Batoclimab as an add-on therapy in neuromyelitis optica spectrum disorder patients with acute attacks.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder (NMOSD) is a severe neurological inflammatory disease mainly caused by pathogenic aquaporin-4 antibodies (AQP4-IgG). The safety and efficacy of the neonatal Fc receptor antagonist batoclimab addition to conventional intravenous methylprednisolone pulse (IVMP) therapy in patients with NMOSD acute attacks was assessed. METHODS: In an open-label, dose-escalation phase 1b study, NMOSD patients with acute myelitis and/or optic neuritis received four doses of weekly subcutaneous injections of either 340 mg or 680 mg batoclimab with concurrent IVMP and were followed up for 27 weeks. The primary end-points were safety and tolerability. Secondary end-points included pharmacodynamics and efficacy, with key efficacy assessment at week 4. RESULTS: In total nine NMOSD patients were enrolled, including two and seven in the 340 and 680 mg groups. Five patients had acute myelitis, while the remaining four had unilateral optic neuritis. Batoclimab add-on therapy had an overall good safety profile without serious adverse events. In the 680 mg group, mean immunoglobulin G (IgG) reached its maximum reduction at the last dose (day 22). In the meantime, AQP4-IgG was undetectable in six of seven subjects whose baseline AQP4-IgG titers ranged from 1:32 to 1:320. Expanded Disability Status Scale score was reduced by 1.3 ± 0.4 at week 4 (2.7 ± 1.3) compared with baseline (4.0 ± 1.0). CONCLUSIONS: Batoclimab add-on therapy to IVMP is safe and tolerated in patients with NMOSD. Preliminary evidence suggests a beneficial neurological effect. A randomized controlled trial would be needed to prove the efficacy.

[Diurnal differences in acute gout attacks: A clinical study of male gout patients].

OBJECTIVE: To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment. METHODS: Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators. RESULTS: A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks. CONCLUSION: No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

Correlation between galectin-3, RDW, Hepc, HS and ferritin and prognosis of patients with acute onset of chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is characterized by a high hospitalization rate and a high mortality rate. It is particularly important to identify biomarkers for predicting the prognosis of patients with acute attack of CHF. PURPOSE: To observe the correlation between galectin-3, RDW, Hepc, HS and ferritin and the prognosis of patients with acute onset of CHF. METHODS: The study included 92 patients with acute onset of CHF who received treatment at our hospital between August 2020 and December 2021. After treatment, the patients were divided into the effective group and the non-effective group based on the effectiveness of treatment. The levels of galectin-3, RDW, Hepc, HS and ferritin before and after treatment were compared between the two groups and the correlation between prognosis of patients with acute attack of CHF and galectin-3, RDW, Hepc, HS and ferritin was observed. RESULTS: The effective rate was 71.74% (66/92) and the ineffective rate was 28.26% (26/92) in the 92 patients with acute attack of CHF in the study. Before and after treatment, the levels of galectin-3, RDW, Hepc, and HS were lower in the effective group than those of the non-effective group while the level of ferritin was higher in the effective group than that of the non-effective group (P < 0.05). Spearman correlation analysis showed that the level of prognosis of patients with acute attack of CHF was positively correlated with galectin-3, RDW, Hepc, and HS (r = 0.217, 0.109, 0.376, 0.765, P = 0.026, 0.032, 0.021, 0.006), and negatively correlated with ferritin (r = - 0.127, P = 0.037). The independent variables were galectin-3, RDW, Hepc, HS and ferritin and the dependent variable was prognosis of patients with acute attack of CHF. Univariate logistic regression analysis showed that alectin-3, RDW, Hepc, HS, and ferritin were protective factors for the prognosis of patients with acute attack of CHF. The independent variables were galectin-3, RDW, Hepc, HS and ferritin, dependent variables and the dependent variable was prognosis of patients with acute attack of CHF. Multivariate logistic regression analysis revealed that galectin-3, RDW, and Hepc were risk factors of the prognosis of patients with acute attack of CHF. CONCLUSION: Galectin-3, RDW, Hepc, HS and ferritin were closely related with the prognosis of patients with acute attack of CHF and galectin-3, RDW, and Hepc were risk factors of the prognosis of patients with acute attack of CHF.

Effects of budesonide combined with salbutamol on pulmonary function and peripheral blood eosinophiles and IgE in patients with acute attack of bronchial asthma.

Objectives: To explore the effect and value of salbutamol and budesonide in the treatment of patients with acute attack of bronchial asthma. Methods: Medical records of patients with acute attack of bronchial asthma treated in our hospital from February 2020 to March 2021 were retrospectively analyzed. Of them, 30 patients received salbutamol atomization inhalation treatment in addition to routine treatment such as cough relief, oxygen inhalation and asthma relief (Group-I), and 40 patients received routine treatment and budesonide and salbutamol atomization inhalation (Group-II). The time of symptom improvement, the improvement in pulmonary function indexes and in peripheral blood eosinophile (EOS) and IgE levels were retrospectively analyzed and compared between the two schemes. Results: After the treatment, the average time of respiratory restriction, cough, shortness of breath and wheezing improvement in patients, treated with Group-II were lower than those in Group-I (P<0.05). Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF) in Group-II were significantly higher than those in Group-I (P<0.05). Post treatment levels of EOS and IgE in peripheral blood of Group-II were significantly lower than those of Group-I (P<0.05). Conclusion: On the basis of routine treatment, budesonide combined with salbutamol atomization inhalation for the treatment of patients with acute attack of asthma can be more efficient in improving symptoms and pulmonary, function and promote the effective reduction of EOS and IgE levels in peripheral blood.

[Anatomical and morphometric features of anterior eye segment structures in hyperopia and the risk of developing primary angle-closure glaucoma]. / Anatomo-morfometricheskie osobennosti struktur perednego segmenta glaza pri gipermetropii i risk razvitiya pervichnoi zakrytougol'noi glaukomy.

PURPOSE: To study features of anatomical and morphometric parameters of the structures of anterior eye segment in young patients with moderate and high hyperopia in order to identify the signs of an increased risk of developing primary angle-closure glaucoma (PACG) and its acute attack. MATERIAL AND METHODS: The study included 160 eyes (80 patients) with axial length (AL) of less than 23 mm. Patients with moderate or high hyperopia were divided into two groups according to their age ranges (the 1st - 27 patients (54 eyes) under 40 years old; the 2nd - 27 patients (54 eyes) of 41-50 years old, the comparison group - 26 patients (52 eyes) of 42-50 years old with the initial stage of PACG. AL of the eyes, anterior chamber (AC) depth in the central zone, lens thickness (LT) in the optical zone were measured using IOL Master 700 («Carl Zeiss Meditec AG¼, Germany). AC volume and peripheral AC depth were measured using rotating Scheimpflug camera Pentacam («Oculus¼, Germany). RESULTS: While the average values of AL in patients of the 1st and 2nd groups were comparable, a statistically significant decrease in AC depth and a significant increase in LT were revealed in the 2nd group. There was a statistically significant increase in LT, a decrease in peripheral AC depth and AC volume in the comparison group relative to the 2nd group. In the 1st group: in 2 eyes of one 38-year-old patient the maximum proximity of all 3 indices to the median values of the group of patients with PACG was found; in 4 eyes of two other patients (35 and 38 years old), a combination of small AC volume with increased LT or small AC volume with small AC on the periphery was noted. CONCLUSION: Significant differences in terms of LT, peripheral AC depth and AC volume were found between age-comparable (41-50 years old) healthy individuals with short eyes and patients with initial PACG. In 11% of the eyes of healthy patients with hyperopia aged 21 to 40 years, there was a combination of two or three of the studied morphometric signs, which may indicate the risk of developing PACG.

Penetrance and predictive value of genetic screening in acute porphyria.

OBJECTIVE: Penetrance, predictive value and female patients' perspectives on genetic testing were evaluated among Finnish patients with acute porphyria. We conducted a retrospective study to evaluate prognosis among at-risk female family members depending on the primary method of diagnosis. METHODS: The penetrance was calculated among 23 genetically heterogeneous families selected from the Finnish porphyria registry (n = 515, AIP 333; VP 182). We included kindreds with ≥9 patients in a family (range 9-23 patients, total 216 AIP; 129 VP). In 2015, the registry included 164 living female subjects between 14 and 85 years of age. A questionnaire was sent to 143 women, of whom 107 (75%, AIP 67; VP 40) replied. Female at-risk relatives (AIP 54; VP 30) were divided into two groups based on the primary method of diagnosis: mutation analysis (Group A, n = 40) or biochemical analysis (Group B, n = 44). RESULTS: Mean penetrance for all acute symptoms was 35% among AIP and 40% among VP families. In both study groups, the penetrance was higher among female (AIP 50%; VP 44%) than male patients (AIP 17%; VP 33%). Penetrance for hospitalized attacks was 30% among AIP families (range 10-80%, for women 41%) and 25% in VP (range 0-50%, for women 27%) demonstrating wide variations among families even with the similar genotype. Acute porphyria was diagnosed at the median age of 26 years (range 0-76 years) among female patients, commonly after the onset of acute symptoms. Diagnostic delay was an average of 7.4 years (range 1-30 years). Acute symptoms occurred at the median age of 24 years (range 10-57 years) and the first hospitalization at the median age of 26.5 years (range 15-57 years). At the onset of symptoms, 38% of the women were ≤ 20 years of age. According to the life table analysis, acute attacks occurred mainly during the following five years after the diagnosis and the attack risk diminished after 35 years of age. The annual risk for hospitalization due to an acute attack during fertile years was lower in Group A than Group B (0.002 vs. 0.010, p = .018), but the risk of all subsequent acute symptoms did not diminish (Group A 0.017 vs. Group B 0.019, p = .640). The cumulative risk of acute symptoms among asymptomatic patients at the time of diagnosis was 26.7% for Group A and 58.3% for Group B. The cumulative risk of the first subsequent attack requiring hospitalization after the diagnosis among all at-risk relatives was similarly less frequent in Group A than in Group B (OR 0.180; 95% CI 0.041-0.789, p = .041). If attacks were followed among symptomatic patients only, attack-free years were more frequent in Group A than in Group B. Patients preferred genetic screening before puberty to minimize the risk of acute symptoms and genetic discrimination was rare. 44% of the patients reported social, psychological or physical impairment due to acute hepatic porphyria, emphasizing the importance of supporting patients' emotional and resilience capacity. CONCLUSIONS: Among female at-risk relatives the annual risk for hospitalization due to an acute attack is <1% and for acute symptoms <2% during the fertile years. Genetic testing of relatives diminishes the risk of acute attacks. Diagnosis before symptom onset is key for subjects to remain asymptomatic during follow-up, and genetic screening should be done earlier than currently.

A case series of topiramate-induced angle closure crisis - an ophthalmic emergency.

BACKGROUND: Topiramate is a drug commonly used by physicians. However, it has various systemic and ocular adverse effects. Bilateral angle closure crisis is a potentially blinding adverse reaction that is seldom reported in non-ophthalmic journals. OBJECTIVE: This article aims to report a case series of topiramate-induced angle closure crisis in the eyes. METHODS AND MATERIAL: Most patients presented to us with blurred vision and high intra-ocular pressure within days of starting topiramate tablet for headache. However, the attack resolved in those who presented early with prompt treatment, which included stopping topiramate. CONCLUSIONS: Physicians prescribing topiramate must be well aware of this potentially blinding adverse effect. Educating the patient about this possible side effect is important. Timely referral and treatment can prevent blindness in these individuals.

[Acute hepatic porphyrias: pathophysiology and pathogenesis of acute attacks].

Heme is an iron-containing molecule essential for virtually all living organisms. However, excessive heme is cytotoxic, necessitating tight regulation of intracellular heme concentration. The acute hepatic porphyrias (AHPs) are a group of rare inborn errors of heme biosynthesis that are characterized by episodic acute neurovisceral attacks that are precipitated by various factors. The AHPs are often misdiagnosed, as the acute attack symptom are non-specific and can be attributed to other more common causes. Understanding how heme biosynthesis is dysregulated in AHP patients and the mechanism by which acute attacks are precipitated will aid in accurate and rapid diagnoses, and subsequently, appropriate treatment of these disorders. Therefore, this review article will focus on the biochemical and molecular changes that occur during an acute attack and present what is currently known regarding the underlying pathogenesis of acute attacks.

Efficacy and safety of apheresis therapy in AQP4 antibody-positive NMOSD attack: A propensity score-matched cohort study.

OBJECTIVE: Plasma exchange (PE) and immunoadsorption (IA) are recognized as effective ways to treat attacks in AQP4 antibody-positive NMOSD, but high-quality evidence was lacking. To evaluate the efficacy and safety of PE/IA plus intravenous methylprednisolone (IVMP) in NMOSD attacks using propensity scores to match IVMP as control. METHODS: Patients were from a prospective observational cohort study. Stratification and interval propensity score matching (PSM) were used to reduce selection bias by matching baseline characteristics (gender, age, time to IVMP, EDSS at attack) between PE/IA + IVMP and IVMP group (in a ratio of 1:2). The primary endpoint of efficacy was EDSS change at 6 months. Adverse events and changes in laboratory tests were recorded. RESULTS: Four hundred and eleven attacks of 336 patients were screened for PSM, and 90 attacks (30 PE/IA + IVMP and 60 IVMP) were included in the analysis. There were significant differences in EDSS [6.25 vs. 6.75; IQR (4.50-8.38 vs. 5.00-8.00), p = 0.671] and visual acuity [median logMAR = 0.35 vs. 1.00; IQR (0.30-0.84 vs. 0.95-1.96), p = 0.002] change between two groups at 6 months. PE/IA + IVMP treatment demonstrated predictive capacity for good recovery as indicated by an area under the curve (AUC) of 0.726. Fibrinogen reduction was found during PE/IA + IVMP treatment [n = 15 (50.00%)], but no severe adverse events led to apheresis treatment discontinuation. DISCUSSION: After PSM analysis, IVMP+PE/IA in acute attack of NMOSD achieved better and continuous improvement in neurological function within 6 months compared with IVMP alone. PE/IA treatment showed a good safety profile.

Acute gout attacks during the perioperative period and risk factors of recurrence after orthopedic surgery among untreated gout patients.

BACKGROUND: This study aimed to explore the clinical characteristics of perioperative acute gout attacks in patients with varying uric acid levels undergoing orthopedic surgery, identify the risk factors for gout recurrence within the first postoperative year, and provide a disease prevention and diagnostic reference. METHODS: This hospital-based retrospective study was conducted between January 2018 and December 2020. According to the blood uric acid levels at admission, the patients were grouped into either the normal uric acid level group or the hyperuricemia group. Patient comorbidities, serum uric acid levels, inflammatory indicators, follow-up recurrence rates, and other indicators were compared. RESULT: The uric acid decline ratio and the inflammatory indexes (white blood cell count and C-reactive protein level) at the time of the attack were significantly higher in the normal uric acid level group than in the hyperuricemia group (P < 0.05). Patients in the hyperuricemia group with diabetes and tophi and those administered diuretics were more prone to acute gout attacks than those in the normal uric acid level group (P < 0.05). In the normal uric acid level group, 22 patients (84.6%) exhibited single joint involvement, whereas only 18 patients (47.4%) in the hyperuricemia group demonstrated single joint involvement (P < 0.05). After 1 year of follow-up, the gout recurrence rate in the hyperuricemia group was 44.7%, which was significantly higher that the recurrence rate in the normoglycemic group (11.5%; P < 0.05). Presenting tophi in perioperative orthopedic surgery patients was found to be an independent risk factor for gout recurrence within 1 year (RR = 4.80; P = 0.029). CONCLUSION: The recurrence rate of gout in patients with hyperuricemia during perioperative period increased 1 year after operation. Therefore, it is crucial to monitor the uric acid level to prevent acute gout attacks during the perioperative period and recurrence during the 1-year follow-up period. Moreover, the risk of an acute gout recurrence 1 year after operation increased in patients who presented tophi; therefore, it is necessary to maintain appropriate blood uric acid level during perioperative period among patients undergoing orthopedic surgery.

Serum metabolomics study for acute attack of chronic pancreatitis.

BACKGROUND & AIMS: Chronic pancreatitis (CP) is an inflammatory disease characterized by irreversible changes. However, acute CP attacks can lead to various complications and affect patient prognosis. Therefore, this study aimed to identify reliable candidate metabolic biomarkers for diagnosing acute CP attacks and complement candidate diagnostic markers for CP. METHODS: A total of 139 serum specimens were prospectively included in three consecutive exploratory, identification, and validation studies. All samples were analyzed for candidate diagnostic biomarkers and metabolic pathways using a liquid chromatography-mass spectrometer. RESULTS: Serum metabolic profiles differed between patients with CP and non-pancreatic disease controls, and 239 potential metabolic biomarkers for diagnosing CP were identified. Based on identification and validation studies, Diacylglycerol(16:0/18:4), 16-F1-PhytoP, N-(hexacosanoyl)-tetradecasphing-4-enine, carnosic acid, and Auxin b were identified as biomarkers for distinguishing acute attacks from non-acute attacks in patients with CP. The area under the curve of the Diacylglycerol(16:0/18:4) was 0.969 (95% confidence interval, 0.869-1) in the validation study. CONCLUSIONS: To the best of our knowledge, this is the first prospective cohort study to identify and validate a metabolomic signature in serum for diagnosing acute attacks of CP. In addition, our study identified 239 potential biomarkers for CP diagnosis.

Hereditary angioedema with an acute attack resolved after bone marrow transplantation for acute myeloid leukemia: a case report.

BACKGROUND: Hereditary angioedema (HAE), which is caused by C1-inhibitor (C1-INH) deficiency or dysfunction, is a rare and potentially life-threatening disease. In patients with HAE, excess production of bradykinin causes acute unpredictable recurrent attacks of angioedema in localized regions, including the larynx and intestines. Given the fact that HAE is an autosomal dominant disease, C1-INH produced in patients with HAE is 50% of that produced in healthy individuals. However, most patients with HAE present plasma C1-INH function of < 25% owing to the chronic consumption of C1-INH by kallikrein-kinin, contact, complement, coagulation, and fibrinolysis cascades. Recently, several therapeutic options have been developed for acute attacks and prophylaxis in the treatment of HAE; however, currently, there is no curative therapy for HAE. CASE PRESENTATION: Here we report the case of a 48-year-old male patient who presented with a long-standing history of HAE and underwent bone marrow transplantation (BMT) for acute myeloid leukemia (AML) at the age of 39 years and has been in complete remission of AML and HAE thereafter. Notably, after BMT, his C1-INH function gradually increased as follows: < 25%, 29%, 37%, and 45.6%. Since his 20 s, he intermittently presented with an acute attack of HAE once every 3 months from the initial attack. Further, after undergoing BMT, the number of acute attacks decreased to twice within 4 years until the age of 45 years, and subsequently, the patient has been free of acute attacks. C1-INH is mainly synthesized by hepatocytes, but it is known to be partially produced and secreted from peripheral blood monocytes, macrophages, endothelial cells, and fibroblasts. We speculate that the C1-INH function may be increased by extrahepatic production of C1-INH, possibly synthesized by differentiated cells derived from hematopoietic and mesenchymal stem cells after BMT. CONCLUSIONS: This case report supports efforts to focus on extrahepatic production of C1-INH in the next strategy of new treatment development for HAE.

Multidisciplinary Prophylactic Strategies for Recurrence of Laryngeal Edema After Tooth Extraction in a Patient With Hereditary Angioedema: A Case Report.

Hereditary angioedema (HAE), caused by C1-inhibitor (C1-INH) deficiency or dysfunction, is a rare and potentially life-threatening disease that leads to unpredictable recurrent attacks of angioedema in localized regions, including the larynx. As medical or dental procedures can trigger laryngeal edema, resulting in asphyxiation, major global guidelines recommend short-term prophylaxis prior to invasive procedures and long-term prophylaxis to prevent acute attacks and achieve near-normal lives. Here, we report the case of a 63-year-old male who experienced asphyxiation after tooth extraction. Emergency tracheotomy had saved his life at the age of 40 years, before the diagnosis of HAE. At the age of 63, when he had another opportunity for tooth extraction, he was definitively diagnosed with HAE. Administering short-term prophylaxis with ongoing long-term prophylaxis for HAE and perioperative multidisciplinary management for tooth extraction helped prevent recurrent fatal angioedema due to dental procedures and this can be useful when managing patients with HAE.

Effect of Influenza Vaccine on Prevention of Acute Attack of Chronic Airway Disease in Elderly Population.

This study investigated the effect of influenza vaccination on prevention of acute attacks in elderly patients with chronic airway disease and provides evidence for the prevention and control strategy of chronic airway disease in the elderly population. A total of 348 elderly patients in Linquan County, Anhui Province, China, who were also in stationary phases of chronic airway disease and were vaccinated with either the tetravalent or trivalent influenza vaccine were selected. The number of patients with acute attacks, the number of outpatients with acute attacks, the number of outpatients, the number of inpatients, the total cost of patients, the cost of outpatients, the cost of hospitalization, and the length of hospitalization were collected before vaccination and after a one-year follow-up. There was no significant difference in age and sex ratio among the two vaccination groups. The ratios of acute attacks, outpatient visits, and hospitalizations and number of outpatient visits, number of hospitalizations, total medical expenses, outpatient expenses, and hospitalization expenses were significantly higher before vaccination than those after vaccination in both the trivalent-vaccination group and tetravalent-vaccination group. Additionally, there was no significant difference in the length of stay between before and after vaccination in either the trivalent-vaccination group or tetravalent-vaccination group. The protection effect between the trivalent-vaccination group and tetravalent-vaccination group was not significant. Influenza vaccination can effectively prevent the acute attack of chronic airway disease and delay the progress of chronic airway disease.

Long-term follow-up of acute porphyria in female patients: Update of clinical outcome and life expectancy.

BACKGROUND: Acute hepatic porphyria includes four inherited disorders caused by partial deficiencies of enzymes related to the heme biosynthesis. Clinical manifestations include acute attacks, occurring mainly among female patients. This study describes the diversity of acute symptoms, changes in triggering factors and life expectancy among female patients during the past five decades. METHODS: 107 Finnish female patients were enrolled into a retrospective, longitudinal study during 2015. Clinical, biochemical and genetic data was obtained from the medical reports, registry data and a questionnaire designed for the study. Causes of death were studied in additional 32 female patients. RESULTS: Of the 43 patients with hospitalization, 33% had non-complicated, 35% prolonged and 28% severe attacks with no correlation with the disease-causing mutation. Of the deceased patients, 31% died of an acute attack during 1957-1979. Thereafter the incidence and severity of acute attacks have decreased substantially. 55% of the subjects reported acute symptoms (dysautonomia and mental symptoms) without hospitalization, 29% had porphyria symptoms >10 times, and 23% within the last year. Despite 22% of the female patients had died of primary liver cancer, the life expectancy increased more than 10 years during the follow-up, and did not differ from the normal population at present. CONCLUSIONS: The incidence of acute attacks requiring hospitalization has decreased, but more than half of the female patients reported acute symptoms affecting their well-being. Symptoms are currently triggered by hormonal changes and weight loss emphasizing the importance of early recognition and active management to avoid disease exacerbation. Death due to primary liver cancer is common and should be screened regularly.

Persistently Gadolinium-Enhancing Lesion Is a Predictor of Poor Prognosis in NMOSD Attack: a Clinical Trial.

Gadolinium (Gd)-contrast MRI for reliable detection of blood-brain barrier (BBB) breakdown is widely used in neuromyelitis optica spectrum disorder (NMOSD) attack. Nonetheless, little is known about the predictive role of gadolinium-enhancing lesion in prognosis of NMOSD attack. The aim of this work is to investigate the predictive value of persistently Gd-enhanced lesions to medium-term outcome after attack. Data for this analysis came from an ongoing prospective cohort study (CLUE). NMOSD patients with acute attack were enrolled from January 2019 to March 2020. All patients underwent Gd-contrast MRI at baseline and 1 month, and disability was assessed by Expanded Disability Status Scale (EDSS). Primary outcome was EDSS improvement from baseline to month 6. Multiple logistic regression identified predictors for poor recovery of NMOSD attack. Forty-one participants were analyzed, of which 21 patients had persistently Gd-enhancing lesions. Patients in no enhancement (NE) group showed a significant shift in 6-month EDSS distributions compared with those in persistent enhancement (PE) group (p = 0.005). Poor recovery rate of the PE group was higher than that of the NE group at 6 months (p = 0.033). In patients with aquaporin-4-positive, first-attack, transverse myelitis or in a high-dose steroid treatment subgroup, the improvement of EDSS scores in the PE group was still less compared with that in the NE group (p < 0.05). The presence of persistently Gd-enhancing lesion appears to be associated with poor recovery after attack (OR = 5.473, p = 0.014). Our study found that persistently gadolinium-enhancing lesion is a poor prognosis predictor after NMOSD attack. Trial registration ID: NCT04106830.

Early Initiation of Tocilizumab Treatment Against Moderate-to-Severe Myelitis in Neuromyelitis Optica Spectrum Disorder.

Background: Interleukin-6 receptor blockade is effective in reducing the risk of relapses in neuromyelitis optica spectrum disorder (NMOSD). However, its efficacy during acute attacks of NMOSD remains elusive. Objective: We investigated the effects of tocilizumab on disability during acute attacks, as well as its maintenance, in patients with moderate-to-severe myelitis. Methods: Nineteen patients with NMOSD received tocilizumab treatment as add-on to high-dose methylprednisolone (HDMP) in acute myelitis and twenty-two patients who only received HDMP were compared. Disease disability was assessed using a multi-level scaling system that included the expanded disability status scale (EDSS), Hauser ambulation index (HAI), modified Rankin scale (mRS), pain numerical rating scale (NRS), functional assessment of chronic illness therapy-fatigue scale (FACIT-F), activity of daily living (ADL), EuroQol five-dimensions-three-level questionnaire (EQ-5D-3L), and sensory function score and bowel and bladder function score in Kurtzke functional systems scores (FSS). Results: Improved EDSS, HAI, and mRS, as well as increased ADL and EQ-5D-3L were significant in patients on tocilizumab compared with those on steroids as monotherapy at 3 months (p < 0.05). Both groups of patients showed improved pain, fatigue, sensory function, and autonomic function at follow-ups, compared with baseline respectively. The changes in NRS, FACIT-F, and sensory and autonomic FSS showed no significant differences between the two groups. Tocilizumab significantly lowered the risk of relapses (HR = 0.21, 95% CI 0.06-0.76, p = 0.017) and reduced the annualized relapse rate compared with those by steroids (0.1 ± 0.2 vs 0.5 ± 0.6, p = 0.013). Conclusion: Early initiation of tocilizumab provided a safe and effective add-on alternative during attacks, and its maintenance contributed to a significant reduction of relapse rate in NMOSD.

Therapeutic Response and Possible Biomarkers in Acute Attacks of Neuromyelitis Optica Spectrum Disorders: A Prospective Observational Study.

Objective: To explore the outcomes of NMOSD attacks and investigate serum biomarkers for prognosis and severity. Method: Patients with NMOSD attacks were prospectively and observationally enrolled from January 2019 to December 2020 at four hospitals in Guangzhou, southern China. Data were collected at attack, discharge and 1/3/6 months after acute treatment. Serum cytokine/chemokine and neurofilament light chain (NfL) levels were examined at the onset stage. Results: One hundred patients with NMOSD attacks were included. The treatment comprised intravenous methylprednisolone pulse therapy alone (IVMP, 71%), IVMP combined with apheresis (8%), IVMP combined with intravenous immunoglobulin (18%) and other therapies (3%). EDSS scores decreased significantly from a medium of 4 (interquartile range 3.0-5.5) at attack to 3.5 (3.0-4.5) at discharge, 3.5 (2.0-4.0) at the 1-month visit and 3.0 (2.0-4.0) at the 3-month visit (p<0.01 in all comparisons). The remission rate was 38.0% at discharge and 63.3% at the 1-month visit. Notably, relapse occurred in 12.2% of 74 patients by the 6-month follow-up. Higher levels of T helper cell 2 (Th2)-related cytokines, including interleukin (IL)-4, IL-10, IL-13, and IL-1 receptor antagonist, predicted remission at the 1-month visit (OR=9.33, p=0.04). Serum NfL levels correlated positively with onset EDSS scores in acute-phase NMOSD (p<0.001, R2 = 0.487). Conclusions: Outcomes of NMOSD attacks were generally moderate. A high level of serum Th2-related cytokines predicted remission at the 1-month visit, and serum NfL may serve as a biomarker of disease severity at attack. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04101058, identifier NCT04101058.

A pilot study comparing treatments for severe attacks of neuromyelitis optica spectrum disorders: Intravenous methylprednisolone (IVMP) with add-on plasma exchange (PLEX) versus simultaneous ivmp and PLEX.

BACKGROUND: Our previous retrospective study demonstrated that NMOSD patients with an acute attack who did not respond to IVMP alone, however, showed further significant improvement after treatment with PLEX at 6 month-follow-up. OBJECTIVE: To compare the efficacy between treatments with intravenous methylprednisolone (IVMP) with subsequent add-on plasma exchange (PLEX) and a combination of simultaneous IVMP and PLEX in neuromyelitis optica spectrum disorders (NMOSD) patients with a severe acute attack. METHOD: We conducted a prospective, randomized, controlled, pilot study of the treatments for a severe acute attack in NMOSD patients. RESULTS: There were eleven AQP4-positive NMOSD patients in the study. One received only IVMP, five received IVMP with subsequent add-on PLEX treatment, and the other five received simultaneous IVMP and PLEX treatment. The attacks comprised myelitis (57.1%) and optic neuritis (42.9%). Both treatments with IVMP followed by subsequent add-on PLEX when needed (not-respond to IVMP treatment) and a combination treatment of simultaneous IVMP+PLEX from the outset showed clinical improvement measured by EDSS at 6 months follow-up, compared to those at the attacks (p-value = 0.07 in IVMP add-on PLEX group and p-value = 0.05 in IVMP+PLEX group), respectively. Although, a trend of a better outcome stratified by EDSS toward early PLEX initiation with IVMP+PLEX treatment was observed at 6 months follow-up, however not significantly. CONCLUSION: Early treatment with PLEX should be encouraged especially in NMOSD with a severe acute attack.

Intravenous immunoglobulin for acute attacks in neuromyelitis optica spectrum disorders (NMOSD).

BACKGROUND: During acute attacks of neuromyelitis optica spectrum disorder (NMOSD), intravenous immunoglobulin (IVIG) maybe useful building on experience treating autoimmune disorders. METHODS: We conducted a retrospective study of several treatment modes for NMOSD attacks at Beijing Tiantan Hospital and Tianjin Medical University General Hospital. Clinical outcomes were defined as the short-term remission status. The good (GR), moderate (MR) or poor remission (PR) was respectively defined to triple-grade based on percentage change of initial and follow-up Expanded Disability Status Scale (EDSS) scores. RESULTS: A total of 243 attacks was analyzed in 198 patients from 2014 to 2019. Treatment groups included 153 attacks given high-dose intravenous steroids (HD-S), 14 given IVIG, 69 episodes of IVIG plus HD-S and 7 treated with plasma exchange. The proportion of patients with better outcomes were significantly lower in IVIG alone group than HD-S alone group (p = 0.004). However, sequential treatments for IVIG and HD-S yielded a higher likelihood of clinical improvement in severe attacks with EDSS ≥ 6.5 (OR = 5.85, p = 0.007). CONCLUSION: These results did not support IVIG-alone therapy as a first-line option for acute NMOSD. However, adding HD-S to IVIG therapy was superior to HD-S alone for patients with high-onset EDSS.