Clinical Treatment Modalities Research Articles

Acute coronary syndrome in young (≤45 Years) patients: a multicenter observational study

Introduction: Acute Coronary Syndrome (ACS) in young individuals (≤45 y) is increasingly recognized as a significant health concern, yet research in this demographic remains limited, particularly within the Palestinian context. This study aims to bridge this gap by comprehensively investigating the clinical characteristics, age-specific profiles, gender disparities, treatment modalities, and angiographic patterns of ACS in young patients compared to their older counterparts. Materials and Methods: A multicenter observational study was conducted, enrolling 468 participants aged 18-55 diagnosed with ACS and admitted to three prominent Palestinian hospitals. Data were collected from medical records, and statistical analysis was performed to assess demographic characteristics, clinical presentations, risk factors, treatment strategies, and outcomes. Results: The majority of participants were male (87%), with a higher proportion in the older age group (>45 y). Clinical presentations varied, with Non-ST Segment Elevation Myocardial Infarction (NSTEMI) being the most common diagnosis (48%). Risk factors such as smoking, hypertension, and diabetes were prevalent, with notable gender and age-specific differences. Percutaneous Coronary Intervention (PCI) was the predominant treatment strategy (83%), with consistent medication use across age groups. Conclusion: ACS in young patients poses a significant public health challenge in Palestine, necessitating tailored preventive strategies and comprehensive management approaches. Understanding the unique demographic and clinical characteristics of young ACS patients is crucial for informing targeted interventions and policies aimed at reducing the burden of cardiovascular disease in this population. These findings contribute valuable insights to the existing literature and underscore the importance of further research in this area to improve outcomes and mitigate the impact of ACS in young individuals globally.

Primary Retroperitoneal Tumors: A Report of 08 Cases at the General Surgery Department of The Mohamed VI University Hospital in Marrakech

Primary retroperitoneal tumors are a rare and heterogeneous group of neoplasms arising within the retroperitoneal space, excluding the kidneys, urinary tract, adrenal glands, major blood vessels, and adjacent viscera. Treatment involves surgical resection, often requiring sacrifices of adjacent organs, with adjuvant chemotherapy considered in some cases. Histologically, mesodermal tumors were most common, with myxoid liposarcomas being predominant. Long-term outcomes vary, with some cases showing favorable evolution but others experiencing recurrence or mortality post-surgery. This study aims to provide insights into the clinical presentation, diagnostic approach, treatment modalities, and long-term outcomes of primary retroperitoneal tumors based on a retrospective analysis of cases treated at the general surgery department of the Mohamed VI University Hospital in Marrakech. By elucidating the characteristics and management of these tumors, this study seeks to contribute to the understanding of primary retroperitoneal tumors and guide future diagnostic and therapeutic strategies to improve patient outcomes.

Locally advanced nasopharyngeal carcinoma in adolescents treated with tomotherapy: Experience at King Faisal Specialist Hospital and Research Centre.

Nasopharyngeal carcinoma (NPC) is a rare disease worldwide; To the best of our knowledge, there is no established standard of care specifically tailored for the adolescent population. The majority of existing research relies on retrospective data analysis. Evaluate clinical features, treatment results, prognostic factors and late toxicities of locally advanced NPC patients treated with tomotherapy. Retrospective. Tertiary care hospital. Between January 2007 and January 2020, we treated patients with NPC, aged between 14 and 21 years, with concomitant chemoradiotherapy using tomotherapy at our institution. We prospectively collected details of clinical characteristics, treatment modalities, outcomes and prognostic factors of these patients and then analysed them retrospectively. 3-5 years overall survival (OS), 3-5 years locoregional control rate, 3-5 years disease-free survival (DFS), prognostic factors. 51 patients. There were 26 male and 25 female patients included in our study. The mean age was 16.5 years, 5 (9.8%) patients with stage III, and 46 (90.2%) with stage IVa according to the American Joint Committee on Cancer, 8th edition staging system. Most patients (98%) received two or more cycles of induction chemotherapy. All patients received concomitant chemoradiotherapy. The median total dose of radiotherapy delivered was 6600 cGy (range 4800-7000). With a median follow-up of 73 months (range 9-168 months), a 5-year locoregional control rate, 5-year OS and 5-year DFS rates were 100%, 86.8% and 71.7%, respectively. Five years later, disease control was 71.7%. Ten (19.6%) patients had disease recurrence in the form of distant metastases during the follow up. Helical tomotherapy has an excellent late toxicity profile without compromising clinical outcome for patients with NPC. Radiotherapy remains the mainstay of treatment of nasopharyngeal carcinoma to achieve remarkable local control rates. Single institution experience, small number of patients, and retrospective design.

Clinico-radiological presentation and outcome of brain abscess in congenital cyanotic heart disease

Introduction Patients with congenital cyanotic heart disease (CCHD) are at increased risk of developing brain abscesses. Having a brain abscess is itself a risk for the patient and concomitant cyanotic heart disease makes it a double jeopardy. The management of brain abscesses depends on the size, number, stage, and location of the abscess and can be medical and surgical. Methods This retrospective chart review was conducted at Tribhuvan University Teaching Hospital, Kathmandu, Nepal between January 2019 and December 2023. Demographic and clinical profiles, imaging studies, treatment modalities, and outcomes were analyzed. Results Out of 17 patients, 11 were males and six were females. The mean age of the study population was 13.41 +/- 11.08 years. The most common associated cardiac problem was Tetralogy of Fallot seen in six (35.3%) patients and the most common abscess site was the parietal lobe (38%). The most common presenting symptom was vomiting, seen in 76%. Twelve patients underwent burrhole and aspiration and 17.6% of patients underwent surgical excision of the abscess wall whereas 11.7% of the patients were managed conservatively. Positive culture was seen in 33.3%. S. aureus was the most common organism grown. There was no mortality. Conclusion High index of suspicion for brain abscess is necessary in patients with congenital cyanotic heart disease. Early diagnosis and treatment lead to a favorable outcome.

Systematic Review: Seventy-Seven Cases of Signet Ring Cell Adenocarcinoma of the Bladder

Background: Signet ring cell adenocarcinoma (SRCC) of the bladder is a rare and aggressive histological subtype of bladder cancer. Due to its infrequency, the understanding of its clinical behaviour, treatment strategies, and outcomes remains limited, being primarily derived from isolated case reports and series. Objective: To systematically review and analyse the available literature on SRCC of the bladder, emphasizing its clinical characteristics, diagnostic approaches, treatment modalities, and outcomes. Material and Methods: A comprehensive search was conducted across PubMed, Embase, and Medline following the PRISMA guidelines, including case reports, case series, observational studies, and clinical trials reporting on bladder SRCC. Results: We included 38 articles reporting on 77 patients, primarily males (79.2%), with a median age of 64 years. The most common presenting symptoms were haematuria (64.8%) and lower urinary tract symptoms (46.3%). All the diagnoses were based on histopathological examination of bladder tissue samples and immunohistochemistry. Mixed histological types of bladder cancer were found in 20.7% of cases, most commonly urothelial carcinoma (61.1%). The treatments varied, with 53.2% of patients undergoing radical cystectomy, 24.7% receiving radiotherapy, and 16.9% receiving chemotherapy. The five-year survival rates were 9.4%. Conclusion: Bladder SRCC presents aggressively, with varied treatment strategies; however, radical cystectomy appears to be the optimal means of surgical management for organ-confined disease. The overall survival rate is low, highlighting the need for further research to understand and manage this rare bladder cancer variant. All patients should undergo evaluation to exclude extravesical primaries. This systematic review contributes to a better understanding of this disease and may guide clinical management strategies.

Angioarchitecture Classification and Treatment Modalities of Craniocervical Junction Arteriovenous Fistulas: A Cohort Study of 155 Patients.

Craniocervical junction (CCJ) arteriovenous fistulas (AVFs) are rare. Variability in clinical manifestations and treatment strategies for CCJ AVFs stems from differences in their angioarchitecture. Our study aims to categorize CCJ AVFs based on their angioarchitecture and explore the associated clinical features and treatment modalities for distinct CCJ AVF types. The authors conducted a retrospective analysis of patients with CCJ AVFs treated at a single neurosurgical facility over the past decade. These patients were classified based on the angioarchitecture of their CCJ AVFs. The analysis included an evaluation of angioarchitecture, clinical characteristics, treatment strategies, and outcomes. The study included 155 patients, with a median age of 56 years, collectively manifesting 165 CCJ AVFs. Our classification identified 4 distinct CCJ AVF types: epidural AVFs (19 [11.5%]), dural AVFs (98 [59.4%]), radicular AVFs (33 [20.0%]), and perimedullary AVFs (15 [9.1%]). Further differentiation was applied based on the presence of pial feeders. The predominant fistula location was at cervical-1 (77.0%). Ascending intradural drainage (52.7%) and descending intradural drainage (52.1%) were frequently observed drainage patterns. Patients with dural AVF predominantly presented with venous hypertensive myelopathy, whereas patients with other types of CCJ AVFs showed a higher incidence of subarachnoid hemorrhage (P = .012). Microsurgery was the predominant treatment, applied in the management of 126 (76.4%) AVFs, whereas 8 (4.8%) AVFs exclusively underwent interventional embolization and 25 (15.2%) received a combination of interventional embolization and microsurgical treatment. CCJ AVFs can be distinguished based on the fistula location and the arterial feeders. Currently, microsurgery stands as the preferred treatment strategy for CCJ AVFs, whereas interventional embolization plays a distinctive role in cases with specific angioarchitecture or as a pretreatment measure before microsurgery.

Cardiac delivery of modified mRNA using lipid nanoparticles: Cellular targets and biodistribution after intramyocardial administration

Despite research efforts being made towards preserving (or even regenerating) heart tissue after an ischemic event, there is a lack of resources in current clinical treatment modalities for patients with acute myocardial infarction that specifically address cardiac tissue impairment. Modified messenger RNA (modRNA) presents compelling properties that could allow new therapeutic strategies to tackle the underlying molecular pathways that ultimately lead to development of chronic heart failure. However, clinical application of modRNA for the heart is challenged by the lack of effective and safe delivery systems. Lipid nanoparticles (LNPs) represent a well characterized class of RNA delivery systems, which were recently approved for clinical usage in mRNA-based COVID-19 vaccines. In this study, we evaluated the potential of LNPs for cardiac delivery of modRNA. We tested how variations in C12–200 modRNA-LNP composition affect transfection levels and biodistribution after intramyocardial administration in both healthy and myocardial-infarcted mice, and determined the targeted cardiac cell types. Our data revealed that LNP-mediated modRNA delivery outperforms the current state of the art (modRNA in citrate buffer) upon intramyocardial administration in mice, with only minor differences among the formulations tested. Furthermore, we determined both in vitro and in vivo that the cardiac cells targeted by modRNA-LNPs include fibroblasts, endothelial cells and epicardial cells, suggesting that these cell types could represent targets for therapeutic interference with these LNP formulations. These outcomes may serve as a starting point for LNP development specifically for therapeutic mRNA cardiac delivery applications.

Clinical profile, treatment modalities and outcomes among patients with upper aero-digestive tract emergencies at Bugando Medical Centre, Mwanza, Tanzania

Background: Upper aero-digestive tract emergencies (UADTEs) are common in our setting and can be life-threatening and challenging to otolaryngologists. However, there is a paucity of clinical studies on these emergencies. This study aimed to determine the clinical profile, treatment modalities and outcomes of upper aero-digestive tract emergencies at Bugando Medical Centre (BMC), Mwanza, Tanzania. Methods: Between January and May 2019, a cross-sectional study involving patients presenting with a clinical diagnosis of UADTEs was conducted at BMC. Results: Of 487 ENT emergencies seen during the study period, 128 (26.3%) patients had UADTEs. Males outnumbered females by a ratio of 1.5: 1. Their median age at presentation was 5 [range, 2-40] years. The major causes of UADTEs were foreign body ingestion, head and neck tumours, foreign body aspiration and cut-throat injuries that were seen in 56(43.8%), 33(25.8%), 25(19.5%) and (3.9%), respectively. The most frequent presentations were dysphagia 81(63.3%), difficulty in breathing 61(47.7%) and odynophagia 56(43.8). Age ≤ 40 years (p=0.02), prolonged duration to treatment (p=0.04) and low blood oxygen saturation (SPO2) (p=0.04) were significantly associated with poor outcomes following esophagoscopy. In addition, delayed duration to treatment (p=0.01) and foreign body ingestion (p=0.001) were significantly associated with prolonged hospital stay. Conclusion: UADTEs are common at BMC and constitute a significant cause of otorhinolaryngological admission with foreign bodies in the aerodigestive tract as the most typical cause of these emergencies. Most of these injuries can be prevented through public enlightenment campaigns. Early detection and management of UADTEs is essential to reduce morbidity and mortality associated with these emergencies.

CLINICAL CHARACTERISTICS, TREATMENT MODALITIES, AND THEIR ASSOCIATION WITH LONG-TERM VISUAL OUTCOMES IN UVEAL EFFUSION SYNDROME.

Uveal effusion syndrome (UES) is a rare eye condition characterized by fluid accumulation in the uveal layer. We investigated its clinical characteristics and treatment modalities and their association with long-term visual outcomes. This retrospective cohort study included patients with UES treated at two tertiary hospitals between November 2005 and June 2023. Clinical characteristics and treatment outcomes by modality were compared between nanophthalmic Type 1 UES (UES-1) and non-nanophthalmic Type 2 UES (UES-2), and between initial and final visits. Logistic regression analysis was used to identify factors associated with vision loss. Twenty-three eyes were included (UES-1, n = 10; UES-2, n = 13). Retinal pigment epithelium mottling was significantly more common in UES-1 than in UES-2 ( P = 0.043); no other between-group differences were observed. Post-treatment, in UES-1, best-corrected visual acuity ( P = 0.028) and central macular thickness ( P = 0.046) significantly decreased; in UES-2, best-corrected visual acuity significantly improved ( P = 0.021), and subfoveal choroidal thickness ( P = 0.048), central subretinal fluid height ( P = 0.011), and central macular thickness ( P = 0.010) significantly decreased. UES-2 was associated with a lower risk of vision loss (odds ratio, 0.024; P = 0.044). No other associated factors were identified. The UES type was the sole independent prognostic factor for vision loss, whereas treatment modalities had no significant impact on visual outcomes.

Unveiling the Eschar: A Mite’s Mark in Scrub Typhus

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a Gram-negative intracellular organism transmittedby Leptotrombidium mites, with wild rats serving as natural reservoirs. The disease is more common in the TsutsugamushiTriangle, often afflicting travelers and creating diagnostic challenges in clinical practice. We present the case of a diabeticpatient who acquired the infection while visiting an agricultural farm. Our discussion covers clinical manifestations,diagnostic markers and treatment modalities, emphasizing the significance of early recognition and the benefits of prompttreatment. The importance of searching for an eschar, a key physical sign, is underscored and potential serious outcomesare discussed. Recent advances and preventive measures are also highlighted. This synthesis of research and clinical insightsaims to enhance global awareness, prompt diagnosis and effective management of scrub typhus.

Abstract 5019: Comprehensive pan-cancer analysis of cfDNA methylation marks in tumors reveals complex epigenetic regulatory circuits and diagnostic biomarkers

Abstract Early detection of tumor activity in clinically asymptomatic patients has the potential to improve quality of life and prevent unnecessary exposure to toxic therapies. DNA methylation is one of the most studied, stable, and fundamental epigenetic marks and represents a prominent alteration in most cancers. Analysis of DNA methylation, particularly in liquid biopsies has been introduced in cancer diagnosis and risk stratification. Despite indisputable achievements, translation into clinical practice is lagging behind, primarily due to 1) challenges associated with the analysis of DNA methylation, 2) the fragmented nature of cell-free DNA (cfDNA), aggravated by bisulfite treatment, 3) lack of clinical validation of reported cfDNA methylation marks, and 4) the paucity of knowledge about the functional consequences of cfDNA methylation marks within tumors. Using a sample pooling strategy, complemented with robust whole genome and reduced representation methylation sequencing, we establish a pan-cancer cfDNA methylation resource encompassing 12 cancer entities with diverse clinical phenotypes and treatment modalities. We built this compendium using a robustly performing whole genome and reduced representaion enzymatic methylation sequencing of more than 150 cfDNA and tumor DNA. We complement our data by analyzing DNA methylation data from 15 cancer entities (more than 7,000 patients) within the TCGA. We developed an enzymatic digital PCR (dPCR) approach for pan-cancer but also entity-specific analysis of cfDNA methylation at single base-resolution. Using this dPCR assay, we analyzed cfDNA and tumor DNA samples from more than 400 patients and compared enzymatic digestion with bisulfite treatment. We demonstrate that this resource can allow for the identification of entity-agnostic and specific markers, and that cfDNA methylation patterns are mirrored in tumor samples. The approach can be applied for methylation profiling of yet unanalyzed entities. Finally, we demonstrate unconventional epigenetic regulation of gene expression by methylated DNA-binding transcription factors whose activities are tissue- and context-specific and dosage-dependent. This work, therefore, provides a reference resource to identify minimally invasive, entity-specific and pan-cancer markers applicable for diagnostics, surveillance and patient stratification. It also sets the stage for further investigation of tissue- and context-specific epigenetic regulation of gene expression in health and disease by methylated DNA-binding transcription factors. Citation Format: Smiths Sengkwawoh Lueong, Martin Metzenmacher, Gregor Zaun, Gina Lauren Mayer, Erik Jan Hemmer, Katharina Lückerath, Kelsey Pomykala, Balazs Hegedüs, Peter A. Horn, Marija Trajkovic-Arsic, Tibor Szarvas, Renáta Váraljai, Corinna Keup, Ingeborg Tinhofer, Stephen George, Sabine Kasimir-Bauer, Samuel Peña-Llopis, Alexander Roesch, Cornelius Kürten, Lukas Boosfeld, Kirsten Bruderek, Christopher Darr, Thomas Hilser, Viktor Grünwald, Sven Brandau, Boris Hadaschik, Hans Neubauer, Irene Irene Esposito Irene Esposito, Tanja Fehm, Csilla Oláh, Anita Csizmarik, Fabinshy Thangarajah, Laura Reetz, Ghanam Jamal, Basant Kumar Thakur, Halime Kalkavan, Alexander Schramm, Martin Schuler, Jens T. Siveke. Comprehensive pan-cancer analysis of cfDNA methylation marks in tumors reveals complex epigenetic regulatory circuits and diagnostic biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5019.

Neuroendocrine and undifferentiated sinonasal and skull base tumors: An up-to-date narrative review.

Tumors located in the nasal cavity, paranasal sinuses and the skull base comprise a wide range of histologic subtypes. Among them, neuroendocrine and undifferentiated tumors are rare but noteworthy, because of their distinctive features, aggressive nature, and diagnostic complexities. A literature search was conducted in the PubMed/MEDLINE and the Scopus databases from 2019 until inception. The keywords "neuroendocrine", "undifferentiated", "nose", "sinonasal", "paranasal", "skull base" were used. Thirty-eight articles referring to neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base were finally included and analyzed. Neuroendocrine and undifferentiated tumors of the nose, paranasal sinuses and the skull base are infrequent malignancies, most commonly affecting middle-aged men. They usually present with non-specific symptoms, even though ocular or neurologic manifestations may occur. Prognosis is generally poor; however, novel targeted and immunological therapies have shown promising results. Sinonasal Neuroendocrine Carcinomas (SNECs) carry distinct histological and immunohistochemical features. Management consists of surgical resection coupled with systematic therapy. Sinonasal Undifferentiated Carcinomas (SNUCs) lack specific squamous or glandular features. They typically stain positive for pancytokeratin and INI1 antibody. Treatment includes induction chemotherapy, followed by a combination of chemotherapy and radiotherapy. Olfactory neuroblastomas (ONBs) have neuroepithelial or neuroblastic features. They show diffuse positivity for various markers, including synaptophysin, chromogranin, and neuron-specific enolase (NSE). Surgical resection plus radiotherapy is considered the treatment of choice. In conclusion, neuroendocrine and undifferentiated tumors arising from the nose, paranasal sinuses and the skull base represent a unique group of malignancies. A thorough understanding of their clinical features, molecular changes, diagnostic approaches, treatment modalities, and prognostic factors is critical for providing optimal patient care. Still, continued research efforts and multidisciplinary collaboration are warranted, in order to improve outcomes for patients diagnosed with these rare and aggressive tumors.

Adrenocortical Cancer in the Real World: A Comprehensive Analysis of Clinical Features and Management from the Turkish Oncology Group (TOG)

IntroductionAdrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and treatment modalities of ACC, providing insights into the disease's prognosis. Materials and MethodsA retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan–Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses. ResultsThe median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval [CI] 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses. ConclusionACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.

Clinical and prognostic differences in oropharyngeal squamous cell carcinoma in USA and Denmark, two HPV high-prevalence areas

BackgroundUncertainty persists regarding clinical and treatment variations crucial to consider when comparing high human papillomavirus (HPV)-prevalence oropharyngeal squamous cell carcinoma (OPSCC) cohorts for accurate patient stratification and replicability of clinical trials across different geographical areas. MethodsOPSCC patients were included from The University of Texas MD Anderson Cancer Center (UTMDACC), USA and from The University Hospital of Copenhagen, Denmark from 2015–2020, (n = 2484). Outcomes were 3-year overall survival (OS) and recurrence-free interval (RFI). Subgroup analyses were made for low-risk OPSCC patients (T1–2N0M0) and high-risk patients (UICC8 III-IV). ResultsThere were significantly more HPV-positive (88.2 % vs. 63.1 %), males (89.4 % vs. 74.1 %), never-smokers (52.1 % vs. 23.7 %), lower UICC8-stage (I/II: 79.3 % vs. 68 %), and fewer patients treated with radiotherapy (RT) alone (14.8 % vs. 30.3 %) in the UTMDACC cohort. No difference in the adjusted OS was observed (hazard ratio [HR] 1.21, p = 0.23), but a significantly increased RFI HR was observed for the Copenhagen cohort (HR: 1.74, p = 0.003). Subgroup analyses of low- and high-risk patients revealed significant clinical and treatment differences. No difference in prognosis was observed for low-risk patients, but the prognosis for high-risk patients in the Copenhagen cohort was worse (OS HR 2.20, p = 0.004, RFI HR 2.80, p = 0.002). ConclusionsWe identified significant differences in clinical characteristics, treatment modalities, and prognosis between a Northern European and Northern American OPSCC population. These differences are important to consider when comparing outcomes and for patient stratification in clinical trials, as reproducibility might be challenging.

Primary Immune Thrombocytopenic Purpura (ITP) and ITP Associated with Systemic Lupus Erythematosus: A Review of Clinical Characteristics and Treatment Modalities.

Immune thrombocytopenic purpura (ITP) is an immune-mediated disorder characterized by the destruction of platelets and megakaryocytes due to autoantibodies against the platelet surface proteins. ITP without any apparent cause of thrombocytopenia is defined as primary ITP, and ITP in the setting of SLE is secondary ITP, which can be diagnosed after excluding other causes of thrombocytopenia by history, physical examination, and laboratory testing. Patients with ITP associated with SLE have higher median platelet count and less bleeding manifestations compared to the patients with primary ITP. It can be very challenging to diagnose primary ITP in SLE patients as other causes of thrombocytopenia including drug-induced thrombocytopenia, antiphospholipid syndrome, and thrombotic microangiopathic process should be ruled out. Corticosteroids are the main modality of treatment. IVIG can be used in severe cases. Splenectomy was found to be less effective in ITP associated with SLE compared to primary ITP. Control of disease activity with immunosuppressive therapy can be helpful in some cases associated with active disease flares in SLE patients.

Clinical analysis of infectious endophthalmitis following glaucoma filtration surgery

BackgroundThis study aimed to evaluate the clinical correlative factors and outcomes of treatment of bleb-associated endophthalmitis (BAE) following glaucoma filtration surgery in a Chinese population from the year 2012 to 2022, and to compare them with the clinical course during the coronavirus disease (COVID-19) pandemic period.MethodsThis was a retrospective analysis of consecutive cases of BAE treated at the Eye & ENT Hospital of Fudan University, Shanghai, China, between January 1, 2012, and December 31, 2022. The clinical presentation, treatment modality, microbiological data, clinical course, and outcomes of visual acuity (VA) and intraocular pressure (IOP) in all BAE cases were collected and analyzed.ResultsA total of 28 eyes with BAE were examined, predominantly in male patients (71.4%, p = 0.023). Most patients underwent trabeculectomy (89.3%, p ≤ 0.001), while a smaller proportion underwent Ex-PRESS implantation (10.7%). Primary open-angle glaucoma (POAG) was the most common type of glaucoma (39.3%, p ≤ 0.001). Most patients (96.4%) presented with poor visual acuity, worse than 20/400, and IOP ranged from 3–60 mmHg. Treatment, including initial tap-and-inject procedure of antibiotics (Ceftazidime and Norvancomycin) or initial pars plana vitrectomy (PPV), was initiated 5.0 ± 7.1 days after BAE onset. Streptococcus was the most common causative organism (53.6% of cases, p ≤ 0.001). The visual acuity significantly improved from 2.58 ± 0.27 to 2.14 ± 0.85 (reported in logMAR) after treatment (p ≤ 0.001), and most patients maintained normal tension during follow-up. Poisson regression model analysis showed the annual incidence of BAE during the COVID-19 pandemic period was significantly twice greater than that of previous years.ConclusionsBAE may cause irreversible visual impairment. POAG filtering surgery with male sex and the COVID-19 pandemic period might be potentially relevant factors for BAE. Culture positivity was closely related to BAE prognosis, with Streptococcus species being the leading pathogenic organisms. Online outpatient services, early diagnosis, and timely treatment may rescue vision and maintain IOP control in the presence of BAE.

Neglected Preauricular Sinus Abscess Extending to the Scalp: A Case Report of Complications and Management Challenges

Preauricular sinus, a congenital malformation resulting from incomplete fusion of the first and second branchial arches, is a relatively common condition with a reported prevalence of 0.1% to 0.9%. While mostly asymptomatic, it can lead to abscess formation when infected. We present a unique case of a neglected preauricular sinus abscess that extended to the scalp, causing significant complications. The report discusses the clinical presentation, diagnostic approach, treatment modalities, and potential complications associated with this unusual and severe presentation. Prompt and appropriate management, combined with conservative treatment and surgical intervention, led to successful outcomes. This case highlights the importance of recognizing potential risks and implementing a systematic approach in managing recurrent preauricular sinus abscesses.

A novel therapeutic outlook: Classification, applications and challenges of inhalable micron/nanoparticle drug delivery systems in lung cancer (Review).

Lung cancer represents a marked global public health concern. Despite existing treatment modalities, the average 5‑year survival rate for patients with patients with lung cancer is only ~20%. As there are numerous adverse effects of systemic administration routes, there is an urgent need to develop a novel therapeutic strategy tailored specifically for patients with lung cancer. Non‑invasive aerosol inhalation, as a route of drug administration, holds unique advantages in the context of respiratory diseases. Nanoscale materials have extensive applications in the field of biomedical research in recent years. The present study provides a comprehensive review of the classification, applications summarized according to existing clinical treatment modalities for lung cancer and challenges associated with inhalable micron/nanoparticle drug delivery systems (DDSs) in lung cancer. Achieving localized treatment of lung cancer preclinical models through inhalation is deemed feasible. However, further research is required to substantiate the efficacy and long‑term safety of inhalable micron/nanoparticle DDSs in the clinical management of lung cancer.

Cellular forgetting, desensitisation, stress and ageing in signalling networks. When do cells refuse to learn more?

Recent findings show that single, non-neuronal cells are also able to learn signalling responses developing cellular memory. In cellular learning nodes of signalling networks strengthen their interactions e.g. by the conformational memory of intrinsically disordered proteins, protein translocation, miRNAs, lncRNAs, chromatin memory and signalling cascades. This can be described by a generalized, unicellular Hebbian learning process, where those signalling connections, which participate in learning, become stronger. Here we review those scenarios, where cellular signalling is not only repeated in a few times (when learning occurs), but becomes too frequent, too large, or too complex and overloads the cell. This leads to desensitisation of signalling networks by decoupling signalling components, receptor internalization, and consequent downregulation. These molecular processes are examples of anti-Hebbian learning and 'forgetting' of signalling networks. Stress can be perceived as signalling overload inducing the desensitisation of signalling pathways. Ageing occurs by the summative effects of cumulative stress downregulating signalling. We propose that cellular learning desensitisation, stress and ageing may be placed along the same axis of more and more intensive (prolonged or repeated) signalling. We discuss how cells might discriminate between repeated and unexpected signals, and highlight the Hebbian and anti-Hebbian mechanisms behind the fold-change detection in the NF-κB signalling pathway. We list drug design methods using Hebbian learning (such as chemically-induced proximity) and clinical treatment modalities inducing (cancer, drug allergies) desensitisation or avoiding drug-induced desensitisation. A better discrimination between cellular learning, desensitisation and stress may open novel directions in drug design, e.g. helping to overcome drug resistance.

Epidemiology, Characteristics, and Prognostic Factors of Primary Atypical Teratoid/Rhabdoid Tumors in the Spinal Canal: A Systematic Review.

Primary atypical teratoid/rhabdoid tumors (AT/RTs) in the spinal canal are rare central nervous system (CNS) neoplasms that are challenging to diagnose and treat. To date, there has been no standard treatment regimen for these challenging malignant tumors. Thus, we conducted this research to explore potential prognostic factors and feasible treatment modalities for improving the prognosis of these tumors. Articles were retrieved from the PubMed, MEDLINE, and Embase databases, using the keywords "atypical teratoid/rhabdoid tumor," "rhabdoid tumor," "spine," "spinal," "spinal neoplasm", and "spinal cord neoplasm." All eligible cases demonstrated SMARCB1-deficient expression validated by pathological examination. We collected and analyzed data related to clinical presentation, radiological features, pathological characteristics, treatment modalities and prognosis via Kaplan-Meier and Cox regression analyses. Thirty-six articles comprising 58 spinal AT/RT patients were included in the study. The median progression-free survival (PFS) and overall survival (OS) were 18 and 22 months, respectively. Kaplan-Meier analysis demonstrated significant survival improvements for OS in the nonmetastasis, male, radiotherapy and intrathecal chemotherapy groups as well as for PFS in the chemotherapy and radiotherapy groups. Multivariate analysis revealed that chemotherapy and radiotherapy were prognostic factors for improved PFS, and that intrathecal chemotherapy reduced the risk of mortality. Spinal AT/RTs are uncommon malignant entities with a dismal survival rate. Although our review is limited by variability between cases, there is some evidence revealing potential risk factors and the importance of systematic chemotherapy, intrathecal chemotherapy and radiotherapy in spinal AT/RT treatment modalities.