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Introduction: The diagnosis and management of common chronic respiratory diseases depend on various parameters obtained from pulmonary function tests (PFTs), such as spirometry, plethysmography, and carbon monoxide diffusion capacity (DLCO). These tests are interpreted following guidelines established by reputable scientific societies like the European Respiratory Society and the American Thoracic Society (ERS/ATS). Aim and Methods: This review aimed to offer a comprehensive framework for interpreting PFTs, incorporating the latest ERS/ATS update (i.e.; 2022), and to briefly explore some complex cases to shed light on their implications for understanding PFTs. Results: The ERS/ATS update outlines a systematic approach to interpreting PFT results, which involves several steps. Initially, results are compared to those of a healthy reference population to determine normal, low, or high parameters. Then, potential ventilatory impairments (VIs), such as obstructive or restrictive VIs, are identified, which could indicate specific chronic respiratory or extra-respiratory diseases. The severity of identified VIs or reductions in DLCO is then assessed. If bronchodilator testing is performed, its response is evaluated. Lastly, any significant changes in PFT parameters over time are noted by comparing current results with previous ones, if available. Despite the clarity provided by the ERS/ATS update, certain uncertainties persist and require clarification, such as the identification of new patterns (e.g.; non-obstructive abnormal spirometry, isolated low forced expiratory volume in 1 s), and classifications of mixed VI or lung hyperinflation in terms of functional severity. Conclusion: This review is a comprehensive framework for interpreting PFTs. Since some issues pose uncertainty in clinical practice, it would be beneficial to the ERS/ATS to reconcile some inconsistencies and provide clearer guidance on different classifications and VIs.

Vaginismus affects up to 1% of the female population and often represents a physical manifestation of an underlying psychological problem. Our objective was to investigate the psychosomatic impact of vaginismus in pregnant women and evaluate the quality of their therapeutic care in Tunisia. We included pregnant patients with vaginismus who presented at our obstetric emergency department between October 2016 and March 2017. All patients were interviewed by one expert psychiatrist and gynecologist using a standardized questionnaire. The State-Trait Anxiety Inventory (STAI) was used to determine anxiety and depression levels. Patients were prospectively followed until their postpartum period and were interviewed by the same experts after delivery. Sixteen weeks after hospital discharge, we contacted all patients via phone. All the information was simultaneously recorded in written form. Twenty pregnant patients with vaginismus were included (85% primary, 15% secondary). Most women described a conservative family background (70%) in which they received little or no sexual education (60%). All women described a feeling of anxiety and anger immediately before sexual intercourse and 40% have never sought medical consultation regarding their vaginismus before. Only 50% reported regular follow-up visits during their pregnancy (without vaginal examination), whereas 25% reported irregular follow-up visits with subjectively bad experiences during attempts of vaginal examinations. Pregnant women with vaginismus are at risk of non-follow-up during their pregnancy due to underlying feelings of shame and experienced lack of understanding by medical staff. Obstetricians should carefully and attentively approach pregnant women with vaginismus in order to ensure adequate medical care during pregnancy.

Muscle biopsy (MB) is an important tool to help differentiate idiopathic inflammatory myopathies (IIMs) from hereditary muscular diseases (HMDs). The usefulness of immunohistochemical stains of the major histocompatibility complex class I and the membrane attack complex are controversial, as both may be identified in some HMDs. More sensitive markers of IIMs have recently been used, such as myxovirus resistance A (MxA), a type I interferon-inducible protein. We selected skeletal MB samples from 81 patients diagnosed with IIM and HMD harbouring overt inflammatory infiltrates on their MBs in the period between March 2022 and September 2024. Two groups were identified: the IIM group (46 cases) and the HMD group (35 cases). We characterized and compared the patterns of MxA protein expression among the two groups. In the IIM group, positive sarcoplasmic MxA expression was detected on the myofibres of 10 patients (24%), among whom were eight dermatomyositis patients. In the HMD group, we did not identify any sarcoplasmic positivity. However, five patients (14%) showed positive labelling restricted to the sarcolemmal membrane, including non-necrotic or regenerating fibres. Our study demonstrates the value of MxA for increasing dermatomyositis diagnostic accuracy and suggests the potential role of interferon type I in the pathophysiology of HMD.

The frequency of extractable nuclear antigen (ENA) seropositivity in patients with negative antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) remains insufficiently characterized. We aimed to estimate the frequency of ENA seropositivity among ANA-IIF-negative individuals (ENA+/IIF-), and to identify associated clinical and methodological determinants. A systematic search of PubMed, EMBASE, Web of Science, and Scopus was conducted for studies published up to January 31, 2025. Studies evaluating ENA seropositivity in ANA-IIF-negative patients using HEp-2 or HEp-2000 substrates were included. Meta-analysis was performed using the Freeman-Tukey double arcsine transformation and random-effects models. Twenty-eight studies, comprising 33 distinct patient groups and 28,552 ANA-IIF-negative samples, were included. The pooled proportion of ENA+/IIF- was 14.1% (95% CI: 10%-18.7%), with substantial heterogeneity (I² = 99%). Subgroup analysis demonstrated significant variation according to clinical indication: 1.4% (95% CI: 1.1%-1.9%) in unspecified indications, 8.1% (95% CI: 6%-10.5%) in suspected connective tissue disease (CTD), and 44.1% (95% CI: 32.3%-54.6%) in confirmed CTD (p < 0.0001). Multivariable meta-regression identified the IIF cut-off dilution, anti-SSA/Ro antibodies, and anti-tRNA synthetase antibodies as significant determinants of ENA+/IIF- frequency. This meta-analysis confirmed that ENA seropositivity is not uncommon in ANA-IIF-negative individuals, and it varies according to clinical context. A negative ANA-IIF result does not reliably exclude CTD, particularly in patients with strong clinical suspicion of CTD. These findings support a targeted, clinically driven ENA testing strategy, especially in conditions such as Sjögren syndrome and inflammatory myopathies. https://www.crd.york.ac.uk/PROSPERO/view/, identifier CRD420250654499.

Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and anti-N-methyl-D- aspartate receptor (NMDAR) encephalitis pediatric cases are especially challenging due to phenotypic variability, limited literature, and the absence of standardized treatment protocols. We present the first documented African case of pediatric MOG and NMDAR overlapping syndrome (MNOS), with a review of all pediatric MNOS cases reported thus far in the literature. A previously healthy seven-year-old boy developed rapid-onset sleep disturbances, neuropsychiatric symptoms, multiple cranial nerve palsies, and hyperkinetic movements. Serological and cerebrospinal fluid (CSF) analyses confirmed dual positivity for anti- MOG and anti- NMDAR antibodies. The patient responded favorably to first line immunotherapy with intravenous immunoglobulin and corticosteroids, showing marked clinical improvement by the six-month follow-up. A corticosteroid taper was initiated thereafter. At fourteen-month follow-up, he had a second episode with a MOGAD- associated cerebral cortical encephalitis phenotype. Antibody screening confirmed persistent dual positivity for both anti-NMDAR and anti-MOG antibodies. The clinical outcome was favorable following first-line immunotherapy combined with oral immunosuppressants. This case highlights the uniqueness of this entity, where antibody dynamics are closely tied to the clinical course.

Introduction Post-COVID syndrome (PCS) is characterized by a polymorphism of symptoms with hypothetical pathophysiological mechanisms. Here, we aimed to analyze the profile of inflammatory cytokines in patients with PCS and to study the relationship between this profile, the clinical symptoms as well as the endothelial function in PCS. Methods Our analytical study involved all eligible patients ( n  = 66) with PCS included from April 2021 to December 2021. The serum concentration of cytokines IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-27, IP-10, MCP-1 and TNF-α was quantified by flow cytometry. Endothelial function was explored by assessing microvascular flow and reactivity using thermal probes. A comparative study was carried out according to the presence of each PCS symptom. Results The average age of our patients was 55.9 ± 16.2 years. The sex ratio was 0.69. Forty-one patients (62%) presented with a severe form of acute infection. The most frequently reported symptoms were dyspnea (67%), fatigue (50%), and memory problems (32%). Fifty-seven patients (86%) had endothelial dysfunction. The majority of patients had increased levels of IP-10 (100%), IL-8 (95%), IFN-γ (95%), MCP-1 (80%), and TNF-α (70%). The serum concentration of IL-10 was below the threshold of quantification in 89% of subjects. The severe form of acute infection was associated with elevated IL-10, MCP-1, and IL-27. Increased IL-6 and IL-27 levels were associated with fatigue while IL-8 concentrations were higher in patients who reported dyspnea. Elevation of IL-8 level was more common in patients with profound impairment of endothelial function. Conclusion Our results further support the presence of endothelial dysfunction in PCS and show an elevation of pro-inflammatory cytokines with a downmodulation of the IL-10- anti-inflammatory response. In addition, immuno-clinical phenotypes emerge, such as an inflammatory profile mediated by IL-6 and IL-27 in fatigue and IL-8 in dyspnea. The identification of immuno-clinical phenotypes would allow a better understanding of the pathophysiology of PCS symptoms.

Alpha-Mannosidosis (AM) is an ultra-rare storage disorder caused by a deficiency of lysosomal alpha-mannosidase encoded by the MAN2B1 gene. Clinical presentation of AM includes mental retardation, recurrent infections, hearing loss, dysmorphic features, and motor dysfunctions. AM has never been reported in Tunisia. We report here the clinical and genetic study of six patients from two Tunisian families with AM. The AM diagnosis was confirmed by an enzymatic activity assay. Genetic investigation was conducted by Sanger sequencing of the mutational hotspots for the first family and by ES analysis for the second one. In the first family, a frameshift duplication p.(Ser802GlnfsTer129) was identified in the MAN2B1 gene. For the second family, ES analysis led to the identification of a missense mutation p.(Arg229Trp) in the MAN2B1 gene in four affected family members. The p.(Ser802GlnfsTer129) mutation induces a premature termination codon which may trigger RNA degradation by the NMD system. The decrease in the levels of MAN2B1 synthesis could explain the severe phenotype observed in the index case. According to the literature, the p.(Arg229Trp) missense variant does not have an impact on MAN2B1 maturation and transportation, which correlates with a moderate clinical sub-type. To explain the intra-familial variability of cognitive impairment, exome analysis allowed the identification of two likely pathogenic variants in GHR and SLC19A3 genes potentially associated to cognitive decline. The present study raises awareness about underdiagnosis of AM in the region that deprives patients from accessing adequate care. Indeed, early diagnosis is critical in order to prevent disease progression and to propose enzyme replacement therapy.

Peach allergy represents a significant clinical problem in Mediterranean populations, yet molecular characterization remains limited in North African countries. This study provides the first comprehensive analysis of peach sensitization patterns in Tunisia using component-resolved diagnostics. To characterize molecular sensitization profiles to peach allergen components, correlate these with clinical manifestations, and evaluate predictive biomarkers in a Tunisian cohort. A retrospective study was conducted including 63 patients referred for suspected peach allergy to the Pasteur Institute of Tunisia between March 2022 and March 2025. After application of exclusion criteria, 49 patients were included in the final analysis. Total and specific IgE levels were measured using ImmunoCAP technology. Component-resolved diagnostics targeted rPru p 1, rPru p 3, rPru p 4, and rPru p 7. Reaction severity was assessed using oFASS-3. Statistical analyses included correlation studies and ROC curve analysis. Thirty-eight patients (77.5%) demonstrated peach allergy with median age 10 years [7-14]. Clinical manifestations included urticaria (86.6%), angioedema (39.4%), respiratory symptoms (rhinitis 42.1%, bronchospasm 23.6%), oral allergy syndrome (32.4%), and anaphylaxis (10.5%). Pru p 3 was predominant (84.2% of patients, median 1.215 kUA/L). Pru p 7, Pru p 1, and Pru p 4 sensitization occurred in 10.5%, 7.8%, and 2% respectively. Peach-specific IgE predicted Pru p 3 sensitization with 100% sensitivity and 66.7% specificity (cut-off 0.23 kUA/L). Strong correlation existed between peach-specific IgE and Pru p 3 levels (ρ = 0.942). No associations were identified between biomarkers and clinical severity. Peach allergy in Tunisia follows the Mediterranean phenotype with predominant Pru p 3 sensitization and significant clinical severity. These findings establish the molecular foundation for evidence-based diagnosis while highlighting the need for region-specific therapeutic approaches.

Anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) myopathy is a rare idiopathic inflammatory myopathy characterized by severe muscle damage and minimal extra-muscular involvement. This report presents the first documented case of severe, treatment-resistant HMGCR-myopathy in a Tunisian and North African patient. A 43-year-old man with no significant medical history experienced progressive muscle weakness over one year, leading to difficulty walking. Examination revealed pronounced proximal muscle weakness, particularly in the lower limbs, with significant quadriceps atrophy. Laboratory results indicated elevated Creatine Kinase (CK) levels at 10000 UI/l and Lactate dehydrogenase (LDH) at 400 UI/l. Electromyography confirmed myogenic damage, and muscle biopsy revealed extensive muscle necrosis and regeneration with moderate inflammatory infiltrates. Screening for anti-HMGCR antibodies was positive. Initial treatment with high-dose prednisone showed a good response but led to flares upon tapering. Subsequent treatment with methotrexate, azathioprine, and rituximab resulted in partial clinical and biological improvement. This case underscores the challenges in diagnosing and managing anti-HMGCR myopathy due to limited awareness and access to testing.

Anti-neutrophil cytoplasmic antibodies (ANCAs) have been reported in systemic lupus erythematosus (SLE). Their clinical significance remains unclear especially in the African populations. This study aimed to assess the prevalence, antigenic targets, and clinical correlations of ANCAs in SLE patients in a Tunisian (North African) cohort. We conducted a cross-sectional case-control study involving 30 patients with systemic lupus erythematosus (SLE) and 30 healthy controls. Blood samples were screened for antineutrophil cytoplasmic antibodies (ANCAs) using indirect immunofluorescence (IIF) (FA 1201-1005-13, Euroimmun ). Enzyme-linked immunosorbent assay (ELISA) (Euroimmun ) was performed on IIF-positive samples to assess six ANCA antigenic targets: proteinase 3, lactoferrin, myeloperoxidase, elastase, cathepsin G, and bactericidal/permeability-increasing protein (BPI). Clinical and immunological evaluations were conducted for all SLE patients at the time of the study. No ANCA- associated vasculitis-SLE overlap cases were identified. ANCAs were detected in 16 of 30 SLE patients (53%) and in 1 of 30 healthy controls (3%). Among the ANCA-positive patients, nine showed reactivity to lactoferrin, while the antigenic target remained undetermined in 7 cases. The median SLEDAI-2K score at inclusion was 8 [1.75-12]. In univariate study, ANCA positivity was significantly associated with acute cutaneous manifestations (p=0.021), lupus nephritis (p=0.001), as well as use of glucocorticoids (p=0.014) and mycophenolate mofetil (p=0.009). Besides, it was associated with lower C3 (p=0.0036) and C4 (p=0.0032) titers and higher anti-dsDNA titers (p<0.0001). In multivariate analysis, ANCA positivity was correlated to anti-ds DNA (p=0.008). When comparing anti-LF positive and anti-LF negative patients, univariate analysis found an association with articular involvement (p=0.011), renal activity index (p=0.036) and ELISA titers (p=0.0004). ANCAs were frequent in our SLE cohort, with lactoferrin as the only identifiable antigenic target, unlike previous reports, which suggests a role to ethnicity and environment components. Their presence was associated with higher disease activity and more severe renal involvement.