI. An EF/PL ratio ≥ 0.65 was also associated with significantly higher mortality and fewer ventilator free days.
Non-invasive measurement of the EF/PL ratio is a safe and reliable bedside method for rapidly determining the etiology of acute pulmonary edema that can be used at the bedside in both developed and developing countries.
PMCID: PMC2819058  PMID: 19741024
acute pulmonary edema; acute lung injury; acute respiratory distress syndrome; alveolar capillary membrane permeability; diagnosis
4.  Bilateral Reversible Corneal Edema Associated With Amantadine Use 
In this article, we report a case of bilateral severe reversible corneal edema caused by amantadine therapy.
A 39-year-old women was referred to us for evaluation of bilateral corneal edema. Her past medical history was significant for multiple sclerosis, anorexia, and seizures. She developed painless progressive bilateral loss of vision for the past 6 months. She was evaluated by several ophthalmologists elsewhere who felt that the patient’s visual loss was secondary to a nutritional deficiency as opposed to related to multiple sclerosis. She was started on vitamin B-12 medication without improvement in her symptoms. She was then evaluated by neuro-ophthalmology. The examination revealed severe bilateral corneal edema and was referred to our corneal service for further evaluation of her corneal condition. Our examination revealed best corrected visual acuity of 20/400 bilaterally. Corneal thickness was 940 µm in the right eye and 802 µm in the left. Color vision was intact. Conjunctivas were white bilaterally. Cornea evaluation revealed diffuse stromal edema and Descemet’s folds and microcystic subepithelial edema with to guttae noted. Anterior chambers were deep and quiet. A specular microscopy revealed significant pleomorphism and polymegathism with an endothelial cell count of 1,504 cells in the right eye and 1,596 in the left eye.
Review of the patient’s medical information revealed therapy with amantadine 2 months prior to the appearance of the patient’s symptoms as a means to control the patient’s tremors. The patient experienced rapid resolution of the corneal edema within the next 2 months after discontinuation of the agent with recovery of best corrected visual acuity of 20/40 in the right eye and 20/30 in the left.
In cases of unexplained corneal edema and in the absence of any identifiable ocular cause, a review of toxic effects of systemic medications should be performed. Early diagnosis may prevent irreversible endothelial damage. Amantadine can cause endothelial failure and needs to be considered as part of the differential diagnosis of corneal edema.
PMCID: PMC3096536  PMID: 20028266
5.  Lymphoplasmacyte-rich meningioma: our experience with 19 cases and a systematic literature review 
Objective: To investigate the clinicopathological characteristics, prognosis, pathology, and differential diagnosis of LPM by analyzing our experience and reviewed relevant literature. We also postulated the necessity of postoperative adjuvant therapy. Methods: 19 patients with LPM underwent surgical treatment from 2007 through 2010 in our department. The clinical charts of the patients, including surgical, histological, and follow-up records, as well as imaging studies, were analyzed retrospectively. Other 43 cases searched from the literature were also included, so that 62 LPM cases were summarized and reviewed together. Results: The summarized 62 patients comprised 30 males and 31 females aged 9 years to 79 years (40.7±18.3 years). The most common locations were convexity, skull base, para-sagittal and cervical canal. Multiple or diffuse lesions were found in 8 cases. There were 13 patients had peripheral blood abnormalities (21%). One-third of the cases had moderate to severe peritumoral brain edema. Thirty-eight patients had total resection, 12 patients not specified while 12 received subtotal resection or only biopsy. MIB-1 was available in 24 cases and a third of them were higher than 3%. Follow-up more than 3 year was only completed in 19/62 cases. Seven cases suffered recurrence and two of them died after 2 years of operation. Conclusion: LPM is a very rare benign variant of intracranial meningioma. Both lesions and hematological abnormalities have a predilection for younger individuals. Preoperative diagnosis of this subtype of meningioma is still difficult. Surgical resection is the primary treatment option, and supportive care for those not totally removed is very important, because the recurrence rate for this subtype is rather low. However, the massive infiltration of lymphocytes and plasma cells in LPMs are still controversial and the long-term follow-ups are needed. Radiotherapy is not recommended, and hormonal or immune-inhibitor therapy might be helpful.
PMCID: PMC3731181  PMID: 23936588
Diagnosis; differential diagnosis; edema; lymphoplasmacyte-rich meningioma; prognosis
6.  Tumefactive perivascular spaces mimicking cerebral edema in a patient with diabetic hyperglycemic hyperosmolar syndrome: a case report 
Acute cerebral edema is a significant cause of death in patients treated for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome.
Case presentation
We present the case of a 44-year-old African American woman admitted with acute severe headache and diagnosed with diabetic hyperglycemic hyperosmolar syndrome. Computed tomography of the head showed diffuse leukoencephalopathy, but sparing of the cortex. We were concerned for acute cerebral edema secondary to hyperglycemic hyperosmolar syndrome. Magnetic resonance imaging of the brain showed numerous collections of cystic spaces in the white matter of both hemispheres representing tumefactive perivascular spaces. Her headache improved with correction of the hyperglycemic hyperosmolar state.
Although the clinical presentation and head computed tomography were concerning for cerebral edema, the distinctive features on brain magnetic resonance imaging helped to clarify the diagnosis and differentiate it from other processes.
PMCID: PMC3599740  PMID: 23432798
Tumefactive perivascular spaces; Cerebral edema; Hyperglycemic hyperosmolar syndrome
7.  Itraconazole associated quadriparesis and edema: a case report 
Itraconazole is an anti-fungal agent widely used to treat various forms of mycosis. It is particularly useful in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Side effects are uncommon and usually mild. Mild neuropathy is noted to occur very rarely. We present an unusual and, to the best of our knowledge, as yet unreported case of severe neuropathy and peripheral edema due to itraconazole in the absence of a concomitant risk factor.
Case presentation
A 72-year-old Caucasian man was started on itraconazole following diagnosis of severe asthma with fungal sensitization. One month later he presented with severe bilateral ankle edema with an elevated serum itraconazole level. The itraconazole dose was reduced but his ankle edema persisted and he developed weakness of all four limbs. Itraconazole was completely stopped leading to improvement in his leg edema but he became bed bound due to weakness. He gradually improved with supportive care and neurorehabilitation. On review at six months, our patient was able to mobilize with the aid of two elbow crutches and power had returned to 5/5 in distal extremities and 4+/5 in proximal extremities. The diagnosis was established based on the classical presentation of drug-induced neuropathy and negative investigatory findings for any alternative diagnoses.
We report the case of a patient presenting with an unusual complication of severe neuropathy and peripheral edema due to itraconazole. Clinicians should be alert to this association when encountered with neuropathy and/or edema in an itraconazole therapy recipient.
PMCID: PMC3080323  PMID: 21477327
8.  Preliminary Assessment of Celecoxib and Microdiode Pulse Laser Treatment of Diabetic Macular Edema 
Retina (Philadelphia, Pa.)  2010;30(3):459-467.
Inflammation may play an important role in the pathogenesis of diabetic macular edema, a major cause of vision loss in persons with diabetes. The purpose of this study was to evaluate combined antiinflammatory therapy and laser approaches for treating patients with diabetic macular edema.
In this prospective, factorial, randomized, multicenter trial, we compared cyclo-oxygenase-2 inhibitor (celecoxib) with placebo and diode grid laser with standard Early Treatment Diabetic Retinopathy Study focal laser treatment in 86 participants with diabetic macular edema. The primary outcome is change in visual acuity of ≥15 letters from baseline, and the secondary outcomes include a 50% reduction in the retinal thickening of diabetic macular edema measured by optical coherence tomography and a 50% reduction in leakage severity on fluorescein angiography.
Visual acuity and retinal thickening data from >2 years of follow-up did not show evidence of differences between the medical and laser treatments. However, participants assigned to the celecoxib group were more likely to have a reduction in fluorescein leakage when compared with the placebo group (odds ratio = 3.6; P < 0.01).
This short-term study did not find large visual function benefits of treatment with celecoxib or diode laser compared with those of standard laser treatment. A suggestive effect of celecoxib in reducing fluorescein leakage was observed.
PMCID: PMC3025102  PMID: 20038863
diabetic macular edema; celecoxib; diode grid laser photocoagulation; ETDRS type focal photocoagulation; optical coherence tomography
9.  Evaluation of Changes of Macular Thickness in Diabetic Retinopathy after Cataract Surgery 
To assess the macular thickness changes after cataract surgery in diabetic patients using optical coherence tomography (OCT).
We retrospectively reviewed the records of 104 diabetic patients who underwent cataract surgery. We examined the changes of macular thickness using OCT before cataract surgery and 1 week, 1-, 2- and 6-months after surgery. The central subfield mean thickness (CSMT) was used to evaluate macular edema which was defined as an increase of CSMT (ΔCSMT) > 30% from the baseline. The association between prior laser treatment or severity of diabetic retinopathy and macular thickness were also analyzed.
Macular edema occurred in 19 eyes (18%) from the diabetic group and 63% of macular edema developed at 1 month after surgery. Thirteen (68%) out of 19 eyes with macular edema showed the resolution of macular edema by 6 months after surgery without treatment. ΔCSMT of eyes without a history of laser treatment was statistically greater compared to eyes with a history of laser treatment in at 1- and 2-months after surgery, but was not different than eyes who had laser treatment at 6-months after surgery. The severity of diabetic retinopathy was not significantly correlated to macular edema, but there was statistical difference when patients who had a history of prior laser treatment were excluded.
The incidence of macular edema after cataract surgery in diabetic patients was 18%. Its peak incidence was at 1 month post surgery and it resolved spontaneously in 68% of patients by 6 months post surgery. Prior laser treatment might prevent postoperative macular edema until 2 months after cataract surgery in diabetic patients. However, macular edema did not affect the severity of diabetic retinopathy.
PMCID: PMC3149133  PMID: 21860569
Cataract extraction; Diabetic retinopathy; Macular edema; Macular thickness
10.  The Use of Optical Coherence Tomography to Determine the Effect of Thiazolidinediones on Retinal Thickness in Patients with Type 2 Diabetes 
Thiazolidinediones (TZDs) are insulin-sensitizing agents that are associated with peripheral edema and have been reported to be associated with diabetic macular edema (DME). We hypothesized that TZDs produce subclinical increases in retinal thickness that may be detected by optical coherence tomography (OCT) but are not seen on routine dilated funduscopic examination.
Research Design and Methods
We used OCT to screen for subclinical DME in a cross-sectional study of patients with type 2 diabetes; 29 patients were taking TZDs and 58 were not taking TZDs. We analyzed data using multiple linear regression analysis to investigate associations of retinal thickness with clinical characteristics.
There was no significant difference between the central subfield retinal thickness in the non-TZD group (206.4 ± 28.0 microns; n = 59) and TZD group (204.1 ± 26.1 microns; n = 29) (p = .72) nor were there significant differences in any other retinal subfield. There was no significant correlation of retinal thickness with laboratory results studies—peripheral edema, gender, age, duration of diabetes, individual, or combinations of medications. Retinal thickness differences between regions displayed normal anatomical variation. However, ethnic differences were found in which African-Americans had thinner retinas in all regions than Caucasians regardless of whether or not they used TZDs.
These data suggest that TZDs do not cause subclinical DME in a demographically diverse patient population with diabetes. The established normal ranges for macular thickness may require adjustment based on ethnicity.
PMCID: PMC3192602  PMID: 21880238
diabetic macular edema; optical computerized tomography; oral antidiabetic agents; retinal thickness; type diabetes 2 diabetes mellitus; thiazolidinediones
11.  Autofluorescence Imaging for Diagnosis and Follow-up of Cystoid Macular Edema 
Lipofuscin results from digestion of photoreceptor outer segments by the retinal pigment epithelium (RPE) and is the principal compound that causes RPE fluorescence during autofluorescence imaging. Absorption of the 488-nanometer blue light by macular pigments, especially by the carotenoids lutein and zeaxanthin, causes normal macular hypo-autofluorescence. Fundus autofluorescence imaging is being increasingly employed in ophthalmic practice to diagnose and monitor patients with a variety of retinal disorders. In macular edema for example, areas of hyper-autofluorescence are usually present which are postulated to be due to dispersion of macular pigments by pockets of intraretinal fluid. For this reason, the masking effect of macular pigments is reduced and the natural autofluorescence of lipofuscin can be observed without interference. In cystic types of macular edema, e.g. cystoid macular edema due to retinal vein occlusion, diabetic macular edema and post cataract surgery, hyper-autofluorescent regions corresponding to cystic spaces of fluid accumulation can be identified. In addition, the amount of hyper-autofluorescence seems to correspond to the severity of edema. Hence, autofluorescence imaging, as a noninvasive technique, can provide valuable information on cystoid macular edema in terms of diagnosis, follow-up and efficacy of treatment.
PMCID: PMC3520597  PMID: 23264870
Autofluorescence; Cystoid Macular Edema; Lipofuscin
12.  Real-Life Effectiveness and Tolerability of Vildagliptin and Other Oral Glucose-Lowering Therapies in Patients with Type 2 Diabetes in Germany 
Diabetes Therapy  2014;5(1):183-191.
Metformin is an established first-line treatment for patients with type 2 diabetes mellitus (T2DM), but treatment intensification with other oral antidiabetes drugs (OADs) is usually required over time. Effectiveness of diabetes control with vildagliptin and vildagliptin/metformin was a 1-year, large observational study of 45,868 patients with T2DM across 27 countries which assessed effectiveness and safety of vildagliptin as add-on therapy to other OADs versus other comparator OAD combinations. Here, we present the data from Germany.
Patients inadequately controlled with monotherapy were eligible only after the add-on treatment was finalized. Patients were assigned to either vildagliptin or comparator OADs [sulfonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors or metformin, excluding dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon-like peptide-1 mimetic/analogues]. The primary efficacy endpoint was the proportion of patients achieving a glycosylated hemoglobin (HbA1c) reduction of >0.3% without peripheral edema, hypoglycemia, discontinuation due to a gastrointestinal event or weight gain ≥5%. One secondary efficacy endpoint was the proportion of patients achieving HbA1c <7% without hypoglycemia and weight gain. Change in HbA1c from baseline to study endpoint and safety were assessed.
Of 8,887 patients enrolled in Germany, 6,679 received vildagliptin and 1,695 received other OADs. The mean ± SD baseline age, HbA1c, and T2DM duration were 62.8 ± 11.0 years, 7.7 ± 1.2%, and 5.8 ± 4.9 years, respectively. The proportion of patients achieving the primary (34.5% vs. 30.5%, p < 0.01) and secondary (25.4% vs. 21.7%, p = 0.01) endpoints was higher with vildagliptin than comparator OADs. Vildagliptin showed a numerically greater reduction in HbA1c (0.7%) from baseline vs. comparator OADs (0.6%). The overall incidence of adverse events was similar.
In real life, treatment with vildagliptin is associated with a higher proportion of patients reaching target HbA1c without hypoglycemia and weight gain compared with other OADs in Germany.
Electronic supplementary material
The online version of this article (doi:10.1007/s13300-014-0060-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4065295  PMID: 24643724
Diabetes; Dipeptidyl peptidase 4 inhibitors; Endocrinology; Glycosylated hemoglobin; Observational study; Oral antidiabetes agents; Real life; Type 2 diabetes mellitus; Vildagliptin
13.  Safety and effectiveness of a fixed-dose combination of olmesartan, amlodipine, and hydrochlorothiazide in clinical practice 
Clinical trials indicate that the use of fixed-dose combinations (FDCs) is associated with a higher level of treatment adherence and prolonged blood pressure (BP) control. The aim of this study was to document the safety and effectiveness of the FDC olmesartan/amlodipine/hydrochlorothiazide in patients with essential hypertension in clinical practice.
This multicenter, prospective, 24-week, noninterventional study enrolled 5,831 patients from primary care offices in Germany and Austria. Inclusion criteria were a diagnosis of essential hypertension and newly initiated treatment with the FDC.
The mean age of patients was 63.5 years, almost 50% of patients had a time since diagnosis of essential hypertension of over 5 years, and approximately 70% of patients had at least one cardiovascular risk factor, including 29.4% of patients with diabetes mellitus. Following approximately 24 weeks of treatment, the mean reduction in systolic/diastolic BP was 29.0/14.0 mmHg, a BP response was observed by 94.2% of patients, and a target BP of <140/90 mmHg was attained in 67.5% of patients. At least one adverse drug reaction (ADR) was experienced by 1.2% of patients, with the most common being peripheral edema. Subanalyses demonstrated that the following factors did not have a significant influence on the ADR rate: age (<65 years versus ≥65 years), diabetes mellitus (no/yes), cardiovascular risk (low/high), and concomitant medication (no/yes).
This study demonstrates that in clinical practice, treatment with the three-drug combination as an FDC tablet resulted in a very high proportion of patients with a BP response and control, accompanied by a very low rate of ADRs.
PMCID: PMC4275113  PMID: 25565857
hypertension; clinical practice; fixed-dose combination; blood pressure; adverse drug reactions
14.  The clinical usefulness of extravascular lung water and pulmonary vascular permeability index to diagnose and characterize pulmonary edema: a prospective multicenter study on the quantitative differential diagnostic definition for acute lung injury/acute respiratory distress syndrome 
Critical Care  2012;16(6):R232.
Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by features other than increased pulmonary vascular permeability. Pulmonary vascular permeability combined with increased extravascular lung water content has been considered a quantitative diagnostic criterion of ALI/ARDS. This prospective, multi-institutional, observational study aimed to clarify the clinical pathophysiological features of ALI/ARDS and establish its quantitative diagnostic criteria.
The extravascular lung water index (EVLWI) and the pulmonary vascular permeability index (PVPI) were measured using the transpulmonary thermodilution method in 266 patients with PaO2/FiO2 ratio ≤ 300 mmHg and bilateral infiltration on chest radiography, in 23 ICUs of academic tertiary referral hospitals. Pulmonary edema was defined as EVLWI ≥ 10 ml/kg. Three experts retrospectively determined the pathophysiological features of respiratory insufficiency by considering the patients' history, clinical presentation, chest computed tomography and radiography, echocardiography, EVLWI and brain natriuretic peptide level, and the time course of all preceding findings under systemic and respiratory therapy.
Patients were divided into the following three categories on the basis of the pathophysiological diagnostic differentiation of respiratory insufficiency: ALI/ARDS, cardiogenic edema, and pleural effusion with atelectasis, which were noted in 207 patients, 26 patients, and 33 patients, respectively. EVLWI was greater in ALI/ARDS and cardiogenic edema patients than in patients with pleural effusion with atelectasis (18.5 ± 6.8, 14.4 ± 4.0, and 8.3 ± 2.1, respectively; P < 0.01). PVPI was higher in ALI/ARDS patients than in cardiogenic edema or pleural effusion with atelectasis patients (3.2 ± 1.4, 2.0 ± 0.8, and 1.6 ± 0.5; P < 0.01). In ALI/ARDS patients, EVLWI increased with increasing pulmonary vascular permeability (r = 0.729, P < 0.01) and was weakly correlated with intrathoracic blood volume (r = 0.236, P < 0.01). EVLWI was weakly correlated with the PaO2/FiO2 ratio in the ALI/ARDS and cardiogenic edema patients. A PVPI value of 2.6 to 2.85 provided a definitive diagnosis of ALI/ARDS (specificity, 0.90 to 0.95), and a value < 1.7 ruled out an ALI/ARDS diagnosis (specificity, 0.95).
PVPI may be a useful quantitative diagnostic tool for ARDS in patients with hypoxemic respiratory failure and radiographic infiltrates.
Trial registration
PMCID: PMC3672621  PMID: 23232188
15.  Magnetic Resonance Imaging of Diabetic Muscle Infarction: Report of Two Cases 
Diabetic muscle infarction (DMI) occurs as a rare complication of long standing or severe diabetes mellitus. The condition usually occurs spontaneously and patients usually present with acute pain and swelling of affected muscles which persists for weeks, and resolves spontaneously without intervention. Magnetic resonance (MR) imaging is the modality of choice in patients with suspected DMI based on appropriate clinical setting and plays a major role in the diagnosis, assessing the extent of involvement and differentiating DMI from other conditions. The DMI affected muscles are bulky and appear heterogeneous with hyperintense signals on T2-weighted and STIR sequences, hypo or isointense on T1-weighted images with loss of normal fatty intramuscular septae. Subcutaneous and perifascial edema can be present. On postgadolinium scans, there is diffuse heterogeneous enhancement with non-enhancing foci, which may represent areas of necrosis. Biopsy can be avoided as MR findings are highly sensitive and specific. Treatment is usually conservative. Surgical intervention is required only in patients who do not respond to conservative management. The common differential diagnosis includes cellulitis, abscess, necrotizing fasciitis and polymyositis. We present two cases below to highlight the clinical, MR imaging findings and differential diagnosis of DMI.
PMCID: PMC4127726  PMID: 25328463
16.  Effects of Beraprost Sodium on Subjective Symptoms in Diabetic Patients with Peripheral Arterial Disease 
Clinics in Orthopedic Surgery  2013;5(2):145-151.
This study evaluated the effects of Beraprost sodium (Berasil) on subjective leg symptoms in patients with peripheral arterial disease caused by diabetes mellitus.
Ninety-four diabetic patients with peripheral arterial disease were treated with Beraprost in a fixed-dose, prospective, multicenter, cohort study. Beraprost (40 µg) was administered orally 3 times daily (120 µg/day) for 12 weeks. We developed a new disease-specific symptom questionnaire, which evaluated the effect of peripheral arterial disease on leg discomfort in daily life and assessed therapeutic responses to treatment. Patients were asked for their subjective assessment of symptoms on a written questionnaire before treatment and after 12 weeks of therapy.
There was significant improvement in all estimated subjective symptoms (burning, coldness, edema, exertional pain, stabbing, and paresthesias) in the lower extremities at 12 weeks (p < 0.001). There were 18 patients with neuropathy in whom significant improvement was noted for 6 subjective symptoms at 12 weeks (p < 0.05). Adverse events considered to be drug-related were observed in 4 patients (4.3%), all of which were mild and resolved with discontinuation of the medication.
Beraprost is effective as a treatment for improving various subjective symptoms in the lower extremities, such as burning, coldness, edema, exertional pain, stabbing, and paresthesias, in diabetic patients with peripheral arterial disease.
PMCID: PMC3664675  PMID: 23730480
Peripheral arterial disease; Intermittent claudication; Diabetes mellitus; Beraprost sodium; Prostaglandin I2
17.  Vascular Protection in Patients with Diabetes Admitted for Vascular Surgery in a Canadian Tertiary Care Hospital: Pilot Study 
Patients with peripheral artery disease are 6 times as likely as healthy individuals to die of cardiovascular causes within 10 years after diagnosis. Combination therapy with a statin, an angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB), and an antiplatelet agent is recommended to reduce cardiovascular events in patients with peripheral artery disease, especially those with concomitant diabetes mellitus and those who have undergone vascular surgery.
The primary objective was to determine the proportion of patients with concurrent diabetes and peripheral artery disease who were receiving therapy with a statin, ACE inhibitor or ARB, and antiplatelet agent (acetylsalicylic acid or clopidogrel) at the time of discharge after vascular surgery. The secondary objectives were to determine if target blood pressure was achieved and if smoking cessation therapy was offered and/or provided.
This pilot study was a retrospective, cross-sectional chart analysis. The health records database for Alberta Health Services was searched to identify patients with diabetes who underwent vascular surgery at the Foothills Hospital in Calgary with discharge between January 1 and June 30, 2010. In addition to baseline demographic characteristics, blood pressure values at the time of admission and discharge were collected. Discharge medications, including cardiovascular medications such as statins, ACE inhibitor or ARB, and antiplatelet agents, were recorded. Descriptive analysis of the data was performed.
Of the 42 patients for whom charts were obtained, 25 (60%) had prescriptions for cardiovascular triple therapy (statin, ACE inhibitor or ARB, antiplatelet agent). Just over half of the patients (23 [55%]) had achieved target blood pressure (< 130/80 mm Hg) at the time of discharge. Of the 14 current smokers, 9 (64%) had documented evidence in the chart that smoking cessation counselling was offered and/or drug therapy was provided.
Only about half of the patients in this study were receiving cardiovascular triple therapy, which suggests that many patients were not receiving optimal vascular protection. A larger study is needed to review prescribing patterns for patients with peripheral artery disease.
PMCID: PMC3743854  PMID: 23950606
peripheral artery disease; diabetes mellitus; vascular protection; maladie artérielle périphérique; diabète sucré; protection vasculaire
18.  Does age matter? - A MRI study on peritumoral edema in newly diagnosed primary glioblastoma 
BMC Cancer  2011;11:127.
Peritumoral edema is a characteristic feature of malignant glioma related to the extent of neovascularisation and to vascular endothelial growth factor (VEGF) expression.
The extent of peritumoral edema and VEGF expression may be prognostic for patients with glioblastoma. As older age is a negative prognostic marker and as VEGF expression is reported to be increased in primary glioblastoma of older patients, age-related differences in the extent of peritumoral edema have been assessed.
In a retrospective, single-center study, preoperative magnetic resonance imaging (MRI) scans of steroid-naïve patients (n = 122) of all age groups were analysed. Patients with clinically suspected, radiologically likely or known evidence of secondary glioblastoma were not included.
Extent of brain edema was determined in a metric quantitative fashion and in a categorical fashion in relation to tumor size. Analysis was done group-wise related to age. Additionally, tumor size, degree of necrosis, superficial or deep location of tumor and anatomic localization in the brain were recorded.
The extent of peritumoral edema in patients >65 years (ys) was not different from the edema extent in patients ≤ 65 ys (p = 0.261). The same was true if age groups ≤ 55 ys and ≥ 70 ys were compared (p = 0.308). However, extent of necrosis (p = 0.023), deep tumor localization (p = 0.02) and frontal localisation (p = 0.016) of the tumor were associated with the extent of edema. Tumor size was not linearly correlated to edema extent (Pearson F = 0.094, p = 0.303) but correlated to degree of necrosis (F = 0.355, p < 0.001, Spearman-Rho) and depth of tumor (p < 0.001). In a multifactorial analysis of maximum edema with the uncorrelated factors age, regional location of tumor and degree of necrosis, only the extent of necrosis (p = 0.022) had a significant effect.
Age at diagnosis does not determine degree of peritumoral edema, and tumor localization in the white matter is associated with greater extent of edema. The area of necrosis is reflective of volume of edema. In summary, the radiographic appearance of a glioblastoma at diagnosis does not reflect biology in the elderly patient.
PMCID: PMC3094323  PMID: 21481277
age; brain tumor; glioblastoma; imaging; necrosis; vascular endothelial growth factor
19.  Comparison of 1.5T and 3T MRI scanners in evaluation of acute bone stress in the foot 
Bone stress injuries are common in athletes and military recruits. Only a minority of bone stress changes are available on plain radiographs. Acute bone stress is often visible on MRI as bone marrow edema, which is also seen in many other disease processes such as malignancies, inflammatory conditions and infections. The purpose of this study was to investigate the ability of radiographs, 1.5T and 3T MRI to identify acute bone marrow changes in the foot.
Ten patients with 12 stress fractures seen on plain radiographs underwent MRI using 1.5T and 3T scanners. T1 FSE and STIR axial, sagittal, and coronal view sequences were obtained. Two musculoskeletal radiologists interpreted the images independently and by consensus in case of disagreement.
Of the 63 acute bone stress changes seen on 3T images, 61 were also seen on 1.5T images. The sensitivity of 1.5T MRI was 97% (95% CI: 89%-99%) compared with 3T. The 3T MRI images where, therefore, at least equally sensitive to 1.5T scanners in detection of bone marrow edema. On T1-weighted sequences, 3T images were slightly superior to 1.5T images in visualizing the demarcation of the edema and bone trabeculae. The kappa-value for inter-observer variability was 0.86 in the MRI indicating substantial interobserver agreement.
Owing to slightly better resolution of 3T images, edema characterization is easier, which might aid in the differential diagnosis of the bone marrow edema. There was, however, no noteworthy difference in the sensitivity of the 1.5T and 3T images to bone marrow edema. Routine identification of acute bone stress changes and suspected stress injuries can, therefore, be made with 1.5T field strength.
PMCID: PMC3121660  PMID: 21645348
20.  Rare complications of pediatric diabetic ketoacidosis 
World Journal of Diabetes  2015;6(1):167-174.
The incidence of type 1 diabetes (T1D) among youth is steadily increasing across the world. Up to a third of pediatric patients with T1D present with diabetic ketoacidosis, a diagnosis that continues to be the leading cause of death in this population. Cerebral edema is the most common rare complication of diabetic ketoacidosis in children. Accordingly, treatment and outcome measures of cerebral edema are vastly researched and the pathophysiology is recently the subject of much debate. Nevertheless, cerebral edema is not the only sequela of diabetic ketoacidosis that warrants close monitoring. The medical literature details various other complications in children with diabetic ketoacidosis, including hypercoagulability leading to stroke and deep vein thrombosis, rhabdomyolysis, pulmonary and gastrointestinal complications, and long-term memory dysfunction. We review the pathophysiology, reported cases, management, and outcomes of each of these rare complications in children. As the incidence of T1D continues to rise, practitioners will care for an increasing number of pediatric patients with diabetic ketoacidosis and should be aware of the various systems that may be affected in both the acute and chronic setting.
PMCID: PMC4317308
Type 1 diabetes; Diabetic ketoacidosis; Complications; Pediatric; Review
21.  A diabetic woman with a swollen forearm 
Diabetic muscle infarction (DMI) is an unusual complication of diabetes mellitus. It is usually seen in long-standing diabetes mellitus. This article presents a case of DMI in the left forearm of a 58-year-old woman. She had a swollen forearm. The level of creatine kinase was 5930 U/L. Her condition was initially suspected for either cellulitis or venous thrombosis. A magnetic resonance imaging (MRI) study of the forearm showed diffuse edema and abnormal signals of the left forearm. The diagnosis of DMI was made. She was treated conservatively and her symptoms resolved within a short period of time. DMI should be considered as a differential diagnosis of any painful and swollen limb in diabetic patients.
PMCID: PMC3697219  PMID: 23826021
Diabetes mellitus; infarction; muscle
22.  Increased vascular permeability after CABG in diabetic patients is associated with increased expression of VEGF and HGF 
Several inflammatory mediators such as vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are known to play a critical role in the regulation of vascular permeability and angiogenesis. We studied the serum levels of growth factors and gene expression profiles of genes involved in the growth factor signaling in the peripheral blood of diabetic (DM) and non-diabetic (ND) patients following cardiopulmonary bypass (CPB) and cardioplegic-arrest (C).
Methods and Results
Serum and total RNA were obtained from the blood samples collected from DM and matched ND patients (n=7 patients each) who underwent coronary artery bypass graft (CABG); before (pre), 6-hours (6h), and 4-days (4d) after CPB/C. The cytokine panel consisting of growth factors such as VEGF, HGF, FGF, and EGF was quantified in DM and ND patients; pre, 6h, and 4d post-CPB/C using multiplex cytokine quantification system. cDNA microarray analysis was performed and fold-change was calculated. Length of hospitalization (10 vs. 6 days; p=0.04) and weight gain (5 vs. 2.5 kg; p=0.001) were significantly greater for DM compared to ND patients. The serum levels of VEGF and HGF were significantly elevated in DM patients when compared to ND patients; pre vs. 6h post-CPB/C. In addition, significantly elevated mRNA expression of HIF1α, CREB, and EP300 (> 2 fold) was observed, 4d post-CPB/C exclusively in DM patients.
The differential profile of gene and protein expression of growth factors and their related genes in DM vs. ND patients could be associated with increased edema and weight gain in DM patients after CPB/C.
PMCID: PMC2762706  PMID: 19577077
23.  86 The Efficacy and Safety of Human Plasma-derived C1-Inhibitor Concentrate Administered for the Treatment of Attacks in Pediatric Patients with Hereditary Angioedema Due to C1-Inhibitor Deficiency 
The World Allergy Organization Journal  2012;5(Suppl 2):S45-S46.
Hereditary angioedema due to C1-inhibitor deficiency (HAE-C1-INH) is a life-threatening, rare disease characterized by recurrent edematous attacks. In 50% of cases, the initial onset of symptoms occurs between 5 and 11 years of age. There are limited data on the emergency treatment of acute episodes in pediatric patients. Our aim was to analyze the efficacy and safety of human plasma-derived C1-INH concentrate in our pediatric patient population with HAE-C1-INH.
50 pediatric patients (23 boys, 27 girls; 45 HAE type I, 5 HAE type II patients) were enrolled. The follow-up period began at the time of diagnosis and ended when the patient turned 18 years old. The indications for the use of C1-INH concentrate were upper airway oedema of any severity; moderate-to-severe abdominal edema; edema of face, neck, or lips and severe edema of the extremities and trunk. Clinical and laboratory data were entered into the Hungarian HAE Registry.
152 attacks out of 1392 experienced by 42 patients were treated with C1-INH concentrate (28% of attacks at home and 72% at the clinic). The distribution of C1-INH-treated attacks by location was as follows: 38% subcutaneous, 32% abdominal, 30% upper airway. In all locations, the clinical symptoms were consistently relieved by 500 IU C1-INH concentrate. An additional 500 IU dose of C1-INH concentrate was required in 4 cases only. The symptoms improved within 15 to 60 minutes of drug administration. Time to complete resolution was 24 to 48 hours in subcutaneous edema, 12 to 24 hours in abdominal attacks, and less than 12 hours when the edema involved the upper airways. No progression or recurrence of the attack was observed. Repeated administration did not reduce therapeutic efficacy of the drug. Adverse events did not occur. Transmission of viral infections (HIV, HBV, HBC, Parvo virus B19) was not detected. Comparing the first and last year of follow-up, anti-C1-INH antibodies (IgA, IgG, IgM types) did not show any relationship with the administration of C1-INH concentrate.
Our prospective study demonstrated that the administration of C1-INH concentrate is highly effective and safe for the treatment of edematous attacks – regardless their location – in pediatric patients with HAE-C1-INH.
PMCID: PMC3513084
24.  Conventional and Functional MR Imaging of Peripheral Nerve Sheath Tumors: Initial Experience 
Differentiating benign from malignant peripheral nerve sheath tumors can be very challenging using conventional MR imaging. Our aim was to test the hypothesis that conventional and functional MR imaging can accurately diagnose malignancy in patients with indeterminate peripheral nerve sheath tumors.
This institutional review board–approved, Health Insurance Portability and Accountability Act–compliant study retrospectively reviewed 61 consecutive patients with 80 indeterminate peripheral nerve sheath tumors. Of these, 31 histologically proved peripheral nerve sheath tumors imaged with conventional (unenhanced T1, fluid-sensitive, contrast-enhanced T1-weighted sequences) and functional MR imaging (DWI/apparent diffusion coefficient mapping, dynamic contrast-enhanced MR imaging) were included. Two observers independently assessed anatomic (size, morphology, signal) and functional (ADC values, early arterial enhancement by dynamic contrast-enhanced MR) features to determine interobserver agreement. The accuracy of MR imaging for differentiating malignant from benign was also determined by receiver operating characteristic analysis.
Of 31 peripheral nerve sheath tumors, there were 9 malignant (9%) and 22 benign ones (81%). With anatomic sequences, average tumor diameter (6.3 ± 1.8 versus 3.9 ± 2.3 mm, P = .009), ill-defined/infiltrative margins (77% versus 32%; P = .04), and the presence of peritumoral edema (66% versus 23%, P = .01) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. With functional sequences, minimum ADC (0.47 ± 0.32 × 10−3 mm2/s versus 1.08 ± 0.26 × 10−3 mm2/s; P [H11021] .0001) and the presence of early arterial enhancement (50% versus 11%; P = .03) were different for malignant peripheral nerve sheath tumors and benign peripheral nerve sheath tumors. The minimum ADC (area under receiver operating characteristic curve was 0.89; 95% confidence interval, 0.73– 0.97) and the average tumor diameter (area under the curve = 0.8; 95% CI, 0.66 – 0.94) were accurate in differentiating malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors. With threshold values for minimum ADC ≤ 1.0 × 10−3 mm2/s and an average diameter of ≥4.2 cm, malignancy could be diagnosed with 100% sensitivity (95% CI, 66.4%–100%).
Average tumor diameter and minimum ADC values are potentially important parameters that may be used to distinguish malignant peripheral nerve sheath tumors from benign peripheral nerve sheath tumors.
PMCID: PMC4332811  PMID: 24763412
25.  Blood Flow Parameters of the Central Retinal and Internal Carotid Arteries in Asymmetric Diabetic Retinopathy 
To investigate the correlation between diabetic retinopathy severity and blood flow parameters in the central retinal artery (CRA) and internal carotid artery (ICA).
This comparative study included 40 eyes of 20 patients with asymmetric diabetic retinopathy. Twelve subjects had asymmetric diabetic macular edema while eight patients had proliferative diabetic retinopathy (PDR) in one eye and non-proliferative diabetic retinopathy (NPDR) in the fellow eye. Bilateral color Doppler imaging (CDI) of the CRA and ICA was performed to determine resistance index (RI) and peak systolic velocity (PSV). RI and PSV values were compared between eyes with higher grades of macular edema (> 2 grades of difference with the fellow eye) and fellow eyes with less severe macular edema, as well as between eyes with PDR and fellow eyes with NPDR.
Mean RI of the CRA in eyes with higher grades of macular edema was 0.78±0.11 as compared to 0.69±0.08 in fellow eyes with less severe macular edema (P=0.012), while PSV of the CRA was 58.83±18.93 cm/s in eyes with higher grades of macular edema versus 59.75±11.83 cm/s in fellow eyes with less severe macular edema (P=1.00). Mean PSV of the ICA was 55±23.94 cm/s in eyes with PDR and 69.25±34.30 cm/s in eyes with NPDR (P=0.008) while mean RI of the ICA was 0.81±0.13 in eyes with PDR and 0.76±0.12 in eyes with NPDR (P=1.00).
Evaluation of RI in the CRA and PSV in the ICA by CDI in diabetic patients may identify eyes at risk of more severe macular edema and PDR.
PMCID: PMC3595584  PMID: 23503081
Color Doppler Imaging; Central Retinal Artery; Internal Carotid Artery; Diabetic Retinopathy

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