Severe Course Research Articles

Relationship between periodontitis, type 2 diabetes mellitus and COVID-19 disease: a narrative review

Inflammation plays a fundamental role in the development and bidirectional association of di-verse diseases, such as periodontitis and type 2 diabetes mellitus (T2DM), which generates important clinical complications, where chronic exposure to high levels of blood glucose affects the repair process of periodontal tissues. Likewise, it has been observed that comorbidity, between these two diseases, influences the development of the COVID-19 disease towards a more severe course. However, there is currently very little scientific evidence on the relationship between periodontitis, T2DM and COVID-19 disease. This narrative review aims to provide an understanding of the current and most relevant aspects of the relationship between periodontitis, T2DM and COVID-19 disease. A narrative review was performed through a systematic search of published studies, without date restrictions, indexed in the electronic databases of PubMed, for the inclusion of articles in English, and LILACS for the inclusion of articles in Spanish. This review included different articles, which addressed the most important aspects to present a current perspective on the relationship and influence between periodontitis, T2DM and COVID-19 disease. Comorbidity between periodontitis and T2DM represents a greater risk of developing a more severe course of COVID-19 disease, because these three diseases share three important axes: a clinicopathological axis; an axis associated with glycemia, and an immunological axis associated with inflammation.

The state of the hemostasis system in patients suffering from a severe course of the coronavirus infection SARS-CoV-2 COVID-19, during hospitalization (results of a randomized clinical study)

Objective: to assess the state of the hemostasis system and the effectiveness of a prophylactic dose of anticoagulants in patients suffering from severe COVID-19 coronavirus infection during hospitalization.Materials and methods. The study included patients diagnosed with acute community-acquired pneumonia who were admitted to the intensive care unit of the Kursk City Hospital No. 6, specialized during the pandemic in providing assistance to the adult population with coronavirus infection in the period from December 2020 to December 2021. The sample included data from 127 patients. All patients underwent CT scanning upon admission to confirm the diagnosis of bilateral pneumonia and PCR testing to confirm the diagnosis of COVID-19. A study of the blood hemostasis system was also performed for everyone within the first 24 hours after hospitalization. The diagnostic laboratory system "T2 Thrombodynamics Registrar" ("Gemacor", Moscow) was used.Results. We found statistically significant differences between laboratory parameters in surviving and deceased patients: leukocytosis level, C-reactive protein level, blood lactate. It was found that in the first sample, these parameters were significantly lower than in the second. The conducted correlation analysis showed that deceased patients had a more pronounced state of hypercoagulation of the blood coagulation system and a higher risk of developing thromboinflammatory syndrome.Conclusion. The state of the hemostasis system was assessed in patients suffering from severe coronavirus infection COVID-19 caused by SARS-CoV-2, immediately upon hospitalization. The results suggest that the use of prophylactic anticoagulant therapy in patients with a new coronavirus infection may be ineffective and even dangerous due to the relationship between hemostasis disorders and adverse outcomes. Dosing of anticoagulants such as low molecular weight or unfractionated heparins should be based on clear targets, such as thrombodynamic parameters. This approach will significantly optimize the effectiveness of anticoagulant therapy in patients with COVID-19.

The effect of childhood trauma on bipolar depression

Childhood trauma (CT) is associated with an earlier onset and a more severe course of bipolar disorder (BD). However, the specific impact of CT on bipolar depression remains unclear. Herein, this study aimed to investigate the effect of CT using depressive episode frequency as a threshold for disease burden and severity. A cohort of 146 participants with BD was followed for 3 years. The effects of CT on mood episodes, hospital readmissions, suicidal ideation, and behavior were analyzed. A high number of depressive episodes were identified in participants with BD and CT exposure, with the effect being more pronounced in BD II than in BD I. A threshold of ≥4 depressive episodes serves as a sensitivity cutoff point to detect associations with severe outcomes, such as early readmission and suicidal ideation and behavior. The presence of CT increases the risk of experiencing at least one severe outcome by 80%. In our cohort, a cutoff point of ≥4 depressive episodes mediated the effect of CT on at least one severe outcome (early readmission or suicidal ideation and behavior). The study is limited by its non-probabilistic sample, recall bias, and moderate receiver operating characteristic curve value. The findings reinforce the association between CT and BD severity, highlighting the significantly higher number of depressive episodes in individuals with CT. This underscores CT as a risk factor for depressive predominant polarity and more frequent mood episodes in BD.

Long-Term Outcome of Paediatric Crohn's Disease Patients With Deep Ulcerations at Diagnosis.

Presence of deep ulcerations (DU) at diagnosis seems to be predictive of a more severe phenotype in adult Crohn's disease (CD). The aim of our study was to investigate if the presence of DU at diagnosis was associated with a more severe disease course over time in children. In this monocentric retrospective study, we analysed data from paediatric patients with a new diagnosis of CD from 2009 to 2017. Clinical, laboratory data, treatments and complications were recorded for each patient at diagnosis and at 1, 3 and 5 years of follow-up. Patients were compared according to the presence or absence of DU on colonoscopy. Among the 116 patients included in the study, 52 patients had DU at diagnosis. Comparison showed an increased risk for patients with DU to develop abdominal abscesses (p = 0.045) and to experience more relapses (p = 0.013) at 1 year. At 3 and 5 years, there was no longer any difference between groups. The time from diagnosis to first anti-TNF alpha was shorter in DU patients. The presence of DU at diagnosis is associated with more complications during the first year of follow-up but not after, due to a more active therapeutic management.

The effect of phototherapy on the expression of innate immunity genes in patients with psoriasis

BACKGROUND: Phototherapy is one of the most effective methods in the treatment of psoriasis, but the mechanism of its action on innate immunity has not been studied. AIM: Investigation of the local expression profile of innate immunity factors in patients with psoriasis during phototherapy. MATERIALS AND METHODS: The study included 31 patients diagnosed with inpatient psoriasis vulgaris. The material for the study was obtained from areas of affected and unaffected skin. Patients with vulgar psoriasis received a course of UVB-311 nm phototherapy lasting from 5 to 7 weeks with a total dose of 35.2 to 44.6 J/cm2. There were 30 healthy people in the control group. Gene expression analysis was performed before treatment and at the end of the phototherapy course. The data obtained were statistically processed. RESULTS: According to the results of the study, gene expression data were obtained: for example, increased expression of the TLR2 and TLR9 genes was observed in the main group after treatment, as well as in samples of unaffected skin from patients. The increased level of the TLR4 gene expression was registered in unaffected skin samples from patients with psoriasis. The expression of the β-defensin 1 gene was elevated in unaffected skin and post-treatment skin. For the cathelicidin gene, there is a difference between the groups of affected and unaffected skin samples before treatment. The expression level of the IL-13 gene was higher before treatment. CONCLUSION: The revealed local imbalance of factors of innate immunity can lead to a more severe course of the disease. The course of phototherapy leads to normalization of the expression profile of receptor and effector molecules of innate immunity, which leads to a stable positive clinical effect.

Modern clinical and laboratory indicators of severe Plasmodium falciparum malaria

According to WHO Report 2024, malaria is still a global health challenge, especially in Africa, Asia and South America. In the opinion of the authors, errors made in adequate assessment of clinical and laboratory indicators of P. falciparum malaria (tropical malaria) in a patient are the major reasons that can lead to a lethal disease outcome. The aim of our research was to describe the clinical and laboratory indicators of severe tropical malaria with a severe and complicated course of disease in a female patient, taking into account the analysis of data from modern scientific and medical literature, and our own experience. An abstract of the case history of patient M., 56 years old, is presented. The patient underwent medical treatment in an infectious disease hospital under the primary diagnosis of Plasmodium falciparum malaria with cerebral complications and acute renal failure, severe course of illness. She fell ill on Day 7 after her journey to Tanzania (Zanzibar Island). The disease developed in a severe, complicated form with acute renal failure, sepsis, severe anemia, bilateral polysegmental pneumonia, and nosebleeds. The parasitemia level reached 1,428,000 per microliter of blood. The treatment regimen of malaria included Coartem. Due to ongoing intensive therapy, positive changes were achieved. A stable absence of parasitemia was observed, however a peripheral edema and a high level of azotemia persisted. The patient continued to undergo treatment in the Department of Nephrology, where a significant clinical outcome in the form of decreased azotemia levels was achieved. The woman was discharged home in a satisfactory condition. The clinical case example fully reflects modern clinical and laboratory criteria for severe, complicated tropical malaria, and demonstrates rapid development of serious complications as a result of late admission to hospital. It represents a practical interest not only for infectious disease experts, but also for therapists, nephrologists, neurologists, resuscitationists and physicians of other specialties.

Autoantibody development is associated with clinical severity of COVID-19: A cohort study.

Autoantibody development is associated with clinical severity of COVID-19: A cohort study.

Psoriasis in the context of comorbidity: focus for hypertension

Purpose. Compare the frequency of occurrence of comorbid pathologies in patients with psoriasis and concomitant hypertension and patients with psoriasis without hypertension, evaluate the severity of psoriasis in patients with concomitant hypertension. Material and methods. The study was attended by 120 patients with psoriasis, divided into 2 groups: 1st (n=60) – patients with psoriasis and hypertension; 2nd (n=60) – patients with psoriasis without hypertension. The study included the analysis of the stories of the disease, the collection of complaints, the anamnesis of the disease, the anamnesis of life, the physical examination, the measurement of blood pressure, the calculation of the prevalence index and the severity of psoriasis (PASI). Results. In patients with psoriasis and concomitant hypertension, the course of the underlying disease took place in a more severe form with a high PASI index. The predominance of exudative forms of the disease, the progressive stage with damage to the scalp, trunk, upper and lower extremities, was noted, and in 43.3% of patients and involving the skin of the face in the pathological process. The number of related diseases and the percentage of patients with polymorbid pathology in a group of patients with psoriasis and hypertension were significantly greater. In this group of patients, a longer stay in the hospital was also noted. Conclusion. In patients with psoriasis, the concomitant hypertension contributes to a more severe course of the skin process, increase the comorbid load, increase polymorbidity and lengthen the temporary disability, thereby worsening the quality of life of patients.

Triple positivity for autoantibodies in patients with rheumatoid arthritis is associated with a severe course of the disease but not with bone turnover markers

IntroductionRheumatoid arthritis (RA) is a prevalent autoimmune disorder characterized by chronic joint inflammation and progressive bone erosion. Traditional autoantibodies, such as anti-citrullinated peptide antibodies (ACPAs) and rheumatoid factor (RF), are established markers associated with disease severity. Recent studies have identified anti-carbamylated protein (anti-CarP) antibodies as potential indicators of disease progression. Additionally, bone turnover markers and specific single nucleotide polymorphisms (SNPs) may influence RA pathogenesis. This study aimed to evaluate the correlation between autoantibody profiles, disease activity, bone turnover markers, and selected SNPs in a cohort of Polish RA patients.Material and methodsA total of 138 RA patients from the Department of Rheumatology, Medical University of Lodz, were enrolled. Disease activity was assessed using the Disease Activity Score in 28 joints by C-reactive protein (DAS28-CRP). Serum levels of RF, ACPAs, anti-CarP antibodies, and bone turnover markers (sclerostin, periostin, and Dickkopf-1) were measured using immunoassays. Genotyping for SNPs in PADI4 (rs2240340), STAT4 (rs7574865), and PTPN22 (rs2476601) genes was performed. Patients were categorized into two groups: those positive for anti-CarP antibodies, RF, and ACPA (triple-positive, <i>n</i> = 27) and those with other antibody combinations (<i>n</i> = 111).ResultsDemographic characteristics, including age (mean approx. 61 years), gender distribution (approx. 75% female), treatment rates (approx. 75%), and glucocorticosteroid use (approx. 40%), were comparable between groups. The triple-positive group exhibited higher disease activity, with a greater number of painful joints (mean 10.07 vs. 7.72; <i>p</i> = 0.017), higher Visual Analogue Scale (VAS) scores for pain (mean 6.26 vs. 5.06; <i>p</i> = 0.018), elevated DAS28-CRP scores (mean 4.75 vs. 4.07; <i>p</i> = 0.037), and increased erythrocyte sedimentation rate (ESR) (mean 32.92 mm/h vs. 22.82 mm/h; <i>p</i> = 0.019). Serologically, the triple-positive group had significantly higher levels of anti-CarP (mean 29.19 ng/ml vs. 16.29 ng/ml; <i>p</i> < 0.0001) and ACPAs (mean 395.45 vs. 368.70; <i>p</i> < 0.0001), but lower RF levels (mean 164.01 vs. 453.40; <i>p</i> = 0.004). Bone turnover markers showed no significant differences between groups, though the difference in sclerostin levels approached statistical significance (<i>p</i> = 0.085), suggesting a possible association of higher bone formation inhibition with triple-positive status. No significant associations were found between the autoantibody profiles and the selected SNPs.ConclusionsThe presence of anti-CarP antibodies, RF, and ACPA is associated with increased disease activity in RA patients. However, these autoantibody profiles do not significantly correlate with bone turnover markers or the selected genetic polymorphisms in this Polish cohort. Further research is warranted to elucidate the complex interactions between autoantibodies, bone metabolism, and genetic factors in RA.

Commentary: Integrated Clinical Genetic Analysis of Meningiomas Causing Bony Hyperostosis Shows More Severe Clinical Course and Overexpression of Secreted Pro-Osteogenic Factor.

Commentary: Integrated Clinical Genetic Analysis of Meningiomas Causing Bony Hyperostosis Shows More Severe Clinical Course and Overexpression of Secreted Pro-Osteogenic Factor.

Integrated Clinical Genetic Analysis of Meningiomas Causing Bony Hyperostosis Shows More Severe Clinical Course and Overexpression of Secreted Pro-osteogenic Factors.

Meningiomas are the most common primary tumor of the brain and may elicit hyperostosis of the adjacent bone. Whether hyperostosis is related to reactive changes of the overlying bone or by invasion of the tumor itself is unclear. In this article, we characterize the clinical and molecular differences of meningiomas with hyperostosis from those without hyperostosis. One hundred and eighty-one primary, nonsyndromic, nonradiation-induced meningiomas with DNA and RNA sequencing were included in a retrospective study. Preoperative MRI and computed tomography scans were reviewed by a fellowship-trained neuroradiologist to identify the presence of hyperostosis or bone invasion. Clinical, radiographic, and surgical data were gathered for each patient. Bulk RNA sequencing was performed, and data were analyzed for gene set enrichment analysis, gene ontologies, and differentially expressed genes along with chromosomal deletions and canonical mutations. Sixty-six (36.5%) meningiomas had radiographic evidence of hyperostosis compared with 115 (63.5%) without hyperostosis. Patients with hyperostosis had more severe presentation with increased rates of emergency department admissions (P = .0320) and seizure presentation (P = .0480). Hyperostotic tumors preferentially manifested in the olfactory groove location (P = .004). Radiographically, tumors with hyperostosis had higher rates of edema (P = .0280), midline shift (P = .010), nonhomogeneous enhancement (P = .001), T2 hyperechoic signal (P = .001), and bone invasion (P < .001). Patients with hyperostosis had increased estimated blood loss intraoperatively (P = .006), longer time in the operating room (P = .045), and higher rates of craniectomy and cranioplasty (P < .001 and P = .001). Fifty-five percent of all upregulated differentially expressed genes in hyperostotic tumors are secreted, and many are related to skeletal system development (BMP3, RBP4, MATN4, CILP2, and FGF7). In a retrospective study, meningiomas with hyperostosis are region-specific, are related to higher intraoperative complications, and present with distinct radiographic features. Transcriptional analysis revealed upregulation of secreted proteins that positively influence bone development and growth.

A retrospective study on factors related to in-hospital mortality among patients with COVID-19, March 2020 to November 2021.

Four years since the pandemic was declared, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains an important cause of illness around the world. Although many countries were able to overcome the health crisis at its peak, there are still individuals at high risk of a severe course of coronavirus disease 2019 (COVID-19). Therefore, it is important to continue research on the factors that could predict disease severity and adverse outcomes. We conducted a retrospective study on 171 consecutive hospitalized cases of COVID-19 from March 2020 to November 2021. Past medical history, drug history, clinical and laboratory parameters on admission, and the choice of treatment during hospital stay were obtained and associated with in-hospital mortality. Older age was significantly associated with mortality. Non-survivors also showed a significantly lower PaO2/FiO2 (P/F) ratio at the time of hospital admission; a lower lymphocyte count; and increased levels of white blood cell count, C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, and creatinine. Significant differences were also observed with regards to both long-term medications and treatments administered during hospital stay. Our findings highlight the importance of age, clinical features, biochemical biomarkers, and therapeutic interventions in predicting COVID-19 disease severity and outcomes.

A case Report: Q Fever With Acute Hepatitis

A Case Report: Q Fever with Acute Hepatitis Bozyaka Training and Research Hospital, Department of Internal Medicine, İZMİR Elif Ertan, Talha Özüdoğru, İsmail Demir Abstract Q fever is a zoonotic bacterial infection caused by Coxiella burnetii. The primary sources of this pathogen are small and large livestock. The causative agent is disseminated into the environment through the birth products, milk, feces, and urine of infected animals. This bacterium is highly resistant to environmental conditions. Transmission from animals to humans and/or from humans to humans occurs via inhalation. The acute disease presentation can be asymptomatic or resemble influenza-like symptoms, and it can also lead to more severe manifestations such as fever, pneumonia, and hepatitis. In cases with severe clinical courses, Q fever should be considered in the differential diagnosis, especially considering epidemiological risks. This paper discusses a case presenting with fever, jaundice, and hepatitis, subsequently diagnosed as Q fever.

Prediction of fatal outcome in patients with pneumonia caused by carbapenem-resistant Klebsiella pneumoniae

Pneumonia caused by carbapenem-resistant K. pneumoniae often has a severe course and a significant risk of unfavorable outcome. Various scales and indices have been proposed for timely assessment of the patient's condition and detection of a high risk of unfavorable outcome. For the attending physician, the ease of use and prognostic accuracy of the index used in the assessment are important. The aim of the study was to evaluate the diagnostic significance of clinical and laboratory parameters for predicting a fatal outcome in patients with pneumonia caused by carbapenem-resistant K. pneumoniae. A total of 71 cases of pneumonia caused by K. pneumoniae with multiple and extreme drug resistance were retrospectively analyzed. Two groups of patients were formed depending on the outcome: group 1 – 41 patients discharged from the hospital upon completion of treatment; group 2 – 30 patients with a fatal outcome. The structure of concomitant diseases, body mass index (BMI), blood saturation (SpO2), hemogram parameters, C-reactive protein (CRP) were analyzed. It was found that patients with a fatal outcome were characterized by higher leukocyte counts, neutrophils in the hemogram, neutrophil/lymphocyte ratio (NLR), CRP, BMI; lower lymphocyte counts, SpO2. The most significant prognostic indicators of an unfavorable outcome are lymphocytes, neutrophils, NLR, BMI. To predict the risk of death, we proposed the index (BMI*NLR)/SpO2. ROC analysis was performed: the AUC was 0,99 (0,93–1,00), test sensitivity 100,0 %, specificity 97,6 % at a cutoff point of &gt; 1,53, Youden index 0,98. Diagnostic value of the index (BMI*NLR)/SpO2 (at a threshold value &gt; 1,53): test sensitivity is 100,0 %, specificity is 95,1 %, positive predictive value is 93,8 %, negative predictive value is 100,0 %, accuracy is 97,2 %. The proposed index (BMI*NLR)/SpO2 (at a level &gt; 1,53) may be preferable for predicting a fatal outcome of pneumonia caused by carbapenem-resistant K. pneumoniae, due to its high sensitivity (100 %) and specificity (97,6 %), as well as ease of use.

Uncomplicated SARS-CoV-2 Infections with Preserved Lung Function in Pediatric Patients with Cystic Fibrosis: A Three-Year Single-Centre Experience.

Background/Objectives: Patients with chronic lung diseases, such as cystic fibrosis, were considered a risk group for a severe course of coronavirus disease 2019 at the beginning of the pandemic. However, mounting evidence suggests that this group may not face an elevated risk for a severe SARS-CoV-2 infection. Methods: Here, we present data on the incidence and clinical course of SARS-CoV-2 infections in a single pediatric CF centre in Austria. Clinical variables were analyzed for their potential impact on disease acquisition and severity. A total of 135 young people with CF were assessed from February 2020 until December 2022. Results: Eighty-four patients were infected with SARS-CoV-2, out of which nine patients reported re-infection, resulting in 93 SARS-CoV-2 infections. Most infections, 76/93 (82%), occurred during the period of omicron variant predominance. Higher body mass index and respiratory colonization with Haemophilus influenzae before the beginning of the pandemic were significantly associated with the risk of acquiring SARS-CoV-2 infection. All patients had an uncomplicated COVID-19 course, regardless of the SARS-CoV-2 variant and COVID-19 vaccine status at infection. The most frequent symptoms were rhinitis (53%), fatigue (49%), cephalea (43%), and fever (38%). Neither oxygen therapy nor hospitalization were needed for any of the patients. Lung function parameters (FEV1, FVC, FEF50, LCI), both in the early post-viral as well as late post-viral stages, were not significantly impacted by SARS-CoV-2 infections. No long-term post-COVID-19 effects were reported. Conclusions: Our single-centre experience suggests that the course of SARS-CoV-2 infections in children and adolescents with CF is primarily mild and uncomplicated.

The Complexity of Patients with STAT Pathway Immunodeficiency

Background Patients with STAT pathway immunodeficiency have a diverse phenotype, presenting a challenge in establishing treatment guidelines. HSCT is often reserved for complicated and young patients. JAK inhibitors provide an important therapeutic option, yet data on the benefits and optimal patient selection are lacking. Objective To evaluate the spectrum of patients with STAT pathway immunodeficiency and immune dysregulation and the therapeutic experience with Jakinhibs and other therapeutic options. Methods We included patients followed by the immunology service at Schneider's Children Medical Center of Israel. Clinical, laboratory, genetic, and therapeutic data were gathered. Results 9 patients, all of which had different STAT pathway mutations, were followed during the study period 2012-2024. 5 had STAT1 GOF mutations, 1 had partial STAT1 LOF, 2 had STAT3 GOF mutations, and 1 had STAT3 LOF HIGES. The clinical presentation of patients with STAT1 GOF mutations was varied, from a severe neonatal course to a more typical course of mucocutaneous candidiasis. 3/5 of the patients with STAT1 mutations suffered from CMV viremia, 4/5 had significant bowel disease, and 3/5 had NTM infection. One patient underwent a successful HSCT. 2 patients were successfully treated with Ruxolitinb. 2 patients had severe esophagitis due to Candida albicans infections. Both had evolved to Candida strains resistant to azoles. One patient received oral amphotericin and the other is currently on IV Caspofungin. He is now starting Ruxolitinib treatment and underwent balloon dilatation of the esophagus. 2 patients had severe neurological manifestations of chronic meningitis and peripheral neuropathy. Increased ICP occurred in 2 patients. Both patients with STAT3 GOF presented with immune cytopenias. Both were treated with Ruxolitinib. One stopped treatment due to significant weight gain. Conclusion STAT mutations causing immunodeficiency and immune dysregulation cause significant morbidity. Resistant C. albicans esophagitis, CMV and NTM infections, and enteropathy were the major symptoms of STAT1 mutations in our cohort, whereas immune cytopenias and lymphoproliferation were the common presenting picture in patients with STAT3 GOF. 3 patients suffered from severe neurological complications. Ruxolitinib therapy is effective but not without side effects. One patient presenting and diagnosed before one year of age underwent successful bone marrow transplantation Table 1.

Statin Use is Associated with a Less Severe Disease Course In Inflammatory Bowel Disease: A Nationwide Cohort Study 2006-2020.

Statins reduce the risk of inflammatory bowel disease (IBD), however their effect on IBD disease progression is largely unknown. We linked Swedish healthcare registers and performed a nationwide cohort study (2006-2020) of 19 788 adults (≥18 years) with ulcerative colitis (UC) and 12 582 with Crohn's disease (CD). Of these, 1733 with UC and 962 with CD were identified as incident statin users after UC or CD diagnosis. After 1:1 propensity score matching, we compared statin users with non-users to estimate the risk of IBD-related surgery, hospitalizations, and disease flares expressed as incidence rates (IRs) and multivariable-adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). For outcomes with statistically significant estimates, we calculated the numbers needed to treat (NNT). During a median follow-up of 3.4 years we observed a reduced risk of IBD-related surgery in statin users (UC, IR: 3.4 [95%CI: 2.1-4.8] per 1000 person-years; CD, IR: 9.2 [6.2-12.2]) compared with non-users in UC (IR: 6.3 [4.2-8.5]; aHR: 0.55 [0.31-0.97]) and CD (IR: 15.4 [11.0-19.7]; aHR: 0.54 [0.33-0.88]). The NNT to avoid one IBD-related surgical event per year of statin treatment were 345 (UC) and 161 (CD). For statin users, the risks of hospitalizations (IR: 17.0 [13.9-20.2]; aHR: 0.68 [0.51-0.91]) and disease flares (IR: 207.4 [193.2-221.6]; aHR: 0.86 [0.77-0.97]) were reduced in UC, but not in CD (IR: 20.3 [15.8-24.9]; aHR: 0.78 [0.56-1.09] and IR: 245.5 [223.9-267.1]; aHR: 1.02 [0.88-1.19]). In UC, NNT for hospitalizations and disease flares were 145 and 15. Statins were associated with a reduced risk of IBD-related surgery, hospitalizations, and disease flares in patients with UC, and with a reduced risk of IBD-related surgery in patients with CD.

Common Variable Immunodeficiency Clinical Manifestations Are Shaped by Presence and Type of Heterozygous NFKB1 Variants

Background NFKB1 encodes p105, which is processed to p50 to mediate canonical NF-κB signaling. Though NF-κB is a central driver of inflammation and heterozygous NFKB1 variants are considered the most common monogenic etiologies of common variable immunodeficiency (CVID), few studies have explored how NFKB1 variants shape clinical course or inflammation in CVID. Objective We leveraged a regional cohort of CVID patients with and without heterozygous NFKB1 variants to assess how clinical and inflammatory features of CVID are shaped by the presence of these variants. Methods We compared clinical complications, immunological features, and plasma cytokine levels of 15 CVID patients with heterozygous NFKB1 variants with 77 genetically undefined CVID patients from the same referral base. We also assessed differences between CVID patients with frameshift or nonsense NFKB1 variants compared with those with missense NFKB1 variants. Results We found CVID patients with heterozygous NFKB1 variants to have increased autoimmune disease, bronchiectasis, gastrointestinal infections, inflammatory bowel disease (IBD), and plasma cytokines compared with genetically undefined CVID patients. These findings were more pronounced and included elevation of monocytes, in CVID patients with frameshift or nonsense NFKB1 variants relative to those with missense NFKB1 variants. Conclusion In a regional cohort, heterozygous NFKB1 variants were associated with worsened CVID clinical course and increased evidence of inflammation in the blood. CVID patients with frameshift or nonsense NFKB1 variants had more significant increases in noninfectious complications and peripheral monocytes than those with missense NFKB1 variants. Presence of pathogenic NFKB1 variants in CVID patients may be associated with more severe disease course and warrant closer monitoring.

Fecal Microbiome Reflects Disease State and Prognosis in Inflammatory Bowel Disease in an Adult Population-Based Inception Cohort.

We aimed to determine the diagnostic and prognostic potential of baseline microbiome profiling in inflammatory bowel disease (IBD). Participants with ulcerative colitis (UC), Crohn's disease (CD), suspected IBD, and non-IBD symptomatic controls were included in the prospective population-based cohort Inflammatory Bowel Disease in South-Eastern Norway III (third iteration) based on suspicion of IBD. The participants donated fecal samples that were analyzed with 16S rRNA sequencing. Disease course severity was evaluated at the 1-year follow-up. A stringent statistical consensus approach for differential abundance analysis with 3 different tools was applied, together with machine learning modeling. A total of 1404 individuals were included, where n = 1229 samples from adults were used in the main analyses (n = 658 UC, n = 324 CD, n = 36 IBD-U, n = 67 suspected IBD, and n = 144 non-IBD symptomatic controls). Microbiome profiles were compared with biochemical markers in machine learning models to differentiate IBD from non-IBD symptomatic controls (area under the receiver operating curve [AUC] 0.75-0.79). For UC vs controls, integrating microbiome data with biochemical markers like fecal calprotectin mildly improved classification (AUC 0.83 to 0.86, P < .0001). Extensive differences in microbiome composition between UC and CD were identified, which could be quantified as an index of differentially abundant genera. This index was validated across published datasets from 3 continents. The UC-CD index discriminated between ileal and colonic CD (linear regression, P = .008) and between colonic CD and UC (P = .005), suggesting a location-dependent gradient. Microbiome profiles outperformed biochemical markers in predicting a severe disease course in UC (AUC 0.72 vs 0.65, P < .0001), even in those with a mild disease at baseline (AUC 0.66 vs 0.59, P < .0001). Fecal microbiome profiling at baseline held limited potential to diagnose IBD from non-IBD compared with standard-of-care. However, microbiome shows promise for predicting future disease courses in UC.

Multimodal prognostication of autoimmune encephalitis: an Australian autoimmune encephalitis consortium study

Background and objectivesTo identify factors predictive of a favourable modified Rankin score (mRS) at 12 months in patients with autoimmune encephalitis (AE). To evaluate predictors of a binary composite clinical-functional outcome measure, encompassing mRS, drug-resistant epilepsy (DRE) and memory impairment, at 12 months.MethodsUnivariable and multivariable logistic regression analyses for predictors of a favourable mRS (i.e. mRS ≤ 2) and a composite clinical-functional outcome at 12 months were used.ResultsA total of 231 patients with AE were recruited. Multivariable logistic regression identified factors predictive of reduced odds of favourable mRS at 12 months were older age (OR 0.97; 95% CI 0.95, 0.98; p < 0.001), T2/FLAIR hyperintensity on initial MRI (OR 0.27; 95% CI 0.13, 0.56; p < 0.001), RSE (OR 0.17; 95% CI 0.06, 0.52; p = 0.002) and first-line immunotherapy failure (OR 0.18; 95% CI 0.09, 0.37; p < 0.001). Anti-LGI1 antibody-mediated encephalitis relative to other subtypes (OR 4.46; 95% CI 1.55, 12.80; p = 0.006) was associated with a better 12-month mRS. We found concordant associations for a composite outcome at 12 months, with the addition of a diagnosis of definite autoimmune limbic encephalitis (AILE) predicting a poor outcome.DiscussionOlder age, MRI T2/FLAIR hyperintensity, RSE and first-line immunotherapy failure predicted worse mRS and composite clinical-functional outcome at 12 months, while a diagnosis of anti-LGI1 antibody-mediated encephalitis was associated with favourable outcomes. Our data highlight acute clinical factors predictive of a more severe clinical and functional course at 12 months.