Noninfectious Inflammatory Disorders Research Articles

Fever of Unknown Origin (FUO) Criteria Influences Diagnostic Outcomes: A Systematic Review and Meta-Analysis.

BackgroundCriteria classifying fever of unknown origin (FUO) patients remains subject to discrepancies. A minimal standardized set of investigative tests serves as the foundation for the qualitative criteria, whereas quantitative incorporates the length of evaluation (7 or 3 days). A systematic review of studies would help physicians anticipate the frequency of illness types that could influence management. MethodsProspective studies published in Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997, to July 31, 2022, were included. A meta-analysis estimated associated pooled proportions between these criteria and diagnostic outcomes adjusted to the International Classification of Diseases, 10th edition (ICD-10) definitions. ResultsFive qualitative studies corresponded to an increase of 15.3% (95% CI: 2.3-28.3%, p=0.021) in undiagnosed FUO proportions compared to eleven quantitative studies. Quantitative studies had 19.7% (95% CI: 6.0-33.4%, p=0.005) more in adjusted infectious disease proportions than qualitative studies. No significant differences in proportions between FUO defining criteria were noted for adjusted noninfectious inflammatory disorders (p=0.318), oncology (p=0.901), non-inflammatory miscellaneous disorders (p=0.321), diagnostic evaluation process, gross national income (GNI), or World Health Organization (WHO) geographic region. ConclusionsUse of either qualitative or quantitative FUO criteria was associated with a statistically significant risk of over- or under-estimating infectious diseases and undiagnosed illnesses when using an ICD-10 adjusted FUO five-category system. Clinicians should anticipate differences depending on which criteria are used. While further research is warranted, qualitative criteria provide the best framework for study comparisons.

Comparison of diagnostic spectrum between inflammation of unknown origin and fever of unknown origin: A systematic review and meta-analysis

BackgroundPatients with inflammation of unknown origin (IUO) and fever of unknown origin (FUO) are commonly considered a single population. Differences in underlying causes between both groups may steer the diagnostic work-up. MethodsPubMed, Embase, Web of Science, and ClinicalTrials.gov were searched from July 2009 through December 2023. Studies including both FUO and IUO patients with a sample size of ≥20 were considered. The primary outcome was the difference in the rate of patients affected by predefined diagnostic categories according to meeting FUO or IUO criteria. Data were pooled using random-effects models. ResultsA total of 8 studies met criteria for inclusion, with a total of 1452 patients (466 with IUO and 986 with FUO). The median rate of IUO patients among the included studies was 32 % (range 25–39 %). Patients with IUO had a lower likelihood of infection (OR 0.59 [95 % CI; 0.36–0.95]; I2 0 %). There were no significant differences in the rate of noninfectious inflammatory disorders, malignancies, miscellaneous disorders, or remaining undiagnosed. Comparison of diagnostic subgroups revealed that IUO patients were less likely to have systemic autoinflammatory disorders (OR 0.17 [95 % CI, 0.05–0.58]; I2 42 %) and more likely to have vasculitis (OR 2.04 [95 % CI, 1.23–3.38]; I2 21 %) and rheumatoid arthritis or spondylarthritis (OR 3.52 [95 % CI, 1.16–10.69]; I2 0 %). ConclusionBased on our findings, there is little reason to assume that FUO and IUO patients would benefit from a different initial diagnostic approach.

Cost-effective <i>Siddha</i> Management of Psoriasis Vulgaris with Special Reference to <i>Kalanjagapadai</i> – A Case Report

Psoriasis is a non-infectious and chronic inflammatory skin disorder that is characterized by well-defined erythematous plaques with silvery scales over the epidermis. It significantly affects a patient’s social and psychological well-being. Contemporary medicine offers no definitive treatment. However, corticosteroids are the drug of choice for treating psoriasis. Currently, available therapeutics cause severe side effects on the body. In the Siddha system of medicine, psoriasis can be compared with Kalanjagapadai, because most of the signs and symptoms mimic that of Plaque psoriasis. However, the principle based on the Siddha medicine approach has proven to be effective. This article presents a case of psoriasis treated for 3 months with Siddha herbo-mineral preparations and dietary restrictions. A 40-year-old male patient presented with complaints of well-defined erythematous itchy skin lesion, burning sensation, and silvery scaling all over the body for the past 3 months. Based on the symptoms Kalanjagapadai treatment was adopted here. After giving purgation therapy (Viresanam), and internal and external medications, the patient’s erythema, itching, and scaling symptoms subsided. The Psoriasis Area and Severity Index (PASI) score was decreased. Although psoriasis is intricate to treat, Siddha treatment has proven to be beneficial when using appropriate medications and therapies. In this case report, attempts were given for further scope on Psoriasis in wide-based extensive clinical trials.

Autoimmune Encephalitis: A Literature Review

Autoimmune encephalitis (AIE) defines brain inflammation caused by a misdirected immune response against self-antigens expressed in the central nervous system. AIE encompasses a group of non-infectious immune-mediated inflammatory disorders of the brain parenchyma often involving the cortical or deep gray matter with or without involvement of the white matter, meninges, or the spinal cord. Suggested mechanisms that may trigger AIE include tumors (paraneoplastic), infections (para-infectious), or it may be cryptogenic. This study represents a review of the common forms of AIE, exploring their causes, diagnostic approaches, and management strategies. The previous and ongoing investigations in this field have been driven by the identification of several pathogenic autoantibodies that cause polysymptomatic neuropsychiatric and neurological diseases. AIE comprises a heterogeneous group of disorders that are at least as common as infectious causes of encephalitis. Early treatment is associated with better prognosis and is crucial for the prevention of severe complications. The underlying mechanisms for activation and autoimmune response in the CNS are still unclear. Further investigations are needed to better explain how immune mechanisms affect nervous system functions.

PD02-12 REVISITING THE ROLE OF INFLAMMATORY CYTOKINE-TARGETING APTAMERS IN CHRONIC PROSTATITIS

You have accessJournal of UrologyCME1 Apr 2023PD02-12 REVISITING THE ROLE OF INFLAMMATORY CYTOKINE-TARGETING APTAMERS IN CHRONIC PROSTATITIS Tsun-Hsiang Cheng, Dong-Ru Ho, Hao-Chih Yang, Wai-Nga Chan, Jian-Hui Lin, and Pey-Jium Chang Tsun-Hsiang ChengTsun-Hsiang Cheng More articles by this author , Dong-Ru HoDong-Ru Ho More articles by this author , Hao-Chih YangHao-Chih Yang More articles by this author , Wai-Nga ChanWai-Nga Chan More articles by this author , Jian-Hui LinJian-Hui Lin More articles by this author , and Pey-Jium ChangPey-Jium Chang More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Chronic prostatitis is a non-infectious inflammatory disorder that plays an important role in the development lower urinary tract disease. Pro-inflammatory cytokines are key regulators of the inflammation process in prostate. IL-1β can directly attract innate inflammatory cells, cause tissue destruction, altered pain threshold, and initiate adaptive immunity. We hope to study the effectiveness of DNA aptamers to inhibit IL-1β mediated prostate inflammation in an experimental rat model of non-bacterial prostatitis (NBP). METHODS: In this study, we investigated the effects of inflammatory cytokine targeting aptamers (ICTA), a putative neutralizer of TNF-α and IL-1β activation, on local carrageenan-induced prostate inflammation in aged rats. The von Frey filament and tail-flick tests were performed to determine mechanical allodynia (a painful sensation caused by innocuous stimuli, e.g., light touch) and thermal hyperalgesia (a condition of altered perception of temperature), respectively, and prostate inflammation was examined 7 days after the administration of drugs. RESULTS: The levels of mononuclear cell infiltration, pro-inflammatory cytokine interleukin-1β, caspase 1(casp-1), and NALP 3 (NALP3) in the prostate of aged rats were increased 168 h after the NBP induction. Treatment with ICTA significantly attenuated carrageenan-induced allodynia, hyperalgesia, the increase in prostate glandular hyperplasia, and immune cell infiltration, and elevated levels of downstream cytokines including IL-18, TNF-α, and IL-33 in aged rats. Apoptosis markers, Bcl-2 and caspase-3, were found elevated. CONCLUSIONS: Our results showed that ICTA provides protection against local carrageenan exposure-induced enhanced pain sensitivity (allodynia and hyperalgesia), and that the protective effects may be associated with its ability to neutralize carrageenan-induced IL-1β activation, and result in apoptosis in the prostate of aged rats. Source of Funding: This research was funded by the Chang Gung Medical Foundation, Grant Number CMRPG6L0421-23, CORPG6M0011, CMRPG6L0211-12, CMRPG6M0161, NMRPG6M0071 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e73 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tsun-Hsiang Cheng More articles by this author Dong-Ru Ho More articles by this author Hao-Chih Yang More articles by this author Wai-Nga Chan More articles by this author Jian-Hui Lin More articles by this author Pey-Jium Chang More articles by this author Expand All Advertisement PDF downloadLoading ...

A Successful Bisphosphonates Monotherapy in Spinal Form of Paediatric Chronic Recurrent Multifocal Osteomyelitis (CRMO)—Case Report

Chronic recurrent multifocal osteomyelitis (CRMO) is a non-infectious inflammatory disorder resulting from the multifocal bone and bone marrow lesions with periodic relapses and remissions and with an uncertain prognosis. Treatment options in CRMO are based on expert opinion and relatively small groups of patients. A nine-year-old female patient with no significant past medical history presented with compression fractures and multifocal bone lesions in the thoracic and lumbar spine, as shown in imaging (CT, MRI). Densitometry revealed a diffuse decrease in bone density. Based on the patient's clinical image and above examinations, the other possible aetiologies-infectious (including tuberculosis), neoplasms, Langerhans cell histiocytosis-were ruled out, which led to eventual final diagnosis-CRMO. The patient was successfully treated with pamidronate infusion initiated in cycles over three consecutive days every 3 months. In addition to clinical improvement, there was a significant remission of inflammation and bone structure healing assessed by MRI after four treatment cycles. Intravenous bisphosphonates usage seems to be a good therapeutic option in CRMO paediatric patients with spinal localization of the lesions complicated by compressive fractures. However, more data, based on larger patient populations, are needed to provide a detailed paediatric CRMO treatment algorithm.

Investigator-Determined Categories for Fever of Unknown Origin (FUO) Compared With International Classification of Diseases-10 Classification of Illness: A Systematic Review and Meta-analysis With a Proposal for Revised FUO Classification.

Classifying fever of unknown origin (FUO) into categorical etiologies (ie, infections, noninfectious inflammatory, oncologic, miscellaneous, and undiagnosed disorders) remains unstandardized and subject to discrepancies. As some disease classifications change, a systematic review of studies would help physicians anticipate the frequency of illness types they may encounter that could influence care. We systematically reviewed prospective FUO studies published across the Medline (PubMed), Embase, Scopus, and Web of Science databases from January 1, 1997, to July 31, 2022. We performed a meta-analysis to estimate associated pooled proportions between the investigator-determined choice of disease category and those determined by the International Classification of Diseases, 10th edition (ICD-10), methodology. The proportion of patients with a difference between the investigator and ICD-10-adjusted noninfectious inflammatory disorder category was 1.2% (95% CI, 0.005-0.021; P < .001), and the proportion was similar for the miscellaneous category at 1.5% (95% CI, 0.007-0.025; P < .001). The miscellaneous and noninfectious inflammatory disorders categories demonstrated significant across-study heterogeneity in the proportions of patients changing categories, with 52.7% (P = .007) and 51.0% (P = .010) I2 , respectively. Adjusting FUO-associated diagnoses by ICD-10 methodology was associated with a statistically significant risk of over- or underestimation of disease category frequency approximation when using a 5 FUO category system. An FUO diagnostic classification system that better reflects mechanistic understanding would assist future research and enhance comparability across heterogenous populations and different geographic regions. We propose an updated FUO classification scheme that streamlines categorizations, aligns with the current understanding of disease mechanisms, and should facilitate empirical decisions, if necessary.

Higher diagnostic yield of 18F-FDG PET in inflammation of unknown origin compared to fever of unknown origin

Objective18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an important imaging technique in the workup of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Studies comparing the diagnostic yield of 18F-FDG PET between both entities are lacking. MethodsRetrospective analysis of FUO/IUO patients who underwent 18F-FDG PET between 2000 and 2019 in the University Hospitals of Leuven (Belgium). 18F-FDG PET images were assessed for accuracy and contribution towards the final diagnosis. Logistic regression was performed to evaluate the association between meeting FUO or IUO criteria and diagnostic contribution of 18F-FDG PET with and without adjustment for confounders. ResultsOut of 604 patients, 439 (73%, mean age 56 years, 43% female) underwent 18F-FDG PET imaging, including 349 (79%) classified as FUO and 90 (21%) as IUO. Noninfectious inflammatory disorders were significantly more frequent in the IUO group (37% versus 25%; P = 0.03). 18F-FDG PET imaging had a sensitivity of 93% (89–96%), a specificity of 35% (29–42%), and made a positive contribution to the final diagnosis in 25% (21–29%) of cases. IUO was significantly associated with contributive 18F-FDG PET imaging compared to FUO (aOR 2.21 [95% CI 1.31–3.72]; P = 0.003). Among those with contributive 18F-FDG PET imaging, giant cell arteritis (IUO 25% versus FUO 12%) and polymyalgia rheumatica (IUO 17% versus FUO 1%) were numerically more frequent in the IUO group. ConclusionThe diagnostic contribution of 18F-FDG PET was higher among those with IUO, most likely due to differences in diagnostic spectrum.

Modeling of Transmembrane Domain and Full-Length TLRs in Membrane Models.

Toll-like receptors (TLRs), classified as pattern recognition receptors, have a primordial role in the activation of the innate immunity. In particular, TLR4 binds to lipopolysaccharides (LPS), a membrane constituent of Gram-negative bacteria, and, together withMyeloid Differentiation factor 2(MD-2) protein, forms a heterodimeric complex which leads to the activation of the innate immune system response. Identification of TLRs has sparked great interest in the therapeutic manipulation of the innate immune system. In particular, TLR4 antagonists may be useful for the treatment of septic shock, certain autoimmune diseases, noninfectious inflammatory disorders, and neuropathic pain, and TLR4 agonists are under development as vaccine adjuvants in antitumoral treatments. Therefore, TLR4 has risen as a promising therapeutic target, and its modulation constitutes a highly relevant and active research area. Deep structural understanding of TLR4 signaling may help in the design and discovery of TLR4-modulating molecules with desirable therapeutic properties.Computational studies of the different independent domains composing the TLR4 were undertaken, to understand the differential domain organization of TLR4 in aqueous and membraneenvironments, including Liquid-disordered (Ld)and Liquid-ordered (Lo)membrane models, to account for the TLR4 recruitment in lipid rafts over activation. We modeled, by means of all-atom Molecular Dynamics (MD) simulations, the structural assembly of plausible full-length TLR4 models embedded into a realistic plasma membrane, accounting for the active (agonist) state of the TLR4, thus providing an analysis at both atomic/molecular and thermodynamic levels of the TLR4 assembly and biological activity. Our results unveil relevant molecular aspects involved in the mechanism of receptor activation, and adaptor recruitment in the innate immune pathways, and will promote the discovery of new TLR4 modulators and probes.

Ayurvedic Management of Ekakushtha (Psoriasis) by Single-Drug Therapy

ABSTRACT Well-defined erythematous plaques with silvery-white scales are the hallmarks of the chronic, noninfectious inflammatory skin disorder known as psoriasis. Due to recurrence, it has remained a serious problem. There is no treatment for this condition. The Ayurvedic diagnosis is Ekakushtha, which is a Vata-Kappa-predominant Kshudrakushtha. A 30-year-old female patient visited Ocean Healing Centre in Karnal, India, with complaints of Keshbhoomi rukshata (dryness of scalp), flanks/scales over the back, head, hands, and legs, and itching over the past 3 years. She has taken steroidal medication, but there has been no improvement. Kutaja Kwatha (Wrightia tinctoria), 40 mL BD, was used to treat the ailment before meal internally and Bruhath Dantphladi taila (W. tinctoria) for external application five times a day. The patient was advised to take a capsule of Mahatikta Ghrita once a day after treatment for 1 month. In Avara Satva or Avara Bala patients, Shodhan is contraindicated, in that condition, this Shamana chikitsa is very beneficial and easy to follow. As Kutaja is tikta rasa pradhan and having Rakta dhatu Shodhan property, that’s why Kutaja is used externally and internally in this study and Mahatikta Ghrita prevents dryness of skin as well as prevent relapsing of symptoms. The treatment protocol was found effective in the restoration of normal skin and prevention of recurrence of psoriasis.

Ocular microbiota promotes pathological angiogenesis and inflammation in sterile injury-driven corneal neovascularization

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b+Ly6C+ and CD11b+Ly6G+ myeloid cells, not Foxp3+ regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation.

Etiological spectrum and outcome of fever and inflammation of unknown origin. Does symptom duration matter?

ObjectiveEvidence suggests that the symptom duration may affect the occurrence of certain fever (FUO) and inflammation (IUO) of unknown origin associated conditions. It is unclear if this could potentially guide diagnostic evaluations. We examined the association between symptom duration and diagnostic and prognostic outcomes in FUO/IUO. MethodsWe retrospectively analyzed a cohort of adult patients meeting criteria for FUO/IUO from a tertiary care center in Belgium between 2000 and 2019. The association between symptom duration and outcomes of interest were estimated by Cox proportional hazards models. ResultsAmong 602 patients who met criteria for FUO/IUO (mean age 54 years, 43% female), 132 (22%) and 68 (11%) had symptoms for 3–12 months and >12 months, respectively. There were no significant differences in diagnosis or all-cause mortality between a symptom duration of <3 months and 3–12 months. In contrast, those who had a symptom duration of >12 months were less likely to receive a final diagnosis (aHR 0.42, 95% CI 0.30–0.60), in particular a diagnosis of infectious disorders (aHR 0.29, 95% CI 0.12–0.74), malignancies (aHR 0.11, 95% CI 0.03–0.46), and miscellaneous conditions (aHR 0.22, 95% CI 0.07–0.71), but no significant differences were seen in noninfectious inflammatory disorders (aHR 0.74, 95% CI 0.48–1.15) or all-cause mortality (aHR 0.55, 95% CI 0.19–1.54). ConclusionsThe symptom duration may be used to guide the diagnostic workup among patients with FUO and IUO, in particular those with longstanding symptoms.

Geographic Influence Upon Noninfectious Diseases Accounting for Fever of Unknown Origin: A Systematic Review and Meta-Analysis.

BackgroundDiagnostic outcomes for fever of unknown origin (FUO) remain with notable numbers of undiagnosed cases. A recent systemic review and meta-analysis of studies reported geographic variation in FUO-related infectious diseases. Whether geography influences types of FUO noninfectious diagnoses deserves examination.MethodsWe systematically searched Medline (PubMed), Embase, Scopus, and Web of Science databases using medical subject headings published from January 1, 1997 to March 31, 2021. Prospective clinical studies investigating participants meeting adult FUO defining criteria were selected if they assessed final diagnoses. Meta-analyses were based on the random-effects model according to World Health Organization (WHO) geographical regions.ResultsNineteen studies with significant heterogeneity were analyzed, totaling 2667 participants. Noninfectious inflammatory disorders had a pooled estimate at 20.0% (95% confidence interval [CI], 17.0%–23.0%). Undiagnosed illness had a pooled estimate of 20.0% (95% CI, 14.0%–26.0%). The pooled estimate for cancer was 15.0% (95% CI, 12.0%–18.0%). Miscellaneous conditions had a pooled estimate of 6.0% (95% CI, 4.0%–8.0%). Noninfectious inflammatory disorders and miscellaneous conditions were most prevalent in the Western Pacific region with a 27.0% pooled estimate (95% CI, 20.0%–34.0%) and 9.0% (95% CI, 7.0%–11.0%), respectively. The highest pooled estimated for cancer was in the Eastern Mediterranean region at 25.0% (95% CI, 18.0%–32.0%). Adult-onset Still’s disease (114 [58.5%]), systemic lupus (52 [26.7%]), and giant-cell arteritis (40 [68.9%]) predominated among the noninfectious inflammatory group. Lymphoma (164 [70.1%]) was the most common diagnosis in the cancer group.ConclusionsIn this systematic review and meta-analysis, noninfectious disease diagnostic outcomes varied among WHO-defined geographies. Evaluations for FUO should include local variations in disease prevalence.

Role of the pathologist in the diagnosis of autoimmune encephalitis.

Autoimmune encephalitis is a group of non-infectious immune-mediated inflammatory disorders manifesting with epilepsy and encephalitis syndromes that are associated with autoantibodies in the serum and/or cerebrospinal fluid (CSF). Pathogenic autoantibodies have been discovered against intracellular onconeural antigens, surface neuronal, or synaptic antigens with distinctive pathogenesis that underlie differences in response to immunotherapy. The onconeural antigens incite cytotoxic T-cell-mediated neuronal destruction, whereas surface antigens trigger direct damage by autoantibodies via complement mediated pathways, and hence respond well to immunomodulatory therapy, in contrast to poor response in the former. Neuroimaging, electroencephalogram, and CSF findings being non-specific, detection of autoantibodies is essential for a confirmatory diagnosis. Detection methods available include tissue-based assay, cell-based assays, immunoblot, cell culture, flow cytometry, and enzyme-linked immunosorbent assays. In this review, we discuss the various testing modalities available for onconeural and cell surface antibodies, their sensitivity and specificity and the emerging role of the pathologist in the diagnosis of autoimmune encephalitis. Early diagnosis is crucial for instituting treatment and preventing morbidity and mortality.

Advances in lipid-based pulmonary nanomedicine for the management of inflammatory lung disorders.

Inflammatory lung disorders have become one of the fastest growing global healthcare concerns, with more than 500 million annual cases of disorders such as chronic obstructive pulmonary disease, asthma and pulmonary fibrosis. Owing to environmental changes and socioeconomic disparity, the numbers are expected to grow even more in years to come. The therapeutic strategies and approved drugs currently employed in the management of inflammatory lung disorders show dose-dependent resistance and pharmacokinetic limitations. This review comprehensively discusses lipid-based pulmonary nanomedicine as a potential platform to overcome these barriers while ensuring site-specific drug delivery and minimal side effects in nontargeted tissues for the management of noninfectious inflammatory lung disorders.

Positron Emission Tomography with Computed Tomography in Evaluations of Classical Fever of Unknown Origin and Length of Hospitalization: A 10-Year Medical Record Review of a Tertiary Hospital.

Positron emission tomography with computed tomography (PET/CT) has proven its value for the differential diagnosis of fever of unknown origin (FUO). However, the extent to which PET/CT during FUO evaluation can shorten the length of hospital stay (LOS) remains unclear. A retrospective review of the medical records over a 10-year period from January 2009 to December 2018 of a tertiary university hospital was performed. The inclusion criteria were symptoms with fever persisting for >3 weeks before admission, as defined in classical FUO. Medical records in which PET/CT was performed after the final diagnosis, such as neoplastic causes, were excluded. Moreover, in the neoplasm category evaluated using PET/CT, only diagnostic PET/CT cases were enrolled; PET/CT cases for confirming metastasis or staging were excluded. Final diagnoses were categorized as infection, neoplasm, noninfectious non-neoplastic inflammatory disorder, miscellaneous, and uncategorizable. Each category was separated into evaluation with and without PET/CT for statistical analyses. In total, 91 patients underwent evaluation for FUO and about one in three underwent PET/CT. Overall LOS was not different between the PET/CT and non-PET/CT groups; however, there were differences in LOS within the categories. For infectious causes, the mean LOS was 21.1 and 11.1 days in the PET/CT and non-PET/CT groups, respectively (P = 0.022). For neoplastic causes, the mean LOS was 11.4 and 36.0 days in the PET/CT and non-PET/CT groups, respectively (P = 0.02). Most patients with FUO were aged 50 - 60 years, and their family and work roles were crucial. A lower LOS may benefit both the patients' families and society at large. Interestingly, PET/CT may contribute to shortening the LOS during FUO evaluation when the causes are neoplastic, by approximately 24 days.

Chronic Recurrent Multifocal Osteomyelitis (CRMO): An Unusual Presentation of Limb Pain

Chronic recurrent multifocal osteomyelitis (CRMO), known as nonbacterial osteomyelitis, is an autoinflammatory disease with periodic exacerbations, also known as nonbacterial osteomyelitis. It is a rare, noninfectious inflammatory disorder characterized by multifocal bony lesions with pain. Conventional X-ray and CT imaging show multiple osteolytic and sclerotic lesions in the affected limbs. It is a great challenge for pediatricians to diagnose this disease for its rarity. Early diagnosis, regular follow-up and appropriate treatments are mandatory to reduce morbidity and prevent these disease complications. We report here two cases of CRMO who presented with pain, swelling and redness of multiple sites of lower limbs from the Department of Paediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU). Clinical features, laboratory findings, and characteristic radiological findings were strongly suggestive of CRMO.

Human Chorionic Gonadotropin and Related Peptides: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis.

Sepsis continues to be a major cause of morbidity, mortality, and post-recovery disability in patients with a wide range of non-infectious and infectious inflammatory disorders, including COVID-19. The clinical onset of sepsis is often marked by the explosive release into the extracellular fluids of a multiplicity of host-derived cytokines and other pro-inflammatory hormone-like messengers from endogenous sources (“cytokine storm”). In patients with sepsis, therapies to counter the pro-inflammatory torrent, even when administered early, typically fall short. The major focus of our proposed essay is to promote pre-clinical studies with hCG (human chorionic gonadotropin) as a potential anti-inflammatory therapy for sepsis.

Anatomical Basis of Clinical Manifestations Seen in Cavernous Sinus Syndrome: A Narrative Review

Pathology involving the Cavernous Sinus (CS), generally referred to as Cavernous Sinus Syndrome (CSS), can arise from vascular disorders, neoplasms, infections, and non-infectious inflammatory disorders. An acute understanding of the CS and its regional anatomical structures is therefore pertinent in expounding the highly variable clinical manifestations seen in CSS as well as laying the groundwork for surgical intervention. Though the neuroanatomy of the cavernous sinus has been substantially chronicled in literature, their correlation to clinical signs has only been minimally described. This narrative review serves to address this knowledge gap and aims to comprehensively correlate the clinical manifestations of CSS with the relevant neuroanatomy, thereby allowing medical practitioners to better navigate the diagnostic quandary. We conducted a scoping review of the literature concerning CS anatomy and CSS, complied through MEDLINE/OVID and cross-referencing of articles on PubMed and Google Scholar with the keywords cavernous sinus, cavernous sinus syndrome, clinical signs/manifestations, neuroanatomy, CS pathology, Cavernous Sinus Thrombus (CST) and cavernous sinus neoplasms/tumours.

Sub-Acute Thyroiditis Presenting as Pyrexia of Uknown Origin

Introduction: Pyrexia of unknown origin (PUO) is often a diagnostic challenge. Common causes currently reported include non-infectious inflammatory disorders (NIID) (30.6%), infections (23.1%), malignancy (10.7%) and miscellaneous (12.4%). However, 23.1% remain undiagnosed despite extensive investigations. Fever is a component of subacute thyroiditis (SAT) in 28-83% of subjects reported in the literature. But its presentation as a PUO is reported only in a handful of subjects. Case Presentation: A 71-year-old Asian male presented with evening fevers of 2-3 weeks duration. He had no accompanying sweats, cough, breathlessness, or weight loss. He had a past history of TB, polio, hydatid cyst and hypertension for which he was on treatment. He was a teetotaler. Several family members living in his native land had active TB and he visited them often. Clinical examination at initial presentation was unremarkable. He interrupted investigations to go back to Asia, and became unwell for over 6 weeks with evening fevers and sweating, a weight loss of over 7 kg, and a poor appetite. At this point he had no neck pain, palpitations or bowel abnormalities. Clinical examination continued to be normal upon his return to the UK and in the Endocrine Clinic. Investigations: Investigations were done to exclude (a) infections - There was no growth of pathogenic organisms in repeated blood, urine and sputum cultures. Screening tests for TB, hepatitis, and glandular fever were negative. Blood screens for malarial parasites, amoebic and Brucella serology, and stools examination and culture were also negative. Echocardiography was normal. (b) Malignancy - Urine Bence Jones proteins and serum protein electrophoresis were normal. Bone marrow examination was suggestive of Leishmaniasis but a PCR test excluded this diagnosis. Humoral markers of malignancy were negative. CT scans of the thorax, abdomen and pelvis were normal and did not show any evidence of visceral abnormalities (c) NIID - CRP 120, ESR 130, with blood tests consistent with iron deficiency. Autoimmune screening for dsDNA, ANA, ANCA were negative. Upon return to the UK a PET/CT scan showed the diffuse tracer uptake in both thyroid lobes and changes consistent with a large left lobe. Free thryroxine was 28pmol/l (reference range 9-19.1), and TSH was undetectable (<0.004 mU/l). Thyrotrophin receptor antibodies were negative. Management and conclusion He was given carbimazole initially but this was stopped as he became severely hypothyroid. This hypothyroidism persisted for several months even after stopping carbimazole but reversed spontaneously. He therefore had a biphasic pattern of thyroiditis typical of SAT. There are only 9 previous cases reported of SAT presenting as PUO. Although SAT is a rare cause of PUO, early thyroid testing and if necessary, functional thyroid imaging should be considered in subjects with PUO to confirm it.