The value of the current histological scores and classifications of ANCA glomerulonephritis in predicting long-term outcome.

Background: Three different histological scores-histopathologic classification (Berden), Renal Risk Score (RRS) and the Mayo Clinic Chronicity Score (MCCS)-for anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (ANCA-GN) were compared to evaluate their association with patient and kidney prognosis of ANCA-GN. Methods: Patients aged >18 years with at least 1 year of follow-up and biopsy-proven ANCA-GN entered this retrospective study. Renal biopsies were classified according to Berden's classification, RRS and MCCS. The first endpoint was end-stage kidney disease (ESKD), defined as chronic dialysis or estimated glomerular filtration rate <15 mL/min/1.73 m2. The second endpoint was ESKD or death. Results: Of 152 patients 84 were males, with median age of 63.8 years and followed for 46.9 (interquartile range 12.8-119) months, 59 (38.8%) reached the first endpoint and 20 died. The Kaplan-Meier curves showed that Berden and RRS were associated with first (Berden: P = .004, RRS: P < .001) and second (Berden: P = .001, RRS: P < .001) endpoint, MCCS with the first endpoint only when minimal + mild vs moderate + severe groups were compared (P = .017), and with the second endpoint (P < .001). Among the clinical/histological presentation features, arterial hypertension [odds ratio (OR) = 2.75, confidence interval (95% CI) 1.50-5.06; P = .0011], serum creatinine (OR = 1.17, 95% CI 1.09-1.25; P < .0001), and the percentage of normal glomeruli (OR = 0.97, 95% CI 0.96-0.99; P = .009) were the independent predictors of ESKD at multivariate analysis. When the three scores were included in multivariate analysis, RRS (OR = 2.21, 95% CI 1.15-4.24; P = .017) and MCCS (OR = 2.03, 95% CI 1.04-3.95; P = .037) remained predictive of ESKD, but Berden (OR = 1.17, 95% CI 0.62-2.22; P = .691) did not. Conclusion: RRS and MCCS scores were independent predictors of kidney survival together with high serum creatinine and arterial hypertension at diagnosis, while Berden classification was not.

Acute Urticaria: Symptoms, Causes, and Evaluation of Phenotypes Prone to Chronicity.

INTRODUCTION: Urticaria is a condition that is characterized by the development of wheals (hives), angioedema, or both. If symptoms persist for less than 6 weeks, it is classified as acute urticaria (AU), and if they persist for longer than 6 weeks, it is classified as chronic urticaria (CU). Disease activity is evaluated using validated patient-reported outcome measures (PROMs) such as the 7-day urticaria activity score (UAS-7) and urticaria control test (UCT). In this study, we aimed to determine whether there was a difference between patients with chronic and recovered urticaria in terms of age, sex, symptoms, disease severity, disease control, and triggering factors by following patients with AU for 6 months. METHODS: The routine tests were requested at the first admission of the patients. If previously examined, anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody, etc., were recorded. After the first examination, the patients were evaluated again using a visual analog scale (VAS), UCT, UAS-7, and medication scores (MSs) in the 1st, 3rd, and 6th months. RESULTS: One hundred nine (F/M: 80/29) patients were included in the study. Twenty-seven patients had a previous history of AU, 22 of these patients were evaluated as having recurrent AU, and five became chronic during follow-up. Urticaria continued in 22 of 82 patients who presented with first-attack AU in the 3rd month and 17 in the 6th month. We had a chronicity rate of 24.7%. It was determined that having positive anti-TPO increased the risk of CU 1.69 times. A statistically significant improvement was found in the mean VAS, UCT, UAS-7, and MSs evaluated in the 1st, 3rd, and 6th months of patients with CU compared with baseline. CONCLUSION: AU is a common disease and usually heals in a short time without becoming chronic. Studies on the causes of chronicity are limited. Testing anti-TPO in patients presenting with AU may be useful in terms of disease course and risk of chronicity.

Direct-Acting Antiviral Treatment for Acute Hepatitis C in Japanese Patients: Clinical Course and Outcomes.

We diagnosed six cases of acute hepatitis C virus (HCV) infection at our hospital between October 2003 and December 2022. During the same period, we diagnosed 402 cases of chronic HCV infection and 636 cases of acute hepatic injury. Acute HCV infection cases accounted for 1.4% of all HCV infections and 0.9% of all acute hepatic injury cases. The acute HCV infection group was younger, had more severe hepatitis, and exhibited higher levels of bilirubinemia compared to the chronic HCV infection group. Two acute HCV infection cases achieved spontaneous viral clearance, while the remaining four cases progressed to chronic infection and were treated with direct-acting antivirals (DAAs). Liver enzyme elevation and liver function deterioration did not differ significantly between the acute HCV and other acute liver injury groups. Notably, DAA treatment was equally effective for acute and chronic HCV cases (75% vs. 90%, p = 0.34). Early DAA treatment in acute cases might contribute to interrupting viral transmission among high-risk populations, such as people who inject drugs or men who have sex with men. While there are currently no specific guidelines for acute HCV infection treatment in Japan, our findings suggest that DAA therapy should be initiated immediately following diagnosis. Further studies with larger patient cohorts are warranted to confirm these observations.

Setting the Stage for Cancer: Stay Soft and Optimistic.

In the Netherlands, one out of two people will be confronted with the diagnosis of cancer sometime in their life. Against this increased number of patients, a large proportion luckily can be cured. Today, a rather high proportion of people receive treatment to control cancer growth or stabilize the disease, sometimes, for the rest of their lives. If such long-standing treatment is administered for more than 10-20 years, the stage of cancer is presently often not referred to as "palliative" anymore, but much more often as "chronic." It could be argued that regardless of the cancer disease stage you are in and whether you are or can be cured, your cancer diagnosis nevertheless has become part of your life, including the experience of chronicity. Discussions surrounding the chronicity of cancer in the context of cancer are still ongoing. This is especially the case because "experiencing chronicity" is dependent on the type of cancer and is less applicable in cancers where the prognosis is often less than one year, such as is more frequently the case with lung or pancreatic cancer. In all situations, experiencing chronicity nevertheless brings along uncertainty, either with or without chronic stress. Combatting stress by choosing the right wording, maintaining an optimistic stance along with physical activity and/or psychosocial education seems important to optimize well-being and to stabilize tumor growth or remove the tumor. In conclusion, chronicity in the context of treating and caring for cancer seems a somewhat gray area. However, regardless in how we, as medical professionals, speak about cancer with long-standing disease trajectories (that sometimes even can be cured), it first of all seems important to approach, take care, and treat patients well. This can facilitate discussions with patients about their disease and disease experiences. Moreover, it can stimulate patients themselves to take responsibility for their own health, which can be of added value to the entire disease trajectory.

Clinical and histological comparison of IgA nephritis and renal IgA vasculitis.

BACKGROUND: IgA nephritis (IgAN) and renal IgA vasculitis (IgAV) show renal IgA deposits, but whether these two diseases are distinct entities or a spectrum of the same condition is under debate. In this study, we add perspective by contrasting the clinical course and histological presentation using the Oxford classification and the National Institutes of Health lupus nephritis activity index (LN-AI) and chronicity index (LN-CI) in IgAN and IgAV. METHODS: In this single-center, retrospective study, kidney biopsies of 163 adult patients with IgAN and 60 adult patients with IgAV were compared according to the Oxford MEST-C Score, LN-AI, and LN-CI. At the time of biopsy, clinical presentation was compared in terms of age, arterial hypertension, diabetes mellitus, extrarenal manifestations, as well as estimated glomerular filtration rate, proteinuria, and urine sediment. IgAV patients and all IgAN patients with crescents received immunosuppressive treatment. After biopsy, kidney function was followed until patients reached end-stage renal disease (ESRD) or they died. RESULTS: The clinical course and kidney histology differ in IgAN and IgAV. IgAV patients showed more microhematuria and nephritic sediment, while IgAN patients had a greater history of arterial hypertension, more proteinuria, and a higher risk for ESRD. These clinical differences were associated with histological differences, as kidney biopsies of IgAN patients were characterized by glomerulosclerosis and tubular atrophy, while kidney biopsies of IgAV patients were characterized by endocapillary hypercellularity and crescents. Overall, tubular atrophy and a LN-CI ≥ 4 were associated with a higher risk for ESRD in IgAN and IgAV. CONCLUSION: Our study supports the notion that IgAN and IgAV follow distinct courses, suggesting that they require different treatment strategies. Moreover, we make a point that the Oxford classification and LN-CI can be useful in categorizing and predicting long-term prognosis not only in IgAN, but also in IgAV.

Banff-based histologic chronicity index is associated with graft failure but has poor interobserver reproducibility.

BACKGROUND: Antibody-mediated rejection (AMR) often leads to chronic kidney allograft damage and is a critical cause of allograft failure. The Banff classification, used to diagnose AMR, has become complex and challenging for clinicians. A Banff-based histologic chronicity index (CI) was recently proposed as a simplified prognostic indicator. Its reliability and reproducibility have not been externally validated. METHODS: This study investigated 71 kidney allograft biopsies diagnosed with AMR. Interobserver reproducibility of the recently proposed CI and its components (cg, cv, ct, and ci) were assessed. The association between CI and allograft failure was analyzed, and CI cut-off values were evaluated by Cox proportional hazards regression and Kaplan-Meier estimator with log-rank test. RESULTS: The study confirmed the association of CI with allograft failure, but also revealed that the assessment of CI varied between pathologists, impacting its reproducibility as a prognostic tool. Only 49 (69.0%) of the biopsies showed complete agreement on the proposed cut-off value of CI < 4 or CI ≥ 4. Furthermore, this cut-off did not reliably stratify allograft failure. Notably, the cg score, which carries significant weight in the CI calculation, had the lowest agreement between observers (kappa = .281). CONCLUSIONS: While a simplified prognostic indicator for AMR is needed, this study highlights the limitations of CI, particularly its poor interobserver reproducibility. Our findings suggest that clinicians should interpret CI cautiously and consider establishing their own cut-off values. This study underscores the need to address interobserver reproducibility before CI can be widely adopted for AMR management.

Predictive Factors of Renal Recovery and Progression to End-Stage Kidney Disease in Patients With Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis With Severe Kidney Disease.

Introduction: A significant number of patients with antineutrophil cytoplasmic antibodies (ANCA)- associated vasculitis (AAV) with glomerulonephritis (AAV-GN) still progress to end-stage kidney disease (ESKD, estimated glomerular filtration rate [eGFR] <15 ml/min per 1.73 m2) despite advances in remission-induction treatment. Methods: This is a retrospective cohort study on myeloperoxidase (MPO)-ANCA or proteinase 3 (PR3)-ANCA positive patients with AAV (microscopic polyangiitis, MPA; or granulomatosis with polyangiitis, GPA) and eGFR <15 ml/min per 1.73 m2 or ESKD at presentation. Renal recovery, dialysis discontinuation, and persistence of ESKD after standard remission-induction, with or without the use of plasma exchange (PLEX) were analyzed. Results: We analyzed 166 patients with biopsy-proven active AAV-GN and eGFR <15 ml/min per 1.73 m2 at the time of diagnosis. Patients received glucocorticoids with cyclophosphamide (CYC) (n = 84) or with rituximab (RTX) (n = 72) for remission-induction, and 49 received PLEX. The predictors of renal recovery were erythrocyte sedimentation rate, serum creatinine (SCr) at diagnosis, and minimal or mild chronicity changes. We further analyzed 71 patients who started dialysis with or without PLEX within 4 weeks of AAV-GN diagnosis. The predictors of dialysis discontinuation were minimal chronicity changes in kidney biopsy at diagnosis (odds ratio = 6.138; 95% confidence interval [CI]: 1.389-27.118; P = 0.017). Predictors of persistence of ESKD within 12 months included higher SCr at diagnosis (incidence rate ratio [IRR] = 1.086; 95% CI: 1.005-1.173; P = 0.037), and moderate (IRR = 3.797; 95% CI: 1.090-13.225; P = 0.036), or severe chronicity changes in kidney biopsy (IRR = 5.883; 95% CI: 1.542-22.439; P =0.009). Conclusion: In our cohort, kidney recovery, dialysis discontinuation, and persistence of ESKD in patients with AAV-GN and eGFR <15 ml/min per 1.73 m2 depended on SCr and histologic findings on kidney biopsies at the time of diagnosis and was not affected by the addition of PLEX.

[An analysis on clinical characteristics and prognosis-related risk factors in patients with drug-induced liver injury].

Objective: To explore the drugs and clinical characteristics causing drug-induced liver injury (DILI) in recent years, as well as identify drug-induced liver failure, and chronic DILI risk factors, in order to better manage them timely. Methods: A retrospective investigation and analysis was conducted on 224 cases diagnosed with DILI and followed up for at least six months between January 2018 and December 2020. Univariate and multivariate logistic regression analyses were used to identify risk factors for drug-induced liver failure and chronic DILI. Results: Traditional Chinese medicine (accounting for 62.5%), herbal medicine (accounting for 84.3% of traditional Chinese medicine), and some Chinese patent medicines were the main causes of DILI found in this study. Severe and chronic DILI was associated with cholestatic type. Preexisting gallbladder disease, initial total bilirubin, initial prothrombin time, and initial antinuclear antibody titer were independent risk factors for DILI. Prolonged time interval between alkaline phosphatase (ALP) and alanine aminotransferase (ALT) falling from the peak to half of the peak (T(0.5ALP) and T(0.5ALT)) was an independent risk factor for chronic DILI [area under the receiver operating characteristic curve (AUC) = 0.787, 95%CI: 0.697~0.878, P < 0.001], with cutoff values of 12.5d and 9.5d, respectively. Conclusion: Traditional Chinese medicine is the main contributing cause of DILI. The occurrence risk of severe DILI is related to preexisting gallbladder disease, initial total bilirubin, prothrombin time, and antinuclear antibodies. T(0.5ALP) and T(0.5ALT) can be used as indicators to predict chronic DILI.

Severe enduring anorexia nervosa (SE-AN) treatment options and their effectiveness: a review of literature.

INTRODUCTION:  For nearly 20% of patients diagnosed with Anorexia Nervosa (AN), the eating disorder (ED) is prolonged and becomes long-lasting. It has been reported that patients diagnosed with Severe Enduring Anorexia Nervosa (SE-AN) have worse ED symptoms, higher rates of lifetime hospitalization, and lower psychosocial well-being compared to patients with shorter disease duration. OBJECTIVES:  This review aims to describe the treatments proposed to date and their effectiveness on SE-AN-related outcomes. METHODS:  We conducted a PubMed search for studies addressing the issue of treatment approach to SE-AN adults, that were published between 2003 and 2023, peer-reviewed, written in the English language, and available in full-text. Next, we inductively created relevant macro-themes by synthesizing the data from the included articles. RESULTS:  Of 251 PubMed studies, 25 articles were considered for data extraction, all published between 2003 and 2022. We identified three macro-themes. The first macro-theme, "Psychotherapy", mostly takes into consideration treatment effectiveness of cognitive behavioral therapy (CBT). Various reports determined its greater effectiveness compared to Specialist Supportive Clinical Management (SSCM), and one study proved that outpatient CBT is a valid alternative to hospitalization. The second one involves "Pharmacological Treatments". Research on dronabinol, a synthetic orexigenic cannabinoid, antipsychotics (in particular, olanzapine and haloperidol), and ketamine showed some mixed results regarding the often-complementary areas of weight gain and improvement in ED-related symptoms. Regarding the third macro-theme, "Brain Stimulation Therapies," such as Repetitive Transcranial Magnetic Stimulation (rTMS) and Deep Brain Stimulation (DBS), we found promising results in improving ED-related psychological traits (such as mood and anxiety), affective regulation, and quality of life. However, we have observed divergent results regarding outcome measures such as BMI and weight gain. CONCLUSIONS:  SE-AN patients are predicted to encounter both medical complications and psychological distress of increasing severity that will inevitably affect their quality of life; to our knowledge, research evidence on treatment options for SE-AN remains limited, and the methodological quality of studies is generally low. These findings denote the need to focus future research efforts on effective treatment strategies specific to long-lasting EDs.

For nearly 20% of patients diagnosed with Anorexia Nervosa, the eating disorder is prolonged and becomes long-lasting. Those patients have worse ED symptoms, higher rates of lifetime hospitalization, and lower psychosocial well-being compared to patients with shorter disease duration. This review aims to describe the treatments proposed to date and their effectiveness on severe enduring anorexia nervosa related outcomes. The data obtained show how the intervention techniques primarily used in these patients are psychotherapy (in particular, cognitive behavioral therapy and Specialist Supportive Clinical Management), pharmacological treatments, and Brain Stimulation Therapies (such as Repetitive Transcranial Magnetic Stimulation and Deep Brain Stimulation). To our knowledge, research evidence on treatment options for SE-AN remains limited and these findings denote the need to focus future research efforts on effective treatment strategies specific to long-lasting eating disorders.

Reproducibility and prognostic ability of chronicity parameters in kidney biopsy - Comprehensive evaluation comparing microscopy and artificial intelligence in digital pathology.

INTRODUCTION: Semi-quantitative scoring of various parameters in renal biopsy is accepted as an important tool to assess disease activity and prognostication. There are concerns on the impact of interobserver variability in its prognostic utility, generating a need for computerized quantification. METHODS: We studied 94 patients with renal biopsies, 45 with native diseases and 49 transplant patients with index biopsies for Polyomavirus nephropathy. Chronicity scores were evaluated using two methods. A standard definition diagram was agreed after international consultation and four renal pathologists scored each parameter in a double-blinded manner. Interstitial fibrosis (IF) score was assessed with five different computerized and AI-based algorithms on trichrome and PAS stains. RESULTS: There was strong prognostic correlation with renal function and graft outcome at a median follow-up ranging from 24 to 42 months respectively, independent of moderate concordance for pathologists scores. IF scores with two of the computerized algorithms showed significant correlation with estimated glomerular filtration rate (eGFR) at biopsy but not at the end of follow-up. There was poor concordance for AI based platforms. CONCLUSION: Chronicity scores are robust prognostic tools despite interobserver reproducibility. AI-algorithms have absolute precision but are limited by significant variation when different hardware and software algorithms are used for quantification.

Significance of the total renal chronicity score in predicting renal outcome in PLA2R-associated membranous nephropathy.

BACKGROUND: Phospholipase A2 receptor (PLA2R)-associated membranous nephropathy accounts for the majority of membranous nephropathy; however, few studies have determined the prognostic impact and clinical application of renal pathologic change on this disease. METHODS: A retrospective cohort study of 262 patients with PLA2R-associated membranous nephropathy was conducted. The total renal chronicity score calculated according to the degree of glomerulosclerosis, interstitial fibrosis, tubular atrophy, and arteriosclerosis was applied to evaluate renal chronicity. Baseline bias was adjusted by inverse probability weight when assessing the prognostic impact of chronicity, and multiple parameters were used to evaluate the application value of renal chronicity. RESULTS: During a median follow-up of 24.5 months, renal outcome (kidney function deterioration and/or end-stage kidney disease) was observed in 22 (8.40%) patients. Not only did a higher total renal chronicity score independently predict renal outcome [odds ratio (OR): 1.562, 95% confidence interval (CI) 1.073-2.273, P = 0.020], but non-minimal chronicity was also an independent risk factor for renal outcome (OR: 3.170, 95% CI 1.040-9.659, P = 0.042). Moreover, the membranous nephropathy risk classification in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline integrated with non-minimal chronicity showed improvements in categorical net reclassification (0.174, 95% CI 0.012-0.335, P = 0.035), continuous net reclassification (0.462, 95% CI 0.087-0.838, P = 0.016), and integrated discrimination (0.019, 95% CI 0.003-0.035, P = 0.020) compared to the original classification. CONCLUSIONS: Renal chronicity is closely associated with renal outcomes in PLA2R-associated membranous nephropathy, and combining the KDIGO risk classification with chronicity scores may provide a more accurate prognostic prediction.

Risk Factors for Rerupture After Proximal Hamstring Avulsion Injury Including the Optimal Timing for Surgery.

BACKGROUND: Despite the prevalence of proximal hamstring avulsion injuries (PHAIs), the understanding of rerupture risk factors and the influence of injury chronicity on these rates remain limited. PURPOSE: To investigate the rerupture rate after PHAI repair and identify its associated risk factors and the optimal time to primary surgery. STUDY DESIGN: Case-control study; Level of evidence, 3. METHOD: This is a retrospective analysis of prospectively collected data from the French Proximal Hamstring Avulsion Surgery Cohort Study targeting patients surgically treated for PHAI between 2002 and 2022. The primary outcome measure of this study was the rerupture rate of PHAI repair. The secondary outcome measures included the assessment of the potential risk factors for rerupture as well as the investigation of the incidence rate of rerupture for 100 person-years depending on various injury-surgery delay definitions. RESULTS: This study analyzed 740 patients with a mean age of 45.9 years (SD, 13.6 years) and followed up for a mean of 4.9 years (SD, 3.9 years). The rerupture rate was 4.59% (34/740). Most reruptures (75%) occurred within the first 6 months after surgery (median, 88.5 days; interquartile range, 39.5-182 days), and 74% were atraumatic. Univariate analysis identified potential risk factors: longer initial surgery delay (hazard ratio [HR], 1.03; 95% CI, 1.01-1.04; P = .04) and initial complete ruptures (HR, 4.47; 95% CI, 1.07-18.7; P = .04). Receiver operating characteristic curve analysis found the optimal injury-surgery delay cutoff predicting rerupture to be 32 days (area under the curve, 0.62; 95% CI, 0.53-0.71). The relative Youden index was calculated at 0.24, corresponding to a sensitivity of 65% and a specificity of 59%. Surpassing this cutoff showed the highest HR (2.56), narrowest 95% CI (1.27-5.17), and highest incidence of rerupture (1.42 per 100 person-years) (P = .01). In the multivariate analysis, an injury-surgery delay of >32 days (HR, 2.5; 95% CI, 1.24-5.06; P = .01) and initial complete ruptures (HR, 4.33; 95% CI, 1.04-18.08; P = .04) emerged as significant risk factors for rerupture. CONCLUSION: This study found a 4.59% rerupture risk after PHAI repair. Most reruptures (75%) occurred within the first 6 months after surgery. Risk factors for rerupture included chronicity and initial complete injury. The optimal threshold for chronicity of PHAI lesions, based on rerupture rate, was marked by an injury-surgery delay of >32 days.

Integrins regulation of wound healing processes: insights for chronic skin wound therapeutics.

Integrins are heterodimers composed of non-covalently associated alpha and beta subunits that mediate the dynamic linkage between extracellular adhesion molecules and the intracellular actin cytoskeleton. Integrins are present in various tissues and organs and are involved in different physiological and pathological molecular responses in vivo. Wound healing is an important process in the recovery from traumatic diseases and consists of three overlapping phases: inflammation, proliferation, and remodeling. Integrin regulation acts throughout the wound healing process to promote wound healing. Prolonged inflammation may lead to failure of wound healing, such as wound chronicity. One of the main causes of chronic wound formation is bacterial colonization of the wound. In this review, we review the role of integrins in the regulation of wound healing processes such as angiogenesis and re-epithelialization, as well as the role of integrins in mediating bacterial infections during wound chronicity, and the challenges and prospects of integrins as therapeutic targets for infected wound healing.

[Spontaneous remission of urticaria: does it exist and if so, when?] / Spontanremission der Urtikaria: Gibt es das, und wenn ja, wann?

BACKGROUND: Urticaria mostly occurs acutely with a very high probability of spontaneous remission. When it persists for more than 6 weeks a chronic urticaria is manifest, which occurs either spontaneously or inducible by specific triggers. The underlying mechanisms are not fully understood but recent research points to defined pathogenetic factors. QUESTION AND AIM: Whether spontaneous remission is possible in urticaria is summarized descriptively in this review, and suggestions are given for the "step down" of urticaria treatment after remission. The mechanisms including autoallergic, immunoglobulin E (IgE)-dependent type I reactions and autoimmune, activating IgG-dependent type IIb reactions are presented. These are discussed in the context of spontaneous remission and the possibilities of induced remission.

Association between psychiatric admissions in patients with schizophrenia and IL-6 plasma levels polygenic score.

Schizophrenia diagnosis and admission history were associated with a polygenic score (PGS) for schizophrenia based on a subset of variants that act by modifying the expression of genes whose expression is also modified by antipsychotics. This gene set was enriched in cytokine production. Interleukin-6 (IL-6) is the only cytokine whose plasma levels were associated both with schizophrenia diagnosis and with acute decompensations in the largest meta-analysis. Therefore, we hypothesized that an IL-6 PGS, but not other cytokines PGSs, would be associated with schizophrenia chronicity/psychiatric admissions. Using the IL-6 PGS model from The PGS Catalog, IL-6 PGS was calculated in 427 patients with schizophrenia and data regarding admission history. Association between IL-6 PGS and chronicity, measured as number and duration of psychiatric admissions, or ever readmission was analyzed by multivariate ordinal and logistic regression, respectively. Specificity of results was assessed by analysis of PGSs from the other cytokines at The PGS Catalog with meta-analytic evidence of association with schizophrenia diagnosis or acute decompensations, IL-1RA, IL-4, IL-8, and IL-12. IL-6 PGS was associated with schizophrenia chronicity, explaining 1.51% of variability (OR = 1.29, 95% CI 1.07-1.55, P = 0.007). There was no association with ever readmission. Other cytokines PGSs were not associated with chronicity. Association with IL-6 PGS was independent of association with schizophrenia PGS. Our results provide evidence that genetically regulated higher levels of IL-6 are involved in schizophrenia chronicity, highlighting the relevance of immunity processes for a subgroup of patients.

Intimate Partner Violence-Related Brain Injury: Unmasking and Addressing the Gaps.

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Kidney Diseases Associated With Inflammatory Bowel Disease: Impact of Chronic Histologic Damage, Treatments, and Outcomes.

Introduction: Kidney disease is a well-known extraintestinal manifestation (EIM) associated with inflammatory bowel disease (IBD), with a variety of underlying etiologies. However, little is known about the overall outcomes and predictors. Methods: This is a retrospective, observational cohort study. Patients with IBD in whom a native kidney biopsy was performed at Mayo Clinic (Rochester, MN) between 1994 and 2022, were included. Demographic, clinical, and histologic characteristics of prognostic interest were collected. The main outcomes were kidney failure, disease remission, kidney function changes at last follow-up, and death. Results: From a total cohort of 318 patients, we selected a study group of 111 patients followed-up with at our institution (45 ulcerative colitis [UC] and 66 Crohn's disease [CD]), with a mean age of 48 ± 17 years (40% females). IgA nephropathy (IgAN), chronic interstitial nephritis (CIN), and acute interstitial nephritis (AIN) were the most common diagnoses (22%, 19%, 13%, respectively). Median estimated glomerular filtration rate (eGFR) at presentation was 30 ml/min per 1.73 m2 (interquartile range [IQR]: 17-54) and urinary protein-to-creatinine ratio [UPCR] 0.8 g/g (0.3-3.4), without differences between IBD types. During a median follow-up of 59 months (12-109), 29 patients (26%) reached kidney failure. By multivariable analysis, the main predictors of kidney failure were age (hazard ratio [HR]: 1.04; P = 0.002), baseline eGFR (HR: 0.94; P = 0.003) and histologic chronicity score (HR: 4.01; P < 0.001). Therapeutic management varied according to underlying etiology. Global survival (kidney failure + death) was significantly better in patients who achieved complete or partial remission, or stabilization or improvement of kidney function. Conclusion: One-fourth of patients with IBD with kidney disease may reach kidney failure, and the main determinants of this outcome is age, baseline eGFR, and degree of chronicity in kidney biopsy.

Non-invasive prediction of the chronic degree of lupus nephropathy based on ultrasound radiomics.

OBJECTIVE: Through machine learning (ML) analysis of the radiomics features of ultrasound extracted from patients with lupus nephritis (LN), this attempt was made to non-invasively predict the chronicity index (CI)of LN. METHODS: A retrospective collection of 136 patients with LN who had renal biopsy was retrospectively collected, and the patients were randomly divided into training set and validation set according to 7:3. Radiomics features are extracted from ultrasound images, independent factors are obtained by using LASSO dimensionality reduction, and then seven ML models were used to establish predictive models. At the same time, a clinical model and an US model were established. The diagnostic efficacy of the model is evaluated by analysis of the receiver operating characteristics (ROC) curve, accuracy, specificity, and sensitivity. The performance of the seven machine learning models was compared with each other and with clinical and US models. RESULTS: A total of 1314 radiomics features are extracted from ultrasound images, and 5 features are finally screened out by LASSO for model construction, and the average ROC of the seven ML is 0.683, among which the Xgboost model performed the best, and the AUC in the test set is 0.826 (95% CI: 0.681-0.936). For the same test set, the AUC of clinical model constructed based on eGFR is 0.560 (95% CI: 0.357-0.761), and the AUC of US model constructed based on Ultrasound parameters is 0.679 (95% CI: 0.489-0.853). The Xgboost model is significantly more efficient than the clinical and US models. CONCLUSION: ML model based on ultrasound radiomics features can accurately predict the chronic degree of LN, which can provide a valuable reference for clinicians in the treatment strategy of LN patients.

Complexity of needs in amyotrophic lateral sclerosis (ALS) patients using the ENP-E scale in the north-eastern region of Spain.

OBJECTIVES: This study aimed to explore the clinical characteristics of amyotrophic lateral sclerosis (ALS) patients in Spain's north-eastern region, their inclusion in chronic care programmes, and their psychosocial and spiritual needs (PSNs). METHODS: A longitudinal descriptive study in adult patients with ALS. We analyzed clinical variables and participation in chronicity and PSNs assessment using the tool Psychosocial and Spiritual Needs Evaluation scale in end-of-life patients (ENP-E scale). RESULTS: 81 patients (average age 65.6 ± 11.7) were studied. At the study's outset, 29.7% employed non-invasive ventilation (NIV), increasing to 51.9% by its conclusion. Initial percutaneous endoscopic gastrostomy (PEG) utilization was 14.8%, rising to 35.85%. Chronic care programme participation was as follows: home care (24.7% initially, 50.6% end), palliative care (16% initially, 40.7% end), case management (13.6% initially, 50.6% end), and advance care planning registration (6.2% initially, 35.8% end). At study start, 47.8% of patients (n = 46) showed moderate-to-severe complexity in PSNs assessment using the ENP-E scale, without showing differences in age, sex, and time of evolution; whereas, on the evolutionary analysis, it was 75% (n = 24). A higher evolutionary complexity was observed in males <60 and >70 years, with no PEG and evolution of ALS of <2 and ≥5 years, and not included in chronicity programmes. When assessing concerns, physical pain and family aspects stand out in all measurements. Forty-eight percent of patients at study start and 71% at end of study showed external signs of emotional distress. SIGNIFICANCE OF RESULTS: Most ALS patients showed a high degree of complexity and were not integrated in chronicity programmes. A "care path" is proposed to integrate ALS patients in these programmes and systematically assess their needs.