Sex-Related Differences in the Phenotype and Course of Inflammatory Bowel Disease: SEXEII Study of ENEIDA.

BACKGROUND & AIMS: The impact of patient sex on the presentation of inflammatory bowel disease (IBD) has been poorly evaluated. Our aims were to assess potential disparities in IBD phenotype and progression between sexes. METHODS: We performed an observational multicenter study that included patients with Crohn's disease (CD) or ulcerative colitis from the Spanish ENEIDA registry. Data extraction was conducted in July 2021. RESULTS: A total of 51,595 patients with IBD were included, 52% were males and 25,947 had CD. The median follow-up period after diagnosis was 9 years in males and 10 years in females. In CD, female sex was an independent risk factor for medium disease onset (age, 17-40 y) (relative risk ratio, 1.45; 95% CI, 1.31-1.62), later disease onset (age, >40 y) (relative risk ratio, 1.55; 95% CI, 1.38-1.73), exclusive colonic involvement (odds ratio, 1.24; 95% CI, 1.14-1.34), inflammatory behavior (odds ratio, 1.14; 95% CI, 1.07-1.21), and extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.38-1.59). However, female sex was a protective factor for upper gastrointestinal involvement (odds ratio, 0.84; 95% CI, 0.79-0.90), penetrating behavior (odds ratio, 0.76; 95% CI, 0.70-0.82), perianal disease (odds ratio, 0.77; 95% CI, 0.71-0.82), and complications (odds ratio, 0.73; 95% CI, 0.66-0.80). In ulcerative colitis, female sex was an independent risk factor for extraintestinal manifestations (odds ratio, 1.48; 95% CI, 1.26-1.61). However, female sex was an independent protective factor for disease onset from age 40 onward (relative risk ratio, 0.76; 95% CI, 0.66-0.87), left-sided colonic involvement (relative risk ratio, 0.72; 95% CI, 0.67-0.78), extensive colonic involvement (relative risk ratio, 0.59; 95% CI, 0.55-0.64), and abdominal surgery (odds ratio, 0.78; 95% CI, 0.69-0.88). CONCLUSIONS: There is sexual dimorphism in IBD. The patient's sex should be taken into account in the clinical management of the disease.

Prevalence and clinical profiles of primary sclerosing cholangitis in China: Data from electronic medical records and systematic literature retrieval.

BACKGROUND & AIMS: Epidemiology of primary sclerosing cholangitis (PSC) is lacking in China. We aimed to estimate the period prevalence and depict the clinical features of PSC in China. METHODS: We identified and included PSC cases between 2000 and 2023 from two sources: electronic medical records (EMR) and systematical literature retrieval (SLR). The period prevalence of PSC was estimated by the multiplier method. Rate ratios (RRs) for PSC prevalence in relation to macroeconomic indicators were calculated by the negative binomial regression model. RESULTS: A total of 1358 PSC cases were retrieved from 299 hospitals (162 from EMR and 1196 from SLR). Males accounted for 55.7 % of the PSC cases and 25.7 % had concomitant inflammatory bowel disease (IBD). The estimated period prevalence of PSC from 2000 to 2023 was 2.36 (95 % CI: 1.82, 3.34) per 100,000. Males had a numerically higher PSC prevalence than females (2.56, 95 % CI: 1.97, 3.63 vs. 2.14, 95 % CI: 1.65, 3.04 per 100,000). The highest prevalence of PSC was in East China at 4.87 (95 % CI: 3.44, 7.18) per 100,000, followed by North China at 2.94 (95 % CI: 2.33, 3.74) per 100,000, and the lowest in South China at 0.92 (95 % CI: 0.66, 1.30) per 100,000. Regional per capita GDP (RR 1.65, 95 % CI: 1.03, 2.65) and healthcare expenditure (RR 1.94, 95 % CI: 1.13, 3.38) were identified to be associated with PSC prevalence. CONCLUSION: Our study showed the estimated PSC prevalence varied within China, but was generally lower than that in Western countries.

Clinical and patient-reported outcomes and neurofilament response during tofersen treatment in SOD1-related ALS-A multicenter observational study over 18 months.

INTRODUCTION/AIMS: In amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (SOD1-ALS), tofersen received accelerated approval in the United States and is available via expanded access programs (EAP) outside the United States. This multicenter study investigates clinical and patient-reported outcomes (PRO) and serum neurofilament light chain (sNfL) during tofersen treatment in an EAP in Germany. METHODS: Sixteen SOD1-ALS patients receiving tofersen for at least 6 months were analyzed. The ALS progression rate (ALS-PR), as measured by the monthly change of the ALS functional rating scale-revised (ALSFRS-R), slow vital capacity (SVC), and sNfL were investigated. PRO included the Measure Yourself Medical Outcome Profile (MYMOP2), Treatment Satisfaction Questionnaire for Medication (TSQM-9), and Net Promoter Score (NPS). RESULTS: Mean tofersen treatment was 11 months (6-18 months). ALS-PR showed a mean change of -0.2 (range 0 to -1.1) and relative reduction by 25%. Seven patients demonstrated increased ALSFRS-R. SVC was stable (mean 88%, range -15% to +28%). sNfL decreased in all patients except one heterozygous D91A-SOD1 mutation carrier (mean change of sNfL -58%, range -91 to +27%, p < .01). MYMOP2 indicated improved symptom severity (n = 10) or yet perception of partial response (n = 6). TSQM-9 showed high global treatment satisfaction (mean 83, SD 16) although the convenience of drug administration was modest (mean 50, SD 27). NPS revealed a very high recommendation rate for tofersen (NPS +80). DISCUSSION: Data from this EAP supported the clinical and sNfL response to tofersen in SOD1-ALS. PRO suggested a favorable patient perception of tofersen treatment in clinical practice.

Comparative evaluation of disease dynamics in wild boar and domestic pigs experimentally inoculated intranasally with the European highly virulent African swine fever virus genotype II strain "Armenia 2007".

Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.

Multisystemic Inflammation Influences Prognosis in Fulminant Lymphocytic Myocarditis.

BACKGROUND: Multisystem inflammatory syndrome (MIS) is a hyperinflammatory shock associated with cardiac dysfunction and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, there are no reports on using MIS criteria, such as multisystemic inflammation (MSI) in fulminant myocarditis, without SARS-CoV-2 infection. This study investigated the differences in clinical characteristics and course between patients with fulminant lymphocytic myocarditis (FLM) plus MSI and those without MSI. METHODS AND RESULTS: This multicenter retrospective cohort study included 273 patients with FLM registered in the JROAD-DPC database between April 2014 and March 2017. We evaluated the presence of MSI using criteria modified from previously reported MIS criteria and compared the characteristics and risk of mortality or heart transplantation between FLM patients with MSI and without MSI. Of the 273 patients with FLM, 107 (39%) were diagnosed with MSI. The MSI group was younger (44 vs. 57 years; P<0.0001) and had more females (50% vs. 36%; P=0.0236), a higher incidence of pericardial effusion (58% vs. 40%; P=0.0073), and a lower 90-day mortality rate (19% vs. 33%; P=0.0185) than the non-MSI group. The risk of mortality at 90 days was lower in FLM patients aged <50 years with MSI aged <50 years than in those without MSI (P=0.0463). CONCLUSIONS: These results suggest that MSI may influence the prognosis of FLM, especially in patients aged <50 years.

Different psychopathological courses between chronic interictal psychosis and schizophrenia.

OBJECTIVE: The clinical course of interictal psychosis (IIP) has not yet been investigated. We aimed to compared the psychopathology and time-relevant indices between chronic IIP (CIIP) and schizophrenia (SC) METHODS: In this comprehensive psychopathological study, patients with chronic psychosis with and without epilepsy (127 with CIIP and 187 with SC) were compared. Psychopathology was measured using the Brief Psychiatric Rating Scale (BPRS): total, negative symptoms (NSs), positive symptoms (PSs), and anxiety-depressive symptoms (ADSs). Time-relevant indices included age at the time of evaluation, age at the onset of psychosis, and duration of psychosis. The psychopathology of psychosis types and time-relevant indices were analyzed using Pearson's correlation coefficient analysis of covariance. RESULTS: 　Age at the time of evaluation was significantly correlated with NS, and ADS scores. Age-relevant trajectories significantly interacted with psychosis types. As age advanced, patients with SC exhibited increased scores, whereas patients with CIIP often exhibited decreased (or unchanged) scores. Age at onset of psychosis was significantly correlated with NS and ADS outcomes in patients with CIIP, whereas it was not correlated in patients with SC. There were significant interactions between age at onset and psychosis types. Patients with early-onset CIIP exhibited higher NS and lower ADS scores, whereas patients with SC exhibited no particular trajectory. The duration of psychosis significantly interacted with the psychosis types in the BPRS total, NSs and PSs. As duration increased, patients with CIIP exhibited no significant relationship, whereas patients with SC exhibited significantly higher psychotic scores. CONCLUSION: Psychopathological courses differ between patients with CIIP and SC. Although patients with SC often exhibit deteriorations in psychotic symptoms, patients with CIIP exhibit no distinct deterioration. These findings can contribute psychiatric nosology, treatment strategies, and prediction outcomes.

Features of the clinical course of Autoimmune Encephalitis Associated with various antibodies.

Despite the increasing incidence of autoimmune encephalitis and the incomplete recovery observed in patients post-affliction, the issue of timely diagnosis remains unresolved. The primary objective of this study is identification the distinctive clinical presentation features evaluation the management strategies, and assess the outcomes of the disease in patients with various forms of autoimmune encephalitis. The research aims to contribute in a better understanding of the disease progression and facilitate the selection of optimal therapeutic interventions. A retrospective observational study enrolled 68 patients aged 18 years and older with verified autoimmune encephalitis who underwent treatment in state hospitals in Sofia, Bulgaria, from the beginning of 2014 to the end of 2022. The number of patients with pathology linked to antibodies against glycine receptors (Gly-R) was half as much, with 32 and 17 patients, respectively. The primary manifestations of autoimmune encephalitis included cognitive impairments observed in 51 patients, seizures occurring in 44 patients, and mood disorders observed in 22 patients. While the findings of imaging studies were nonspecific, hospitalizations for patients with this pathology, especially those with antibodies to CASPR2 and DPPX, were prolonged (114 and 232 days, respectively). In the vast majority of cases, incomplete recovery with residual symptoms was noted. Among the diverse forms of autoimmune encephalitis, the most prevalent is NMDA-R. Cognitive impairments predominate in the autoimmune encephalitis clinical presentation. Prolonged hospitalization periods and incomplete recovery of patients are characteristic features of autoimmune encephalitis, despite combined therapy involving intravenous administration of methylprednisolone and immunoglobulins.

Exploring the Interplay between Complex Post-Traumatic Stress Disorder and Obsessive-Compulsive Disorder Severity: Implications for Clinical Practice.

Background and Objectives: Traumatic events adversely affect the clinical course of obsessive-compulsive disorder (OCD). Our study explores the correlation between prolonged interpersonal trauma and the severity of symptoms related to OCD and anxiety disorders. Materials and Methods: The study follows a cross-sectional and observational design, employing the International Trauma Questionnaire (ITQ) to examine areas linked to interpersonal trauma, the Hamilton Anxiety Rating Scale (HAM-A), and the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) to assess anxious and obsessive-compulsive symptoms, respectively. Descriptive analysis, analysis of variance (ANOVA), and logistic regression analyses were conducted. Results: We recruited 107 OCD-diagnosed patients, categorizing them into subgroups based on the presence or absence of complex post-traumatic stress disorder (cPTSD). The ANOVA revealed statistically significant differences between the two groups in the onset age of OCD (p = 0.083), psychiatric familial history (p = 0.023), HAM-A, and Y-BOCS (p < 0.0001). Logistic regression indicated a statistically significant association between the presence of cPTSD and Y-BOCS scores (p < 0.0001). Conclusions: The coexistence of cPTSD in OCD exacerbates obsessive-compulsive symptoms and increases the burden of anxiety. Further advancements in this field are crucial for mitigating the impact of early trauma on the trajectory of OCD and associated anxious symptoms.

Etiological differences in demographics, clinical course and consequences of acute pancreatitis: a retrospective study.

OBJECTIVE: Aim: The study is intended to consider acute pancreatitis from the point of view of its etiological structure, as well as demographic description, features of the clinical course, distribution of morphological forms, severity and consequences of the disease in different etiological variants. PATIENTS AND METHODS: Materials and Methods: The work was based on a retrospective analysis of the medical records of 677 patients with acute pancreatitis who underwent inpatient treatment from 2017 to 2022 in an emergency hospital and a tertiary regional hospital in Vinnytsia, Ukraine. RESULTS: Results: The etiological structure of the general sample was as follows: the alimentary factors - 37,5% of cases, biliary - 18,6%, alcohol - 14,0% and postoperative - 7,8%, respectively. The oldest patients were observed in the group with biliary AP (age [median, interquartile range] 61 [46-72] years), the youngest - in the group with alcoholic AP (age [median, interquartile range] 40 [35-47] years). Men significantly predominated in the groups with alimentary and alcoholic AP. A significant predominance of women was observed in the group with biliary AP (62,7% vs. 37,3%, p=0,0003). The highest mortality was in the alcoholic AP group (22,1%), also here was a significantly lower rate of inpatient bed days (6,0). Edematous AP was dominant in all etiological variants. While infected necrotic pancreatitis was significantly more often found in patients with alcoholic genesis (7,4%). CONCLUSION: Conclusions: The etiologic variations of acute pancreatitis differ by demographic and clinical indicators and require more detailed study to understand its prognosis, management, and development of effective prevention and treatment strategies.

Do the current MS clinical course descriptors need to change and if so how? A survey of the MS community.

BACKGROUND AND OBJECTIVES: The current clinical course descriptors of multiple sclerosis (MS) include a combination of clinical and magnetic resonance imaging (MRI) features. Recently there has been a growing call to base these descriptors more firmly on biological mechanisms. We investigated the implications of proposing a new mechanism-driven framework for describing MS. METHODS: In a web-based survey, multiple stakeholders rated the need to change current MS clinical course descriptors, the definitions of disease course and their value in clinical practice and related topics. RESULTS: We received 502 responses across 49 countries. In all, 77% of the survey respondents supported changing the current MS clinical course descriptors. They preferred a framework that informs treatment decisions, aids the design and conduct of clinical trials, allows patients to understand their disease, and links disease mechanisms and clinical expression of disease. Clinical validation before dissemination and ease of communication to patients were rated as the most important aspects to consider when developing any new framework for describing MS. CONCLUSION: A majority of MS stakeholders agreed that the current MS clinical course descriptors need to change. Any change process will need to engage a wide range of affected stakeholders and be guided by foundational principles.

Does a history of cannabis use influence onset and course of schizophrenia?

INTRODUCTION: While evidence strongly supports a causal effect of cannabis on psychosis, it is less clear whether the symptom pattern, clinical course, and outcomes differ in cases of schizophrenia with and without a background of cannabis use. METHODS: Analysis of medical records from a longitudinal follow-up of Swedish conscripts with data on cannabis use in adolescence and subsequent incidence of schizophrenia. One hundred sixty patients with schizophrenia were assessed using the OPCRIT protocol. Cases were validated for diagnosis schizophrenia according to OPCRIT. RESULTS: Patients with a cannabis history (n = 32), compared to those without (n = 128), had an earlier age at onset, a higher number of hospital admissions and a higher total number of hospital days. There was no significant difference in type of onset and clinical symptom profiles between the groups. CONCLUSION: Our findings indicate that the disease burden of schizophrenia is greater in individuals who use cannabis during adolescence. Strengthening evidence on causality and teasing out long-term effects of pre-illness cannabis use from continued post-illness has clinical implications for improving schizophrenia outcomes.

Atopic dermatitis is associated with the clinical course of inflammatory bowel disease.

OBJECTIVES: There are a few studies about the relationship between inflammatory bowel disease (IBD) and atopic dermatitis (AD). It is implied that both diseases have common pathophysiologic mechanisms and can affect each other. However, little information is available on the effect of AD on the clinical course of patients with IBD. METHODS: This is a multi-center, retrospective, observational study. We define AD as a chronic eczematoid dermatosis diagnosed by dermatologists. Patients with concurrent IBD and AD were defined as a case group. Age, gender, and IBD subtype-matched patients without AD were included as a reference group. RESULTS: The numbers of patients in the case and reference groups were 61 and 122 respectively. There was a significantly shorter biologics-free survival in the case group than that in the reference group according to the multivariable-adjusted Cox regression analysis with the onset age, disease duration, smoking status, use of steroid, use of immunomodulator, initial C-reactive protein, initial erythrocyte sedimentation rate, presence of other allergic diseases and initial disease severity [hazard ratio (HR) 1.828, 95% confidence interval (CI) 1.022-3.271, p = .042]. The trend was consistent in the subgroup analysis with ulcerative colitis (HR 3.498, 95% CI 1.066-11.481, p = .039), but not with Crohn's disease (HR 1.542, 95% CI 0.720-3.301, p = .265). CONCLUSIONS: AD showed a significant effect on the biologics-free survival of patients with IBD and especially the UC subtype. Further mechanistic research is required to elucidate the pathogenesis of AD on the clinical course of IBD.

Differences between patients with inpatient-onset and outpatient-onset acute lower gastrointestinal bleeding: An observational study.

BACKGROUND AND AIM: The clinical severity and course of acute lower gastrointestinal bleeding (ALGIB) are believed to differ between inpatient-onset and outpatient-onset cases, but no reports have investigated these issues in detail. We aimed to evaluate the clinical differences between inpatient-onset and outpatient-onset ALGIB. METHODS: Medical records of patients who had undergone emergency colonoscopy for ALGIB were retrospectively reviewed. The severity was evaluated using the NOBLADS score. Patients with obvious ALGIB relapse and/or persistent iron-deficiency anemia after emergency colonoscopy were considered to exhibit a poor clinical course. RESULTS: We reviewed 723 patients with ALGIB and divided them into the inpatient-onset cohort (172 patients) and outpatient-onset cohort (551 patients). Compared with the outpatient-onset cohort, the inpatient-onset cohort had a significantly higher proportion of patients with a poor clinical course (51.2% vs 21.6%; P < 0.001) and a significantly higher mean NOBLADS score (3.6 ± 1.1 vs 2.5 ± 1.0; P < 0.001). The most common bleeding source was acute hemorrhagic rectal ulcer (52.3%) in the inpatient-onset cohort and colonic diverticular bleeding (29.4%) in the outpatient-onset cohort. Multivariate analysis showed that a platelet count < 15 × 104 /µL and albumin concentration < 3 g/dL were significantly associated with a poor clinical course in the inpatient-onset cohort. CONCLUSIONS: The clinical course was significantly worse in the inpatient-onset cohort than in the outpatient-onset cohort. The bleeding source, clinical characteristics, and clinical course differed between the inpatient-onset and outpatient-onset cohorts. The clinical course in the inpatient-onset cohort may depend on the patient's condition at ALGIB onset.

Long-Term Clinical Course after Successful Initial Treatment in Patients with Mild Erosive Esophagitis: A Prospective Follow-Up Study.

INTRODUCTION: This study aimed to investigate the clinical course of patients with healed mild erosive esophagitis and clarify the predictive factors for continuous treatment. METHOD: Fifty-one patients with mild erosive esophagitis who confirmed mucosal healing by endoscopy after initial treatment with vonoprazan (VPZ) were enrolled. The patients continued subsequent treatment of their choice: maintenance therapy with VPZ 10 mg (n = 15), on-demand therapy with VPZ 20 mg (n = 19), or no medication (n = 17). Each patient was prospectively followed up for over 2 years, and the treatment was switched to other options appropriately according to their symptoms. RESULTS: During the mean follow-up period of 3.1 years (range: 2.0-3.9 years), 2 patients who chose maintenance therapy switched to on-demand therapy. One patient who chose on-demand therapy switched to maintenance therapy, while 3 patients switched to no medication. Recurrence of symptoms occurred in 9 patients who chose no medication. They were administered maintenance therapy and five of them were subsequently switched to on-demand therapy. Ultimately, the proportion of patients receiving each treatment was 35.3% (18/51) for maintenance therapy, 43.1% (22/51) for on-demand therapy, and 21.6% (11/51) for no medication. A predictive factor for the need for continuous treatment was the presence of esophageal hiatal hernia (odds ratio: 6.03, 95% confidence interval: 1.43-25.3, p = 0.014). CONCLUSION: Among patients with healed mild erosive esophagitis, 78.4% required continuous treatment with VPZ, while 21.6% remained symptom free with no medication. On-demand therapy was the most common treatment, and continuous treatment may be recommended for patients with esophageal hiatal hernia.

A Marked Eosinophilic Infiltration in Mucosa Could Be a Better Predictive Factor for Intractable Non-Esophageal Eosinophilic Gastrointestinal Disorders.

INTRODUCTION: Non-esophageal eosinophilic gastrointestinal disorders (non-EoE EGIDs) are rare, but their prevalence has recently increased. Although it has been reported that one-half of patients with non-EoE EGIDs have intractable clinical courses, their clinical features are not fully understood. METHODS: This is a multicenter retrospective study in which 10 institutions in Japan participated. Clinical databases from January 1998 to December 2020 were reviewed to identify patients with non-EoE EGIDs. A total of 44 patients were identified; they were divided into two groups based on their clinical course: an intractable group and a non-intractable group. The clinical features were compared between the two groups by a logistic regression analysis. Remarkable eosinophilic infiltration (REI) was defined histologically when the maximal counts of mucosal eosinophils reached a threshold level in the respective area of biopsy. RESULTS: Prevalence of drug allergy and eosinophil counts more than 500/µL (EOS), vomiting symptoms, abnormalities of the stomach, duodenum, and jejunum on computed tomography (upper gastrointestinal abnormality on computed tomography [UACT]), and REI were significantly different between the two groups. Among the factors that were potentially associated with an intractable clinical course, logistic regression revealed that REI, EOS, and UACT were significant factors. Based on an analysis of the area under the receiver operator characteristic curve, a combination of REI and EOS had the lowest Akaike's information criterion, indicating the best model to predict an intractable clinical course. CONCLUSIONS: REI may predict an intractable course in patients with non-EoE EGIDs. In addition, the combination of REI and EOS was a better predictor than REI alone.

The Paradoxical Clinical Course of Persons with Gambling Disorder and Comorbid Attention-Deficit/Hyperactivity Disorder (ADHD).

The co-occurrence of gambling disorder (GD) and attention-deficit/hyperactivity disorder (ADHD) has been widely reported. In this study, we aimed to investigate the social background, clinical characteristics, and clinical course of initial-visit GD patients with and without ADHD in a Japanese psychiatric hospital. We recruited 40 initial-visit GD patients and collected comprehensive information by self-report questionnaires, direct interviews, and medical records. 27.5% of the GD patients had comorbid ADHD. Compared to the GD patients without ADHD, those with ADHD had significantly higher comorbidity rates of autism spectrum disorder (ASD), lower rates of marriage, slightly less years of education and marginally lower employment rates. On the other hand, the GD patients with ADHD showed higher treatment retention rates and participation rates in the mutual support group. Despite presenting with disadvantageous characteristics, GD patients with ADHD exhibited a more favourable clinical course. Therefore, clinicians should be mindful of the possibility of ADHD comorbidity and the potential for better clinical outcomes among GD patients with ADHD.

COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease.

OBJECTIVES: To evaluate the impact of familial Mediterranean fever (FMF) features on the clinical course and outcomes of coronavirus disease 2019 (COVID-19) and clinical course of FMF after COVID-19. METHODS: Consecutive FMF patients with COVID-19 were enrolled from three referral hospitals. Clinical features of FMF and detailed COVID-19 information were obtained from patient interviews and medical records. RESULTS: Seventy-three FMF patients were included in the study. 94.5% of patients had clinical symptoms of COVID-19. We found 24.7% hospitalization, 12.3% respiratory support, 4.1% intensive care unit admission, 6.8% complication, and 1.4% mortality rate in patients. The risk factors of hospitalization for respiratory support were male gender [OR: 7.167 (95% CI: 1.368-37.535)], greater age [OR: 1.067 (95% CI: 1.016-1.121)], and non-adherence to colchicine treatment before the infection [OR: 7.5 (95% CI: 1.348-41.722)]. One-third of patients had reported attacks after COVID-19. The patterns of triggered attacks were fever, peritonitis, pleuritis, transient arthritis, chronic knee mono-arthritis, and protracted febrile myalgia. CONCLUSIONS: FMF characteristics were not associated with worse outcomes of COVID-19. Colchicine non-adherence was the risk factor of hospitalization for oxygen support. The rate of FMF attacks after COVID-19 is prominently increased, with some of them being protracted and destructive.

Isolated central nervous system relapses in patients with high-risk neuroblastoma -clinical presentation and prognosis: experience of the Polish Paediatric Solid Tumours Study Group.

Although isolated central nervous system (CNS) relapses are rare, they may become a serious clinical problem in intensively treated patients with high-risk neuroblastoma (NBL). The aim of this study is the presentation and assessment of the incidence and clinical course of isolated CNS relapses. Retrospective analysis involved 848 NBL patients treated from 2001 to 2019 at 8 centres of the Polish Paediatric Solid Tumours Study Group (PPSTSG). Group characteristics at diagnosis, treatment and patterns of relapse were analysed. Observation was completed in December 2020. We analysed 286 high risk patients, including 16 infants. Isolated CNS relapse, defined as the presence of a tumour in brain parenchyma or leptomeningeal involvement, was found in 13 patients (4.5%; 8.4% of all relapses), all of whom were stage 4 at diagnosis. Isolated CNS relapses seem to be more common in young patients with stage 4 MYCN amplified NBL, and in this group they may occur early during first line therapy. The only or the first symptom may be bleeding into the CNS, especially in younger children, even without a clear relapse picture on imaging, or the relapse may be clinically asymptomatic and found during routine screening. Although the incidence of isolated CNS relapses is not statistically significantly higher in patients after immunotherapy, their occurrence should be carefully monitored, especially in intensively treated infants, with potential disruption of the brain-blood barrier.

Characterizing the longitudinal course of symptoms and functioning in bipolar disorder.

BACKGROUND: The course of Bipolar Disorder (BD) is highly variable, with marked inter and intra-individual differences in symptoms and functioning. In this study, we identified illness trajectories across major clinical domains that could have etiological, prognostic, and therapeutic relevance. METHODS: Using the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study, we performed univariate and multivariate trajectory modeling of depressive symptoms, manic symptoms, and psychosocial functioning. Multinomial regression was performed to identify baseline variables associated with poor outcome trajectories. RESULTS: Depressive symptoms predominated, with most subjects being found in trajectories characterized by various degrees of depressive symptoms and 13% of subjects being classified in a poor outcome 'persistently depressed' trajectory. Most subjects experienced few manic symptoms, although approximately 10% of subjects followed a trajectory of persistently manic symptoms. Trajectory analysis of psychosocial functioning showed impairment in most of the sample, with little improvement during follow up. Multi-trajectory analyses highlighted significant impairment in subjects with persistently mixed and persistently depressed trajectories of illness. In general, poor outcome trajectories were marked by lower educational attainment, higher unemployment and disability, and a greater likelihood of adverse clinical features (rapid cycling and suicide attempts) and comorbid diagnoses (anxiety disorders, PTSD, and substance abuse/dependence disorders). CONCLUSIONS: Subjects with BD can be classified into several trajectories of clinically relevant domains that are prognostically relevant and show differing degrees of associations with a broad range of negative clinical risk factors. The highest level of psychosocial disability was found in subjects with chronic mixed and depressive symptoms, who show limited improvement despite guideline-based treatment.

Crosstalk of miRNAs with signaling networks in bladder cancer progression: Therapeutic, diagnostic and prognostic functions.

Urological cancers are considered as life-threatening diseases around the world. Bladder cancer is one of the most malignant urological tumors with high mortality and morbidity. Bladder cancer is a heterogenous disease and genetic alterations have shown to be key players in regulating its progression. Although conventional therapies are somewhat beneficial in improving prognosis and survival, bladder cancer patients suffer from recurrence. MicroRNAs (miRNAs) are endogenous short RNA molecules that do not encode proteins and show dysregulated expression in human cancers. miRNAs are regulators of vital biological processes in cells such as proliferation, migration, differentiation and apoptosis. Dysregulation of miRNAs is observed in bladder cancer and they are used as biomarkers for diagnosis and prognosis of patients. LncRNAs and circRNAs are modulators of bladder cancer progression via miRNA expression regulation. Overexpression of onco-suppressor miRNAs impairs bladder cancer progression, while oncogenic miRNAs drive tumor progression. Glycolysis and EMT mechanisms are two important factors for proliferation and migration of bladder cancer that are modulated by miRNAs. Furthermore, miRNAs can affect STAT3 and Wnt/ß-catenin as instances of molecular factors in regulating bladder tumor progression. Bladder tumor response to drug therapy and radiotherapy is regulated by miRNAs. Hence, aim of current review is to provide function of miRNAs in bladder cancer based on their crosstalk with other molecular pathways and interaction with biological processes.