[Cortico-basal syndrome and cortico-basal degeneration: From the clinical diagnosis to the lesional substrate for an adapted care]. / Le syndrome cortico-basal et la dégénérescence cortico-basale : du diagnostic clinique au substrat lésionnel pour une prise en charge adaptée.

Cortico-basal degeneration is a relatively uncommon cause of degenerative parkinsonism in the elderly. From a clinical point of view, it manifests as a cortico-basal syndrome (CBS), featuring a highly asymmetrical akinetic-rigid syndrome, dystonia, myoclonus and cognitive-behavioral impairment with predominant apraxia. Other clinical phenotypes are possible, including variants with mainly language or behavioral impairment, or with axial, symmetrical parkinsonism resembling progressive supranuclear palsy (PSP). Current diagnostic criteria take into account the heterogeneity of clinical presentations. However, a diagnosis of certainty can only be reached by a pathological study, with the evidence of TAU-positive intraneuronal inclusions. Indeed SCB may be underpinned by other lesional substrates, ranging from frontotemporal degeneration to Alzheimer's disease. Symptom management must be early, multidisciplinary and adapted to the progression of the disorder. The identification of the pathological substrate is an essential prerequisite for pathophysiological therapeutic trials.

Canakinumab treatment real world evidence in 3 monogenic periodic fever syndromes in 2009-2022: an interim analysis using the French JIR cohort database.

BACKGROUND: Our study aimed to provide real-world evidence on the treatment patterns, effectiveness and safety of canakinumab in France in Familial Mediterranean Fever (FMF), Mevalonate Kinase Deficiency (MKD), and Tumor necrosis factor Receptor Associated Periodic Syndrome (TRAPS). METHODS: This study used the JIR cohort, a multicentre international registry created in 2013 to collect data on patients with juvenile inflammatory rheumatic diseases. French patients diagnosed with FMF, MKD or TRAPS and treated with canakinumab were included in this study. RESULTS: 31 FMF, 26 MKD and 7 TRAPS patients received canakinumab during the study period. Most of them initiated canakinumab at the recommended dose of 2 mg/kg or 150 mg, but less than half of FMF and MKD patients initiated it at the recommended frequency (every 4 weeks). Two years after initiation, the rate of patients still on treatment was 78.1% in FMF, 73.7% in MKD, and 85.7% in TRAPS patients. While the dose per injection remained globally the same over the course of the treatment, some adjustments of the dose intervals were observed. Six patients had a severe adverse event reported. Of those, three were possibly related to canakinumab. CONCLUSION: This interim analysis showed a good maintenance of canakinumab treatment 2 years after initiation and confirmed its safety profile in real-life practice in France in patients diagnosed with FMF, MKD and TRAPS. The high variety of dose and interval combinations observed in canakinumab treated patients let suppose that physicians adapt the posology to individual situations rather than a fixed treatment plan.

A novel mutation in the NR3C1 gene associated with reversible glucocorticoid resistance.

OBJECTIVE: Glucocorticoid resistance is a rare endocrine disease caused by variants of the NR3C1 gene encoding the glucocorticoid receptor (GR). We identified a novel heterozygous variant (GRR569Q) in a patient with uncommon reversible glucocorticoid resistance syndrome. METHODS: We performed ex vivo functional characterization of the variant in patient fibroblasts and in vitro through transient transfection in undifferentiated HEK 293T cells to assess transcriptional activity, affinity, and nuclear translocation. We studied the impact of the variant on the tertiary structure of the ligand-binding domain through 3D modeling. RESULTS: The patient presented initially with an adrenal adenoma with mild autonomous cortisol secretion and undetectable adrenocorticotropin hormone (ACTH) levels. Six months after surgery, biological investigations showed elevated cortisol and ACTH (urinary free cortisol 114 µg/24 h, ACTH 10.9 pmol/L) without clinical symptoms, evoking glucocorticoid resistance syndrome. Functional characterization of the GRR569Q showed decreased expression of target genes (in response to 100 nM cortisol: SGK1 control +97% vs patient +20%, P < .0001) and impaired nuclear translocation in patient fibroblasts compared to control. Similar observations were made in transiently transfected cells, but higher cortisol concentrations overcame glucocorticoid resistance. GRR569Q showed lower ligand affinity (Kd GRWT: 1.73 nM vs GRR569Q: 4.61 nM). Tertiary structure modeling suggested a loss of hydrogen bonds between H3 and the H1-H3 loop. CONCLUSION: This is the first description of a reversible glucocorticoid resistance syndrome with effective negative feedback on corticotroph cells regarding increased plasma cortisol concentrations due to the development of mild autonomous cortisol secretion.

Cancer symptom clusters, cardiovascular risk, and quality of life of patients with cancer undergoing chemotherapy: A longitudinal pilot study.

Patients with cancer undergoing chemotherapy may have different cancer symptom clusters (CSC) that negatively impact their quality of life (QoL). These symptoms can sometimes arise from the disease itself or as a result of their cancer treatment. This study aimed to: examine the feasibility of longitudinal testing of CSC pattern and QoL in a sample of adult cancer patients undergoing outpatient chemotherapy; to identify the cardiovascular risk of patients with cancer undergoing outpatient chemotherapy; and to investigate the most prevalent CSC and their impact on the QoL of these patients. A longitudinal pilot study was conducted with eleven participants with a mean age of 56.09 years (range: 27-79) diagnosed with malignant neoplasm and undergoing outpatient chemotherapy treatment were evaluated during 6 cycles of chemotherapy. The CSC, cardiovascular risk, and QoL were assessed using the MSAS, FRS, and EQ-5D-3L™, respectively. Descriptive statistical and non-parametric bivariate analyses were performed. Patients who started chemotherapy treatment generally had a low to moderate cardiovascular risk and were likely to have a family history of hypertension, acute myocardial infarction, and stroke. Cardiovascular risk was found to be correlated with patient age (Rhos = 0.64; P = .033). In addition, the results showed a reduction in the QoL scoring over the 6 chemotherapy sessions. Regarding the most prevalent CSC, 2 clusters were identified: the neuropsychological symptom cluster (difficulty concentrating-sadness-worry) and the fatigue-difficulty sleeping cluster. Between the first and sixth chemotherapy sessions, there was a decrease in the perception of "mild" severity (P = .004) and an increase in the perception of "severe" and "very severe" (P = .003) for all symptoms. Adequate attention to CSC should be the basis for the accurate planning of effective interventions to manage the symptoms experienced by cancer patients.

Can essential fatty acids (EFAs) prevent and ameliorate post-COVID-19 long haul manifestations?

It is hypothesized that COVID-19, post-COVID and post-mRNA COVID-19 (and other related) vaccine manifestations including "long haul syndrome" are due to deficiency of essential fatty acids (EFAs) and dysregulation of their metabolism. This proposal is based on the observation that EFAs and their metabolites can modulate the swift immunostimulatory response of SARS-CoV-2 and similar enveloped viruses, suppress inappropriate cytokine release, possess cytoprotective action, modulate serotonin and bradykinin production and other neurotransmitters, inhibit NF-kB activation, regulate cGAS-STING pathway, modulate gut microbiota, inhibit platelet activation, regulate macrophage and leukocyte function, enhance wound healing and facilitate tissue regeneration and restore homeostasis. This implies that administration of EFAs could be of benefit in the prevention and management of COVID-19 and its associated complications.

[THE 12TH CONGRESS OF THE INTERNATIONAL SOCIETY OF SYSTEMIC AUTOINFLAMMATORY DISEASES (ISSAID) HELD ON 15-18 MAY 2023, TORONTO, CANADA].

INTRODUCTION: THE 12TH CONGRESS OF THE INTERNATIONAL SOCIETY OF SYSTEMIC AUTOINFLAMMATORY DISEASES (ISSAID) HELD ON 15-18 MAY 2023, TORONTO, CANADA.

Cranial Neuralgias.

OBJECTIVE: The cranial neuralgias are relatively rare, but recognizing these syndromes and distinguishing among them is critical to reducing unnecessary pain and disability for affected patients. Despite their distinctive features, cranial neuralgias may go undiagnosed or misdiagnosed for several years. A notable proportion of cranial neuralgia presentations are due to secondary causes and require targeted treatment. The purpose of this article is to review the diagnosis and management of cranial neuralgias encountered in clinical practice. LATEST DEVELOPMENTS: In 2020, the International Classification of Orofacial Pain was released for the first time. Modeled after the International Classification of Headache Disorders, it includes updated terminology for cranial neuralgias. The underlying pathophysiology of the cranial neuralgias is currently believed to be rooted in both peripheral and central nociceptive systems. In addition, a growing number of familial cases are being identified. Recent therapeutic advancements include a better understanding of how to utilize older therapies and procedures more effectively as well as the development of newer approaches. ESSENTIAL POINTS: Cranial neuralgia syndromes are rare but important to recognize due to their debilitating nature and greater likelihood of having potentially treatable underlying causes. While management options have remained somewhat limited, scientific inquiry is continually advancing the understanding of these syndromes and how best to address them.

[Research and development strategy of new traditional Chinese medicine drugs for syndromes based on human use experience].

Chinese drug registration laws and regulations have always reserved a place for the new traditional Chinese medicine(TCM) drugs for syndromes, but so far no such new drugs have been approved for registration. This paper expounded on the relevant policies, regulations, and technologies of new TCM drugs for syndromes in China and pointed out that the application of the animal model of TCM syndromes to carry out pharmacodynamics research and clinical efficacy evaluation criteria of TCM syndromes were the main technical difficulties in the research and development of new TCM drugs for syndromes. Not all syndromes are suitable for developing new drugs, and the indications for new TCM drugs should be constant syndromes. Among the three research and development models of simple syndrome, syndrome-unified disease, and combined disease and syndrome, the research and development model of combined disease and syndrome is recommended. Clinical positioning is the key to new TCM drugs for syndromes. It is encouraged to conduct high-quality human use experience studies to determine the clinical positioning of new TCM drugs for syndromes, as well as the target population, dose, course of treatment, and initial therapeutic and safety, and apply for exemption from non-clinical effectiveness studies. Clinical trials of new TCM drugs for syndromes should take the target symptoms or signs as the main efficacy index and the efficacy of TCM syndromes as the secondary efficacy index. Clinical research program design should implement the "patient-centered" concept and introduce clinical outcome evaluation indicators. In the clinical safety evaluation, special conditions such as characteristic syndromes and changes should be considered. With the construction of the human use experience technology system and the promotion of the TCM registration and evaluation evidence system featuring the "combination of TCM theory, human use experience, and clinical trials", it is believed that many high-quality new TCM drugs for syndromes will be developed in the future.

[Methods for traditional Chinese medicine syndrome-based efficacy evaluation: a review].

Traditional Chinese medicine(TCM) syndrome-based efficacy is an evaluation index which is unique to TCM and can reflect the advantages of TCM. The development of the methods and measurement tools for evaluating TCM syndrome-based efficacy can provide objective and quantitative evidence for the clinical efficacy evaluation of TCM and the development of new Chinese medicine preparations, being the exploration direction of innovative methods and technologies for evaluating TCM efficacy. The conventional evaluation methods are subjective and limited to the mitigation of symptoms and the improvement of physical signs, which make it difficult to form a unified evaluation standard. In addition, the evaluation methods lack unity, objectivity, and quantitative research. The scientific connotation, evaluation ideas and methods, and key technologies of the evaluation for the therapeutic effect on syndromes remain unclear, which leads to diverse evaluation modes, methods, and indexes. The syndrome-based efficacy scale provides a new idea for the objective quantification and standardization of TCM syndromes. This review systematically summarizes the methods and problems, introduces the research progress in the evaluation scales, and puts forward some thoughts on the characteristics of TCM syndrome-based efficacy evaluation, aiming to provide insights for the research in this field.

[Transcriptome data mining combined with clinical and animal experiments for identification of syndrome element marker genes during entire course of steroid-induced osteonecrosis of femoral head].

A research strategy combining transcriptome data mining and experimental verification was adopted to identify the marker genes characterizing the syndrome elements of phlegm, stasis, and deficiency in steroid-induced osteonecrosis of the femoral head(SONFH). Firstly, the common differentially expressed gene sets of SONFH with the syndromes of phlegm-stasis obstructing collaterals, vessel obstruction, and liver-kidney deficiency were obtained from the clinical transcriptomic analysis of a previous study. The differential expression trend analysis and functional gene mining were then employed to predict the candidate marker gene sets representing phlegm, stasis, and deficiency. The whole blood samples from SONFH patients, whole blood samples from SONFH rats, and affected femoral head tissue samples were collected for qPCR, which aimed to determine the expression levels of the candidate marker genes mentioned above. Furthermore, the receiver operating characteristic curve(ROC) was established to objectively evaluate the syndrome differentiation effectiveness of the candidate marker genes mentioned above. The transcriptome data analysis results showed that the candidate marker genes for phlegm was ELOVL fatty acid elongase 6(ELOVL6), and those for stasis were ankyrin 1(ANK1), glycophorin A/B(GYPA/B), and Rh-associated glycoprotein(RHAG). The candidate marker genes for deficiency were solute carrier family 2 member 1(SLC2A1) and stomatin(STOM). The qPCR results showed that compared with that in the non-SONFH group, ELOVL6 had the lowest expression level in the peripheral blood of the SONFH patients with the syndrome of phlegm-stasis obstructing collaterals(P<0.05). Compared with that in the normal control group, ELOVL6 had the lowest expression level in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 4 weeks(P<0.01), and it showed better syndrome differentiation effectiveness of rats modeled for 4 weeks(AUC=0.850, P=0.006) than at other modeling time points(8, 12, 16, and 21 weeks, AUC of 0.689, 0.766, 0.588, and 0.662, respectively). Compared with that in the non-SONFH group, the expression levels of ANK1, GYPA, and RHAG were the lowest in the peripheral blood of SONFH patients with the vessel obstruction syndrome(P<0.05). The expression levels of the three genes were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 12 weeks(P<0.05, P<0.01), and their syndrome differentiation effectiveness in the rats modeled for 12 weeks(GYPA: AUC=0.861, P=0.012; ANK1: AUC=0.855, P=0.006; RHAG: AUC=0.854, P=0.009) was superior to that for 4, 8, 16, and 21 weeks(GYPA: AUC=0.646, 0.573, 0.691, and 0.617, respectively; ANK: AUC1=0.630, 0.658, 0.657, and 0.585, respectively; RHAG: AUC=0.592, 0.511, 0.515, and 0.536, respectively). Compared with the non-SONFH group, both SLC2A1 and STOM had the lowest expression levels in the peripheral blood of patients with the syndrome of liver and kidney deficiency(P<0.05). Compared with the normal control group, their expression levels were the lowest in the peripheral blood and affected femoral head tissue of SONFH rats modeled for 21 weeks(P<0.05, except STOM in the peripheral blood of rats). Moreover, the syndrome differentiation effectiveness of SLC2A1 in the rats modeled for 21 weeks(AUC=0.806, P=0.009) was superior to that for 4, 8, 12, and 16 weeks(AUC=0.520, 0.580, 0.741, 0.774, respectively), and STOM was meaningless in syndrome differentiation. In summary, the candidate marker gene for phlegm in SONFH is ELOVL6; the candidate marker genes for stasis are GYPA, RHAG, and ANK1; the candidate marker gene for deficiency is SLC2A1. The results help to reveal the biological connotations of phlegm, stasis, and deficiency in SONFH at the genetic level.

[Retrospective cross-sectional survey of clinical characteristics and syndrome elements distribution at different stages of coronary heart disease].

The clinical data of coronary heart disease(CHD) patients treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from January 2022 to March 2023 were retrospectively collected. This study involved the descriptive analysis of demographic characteristics, clinical symptoms, and tongue and pulse features. The χ~2 test was conducted to analyze the distribution of syndrome elements and their combinations at diffe-rent stages of CHD, so as to reveal the clinical characteristics and syndrome patterns at various pathological stages of CHD. This study extracted 28 symptom entries, 10 tongue manifestation entries, and 7 pulse manifestation entries, summarized the 5 main disease locations of the heart, lung, liver, spleen, and kidney, and the 8 main disease natures of blood stasis, phlegm turbidity, Qi stagnation, heat(fire), fluid retention, Qi deficiency, Yin deficiency, and Yang deficiency and 8 combinations of disease natures. The χ~2 test showed significant differences in the distribution of syndrome elements including the lung, liver, spleen, kidney, blood stasis, heat(fire), Qi stagnation, heat syndrome, water retention, Qi deficiency, Yin deficiency, and Yang deficiency between different disease stages. Specifically, the liver, blood stasis, heat(fire), and Qi stagnation accounted for the highest proportion during unstable stage, and the lung, spleen, kidney, water retention, Qi deficiency, Yin deficiency, and Yang deficiency accounted for the highest proportion at the end stage. The distribution of Qi deficiency varied in the different time periods after percutaneous coronary intervention(PCI). As shown by the χ~2 test of the syndrome elements combination, the distribution of single disease location, multiple disease locations, single disease nature, double disease natures, multiple natures, excess syndrome, and mixture of deficiency and excess varied significantly at different stages of CHD. Specifically, single disease location, single disease nature, and excess syndrome accounted for the highest proportion during the stable stage, and double disease natures accounted for the highest proportion during the unstable stage. Multiple disease locations, multiple disease natures, and mixture of deficiency and excess accounted for the highest proportion during the end stage. In conclusion, phlegm turbidity and blood stasis were equally serious during the stable stage, and a pathological mechanism caused by blood stasis and toxin existed during the unstable stage. The overall Qi deficiency worsened after PCI, and the end stage was accompanied by the Yin and Yang damage and the aggravation of water retention. There were significant differences in the distribution of clinical characteristics and syndrome elements at different stages of CHD. The pathological process of CHD witnessed the growth and decline of deficiency and excess and the combination of phlegm turbidity and blood stasis, which constituted the basic pathogenesis.

[Analysis of clinical research features and outcome indexes of traditional Chinese medicine intervention in septic kidney injury].

This study aims to systematically review the clinical features and outcome indicators in randomized controlled trial(RCT) of traditional Chinese medicine(TCM) intervention in septic kidney injury and provide a reference for optimizing clinical study design and building the core outcome set(COS) of TCM treatment of septic kidney injury. Computer searches were conducted on PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, VIP, and SinoMed to find published RCT of TCM intervention in septic kidney injury in the past five years, extract the basic characteristics, intervention measures, outcome indicators, and other data of included studies, and conduct descriptive analysis. 53 RCTs were included, and the sample size was mostly concentrated in 60-80 cases, with abdominal infection being the most common(15 articles, 83.3%) and the TCM syndrome of blood stasis being the most frequent(9 articles, 50.0%). The frequency of intervention methods from high to low were TCM decoction(28 articles, 52.8%), Chinese patent medicine(22 articles, 41.5%), and combined TCM therapy(3 articles, 7.5%); the intervention time of the trial was more than 7 d(34 articles, 69.4%). The risk of bias in included studies was unclear. A total of 84 outcome indicators were involved, which were divided into 9 fields, including 63 physical and chemical tests(305 times, 72.2%), 4 kinds of disease degree(48 times, 11.6%), 4 kinds of clinical effective rate(15 times, 3.6%), 1 kind of quality of life(1 time, 0.2%), 2 kinds of economic evaluation(14 times, 3.3%), 1 kind of TCM disease(9 times, 2.1%), 2 kinds of long-term prognosis(16 times, 3.8%), 2 kinds of safety events(6 times, 1.4%), and 5 other indicators(8 times, 0.7%). The cumulative frequency was 422 times, among which the outcome indicators with higher frequency were inflammatory factors(42 articles, 79.2%) and markers of renal function and kidney injury(40 articles, 75.5%). Only 1(1.9%) of the included articles mentioned primary and secondary outcome indicators, and 6 articles(11.3%) mentioned safety events, 13 articles(24.5%) mentioned economic assessment. The RCT quality of TCM intervention in septic renal injury was generally low, and the reference standards for sepsis, kidney injury, and TCM syndrome diagnosis were not uniform. There are some problems in outcome indicators, such as unclear distinction between primary and secondary indicators, neglect of endpoint indicators, lack of application of TCM characteristic indicators, and insufficient attention to safety events and economic assessment. It is suggested that the quality of clinical research methodology should be improved in the future, and the COS should be constructed to provide high-level evidence-based evidence for TCM intervention in septic kidney injury.

[Prenatal diagnosis of fetal microdeletion and microduplication syndromes among pregnant women with advanced maternal ages].

OBJECTIVE: To assess the value of combined chromosomal karyotyping and chromosomal microarray analysis (CMA) and/or copy number variation sequencing (CNV-seq) for the prenatal diagnosis for women with advanced maternal ages, and to explore the challenges of prenatal genetic counseling brought by the types of fetal CNVs and uncertainty of related phenotypes. METHODS: A retrospective analysis was carried out on 1 841 women with advanced maternal age who underwent interventional prenatal diagnosis at the Prenatal Diagnosis Center of Xiamen University Affiliated Women and Children's Hospital from January 2017 to December 2020. Routine chromosomal karyotyping analysis and CMA/CNV-seq detection were carried out. RESULTS: CMA/CNV-seq had detected pathogenic variants in 2 cases which had failed karyotyping analysis. Two hundred and twenty one fetal chromosomal abnormalities were detected by karyotyping analysis, among which 187 were detected by CMA/CNV-seq. CMA/CNV-seq analysis of 23 cases with balanced chromosome structural aberrations and 10 cases with low proportion mosaicisms (including a marker chromosome) had yielded a negative result. In addition, 26 cases (26/1 841, 1.4%) with pathogenic CNVs were discovered among those with a normal karyotype, of which 13 (50.0%) were recurrent CNVs associated with neurocognitive impairment, with 22q11.21 microdeletions and microduplications being the most common types (26.92%). CONCLUSION: The combination of karyotyping analysis and CMA/CNV-seq not only increased the rate of prenatal diagnosis, but also complemented with each other, which has facilitated genetic counseling and formulation of prenatal diagnosis strategy for the affected families.

Post-COVID syndrome: analysis of the prevalence of chemosensory dysfunction and predictive factors of recovery in COVID-19 long-haulers in Jordan.

OBJECTIVE: One of the major concerns of the post-COVID-19 era is elucidating and addressing the long-term complications of COVID-19. SUBJECTS AND METHODS: A web-based questionnaire was distributed in Jordan to assess the prevalence and recovery from chemosensory dysfunction among COVID-19 long-haulers in Jordan. RESULTS: A total of 611 respondents complained of chemosensory dysfunction (age range = 18-68 years), and the majority of the respondents were female (88.4%). Parosmia was the most prevalent olfactory dysfunction reported (n = 337, 33.3%), and parageusia was the most frequently reported gustatory dysfunction (n = 239, 36.4%). Medications were not reported to be associated with a better perception of smell or taste by nearly half of those who had been treated (n = 146, 46.1%). Among participants who had received olfactory rehabilitation/training (n = 215, 35.2%), 43.7% (n = 94) reported modest improvement, with the most frequently helpful scents being coffee (n = 80, 24.8%), aromatic oils (n = 74, 23%), and perfumes/colognes (n = 73, 22.7%). Age was found to have a significant negative correlation with complete recovery. In addition, age (p < .05), anosmia (p < .001), hyperosmia (p < .001), ageusia (p < .05), and duration of olfactory dysfunction (p < .001) were all independent predictors of complete recovery. CONCLUSIONS: Chemosensory dysfunctions are largely subjective; therefore, more objective examinations are required to draw more definite conclusions.

Illness Perceptions as a Predictor of Symptom Cluster Trajectories in Patients With Inflammatory Bowel Disease: A Latent Growth Mixture Model.

The aims of this study were to (a) identify the trajectory of symptom clusters in patients with inflammatory bowel disease up to 28 weeks after initiation of infliximab therapy and (b) examine the illness perceptions associated with symptom cluster trajectories. This was a prospective study where participants completed the symptom cluster scale at baseline, 14 weeks, and 28 weeks. A latent growth mixture modeling was used to identify trajectories of symptom clusters that were predicted, using baseline covariates (Brief Illness Perception Questionnaire). A total of 206 patients were included and identified as three latent classes: moderate symptom cluster-stable decline group (C1), high symptom cluster-rapid decline group (C2), and stable symptom cluster-stable trend group (C3). C1 was predicted by cognitive illness perceptions (odds ratio [95% confidence interval]: 1.134 [1.071, 1.200], p < .001). C2 was also predicted by cognitive and emotional illness perceptions (odds ratio [95% confidence interval]: 1.169 [1.095, 1.248], p < .001; odds ratio [95% confidence interval]: 1.174 [1.038, 1.328], p = .011). Patients with inflammatory bowel disease, initiating infliximab therapy, had different symptom cluster trajectories. Illness perceptions were associated with symptom cluster classes, which underline the complexity of symptoms. Paying attention to these factors and providing necessary knowledge and psychological supporting care after infliximab therapy would effectively improve patients' symptom burden.

The Pseudotumor Cerebri Syndrome.

Pseudotumor cerebri syndrome is a syndrome of increased cerebrospinal fluid pressure without ventriculomegaly, mass lesion, or meningeal abnormality. It is either primary (idiopathic intracranial hypertension, IIH) or secondary. A secondary cause is unlikely when adhering to the diagnostic criteria. Permanent visual loss occurs if undetected or untreated, and the associated headaches may be debilitating. Fulminant disease may result in blindness despite aggressive treatment. This study addresses the diagnosis and management of IIH including new insights into the pathobiology of IIH, updates in therapeutics and causes of overdiagnosis.

Proteasome-Associated Syndromes: Updates on Genetics, Clinical Manifestations, Pathogenesis, and Treatment.

The ubiquitin-proteasome system (UPS) has a critical role in post-translational protein modification that is essential for the maintenance of all cellular functions, including immune responses. The proteasome complex is ubiquitously expressed and is responsible for degradation of short-lived structurally abnormal, misfolded and not-needed proteins that are targeted for degradation via ubiquitin conjugation. Over the last 14 years, an increasing number of human diseases have been linked to pathogenic variants in proteasome subunits and UPS regulators. Defects of the proteasome complex or its chaperons - which have a regulatory role in the assembly of the proteasome - disrupt protein clearance and cellular homeostasis, leading to immune dysregulation, severe inflammation, and neurodevelopmental disorders in humans. Proteasome-associated diseases have complex inheritance, including monogenic, digenic and oligogenic disorders and can be dominantly or recessively inherited. In this review, we summarize the current known genetic causes of proteasomal disease, and discuss the molecular pathogenesis of these conditions based on the function and cellular expression of mutated proteins in the proteasome complex.

Rhupus syndrome in the pediatric population: A comprehensive systematic literature review.

INTRODUCTION: The term "Rhupus" was employed to descriptively illustrate the overlap observed in some pediatric patients displaying features of both juvenile idiopathic arthritis (JIA) and systemic lupus erythematosus (SLE). Although "Rhupus" is traditionally used in adults, we applied it broadly to emphasize this clinical overlap. METHODS: We sought to identify studies that registered signs, symptoms, imaging characteristics, and treatments given to patients with JIA and SLE. We searched four databases using a Boolean search string, resulting in 231 articles after duplicate removal. Title and abstract screening yielded 57 articles for full-text assessment. Full reviewed 13 extracted data regarding sex, age of onset, serologic and imaging findings, and management strategies. The NIH quality assessment tool was applied to ensure the internal validity of the articles. RESULTS: From the 13 articles evaluated that meet inclusion criteria, none had standardized diagnostic algorithms. The total number of patients in those articles is 26, without discussing treatment guidelines. DISCUSSION: Clinical presentation, diagnostic parameters, and treatment of pediatric Rhupus were synthesized in this review. Fundamental keys help distinguish the joint presentation when Juvenile Idiopathic Arthritis or Lupus is present, compared with the signs and symptoms when developing the overlapping syndrome. We highlight the importance of physicians knowing about this rare condition and call all specialists to report new cases of the disease so a consensus can be reached to establish standardized guidelines for diagnosing and treating Rhupus syndrome.

Sudden Infant Death Syndrome (SIDS): State of the Art and Future Directions.

Sudden infant death syndrome (SIDS) is a type of death that occurs suddenly and without any apparent explanation, affecting infants between 28 days of life and up to a year. Recognition of this entity includes performing an autopsy to determine if there is another explanation for the event and performing both an external and internal examination of the different tissues to search for possible histopathological findings. Despite the relative success of awareness campaigns and the implementation of prevention measures, SIDS still represents one of the leading causes of death among infants worldwide. In addition, although the development of different techniques has made it possible to make significant progress in the characterization of the etiopathogenic mechanisms underlying SIDS, there are still many unknowns to be resolved in this regard and the integrative consideration of this syndrome represents an enormous challenge to face both from a point of view scientific and medical view as humanitarian. For all these reasons, this paper aims to summarize the most relevant current knowledge of SIDS, exploring from the base the characterization and recognition of this condition, its forensic findings, its risk factors, and the main prevention measures to be implemented. Likewise, an attempt will be made to analyze the causes and pathological mechanisms associated with SIDS, as well as potential approaches and future paths that must be followed to reduce the impact of this condition.

Serum klotho levels and mortality patterns in frail individuals: unraveling the u-shaped association.

BACKGROUND: Frailty, a clinical syndrome intricately linked with the aging process, stands as a harbinger of numerous adverse outcomes, most notably mortality. This study aimed to elucidate the association between serum α-klotho concentration and mortality patterns, including all-cause and cause-specific mortality, in patients with frailty. METHODS: The study employed Cox proportional hazard models, smoothed curve fitting, and supplementary analyses, encompassing threshold effect analysis, subgroup and sensitivity analyses, to explore the relationship between α-klotho levels and mortality, including all-cause, CVD, and cancer-related mortality. RESULTS: Among the 2,608 frail individuals (mean age: 60.78 [SD 10.48] years; 59.89% female), the mortality stood at 25.35% during a median follow-up period of 6.95 years. Both unadjusted and adjusted models revealed a significant inverse association between higher serum α-klotho levels and the risk of all-cause and CVD-related mortality ([mean(95% CI) 0.68 (0.55, 0.83)] for all-cause mortality; [mean(95% CI) 0.48 (0.32, 0.74)] for CVD-related mortality, all P for trend < 0.001). Notably, log2-klotho displayed a U-shaped correlation with all-cause mortality and cancer mortality, characterized by thresholds of 9.48 and 9.55, respectively. The robustness of these findings was consistently supported by subgroup and sensitivity analyses. CONCLUSION: This study unveils a U shaped association between serum α-klotho levels and both all-cause and cancer-related mortality among middle-aged and elderly individuals with frailty in the United States. The identified serum α-klotho thresholds, at 714.8 pg/ml for all-cause mortality and 750.6 pg/ml for cancer-related mortality, hold promise as potential targets for interventions aimed at mitigating the risks of premature death and cancer within this vulnerable population.