Variable Clinical Presentation Research Articles

Diagnostic value of D-dimer to fibrinogen ratio for pulmonary embolism in postpartum women

BackgroundPulmonary embolism is a common disease associated with high mortality and morbidity. Diagnosing pulmonary embolism is challenging due to diverse clinical presentations and the lack of specific biomarkers. The study aimed to investigate the diagnostic value on pulmonary embolism for postpartum women by D-dimer to fibrinogen ratio, and it combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio.MethodsA total of 537 women with suspected pulmonary embolism were selected as the research subjects from the Shanghai First Maternity and Infant Hospital between 1 January 2019 and 31 October 2022. The D-dimer to fibrinogen ratio and it combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio were applied to evaluate the clinical probability of pulmonary embolism, and the positive predictive value of both scores were calculated using computed tomography pulmonary arteriography as a gold standard. The diagnostic value of D-dimer to fibrinogen ratio, combined with neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio was evaluated by the area under the curve, sensitivity, specificity, and other indicators in the receiver operator characteristic curve.ResultsAmong the 502 women included for analysis, 194 (38.65%) were definitely diagnosed as pulmonary embolism. The positive predictive values of D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 70.1%, 50.5%, and 56.5%, respectively in the postpartum women, the area under the curve for the D-dimer to fibrinogen ratio and it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 0.606 (95%CI: 0.562–0.650), 0.624 (95%CI: 0.575–0.673), and 0.639 (95%CI: 0.592–0.686), respectively. The negative predictive values of D-dimer to fibrinogen ratio, it combined with platelet-to-lymphocyte ratio or neutrophil-to-lymphocyte ratio were 50.5%, 70.1%, and 69.8%, respectively.ConclusionThe diagnostic value of the D-dimer to fibrinogen ratio was higher than the D-dimer for the postpartum women with suspected pulmonary embolism. The combination of either the neutrophil-to-lymphocyte ratio or the platelet-to-lymphocyte ratio with D-dimer to fibrinogen ratio is an appropriate strategy to rule out pulmonary embolism.

Pediatric Autoimmune Encephalitis: A Nationwide Study in Latvia.

Autoimmune encephalitis (AE) is the third most common encephalitis in children. Diagnosis can be challenging due to overlapping and diverse clinical presentations as well as various investigation results. This study aims to characterize the clinical, diagnostic features, as well as treatment and outcomes of AE in children and determine the incidence of pediatric AE in Latvia. The study was conducted at the Children's Clinical University Hospital in Riga. The study participants were patients under the age of 18 years diagnosed with AE from 2014 to 2022. Data regarding clinical characteristics, investigation findings, treatment strategy, and outcomes were retrospectively collected from the medical history data system. We included 18 pediatric patients diagnosed with AE. The mean incidence of pediatric AE in Latvia was 0.56 per 100,000 children. Most patients (66.6%) had seronegative AE. In the seropositive group, the most common was anti-methyl-D-aspartate receptor AE, with two patients having other antibodies. The most prevalent clinical features were personality change, cognitive impairment, autonomic dysfunction, and movement disorders. The majority of patients (58.8%) received first-line treatment only. More than half (55.6%) of our AE patient group had long-term sequelae. Our study shows that the pediatric AE incidence in Latvia is similar to what has been previously reported in other studies. A relatively high proportion of seronegative AE was present in our cohort, indicating that awareness of possible misdiagnosis should be raised. Further research is needed to better understand the underlying mechanisms, characterize clinical features, and determine the treatment of choice in different situations to improve long-term outcomes.

Elemental Mercury Poisoning by Self-Injection - A Report of Two Cases.

Injection of mercury into the upper limb is a rare method of self-harm. We report two patients with varied clinical presentations - a 19-year-old male student who injected himself with mercury extracted from a sphygmomanometer bulb and reported to our emergency department 24 hours after the event and a 34-year-old industry worker who presented 2 years after injecting himself with elemental mercury. The management of mercury poisoning is described along with a brief review of literature. Mercury is a toxic element and adequate safety precautions must be taken by the surgical team in the management of such patients. Level of Evidence: Level V (Therapeutic).

Hypertrophic Cardiomyopathy: From Medical Treatment to Advanced Heart Failure Therapies.

There has been much debate surrounding novel medical therapies and heart transplantation listing challenges in patients with hypertrophic cardiomyopathy (HCM). Recent clinical trials led to FDA approval of mavacamten (a cardiac myosin inhibitor), offering symptom relief and potentially delaying/avoiding invasive septal reduction therapies for some patients with HCM and left ventricular outflow obstruction (LVOTO). For those with refractory symptoms and end-stage heart failure, heart transplantation remains the gold standard. However, the concern for the organ allocation system failing to prioritize those individuals persists. HCM is a heterogeneous genetic condition with variable penetration and clinical presentation. Even though a large portion of patients remain asymptomatic, an important minority develops debilitating symptoms refractory to medical therapy. Post-HT short- and long-term outcomes are favorable. However, HT waitlist mortality remains high. For highly selected patients with HCM, a left ventricular assist device is a viable option.

Distinct Profiles of Pulmonary Embolism: Insights from a Case Series

Pulmonary embolism (PE) is a serious and potentially life-threatening condition with significant diagnostic and therapeutic challenges. Here, we present a case series of three patients with PE, each with a distinct clinical profile and severity, to provide insights into the heterogeneity of this condition. The cases illustrate the importance of timely diagnosis and individualised management approaches for optimal patient outcomes. The study presents a comprehensive analysis of the clinical, electrocardiographic, and radiological findings and therapeutic interventions employed in managing the cases. Our report highlights the need for continued research and clinical awareness of this complex condition to improve understanding and management. This case series adds to the existing literature on the diverse clinical presentations of PE and emphasises the critical importance of tailored management strategies.

Endometriosis and Adenomyosis: Modern Concepts of Their Clinical Outcomes, Treatment, and Management

Endometriosis and adenomyosis are complex gynecological conditions characterized by diverse clinical presentations, including superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The hallmark features of these pathologies involve the manifestation of pain symptoms and infertility, and approximately 30% of patients are asymptomatic. Despite ongoing research, definitive treatments for these conditions remain elusive, and clinical management primarily revolves around medical or surgical interventions. Recent advancements in our understanding of the efficacy of various treatment modalities, including medical therapy and surgical interventions, have provided clinicians with valuable insights into pain relief and fertility preservation. This review aims to provide an updated overview of the latest literature on clinical outcomes, treatment options, and management strategies for different types of endometriosis. By synthesizing the newest available data, this review seeks to inform clinicians and guide decision making based on factors such as patients’ symptom severity, childbearing desire, and overall health.

Endometriosis and Adenomyosis: Modern Concepts of Their Clinical Outcomes, Treatment, and Management

Endometriosis and adenomyosis are complex gynecological conditions characterized by diverse clinical presentations, including superficial peritoneal endometriosis (SPE), ovarian endometrioma (OMA), and deep infiltrating endometriosis (DIE). The hallmark features of these pathologies involve the manifestation of pain symptoms and infertility, and approximately 30% of patients are asymptomatic. Despite ongoing research, definitive treatments for these conditions remain elusive, and clinical management primarily revolves around medical or surgical interventions. Recent advancements in our understanding of the efficacy of various treatment modalities, including medical therapy and surgical interventions, have provided clinicians with valuable insights into pain relief and fertility preservation. This review aims to provide an updated overview of the latest literature on clinical outcomes, treatment options, and management strategies for different types of endometriosis. By synthesizing the newest available data, this review seeks to inform clinicians and guide decision making based on factors such as patients’ symptom severity, childbearing desire, and overall health.

Lichen sclerosus of the oral mucosa: a hidden phenomenon.

Oral lichen sclerosus (OLS) represents a diagnostic challenge even for expert dermatologists due to its rarity and subtle clinical manifestations. Only few cases have been reported in literature to date. OLS typically presents with whitish macules in the oral cavity. Histopathological examination remains crucial for definitive diagnosis, with characteristic features including epithelial atrophy, subepithelial hyalinization, loss of elastic fibers, and lymphocytic infiltration. Management strategies vary depending on lesion size and symptomatic presentation, with topical or intralesional corticosteroids being the most commonly used treatment modalities. Long-term monitoring is recommended due to the potential for malignant transformation, although no cases have been reported to date. Greater awareness and understanding of OLS are essential for accurate diagnosis and effective management. Based on these findings, we recommend performing an accurate evaluation of the oral mucosa, especially when dealing with patients affected by genital or extragenital lichen sclerosus (LS). Moreover, we emphasize the importance of multidisciplinary collaboration between dermatologists and other specialists of oral disorders, such as dentists. This short review briefly summarizes available data on OLS, highlighting its diverse clinical presentations and diagnostic challenges. Despite its infrequent occurrence, OLS should be considered in the differential diagnosis of white macules in the oral cavity.

Anti-HMGCR myopathy: diversity of clinical presentations in a national cohort in New Zealand

AimsWe describe the varied clinical presentations, barriers in diagnosis and outcomes of anti-HMGCR myopathy in a large national cohort. MethodsAdults found positive for serum anti-HMGCR autoantibodies via line blot or enzyme-immunoassay followed by immunoprecipitation were included in the study. ResultsOf 75 patients identified, the records of 72 (96%) described weakness as the presenting symptom. The records of 65 gave a reliable description of proximal weakness. In 22/65 (33.8%) the weakness was described as predominantly or solely lower limb weakness. Forty-five of 75 (60%) presented with a subacute onset (duration of symptoms >4 weeks -<6 months), whilst 22/75 (29.3%) presented with a more indolent chronic onset (duration of symptoms >6 months). Eighteen of 75 (24%) suffered falls and 2/75 (2.7%) had “general decline”. In three patients no weakness was described: two presented with myalgia and one with a skin rash characterized as Jessner lymphocytic skin rash. Median creatine kinase at presentation was 7337 U/L (range 1050-25500). Muscle biopsy was performed in 38 (50.7%). Associated malignancy was infrequent. Four patients recovered without immunosuppression. Five-year and 10-year survival was 92.7% (95% CI 80.6-97.4%), and 82.5% (95% CI 61.2-92.8%) respectively. ConclusionRecurrent falls, a long prodrome and dominant lower limb proximal weakness were common in this anti-HMGCR myopathy cohort. These features overlap with frailty syndrome and sporadic inclusion body myositis emphasizing the importance of considering anti-HMGCR myopathy in that clinical context. A minority of patients recover after statin withdrawal alone.

Illuminating characteristic patterns of inflammatory dermatoses: A comprehensive dual-imaging approach using Optical coherence tomography and Line-field confocal optical coherence tomography.

Inflammatory skin diseases, such as psoriasis, atopic eczema, and contact dermatitis pose diagnostic challenges due to their diverse clinical presentations and the need for rapid and precise diagnostic assessment. While recent studies described non-invasive imaging devices such as Optical coherence tomography and Line-field confocal OCT (LC-OCT) as possible techniques to enable real-time visualization of pathological features, a standardized analysis and validation has not yet been performed. One hundred forty lesions from patients diagnosed with atopic eczema (57), psoriasis (50), and contact dermatitis (33) were imaged using OCT and LC-OCT. Statistical analysis was employed to assess the significance of their characteristic morphologic features. Additionally, a decision tree algorithm based on Gini's coefficient calculations was developed to identify key attributes and criteria for accurately classifying the disease groups. Descriptive statistics revealed distinct morphologic features in eczema, psoriasis, and contact dermatitis lesions. Multivariate logistic regression demonstrated the significance of these features, providing a robust differentiation between the three inflammatory conditions. The decision tree algorithm further enhanced classification accuracy by identifying optimal attributes for disease discrimination, highlighting specific morphologic criteria as crucial for rapid diagnosis in the clinical setting. The combined approach of descriptive statistics, multivariate logistic regression, and a decision tree algorithm provides a thorough understanding of the unique aspects associated with each inflammatory skin disease. This research offers a practical framework for lesion classification, enhancing the interpretability of imaging results for clinicians.

Unusual Presentation of Chromoblastomycosis Masquerading as Cutaneous Abscess on the Back: A Case Report

Chromoblastomycosis, a chronic cutaneous mycosis caused by pigmented fungi, is typically associated with trauma in the exposed parts of the body. We report a 68-year-old male farmer diagnosed with chromoblastomycosis clinically mimicking a cutaneous abscess on the back, an unusual location. Histopathological and mycological examination identified Fonsecaea pedrosoi. Treatment with itraconazole and cryotherapy showed improvement after 4 months. High suspicion index and biopsy are imperative for early diagnosis of chromoblastomycosis. This case adds to the limited cases reported in Korea, emphasizing the importance of considering chromoblastomycosis in diverse clinical presentations.

DISCOVERY OF DYSKERATOSISCONGENITA BY APLASTICHEMORRHAGE: A REVEALINGCLINICAL CASE

Dyskeratosiscongenita (DC) is a rare geneticdisordercharacterized by a distinctive clinicaltriadaffecting the skin, mucous membranes and bonemarrow. Although the condition has been described for over a century, itoftenremainsunrecognized and under-diagnosed due to its variable clinicalpresentation. Typicalclinical manifestations of DC includereticular skin pigmentation, naildystrophy and mucosallesionssuch as oral leukoplakia. However, the clinicalpresentation can beheterogeneous, sometimescomplicating the diagnosis. In addition to cutaneous and mucosalsymptoms, DC can also lead to serious complications such as bonemarrowfailure, increasing the risk of anemia, thrombocytopenia and neutropenia. In addition, patients with DC have an increasedrisk of neoplastic complications.Wepresent the case of a 7-year-old childfrom a first-degreeconsanguineousmarriage, whoconsulted for the first time with an anemic syndrome. Afterdetailedevaluation, the diagnosis of bonemarrowaplasia syndrome on a background of dyskeratosiscongenitawasestablished. This observation highlights the diagnostic challenges encountered in DC and underscores the importance of early recognition and appropriate management to improve patient prognosis.

An uncommon diagnosis of a young female with fever of unknown origin (FUO): Idiopathic Hemophagocytic Lymphohistiocytosis (HLH)

Background. Hemophagocytic Lymphohistiocytosis (HLH), characterized by the uncontrolled activation of immune cells leading to a hyperinflammatory state, is seldom considered in the initial differential diagnosis of FUO. The rarity of idiopathic HLH, especially in young individuals without an identifiable trigger, emerges as an uncommon and particularly challenging diagnosis. This case report presents a compelling narrative of a young female grappling with the complexities of FUO, ultimately revealing the rare and life-threatening entity of idiopathic HLH. Case report. A 25 year old female was referred to our hospital in view of persistent high grade fever since 3 months. Patient has no other complaints. Vitals stable. General and systemic examination normal. Lab investigations showed a total leukocyte count 18000 cell/μL, hemoglobin 9.2 g/dL, and platelets 68000 cells/μL. Other blood investigations showed erythrocyte sedimentation rate (ESR) 88 mm/h, C-reactive protein 21 mg/L, ferritin 670 ng/mL, triglyceride 281 mg/dL, and fibrinogen 1.2g/L. She also had transaminitis with AST 80, ALT 92 and ALP 1442. The entire infectious diseases panel was done which came negative for all, including viral serologies and hepatitis markers. Procalcitonin level was normal and no other relevant investigations came positive. Autoimmune panel analysis also came negative. Blood cultures came negative in two different samples. Also, there is no evidence of vegetation in echocardiography. Coming to the invasive investigations, bone marrow biopsy and aspiration were done to arrive at a diagnosis and it showed hemophagocytosis. Endoscopy and colonoscopy were done, which came normal. CT thorax and abdomen also showed no significant abnormalities, ruling out the probability of missing any gross malignancies. After all this extensive work up and according to Hscore, which is used to estimate an individual’s risk of having reactive hemophagocytic syndrome, this patient was diagnosed with HLH. According to the current HLH guidelines, initial treatment for the disease consists of etoposide, corticosteroids (dexamethasone), or cyclosporine given for 8 weeks. The patient was started on the same above treatment regimen, but only with corticosteroids for a period of 8 weeks, after a consultation with the hematologist. No recurrence is seen in her 6-months of follow-up. The regimen was well tolerated by the patient. Studies also have shown that therapeutic plasma exchange also has a role in HLH treatment, which can be tried in familial and relapsing cases. Conclusion. In our case, this young female was diagnosed to have idiopathic HLH, after ruling out all the familial and secondary causes of HLH including infections, malignancy and autoimmune diseases. The patient was also started on treatment early after the bone marrow and other relevant investigations according to HScore suggested the diagnosis of HLH and the patient improved accordingly. Hence, apart from clearly knowing the etiology or clinical manifestations, HLH is associated with a high mortality rate if appropriate treatment not given. Generally, the underlying etiology determines the prognosis of the disease. But, it is not a good idea to delay the treatment in order to find the cause and type of HLH, because the exhaustive work up might lead to unacceptable delays in improvement and prognosis of the patient. The diagnostic work up and treatment should be done simultaneously in the patient, which has been done in our case and it lead to a good outcome. Though HLH is a fatal and dangerous disease and also highly challenging to make a diagnosis due its uncommon and largely variable clinical presentation, smart work up and early initiation of treatment will lead to better prognostic outcomes.

Variegated overexpression of chromosome 21 genes reveals molecular and immune subtypes of Down syndrome

Individuals with Down syndrome, the genetic condition caused by trisomy 21, exhibit strong inter-individual variability in terms of developmental phenotypes and diagnosis of co-occurring conditions. The mechanisms underlying this variable developmental and clinical presentation await elucidation. We report an investigation of human chromosome 21 gene overexpression in hundreds of research participants with Down syndrome, which led to the identification of two major subsets of co-expressed genes. Using clustering analyses, we identified three main molecular subtypes of trisomy 21, based on differential overexpression patterns of chromosome 21 genes. We subsequently performed multiomics comparative analyses among subtypes using whole blood transcriptomes, plasma proteomes and metabolomes, and immune cell profiles. These efforts revealed strong heterogeneity in dysregulation of key pathophysiological processes across the three subtypes, underscored by differential multiomics signatures related to inflammation, immunity, cell growth and proliferation, and metabolism. We also observed distinct patterns of immune cell changes across subtypes. These findings provide insights into the molecular heterogeneity of trisomy 21 and lay the foundation for the development of personalized medicine approaches for the clinical management of Down syndrome.

Diagnosis of Pulmonary Embolism: A Review of Evidence-Based Approaches.

Venous thromboembolism, commonly presented as pulmonary embolism and deep-vein thrombosis, is a paramount and potentially fatal condition with variable clinical presentation. Diagnosis is key to providing appropriate treatment in a safe and timely fashion. Clinical judgment and assessment using clinical scoring systems should guide diagnostic testing, including laboratory and imaging modalities, for optimal results and to avoid unnecessary testing.

Clinicopathologic Characterization of Sarcina ventriculi in the Upper Gastrointestinal Tract.

The bacterium Sarcina ventriculi (SV) is rarely identified in the upper gastrointestinal (GI) tract and has been associated with diverse clinical presentations. We aimed to characterize the clinicopathologic features of SV in the GI tract. Seventeen specimens (3 gastrectomy and 14 biopsy specimens) with histologic diagnosis of SV were identified and analyzed. The patients (9 female, 8 male) had a median age of 65 (range 32-86) years. Five (30%) patients presented acutely with GI bleeding or altered mental status. Other relevant symptoms included abdominal pain (n = 6, 35%), diarrhea (n = 4, 24%), dysphagia/dyspepsia (n = 3, 18%), and nausea/vomiting (n = 3, 18%). SV organisms were mainly identified in the stomach (n = 14, 82%), rarely at the gastroesophageal junction (n = 2, 12%), esophagus (n = 2, 12%), or duodenum (n = 1, 6%). Endoscopically, retained food debris was found in 5 of 13 (38%) examined patients. Histologically, the majority of specimens (12 out of 17, 71%) showed mild alterations including reactive gastropathy, inactive gastritis, or reflux (Grade 1). The other 5 specimens (29%) demonstrated erosion, ulcer, necrosis, or perforation (Grade 2). The most commonly associated comorbidities were diabetes mellitus (n = 10, 59%), gastroparesis/outlet obstruction (n = 10, 59%), and gastroesophageal reflux disease (n = 6, 35%). Upon follow-up, 3 (18%) patients with acute phlegmonous gastritis died shortly after gastrectomy. Our case series, the largest reported so far, describes a spectrum of histologic severity associated with SV infection. Diabetes and gastroparesis/outlet obstruction manifested as retained food debris endoscopically are common findings with SV, and may provide a growth medium for this organism and provoke pathogenicity contributing to fatality in acute conditions.

Neuroprotective effects of flavonoids: endoplasmic reticulum as the target.

The incidence of neurological disorders, particularly age-related neurodegenerative pathologies, exhibits an alarming upward trend, while current pharmacological interventions seldom achieve curative outcomes. Despite their diverse clinical presentations, neurological diseases often share a common pathological thread: the aberrant accumulation of misfolded proteins within the endoplasmic reticulum (ER). This phenomenon, known as ER stress, arises when the cell's intrinsic quality control mechanisms fail to cope with the protein-folding burden. Consequently, misfolded proteins accumulate in the ER lumen, triggering a cascade of cellular stress responses. Recognizing this challenge, researchers have intensified their efforts over the past two decades to explore natural compounds that could potentially slow or even reverse these devastating pathologies. Flavonoids constitute a vast and heterogeneous class of plant polyphenols, with over 10,000 identified from diverse natural sources such as wines, vegetables, medicinal plants, and organic products. Flavonoids are generally divided into six different subclasses: anthocyanidins, flavanones, flavones, flavonols, isoflavones, and flavonols. The diverse family of flavonoids, featuring a common phenolic ring backbone adorned with varying hydroxyl groups and additional modifications, exerts its antioxidant activity by inhibiting the formation of ROS, as evidenced by research. Also, studies suggest that polyphenols such as flavonoids can regulate ER stress through apoptosis and autophagy. By understanding these mechanisms, we can unlock the potential of flavonoids as novel therapeutic agents for neurodegenerative disorders. Therefore, this review critically examines the literature exploring the modulatory effects of flavonoids on various steps of the ER stress in neurological disorders.

GCT-15. CLINICAL AND MOLECULAR CHARACTERIZATION OF INFANTILE CENTRAL NERVOUS SYSTEM GERM CELL TUMORS

Abstract BACKGROUND The management of infantile central nervous system germ cell tumors (CNS-GCTs) presents unique challenges, including variable clinical presentations such as tumor size and propensity for hemorrhage. Moreover, data on the clinical and molecular features remain limited. METHODS We conducted a clinical and molecular analysis of CNS-GCTs in children aged 6 years or younger, registered with the Japan Children’s Cancer Group and the iGCT consortium. DNA methylation analysis was performed using the Illumina Methylation EPIC array to identify potential molecular prognostic indicators. RESULTS The cohort comprised 43 patients, with a median age at onset of 6.5 months (0–68 months). Notably, 23 patients (54%) were diagnosed before 1 year of age. The male-female ratio was 27:15. Most common tumor location was cerebellum (13 cases). The median AFP level was 538 ng/ml (0–206460). Pathologically, the tumors were predominantly diagnosed as teratomas and yolk sac tumors. Teratomas were more common in patients diagnosed before 1 year of age, while mixed GCTs were more frequent in those diagnosed after 3 years. Molecular analysis identified four cases as embryonal tumors, including three AT/RTs and one DICER1-mutant intracranial sarcoma. The 3-year overall survival rates varied significantly by diagnosis: mixed GCTs at 100%, teratomas at 90.6%, yolk sac tumors at 30.0%, and embryonal tumors at 0%. Notably, two patients with teratomas developed metachronous tumors more than 10 years post-diagnosis, with both secondary tumors exhibiting mutations in the MAPK pathway absent in the primary tumors. CONCLUSION Infantile CNS-GCTs exhibit distinct clinical and molecular profiles compared to those in older children and adults. Not all tumors classified as GCTs based on molecular characterization were GCTs; some were embryonal tumors, potentially impacting treatment strategy. The genetic analysis suggests that some metachronous GCTs may represent second primary tumors rather than recurrences.

‘Male cystitis does not exist’: A qualitative study of general practitioners’ experiences and management of male urinary tract infections in France

Background Male urinary tract infections (mUTIs) are rare in primary care. The definition of mUTIs varies across countries. The therapeutic management of mUTIs in France is based on a 14-day course of fluoroquinolones despite a high risk of antimicrobial resistance. Objectives The objective of this qualitative study was to explore general practitioners’ (GPs) experiences and behaviours regarding the diagnostic and therapeutic management of mUTIs. Methods GPs were recruited by convenience sampling in Haute Normandie (France) and interviewed individually with semi-structured guides. GPs’ experiences and behaviours were recorded and analysed using an interpretive phenomenological approach. Results From March 2021 to May 2022, 20 GPs were included in the study. Defining a mUTI was perceived as a diagnostic challenge. A diagnosis based on clinical evidence alone was insufficient and complementary tests were required. For GPs: ‘male cystitis does not exist’. A mUTI was considered an unusual disease that could reveal an underlying condition. GPs considered fluoroquinolones to be ‘potent’ antibiotics and treated all patients with the same 14-day course. GPs implemented improvement strategies for antibiotic stewardship and followed the guidelines using a computerised decision support system. Conclusions GPs’ experiences of mUTIs are limited due to low exposure and variable clinical presentations in primary care, representing a diagnostic and therapeutic challenge. In order to modify GPs’ antibiotic prescribing behaviours, a paradigm shift in the guidelines will need to be proposed. KEY MESSAGES Defining a male urinary tract infection represents a diagnostic challenge for GPs. A diagnosis based on clinical evidence alone is insufficient and complementary tests are required. A male urinary tract infection is an unusual disease in primary care and suggests a more serious underlying condition.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.