Therapeutic potential activity of quercetin complexes against Streptococcus pneumoniae.

This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes (QCX1-6) were synthesized by reacting quercetin with various metal salts and boronic acids and characterized using FTIR spectroscopy. Their antibacterial activity alone and in synergism with antibiotics was evaluated against S. pneumoniae ATCC 49619 using disc diffusion screening, broth microdilution MIC determination, and checkerboard assays. Complexes QCX-3 and QCX-4 demonstrated synergy when combined with levofloxacin via fractional inhibitory concentration indices ≤ 0.5 as confirmed by time-kill kinetics. Molecular docking elucidated interactions of these combinations with virulence enzymes sortase A and sialidase. A biofilm inhibition assay found the synergistic combinations more potently reduced biofilm formation versus monotherapy. Additionally, gene-gene interaction networks, biological activity predictions and in-silico toxicity profiling provided insights into potential mechanisms of action and safety.

Septic pulmonary embolism arising from a small temporal boil in a patient with diabetes mellitus type 2: A rare case report.

Septic pulmonary embolism (SPE) can originate from unusual sources like small boils, warranting consideration of diverse etiologies in respiratory distress. Prompt diagnosis, tailored antibiotics, and vigilant complication management optimize outcomes. Early recognition and treatment of minor infections, especially in diabetes are crucial.

BET inhibition reforms the immune microenvironment and alleviates T cell dysfunction in chronic lymphocytic leukemia.

Redundant tumor microenvironment (TME) immunosuppressive mechanisms and epigenetic maintenance of terminal T cell exhaustion greatly hinder functional antitumor immune responses in chronic lymphocytic leukemia (CLL). Bromodomain and extraterminal (BET) proteins regulate key pathways contributing to CLL pathogenesis and TME interactions, including T cell function and differentiation. Herein, we report that blocking BET protein function alleviates immunosuppressive networks in the CLL TME and repairs inherent CLL T cell defects. The pan-BET inhibitor OPN-51107 reduced exhaustion-associated cell signatures resulting in improved T cell proliferation and effector function in the Eµ-TCL1 splenic TME. Following BET inhibition (BET-i), TME T cells coexpressed significantly fewer inhibitory receptors (IRs) (e.g., PD-1, CD160, CD244, LAG3, VISTA). Complementary results were witnessed in primary CLL cultures, wherein OPN-51107 exerted proinflammatory effects on T cells, regardless of leukemic cell burden. BET-i additionally promotes a progenitor T cell phenotype through reduced expression of transcription factors that maintain terminal differentiation and increased expression of TCF-1, at least in part through altered chromatin accessibility. Moreover, direct T cell effects of BET-i were unmatched by common targeted therapies in CLL. This study demonstrates the immunomodulatory action of BET-i on CLL T cells and supports the inclusion of BET inhibitors in the management of CLL to alleviate terminal T cell dysfunction and potentially enhance tumoricidal T cell activity.

Cedirogant in adults with psoriasis: a phase 2, randomized, placebo-controlled clinical trial.

BACKGROUND: Dysregulated interleukin (IL)-17/IL-23 signaling contributes to psoriasis pathogenesis. Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt), a key transcription factor responsible for IL-17 synthesis and a regulator of the T helper 17 cell lineage program. OBJECTIVE: To evaluate the efficacy and safety of cedirogant to treat moderate-to-severe psoriasis. METHODS: In this phase 2b, multicenter, double-blind, 16-week study (NCT05044234), adults aged 18-65 years were randomized 1:1:1:1 to once-daily oral cedirogant 75 mg, 150 mg, 375 mg, or placebo. Assessments included ≥50%/75%/90%/100% improvement from baseline in Psoriasis Area and Severity Index (PASI 50/75/90/100), static Physician Global Assessment 0/1, Psoriasis Symptoms Scale 0, and improvements in itch, adverse events (AEs), pharmacokinetics, and IL-17A/F levels. Efficacy results based on observed cases were summarized descriptively. RESULTS: Of 156 enrolled patients, most were male (70.5%); 39 patients were randomized to each treatment. Only 47 patients completed the study; the study was terminated early due to preclinical findings. At week 16, PASI 75 achievement rates (primary endpoint) were 28.6%, 7.7%, and 41.7% in the cedirogant 75 mg, 150 mg, and 375 mg groups, respectively, and 0% in the placebo group. AE rates were similar in the cedirogant 75 mg, 150 mg, and placebo groups and higher in the cedirogant 375-mg group; most AEs were mild or moderate. CONCLUSIONS: Patients with psoriasis who received cedirogant showed PASI improvement and cedirogant was generally well tolerated. Results should be interpreted in the context of early study termination. Cedirogant development has been discontinued.

Jagged2 targeting in lung cancer activates anti-tumor immunity via Notch-induced functional reprogramming of tumor-associated macrophages.

Signaling through Notch receptors intrinsically regulates tumor cell development and growth. Here, we studied the role of the Notch ligand Jagged2 on immune evasion in non-small cell lung cancer (NSCLC). Higher expression of JAG2 in NSCLC negatively correlated with survival. In NSCLC pre-clinical models, deletion of Jag2, but not Jag1, in cancer cells attenuated tumor growth and activated protective anti-tumor T cell responses. Jag2-/- lung tumors exhibited higher frequencies of macrophages that expressed immunostimulatory mediators and triggered T cell-dependent anti-tumor immunity. Mechanistically, Jag2 ablation promoted Nr4a-mediated induction of Notch ligands DLL1/4 on cancer cells. DLL1/4-initiated Notch1/2 signaling in macrophages induced the expression of transcription factor IRF4 and macrophage immunostimulatory functionality. IRF4 expression was required for the anti-tumor effects of Jag2 deletion in lung tumors. Antibody targeting of Jagged2 inhibited tumor growth and activated IRF4-driven macrophage-mediated anti-tumor immunity. Thus, Jagged2 orchestrates immunosuppressive systems in NSCLC that can be overcome to incite macrophage-mediated anti-tumor immunity.

The Role of Point-of-Care Testing to Improve Acute Care and Health Care Services.

Health care is one of the most important services that need to be provided to any community. Many challenges exist in delivering proper and effective health services, including ensuring timely delivery, providing adequate care through effective management and achieving good outcomes. Point-of-care testing (POCT) plays a crucial role in delivering urgent and appropriate health services, especially in peripheral communities, emergency situations, disaster areas and overcrowded areas. We collected and reviewed secondary data about point-of-care testing from PubMed, Scopus and Google Scholar. Our findings emphasize that POCT provides fast care with minimal waiting time, avoids unnecessary investigations, aids in triage, and provides decision-makers with a clear understanding of the patient's condition to make informed decisions. We recommend point-of-care testing as a frontline investigation in emergency departments, intensive care units, peripheral hospitals, primary health care centers, disaster areas and field hospitals. Point-of-care testing can improve the quality of health services and ensure the provision of necessary health care.

Pharmacokinetics, Safety, and Tolerability of Cedirogant in Healthy Japanese and Chinese Adults.

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma, thymus (RORγt) developed for treatment of psoriasis. This study aimed to characterize pharmacokinetics, pharmacodynamics, safety, and tolerability of cedirogant following a single oral dose in Japanese participants and multiple oral doses in Japanese and Chinese participants. The single doses evaluated in healthy Japanese participants were 75, 225, and 395 mg. The multiple doses evaluated in both healthy Japanese and Chinese participants was 375 mg once daily for 14 days. Cedirogant plasma exposure increased dose proportionally with administration of single doses. Maximum cedirogant plasma concentration was reached within a median time of 4-5 hours after dosing. The harmonic mean elimination half-life ranged from 19 to 25 hours. Cedirogant pharmacokinetics were similar between Japanese and Chinese participants. Compared with healthy Western participants in a cross-study analysis, steady-state cedirogant plasma exposure was 38%-73% higher in Japanese or Chinese participants. Ex vivo interleukin-17 inhibition increased in a dose-dependent manner and was maximized by 375 mg once-daily doses. The cedirogant regimens tested were generally well tolerated, and no new safety issues were identified. The results supported enrollment of Japanese and Chinese subjects in subsequent clinical trials for cedirogant.

Population pharmacokinetics and exposure-response analyses for efficacy and safety of upadacitinib in patients with axial spondyloarthritis.

Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto-immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA). The approvals of upadacitinib for the treatment of AS and nr-axSpA were based on the safety and efficacy data for upadacitinib 15 mg once-daily compared to placebo from the SELECT-AXIS 1 and SELECT-AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr-axSpA. Exposure-response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure-response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure-response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure-response analyses for efficacy and safety presented here supported the favorable benefit-risk profile with the use of upadacitinib 15 mg once-daily for the treatment of axSpA.

Comparative Analysis of Intravenous Opioids Versus Thoracic Epidural Anesthesia in Fractured Rib Pain Management: A Systematic Review and Meta-Analysis.

Rib fractures, common among trauma victims, lead to significant morbidity and mortality. Managing the associated pain is challenging, with IV opioids and thoracic epidural analgesia (TEA) being utilized. While epidural analgesia is often preferred for fractured rib pain, existing data encompasses both lumbar and thoracic approaches. This review aimed to compare TEA and IV opioids for persistent rib fracture pain. A comprehensive search across five databases yielded 987 articles, of which seven met the eligibility criteria. Outcomes were categorized into primary (pain reduction) and secondary (mortality, hospital/ICU stays, analgesia-related complications) endpoints. Analyzed with Review Manager (RevMan) Version 5.4.1 (2020; The Cochrane Collaboration, London, United Kingdom), the pooled data from two sources showed TEA significantly more effective in reducing pain than IV opioids (standardized mean difference (SMD): 2.23; 95%CI: 1.65-2.82; p < 0.00001). Similarly, TEA was associated with shorter ICU stays (SMD: 0.73; 95%CI: 0.33-1.13; p = 0.0004), while hospitalization duration showed no substantial difference (SMD: 0.82; 95%CI: -0.34-1.98). Mortality rates also did not significantly differ between TEA and IV opioids (risk ratio (RR): 1.20; 95%CI: 0.36-4.01; p = 0.77). Subgroup analysis revealed fewer pneumonia cases with TEA (RR: 2.06; 95%CI: 1.07-3.96; P = 0.03), with no notable disparities in other complications. While TEA's superiority in pain relief for rib fractures suggests it is the preferred analgesic, the recommendation's strength is tempered by the low methodological quality of supporting articles.

Maximal Tizanidine withdrawal managed with dexmedetomidine: a vital intervention.

Tizanidine withdrawal is a rare and complex phenomenon characterized by a surge in adrenergic activity upon abrupt discontinuation of the drug. We present a unique case of a 41-year-old male with multiple comorbidities who self-administered an exceptionally high daily dose of Tizanidine, leading to severe withdrawal symptoms. This case report highlights the challenges in managing such cases. The patient, with a history of myofascial pain syndrome, hypertension, anxiety, and depression, experienced distressing symptoms, including tachycardia, rebound hypertension, neuropsychiatric manifestations, and involuntary muscle movements. Unlike previous cases, our patient required the addition of dexmedetomidine in conjunction with benzodiazepines for symptom management. Reintroduction of Tizanidine, carefully controlled and tapered, led to stabilization of hemodynamics and cessation of involuntary movements. This case underscores the importance of individualized treatment and vigilant monitoring when dealing with Tizanidine withdrawal, particularly at elevated daily doses.

Enhancement of Streptomyces thinghirensis WAE1 for production of bioactive metabolites under different optimization strategies.

Isolation of novel bioactive metabolites from Streptomyces strains is a promising source for drug discovery. However, conventional screening approaches have limitations in identifying new leads due to redundant discoveries. Optimization of culture conditions is important but traditionally optimized one factor at a time, failing to consider interactions. This study addressed these gaps by enhancing metabolite production from Streptomyces thinghirensis WAE1 through statistical optimization. Various chemical and physical factors impacting metabolite production were identified. Response surface methodology with a central composite design was applied to optimize significant factors like carbon source, nitrogen source, inoculum size, pH, temperature and incubation period. This optimized production against Streptococcus pneumoniae, increasing antibacterial activity by 74.92%. Gas chromatography-mass spectrometry revealed 19 bioactive compounds, including 1,25-dihydroxyvitamin D3 inhibiting cell wall development. This highlights S. thinghirensis WAE1's potential as a bioresource and emphasizes studying metabolite production from novel Streptomyces strains to discover new antibacterial drugs.

Cedirogant Population Pharmacokinetics and Pharmacodynamic Analyses of Interleukin-17A Inhibition in Two Phase 1 Studies in Healthy Participants and Participants with Moderate to Severe Psoriasis.

Cedirogant (ABBV-157) is an orally bioavailable inverse agonist of retinoic acid-related orphan receptor gamma thymus. Data from 2 Phase 1 studies were used to characterize cedirogant pharmacokinetics and evaluate target engagement. Cedirogant plasma concentrations and ex vivo interleukin 17A (IL-17A) concentrations from healthy participants and participants with moderate to severe psoriasis (PsO) were analyzed in a population pharmacokinetic and pharmacodynamic modeling framework to characterize cedirogant pharmacokinetics following single and multiple doses and assess ex vivo IL-17A inhibition in relation to cedirogant exposure. Cedirogant population pharmacokinetics were best described by a 2-compartment pharmacokinetic model with delayed absorption and an enzyme turnover compartment to describe cytochrome P450 3A autoinduction. The pharmacokinetics of cedirogant were comparable between healthy participants and participants with PsO. Cedirogant steady-state average and maximum plasma concentrations were predicted to be 7.56 and 11.8 mg/L, respectively, for participants with PsO for the 375 mg once-daily regimen on Day 14. The apparent clearance and apparent volume of distribution for cedirogant were estimated to be 24.5 L/day and 28.2 L, respectively. A direct maximum inhibition model adequately characterized the exposure-response relationship of cedirogant and ex vivo IL-17A inhibition, indicating no temporal delay between exposure and response with a saturable inhibition of IL-17A. Model-estimated half-maximal inhibitory concentration and maximum inhibition values for cedirogant inhibition of ex vivo IL-17A were 0.56 mg/L and 0.76, respectively. The established relationship between cedirogant exposure and biomarker effect supported dose selection for the Phase 2 dose-ranging study in patients with PsO.

Upadacitinib: Mechanism of action, clinical, and translational science.

Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases. Through inhibition of JAK, upadacitinib inhibits phosphorylation of downstream effector proteins, which consequently inhibits cytokine signaling for key pathways involved in inflammatory diseases. Upadacitinib more potently inhibits JAK1 than other JAK isoforms. The pharmacokinetics, pharmacodynamics, efficacy, and safety of upadacitinib were characterized in many clinical trials, which demonstrated the superiority of upadacitinib treatment over placebo or an active comparator in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. The safety profile of upadacitinib supported a favorable benefit-risk profile across all the approved indications. In this article, we review the mechanism of action of upadacitinib and describe how the JAK-STAT (Janus kinase-signal transducers and activators of transcription) pathway is involved in the pathogenesis of several chronic and progressive immune-mediated inflammatory diseases. In addition, this review also provides an overview of key clinical trials that were conducted as well as relevant data which supported the clinical development of upadacitinib and informed the recommended dose(s) in each of the approved indications.

Pharmacokinetics, safety, and efficacy of cedirogant from phase I studies in healthy participants and patients with chronic plaque psoriasis.

Cedirogant is an inverse agonist of retinoic acid-related orphan receptor gamma thymus (RORγt) developed for the treatment of moderate to severe chronic plaque psoriasis. Here, we report the results from two phase I studies in which the pharmacokinetics (PK), safety, and efficacy of cedirogant in healthy participants and patients with moderate to severe chronic plaque psoriasis were evaluated. The studies consisted of single (20-750 mg) and multiple (75-375 mg once-daily [q.d.]) ascending dose designs, with effect of food and itraconazole on cedirogant exposure also evaluated. Safety and PK were evaluated for both healthy participants and psoriasis patients, and efficacy was assessed in psoriasis patients. Following single and multiple doses, cedirogant mean terminal half-life ranged from 16 to 28 h and median time to reach maximum plasma concentration ranged from 2 to 5 h across both populations. Cedirogant plasma exposures were dose-proportional after single doses and less than dose-proportional from 75 to 375 mg q.d. doses. Steady-state concentrations were achieved within 12 days. Accumulation ratios ranged from approximately 1.2 to 1.8 across tested doses. Food had minimal effect and itraconazole had limited impact on cedirogant exposure. No discontinuations or serious adverse events due to cedirogant were recorded. Psoriasis Area and Severity Index (PASI) and Self-Assessment of Psoriasis Symptoms (SAPS) assessments demonstrated numerical improvement with treatment of cedirogant 375 mg q.d. compared with placebo. The PK, safety, and efficacy profiles of cedirogant supported advancing it to phase II clinical trial in psoriasis patients.

Applications of Modeling and Simulation Approaches in Support of Drug Product Development of Oral Dosage Forms and Locally Acting Drug Products: a Symposium Summary.

The number of modeling and simulation applications, including physiologically based pharmacokinetic (PBPK) models, physiologically based biopharmaceutics modeling (PBBM), and empirical models, has been constantly increasing along with the regulatory acceptance of these methodologies. While aiming at minimizing unnecessary human testing, these methodologies are used today to support the development and approval of novel drug products and generics. Modeling approaches are leveraged today for assessing drug-drug interaction, informing dose adjustments in renally or hepatically impaired patients, perform dose selection in pediatrics and pregnant women and diseased populations, and conduct biopharmaceutics-related assessments such as establish clinically relevant specifications for drug products and achieve quality assurance throughout the product life cycle. In the generics space, PBPK analyses are utilized toward virtual bioequivalence assessments within the scope of alternative bioequivalence approaches, product-specific guidance development, and food effect assessments among others. Case studies highlighting the evolving and expanding role of modeling and simulation approaches within the biopharmaceutics space were presented at the symposium titled "Model Informed Drug Development (MIDD): Role in Dose Selection, Vulnerable Populations, and Biowaivers - Chemical Entities" and Prologue "PBPK/PBBM to inform the Bioequivalence Safe Space, Food Effects, and pH-mediated DDIs" at the American Association of Pharmaceutical Scientists (AAPS) PharmSci 360 Annual Meeting in Boston, MA, on October 16-19, 2022, and are summarized here.

The Battle of the Pneumonia Predictors: A Comprehensive Meta-Analysis Comparing the Pneumonia Severity Index (PSI) and the CURB-65 Score in Predicting Mortality and the Need for ICU Support.

The CURB-65 (confusion, uremia, respiratory rate, blood pressure, age ≥ 65 years) score and the pneumonia severity index (PSI) are widely used and recommended in predicting 30-day mortality and the need for intensive care support in community-acquired pneumonia. This study aims to compare the performance of these two severity scores in both mortality prediction and the need for intensive care support. A systematic review and meta-analysis was carried out, following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) 2020 guidelines, and PubMed, Scopus, ScienceDirect, and Google Scholar were searched for articles published from 2012 to 2022. The reference lists of the included studies were also searched to retrieve possible additional studies. Twenty-five studies reporting prognostic information for CURB 65 and PSI were identified. ReviewManager (RevMan) 5.4.1 was used to produce risk ratios, and a random effects model was used to pool them. Both PSI and CURB-65 showed a high strength in identifying high-risk patients. However, CURB-65 was slightly better in early mortality prediction and had more sensitivity (96.7%) and specificity (89.3%) in predicting admission to intensive care support. Thus, CURB-65 seems to be the preferred tool in predicting mortality and the need for admission into intensive care support.

Are the outcomes of single-stage open reduction and Dega osteotomy the same when treating DDH in patients younger than 8 years old? A prospective cohort study.

BACKGROUND: The primary objective was to report our early results after a one-stage procedure [open reduction (OR), Dega pelvic osteotomy (DPO), and femoral osteotomy (FO) when needed] for surgical management of a cohort of patients with developmental dysplasia of the hip (DDH). The secondary objective was to compare the functional, radiological, and complications among patients younger and older than 30 months. MATERIALS AND METHODS: This prospective cohort study included 71 hips with DDH in 61 patients with a mean age of 34.3 ± 19.5 months. All patients underwent one-stage surgical procedures, including OR + DPO and FO, if needed. Functional and radiographic assessment at the last follow-up was conducted using the modified Severin grading system and the Severin classification system, respectively, in addition to assessing the acetabular index (AI), osteotomies healing, and presence of complications. We divided patients into two groups, younger than 30 months (group I) and older than 30 months (group II). RESULTS: We included 35 hips in group I and 36 in group II. All hips received OR + DPO, while 25 (69.4%) hips in group II had FO. The operative time was significantly longer in group II (103.19 ± 20.74 versus 72.43 ± 11.59 min, p < 0.001). After a mean follow up of 21.3 ± 2.3 months, the functional outcomes were satisfactory in 62 (87.3%) hips (94.3% in group I and 80.6% in group II, p = 0.35). There was a significant improvement in the AI in all patients compared with preoperative values (27.2° ± 2.9 versus 37° ± 4.2, p < 0.05). Furthermore, 63 (88.7%) hips had satisfactory radiographic outcomes (94.3% in group I and 83.3% in group II, p = 0.26), and all osteotomies showed radiographic healing. The overall complications incidence was significantly lower in group I compared with group II (5.7% versus 30.6%, p < 0.05), and avascular necrosis occurred in 4 (5.6%) hips, all in group II (p = 0.06). CONCLUSION: One-stage procedure entailing open reduction, Dega pelvic osteotomy, and femoral osteotomy when needed for managing DDH in patients younger than eight years old revealed acceptable clinical and radiological outcomes. However, there was a higher need for a concomitant femoral osteotomy in patients older than 2.5 years, and complications were more frequent.

Clinico-Pathological Features and Immunohistochemical Comparison of p16, p53, and Ki-67 Expression in Muscle-Invasive and Non-Muscle-Invasive Conventional Urothelial Bladder Carcinoma.

INTRODUCTION: The identification of bladder detrusor muscle invasion in urothelial cancer is essential for prognosis and management. We studied the clinical, histological, and immunohistochemical expression of p16, p53, and Ki-67 in urothelial detrusor muscle-invasive bladder cancer (MIBC) and urothelial non-detrusor muscle-invasive bladder cancer (NMIBC) in Egyptian patients. METHODS: Sixty-two bladder urothelial cancer cases obtained through TURBT were included and divided into two groups: (MIBC, stage T2) and NMIBC (T1). Tissue blocks were recut and re-examined microscopically; then, the immunostaining of p16, p53, and Ki-67 was performed to compare both groups and evaluate the 13% cut-off for Ki-67, 20% for p53, and p16 intensity in various conditions aided by telepathology technology. RESULTS AND CONCLUSION: Hematuria was the main clinical first presentation, with no significant difference between either group. The mean age was 61.6 years, with male predominance (52 males and 10 females). The absence of papillary histological pattern was associated with a higher stage, including detrusor muscle invasion (p = 0.000). The overall average percent of p53 immunostaining was 12.9%, revealing no significant difference between MIBC and NMIBC when a cut-off of 20% was implicated. The Ki-67 expression was correlated with higher grade and muscle invasion; however, no association was found with the other two markers' expression. The negative immunostaining of p16 was associated with low grade and NMIBC in the case of the preservation of the papillary pattern. We recommend further studies on the cut-off of widely used markers and more immunohistochemical and genetic studies on the p16(INK4A), taking into consideration the histological pattern of conventional carcinomas.

A Cervical Thymic Cyst in an Adult Female; A Case Report and Comprehensive Literature Review.

Introduction: Cervical thymic cyst accounts for (0.3-1) % of cervical cysts in children and are usually present during the first decade of life with few reported cases in adults. Herein, we present a 34-year-old female with a cervical thymic cyst. We conducted a review of all the previously reported cases as well. Case presentation: The patient complained of an anterolateral neck swelling that was noticed one year ago. It was a soft, fluctuant, mobile, non-tender swelling in the midline and the right side of the lower neck. Neck ultrasonography revealed a large thin-walled cyst, with no internal septa, echoes, or solid parts. Post-contrast MRI of the neck showed a well-defined, oblong-shaped, lobulated cystic lesion just beneath the strap muscle. The cyst extended caudally to the superior border of the anterior mediastinum at the level of the upper border of the manubrium sterni. The patient underwent excision of the swelling under general anesthesia via Kocher's collar neck incision. Connection with the thymus gland was detected behind the manubrium sterni which was separated. Pathological examination showed prominent thymic tissue confirming the diagnosis of a cervical thymic cyst. Conclusion: Adult cervical thymic cyst is very rare with a few cases reported in the literature. Surgical excision in symptomatic patients is the treatment of choice. Paper's main novel aspects: • A rare presentation of a cervical thymic cyst in an adult. • A comprehensive literature review including all the previously reported cases in one table.