Shorter Disease Research Articles

Randomized open-label study of second-generation antipsychotics for the treatment of schizophrenia: 104-week final results of the JUMPs study assessing treatment discontinuation, remission, and social functioning

BackgroundWe report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study.MethodsJUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension).ResultsIn total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation.ConclusionsThe 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment.Clinical trial registrationUMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012).

Time to Treat First Acute Attack of Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease

A proportion of people with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) have a relapsing disease course and persistent anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) seropositivity. Few studies have investigated whether treatment of the first MOGAD attack is associated with the long-term disease course and/or MOG-IgG seronegative conversion. To investigate the association of time to treat the first acute MOGAD attack with relapse risk and MOG-IgG serostatus. This was a retrospective, nationwide, multicenter cohort study involving 14 secondary or tertiary hospitals in South Korea between November 2009 and August 2023. People with adult-onset MOGAD, who either had a relapse or were followed up for more than 12 months after disease onset and had a detailed medical record of their first attack, were included. Individuals were excluded for adolescent-onset MOGAD or short disease duration. Patients were categorized based on the time to treat the first acute MOGAD attack: early (<5 days), intermediate (5-14 days), and late (not treated within 14 days). A multivariable analysis for clinical and treatment factors associated with relapsing disease course and/or MOG-IgG seronegative conversion. Further subgroup analyses were conducted among those without long-term nonsteroidal immunosuppressant (NSIS) maintenance treatment. Among the 315 individuals screened, 75 were excluded. A total of 240 patients (median [IQR] age at onset, 40.4 [28.8-56.1] years; 125 female [52.1%]) with median (IQR) disease duration of 3.07 (1.95-6.15) years were included. A total of 110 of 240 patients (45.8%) relapsed after a median (IQR) of 0.45 (0.18-1.68) years, and 29 of 116 patients (25.0%) experienced a conversion to seronegative MOG-IgG. Both the time to treatment of the first MOGAD attack (late vs early: adjusted hazard ratio [aHR], 2.64; 95% CI, 1.43-4.84; P = .002; intermediate vs early: aHR, 2.02; 95% CI, 1.10-3.74; P = .02) and NSIS maintenance treatment (aHR, 0.24; 95% CI, 0.14-0.42; P < .001) were independently associated with the risk of relapse. In a subgroup without NSIS maintenance, the time to treat of the first MOGAD attack was still associated with higher risk of relapse (late vs early: aHR, 3.51; 95% CI, 1.64-7.50; P = .001; intermediate vs early: aHR, 2.68; 95% CI, 1.23-5.85; P = .01). Lastly, the time to treat of the first MOGAD attack was also associated with MOG-IgG seronegative conversion (early vs late: adjusted odds ratio, 7.04; 95% CI, 1.58-31.41; P = .01), whereas NSIS maintenance treatment was not. Results of this cohort study suggest that early treatment of the first acute MOGAD attack was associated with a reduction in the proportion of relapsing disease course and an increase in the likelihood of MOG-IgG seronegative conversion. These data suggest that timing of acute phase treatment for the first MOGAD attack can be associated with the long-term prognosis and autoimmune status of patients.

52808 Guselkumab improves perceived stigmatization in moderate-to-severe psoriasis patients, including obese patients and patients with short disease duration: Results from the real-life G-EPOSS study until Week 76

52808 Guselkumab improves perceived stigmatization in moderate-to-severe psoriasis patients, including obese patients and patients with short disease duration: Results from the real-life G-EPOSS study until Week 76

Parosmia in patients with post-infectious olfactory dysfunction in the era of COVID-19-associated olfactory impairment.

Alarge number of patients with olfactory impairment are affected by parosmia or phantosmia. This study aimed to examine the demographic and clinical characteristics of parosmia. We performed aretrospective data analysis of patients consulting at our Smell and Taste Outpatient Clinic. Atotal of 297 patients were included (203 women, mean age44.4 ± 13.7years). Olfactory function was quantified using the "Sniffin' Sticks" composite TDI (odor threshold, determination, and identification) score. The presence of qualitative olfactory impairment was assessed trough medical history and aparosmia questionnaire. Most of the patients showed olfactory impairment after an infection with SARS-CoV‑2 (84%) and were diagnosed with parosmia (49%). Patients with parosmia (PAR) (n = 201) were significantly younger compared to the group without parosmia (noPAR; n = 92) (PAR 43.2 ± 13years vs. noPAR 47 ± 15.1 years, p = 0.03) and had aslightly shorter duration of disease, without reaching statistical significance (PAR 10.3 ± 4.9months, noPAR 13.6 ± 37.6 months, p = 0.23). They also had higher TDI scores (PAR 24.3 ± 7points, noPAR 21.4 ± 8.2points, p = 0.003). Patients affected by parosmia were younger and had abetter olfactory function compared to patients without parosmia.

The role of kidney biopsy in deciphering diabetic versus non-diabetic origin of kidney disease among patients with type 2 diabetes mellitus and nephrotic range proteinuria: A retrospective study

BackgroundDiabetes mellitus (DM) is tightly associated with the increased prevalence of diabetic kidney disease (DKD). Nonetheless, severe renal function impairment and/or nephrotic range-proteinuria could also result from non-diabetic renal disease (non-DRD) among patients with DM. The ‘Gold standard’ for the differential diagnosis between DKD and non-DRD is kidney biopsy, although no real consensus exists. Thus, this study intends to associate the clinical and biochemical profile of patients with DM and renal disease with the histopathological data of kidney biopsy.In addition, we aimed to evaluate the role of kidney biopsy, especially when other causes, other than DM, are highly suspected among patients with DM and kidney disease. MethodsThirty two patients with T2DM and nephrotic range levels of proteinuria or with co-existing factors pointing towards a non-diabetic origin of kidney disease were studied, retrospectively. All 32 patients underwent kidney biopsy and were classified according to histopathological findings into 3 groups: a) isolated diabetic kidney disease (DKD), b) non-diabetic kidney disease (NDKD) and c) mixed kidney disease (MKD). ResultsFifteen out of the 32 patients had findings of an isolated DKD, while 17 out of 32 patients suffered from NDKD (13 patients) or MKD (4 patients). DKD patients were younger (p = 0.016) and had a higher HbA1c value (p = 0.069, borderline statistical significance), while the NDKD patients had significantly shorter disease duration (p = 0.04). Furthermore, the incidence of diabetic retinopathy (DR) was lower among the NDKD patients (p < 0.001), who had also significantly less interstitial fibrosis (p = 0.02). Finally, the presence of DR, higher levels of interstitial fibrosis and longer T2DM duration were recognized as factors, which were positively associated with DKD. ConclusionThis study advocates the usefulness of kidney biopsy in patients with T2DM and nephrotic range levels of proteinuria, especially when DR is absent and shorter disease duration is observed.

Levodopa-carbidopa intestinal gel for advanced Parkinson's disease: Impact of LRRK2 and GBA1 mutations

BackgroundAdvanced Parkinson's disease (PD) can be treated with Levodopa-Carbidopa Intestinal Gel (LCIG). ObjectiveTo compare descriptive data of LCIG treatment in GBA1-PD and LRRK2-PD. MethodsThis multicenter retrospective study compared clinical data obtained from electronic medical records of PD patients treated with LCIG. Patients were grouped based on their genetic status. ResultsFifty-two iPD, 15 LRRK2-PD and 23 GBA1-PD were included in this study. No difference in daily dose of LCIG or levodopa equivalent daily dose were detected. GBA1-PD had significantly shorter disease duration at LCIG initiation (p = 0.01) and experienced more hallucinations (p = 0.03) compared with LRRK2-PD and iPD. LRRK2-PD and iPD had significantly longer duration of LCIG treatment compared with GBA1-PD (p < 0.01). ConclusionOverall, LCIG treatment was well tolerated in LRRK2-PD and GBA1-PD. GBA1-PD required LCIG earlier in their course of their disease and had higher frequencies of hallucinations during treatment, attesting to a more severe disease course.

Achieving normoglycaemia with tirzepatide: Post hoc exploratory analysis of the SURPASS J-mono and J-combo studies.

Normoglycaemia was achieved in a significant proportion of Japanese participants with type 2 diabetes in two phase 3 studies of tirzepatide. This post hoc exploratory analysis aimed to identify predictive factors associated with normoglycaemia achievement. SURPASS J-mono and SURPASS J-combo study data were pooled for this analysis. Characteristics of participants in whom normoglycaemia [glycated haemoglobin (HbA1c) <5.7%] was achieved were summarized. Logistic regression analyses were performed with HbA1c <5.7% achievement as the target variable. Of 912 participants, normoglycaemia was achieved in 553 (60.6%) following 52 weeks of tirzepatide treatment. Overall, the mean (SD) age was 56.7 (10.6) years and mean diabetes duration was 7.7 (6.0) years, and 76% of participants were men. Mean (SD) change from baseline in HbA1c and bodyweight was -2.87% (0.95) versus -2.47% (1.1) and -10.30 (5.8) kg versus -3.75 (4.3) kg for participants in whom normoglycaemia was and was not reached, respectively. Multivariate regression analyses showed that lower baseline body mass index, shorter disease duration and lower baseline HbA1c were significantly associated with higher rates of normoglycaemia achievement (p = 0.009, p = 0.008, p < 0.001, respectively) as was a tirzepatide dose of 10 or 15 mg compared with 5 mg (p < 0.001). The highest percentage of participants in whom normoglycaemia (94%) was achieved were those with lower baseline HbA1c (<8%) and the greatest weight reduction (≥15%). Baseline HbA1c and body mass index, disease duration and the tirzepatide treatment group were shown to be predictive factors for achieving normoglycaemia. A lower baseline HbA1c was most strongly associated with normoglycaemia achievement.

Rituximab in secondary progressive multiple sclerosis: a meta-analysis.

To evaluate the efficacy of rituximab (RTX) in stabilizing disability progression in secondary progressive multiple sclerosis (SPMS). A systematic review was conducted, encompassing studies from inception to April 2023, utilizing the MEDLINE and EMBASE databases. Inclusion criteria comprised studies with a minimum of 3 SPMS patients receiving intravenous RTX in at least one infusion, with a follow-up duration of at least 6 months. Primary outcome measures included changes in Expanded Disability Status Scale (EDSS) scores. Mean differences in pre- and post-RTX EDSS scores were analyzed using a random-effects model. Meta-regression examined age at RTX initiation, pre-RTX EDSS scores, disease duration, and outcome reported time as variables. Secondary outcomes assessed changes in the annualized relapse rate (ARR). Thirteen studies, involving 604 SPMS patients, met the inclusion criteria. Following a mean follow-up of 2 years, the mean difference in EDSS scores (ΔEDSS = EDSSpre-RTX - EDSSpost-RTX) was -0.21 (95% CI -0.51 to 0.08, p = 0.16), indicating no significant variation. Multivariable meta-regression identified significant associations between EDSS score mean difference and pre-RTX EDSS scores, disease duration at RTX initiation, and outcome reported time. However, age at RTX initiation showed no significant association. Pre- and post-RTX ARR data were available for 245 out of 604 SPMS patients across seven studies, revealing a mean difference in ARR (ΔARR = ARRpre-RTX - ARRpost-RTX) of 0.74 (95% CI 0.19-1.29, p = 0.008). RTX demonstrates efficacy in reducing relapse frequency and exhibits potential in stabilizing disability progression over a 2-year follow-up, particularly among individuals with shorter disease duration.

Clinical and Ultrasonographic Remission in Bio-naïve and Bio-failure Patients with Rheumatoid Arthritis at 24Weeks of Upadacitinib Treatment: The UPARAREMUS Real-Life Study.

Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week24. The proportion of patients achieving clinical remission with different composite indexes at week12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. After 12weeks and 24weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24weeks,63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Relationships between regional burden of tau pathology and age at death and disease duration in PSP

BackgroundA definitive diagnosis of progressive supranuclear palsy (PSP) can only be established through neuropathological evaluations where four cardinal tau lesions are identified. Relationships between regional tau burden and disease duration/age at death is unclear. ObjectiveTo investigate relationships between tau burden in different brain regions and disease duration and age at death in PSP and determine whether association are influenced by PSP subtype (subcortical/cortical) or co-pathologies. MethodsWe identified 45 patients with definite PSP who were evaluated at Mayo Clinic between 2009 and 2023, died and underwent histopathological evaluation. We performed semi-quantitative lesion count for each of four cardinal lesions (pretangles/globose neurofibrillary tangles, threads, tufted astrocytes, and coiled bodies) across 10 brain regions. We fit Bayesian linear hierarchical regression models to estimate the relationship between total pathological burden, and disease duration and age at death by region and the influence of subtype and co-pathologies. ResultsOf the 45 patients, 18 (40 %) were female. Median age at death was 75 (56–87) years and median disease duration was 8 (3,15) years. Younger age at death was associated with greater total tau burden in the pallidum, red nucleus, striatum, and subthalamic nucleus (all p ≤ 0.01). Shorter disease duration was associated with greater total tau burden in the red nucleus (p = 0.05). There was no evidence for a difference in association between lesion types. PSP subtype and co-pathologies did not influence associations. ConclusionsThe findings from this study suggest that age and disease duration influence burden of tau pathology in subcortical regions in PSP.

Association of Body Mass Index and Parkinson Disease: A Bidirectional Mendelian Randomization Study.

The role of body mass index (BMI) in Parkinson disease (PD) is unclear. Based on the Comprehensive Unbiased Risk Factor Assessment for Genetics and Environment in PD (Courage-PD) consortium, we used 2-sample Mendelian randomization (MR) to replicate a previously reported inverse association of genetically predicted BMI with PD and investigated whether findings were robust in analyses addressing the potential for survival and incidence-prevalence biases. We also examined whether the BMI-PD relation is bidirectional by performing a reverse MR. We used summary statistics from a genome-wide association study (GWAS) to extract the association of 501 single-nucleotide polymorphisms (SNPs) with BMI and from the Courage-PD and international Parkinson Disease Genomics Consortium (iPDGC) to estimate their association with PD. Analyses are based on participants of European ancestry. We used the inverse-weighted method to compute odds ratios (ORIVW per 4.8 kg/m2 [95% CI]) of PD and additional pleiotropy robust methods. We performed analyses stratified by age, disease duration, and sex. For reverse MR, we used SNPs associated with PD from 2 iPDGC GWAS to assess the effect of genetic liability toward PD on BMI. Summary statistics for BMI are based on 806,834 participants (54% women). Summary statistics for PD are based on 8,919 (40% women) cases and 7,600 (55% women) controls from Courage-PD, and 19,438 (38% women) cases and 24,388 (51% women) controls from iPDGC. In Courage-PD, we found an inverse association between genetically predicted BMI and PD (ORIVW 0.82 [0.70-0.97], p = 0.012) without evidence for pleiotropy. This association tended to be stronger in younger participants (≤67 years, ORIVW 0.71 [0.55-0.92]) and cases with shorter disease duration (≤7 years, ORIVW 0.75 [0.62-0.91]). In pooled Courage-PD + iPDGC analyses, the association was stronger in women (ORIVW 0.85 [0.74-0.99], p = 0.032) than men (ORIVW 0.92 [0.80-1.04], p = 0.18), but the interaction was not statistically significant (p-interaction = 0.48). In reverse MR, there was evidence for pleiotropy, but pleiotropy robust methods showed a significant inverse association. Using an independent data set (Courage-PD), we replicate an inverse association of genetically predicted BMI with PD, not explained by survival or incidence-prevalence biases. Moreover, reverse MR analyses support an inverse association between genetic liability toward PD and BMI, in favor of a bidirectional relation.

Digital Media Usage Behavior and Its Impact on the Physician-Patient Relationship: Cross-Sectional Study Among Individuals Affected by Psoriasis in Germany.

Psoriasis is a chronic skin disorder with a high burden of disease. People affected with psoriasis increasingly use the internet for health-related reasons, especially those with younger age, higher education, and higher disease severity. Despite advantages such as enhancing the individuals' knowledge with the use of digital media for health-related issues, disadvantages were also present such as quality control, and variability in the individuals' health information literacy. While patients with psoriasis within medical settings generally trust physicians over digital media, they commonly withhold their web-based research findings from health care providers. The study aims to (1) identify further factors associated with regular psoriasis-related internet use, (2) rank specific digital media platforms used, and (3) examine digital media within the physician-patient relationship among individuals with and without dermatological treatment. A cross-sectional, questionnaire-based study was conducted among individuals with self-reported psoriasis in Germany between September 2021 and February 2022. Participants were recruited via digital media platforms and in person at a University Hospital Department of Dermatology in southern Germany. The questionnaire asked about demographic and medical information, individual psoriasis-related digital media use, and the impact of digital media on the physician-patient relationship. Data were analyzed descriptively, and logistic regression models were performed to assess the factors associated with regular psoriasis-related internet use. Among 321 individuals with a median age of 53 (IQR 41-61) years (nonnormally distributed; females: 195/321), female sex, shorter disease duration, moderate mental burden of disease, and good self-assessed psoriasis-related knowledge were associated with regular psoriasis-related internet use. Of the 188 participants with a mean age of 51.2 (SD 13.9) years (normally distributed) who used digital media 106 (56.4%) usually searched for information on psoriasis-based websites and 98 (52.1%) on search engines, primarily for obtaining information about the disease and therapy options, while social media were less frequently used (49/188, 26.1%). Nearly two-thirds of internet users (125/188) claimed that their physicians did not recommend digital media platforms. About 44% (82/188) of the individuals reported to seek for additional information due to the insufficient information provided by their physician. This study revealed the importance of digital media in the context of psoriasis, especially among women, individuals with shorter disease duration, and moderate mental disease severity. The lack of physicians' digital media recommendations despite their patients' desire to receive such and being more involved in health-related decisions seems to be a shortcoming within the physician-patient relationships. Physicians should guide their patients on digital media by recommending platforms with evidence-based information, thereby potentially creating an adequate framework for shared decision-making. Future research should focus on strategies to prevent the spread of false information on digital media and address the needs of patients and physicians to enhance health-related digital media offerings.

Identification of two novel linear epitopes on the E165R protein of African swine fever virus recognized by monoclonal antibodies.

African swine fever (ASF) is a highly fatal infectious disease in pigs, caused by the African swine fever virus (ASFV). It is characterized by short disease duration and high morbidity and mortality. In August 2018, ASF was first reported in China and it subsequently spread rapidly throughout the country, causing serious economic losses for the Chinese pig industry. Early detection plays a critical role in preventing and controlling ASF because there is currently no effective vaccine or targeted therapeutic medication available. Additionally, identifying conserved protective antigenic epitopes of ASFV is essential for the development of diagnostic reagents. The E165R protein, which is highly expressed in the early stages of ASFV infection, can serve as an important indicator for early detection. In this study, we successfully obtained high purity soluble prokaryotic expression of the E165R protein. We then utilized the purified recombinant E165R protein for immunization in mice to prepare monoclonal antibodies (mAbs) using the hybridoma fusion technique. After three subclonal screens, we successfully obtained three mAbs against ASFV E165R protein in cells named 1B7, 1B8, and 10B8. Through immunofluorescence assay (IFA) and Western blot, we confirmed that the prepared mAbs specifically recognize the baculovirus-expressed E165R protein. By using overlapping truncated E165R protein and overlapping peptide scanning analysis, we tentatively identified two novel linear B cell epitopes (13EAEAYYPPSV22 and 55VACEHMGKKC64) that are highly conserved in genotype I and genotype II of ASFV. Thus, as a detection antibody, it has the capability to detect ASFV across a wide range of genotypes, providing valuable information for the development of related immunodiagnostic reagents.

The risk factors affecting the persistence of corpus callosum splenium lesions.

The most compact portion of the corpus callosum (CC) is the corpus splenium (CS). To evaluate the connection between clinical and demographic features to determine whether neuroimaging findings will be permanent or temporary in CS patients. We enrolled 93 patients (age range = 18-86 years) with CS lesions. Demographic and clinical information were recorded. We examined the lesions depending on the location. Group 1 (n = 20) had lesions limited to the CS (egg-shaped or round); group 2 (n = 15) had "boomerang sign" lesions; and group 3 (n = 58) had splenium involvement in conditions affecting the whole brain (Boomerang sign+ plus). Group 1 had a lower mean age, shorter disease duration, and fewer persistent lesions than others (P < 0.01, P < 0.001, and P < 0.001, respectively). The mean disease onset age (in years) in group 1 was higher than that of the other groups (P < 0.045). Group 2 had lower potassium (K) (P < 0.003) and red cell distribution width levels (P < 0.029) than the other groups. Age <41.5 years (P < 0.001), age at illness initiation <48.5 years (P < 0.002), disease duration <5.5 months (P < 0.001), and eosinophil level <0.29 uL (P 0.014) all point to temporary lesions. Cases with limited CS lesions have younger onset ages, lower disease onset ages, and shorter disease durations. Age, age of disease onset, disease duration, and eosinophil level are risk variables that affect whether CS lesions are permanent or temporary.

Fat-suppression T2 relaxation time and water fraction predict response to intravenous glucocorticoid therapy for thyroid-associated ophthalmopathy.

To investigate the value of fat-suppression (FS) T2 relaxation time (T2RT) derived from FS T2 mapping and water fraction (WF) derived from T2 IDEAL to predict the treatment response to intravenous glucocorticoids (IVGC) in patients with thyroid-associated ophthalmopathy (TAO) based on texture analysis. In this study, 89 patients clinically diagnosed with active and moderate-to-severe TAO were enroled (responsive group, 48 patients; unresponsive group, 41 patients). The baseline clinical characteristics and texture features were compared between the two groups. Multivariate analysis was performed to identify the independent predictors of treatment response to IVGC. ROC analysis and the DeLong test were used to assess and compare the predictive performance of different models. The responsive group exhibited significantly shorter disease duration and higher 90th percentile of FS T2RT and kurtosis of WF in the extraocular muscle (EOM) and 95th percentile of WF in the orbital fat (OF) than the unresponsive group. Model 2 (disease duration + WF; AUC, 0.816) and model 3 (disease duration + FS T2RT + WF; AUC, 0.823) demonstrated superior predictive efficacy compared to model 1 (disease duration + FS T2RT; AUC, 0.756), while there was no significant difference between models 2 and 3. The orbital tissues of responders exhibited more oedema and heterogeneity. Furthermore, OF is as valuable as EOM for assessing the therapeutic efficacy of IVGC. Finally, WF derived from T2 IDEAL processed by texture analysis can provide valuable information for predicting the treatment response to IVGC in patients with active and moderate-to-severe TAO. The texture features of FS T2RT and WF are different between responders and non-responders, which can be the predictive tool for treatment response to IVGC. Texture analysis can be used for predicting response to IVGC in TAO patients. TAO patients responsive to IVGC show more oedema and heterogeneity in the orbital tissues. WF from T2 IDEAL is a tool to predict the therapeutic response of TAO.

Clinical and nutritional correlates associated with weight changes in achalasia patients and the impact of laparoscopic Heller myotomy

BackgroundAchalasia is characterized by symptoms of esophageal obstruction, preventing food consumption. However, weight loss is observed only in a subset of patients, and data from literature is conflicting. AimsOur study aimed at evaluating predictors of weight loss in achalasia patients and at verifying the impact of treatment on nutritional status. Methods123 achalasia patients, eligible for laparoscopic Heller myotomy, were studied. Demographic, clinical and nutritional data (calorie intake and macronutrient composition) were recorded at baseline and one-year post-treatment. Significant weight loss/gain was considered for variation of 10 % of body weight at baseline and post-treatment, respectively. Results57.7 % of patients reported weight loss at presentation. These subjects had shorter disease duration, worse symptoms, lower BMI and consumed fewer calories than patients without weight loss. Post-treatment, we observed a considerable improvement in Eckardt score and BMI values. Almost 50 % of the population reported significant weight gain, particularly in individuals with weight loss at baseline. Caloric intake also rose significantly, positively affecting BMI categories. ConclusionWe showed that achalasia-induced weight loss is associated with symptoms’ severity and disease duration. Conversely, over 50 % of treated patients were in the overweight/obese category, highlighting the need for individualized nutritional interventions in achalasia patients.

Severe Hypertriglyceridemia in Patients with Type 2 Diabetes Mellitus Participating in the AMD Annals Initiative.

Background: Familial chylomicronemia syndrome (FCS) is a rare inherited condition due to lipoprotein lipase deficiency, characterized by hyperchylomicronemia and severe hypertriglyceridemia. Diagnosis is often delayed, thus increasing the risk of acute pancreatitis and hospitalization. Hypertriglyceridemia is a common finding in patients with type 2 diabetes (T2D), who may harbor FCS among the most severe forms. Aim of the Study: We investigated the prevalence and clinical characteristics associated with severe hypertriglyceridemia in a range indicative of FCS, in a large population of subjects with T2D. Methods: Within the large population of the AMD Annals Initiative, patients with T2D with a lipid profile suggestive of FCS [triglycerides >880 mg/dL and/or high-density lipoprotein (HDL)-cholesterol <22 mg/dL or non-HDL-cholesterol ≤70 mg/dL] and their clinical features have been identified. Results: Overall, 8592 patients had triglyceride values >880 mg/dL in a single examination, 613 in two examinations, and 34 in three or more measurements. Patients with high triglyceride levels were mostly male (80%), with a relatively young age (54 years), short duration of diabetes (6.3 years), and elevated hemoglobin A1c (HbA1c) levels (9.4%). By stratifying this group of patients according to the severity of hypertriglyceridemia, more severe hypertriglyceridemia (triglyceride levels ≥2000 mg/dL) was associated with an even younger age (52 vs. 54 years), even higher mean HbA1c values (10.0% vs. 9.4%), and significantly higher HDL-cholesterol levels (37.9 vs. 32.4 mg/dL; P < 0.0001). Patients with persistently elevated triglyceride levels (n = 34), on three measurements, had a younger age; lower body mass index, HbA1c, and HDL-cholesterol levels; more frequent use of fibrates and insulin; and a higher prevalence of major cardiovascular events. Conclusions: Severe hypertriglyceridemia is a frequent condition in outpatients with T2D participating in the AMD Annals Initiative, and it is associated with male sex, young age, short disease duration, and a worse glycemic profile. Among patients with persistent severe hypertriglyceridemia, hidden FCS may be present.

Plasma microRNA Environment Linked to Tissue Factor Pathway and Cancer-Associated Thrombosis: Prognostic Significance in Ovarian Cancer.

Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.

Distinct phenotype and prognosis of immune-mediated necrotizing myopathy based on clinical-serological-pathological classification.

The aim of the study was to investigate the characteristics and prognosis of patients with immune-mediated necrotizing myopathy (IMNM) based on clinical, serological and pathological classification. A total of 138 patients with IMNM who met the 2018 European Neuromuscular Center criteria for IMNM including 62 anti-SRP, 32 anti-HMGCR-positive and 44 myositis specific antibody-negative were involved in the study. All patients were followed up and evaluated remission and relapse. Clustering analysis based on clinical, serological, and pathological parameters was used to define subgroups. Clustering analysis classified IMNM into three clusters. Cluster 1 patients (n = 35) had the highest CK levels, the shortest disease course, severe muscle weakness, and more inflammation infiltration in muscle biopsy. Cluster 2 patients (n = 79) had the lowest CK level and moderate inflammation infiltrate. Cluster 3 patients (n = 24) had the youngest age of onset, the longest disease course and the least frequency of inflammatory infiltration. Patients in cluster 3 had the longest time-to-remission (median survival time: 61[18.3, 103.7] vs 20.5[16.2, 24.9] and 27[19.6, 34.3] months) and shortest relapse-free time than those in cluster 1 and 2 (median remission time 95%CI: 34[19.9, 48.0] vs 73[49.0, 68.7] and 73[48.4, 97.6] months). Patients with age of onset >55 years, more regeneration of muscle fibers, more CD4+T infiltration, and MAC deposition had more favorable outcomes regarding time to achieving remission. Stratification combining clinical, serological, and pathological features could distinguish phenotypes and prognosis of IMNM. The pathological characteristics may impact the long-term prognosis of patients with IMNM.

With or without biopsy in coeliac children?-Impact on dietary compliance and quality of life.

Omitting duodenal biopsies in the diagnostic approach of our CD cohort had no adverse effect on dietary adherence and HRQOL. • Since the publication of the ESPGHAN guideline of 2012, duodenal biopsies are no longer obligatory in the diagnostic approach of CD if IgA-antibodies for transglutaminase 2 are ≥10× ULN, endomysial antibodies are positive in a second blood sample and the patient/family agrees with the no-biopsy approach. • Literature on the effect of the no-biopsy approach on dietary adherence and HRQOL is scarce. • Omitting duodenal biopsies does not influence dietary adherence and quality of life. • In our cohort, lower quality of life measured with the CDDUX subscale 'Having CD' is more likely to be related to shorter disease duration than to the diagnostic approach.