MRI-based Neuropathy Score Reporting And Data System (NS-RADS): multi-institutional wider-experience usability study of peripheral neuropathy conditions among 32 radiology readers.

OBJECTIVE: To determine the inter-reader reliability and diagnostic performance of classification and severity scales of Neuropathy Score Reporting And Data System (NS-RADS) among readers of differing experience levels after limited teaching of the scoring system. METHODS: This is a multi-institutional, cross-sectional, retrospective study of MRI cases of proven peripheral neuropathy (PN) conditions. Thirty-two radiology readers with varying experience levels were recruited from different institutions. Each reader attended and received a structured presentation that described the NS-RADS classification system containing examples and reviewed published articles on this subject. The readers were then asked to perform NS-RADS scoring with recording of category, subcategory, and most likely diagnosis. Inter-reader agreements were evaluated by Conger's kappa and diagnostic accuracy was calculated for each reader as percent correct diagnosis. A linear mixed model was used to estimate and compare accuracy between trainees and attendings. RESULTS: Across all readers, agreement was good for NS-RADS category and moderate for subcategory. Inter-reader agreement of trainees was comparable to attendings (0.65 vs 0.65). Reader accuracy for attendings was 75% (95% CI 73%, 77%), slightly higher than for trainees (71% (69%, 72%), p = 0.0006) for nerves and comparable for muscles (attendings, 87.5% (95% CI 86.1-88.8%) and trainees, 86.6% (95% CI 85.2-87.9%), p = 0.4). NS-RADS accuracy was also higher than average accuracy for the most plausible diagnosis for attending radiologists at 67% (95% CI 63%, 71%) and for trainees at 65% (95% CI 60%, 69%) (p = 0.036). CONCLUSION: Non-expert radiologists interpreted PN conditions with good accuracy and moderate-to-good inter-reader reliability using the NS-RADS scoring system. CLINICAL RELEVANCE STATEMENT: The Neuropathy Score Reporting And Data System (NS-RADS) is an accurate and reliable MRI-based image scoring system for practical use for the diagnosis and grading of severity of peripheral neuromuscular disorders by both experienced and general radiologists. KEY POINTS: • The Neuropathy Score Reporting And Data System (NS-RADS) can be used effectively by non-expert radiologists to categorize peripheral neuropathy. • Across 32 different experience-level readers, the agreement was good for NS-RADS category and moderate for NS-RADS subcategory. • NS-RADS accuracy was higher than the average accuracy for the most plausible diagnosis for both attending radiologists and trainees (at 75%, 71% and 65%, 65%, respectively).

Triglycerides and risk of cardiovascular events in statin-treated patients with newly diagnosed type 2 diabetes: a Danish cohort study.

BACKGROUND: Elevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care. METHODS: This cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005-2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors. RESULTS: Among 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0-1.9 mmol/L in 52%, 2.0-2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00-1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12-1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20-1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women. CONCLUSIONS: In statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention.

Fibroblastic and Myofibroblastic Soft-Tissue Tumors: Imaging Spectrum and Radiologic-Pathologic Correlation.

Fibroblastic and myofibroblastic tumors are a variable group of neoplasms ranging from benign to malignant. These lesions may affect patients of any age group but are more frequently encountered in the pediatric population. Patient clinical presentation depends on the location, growth pattern, adjacent soft-tissue involvement, and pathologic behavior of these neoplasms. In the 2020 update to the World Health Organization (WHO) classification system, these tumors are classified on the basis of their distinct biologic behavior, histomorphologic characteristics, and molecular profiles into four tumor categories: (a) benign (eg, fibrous hamartoma of infancy, nodular fasciitis, proliferative fasciitis, fibroma of the tendon sheath, calcifying aponeurotic fibroma); (b) intermediate, locally aggressive (eg, desmoid fibromatosis); (c) intermediate, rarely metastasizing (eg, dermatofibrosarcoma protuberans, myxoinflammatory fibroblastic sarcoma, low-grade myofibroblastic sarcoma, infantile fibrosarcoma); and (d) malignant (eg, sclerosing epithelioid fibrosarcomas; low-grade fibromyxoid sarcoma; myxofibrosarcoma; fibrosarcoma, not otherwise specified). Detection of various components of solid tumors at imaging can help in prediction of the presence of corresponding histopathologic variations, thus influencing diagnosis, prognosis, and treatment planning. For example, lesions with a greater myxoid matrix or necrotic components tend to show higher signal intensity on T2-weighted MR images, whereas lesions with hypercellularity and dense internal collagen content display low signal intensity. In addition, understanding the radiologic-pathologic correlation of soft-tissue tumors can help to increase the accuracy of percutaneous biopsy and allow unnecessary interventions to be avoided. ©RSNA, 2023 Quiz questions for this article are available in the supplemental material.

Small and large fiber sensory polyneuropathy in type 2 diabetes: Influence of diagnostic criteria on neuropathy subtypes.

Diabetic polyneuropathy (DPN) can be classified based on fiber diameter into three subtypes: small fiber neuropathy (SFN), large fiber neuropathy (LFN), and mixed fiber neuropathy (MFN). We examined the effect of different diagnostic models on the frequency of polyneuropathy subtypes in type 2 diabetes patients with DPN. This study was based on patients from the Danish Center for Strategic Research in Type 2 Diabetes cohort. We defined DPN as probable or definite DPN according to the Toronto Consensus Criteria. DPN was then subtyped according to four distinct diagnostic models. A total of 277 diabetes patients (214 with DPN and 63 with no DPN) were included in the study. We found a considerable variation in polyneuropathy subtypes by applying different diagnostic models independent of the degree of certainty of DPN diagnosis. For probable and definite DPN, the frequency of subtypes across diagnostic models varied from: 1.4% to 13.1% for SFN, 9.3% to 21.5% for LFN, 51.4% to 83.2% for MFN, and 0.5% to 14.5% for non-classifiable neuropathy (NCN). For the definite DPN group, the frequency of subtypes varied from: 1.6% to 13.5% for SFN, 5.6% to 20.6% for LFN, 61.9% to 89.7% for MFN, and 0.0% to 6.3% for NCN. The frequency of polyneuropathy subtypes depends on the type and number of criteria applied in a diagnostic model. Future consensus criteria should clearly define sensory functions to be tested, methods of testing, and how findings should be interpreted for both clinical practice and research purpose.

Natural History of Blunt Cerebrovascular Injury: Experience Over a 10-year Period at a Level I Trauma Center.

Background Blunt cerebrovascular injury (BCVI) is associated with increased stroke and mortality risk. However, the most appropriate follow-up strategy remains uncertain. Purpose To better understand the natural history of BCVI and help define the most optimal timing and length of follow-up imaging. Materials and Methods In this retrospective HIPAA-compliant study, data from all patients treated for BCVI at a level I trauma center between April 1, 2005, and June 30, 2015, were reviewed. For patients with at least one follow-up study, time-to-event analysis was performed to assess the trend in injury evolution. Association of injury grade and injury evolution was also assessed. The Fisher exact test and multivariable logistic regression were used to evaluate association of the number of injured vessels, vessel grade, and vessel type (internal carotid artery, vertebral artery) with BCVI-associated stroke. Results A total of 1204 patients (800 men; mean age ± standard deviation, 45 years ± 22) with 1604 vessel injuries were evaluated. High-grade (grades 3-5) injuries were less likely to resolve (hazard ratio [HR], 0.2; P < .001) than low-grade injuries. High-grade injuries were more likely to progress than low-grade injuries (HR, 3.3; P = .005). Of the injuries that improved or resolved (343 of 419 [81.9%]), 76% (259 of 343) changed within 30 days after the initial injury, and the remaining 24% (84 of 343) changed between 30 and 90 days. Of the injuries that progressed (46 of 419 [11.0%]), 87% (40 of 46) changed within 90 days. Beyond 90 days, no improvement or resolution occurred, and only 1.4% (six of 419) of injuries progressed. Higher injury grade (adjusted odds ratio, 2.0 per one-grade increase [95% confidence interval {CI}: 1.6, 2.4]; P < .001), carotid injuries versus vertebral artery injuries (49 of 420 [11.7%] vs 35 of 667 [5.2%]; P < .001), and increasing number of vessels injured per patient (adjusted odds ratio, 1.6 per one-vessel increase [95% CI: 1.3, 2.2]; P < .001) were associated with increased risk for BCVI-related stroke. Conclusion Most blunt cerebrovascular injury-related changes occurred within 30 days; changes rarely occurred beyond 90 days. Follow-up imaging is therefore unlikely to be helpful beyond 90 days. © RSNA, 2020 See also the editorial by Talbott in this issue.

Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia.

The 22 risk factors suggested by the Centers for Disease Control and Prevention (CDC) to predict patients at risk for Mycobacterium tuberculosis have not been evaluated in hospitalised patients with community-acquired pneumonia (CAP). We evaluated which of the CDC risk factors best predict M. tuberculosis in these patients. To our knowledge, this is the first time a score has been developed assessing these risk factors. This was a secondary analysis of 6976 patients hospitalised with CAP enrolled in the Community-Acquired Pneumonia Organization International Cohort Study. Using Poisson regression, we selected the subset of risk factors that best predicted the presence of CAP due to M. tuberculosis. This subset was compared to the CDC risk factors using receiver operating characteristic (ROC) curve analysis. Five risk factors were found to best predict CAP due to M. tuberculosis: night sweats, haemoptysis, weight loss, M. tuberculosis exposure and upper lobe infiltrate. The area under the ROC curve for all CDC risk factors was 71% and 89% for the subset of five risk factors. The CDC-suggested risk factors are poor at predicting the presence of M. tuberculosis in hospitalised patients with CAP. With a subset of five risk factors identified in this study, we developed a new score, which will improve our capacity to isolate patients at risk of CAP due to M. tuberculosis at the time of hospitalisation.

Bacteriophage K antimicrobial-lock technique for treatment of Staphylococcus aureus central venous catheter-related infection: a leporine model efficacy analysis.

PURPOSE: To determine whether a bacteriophage antimicrobial-lock technique can reduce bacterial colonization and biofilm formation on indwelling central venous catheters in a rabbit model. MATERIALS AND METHODS: Cuffed central venous catheters were inserted into the jugular vein of female New Zealand White rabbits under image guidance. Catheters were inoculated for 24 hours with broth culture of methicillin-sensitive Staphylococcus aureus. The inoculum was aspirated, and rabbits were randomly assigned to two equal groups for 24 hours: (i) untreated controls (heparinized saline lock), (ii) bacteriophage antimicrobial-lock (staphylococcal bacteriophage K, propagated titer > 10(8)/mL). Blood cultures were obtained via peripheral veins, and the catheters were removed for quantitative culture and scanning electron microscopy. RESULTS: Mean colony-forming units (CFU) per cm(2) of the distal catheter segment, as a measure of biofilm, were significantly decreased in experimental animals compared with controls (control, 1.2 × 10(5) CFU/cm(2); experimental, 7.6 × 10(3); P = .016). Scanning electron microscopy demonstrated that biofilms were present on the surface of five of five control catheters but only one of five treated catheters (P = .048). Blood culture results were not significantly different between the groups. CONCLUSIONS: In a rabbit model, treatment of infected central venous catheters with a bacteriophage antimicrobial-lock technique significantly reduced bacterial colonization and biofilm presence. Our data represent a preliminary step toward use of bacteriophage therapy for prevention and treatment of central venous catheter-associated infection.

Risk of mortality and recurrence after first-time stroke among patients with type 2 diabetes: A Danish nationwide cohort study.

INTRODUCTION: The prognosis for stroke patients with type 2 diabetes mellitus (T2DM) remains poorly understood. We examined the risk of mortality and stroke recurrence in stroke patients with T2DM and stroke patients without diabetes. PATIENTS AND METHODS: We conducted a population-based cohort study including all patients diagnosed with a first-time ischemic stroke (n = 131,594) or intracerebral hemorrhage (ICH, n = 15,492) in Denmark, 2005-2021. Patients with T2DM were identified using hospital diagnosis codes and glucose-lowering drug prescriptions. We calculated risks, risk differences, and risk ratios, standardized by age, sex, and calendar year of stroke admission. RESULTS: Following ischemic stroke, the 5-year standardized mortality was 46.1% for patients with T2DM and 35.4% for patients without diabetes (standardized risk difference: 10.7% [95% CI 9.9-11.6]; risk ratio: 1.3 [95% CI 1.3-1.3]). The 5-year risk of recurrence following ischemic stroke was 12.7% for patients with T2DM and 11.3% for those without diabetes (risk difference: 1.4% [95% CI 0.9-2.0]; risk ratio: 1.1 [95% CI 1.1-1.2]). Following ICH, the 5-year mortality was 62.8% for patients with T2DM and 53.0% for patients without diabetes (risk difference: 9.8% [95% CI 7.2-12.4)]; risk ratio: 1.2 [95% CI 1.1-1.2]). The 5-year risk of recurrence after ICH was 9.1% for patients with T2DM and 9.7% for patients without diabetes. DISCUSSION AND CONCLUSION: Stroke patients with T2DM were at increased risk of mortality. The risk of stroke recurrence was slightly higher for ischemic stroke patients with T2DM than patients without diabetes, while no difference was observed among ICH patients.

Lipid Levels and Risk of Diabetic Polyneuropathy in 2 Danish Type 2 Diabetes Cohorts.

BACKGROUND AND OBJECTIVES: Reduction of blood lipids may aid in preventing diabetic polyneuropathy (DPN), but evidence remains conflicting. We investigated the association between lipid parameters and DPN risk in individuals with type 2 diabetes mellitus (T2DM). METHODS: We conducted a population-based cohort study of individuals with newly diagnosed T2DM and a cross-sectional study using a clinically recruited T2DM cohort. Triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and non-HDL cholesterol were measured in routine diabetes care. Each lipid parameter was categorized according to the latest cutoffs in clinical guidelines on dyslipidemia. DPN was assessed with validated hospital diagnosis codes in the population-based cohort and with the Michigan Neuropathy Screening Instrument questionnaire in the clinical cohort. We calculated hazard ratios (HRs) using Cox regression and prevalence ratios (PRs) using Poisson regression. RESULTS: We included 61,853 individuals in the population-based cohort (median age 63 [quartiles 54-72] years) and 4,823 in the clinical cohort (median age 65 [quartiles 57-72] years). The incidence rate of hospital-diagnosed DPN in the population-based cohort was 3.6 per 1000 person-years during a median follow-up of 7.3 years. Achieving guideline targets for HDL, LDL, and non-HDL cholesterol showed no association with DPN risk. By contrast, adjusted HRs (95% CI) for DPN were 1.02 (0.89-1.18) for triglyceride levels between 150 and 204 mg/dL (1.7-2.3 mmol/L) and 1.28 (1.13-1.45) for levels >204 mg/dL (2.3 mmol/L). In the clinical cohort with a DPN prevalence of 18%, DPN associated strongly with triglycerides >204 mg/dL (2.3 mmol/L) with an adjusted PR (95% CI) of 1.40 (1.21-1.62). The prevalence of DPN was modestly elevated for individuals with HDL cholesterol <39 mg/dL (1.0/1.3 mmol/L) in men and <50 mg/dL (1.3 mmol/L) in women (PR 1.13 [0.99-1.28]) and for individuals with non-HDL cholesterol >131 mg/dL (3.4 mmol/L) (PR 1.27 [1.05-1.52]). In both cohorts, spline models showed an increasing risk of DPN starting from triglyceride levels >124 mg/dL (1.4 mmol/L). All results were similar among statin users. DISCUSSION: High triglyceride levels are a strong DPN risk factor. Future intervention studies shall determine whether triglyceride reduction is more important for DPN prevention than reduction of other lipids.

Streptococcus anginosus group and osteomyelitis: a single centre clinical experience.

PURPOSE: The Streptococcus anginosus group comprises three species of bacteria classified within the viridans streptococci. This group is known for abscess formation and endocarditis. While a variety of sites in the body claim anginosus streptococci as an agent of infection, osteomyelitis is unusual. The objective of this study was to describe a series of patients with osteomyelitis due to S anginosus group pathogens in terms of demographics, comorbidities, presentation and outcomes. STUDY DESIGN: We reviewed our database for cases of osteomyelitis caused by S anginosus organisms. Data described included demographics, comorbidities, site of infection, route of infection (haematogenous versus contiguous), laboratory data and course. RESULTS: 11 patients with S anginosus group osteomyelitis were identified. All cases arose from a contiguous anatomical site, with the exception of one haematogenous case. Five instances were related to foot osteomyelitis while three, two and one case, respectively, were related to mandibular, cranial and vertebral osteomyelitis. Seventy-five per cent of patients had associated abscesses. The mean length of antibiotic treatment was 10.9 weeks. One patient failed therapy while four others relapsed. CONCLUSIONS: Osteomyelitis due to the S anginosus group is uncommonly reported. Our case series illustrates the virulence of these organisms in the context of osteomyelitis and the importance of aggressive management.

Effects of statins and aspirin on HCC risk in alcohol-related cirrhosis: nationwide emulated trials.

BACKGROUND AND AIMS: Observational studies have shown an association between statin or aspirin use and a decreased risk of HCC, but the effects of a well-defined treatment strategy remain unknown. We emulated trials of the effects of continuous statin or aspirin use on HCC risk in patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis). APPROACH AND RESULTS: We specified target trials for statins and, separately, aspirin and emulated them using Danish health care registries. All eligible patients with ALD cirrhosis diagnosed in 2000-2018 were included in either an exposed or an unexposed arm. Patients were followed until HCC or death without HCC. The 5-year risk of HCC was estimated using marginal structural models with inverse probability weighting. Using statins continuously for 5 years compared with not using statins resulted in a relative risk (RR) of HCC of 0.67 (95% CI: 0.45-0.91). The RR of death without HCC was 0.69 (95% CI: 0.65-0.77). For aspirin, the RR was 1.05 (95% CI: 0.60-1.42) for HCC and 1.02 (95% CI: 0.95-1.09) for death without HCC. CONCLUSIONS: In patients with ALD cirrhosis, 5 years of continuous statin use resulted in a 33% RR reduction of HCC (number needed to treat = 94) and a 31% RR reduction of death without HCC (number needed to treat = 7). Such strong causal effects are implausible and best explained by uncontrollable confounding, highlighting the need for randomized trials. Aspirin use likely does not affect the risk of HCC or death without HCC.

Preoperative Breast MRI: Current Evidence and Patient Selection.

Breast MRI is the most sensitive imaging modality for the assessment of newly diagnosed breast cancer extent and can detect additional mammographically and clinically occult breast cancers in the ipsilateral and contralateral breasts. Nonetheless, appropriate use of breast MRI in the setting of newly diagnosed breast cancer remains debated. Though highly sensitive, MRI is less specific and may result in false positives and overestimation of disease when MRI findings are not biopsied prior to surgical excision. Furthermore, improved anatomic depiction of breast cancer on MRI has not consistently translated to improved clinical outcomes, such as lower rates of re-excision or breast cancer recurrence, though there is a paucity of well-designed studies examining these issues. In addition, current treatment paradigms have been developed in the absence of this more accurate depiction of disease span, which likely has limited the value of MRI. These issues have led to inconsistent and variable utilization of preoperative MRI across practice settings and providers. In this review, we discuss the history of breast MRI and its current use and recommendations with a focus on the preoperative setting. We review the evidence surrounding the use of preoperative MRI in the evaluation of breast malignancies and discuss the data on breast MRI in the setting of specific patient factors often used to determine breast MRI eligibility, such as age, index tumor phenotype, and breast density. Finally, we review the impact of breast MRI on surgical outcomes (re-excision and mastectomy rates) and long-term breast recurrence and survival outcomes.

The Prevalence of Polyneuropathy in Type 2 Diabetes Subgroups Based on HOMA2 Indices of ß-Cell Function and Insulin Sensitivity.

OBJECTIVE: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of ß-cell function and insulin sensitivity. RESEARCH DESIGN AND METHODS: We estimated ß-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM. Patients were categorized into subgroups of hyperinsulinemic (high HOMA2-B, low HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and insulinopenic (low HOMA2-B, high HOMA2-S) T2DM. After a median follow-up of 3 years, patients filled the Michigan Neuropathy Screening Instrument questionnaire (MNSIq) to identify DPN (score ≥ 4). We used Poisson regression to calculate adjusted prevalence ratios (PRs) for DPN, and spline models to examine the association with HOMA2-B and HOMA2-S. RESULTS: A total of 3,397 (77%) patients filled in the MNSIq. The prevalence of DPN was 23% among hyperinsulinemic, 16% among classical, and 14% among insulinopenic patients. After adjusting for demographics, diabetes duration and therapy, lifestyle behaviors, and metabolic syndrome components (waist circumference, triglycerides, HDL cholesterol, hypertension, and HbA1c), the PR of DPN was 1.35 (95% CI 1.15-1.57) for the hyperinsulinemic compared with the classical patients. In spline analyses, we observed a linear relation of higher DPN prevalence with increasing HOMA2-B, independent of both metabolic syndrome components and HOMA2-S. CONCLUSIONS: Hyperinsulinemia marked by high HOMA2-B is likely an important risk factor for DPN beyond metabolic syndrome components and insulin resistance. This should be considered when developing interventions to prevent DPN.

Risk of cardiovascular events associated with pathophysiological phenotypes of type 2 diabetes.

Objective: Hyperglycaemia in type 2 diabetes is caused by varying degrees of two defects: low insulin sensitivity and beta-cell dysfunction. We assessed if subgrouping of patients into three pathophysiological phenotypes according to these defects could identify individuals with high or low risk of future cardiovascular events. Design: This is a prospective cohort study. Methods: We assessed estimates of insulin sensitivity and beta-cell function from the homeostasis model assessment-2 in 4209 individuals with recently diagnosed type 2 diabetes enrolled from general practitioners and outpatient clinics in Denmark. Individuals were followed for a composite cardiovascular endpoint (either atherosclerotic outcomes (myocardial infarction, unstable angina pectoris, stroke, coronary or peripheral revascularization), heart failure, or cardiovascular death) and all-cause mortality. Results: Totally 417 individuals with the insulinopenic phenotype (high insulin sensitivity and low beta-cell function) had substantially lower risk of cardiovascular events (5-year cumulative incidence: 4.6% vs 10.1%; age-/sex-adjusted hazard ratio (aHR): 0.49; 95% CI: 0.30-0.82) compared with 2685 individuals with the classical phenotype (low insulin sensitivity and low beta-cell function), driven by atherosclerotic events. Conversely, 1107 individuals with the hyperinsulinaemic phenotype (low insulin sensitivity and high beta-cell function) had more cardiovascular events (5-year cumulative incidence: 12.6%; aHR: 1.33; 95% CI: 1.05-1.69), primarily driven by increased heart failure and cardiovascular death and increased all-cause mortality. Conclusions: Simple phenotyping based on insulin sensitivity and beta-cell function predicts distinct future risks of cardiovascular events and death in patients with type 2 diabetes. These results suggest that precision medicine according to underlying type 2 pathophysiology potentially can reduce diabetes complications.

Type 2 diabetes classification: a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort.

INTRODUCTION: A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. RESEARCH DESIGN AND METHODS: In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. RESULTS: Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m2 vs 36 kg/m2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. CONCLUSION: Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.

Falls and fractures associated with type 2 diabetic polyneuropathy: A cross-sectional nationwide questionnaire study.

AIMS/INTRODUCTION: To examine the prevalence of falls and fractures, and the association with symptoms of diabetic polyneuropathy (DPN) in patients with recently diagnosed type 2 diabetes. MATERIALS AND METHODS: A detailed questionnaire on neuropathy symptoms and falls was sent to 6,726 patients enrolled in the Danish Center for Strategic Research in Type 2 Diabetes cohort (median age 65 years, diabetes duration 4.6 years). Complete data on fractures and patient characteristics were ascertained from population-based health registries. We defined possible DPN as a score ≥4 on the Michigan Neuropathy Screening Instruments questionnaire. Using Poisson regression analyses, we estimated the adjusted prevalence ratio (aPR) of falls and fractures, comparing patients with and without DPN. RESULTS: In total, 5,359 patients (80%) answered the questions on the Michigan Neuropathy Screening Instruments questionnaire and falls. Within the year preceding the questionnaire response, 17% (n = 933) reported at least one fall and 1.4% (n = 76) suffered from a fracture. The prevalence ratio of falls was substantially increased in patients with possible DPN compared with those without (aPR 2.33, 95% confidence interval [CI] 2.06-2.63). The prevalence ratio increased with the number of falls from aPR 1.51 (95% CI 1.22-1.89) for one fall to aPR 5.89 (95% CI 3.84-9.05) for four or more falls within the preceding year. Possible DPN was associated with a slightly although non-significantly increased risk of fractures (aPR 1.32, 95% CI 0.75-2.33). CONCLUSIONS: Patients with recently diagnosed type 2 diabetes and symptoms of DPN had a highly increased risk of falling. These results emphasize the need for preventive interventions to reduce fall risk among patients with type 2 diabetes and possible DPN.

Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies.

OBJECTIVE: Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death. RESEARCH DESIGN AND METHODS: We linked data from two Danish type 2 diabetes cohorts, the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) and the Danish Centre for Strategic Research in Type 2 Diabetes (DD2), to national health care registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios (IRRs) of CVD and all-cause mortality comparing MNSIq scores ≥4 with scores <4. Analyses were adjusted for a range of established CVD risk factors. RESULTS: In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores <4, MNSIq scores ≥4 were associated with higher incidence rate of CVD, with IRRs of 1.79 (95% CI 1.38-2.31) in ADDITION-Denmark, 1.57 (CI 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥4 did not associate with mortality; combined mortality rate ratio was 1.11 (CI 0.83-1.48). CONCLUSIONS: The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes with a high incidence rate of subsequent CVD. MNSIq scores ≥4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors.

Pediatric Guillain-Barré Syndrome in a 30-Year Nationwide Cohort.

BACKGROUND: Guillain-Barré syndrome is the most common cause of acute flaccid paresis in childhood. Few validated large-scale population-based data are available concerning pediatric Guillain-Barré syndrome, including incidence, risk factors, and initial clinical characteristics. METHODS: In the Danish National Patient Registry, we identified all children aged below 16 years (N = 212) diagnosed with Guillain-Barré syndrome and admitted to any Danish department of pediatrics between 1987 and 2016. A total of 145 (68%) medical files could be retrieved and reviewed, enabling classification of patients with true Guillain-Barré syndrome. The nationwide Guillain-Barré syndrome incidence rate was calculated and stratified by age, gender, time periods, and season. Risk factors and initial Guillain-Barré syndrome characteristics were assessed by medical record review. RESULTS: The positive predictive value of Guillain-Barré syndrome diagnosis codes was 86%. The crude Guillain-Barré syndrome incidence rate was 0.69 per 100,000 person years and peaked at two years of age. The incidence rate was higher among men (0.80) than women (0.58) and was relatively stable over the 30-year period. No seasonal difference of the incidence rate was found. Of the 125 Guillain-Barré syndrome cases, 63% were preceded by infection, whereas none were preceded by surgery or malignant disease. Medically treated pain was documented in 70%, mainly confined to the lower extremities. CONCLUSIONS: Pediatric Guillain-Barré syndrome diagnoses in the Danish National Patient Registry have high validity, the incidence peaks at age two years, and is preceded by infection in two-thirds of children. Lower extremity pain is a common clinical presentation in the acute setting.

Statin Therapy and Risk of Polyneuropathy in Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Statins may reduce the risk of diabetic polyneuropathy (DPN) as a result of lipid-lowering and anti-inflammatory effects, but statins have also been associated with neurotoxicity. We examined whether statin therapy affects the risk of DPN. RESEARCH DESIGN AND METHODS: We identified all Danish patients with incident type 2 diabetes during 2002-2016. New users initiated statins between 180 days before and 180 days after their first diabetes record, while prevalent users had initiated statins before that period. Patients were followed for incident DPN using validated hospital diagnosis codes, starting 180 days after their first diabetes record. Cox proportional hazard analysis was used to compute adjusted hazard ratios (aHRs) for DPN. RESULTS: The study cohort comprised 59,255 (23%) new users, 75,528 (29%) prevalent users, and 124,842 (48%) nonusers; median follow-up time was 6.2 years (interquartile range 3.4-9.6). The incidence rate of DPN events per 1,000 person-years was similar in new users (4.0 [95% CI 3.8-4.2]), prevalent users (3.8 [3.6-3.9]), and nonusers (3.8 [3.7-4.0]). The aHR for DPN was 1.05 (0.98-1.11) in new users and 0.97 (0.91-1.04) in prevalent users compared with statin nonusers. New users had a slightly increased DPN risk during the first year (1.31 [1.12-1.53]), which vanished after >2 years of follow-up. Findings were similar in on-treatment and propensity score-matched analyses and with additional adjustment for pretreatment blood lipid levels. CONCLUSIONS: Statin therapy is unlikely to increase or mitigate DPN risk in patients with type 2 diabetes, although a small acute risk of harm cannot be excluded.

Metabolic Factors, Lifestyle Habits, and Possible Polyneuropathy in Early Type 2 Diabetes: A Nationwide Study of 5,249 Patients in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) Cohort.

OBJECTIVE: To investigate the association of metabolic and lifestyle factors with possible diabetic polyneuropathy (DPN) and neuropathic pain in patients with early type 2 diabetes. RESEARCH DESIGN AND METHODS: We thoroughly characterized 6,726 patients with recently diagnosed diabetes. After a median of 2.8 years, we sent a detailed questionnaire on neuropathy, including the Michigan Neuropathy Screening Instrument questionnaire (MNSIq), to identify possible DPN (score ≥4) and the Douleur Neuropathique en 4 Questions (DN4) questionnaire for possible associated neuropathic pain (MNSIq ≥4 + pain in both feet + DN4 score ≥3). RESULTS: Among 5,249 patients with data on both DPN and pain, 17.9% (n = 938) had possible DPN, including 7.4% (n = 386) with possible neuropathic pain. In regression analyses, central obesity (waist circumference, waist-to-hip ratio, and waist-to-height ratio) was markedly associated with DPN. Other important metabolic factors associated with DPN included hypertriglyceridemia ≥1.7 mmol/L, adjusted prevalence ratio (aPR) 1.36 (95% CI 1.17; 1.59); decreased HDL cholesterol <1.0/1.2 mmol/L (male/female), aPR 1.35 (95% CI 1.12; 1.62); hs-CRP ≥3.0 mg/L, aPR 1.66 (95% CI 1.42; 1.94); C-peptide ≥1,550 pmol/L, aPR 1.72 (95% CI 1.43; 2.07); HbA1c ≥78 mmol/mol, aPR 1.42 (95% CI 1.06; 1.88); and antihypertensive drug use, aPR 1.34 (95% CI 1.16; 1.55). Smoking, aPR 1.50 (95% CI 1.24; 1.81), and lack of physical activity (0 vs. ≥3 days/week), aPR 1.61 (95% CI 1.39; 1.85), were also associated with DPN. Smoking, high alcohol intake, and failure to increase activity after diabetes diagnosis associated with neuropathic pain. CONCLUSIONS: Possible DPN was associated with metabolic syndrome factors, insulin resistance, inflammation, and modifiable lifestyle habits in early type 2 diabetes.