Introduction: ACE inhibitors accounts for 8% of all cases of angioneurotic edema and the overall incidence is 0.1 to 0.7% of patients on ACE inhibitors. It is a leading cause (20-40%) of emergency room visits in the US with angioedema. We report a case of angioedema caused by ACE inhibitors confined to the upper airway after four years on treatment with Lisinopril which persisted for three weeks and required endotracheal intubation and subsequent tracheostomy due to delayed resolution. This case is one of the rare cases presented as upper airway edema which persisted for a long time. Presentation: A 60-year-old Sudanese male patient with osteoarthritis in both knees underwent bilateral total knee replacement under single-shot epidural anesthesia. He had significant past medical history of type II diabetes, bipolar affective disorder and hypertension managed with Lisinopril for the past four years. Postoperatively after 10 hours the patient desaturated and developed airway obstruction requiring intubation. Laryngoscopy revealed an edematous tongue and upper airway and vocal cords were not visualized. In view of this clinical picture a provisional diagnosis of angioedema secondary to Lisinopril was made and it was discontinued. CT scan of the neck and soft tissues revealed severe airway edema with snugly fitting endotracheal tube with no peritubal air. A repeat CT neck on the tenth postoperative day showed no signs of resolution and an elective tracheostomy was performed on the eleventh postoperative day. C1 inhibitor protein and C4 levels were assayed to exclude hereditary angioedema and were found to be within normal range. Decannulation of tracheostomy was done after airway edema resolved on the twenty-fourth postoperative day as confirmed by CT scan. Subsequently he was transferred to the ward and discharged home. Conclusion: ACEI induced angioedema is a well-recognized condition. Early diagnosis based on a high index of suspicion, immediate withdrawal of the offending drug followed by supportive therapy is the cornerstone of management.
angioedema; ACE inhibitor; life threatening.
Diabetes is a common metabolic disorder leading to the development of many complications, among which diabetic retinopathy and macular edema are the most significant. These complications can contribute to blindness if not diagnosed or treated properly, and several studies have been conducted to evaluate the methods for the prevention or slowing down their progression. Therefore, serum lipids, apparently play an effective role in the creation and acceleration of macular edema, we therefore determined the relationship of serum lipid level in patients with diabetic macular edema in the present study.
180 participants were selected from patients with the definite diagnosis of diabetes referred to the eye clinic of Shahid Beheshti and Ayatollah Rouhani Hospitals of Babol during 2011-2012, the patients with a history of taking lipid –lowering drugs and hypertension were excluded from the study. The study data were provided from the medical records of each patients. SPSS Version 18 was used for analyses.
In the present investigation, the mean age of participants was 53.22±with the age range of 18-77 years. Ninety patients with diabetic retinopathy and macular edema were compared with ninety patients with diabetic retinopathy without macular edema (control group) were compared. There was a significant difference in serum cholesterol and LDL-cholesterol between patients and groups (p<0.000).
The results of this study indicate that high serum cholesterol and LDL-cholesterol is associated with severity of diabetic retinopathy particularly with macular edema
Diabetes; Diabetic retinopathy; Macular edema; Lipid profile; Cholesterol.
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).
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.
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.
compression; diabetes; edema; lower extremity
Polytetrafluoroethylene is ubiquitous in materials commonly used in cooking and industrial applications. Overheated polytetrafluoroethylene can generate toxic fumes, inducing acute pulmonary edema in some cases. However, neither the etiology nor the radiological features of this condition have been determined. For clarification, we report an illustrative case, together with the first comprehensive literature review.
A previously healthy 35-year-old Japanese man who developed severe dyspnea presented to our hospital. He had left a polytetrafluoroethylene-coated pan on a gas-burning stove for 10 hours while unconscious. Upon admission, he was in severe respiratory distress. A chest computed tomographic scan showed massive bilateral patchy consolidations with ground-glass opacities and peripheral area sparing. A diagnosis of polytetrafluoroethylene fume–induced pulmonary edema was made. He was treated with non-invasive positive pressure ventilation and a neutrophil elastase inhibitor, which dramatically alleviated his symptoms and improved his oxygenation. He was discharged without sequelae on hospital day 11. A literature review was performed to survey all reported cases of polytetrafluoroethylene fume–induced pulmonary edema. We searched the PubMed, Embase, Web of Science and OvidSP databases for reports posted between the inception of the databases and 30 September 2014, as well as several Japanese databases (Ichushi Web, J-STAGE, Medical Online, and CiNii). Two radiologists independently interpreted all chest computed tomographic images. Eighteen relevant cases (including the presently reported case) were found. Our search revealed that (1) systemic inflammatory response syndrome was frequently accompanied by pulmonary edema, and (2) common computed tomography findings were bilateral ground-glass opacities, patchy consolidation and peripheral area sparing. Pathophysiological and radiological features were consistent with the exudative phase of acute respiratory distress syndrome. However, the contrast between the lesion and the spared peripheral area was striking and was distinguishable from the common radiological features of acute respiratory distress syndrome.
The essential etiology of polytetrafluoroethylene fume–induced pulmonary edema seems to be increased pulmonary vascular permeability caused by an inflammatory response to the toxic fumes. The radiological findings that distinguish polytetrafluoroethylene fume–induced pulmonary edema can be bilateral ground-glass opacity or a patchy consolidation with clear sparing of the peripheral area.
Acute respiratory distress syndrome; Neutrophil elastase inhibitor; Peripheral area sparing; Pulmonary inflammation; Radiological features; Teflon®; Toxic fumes
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.
acute pulmonary edema; acute lung injury; acute respiratory distress syndrome; alveolar capillary membrane permeability; diagnosis
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.
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.
Diagnosis; differential diagnosis; edema; lymphoplasmacyte-rich meningioma; prognosis
Acute cerebral edema is a significant cause of death in patients treated for diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome.
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.
Tumefactive perivascular spaces; Cerebral edema; Hyperglycemic hyperosmolar syndrome
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.
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.
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.
diabetic macular edema; celecoxib; diode grid laser photocoagulation; ETDRS type focal photocoagulation; optical coherence tomography
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.
Cataract extraction; Diabetic retinopathy; Macular edema; Macular thickness
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.
Autofluorescence; Cystoid Macular Edema; Lipofuscin
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.
diabetic macular edema; optical computerized tomography; oral antidiabetic agents; retinal thickness; type diabetes 2 diabetes mellitus; thiazolidinediones
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.
Diabetes; Dipeptidyl peptidase 4 inhibitors; Endocrinology; Glycosylated hemoglobin; Observational study; Oral antidiabetes agents; Real life; Type 2 diabetes mellitus; Vildagliptin
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.
hypertension; clinical practice; fixed-dose combination; blood pressure; adverse drug reactions
Peripheral retinal ischemia not detectable by conventional fluorescein angiography has been proposed to be a driving force for rebound edema in retinal vein occlusions. In this report, we examine the treatment of peripheral retinal ischemia with targeted retinal photocoagulation (TRP) to manage a patient’s rebound edema.
To assess the extent of peripheral nonperfusion, an Optos 200Tx device was used. To target the treatment to peripheral ischemia areas, a Navilas Panretinal Laser was used.
A 64-year-old male with a central retinal vein occlusion and a visual acuity 20/300, and central macular thickness 318 μm presented with rubeosis. Angiography revealed extensive peripheral nonperfusion. Despite TRP to areas of irreversible ischemia, after 2 months, he continued show rubeosis and rebound edema. Additional TRP laser was repeatedly added more posteriorly to areas of reversible nonperfusion, resulting in eventual resolution of rubeosis and edema.
In this study, we demonstrate the use of widefield imaging with targeted photo-coagulation of peripheral ischemia to treat rebound edema, while preserving most peripheral vision. In order to treat rebound edema, extensive TRP, across reversible and nonreversible areas of ischemia, had to be performed – not just in areas of nonreversible peripheral ischemia. These areas need to be mapped during episodes of rebound edema, when ischemia is at its maximum. In this way, by doing the most TRP possible, the cycle of rebound edema can be broken.
macular edema; retinal vein occlusion
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.
UMIN-CTR ID UMIN000003627
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.
age; brain tumor; glioblastoma; imaging; necrosis; vascular endothelial growth factor
Although treatment with C1 esterase inhibitor (C1-INH) concentrate is well established for hereditary angioedema (HAE) attacks in general, data that assess its efficacy for cutaneous attack treatment are sparse.
To assess efficacy of plasma-derived, nanofiltered C1-INH concentrate for cutaneous attack treatment by comparing treated attacks from the uncontrolled I.M.P.A.C.T.2 study with historical data for untreated attacks.
Cutaneous attack data from patients with HAE who were treated for cutaneous edema with 20 IU/kg body weight C1-INH concentrate in the uncontrolled I.M.P.A.C.T.2 study (38 patients) were compared with data from untreated patients from an historical data base (46 patients) and included subset analyses for facial edema (treated group, 21 patients; untreated group, 33 patients) and peripheral edema (30 patients in each group). Average attack duration (AAD) per patient was the efficacy end point used to compare treated and untreated patients. Differences were assessed with a Wilcoxon test (primary analysis) and a log-rank test; AAD per patient was analyzed descriptively and graphically with Kaplan-Meier curves.
The AAD per patient of all cutaneous attacks or facial and peripheral cutaneous attack subsets was significantly faster with C1-INH treatment than without treatment (Wilcoxon and log-rank tests, both p < 0.0001 for all comparisons). Mean AADs per patient for all, facial, and peripheral attacks were 2.04, 1.45, and 2.16 days, respectively, in the C1-INH–treated group, and were 3.74, 4.45, and 2.98 days, respectively, in the untreated group. Kaplan-Meier curves corroborated the observed group differences.
Treatment of cutaneous HAE attacks (all attacks or facial and peripheral attack subsets) with 20 IU/kg C1-INH concentrate provided faster attack resolution compared with no treatment.
C1 esterase inhibitor; C1-INH concentrate; Berinert; cutaneous edema; facial edema; peripheral edema; hereditary angioedema; HAE; angioneurotic edema; I.M.P.A.C.T.2 study.
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.
Peripheral arterial disease; Intermittent claudication; Diabetes mellitus; Beraprost sodium; Prostaglandin I2
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.
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.
Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: “Combinations of oral blood-glucose lowering medicines” (A10BD), “dipeptidyl peptidase-4 (DDP-4) inhibitors” (A10BH), and “other blood glucose lowering medicines” (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment.
For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status.
A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with “other blood glucose lowering medications,” the remaining 2 (13%) with “DDP-4 inhibitors.”
Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs.
Adverse drug reactions; adverse events; clinical notes; glucose-lowering medicines; manual review
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.
Type 1 diabetes; Diabetic ketoacidosis; Complications; Pediatric; Review