Diagnostic Criteria Research Articles

A loop-mediated isothermal amplification test for yaws: a multi-country diagnostic accuracy evaluation

To meet the WHO target of eradicating yaws by 2030, highly sensitive and specific diagnostic tools are needed. A multiplex Treponema pallidum-Haemophilus ducreyi loop-mediated isothermal amplification (TPHD-LAMP) test holds promise as a near-patient diagnostic tool for yaws and H ducreyi. We conducted a prospective evaluation in Cameroon, Côte d'Ivoire, Ghana, and the Republic of the Congo to determine the diagnostic accuracy of the TPHD-LAMP test, as well as to assess its acceptability, feasibility, and cost. Active case searching within schools and communities was used to locate participants with clinically suspicious laws-like lesions. Individuals with serologically confirmed active yaws provided paired lesion swabs between March, 2021, and April, 2023. For each participant, one swab was tested with the TPHD-LAMP at a local district laboratory and the other with reference quantitative PCR (qPCR) tests conducted at national reference laboratories. The primary outcome was TPHD-LAMP test sensitivity and specificity compared with qPCR. Laboratory technicians were interviewed using a multiple-choice survey to gauge acceptability and feasibility of the TPHD-LAMP test. Costs of each test were calculated. Of 3085 individuals with at least one suspected yaws lesion, 531 (17%) were serologically confirmed. We enrolled 493 participants with seropositive yaws and a further 32 with negative serology. The sensitivity of the TPHD-LAMP test for detecting T pallidum was 63% (95% CI 56-70) and the specificity was 66% (95% CI 61-71). Sensitivity and specificity for T pallidum improved to 73% (63-82; p=0·0065) and 75% (68-80; p=0·0003), respectively, in H ducreyi-negative samples. Interviews highlighted challenges in user-friendliness and practicality of the TPHD-LAMP test. The cost of the test per sample was one third of that of qPCR, although the TPHD-LAMP test entailed higher costs to establish the assay. This was the first multi-country diagnostic evaluation of a molecular test for yaws. The TPHD-LAMP testing, in its current form, falls short of the WHO target product profile criteria for yaws diagnostics. These findings highlight the importance of assessing new diagnostics in real-world conditions to ensure their suitability for programmatic use. The EDCTP2 programme supported by the EU.

Multilocular Cystic Renal Neoplasia of Low-grade Malignant Potential: Evolving Diagnostic Criteria: A Case Report with Review of Literature

Multilocular Cystic Renal Neoplasm of Low Malignant Potential (MCRNLMP) is a distinct type of clear cell renal tumor. The diagnostic histological criteria for this entity have evolved, and specific histological features have been modified over the years. The WHO 2022 of Male Urinary System and Male Genital Tumours respecified diagnostic histopathological features. Maximum tumors are asymptomatic and are incidentally detected on radiological examination. Computed tomography using contrast agents is still the gold standard for classifying cystic tumors of kidney. The Bosniak category of renal cystic lesions is crucial for the management of other imaging modalities such as magnetic resonance imaging (MRI) and contrast-enhanced ultrasound, which can be used with the same effectiveness. The prognosis is excellent in MCRNLMP, and there are no reports of cancer progression or metastasis. Minimally invasive nephron-sparing surgery with strict clinical including imaging follow-up with contrast-enhanced computerized tomography and magnetic resonance imaging is a choice of treatment.

Simultaneous diagnosis of adult-onset Still's disease and lymphoma: A case report and systematic review of the literature.

Differentiating Adult-Onset Still's Disease (AOSD) from lymphoma is challenging. A 23-year-old female presented with polyarthralgia, fever, rash, lymphadenopathy, and abnormal labs. She met AOSD criteria and was diagnosed with non-Hodgkin lymphoma. Treatment led to improvement. The differentiation between Adult-onset Still's Disease (AOSD) and lymphoma remains challenging in our context. The Faustrel score facilitates the simultaneous diagnosis of these conditions. A 23-year-old woman presented with chronic polyarthralgia in a febrile context. A physical examination revealed peripheral joint syndrome, a maculopapular rash on the trunk, and peripheral lymphadenopathy. Laboratory tests showed neutrophils leukocytosis, hyperferritinemia, and a glycosylated ferritin fraction of 12%. A lymph node biopsy revealed a malignant non-Hodgkin lymphoma, and the patient met the diagnostic criteria for AOSD according to Faustrel. She received corticosteroid therapy and four courses of Rituximab. After 6 months, clinical and biological improvements were noted. It is essential to consider the possibility of an association between atypical clinical presentations of lymphoma and AOSD.

Metastatic Renal Cell Carcinoma with Fibromyomatous Stroma associated with Tuberous Sclerosis or MTOR, TSC1/TSC2-Mutations: A Series of 4 Cases and a Review of the Literature

Renal cell carcinoma with fibromyomatous stroma (RCCfms) are characterized by a constellation of morphologic findings that include elongated tubules lined by cells with clear to pale eosinophilic cytoplasm and intersecting bands of smooth muscle stroma. Consistent immunohistochemistry findings in RCCfms include diffuse positivity for carbonic anhydrase 9 and variable expression of keratin 7. Molecular profiling of such tumors show either pathogenic alterations of the ELOC (TCEB1) gene, or alterations of MTOR, TSC1, and TSC2. MTOR, TSC1/TSC2-altered RCCfms (M/TSC-RCCfms) has been reported both in the sporadic setting and in association with tuberous sclerosis complex (TSC). The importance of accurate diagnosis of M/TSC-RCCfms includes prompting germline testing in the appropriate clinical context. In addition, it can lead to patient management strategies that are focused on the preservation of renal function, as TSC patients often have multifocal and bilateral disease. As diagnostic criteria for M/TSC-RCCfms have only been recently established, additional data are needed to understand the natural history of this disease. Herein, we report 6 patients with metastatic M/TSC-RCCfms, including four patients from our institutional archives (four males, aged 36 to 58 years at nephrectomy), and two additional cases reported in the literature. Five patients had TSC, and the sixth had an MTOR-altered RCCfms. The majority of patients (5/6, 83%) presented with regional lymph node involvement and one patient developed metastases to the lung. All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.

Correlating symptom severity index, clinical diagnostic criteria of CTS-6 and timed Phalen’s test in clinical evaluation of carpal tunnel syndrome

ABSTRACT Background: Carpal Tunnel Syndrome (CTS) poses significant diagnostic challenges, especially in resource-limited settings. Reliable tools such as the 6-item Symptom Severity Index, Timed Phalen’s Test (TPT) and CTS-6 are promising but under investigated. Correlation between these tools and symptom severity remains underexplored. Aim: To correlate the 6-item Symptom Severity Index and CTS-6 diagnostic tool with TPT in clinically diagnosed CTS cases, evaluating their diagnostic performance. Methods: Prospective cross-sectional study, conducted in a tertiary care hospital in eastern India. 105 patients were enrolled after fulfilling inclusion criteria, assessing them with the 6-item Symptom Severity Index, CTS-6 diagnostic tool and TPT. Pearson’s and Spearman’s correlation coefficients were used, and statistical significance was set at P < 0.05. Results: Of 188 evaluated hands, TPT showed a significant negative correlation with CTS-6 scores (r = -0.59, P < 0.0001), indicating lower scores with higher TPT values. CTS-6 scores positively correlated with symptom severity (r = 0.34, P < 0.0001), indicating higher Symptom Severity Indices associated with increased diagnostic probability. Positive predictive value for TPT was 70.1%, with sensitivity of 83.7% and specificity of 61.1%. Symptom Severity Indexing demonstrated higher sensitivity (100%) but lower specificity (3.3%). Conclusions: This study highlights the utility of integrating subjective and objective assessment tools in CTS diagnosis. The findings underscore the importance of comprehensive evaluation and suggest the potential value of TPT as an adjunctive diagnostic tool. Further research is warranted to validate these findings and refine diagnostic algorithms for CTS management.

Renal nutcracker syndrome presenting with varicocele: A case series

Introduction and importanceNutcracker syndrome (NCS) is a rare condition characterized by left renal vein compression and presents with diverse clinical manifestations. This case series study aims to evaluate the clinical presentations and outcomes of patients with NCS and varicocele. Case presentationWe reviewed the cases of four male patients, aged 15 to 19 years, who presented with recurrent and grade 3 varicocele after varicocelectomy. All patients reported pain in the hypogastric, flank, or groin areas. Despite the absence of hematuria, NCS was diagnosed based on duplex ultrasound and contrast-enhanced computed tomography (CT) scans. Patients underwent open surgical interventions, including gonadal vein transposition or saphenous vein bypass. Clinical discussionThe absence of hematuria in these cases poses a diagnostic challenge, as current diagnostic criteria for NCS relies on its presence. Our findings underscore the need to consider NCS in patients with varicocele, even in the absence of hematuria. Surgical interventions were effective in resolving the symptoms. After NCS surgery, the varicocele in one patient resolved, and three patients underwent varicocelectomy successfully without recurrence throughout the recovery period. ConclusionThis case series highlights the diagnosis of NCS presenting with varicocele and local pain without hematuria, emphasizing the need for improved diagnostic and management approaches.

Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes: A Nationwide Study on Epidemiology and Antibody Testing Performance.

Autoimmune encephalitis (AIE) and paraneoplastic neurologic syndromes (PNSs) encompass a heterogeneous group of antibody-associated disorders. Both the number of syndromes and commercially available antibody tests have increased considerably over the past decade. High-quality population-based data on epidemiology of these disorders and real-world performance of antibody tests are needed. In this nationwide retrospective cohort study, we identified all serum and CSF samples tested for antibodies against intracellular antigens (IAs: Hu [ANNA1], Yo [PCA1], CV2 [CRMP5], Ri [ANNA2], Ma1, Ma2 [Ta], amphiphysin, GAD65, GFAP, KLHL11, CARP VIII) or extracellular antigens (EAs: NMDAR, LGI1, Caspr2, GABA-B-R, GABA-A-R, AMPAR, DPPX, GlyR, mGluR1, VGCC, IgLON5, Tr [DNER]) between January 2016 and December 2021 in the Netherlands. Nationwide coverage was guaranteed for all antibodies except anti-GAD65 and anti-VGCC. We calculated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV); obtained clinical information about patients who tested positive; assigned diagnosis of AIE/PNS according to diagnostic criteria; and calculated incidence rates for IA, EA, and individual antibody-associated syndromes. In the study period, 2,877 (9.5%) of 30,246 samples, belonging to 1,228 patients, tested positive. Sensitivity and specificity were high (>95%) to very high (>99%) for most tests in both serum and CSF. PPVs for several tests were moderate to poor, especially for serum testing of IA antibodies (25%-80%). Clinical data were available for 940 (76.5%) of 1,228 patients. A total of 578 AIE/PNS diagnoses were made. The incidence rate for AIE/PNS (per million person-years) increased from 4.70 (95% CI 3.72-5.85) in 2016 to 5.76 (4.69-7.00) in 2021. Overall, the incidence rate was 5.57 (5.13-6.05), 2.96 (2.64-3.31) for the EA and 2.61 (2.31-2.94) for the IA subgroup. The 4 most common AIE/PNS types were anti-NMDAR, anti-LGI1, anti-Hu, and anti-GAD65, together comprising almost two-thirds of all diagnoses (364/578, 63.0%). Most commercial antibody tests perform well overall, but important pitfalls remain. Although almost all tests had high specificity, PPV was only modest in the setting of these rare diseases and mass testing. We observe trends toward increasing incidence of antibody-associated AIE/PNS.

Electrokinetic indices of erythrocytes as diagnostic criteria for preeclampsia

Objective. To evaluate the features of changes in the morphofunctional status of peripheral blood erythrocytes during normal pregnancy and in preeclampsia based on rapid analysis of biophysical parameters of cells.Materials and methods. A total of 136 pregnant women were examined at 22–24 and 34–35 weeks of gestation. The comparison groups included: 40 pregnant women with moderate preeclampsia (PE), 30 pregnant women with severe preeclampsia, 30 pregnant women with chronic arterial hypertension (CAH), 36 women with normal pregnancy who do not have signs of hypertensive disorders. Electrokinetic features of peripheral blood erythrocytes were studied using cellular microelectrophoresis, the average value of the amplitude of oscillations of mobile erythrocytes (μm) and the proportion of mobile cells (%) were analyzed.Results. At 22–24 weeks, the percentage of immobile erythrocytes in pregnant women with moderate PE increased by 2.8 times (p<0.05), the amplitude of oscillations of mobile cells decreased by 21% (p<0.05). In pregnant women with severe PE, the proportion of immobile erythrocytes increased by 3.2 times (p<0.05), the amplitude decreased by 30% (p<0.05). In pregnant women with CAH, a slight increase in the percentage of immobile cells (8.2 vs 6.8%) and a tendency to a decrease in the average amplitude (21.5 vs 23.2 μm) were noted. At 34–35 weeks in the group with moderate PE, the% of immobile erythrocytes exceeded the corresponding indicator in women with physiological pregnancy by 3.3 times (p<0.05), the average amplitude decreased by 28% (p<0.05), in pregnant women with severe PE, the% of immobile erythrocytes increased by 3.7 times (p<0.05), the amplitude decreased by 36% (p<0.05). In pregnant women with CAH, there was a tendency for a slight increase in the proportion of immobile erythrocytes.Conclusion. The functional and morphological usefulness of erythrocytes as active participants in the pathogenesis of preeclampsia can be objectively assessed using indicators of electrokinetic activity of cells, and erythrocytes can be considered as biomarkers of the disease and a promising tool for stratifying patients for early detection of high-risk pregnancies.

Altered functional connectivity of unimodal sensory and multisensory integration networks is related to symptom severity in autism spectrum disorders

BackgroundAtypical sensory processing is a prevalent feature in autism spectrum disorders (ASD) and constitutes a core diagnostic criterion in the Diagnostic and Statistical Manual of Mental of Disorders, 5th edition (DSM-5). However, neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear. MethodsThis study examined intrinsic functional connectivity (FC) patterns among five unimodal sensory and multisensory integration (MSI) networks in ASD with a large multi-site dataset (n = 646), and investigated the relationships among altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms with correlation and mediation analyses. ResultsRelative to typically developing (TD) controls, the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI-unimodal-sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits. ConclusionsASD-specific olfactory overconnectivity and MSI-unimodal-sensory underconnectivity lend support to the Intense World Theory and Weak Central Coherence Theory, suggesting olfactory hypersensitivity at the expense of multisensory integration as potential neural mechanisms underlying atypical sensory processing in ASD. These atypical FC patterns further suggest potential targets for psychological and neuromodulatory interventions.

Gold Coast Criteria: A New Diagnostic Paradigm in the Era of Disease-Modifying Therapy for Amyotrophic Lateral Sclerosis

Significant progress has been made in the development of disease-modifying drugs for amyotrophic lateral sclerosis (ALS), with the introduction of tofersen, an antisense oligonucleotide drug for familial ALS, marking a turning point in the treatment. These drugs are most effective when administered early in the disease course, highlighting the need for improved diagnostic sensitivity. The 2020 Gold Coast Diagnostic Criteria allow ALS diagnosis in cases without upper motor neuron symptoms, potentially increasing early detection rates. However, careful differential diagnoses are necessary when applying these criteria to maintain diagnostic specificity. This review outlines the key points to consider when using the Gold Coast Criteria, balancing the need for an early diagnosis with caution to avoid overdiagnosis.

Chronic Non-bacterial Osteomyelitis (CNO) In Childhood: A Review.

Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disorder mostly affecting children and adolescents. Although it is considered a rare disease, CNO is likely to be the single most common autoinflammatory bone disease in childhood, underdiagnosed and underreported due to a lack of awareness of the condition in both medics and patients and the absence of validated diagnostic criteria. The exact underlying pathogenesis of CNO remains unknown, making targeted treatment difficult. This issue is exacerbated by the lack of any randomised control trials, meaning that treatment strategies are based solely on retrospective reviews and case series. This review summarises the current concepts in pathophysiology, the clinical features that help differentiate important differential diagnoses, and an approach to investigating and managing children with CNO. Ultimately, the timely and thorough investigation of children and young people with CNO is vitally important to exclude important mimics and initiate appropriate management that can prevent the complications of persistent inflammatory bone disease.

Echocardiographic Assessment of Cardiac Remodeling According to Obesity Class

Evidence supports the existence of cardiac remodeling in obesity, but no standard diagnostic criteria has been proposed or validated.The objective of this study was to identify echocardiographic features of cardiac remodeling according to obesity class and assess the effect of non-surgical weight loss on cardiac structure and function.A total of 120 patients were divided according to their obesity class (Group 1: BMI 18.5-24.9; Group 2: 25-29.9; Group 3: 30-39.9; Group 4: >40) and underwent cross-sectional transthoracic echocardiography. Echocardiographic parameters of cardiac chamber quantification and function were compared between the 4 groups. Echocardiographic parameters were compared pre- and post-non-surgical weight loss in a subgroup of patients. Overall, there was an incremental increase in left ventricular (LV), left atrial (LA), and right ventricular dimensions, LV mass and LV stroke volume (all p<0.0001) across obesity classes. There was no significant difference in LV ejection fraction or right ventricular systolic function as assessed by tricuspid annular plane systolic excursion (TAPSE) but a significant decrease in global longitudinal strain (BMI 18.5-24.9: 22.8%±1.7%; BMI 25-29.9: 22.0%±1.4%; BMI 30-39.9: 20.8%±1.1%; BMI >40: 20.6%±1.3%, p<0.0001) and left atrial strain (BMI 18.5-24.9: 37.7%±2.3%; BMI 25-29.9: 32.8%±2.1%; BMI 30-39.9: 31.5%±1.8%; BMI >40: 29.0%±2.8%, p<0.0001). Allometric height-indexed LV and LA dimensions increased with increasing BMI class (p<0.0001). Echocardiographic parameters did not change significantly after non-surgical weight loss.In conclusion, echocardiographic features can be described according to obesity class. Allometric height indexation may better reflect cardiac remodeling in obesity in comparison to BSA indexation. Non-surgical weight loss was not associated with significant changes in cardiac chamber dimensions and function.

Pre- and postsynaptic signatures in the prelimbic cortex associated with "alcohol use disorder" in the rat.

The transition to alcohol use disorder (AUD) involves persistent neuroadaptations in executive control functions primarily regulated by the medial prefrontal cortex. However, the neurophysiological correlates to behavioral manifestations of AUD are not fully defined. The association between cortical neuroadaptations and behavioral manifestations of addiction was studied using a multi-symptomatic operant model based on the DSM-5 diagnostic criteria for AUD. This model aimed to characterize an AUD-vulnerable and AUD-resistant subpopulation of outbred male Wistar rats and was combined with electrophysiological measurements in the prelimbic cortex (PL). Mirroring clinical observations, rats exhibited individual variability in their vulnerability to develop AUD-like behavior, including motivation to seek for alcohol (crit 1), increased effort to obtain the substance (crit 2), and continued drinking despite negative consequences (crit 3). Only a small subset of rats met all the aforementioned AUD criteria (3 crit, AUD-vulnerable), while a larger fraction was considered AUD-resilient (0 crit). The development of AUD-like behavior was characterized by disruptions in glutamatergic synaptic activity, involving decreased frequency of spontaneous excitatory postsynaptic currents (sEPSCs) and heightened intrinsic excitability in layers 2/3 PL pyramidal neurons. These alterations were concomitant with a significant impairment in the ability of mGlu2/3 receptors to negatively regulate glutamate release in the PL but not in downstream regions like the basolateral amygdala or nucleus accumbens core. In conclusion alterations in PL synaptic activity were strongly associated with individual addiction scores, indicating their role as potential markers of the behavioral manifestations linked to AUD psychopathology.

Application of γδ T cells with different memory phenotypes in clinical diagnosis of active pulmonary tuberculosis

ObjectiveTo investigate the application and clinical significance of different memory phenotypes of γδ T-cell subsets in the clinical diagnosis of pulmonary tuberculosis. MethodsIn total, 42 patients with tuberculosis (TB) according to the diagnostic criteria for tuberculosis (WS288-2017) who were treated at the Infectious Diseases Hospital affiliated with Soochow University from February 2023 to July 2023 were enrolled. Additionally, 16 patients with latent TB infection (LTBI) and 20 healthy controls (HCs) were included. Flow cytometry was used to measure the expression levels of γδ T cells, Vδ1 T-cell subsets/Vδ2 T-cell subsets, naive (CD45RA+CD27+) cells, central memory (CD45RA-CD27+) cells, effector memory (CD45RA-CD27-) cells, and terminally differentiated (CD45RA+CD27-) cells in the peripheral blood. The expression levels at different stages of TB infection were compared. ResultsThere were no significant differences in peripheral blood γδ T cells or Vδ1 T cells among the HC, LTBI and TB groups. The proportion of CD45RA-CD27+Vδ2 T cells in TB patients was significantly lower than that in HCs and LTBI patients, but the proportion of CD45RA+CD27-Vδ2 T cells was greater. ROC curve analysis revealed that CD45RA-CD27+Vδ2 T cells (AUC), CD45RA+CD27-Vδ2 T cells (AUC), and the combination of both (AUC) were effective in differentiating TB patients from LTBI patients. ConclusionThe proportions of CD45RA-CD27+Vδ2 T cells and CD45RA+CD27-Vδ2 T cells are potential biomarkers for the diagnosis of active TB infection and are helpful for distinguishing active TB infection from LTBI.

The Landscape of Randomized Clinical Trial Meta-analyses on Statins for Aneurysmal Subarachnoid Hemorrhage: A Scoping Review.

Aneurysmal subarachnoid hemorrhage (aSAH) is a type of non-traumatic SAH that can have detrimental effects on the central nervous system, resulting in severe disability or death. Early nimodipine is currently the only strongly recommended pharmacological treatment that has shown efficacy in improving neurological/functional outcomes in aSAH patients. Whether statin treatment is of benefit to aSAH patients is an issue that has generated considerable interest and debate. In the present scoping review, we mapped and analyzed the available literature on metaanalyses of randomized clinical trials (RCTs) examining the effect of statins on aSAH. Seventeen meta-analyses of RCTs, published between 2008 and 2023, were identified. Treatments in included meta-analyses were based on various regimens of simvastatin, pravastatin, pitavastatin or atorvastatin for up to 21 days. Eleven of the included reports indicated some beneficial effect of statin treatment, reducing rates of at least one of the following: cerebral vasospasm, delayed cerebral ischemia/delayed ischemic neurologic deficit, mortality or functional/ neurological outcome. In contrast, six meta-analyses, showed no such effects. The limitations reported by several meta-analyses, included low patient numbers or disproportionate representation of patients from certain RCTs, differences in drug treatment, patient diagnostic criteria and outcome evaluation between RCTs, as well as poor data quality or lack of RCTs data. Knowledge of the reported limitations may aid the design of future clinical trials and/or their meta-analyses.

PRPH2-associated Retinal Diseases: A Systematic Review of Phenotypic Findings

PurposePRPH2-associated retinal diseases (PARD) result from pathogenic PRPH2 variants, primarily affecting photoreceptor outer segments and retinal pigment epithelium. The focus of this article is to review and discuss the phenotyping of PARD subtypes. DesignA systematic review MethodsThe review followed PRISMA 2020 guidelines with searches on PubMed, Medline, Web of Science, Google Scholar, and Cochrane Library. Eligible studies were those which discussed molecularly confirmed PARD or described associated diseases such as butterfly pattern dystrophy. Inclusion: cross-sectional, cohort, case-control studies, book chapters. Exclusion: non-English, conference papers, non-peer-reviewed, or non-full text articles. ResultsPARD is responsible for 25% of pattern dystrophy and up to 5% of inherited retinal dystrophies. There is clear evidence of phenotypic variability between individuals carrying the same pathogenic variant. Fundus autofluorescence, fluorescein angiography, optical coherence tomography, while in research adaptive optics reveal detailed phenotypic characteristics, notably in retinal pigment epithelium changes and photoreceptor disruption. The phenotypic of PARD variability presents diagnostic challenges, with phenotypic features often overlapping with other retinal diseases including age-related macular degeneration, Stargardt disease and retinitis pigmentosa. ConclusionThis review emphasizes revising diagnostic criteria by incorporating more recent imaging techniques and confirming diagnosis with the use of genetic testing. Understanding phenotypic diversity and intrafamilial variability in PARD is crucial for developing new treatments and for patient prognosis and future research should focus on larger cohorts studying genotype-phenotype correlations.

An evaluation of measurement invariance of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition borderline personality disorder criteria across heterosexual, lesbian, gay, and bisexual adults.

There is a robust, yet poorly understood relationship between nonheterosexual orientation and borderline personality disorder (BPD), with lesbian, gay, and bisexual individuals evidencing greater BPD symptoms compared to heterosexual individuals. Recent evidence suggests possible psychometric bias in BPD diagnostic criteria leading to greater endorsement among sexual minority individuals, which hinders researchers' ability to make valid group comparisons. The present study utilized an epidemiological sample of 35,995 men and women to evaluate the extent of differential item functioning (DIF) among BPD criteria across sexual orientation groups using a multiple indicators multiple causes approach. All criteria except affective instability and emptiness indicated DIF for at least one sexual minority focal group, although both demonstrated DIF in sensitivity analyses. DIF was most consistently indicated for suicidality, efforts to avoid abandonment, and impulsivity. Contrary to predictions, DIF was mostly nonuniform with greater item discrimination for sexual minority groups compared to their heterosexual counterparts. Finally, all estimated effect sizes were small, suggesting that DIF was not practically meaningful and unlikely to impact the validity of group comparisons for BPD criteria across heterosexual and nonheterosexual men and women. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

OA02 Blood, Sweat and Steroids

Abstract Introduction This 79 year old gentleman was referred to the Rheumatology department with arthralgia, myalgia, erythema nodosum, an ESR elevated at 106 mm/h and IgA 6.45 g/L. His GP commenced him on 30 mg Prednisolone once a day for one week. His symptoms and signs improved significantly with treatment, prior to his first Rheumatology review. Case description He initially presented to his GP with pain and a skin rash in his groin which was thought to be fungal and treated as such. He then developed erythematous tender lumps on his right proximal forearm and left hand which were in keeping with erythema nodosum. He had a background history of ischaemic heart disease, hypertension, hyperlipidaemia, squamous cell carcinoma and an elevated BMI. Once the initial course of prednisolone stopped he experienced recurrence of the skin rash, in addition to night sweats, dizziness and weight loss. Inflammatory markers rose. CT scan of chest, abdomen and pelvis, done to exclude malignancy, was normal. PET CT while off steroid showed uptake in the descending aorta, not in keeping with large vessel vasculitis, and generalised bone marrow uptake consistent with an inflammatory process. Prednisolone was re-commenced. Bloods including HIV, Hepatitis, B12, CMV, EBV, Syphilis, ANA, ANCA and Cryoglobulins were normal. Skin biopsy showed non-specific inflammatory change. Bone marrow biopsy showed myeloid hyperplasia and haemophagocytosis. He required two further inpatient admissions due to shortness of breath, anaemia and skin rash, which coincided with steroid reduction. He responded to an increased dose of steroid and antibiotics. Genetic testing then identified a gene for UBA1, a pathogenic variant causing VEXAS syndrome. Clinical features were in keeping – skin lesions, sweats, elevated inflammatory markers, macrocytic anaemia and steroid responsivity. He was commenced on Tocilizumab and responded well. Bloods normalised and prednisolone was weaned. Neutropenia resulted in stopping Tocilizumab and later Anakinra and Sarilumab. Half dose once monthly Tocilizumab and low dose steroid are now successfully treating his disease. Discussion This gentleman had symptoms and signs in keeping with an auto-inflammatory condition. However, it took a number of specialties to investigate him due to blood results and imaging not naturally leading to a diagnosis. Initial differentials included sarcoid and polyarteritis nodosa. The chest and joints were not involved, serum ACE, calcium and CT Angio were normal so these were excluded. PET CT was done to ensure this was not an atypical large vessel vasculitis and the abnormal bone marrow uptake led us to discuss with haematology. At that time he had a pancytopenia with poor reticulocyte response and so haematology carried out a bone marrow biopsy. The bone marrow biopsy result showed a myeloid shift felt to be reactive and there was a degree of haemophagocytosis but he did not meet diagnostic criteria for haemophagocytic lymphohistiocytosis. Still’s disease was queried but he was not pyrexic, there was no arthritis, no hepatomegaly or splenomegaly and there was neutropenia rather than a neutrophilia. Skin biopsy, while not diagnostic, did query a vasculitic process. Therefore it was decided, despite persisting diagnostic uncertainty that he should be treated with Tocilizumb, which did allow steroid reduction. Eventually genetic testing was sent looking for periodic fevers and that is when the UBA1 gene was identified and the diagnosis of VEXAS syndrome made. Subcutaneous Tocilizumab did cause leucopenia and he suffered from recurrent infections. He had also been trialled on Anakinra and Sarilumab but both of these caused neutropenia. We have been able to switch to intravenous Tocilizumab in order to titrate the dose, and he is now on a small dose of 2 mg/kg 4 weekly which has allowed inflammation to settle without causing a drop in white cell count. Key learning points • There is little guidance on treatment of VEXAS syndrome. This gentleman has been difficult to treat due to drug side effects, and so this case raises the issue of few treatment options in VEXAS. It seems little is known about the disease and so we quickly come to a treatment conundrum when side effects prohibit the use of standard therapies. More research is required in to this condition and its management. • This case also raises the importance of working closely with other specialties. Where there is multi-system involvement, multi-disciplinary working is invaluable. It brings other perspectives and breadth of knowledge to the case, increasing the likelihood of making the correct diagnosis. • This case also reminds us of the value of genetic testing. Where it seems there is an inflammatory syndrome but results don’t seem to add up, we should put our patients forward for testing. • At the BSR case based conference I would like to hear other cases of treating VEXAS and what difficulties and wisdom my colleagues have to share. I would also like to hear if there are other treatment strategies others are aware of.

Prevalence of constipation and associated factors in university hospital inpatients.

We aimed to determine (1) the prevalence of constipation among inpatients, (2) the prevalence and symptoms of difficult defecation among constipated inpatients, and (3) the factors associated with constipation. We performed a retrospective cohort study over a single day at one university hospital. We analyzed the nursing records for inpatients who had been hospitalized for at least 3 days. The survey items included the symptoms associated with defecation difficulty and nutritional intake. The symptoms of difficult defecation were defined as (1) fewer than three spontaneous bowel movements per week; (2) lumpy or hard stools (Bristol stool form scale types 1-2); (3) straining during defecation; and (4) the sensation of incomplete evacuation during defecation, based on the Roma-IV diagnostic criteria. Constipation was defined as the presence of two or more symptoms of defecation difficulty. Univariate and multivariate analyses were performed to determine the constipation status of the patients. The prevalence of constipation in the university hospital was 12.2%, and the department with the highest prevalence of difficulty with defecation was the Psychiatry Department (64.1%). Of the patients with constipation, 36.8% exhibited symptoms of defecation difficulty other than low frequency of defecation. The factor that was significantly associated with constipation after admission was pre-admission constipation (odds ratio=8.92, p<0.01). Subjective assessment has limitations for the accurate determination of constipation status. In addition, patients with a history of constipation before admission require early interventions to aid defecation following their admission.

Brief Report: Alternative Pulmonary Function Measures of Emphysema in People With HIV.

People with HIV (PWH) have nearly twice the risk of emphysema than people without HIV. This risk, which has been associated with HIV-mediated changes in the lung immune environment and more extensive radiographic emphysema, may result in different patterns of airflow limitation on pulmonary function testing (PFT) than those traditionally used in people without HIV. In this prospective cohort of PWH in Atlanta, Georgia, we analyzed PFT and chest computed tomography data from July 2013 through June 2018. After comparing the prevalence of PFT measures of airflow limitation for those with and without radiographic emphysema, we used binary recursive partitioning to identify PFT measures that differentiated between PWH with and without radiographic emphysema. Among 167 PWH who had both PFT and computed tomography data during the study period, 89 (53%) had radiographic emphysema. Those with radiographic emphysema were more likely to have airflow limitations on PFTs. Recursive partitioning identified partitions at a forced expiratory volume in 1 second to forced vital capacity ratio (FEV1/FVC) of 0.78 and a residual volume of 116% predicted. These partitions enabled the identification of 84 (94%) PWH with radiographic emphysema, in contrast to the traditional diagnostic criteria of an FEV1/FVC ratio of 0.7, which only identified 49 (55%) of those with radiographic emphysema. Emphysema in PWH may have different patterns of airflow limitation on PFTs that are not adequately captured by traditional diagnostic criteria. Future studies can seek to validate these findings and determine optimal thresholds for diagnosing HIV-associated emphysema.