The use of statins, which are inhibitors of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) enzyme, may in rare cases be associated with immune-mediated necrotizing myopathy. This condition is characterized by the presence of autoantibodies directed against the HMGCR enzyme. Previously considered very rare, the incidence of this myopathy diagnosis has markedly increased in our rheumatology unit over the past years. We conducted a retrospective analysis of 13 patients diagnosed with statin-associated anti-HMGCR antibody (Ab)-positive immune-mediated necrotizing myopathy (anti-HMGCR-IMNM) over the 5-year period (June 2020–May 2025) at the Turku University Hospital’s rheumatology department serving 490,000 inhabitants. Patients presented with elevated creatine kinase (CK) levels, positive anti-HMGCR-Ab, proximal muscle weakness, and the initial symptom was usually difficulty walking. No other myositis autoantibodies were detected and extra-myopathic symptoms were rare. Most patients responded to immunosuppressive therapy including glucocorticoids, methotrexate or azathioprine, and rituximab with a more severe disease course. Disease severity ranged from mild to fatal. The incidence of statin-associated anti-HMGCR-IMNM was 5.3 cases per million per year, approximately 2.75 per 100,000 statin users per year, higher than previously reported. Statin-associated anti-HMGCR-IMNM is a rare but increasingly recognized condition requiring early diagnosis and immunosuppressive treatment. The clinical presentation is highly variable. Treatment and its intensity must be tailored individually, taking into account the patient’s comorbidities and treatment related risks.
In chronic pancreatitis (CP), a symptomatic benign biliary stricture (BBS) evolves as an adverse event in 3–30
INTRODUCTION:The clearance of brain metabolites increases during sleep, in association with increased spectral power of the three main cerebrospinal fluid (CSF) flow drivers: cardiovascular, respiratory, and vasomotor brain pulsations. However, little is known about how the increased power of these pulsations affects the velocity and direction of fluid flow in the sleeping brain. OBJECTIVES:To address this knowledge gap, we mapped the CSF oscillatory flow velocity in relation to the changing physiological pulsations in the brains of 22 healthy volunteers during sleep and waking. METHODS:We used the ultrafast magnetic resonance imaging sequence known as magnetic resonance encephalography (MREG) for tracing the pulsatile movement of water molecules inside the cranium. First, we conducted a phantom validation study with optical flow analysis to confirm that MREG accurately tracks pulsatile water molecule flow in a porous tissue medium. Next, we obtained MREG recordings for mapping the three physiological pulsations without aliasing in the human brain across the awake and sleep states; we thereby quantified the brain-wide 3D velocity → V $\mathop \to \limits_{\mathrm{V}} $ vectors (i.e., the velocity vs and 3D direction v ̂ ${\mathrm{\hat{v}}}$ ) of each pulsation band, using comprehensive dense optical flow analysis during EEG-verified sleep in comparison to the awake state. Finally, we assessed relationships among the spectral power of the physiological pulsations, their 3D velocity → V $\mathop \to \limits_{\mathrm{V}} $ , and slow-delta EEG power, which is known to depict the increased interstitial volume during sleep. RESULTS:In our phantom study, dense optical flow analysis reliably detected water flow in tissue driven by external pulsations. In healthy volunteers, sleep increased flow velocities ( → V $\mathop \to \limits_{\mathrm{V}} $ ) of the pulsations by more than 20% in concert with elevations in respiratory pulsations and vasomotor waves, while the velocity of cardiovascular pulsations (vs) declined by the same percentage. There was a significant anticorrelation between cardiac mean spectral power and slow delta EEG mean power, and a significant correlation between vasomotor mean spectral power and slow delta EEG mean power over the whole brain. CONCLUSIONS:Phantom studies validated the optic flow analysis of fast MREG recordings. Sleep altered the 3D velocity dynamics of all neurofluidic brain pulsations in a manner consistent with increased interstitial space and greater fluid exchange, thus supporting the glymphatic model wherein physiological pulsations drive bulk flow during sleep.
Generalized pustular psoriasis is an inflammatory disease characterized by potentially life-threatening flares. This study assessed the economic burden of generalized pustular psoriasis in Finland by comparing healthcare resource utilization and both direct and indirect costs to population-based and psoriasis vulgaris control groups and between generalized pustular psoriasis patients with and without flares. Patients with ≥ 2 generalized pustular psoriasis diagnoses (ICD-10: L40.1) at a dermatology clinic in secondary healthcare and matched controls were identified during 1996–2019 from national registers. Direct costs were based on primary and secondary healthcare resource utilization and medications, and indirect costs on productivity loss due to sick leaves, disability pensions, and rehabilitation periods. All-cause annual direct costs were 3-fold higher in generalized pustular psoriasis (mean: €10,323) compared with population-based (€3,345; p < 0.001), and psoriasis vulgaris controls (€3,569; p < 0.001). Having flares was associated with 2.7-fold higher direct costs compared with no flares (cost ratio 2.7; 95% CI, 2.1–3.5; p < 0.001), driven by higher hospitalization rates of patients with flares. Flares were also associated with 2.5-fold higher indirect costs (cost ratio 2.5; 95% CI, 1.6–4.0; p < 0.001) compared with no flares. This first comprehensive economic evaluation of generalized pustular psoriasis highlights the substantial economic impact, in particular in patients with flares, and emphasizes costs due to work disability.
Sleep is essential for maintaining brain tissue homeostasis, which is facilitated by enhanced cerebrospinal fluid (CSF) solute transport. Infraslow (<0.1 Hz) vasomotion, CSF flow, and electrophysiological potential all increase during sleep, but their contributions as potential drivers of CSF flow in human brain remain unknown. To investigate this, we measured these signals in healthy volunteers across sleep-wake states using functional MRI blood oxygen level-dependent (BOLD), electroencephalography, and functional near-infrared spectroscopy. We then studied the directed coupling patterns between the three signals, using phase transfer entropy. In the awake state, electrophysiological potential and water concentration changes both predicted hemodynamic BOLD changes across whole brain, reflecting classical functional hyperemia. During sleep, these interactions changed such that the net directionality was lost and the interactions became more bidirectional. Our results show that in addition to neural changes during sleep, nonneural processes such as vasomotor-driven hydrodynamic waves start to gain more impact on human brain activity.
