Acute-onset Patients Research Articles

Bivalent GAD autoantibody ELISA improves clinical utility and risk prediction for adult autoimmune diabetes.

To investigate the differences in the clinical significance and glutamic acid decarboxylase autoantibody (GADA) affinity between RIA (RIA-GADA) and ELISA (ELISA-GADA) in patients with type 1 diabetes. A total of 415 patients with type 1 diabetes were enrolled, including 199 acute-onset type 1 diabetes, 168 slowly progressive type 1 diabetes (SPIDDM), and 48 fulminant type 1 diabetes. GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 protein, and the diagnostic performance of both assays and the relationship between GADA affinity and the decline of fasting C-peptide (F-CPR) were examined. While the ELISA-GADA displayed a higher sensitivity than the RIA method in diagnosing type 1 diabetes in acute-onset patients, about 40% of SPIDDM patients with low-titer RIA-GADA were determined as negative by the ELISA method. Patients with type 1 diabetes with RIA-GADA alone had an older age of onset, less diabetic ketoacidosis, a higher BMI, and a higher F-CPR compared with patients positive for both RIA-GADA and ELISA-GADA. Additionally, 36% of RIA-GADA-positive patients had low-affinity GADA (<1010 L/mol), which was significantly higher than in the ELISA-GADA-positive patients (4%, P < 0.0001). Furthermore, over a 3 year monitoring period, F-CPR levels decreased in ELISA-GADA-positive SPIDDM, whereas it was maintained in patients with RIA-GADA alone, regardless of GADA affinity. These results suggest that bivalent ELISA for GADA is superior to the RIA method in diagnosing type 1 diabetes. Moreover, the diagnostic superiority of the ELISA-GADA made possible the concurrent identification of SPIDDM patients at high-risk of early progression, and allowed for more accurate clinical diagnosis and management.

Patterns, evolution, and severity of striatal injury in insidious- vs acute-onset glutaric aciduria type 1.

Striatal injury in patients with glutaric aciduria type 1 (GA1) results in a complex, predominantly dystonic, movement disorder. Onset may be acute following acute encephalopathic crisis (AEC) or insidious without apparent acute event. We analyzed clinical and striatal magnetic resonance imaging (MRI) findings in 21 symptomatic GA1 patients to investigate if insidious- and acute-onset patients differed in timing, pattern of striatal injury, and outcome. Eleven patients had acute and ten had insidious onset, two with later AEC (acute-on-insidious). The median onset of dystonia was 10 months in both groups, and severity was greater in patients after AEC (n = 8 severe, n = 5 moderate) than in insidious onset (n = 4 mild, n = 3 moderate, n = 1 severe). Deviations from guideline-recommended basic metabolic treatment were identified in six insidious-onset patients. Striatal lesions were extensive in all acute-onset patients and restricted to the dorsolateral putamen in eight of ten insidious-onset patients. After AEC, the two acute-on-insidious patients had extensive striatal changes superimposed on pre-existing dorsolateral putaminal lesions. Two insidious-onset patients with progressive dystonia without overt AEC also had extensive striatal changes, one with sequential striatal injury revealed by diffusion-weighted imaging. Insidious-onset patients had a latency phase of 3.5 months to 6.5 years between detection and clinical manifestation of dorsolateral putaminal lesions. Insidious-onset type GA1 is characterized by dorsolateral putaminal lesions, less severe dystonia, and an asymptomatic latency phase, despite already existing lesions. Initially normal MRI during the first months and deviations from guideline-recommended treatment in a large proportion of insidious-onset patients substantiate the protective effect of neonatally initiated treatment.

Characteristics of pulmonary mucormycosis and predictive risk factors for the outcome.

Little is known about risk factors for the outcome of pulmonary mucormycosis. We summarized characteristics of this rare disease, and systemically explored risk factors for the outcome. Ninety-two patients with pulmonary mucormycosis, including 12 patients at Peking Union Medical College Hospital and 80 patients published in 62 articles between 2006 and 2016, were retrospectively analyzed. The median age was 47.5 years, and the male to female ratio was 2.8:1. Hematological disorders, diabetes mellitus, renal insufficiency and organ transplantation were main underlying conditions. Twelve percent of patients had no underlying diseases. A predilection for involvement of upper lobes was noted, and thick-walled cavity was described in 37.0% of patients on chest computed tomography. Most of the patients were diagnosed by microscopic analysis (95.7%), mainly histopathology; and only a minority were diagnosed by culture of sterile materials (28.3%). The overall mortality rate was 30.4%. Four independent determinants were associated with a better prognosis: hemoptysis (adjusted OR 7.910; 95% CI 1.411-44.342), chronic onset (adjusted OR 25.269, 95% CI 1.654-385.993), treated with medicine (adjusted OR 53.896, 95% CI 3.072-945.561), and treated with surgery (adjusted OR 5.983, 95% CI 1.497-23.918). Pulmonary mucormycosis is a rare infection with a high mortality. Invasive approach for histopathology and culture are crucial for a definite diagnosis. Acute onset patients had a poorer prognosis, and early treatment with antifungal therapy is imperative. Surgical approach is recommended in appropriate patients for a better outcome.

Patterns, evolution, and severity of striatal injury in insidious- versus acute-onset glutaric aciduria type 1.

Striatal injury in patients with glutaric aciduria type 1 (GA1) results in a complex, predominantly dystonic, movement disorder. Onset may be acute following acute encephalopathic crisis (AEC) or insidious without apparent acute event. We analyzed clinical and striatal magnetic resonance imaging (MRI) findings in 21 symptomatic GA1 patients to investigate if insidious- and acute-onset patients differed in timing, pattern of striatal injury, and outcome. Eleven patients had acute and ten had insidious onset, two with later AEC (acute-on-insidious). The median onset of dystonia was 10months in both groups, and severity was greater in patients after AEC (n= 8 severe, n= 5 moderate) than in insidious onset (n= 4 mild, n= 3 moderate, n= 1 severe). Deviations from guideline-recommended basic metabolic treatment were identified in six insidious-onset patients. Striatal lesions were extensive in all acute-onset patients and restricted to the dorsolateral putamen in eight of ten insidious-onset patients. After AEC, the two acute-on-insidious patients had extensive striatal changes superimposed on pre-existing dorsolateral putaminal lesions. Two insidious-onset patients with progressive dystonia without overt AEC also had extensive striatal changes, one with sequential striatal injury revealed by diffusion-weighted imaging. Insidious-onset patients had a latency phase of 3.5months to 6.5years between detection and clinical manifestation of dorsolateral putaminal lesions. Insidious-onset type GA1 is characterized by dorsolateral putaminal lesions, less severe dystonia, and an asymptomatic latency phase, despite already existing lesions. Initially normal MRI during the first months and deviations from guideline-recommended treatment in a large proportion of insidious-onset patients substantiate the protective effect of neonatally initiated treatment.

Multidisciplinary clinic dedicated to treating youth with pediatric acute-onset neuropsychiatric syndrome: presenting characteristics of the first 47 consecutive patients.

Abrupt, dramatic onset obsessive-compulsive disorder (OCD) and/or eating restriction with at least two coinciding symptoms (anxiety, mood dysregulation, irritability/aggression/oppositionality, behavioral regression, cognitive deterioration, sensory or motor abnormalities, or somatic symptoms) defines pediatric acute-onset neuropsychiatric syndrome (PANS). Descriptions of clinical data in such youth are limited. We reviewed charts of 53 consecutive patients evaluated in our PANS Clinic; 47 met PANS symptom criteria but not all met the requirement for "acute onset." Patients meeting full criteria for PANS were compared with patients who had a subacute/insidious onset of symptoms. Nineteen of 47 (40%) patients in the study had acute onset of symptoms. In these patients, autoimmune/inflammatory diseases and psychiatric disorders were common in first-degree family members (71% and 78%, respectively). Most acute-onset patients had a relapsing/remitting course (84%), prominent sleep disturbances (84%), urinary issues (58%), sensory amplification (66%), gastrointestinal symptoms (42%), and generalized pain (68%). Inflammatory back pain (21%) and other arthritis conditions (28%) were also common. Suicidal and homicidal thoughts and gestures were common (44% and 17%, respectively) as were violent outbursts (61%). Group A streptococcus (GAS) was the most commonly identified infection at onset (21%) and during flares (74%). Rates of the above-mentioned characteristics did not differ between the acute-onset group and the subacute/insidious-onset groups. Low levels of immunoglobulins were more common in the subacute/insidious-onset group (75%) compared with the acute-onset group (22%), but this was not statistically significant (p=0.06). In our PANS clinic, 40% of patients had acute onset of symptoms. However, those with and without acute onset of symptoms had similar symptom presentation, rates of inflammatory conditions, somatic symptoms, and violent thoughts and behaviors. GAS infections were the most commonly identified infection at onset and at symptom flares. Because of the wide variety of medical and psychiatric symptoms, youth with PANS may require a multidisciplinary team for adequate care management.

Type 1 diabetes and autoimmunity.

.Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic β cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset.

Delayed- Versus Acute-Onset Endophthalmitis After Cataract Surgery

To report a large consecutive case series of patients who developed delayed-onset and acute-onset endophthalmitis after cataract surgery. Retrospective consecutive case series. The current study is a retrospective consecutive case series of patients treated between January 2000 and December 2009 for culture-proven endophthalmitis after cataract surgery. The study defined 2 groups after cataract surgery: acute-onset endophthalmitis (≤6 weeks after surgery) and delayed-onset endophthalmitis (>6 weeks after surgery). A total of 118 patients met study criteria; cases included 26 delayed-onset cases and 92 acute-onset cases. The following clinical features and outcomes occurred in delayed- vs acute-onset cases: 1) the presenting visual acuity was ≤5/200 in 31% vs 89%; 2) hypopyon was found in 46% vs 80%; 3) the most frequent isolate was Propionibacterium acnes (11/26) vs coagulase-negative Staphylococcus (57/92); and 4) patients with the most frequent isolate achieved a visual outcome of ≥20/100 in 91% vs 56%. In delayed-onset cases, the intraocular lens was removed or exchanged in 19 of 26 cases (73%). Of these 19 cases, 13 achieved a visual outcome of ≥20/100. Patients with delayed-onset endophthalmitis generally presented with better initial visual acuities, had a lower frequency of hypopyon, and had better visual outcomes compared to acute-onset patients. Propionibacterium acnes and coagulase-negative Staphylococcus species were the most common organisms cultured in delayed- and acute-onset categories, respectively, and were associated with the best visual acuity outcomes in each group.

Effect of human leukocyte antigen class II genes on acute-onset and slow-onset type 1 diabetes in the Japanese population

The contribution of the human leukocyte antigen (HLA) subtype to slow-onset type 1 diabetes (T1D), which includes latent autoimmune diabetes in adults (LADA), remains unclear in the Japanese population. We compared the frequencies of HLA DR-DQ haplotypes and genotypes of 72 acute-onset T1D patients, 100 slow-onset T1D patients, and 292 control subjects. The frequencies of DRB1*0405-DQB1*0401 (DR4) and DRB1*1302-DQB1*0604 (DR13) haplotypes were significantly higher in acute-onset patients, whereas that of the DRB1*1502-DQB1*0601 haplotype was significantly lower than those in slow-onset diabetes patients and controls. In contrast, DRB1*0802-DQB1*0302 (DR8) and DRB1*0901-DQB1*0303 (DR9) haplotypes were significantly more frequent, and the DRB1*1501-DQB1*0602 haplotype was extremely rare, in acute-onset patients and slow-onset diabetes patients. Genotype analysis revealed that DR4/9, DR4/13, and DR9/13 in acute-onset patients indicated high odds ratios (6.81, 12.0, and 15.6, respectively), whereas DR4/8 was significantly more frequent in slow-onset diabetes patients, but not in acute-onset patients. Our study demonstrated for the first time that the DR8 haplotype confers susceptibility to slow-onset T1D in the Japanese population. Moreover, there potentially are hierarchies for predisposing haplotypes, namely, DR13 > DR4 > DR9 > DR8 and for protective haplotypes, namely, DRB1*1501-DQB1*0602 > DRB1*1502-DQB1*0601.

Improved prognosis of renal microscopic polyarteritis in recent years.

To determine if the short- and long-term prognosis of renal micropolyarteritis (including Wegener's granulomatosis) had improved in our Unit in the last 5 years compared to our previous series from 1965 to 1980, we examined data from 26 recent patients, 1981-1986. Twenty were admitted during acute phase and six after a mean of 7.1 months of disease. The acute phase showed mild to severe impairment of renal function, and renal biopsies showed necrotising glomerulitis in all acute patients with extensive crescents in 67%. Acute patients (20) were treated with 'aggressive' immunosuppression including i.v. methylprednisolone (15), plasmapheresis (seven) and cyclophosphamide (ten). Chronic immunosuppressive treatment was continued in most patients. In the 20 acute-onset patients, life survival at 2 and 5 years was 77%; four of five deaths occurred during the acute phase in aged patients with severe renal failure. The notable improvement in life and kidney survival (only one patient underwent chronic dialysis) probably resulted from greater awareness of vasculitis in general practice with early referral of patients to specialised units, and to more aggressive treatment.